Inpatient health care utilization by children and adolescents with systemic lupus erythematosus and kidney involvement.

PubMed

Tanzer, Marie; Tran, Cheryl; Messer, Kassandra L; Kroeker, Amber; Herreshoff, Emily; Wickman, Larysa; Harkness, Courtney; Song, Peter; Gipson, Debbie S

2013-03-01

To evaluate inpatient health care utilization for children with systemic lupus erythematosus (SLE) with and without kidney disease. The Healthcare Cost and Utilization Project Kids' Inpatient Database for the years 2000, 2003, and 2006 was used for this analysis. SLE hospitalizations from the 2006 cohort were identified and classified as those with versus without kidney involvement by International Classification of Diseases, Ninth Revision, Clinical Modification codes. Analyses were performed to examine determinants of hospitalization charges and changes in charges over time. In the US, 7,390 SLE-related pediatric hospitalizations generated $267 million in total charges in 2006. Of these, 4,193 discharges had kidney involvement. The average hospitalization charge was greater for SLE patients with kidney involvement compared to those without kidney involvement ($43,100 versus $28,500; P < 0.0001). In multivariate analysis, kidney involvement remained a significant predictor of hospitalization charges, independent of demographic and hospital characteristics (P < 0.0001). SLE-associated acute kidney failure, transplant, and end-stage kidney disease resulted in greater hospitalization charges than SLE without kidney involvement by $74,900 (P < 0.0001), $32,700 (P = 0.0002), and $27,400 (P < 0.0001), respectively. In the US, >7,000 hospitalizations occurred in 2006 among children with SLE, with nearly 57% demonstrating kidney involvement. Kidney involvement is a major determinant of hospitalization charges for these children. This study represents one of the first large-scale assessments of in-hospital health care utilization by children with SLE. Copyright © 2013 by the American College of Rheumatology.

[The French Chronic Kidney Disease-Renal Epidemiology and Information Network (CKD-REIN) cohort study: To better understand chronic kidney disease].

PubMed

Stengel, Bénédicte; Combe, Christian; Jacquelinet, Christian; Briançon, Serge; Fouque, Denis; Laville, Maurice; Frimat, Luc; Pascal, Christophe; Herpe, Yves-Édouard; Morel, Pascal; Deleuze, Jean-François; Schanstra, Joost P; Pisoni, Ron L; Robinson, Bruce M; Massy, Ziad A

2016-04-01

Preserving kidney function and improving the transition from chronic kidney disease to end stage is a research and healthcare challenge. The national Chronic Kidney Disease-Renal Epidemiology and Information Network (CKD-REIN) cohort was established to identify the determinants, biomarkers and practice patterns associated with chronic kidney disease outcomes. The study will include more than 3000 adult patients with moderate to advanced chronic kidney disease from a representative sample of 40 nephrology clinics with respect to regions and legal status, public or private. Patients are recruited during a routine visit and followed for 5 years, before and after starting renal replacement therapy. Patient-level clinical, biological, and lifestyle data are collected annually, as well as provider-level data on clinical practices, coordinated with the International Chronic Kidney Disease Outcomes and Practice Pattern Study. Blood and urine samples are stored in a biobank. Major studied outcomes include survival, patient-reported outcomes, disease progression and hospitalizations. More than 13,000 eligible patients with chronic kidney disease were identified, 60% with stage 3 and 40% with stage 4. Their median age is 72 years [interquartile range, 62-80 years], 60% are men and 38% have diabetes. By the end of December 2015, 2885 patients were included. The CKD-REIN cohort will serve to improve our understanding of chronic kidney disease and provide evidence to improve patient survival and quality of life as well as health care system performances. Copyright © 2016 Association Société de néphrologie. All rights reserved.

Genetic Drivers of Kidney Defects in the DiGeorge Syndrome.

PubMed

Lopez-Rivera, Esther; Liu, Yangfan P; Verbitsky, Miguel; Anderson, Blair R; Capone, Valentina P; Otto, Edgar A; Yan, Zhonghai; Mitrotti, Adele; Martino, Jeremiah; Steers, Nicholas J; Fasel, David A; Vukojevic, Katarina; Deng, Rong; Racedo, Silvia E; Liu, Qingxue; Werth, Max; Westland, Rik; Vivante, Asaf; Makar, Gabriel S; Bodria, Monica; Sampson, Matthew G; Gillies, Christopher E; Vega-Warner, Virginia; Maiorana, Mariarosa; Petrey, Donald S; Honig, Barry; Lozanovski, Vladimir J; Salomon, Rémi; Heidet, Laurence; Carpentier, Wassila; Gaillard, Dominique; Carrea, Alba; Gesualdo, Loreto; Cusi, Daniele; Izzi, Claudia; Scolari, Francesco; van Wijk, Joanna A E; Arapovic, Adela; Saraga-Babic, Mirna; Saraga, Marijan; Kunac, Nenad; Samii, Ali; McDonald-McGinn, Donna M; Crowley, Terrence B; Zackai, Elaine H; Drozdz, Dorota; Miklaszewska, Monika; Tkaczyk, Marcin; Sikora, Przemyslaw; Szczepanska, Maria; Mizerska-Wasiak, Malgorzata; Krzemien, Grazyna; Szmigielska, Agnieszka; Zaniew, Marcin; Darlow, John M; Puri, Prem; Barton, David; Casolari, Emilio; Furth, Susan L; Warady, Bradley A; Gucev, Zoran; Hakonarson, Hakon; Flogelova, Hana; Tasic, Velibor; Latos-Bielenska, Anna; Materna-Kiryluk, Anna; Allegri, Landino; Wong, Craig S; Drummond, Iain A; D'Agati, Vivette; Imamoto, Akira; Barasch, Jonathan M; Hildebrandt, Friedhelm; Kiryluk, Krzysztof; Lifton, Richard P; Morrow, Bernice E; Jeanpierre, Cecile; Papaioannou, Virginia E; Ghiggeri, Gian Marco; Gharavi, Ali G; Katsanis, Nicholas; Sanna-Cherchi, Simone

2017-02-23

The DiGeorge syndrome, the most common of the microdeletion syndromes, affects multiple organs, including the heart, the nervous system, and the kidney. It is caused by deletions on chromosome 22q11.2; the genetic driver of the kidney defects is unknown. We conducted a genomewide search for structural variants in two cohorts: 2080 patients with congenital kidney and urinary tract anomalies and 22,094 controls. We performed exome and targeted resequencing in samples obtained from 586 additional patients with congenital kidney anomalies. We also carried out functional studies using zebrafish and mice. We identified heterozygous deletions of 22q11.2 in 1.1% of the patients with congenital kidney anomalies and in 0.01% of population controls (odds ratio, 81.5; P=4.5×10 -14 ). We localized the main drivers of renal disease in the DiGeorge syndrome to a 370-kb region containing nine genes. In zebrafish embryos, an induced loss of function in snap29, aifm3, and crkl resulted in renal defects; the loss of crkl alone was sufficient to induce defects. Five of 586 patients with congenital urinary anomalies had newly identified, heterozygous protein-altering variants, including a premature termination codon, in CRKL. The inactivation of Crkl in the mouse model induced developmental defects similar to those observed in patients with congenital urinary anomalies. We identified a recurrent 370-kb deletion at the 22q11.2 locus as a driver of kidney defects in the DiGeorge syndrome and in sporadic congenital kidney and urinary tract anomalies. Of the nine genes at this locus, SNAP29, AIFM3, and CRKL appear to be critical to the phenotype, with haploinsufficiency of CRKL emerging as the main genetic driver. (Funded by the National Institutes of Health and others.).

Evaluation of Digital PCR as a Technique for Monitoring Acute Rejection in Kidney Transplantation.

PubMed

Lee, Hyeseon; Park, Young-Mi; We, Yu-Mee; Han, Duck Jong; Seo, Jung-Woo; Moon, Haena; Lee, Yu-Ho; Kim, Yang-Gyun; Moon, Ju-Young; Lee, Sang-Ho; Lee, Jong-Keuk

2017-03-01

Early detection and proper management of kidney rejection are crucial for the long-term health of a transplant recipient. Recipients are normally monitored by serum creatinine measurement and sometimes with graft biopsies. Donor-derived cell-free deoxyribonucleic acid (cfDNA) in the recipient's plasma and/or urine may be a better indicator of acute rejection. We evaluated digital PCR (dPCR) as a system for monitoring graft status using single nucleotide polymorphism (SNP)-based detection of donor DNA in plasma or urine. We compared the detection abilities of the QX200, RainDrop, and QuantStudio 3D dPCR systems. The QX200 was the most accurate and sensitive. Plasma and/or urine samples were isolated from 34 kidney recipients at multiple time points after transplantation, and analyzed by dPCR using the QX200. We found that donor DNA was almost undetectable in plasma DNA samples, whereas a high percentage of donor DNA was measured in urine DNA samples, indicating that urine is a good source of cfDNA for patient monitoring. We found that at least 24% of the highly polymorphic SNPs used to identify individuals could also identify donor cfDNA in transplant patient samples. Our results further showed that autosomal, sex-specific, and mitochondrial SNPs were suitable markers for identifying donor cfDNA. Finally, we found that donor-derived cfDNA measurement by dPCR was not sufficient to predict a patient's clinical condition. Our results indicate that donor-derived cfDNA is not an accurate predictor of kidney status in kidney transplant patients.

Laser Capture Microdissection and Multiplex-Tandem PCR Analysis of Proximal Tubular Epithelial Cell Signaling in Human Kidney Disease

PubMed Central

Wilkinson, Ray; Wang, Xiangju; Kassianos, Andrew J.; Zuryn, Steven; Roper, Kathrein E.; Osborne, Andrew; Sampangi, Sandeep; Francis, Leo; Raghunath, Vishwas; Healy, Helen

2014-01-01

Interstitial fibrosis, a histological process common to many kidney diseases, is the precursor state to end stage kidney disease, a devastating and costly outcome for the patient and the health system. Fibrosis is historically associated with chronic kidney disease (CKD) but emerging evidence is now linking many forms of acute kidney disease (AKD) with the development of CKD. Indeed, we and others have observed at least some degree of fibrosis in up to 50% of clinically defined cases of AKD. Epithelial cells of the proximal tubule (PTEC) are central in the development of kidney interstitial fibrosis. We combine the novel techniques of laser capture microdissection and multiplex-tandem PCR to identify and quantitate “real time” gene transcription profiles of purified PTEC isolated from human kidney biopsies that describe signaling pathways associated with this pathological fibrotic process. Our results: (i) confirm previous in-vitro and animal model studies; kidney injury molecule-1 is up-regulated in patients with acute tubular injury, inflammation, neutrophil infiltration and a range of chronic disease diagnoses, (ii) provide data to inform treatment; complement component 3 expression correlates with inflammation and acute tubular injury, (iii) identify potential new biomarkers; proline 4-hydroxylase transcription is down-regulated and vimentin is up-regulated across kidney diseases, (iv) describe previously unrecognized feedback mechanisms within PTEC; Smad-3 is down-regulated in many kidney diseases suggesting a possible negative feedback loop for TGF-β in the disease state, whilst tight junction protein-1 is up-regulated in many kidney diseases, suggesting feedback interactions with vimentin expression. These data demonstrate that the combined techniques of laser capture microdissection and multiplex-tandem PCR have the power to study molecular signaling within single cell populations derived from clinically sourced tissue. PMID:24475278

Local therapeutic efficacy with reduced systemic side effects by rapamycin-loaded subcapsular microspheres.

PubMed

Falke, Lucas L; van Vuuren, Stefan H; Kazazi-Hyseni, Filis; Ramazani, Farshad; Nguyen, Tri Q; Veldhuis, Gert J; Maarseveen, Erik M; Zandstra, Jurjen; Zuidema, Johan; Duque, Luisa F; Steendam, Rob; Popa, Eliane R; Kok, Robbert Jan; Goldschmeding, Roel

2015-02-01

Kidney injury triggers fibrosis, the final common pathway of chronic kidney disease (CKD). The increase of CKD prevalence worldwide urgently calls for new therapies. Available systemic treatment such as rapamycin are associated with serious side effects. To study the potential of local antifibrotic therapy, we administered rapamycin-loaded microspheres under the kidney capsule of ureter-obstructed rats and assessed the local antifibrotic effects and systemic side effects of rapamycin. After 7 days, microsphere depots were easily identifiable under the kidney capsule. Both systemic and local rapamycin treatment reduced intrarenal mTOR activity, myofibroblast accumulation, expression of fibrotic genes, and T-lymphocyte infiltration. Upon local treatment, inhibition of mTOR activity and reduction of myofibroblast accumulation were limited to the immediate vicinity of the subcapsular pocket, while reduction of T-cell infiltration was widespread. In contrast to systemically administered rapamycin, local treatment did not induce off target effects such as weight loss. Thus subcapsular delivery of rapamycin-loaded microspheres successfully inhibited local fibrotic response in UUO with less systemic effects. Therapeutic effect of released rapamycin was most prominent in close vicinity to the implanted microspheres. Copyright © 2014 Elsevier Ltd. All rights reserved.

The multifaceted role of the renal mononuclear phagocyte system.

PubMed

Viehmann, Susanne F; Böhner, Alexander M C; Kurts, Christian; Brähler, Sebastian

2018-04-22

The kidney contains a large and complex network of mononuclear phagocytes, which includes dendritic cells (DCs) and macrophages (MØs). The distinction between these cell types is traditionally based on the expression of molecular markers and morphology. However, several classification systems are used in parallel to identify DCs and MØs, leading to considerable uncertainty about their identity and functional roles. The discovery that a substantial proportion of macrophages in tissues like the kidney are embryonically derived further complicates the situation. Recent studies have used newly identified transcription factors such as ZBTB46 and lineage tracing techniques for classifying mononuclear phagocytes. These approaches have shed new light on the functional specialization of these cells in health and disease, uncovered an influence of the renal microenvironment and revealed considerable cellular plasticity, especially in inflammatory situations. In this review, the current knowledge about the developmental origins and versatile functional roles of DCs and MØs in kidney homeostasis and disease is discussed. Copyright © 2018 Elsevier Inc. All rights reserved.

New insights into potential functions for the protein 4.1superfamily of proteins in kidney epithelium

DOE Office of Scientific and Technical Information (OSTI.GOV)

Calinisan, Venice; Gravem, Dana; Chen, Ray Ping-Hsu

2005-06-17

Members of the protein 4.1 family of adapter proteins are expressed in a broad panel of tissues including various epithelia where they likely play an important role in maintenance of cell architecture and polarity and in control of cell proliferation. We have recently characterized the structure and distribution of three members of the protein 4.1 family, 4.1B, 4.1R and 4.1N, in mouse kidney. We describe here binding partners for renal 4.1 proteins, identified through the screening of a rat kidney yeast two-hybrid system cDNA library. The identification of putative protein 4.1-based complexes enables us to envision potential functions for 4.1more » proteins in kidney: organization of signaling complexes, response to osmotic stress, protein trafficking, and control of cell proliferation. We discuss the relevance of these protein 4.1-based interactions in kidney physio-pathology in the context of their previously identified functions in other cells and tissues. Specifically, we will focus on renal 4.1 protein interactions with beta amyloid precursor protein (beta-APP), 14-3-3 proteins, and the cell swelling-activated chloride channel pICln. We also discuss the functional relevance of another member of the protein 4.1 superfamily, ezrin, in kidney physiopathology.« less

Succinate receptor GPR91 provides a direct link between high glucose levels and renin release in murine and rabbit kidney

PubMed Central

Toma, Ildikó; Kang, Jung Julie; Sipos, Arnold; Vargas, Sarah; Bansal, Eric; Hanner, Fiona; Meer, Elliott; Peti-Peterdi, János

2008-01-01

Diabetes mellitus is the most common and rapidly growing cause of end-stage renal disease in developed countries. A classic hallmark of early diabetes mellitus includes activation of the renin-angiotensin system (RAS), which may lead to hypertension and renal tissue injury, but the mechanism of RAS activation is elusive. Here we identified a paracrine signaling pathway in the kidney in which high levels of glucose directly triggered the release of the prohypertensive hormone renin. The signaling cascade involved the local accumulation of succinate and activation of the kidney-specific G protein–coupled metabolic receptor, GPR91, in the glomerular endothelium as observed in rat, mouse, and rabbit kidney sections. Elements of signal transduction included endothelial Ca2+, the production of NO and prostaglandin (PGE2), and their paracrine actions on adjacent renin-producing cells. This GPR91 signaling cascade may serve to modulate kidney function and help remove metabolic waste products through renal hyperfiltration, and it could also link metabolic diseases, such as diabetes, or metabolic syndrome with RAS overactivation, systemic hypertension, and organ injury. PMID:18535668

Genetic Drivers of Kidney Defects in the DiGeorge Syndrome

PubMed Central

Lopez-Rivera, E.; Liu, Y.P.; Verbitsky, M.; Anderson, B.R.; Capone, V.P.; Otto, E.A.; Yan, Z.; Mitrotti, A.; Martino, J.; Steers, N.J.; Fasel, D.A.; Vukojevic, K.; Deng, R.; Racedo, S.E.; Liu, Q.; Werth, M.; Westland, R.; Vivante, A.; Makar, G.S.; Bodria, M.; Sampson, M.G.; Gillies, C.E.; Vega-Warner, V.; Maiorana, M.; Petrey, D.S.; Honig, B.; Lozanovski, V.J.; Salomon, R.; Heidet, L.; Carpentier, W.; Gaillard, D.; Carrea, A.; Gesualdo, L.; Cusi, D.; Izzi, C.; Scolari, F.; van Wijk, J.A.E.; Arapovic, A.; Saraga-Babic, M.; Saraga, M.; Kunac, N.; Samii, A.; McDonald-McGinn, D.M.; Crowley, T.B.; Zackai, E.H.; Drozdz, D.; Miklaszewska, M.; Tkaczyk, M.; Sikora, P.; Szczepanska, M.; Mizerska-Wasiak, M.; Krzemien, G.; Szmigielska, A.; Zaniew, M.; Darlow, J.M.; Puri, P.; Barton, D.; Casolari, E.; Furth, S.L.; Warady, B.A.; Gucev, Z.; Hakonarson, H.; Flogelova, H.; Tasic, V.; Latos-Bielenska, A.; Materna-Kiryluk, A.; Allegri, L.; Wong, C.S.; Drummond, I.A.; D’Agati, V.; Imamoto, A.; Barasch, J.M.; Hildebrandt, F.; Kiryluk, K.; Lifton, R.P.; Morrow, B.E.; Jeanpierre, C.; Papaioannou, V.E.; Ghiggeri, G.M.; Gharavi, A.G.; Katsanis, N.; Sanna-Cherchi, S.

2017-01-01

BACKGROUND The DiGeorge syndrome, the most common of the microdeletion syndromes, affects multiple organs, including the heart, the nervous system, and the kidney. It is caused by deletions on chromosome 22q11.2; the genetic driver of the kidney defects is unknown. METHODS We conducted a genomewide search for structural variants in two cohorts: 2080 patients with congenital kidney and urinary tract anomalies and 22,094 controls. We performed exome and targeted resequencing in samples obtained from 586 additional patients with congenital kidney anomalies. We also carried out functional studies using zebrafish and mice. RESULTS We identified heterozygous deletions of 22q11.2 in 1.1% of the patients with congenital kidney anomalies and in 0.01% of population controls (odds ratio, 81.5; P=4.5×10−14). We localized the main drivers of renal disease in the DiGeorge syndrome to a 370-kb region containing nine genes. In zebrafish embryos, an induced loss of function in snap29, aifm3, and crkl resulted in renal defects; the loss of crkl alone was sufficient to induce defects. Five of 586 patients with congenital urinary anomalies had newly identified, heterozygous protein-altering variants, including a premature termination codon, in CRKL. The inactivation of Crkl in the mouse model induced developmental defects similar to those observed in patients with congenital urinary anomalies. CONCLUSIONS We identified a recurrent 370-kb deletion at the 22q11.2 locus as a driver of kidney defects in the DiGeorge syndrome and in sporadic congenital kidney and urinary tract anomalies. Of the nine genes at this locus, SNAP29, AIFM3, and CRKL appear to be critical to the phenotype, with haploinsufficiency of CRKL emerging as the main genetic driver. (Funded by the National Institutes of Health and others.) PMID:28121514

[Ascites and acute kidney injury].

PubMed

Piano, Salvatore; Tonon, Marta; Angeli, Paolo

2016-07-01

Ascites is the most common complication of cirrhosis. Ascites develops as a consequence of an abnormal splanchnic vasodilation with reduction of effecting circulating volume and activation of endogenous vasoconstrictors system causing salt and water retention. Patients with ascites have a high risk to develop further complications of cirrhosis such as hyponatremia, spontaneous bacterial peritonitis and acute kidney injury resulting in a poor survival. In recent years, new studies helped a better understanding of the pathophysiology of ascites and acute kidney injury in cirrhosis. Furthermore, new diagnostic criteria have been proposed for acute kidney injury and hepatorenal syndrome and a new algorithm for their management has been recommended with the aim of an early diagnosis and treatment. Herein we will review the current knowledge on the pathophysiology, diagnosis and treatment of ascites and acute kidney injury in patients with cirrhosis and we will identify the unmet needs that should be clarified in the next years.

Lung-Kidney Cross-Talk in the Critically Ill Patient.

PubMed

Husain-Syed, Faeq; Slutsky, Arthur S; Ronco, Claudio

2016-08-15

Discoveries have emerged highlighting the complex nature of the interorgan cross-talk between the kidney and the lung. Vascular rigidity, neurohormonal activation, tissue hypoxia, and abnormal immune cell signaling have been identified as common pathways leading to the development and progression of chronic kidney disease. However, our understanding of the causal relationships between lung injury and kidney injury is not precise. This review discusses a number of features and mechanisms of renal dysfunction in pulmonary disorders in relation to respiratory acidosis, impaired gas exchange, systemic congestion, respiratory support/replacement therapies, and other issues relevant to the clinical care of these patients. Biotrauma due to injurious ventilatory strategies can lead to the release of mediators into the lung, which may then translocate into the systemic circulation and cause end-organ dysfunction, including renal dysfunction. Right ventricular dysfunction and congestive states may contribute to alterations of renal perfusion and oxygenation, leading to diuretic resistance and recurrent hospitalization. In patients with concomitant respiratory failure, noninvasive ventilation represents a promising treatment option for the correction of impaired renal microcirculation and endothelial dysfunction. In patients requiring extracorporeal membrane oxygenation, short- and long-term monitoring of kidney function is warranted, as they are at highest risk of developing acute kidney injury and fluid overload.

Varied dose exposures to ultrafine particles in the motorcycle smoke cause kidney cell damages in male mice.

PubMed

Wardoyo, Arinto Y P; Juswono, Unggul P; Noor, Johan A E

2018-01-01

Ultrafine particles (UFPs) are one of motorcycle exhaust emissions which can penetrate the lung alveoli and deposit in the kidney. This study was aimed to investigate mice kidney cell physical damage (deformation) due to motorcycle exhaust emission exposures. The motorcycle exhaust emissions were sucked from the muffler with the rate of 33 cm 3 /s and passed through an ultrafine particle filter system before introduced into the mice exposure chamber. The dose concentration of the exhaust emissions was varied by setting the injected time of the 20s, 40s, 60s, 80s, and 100s. The mice were exposed to the smoke in the chamber for 100 s twice a day. The impact of the ultrafine particles on the kidney was observed by identifying the histological image of the kidney cell deformation using a microscope. The exposure was conducted for 10 days. The kidney observations were carried out on day 11. The results showed that there was a significant linear correlation between the total concentration of ultrafine particles deposited in the kidneys and the physical damage percentages. The increased concentrations of ultrafine particles caused larger cell deformation to the kidneys.

Characterization of kidney CD45intCD11bintF4/80+MHCII+CX3CR1+Ly6C- "intermediate mononuclear phagocytic cells".

PubMed

Lee, Sul A; Noel, Sanjeev; Sadasivam, Mohanraj; Allaf, Mohamad E; Pierorazio, Phillip M; Hamad, Abdel R A; Rabb, Hamid

2018-01-01

Kidney immune cells play important roles in pathogenesis of many diseases, including ischemia-reperfusion injury (IRI) and transplant rejection. While studying murine kidney T cells, we serendipitously identified a kidney mononuclear phagocytic cell (MPC) subset characterized by intermediate surface expression of CD45 and CD11b. These CD45intCD11bint MPCs were further identified as F4/80+MHCII+CX3CR1+Ly6C- cells, comprising ~17% of total CD45+ cells in normal mouse kidney (P < 0.01) and virtually absent from all other organs examined except the heart. Systemic clodronate treatment had more significant depletive effect on the CD45intCD11bint population (77.3%±5.9%, P = 0.03) than on CD45highCD11b+ population (14.8%±16.6%, P = 0.49). In addition, CD45intCD11bint MPCs had higher phagocytic function in the normal kidney (35.6%±3.3% vs. 24.1%±2.2%, P = 0.04), but lower phagocytic capacity in post-ischemic kidney (54.9%±1.0% vs. 67.8%±1.9%, P < 0.01) compared to the CD45highCD11b+ population. Moreover, the CD45intCD11bint population had higher intracellular production of the pro-inflammatory tumor necrosis factor (TNF)-α (58.4%±5.2% vs. 27.3%±0.9%, P < 0.001) after lipopolysaccharide (LPS) stimulation and lower production of the anti-inflammatory interleukin (IL)-10 (7.2%±1.3% vs. 14.9%±2.2%, P = 0.02) following kidney IRI, suggesting a functional role under inflammatory conditions. The CD45intCD11bint cells increased early after IRI, and then abruptly decreased 48h later, whereas CD45highCD11b+ cells steadily increased after IRI before declining at 72h (P = 0.03). We also identified the CD45intCD11bint MPC subtype in human kidney. We conclude that CD45intCD11bint F4/80+MHCII+CX3CR1+Ly6C-population represent a unique subset of MPCs found in both mouse and human kidneys. Future studies will further characterize their role in kidney health and disease.

"Maybe They Don't Even Know That I Exist": Challenges Faced by Family Members and Friends of Patients with Advanced Kidney Disease.

PubMed

O'Hare, Ann M; Szarka, Jackie; McFarland, Lynne V; Vig, Elizabeth K; Sudore, Rebecca L; Crowley, Susan; Reinke, Lynn F; Trivedi, Ranak; Taylor, Janelle S

2017-06-07

Family members and friends of patients with advanced chronic illness are increasingly called on to assist with ever more complex medical care and treatment decisions arising late in the course of illness. Our goal was to learn about the experiences of family members and friends of patients with advanced kidney disease. As part of a study intended to identify opportunities to enhance advance care planning, we conducted semistructured interviews at the Veterans Affairs Puget Sound Health Care System with 17 family members and friends of patients with advanced kidney disease. Interviews were conducted between April of 2014 and May of 2016 and were audiotaped, transcribed, and analyzed inductively using grounded theory to identify emergent themes. The following three themes emerged from interviews with patients' family members and friends: ( 1 ) their roles in care and planning were fluid over the course of the patient's illness, shaped by the patients' changing needs and their readiness to involve those close to them; ( 2 ) their involvement in patients' care was strongly shaped by health care system needs. Family and friends described filling gaps left by the health care system and how their involvement in care and decision-making was at times constrained and at other times expected by providers, depending on system needs; and ( 3 ) they described multiple sources of tension and conflict in their interactions with patients and the health care system, including instances of being pitted against the patient. Interviews with family members and friends of patients with advanced kidney disease provide a window on the complex dynamics shaping their engagement in patients' care, and highlight the potential value of offering opportunities for engagement throughout the course of illness. Copyright © 2017 by the American Society of Nephrology.

Histopathologic Findings of Potential Kidney Donors With Asymptomatic Microscopic Hematuria: Impact on Donation.

PubMed

Hassan, E A; Ali, T Z; Abdulbaki, A; Ibrahim, I A; Almanae, H M; Aleid, H A

2017-10-01

Isolated microscopic hematuria (IMH) is not uncommon in potential kidney donors. The aim was to study the kidney biopsy findings of potential kidney donors with IMH and the impact of the histopathologic diagnoses on the decision to accept or decline such donors from kidney donation. In this retrospective study, all the potential kidney donors with IMH were identified from the medical records of patients who underwent kidney biopsies between January 2010 and December 2016. Forty-five such individuals were identified. The mean age of these potential donors was 32.6 years and 76% were male. All of them had normal blood pressure and no significant proteinuria. Seventeen (38%) biopsies showed histopathologic abnormalities; thin basement membrane disease (n = 13; 28%) was the most common cause followed by immunoglobulin (Ig)A nephropathy (n = 4; 9%). Donors with abnormal biopsy findings were excluded from donation. However, 62% of the potential donors had normal kidney biopsy findings and were accepted for kidney donation. IMH justifies extensive work-up including kidney biopsy to identify donors who may have underlying significant glomerular pathology excluding them from kidney donation. On the other hand, kidney biopsy also helps in accepting the donors if it does not show significant abnormality. Copyright © 2017 Elsevier Inc. All rights reserved.

Identifying Risk for Acute Kidney Injury in Infants and Children Following Cardiac Arrest.

PubMed

Neumayr, Tara M; Gill, Jeff; Fitzgerald, Julie C; Gazit, Avihu Z; Pineda, Jose A; Berg, Robert A; Dean, J Michael; Moler, Frank W; Doctor, Allan

2017-10-01

Our goal was to identify risk factors for acute kidney injury in children surviving cardiac arrest. Retrospective analysis of a public access dataset. Fifteen children's hospitals associated with the Pediatric Emergency Care Applied Research Network. Two hundred ninety-six subjects between 1 day and 18 years old who experienced in-hospital or out-of-hospital cardiac arrest between July 1, 2003, and December 31, 2004. None. Our primary outcome was development of acute kidney injury as defined by the Acute Kidney Injury Network criteria. An ordinal probit model was developed. We found six critical explanatory variables, including total number of epinephrine doses, postcardiac arrest blood pressure, arrest location, presence of a chronic lung condition, pH, and presence of an abnormal baseline creatinine. Total number of epinephrine doses received as well as rate of epinephrine dosing impacted acute kidney injury risk and severity of acute kidney injury. This study is the first to identify risk factors for acute kidney injury in children after cardiac arrest. Our findings regarding the impact of epinephrine dosing are of particular interest and suggest potential for epinephrine toxicity with regard to acute kidney injury. The ability to identify and potentially modify risk factors for acute kidney injury after cardiac arrest may lead to improved morbidity and mortality in this population.

Proteome profiling in the aorta and kidney of type 1 diabetic rats

PubMed Central

Zhu, Rui; Jaffa, Miran A.; Zhao, Jingfu; Mirzaei, Parvin; Ahmed, Adnan; Kobeissy, Firas; Ziyadeh, Fuad N.; Mechref, Yehia

2017-01-01

Diabetes is associated with a number of metabolic and cardiovascular risk factors that contribute to a high rate of microvascular and macrovascular complications. The risk factors and mechanisms that contribute to the development of micro- and macrovascular disease in diabetes are not fully explained. In this study, we employed mass spectrometric analysis using tandem LC-MS/MS to generate a proteomic profile of protein abundance and post-translational modifications (PTM) in the aorta and kidney of diabetic rats. In addition, systems biology analyses were employed to identify key protein markers that can provide insights into molecular pathways and processes that are differentially regulated in the aorta and kidney of type 1 diabetic rats. Our results indicated that 188 (111 downregulated and 77 upregulated) proteins were significantly identified in the aorta of diabetic rats compared to normal controls. A total of 223 (109 downregulated and 114 upregulated) proteins were significantly identified in the kidney of diabetic rats compared to normal controls. When the protein profiles from the kidney and aorta of diabetic and control rats were analyzed by principal component analysis, a distinct separation of the groups was observed. In addition, diabetes resulted in a significant increase in PTM (oxidation, phosphorylation, and acetylation) of proteins in the kidney and aorta and this effect was partially reversed by insulin treatment. Ingenuity pathway analysis performed on the list of differentially expressed proteins depicted mitochondrial dysfunction, oxidative phosphorylation and acute phase response signaling to be among the altered canonical pathways by diabetes in both tissues. The findings of the present study provide a global proteomics view of markers that highlight the mechanisms and putative processes that modulate renal and vascular injury in diabetes. PMID:29121074

Proteome profiling in the aorta and kidney of type 1 diabetic rats.

PubMed

Al Hariri, Moustafa; Elmedawar, Mohamad; Zhu, Rui; Jaffa, Miran A; Zhao, Jingfu; Mirzaei, Parvin; Ahmed, Adnan; Kobeissy, Firas; Ziyadeh, Fuad N; Mechref, Yehia; Jaffa, Ayad A

2017-01-01

Diabetes is associated with a number of metabolic and cardiovascular risk factors that contribute to a high rate of microvascular and macrovascular complications. The risk factors and mechanisms that contribute to the development of micro- and macrovascular disease in diabetes are not fully explained. In this study, we employed mass spectrometric analysis using tandem LC-MS/MS to generate a proteomic profile of protein abundance and post-translational modifications (PTM) in the aorta and kidney of diabetic rats. In addition, systems biology analyses were employed to identify key protein markers that can provide insights into molecular pathways and processes that are differentially regulated in the aorta and kidney of type 1 diabetic rats. Our results indicated that 188 (111 downregulated and 77 upregulated) proteins were significantly identified in the aorta of diabetic rats compared to normal controls. A total of 223 (109 downregulated and 114 upregulated) proteins were significantly identified in the kidney of diabetic rats compared to normal controls. When the protein profiles from the kidney and aorta of diabetic and control rats were analyzed by principal component analysis, a distinct separation of the groups was observed. In addition, diabetes resulted in a significant increase in PTM (oxidation, phosphorylation, and acetylation) of proteins in the kidney and aorta and this effect was partially reversed by insulin treatment. Ingenuity pathway analysis performed on the list of differentially expressed proteins depicted mitochondrial dysfunction, oxidative phosphorylation and acute phase response signaling to be among the altered canonical pathways by diabetes in both tissues. The findings of the present study provide a global proteomics view of markers that highlight the mechanisms and putative processes that modulate renal and vascular injury in diabetes.

Exercise and CKD: Skeletal Muscle Dysfunction and Practical Application of Exercise to Prevent and Treat Physical Impairments in CKD.

PubMed

Roshanravan, Baback; Gamboa, Jorge; Wilund, Kenneth

2017-06-01

Patients with chronic kidney disease experience substantial loss of muscle mass, weakness, and poor physical performance. As kidney disease progresses, skeletal muscle dysfunction forms a common pathway for mobility limitation, loss of functional independence, and vulnerability to disease complications. Screening for those at high risk for mobility disability by self-reported and objective measures of function is an essential first step in developing an interdisciplinary approach to treatment that includes rehabilitative therapies and counseling on physical activity. Exercise has beneficial effects on systemic inflammation, muscle, and physical performance in chronic kidney disease. Kidney health providers need to identify patient and care delivery barriers to exercise in order to effectively counsel patients on physical activity. A thorough medical evaluation and assessment of baseline function using self-reported and objective function assessment is essential to guide an effective individualized exercise prescription to prevent function decline in persons with kidney disease. This review focuses on the impact of kidney disease on skeletal muscle dysfunction in the context of the disablement process and reviews screening and treatment strategies that kidney health professionals can use in clinical practice to prevent functional decline and disability. Copyright © 2017 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.

Role of Uremic Toxins for Kidney, Cardiovascular, and Bone Dysfunction.

PubMed

Fujii, Hideki; Goto, Shunsuke; Fukagawa, Masafumi

2018-05-16

With decreasing kidney function, cardiovascular disease (CVD) and mineral bone disorders frequently emerge in patients with chronic kidney disease (CKD). For these patients, in addition to the traditional risk factors, non-traditional CKD-specific risk factors are also associated with such diseases and conditions. One of these non-traditional risk factors is the accumulation of uremic toxins (UTs). In addition, the accumulation of UTs further deteriorates kidney function. Recently, a huge number of UTs have been identified. Although many experimental and clinical studies have reported associations between UTs and the progression of CKD, CVD, and bone disease, these relationships are very complex and have not been fully elucidated. Among the UTs, indoxyl sulfate, asymmetric dimethylarginine, and p -cresylsulfate have been of particular focus, up until now. In this review, we summarize the pathophysiological influences of these UTs on the kidney, cardiovascular system, and bone, and discuss the clinical data regarding the harmful effects of these UTs on diseases and conditions.

Developing an Android-Based Patient Decision Aid Based on Ottawa Standards for Patients After Kidney Transplant and Its Usability Evaluation.

PubMed

Zare Moayedi, Mahboobeh; Aslani, Azam; Fakhrahmad, Mostafa; Ezzatzadegan J, Shahrokh

2018-01-01

This study was conducted to develop an android based patient decision aid (PDA) as a self-care instrument for patients after kidney transplant and its usability evaluation. In this study, the systematic development process of Android-based self-care application for patients after kidney transplant based on Ottawa standard was included: scoping, assemble steering group, analysis of requirements, designing, develop of a prototype and system evaluation. The PDA is a self-triage system that will help early identification of risk symptoms in patients, and help manage them. System recommendations for risk signs are: Refer to the nearest hospital or healthcare center without delay, refer to the doctor and tell your doctor in the next visit. To identify patient care needs, a semi-structured interview with members of steering group, including patients and clinical experts, was conducted by the researchers. A prototype of the decision aid was made according to identified needs in the previous step. Finally, in order to evaluate its usability rate by using the System Usability Scale (SUS) questionnaire, it was used by exerts and patients. This study identified information needs, risk signs and steps that patients need to make appropriate decisions about them. The main capabilities of the decision aid are features such as reminders for appointment/test, time of taking medication, registration of symptoms, weight, blood pressure, body temperature, advising to patient in case of signs of risk, weight, blood pressure, body temperature and test results which were reported in the diagram. The mean score of system's usability evaluated by medical informatics specialists, clinicians, and patients were 88.33, 95, and 91. PDAs was usable and desirable from the point of view of medical informatics specialists, clinicians and patients.

Risk factors for CKD in persons with kidney stones: a case-control study in Olmsted County, Minnesota.

PubMed

Saucier, Nathan A; Sinha, Mukesh K; Liang, Kelly V; Krambeck, Amy E; Weaver, Amy L; Bergstralh, Eric J; Li, Xujian; Rule, Andrew D; Lieske, John C

2010-01-01

Kidney stones are associated with increased risk of chronic kidney disease (CKD); however, risk factors in the general community are poorly defined. A nested case-control study was performed in residents of Olmsted County, MN, who presented with a kidney stone at the Mayo Clinic in 1980-1994 to contrast patients with kidney stones who developed CKD with a group that did not. Participants were selected from the Rochester Epidemiology Project, an electronic linkage system among health care providers in Olmsted County, MN. Cases were identified by diagnostic code for CKD and confirmed to have an estimated glomerular filtration rate < 60 mL/min/1.73 m(2). Controls were matched 2:1 to cases for age, sex, date of first kidney stone, and length of medical record. Charts were abstracted to characterize stone disease, hypertension, diabetes, obesity, tobacco use, ileal conduit, symptomatic stones, type and number of stones, urinary tract infections, number and type of surgical procedures, and medical therapy. Kidney stone patients with CKD were compared with matched stone patients without CKD. There were 53 cases and 106 controls with a mean age of 57 years at first stone event and 59% men. In kidney stone patients, cases with CKD were significantly more likely (P < 0.05) than controls to have had a history of diabetes (41.5% vs 17.0%), hypertension (71.7% vs 49.1%), frequent urinary tract infections (22.6% vs 6.6%), struvite stones (7.5% vs 0%), and allopurinol use (32.1% vs 4.7%) based on univariate analysis. Potential limitations include limited statistical power to detect associations, incomplete data from 24-hour urine studies, and that stone composition was not always available. As in the general population, hypertension and diabetes are associated with increased risk of CKD in patients with kidney stones. However, other unique predictors were identified in patients with kidney stones that increased the possibility of CKD. Further studies are warranted to elucidate the nature of these associations. Copyright 2009 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.

Metabolomic Perfusate Analysis during Kidney Machine Perfusion: The Pig Provides an Appropriate Model for Human Studies

PubMed Central

Nath, Jay; Guy, Alison; Smith, Thomas B.; Cobbold, Mark; Inston, Nicholas G.; Hodson, James; Tennant, Daniel A.

2014-01-01

Introduction Hypothermic machine perfusion offers great promise in kidney transplantation and experimental studies are needed to establish the optimal conditions for this to occur. Pig kidneys are considered to be a good model for this purpose and share many properties with human organs. However it is not established whether the metabolism of pig kidneys in such hypothermic hypoxic conditions is comparable to human organs. Methods Standard criteria human (n = 12) and porcine (n = 10) kidneys underwent HMP using the LifePort Kidney Transporter 1.0 (Organ Recovery Systems) using KPS-1 solution. Perfusate was sampled at 45 minutes and 4 hours of perfusion and metabolomic analysis performed using 1-D 1H-NMR spectroscopy. Results There was no inter-species difference in the number of metabolites identified. Of the 30 metabolites analysed, 16 (53.3%) were present in comparable concentrations in the pig and human kidney perfusates. The rate of change of concentration for 3-Hydroxybutyrate was greater for human kidneys (p<0.001). For the other 29 metabolites (96.7%), there was no difference in the rate of change of concentration between pig and human samples. Conclusions Whilst there are some differences between pig and human kidneys during HMP they appear to be metabolically similar and the pig seems to be a valid model for human studies. PMID:25502759

Common and rare variants associated with kidney stones and biochemical traits

PubMed Central

Oddsson, Asmundur; Sulem, Patrick; Helgason, Hannes; Edvardsson, Vidar O.; Thorleifsson, Gudmar; Sveinbjörnsson, Gardar; Haraldsdottir, Eik; Eyjolfsson, Gudmundur I.; Sigurdardottir, Olof; Olafsson, Isleifur; Masson, Gisli; Holm, Hilma; Gudbjartsson, Daniel F.; Thorsteinsdottir, Unnur; Indridason, Olafur S.; Palsson, Runolfur; Stefansson, Kari

2015-01-01

Kidney stone disease is a complex disorder with a strong genetic component. We conducted a genome-wide association study of 28.3 million sequence variants detected through whole-genome sequencing of 2,636 Icelanders that were imputed into 5,419 kidney stone cases, including 2,172 cases with a history of recurrent kidney stones, and 279,870 controls. We identify sequence variants associating with kidney stones at ALPL (rs1256328[T], odds ratio (OR)=1.21, P=5.8 × 10−10) and a suggestive association at CASR (rs7627468[A], OR=1.16, P=2.0 × 10−8). Focusing our analysis on coding sequence variants in 63 genes with preferential kidney expression we identify two rare missense variants SLC34A1 p.Tyr489Cys (OR=2.38, P=2.8 × 10−5) and TRPV5 p.Leu530Arg (OR=3.62, P=4.1 × 10−5) associating with recurrent kidney stones. We also observe associations of the identified kidney stone variants with biochemical traits in a large population set, indicating potential biological mechanism. PMID:26272126

Common and rare variants associated with kidney stones and biochemical traits.

PubMed

Oddsson, Asmundur; Sulem, Patrick; Helgason, Hannes; Edvardsson, Vidar O; Thorleifsson, Gudmar; Sveinbjörnsson, Gardar; Haraldsdottir, Eik; Eyjolfsson, Gudmundur I; Sigurdardottir, Olof; Olafsson, Isleifur; Masson, Gisli; Holm, Hilma; Gudbjartsson, Daniel F; Thorsteinsdottir, Unnur; Indridason, Olafur S; Palsson, Runolfur; Stefansson, Kari

2015-08-14

Kidney stone disease is a complex disorder with a strong genetic component. We conducted a genome-wide association study of 28.3 million sequence variants detected through whole-genome sequencing of 2,636 Icelanders that were imputed into 5,419 kidney stone cases, including 2,172 cases with a history of recurrent kidney stones, and 279,870 controls. We identify sequence variants associating with kidney stones at ALPL (rs1256328[T], odds ratio (OR)=1.21, P=5.8 × 10(-10)) and a suggestive association at CASR (rs7627468[A], OR=1.16, P=2.0 × 10(-8)). Focusing our analysis on coding sequence variants in 63 genes with preferential kidney expression we identify two rare missense variants SLC34A1 p.Tyr489Cys (OR=2.38, P=2.8 × 10(-5)) and TRPV5 p.Leu530Arg (OR=3.62, P=4.1 × 10(-5)) associating with recurrent kidney stones. We also observe associations of the identified kidney stone variants with biochemical traits in a large population set, indicating potential biological mechanism.

Inter-rater reliability of postnatal ultrasound interpretation in infants with congenital hydronephrosis.

PubMed

Vemulakonda, V M; Wilcox, D T; Torok, M R; Hou, A; Campbell, J B; Kempe, A

2015-09-01

The most common measurements of hydronephrosis are the anterior-posterior (AP) diameter and the Society for Fetal Urology (SFU) grading systems. To date, the inter-rater reliability (IRR) of these measures has not been compared in the postnatal period. The objectives of this study were to compare the IRR of the AP diameter and the SFU grading system in infants and to determine whether ultrasound findings other than pelvicalyceal dilation are associated with higher SFU grades. Initial postnatal ultrasounds of infants seen from February 1, 2011, to January 31, 2012, with a primary diagnosis of congenital hydronephrosis were included for review. Ultrasound images were de-identified and reviewed by four pediatric urologists. IRR was calculated using the intraclass correlation (ICC) measure. A paired t test was used to compare ICCs. Associations between SFU grade and other ultrasound findings were tested using Chi-square or Fisher's exact tests. A total of 112 kidneys in 56 patients were reviewed. IRR of the SFU grading system was high (right kidney ICC = 0.83, left kidney ICC = 0.85); however, IRR of AP diameter measurement was higher (right kidney ICC = 00.97, left kidney ICC = 0.98; p < 0.001). Renal asymmetry (p < 0.001), echogenicity (p < 0.001), and parenchymal thinning (p < 0.001) were significantly associated with SFU grade 4 hydronephrosis on bivariable and multivariable analysis. The SFU grading system is associated with excellent IRR, although the AP diameter appears to have higher IRR. Physicians may consider ultrasound findings that are not explicitly included in the SFU system when assigning hydronephrosis grade, which may lead to variability in use of this classification system.

Exploratory Cluster Analysis to Identify Patterns of Chronic Kidney Disease in the 500 Cities Project.

PubMed

Liu, Shelley H; Li, Yan; Liu, Bian

2018-05-17

Chronic kidney disease is a leading cause of death in the United States. We used cluster analysis to explore patterns of chronic kidney disease in 500 of the largest US cities. After adjusting for socio-demographic characteristics, we found that unhealthy behaviors, prevention measures, and health outcomes related to chronic kidney disease differ between cities in Utah and those in the rest of the United States. Cluster analysis can be useful for identifying geographic regions that may have important policy implications for preventing chronic kidney disease.

Genetic associations at 53 loci highlight cell types and biological pathways relevant for kidney function.

PubMed

Pattaro, Cristian; Teumer, Alexander; Gorski, Mathias; Chu, Audrey Y; Li, Man; Mijatovic, Vladan; Garnaas, Maija; Tin, Adrienne; Sorice, Rossella; Li, Yong; Taliun, Daniel; Olden, Matthias; Foster, Meredith; Yang, Qiong; Chen, Ming-Huei; Pers, Tune H; Johnson, Andrew D; Ko, Yi-An; Fuchsberger, Christian; Tayo, Bamidele; Nalls, Michael; Feitosa, Mary F; Isaacs, Aaron; Dehghan, Abbas; d'Adamo, Pio; Adeyemo, Adebowale; Dieffenbach, Aida Karina; Zonderman, Alan B; Nolte, Ilja M; van der Most, Peter J; Wright, Alan F; Shuldiner, Alan R; Morrison, Alanna C; Hofman, Albert; Smith, Albert V; Dreisbach, Albert W; Franke, Andre; Uitterlinden, Andre G; Metspalu, Andres; Tonjes, Anke; Lupo, Antonio; Robino, Antonietta; Johansson, Åsa; Demirkan, Ayse; Kollerits, Barbara; Freedman, Barry I; Ponte, Belen; Oostra, Ben A; Paulweber, Bernhard; Krämer, Bernhard K; Mitchell, Braxton D; Buckley, Brendan M; Peralta, Carmen A; Hayward, Caroline; Helmer, Catherine; Rotimi, Charles N; Shaffer, Christian M; Müller, Christian; Sala, Cinzia; van Duijn, Cornelia M; Saint-Pierre, Aude; Ackermann, Daniel; Shriner, Daniel; Ruggiero, Daniela; Toniolo, Daniela; Lu, Yingchang; Cusi, Daniele; Czamara, Darina; Ellinghaus, David; Siscovick, David S; Ruderfer, Douglas; Gieger, Christian; Grallert, Harald; Rochtchina, Elena; Atkinson, Elizabeth J; Holliday, Elizabeth G; Boerwinkle, Eric; Salvi, Erika; Bottinger, Erwin P; Murgia, Federico; Rivadeneira, Fernando; Ernst, Florian; Kronenberg, Florian; Hu, Frank B; Navis, Gerjan J; Curhan, Gary C; Ehret, George B; Homuth, Georg; Coassin, Stefan; Thun, Gian-Andri; Pistis, Giorgio; Gambaro, Giovanni; Malerba, Giovanni; Montgomery, Grant W; Eiriksdottir, Gudny; Jacobs, Gunnar; Li, Guo; Wichmann, H-Erich; Campbell, Harry; Schmidt, Helena; Wallaschofski, Henri; Völzke, Henry; Brenner, Hermann; Kroemer, Heyo K; Kramer, Holly; Lin, Honghuang; Leach, I Mateo; Ford, Ian; Guessous, Idris; Rudan, Igor; Prokopenko, Inga; Borecki, Ingrid; Heid, Iris M; Kolcic, Ivana; Persico, Ivana; Jukema, J Wouter; Wilson, James F; Felix, Janine F; Divers, Jasmin; Lambert, Jean-Charles; Stafford, Jeanette M; Gaspoz, Jean-Michel; Smith, Jennifer A; Faul, Jessica D; Wang, Jie Jin; Ding, Jingzhong; Hirschhorn, Joel N; Attia, John; Whitfield, John B; Chalmers, John; Viikari, Jorma; Coresh, Josef; Denny, Joshua C; Karjalainen, Juha; Fernandes, Jyotika K; Endlich, Karlhans; Butterbach, Katja; Keene, Keith L; Lohman, Kurt; Portas, Laura; Launer, Lenore J; Lyytikäinen, Leo-Pekka; Yengo, Loic; Franke, Lude; Ferrucci, Luigi; Rose, Lynda M; Kedenko, Lyudmyla; Rao, Madhumathi; Struchalin, Maksim; Kleber, Marcus E; Cavalieri, Margherita; Haun, Margot; Cornelis, Marilyn C; Ciullo, Marina; Pirastu, Mario; de Andrade, Mariza; McEvoy, Mark A; Woodward, Mark; Adam, Martin; Cocca, Massimiliano; Nauck, Matthias; Imboden, Medea; Waldenberger, Melanie; Pruijm, Menno; Metzger, Marie; Stumvoll, Michael; Evans, Michele K; Sale, Michele M; Kähönen, Mika; Boban, Mladen; Bochud, Murielle; Rheinberger, Myriam; Verweij, Niek; Bouatia-Naji, Nabila; Martin, Nicholas G; Hastie, Nick; Probst-Hensch, Nicole; Soranzo, Nicole; Devuyst, Olivier; Raitakari, Olli; Gottesman, Omri; Franco, Oscar H; Polasek, Ozren; Gasparini, Paolo; Munroe, Patricia B; Ridker, Paul M; Mitchell, Paul; Muntner, Paul; Meisinger, Christa; Smit, Johannes H; Kovacs, Peter; Wild, Philipp S; Froguel, Philippe; Rettig, Rainer; Mägi, Reedik; Biffar, Reiner; Schmidt, Reinhold; Middelberg, Rita P S; Carroll, Robert J; Penninx, Brenda W; Scott, Rodney J; Katz, Ronit; Sedaghat, Sanaz; Wild, Sarah H; Kardia, Sharon L R; Ulivi, Sheila; Hwang, Shih-Jen; Enroth, Stefan; Kloiber, Stefan; Trompet, Stella; Stengel, Benedicte; Hancock, Stephen J; Turner, Stephen T; Rosas, Sylvia E; Stracke, Sylvia; Harris, Tamara B; Zeller, Tanja; Zemunik, Tatijana; Lehtimäki, Terho; Illig, Thomas; Aspelund, Thor; Nikopensius, Tiit; Esko, Tonu; Tanaka, Toshiko; Gyllensten, Ulf; Völker, Uwe; Emilsson, Valur; Vitart, Veronique; Aalto, Ville; Gudnason, Vilmundur; Chouraki, Vincent; Chen, Wei-Min; Igl, Wilmar; März, Winfried; Koenig, Wolfgang; Lieb, Wolfgang; Loos, Ruth J F; Liu, Yongmei; Snieder, Harold; Pramstaller, Peter P; Parsa, Afshin; O'Connell, Jeffrey R; Susztak, Katalin; Hamet, Pavel; Tremblay, Johanne; de Boer, Ian H; Böger, Carsten A; Goessling, Wolfram; Chasman, Daniel I; Köttgen, Anna; Kao, W H Linda; Fox, Caroline S

2016-01-21

Reduced glomerular filtration rate defines chronic kidney disease and is associated with cardiovascular and all-cause mortality. We conducted a meta-analysis of genome-wide association studies for estimated glomerular filtration rate (eGFR), combining data across 133,413 individuals with replication in up to 42,166 individuals. We identify 24 new and confirm 29 previously identified loci. Of these 53 loci, 19 associate with eGFR among individuals with diabetes. Using bioinformatics, we show that identified genes at eGFR loci are enriched for expression in kidney tissues and in pathways relevant for kidney development and transmembrane transporter activity, kidney structure, and regulation of glucose metabolism. Chromatin state mapping and DNase I hypersensitivity analyses across adult tissues demonstrate preferential mapping of associated variants to regulatory regions in kidney but not extra-renal tissues. These findings suggest that genetic determinants of eGFR are mediated largely through direct effects within the kidney and highlight important cell types and biological pathways.

Genetic associations at 53 loci highlight cell types and biological pathways relevant for kidney function

PubMed Central

Pattaro, Cristian; Teumer, Alexander; Gorski, Mathias; Chu, Audrey Y.; Li, Man; Mijatovic, Vladan; Garnaas, Maija; Tin, Adrienne; Sorice, Rossella; Li, Yong; Taliun, Daniel; Olden, Matthias; Foster, Meredith; Yang, Qiong; Chen, Ming-Huei; Pers, Tune H.; Johnson, Andrew D.; Ko, Yi-An; Fuchsberger, Christian; Tayo, Bamidele; Nalls, Michael; Feitosa, Mary F.; Isaacs, Aaron; Dehghan, Abbas; d'Adamo, Pio; Adeyemo, Adebowale; Dieffenbach, Aida Karina; Zonderman, Alan B.; Nolte, Ilja M.; van der Most, Peter J.; Wright, Alan F.; Shuldiner, Alan R.; Morrison, Alanna C.; Hofman, Albert; Smith, Albert V.; Dreisbach, Albert W.; Franke, Andre; Uitterlinden, Andre G.; Metspalu, Andres; Tonjes, Anke; Lupo, Antonio; Robino, Antonietta; Johansson, Åsa; Demirkan, Ayse; Kollerits, Barbara; Freedman, Barry I.; Ponte, Belen; Oostra, Ben A.; Paulweber, Bernhard; Krämer, Bernhard K.; Mitchell, Braxton D.; Buckley, Brendan M.; Peralta, Carmen A.; Hayward, Caroline; Helmer, Catherine; Rotimi, Charles N.; Shaffer, Christian M.; Müller, Christian; Sala, Cinzia; van Duijn, Cornelia M.; Saint-Pierre, Aude; Ackermann, Daniel; Shriner, Daniel; Ruggiero, Daniela; Toniolo, Daniela; Lu, Yingchang; Cusi, Daniele; Czamara, Darina; Ellinghaus, David; Siscovick, David S.; Ruderfer, Douglas; Gieger, Christian; Grallert, Harald; Rochtchina, Elena; Atkinson, Elizabeth J.; Holliday, Elizabeth G.; Boerwinkle, Eric; Salvi, Erika; Bottinger, Erwin P.; Murgia, Federico; Rivadeneira, Fernando; Ernst, Florian; Kronenberg, Florian; Hu, Frank B.; Navis, Gerjan J.; Curhan, Gary C.; Ehret, George B.; Homuth, Georg; Coassin, Stefan; Thun, Gian-Andri; Pistis, Giorgio; Gambaro, Giovanni; Malerba, Giovanni; Montgomery, Grant W.; Eiriksdottir, Gudny; Jacobs, Gunnar; Li, Guo; Wichmann, H-Erich; Campbell, Harry; Schmidt, Helena; Wallaschofski, Henri; Völzke, Henry; Brenner, Hermann; Kroemer, Heyo K.; Kramer, Holly; Lin, Honghuang; Leach, I. Mateo; Ford, Ian; Guessous, Idris; Rudan, Igor; Prokopenko, Inga; Borecki, Ingrid; Heid, Iris M.; Kolcic, Ivana; Persico, Ivana; Jukema, J. Wouter; Wilson, James F.; Felix, Janine F.; Divers, Jasmin; Lambert, Jean-Charles; Stafford, Jeanette M.; Gaspoz, Jean-Michel; Smith, Jennifer A.; Faul, Jessica D.; Wang, Jie Jin; Ding, Jingzhong; Hirschhorn, Joel N.; Attia, John; Whitfield, John B.; Chalmers, John; Viikari, Jorma; Coresh, Josef; Denny, Joshua C.; Karjalainen, Juha; Fernandes, Jyotika K.; Endlich, Karlhans; Butterbach, Katja; Keene, Keith L.; Lohman, Kurt; Portas, Laura; Launer, Lenore J.; Lyytikäinen, Leo-Pekka; Yengo, Loic; Franke, Lude; Ferrucci, Luigi; Rose, Lynda M.; Kedenko, Lyudmyla; Rao, Madhumathi; Struchalin, Maksim; Kleber, Marcus E.; Cavalieri, Margherita; Haun, Margot; Cornelis, Marilyn C.; Ciullo, Marina; Pirastu, Mario; de Andrade, Mariza; McEvoy, Mark A.; Woodward, Mark; Adam, Martin; Cocca, Massimiliano; Nauck, Matthias; Imboden, Medea; Waldenberger, Melanie; Pruijm, Menno; Metzger, Marie; Stumvoll, Michael; Evans, Michele K.; Sale, Michele M.; Kähönen, Mika; Boban, Mladen; Bochud, Murielle; Rheinberger, Myriam; Verweij, Niek; Bouatia-Naji, Nabila; Martin, Nicholas G.; Hastie, Nick; Probst-Hensch, Nicole; Soranzo, Nicole; Devuyst, Olivier; Raitakari, Olli; Gottesman, Omri; Franco, Oscar H.; Polasek, Ozren; Gasparini, Paolo; Munroe, Patricia B.; Ridker, Paul M.; Mitchell, Paul; Muntner, Paul; Meisinger, Christa; Smit, Johannes H.; Abecasis, Goncalo R.; Adair, Linda S.; Alexander, Myriam; Altshuler, David; Amin, Najaf; Arking, Dan E.; Arora, Pankaj; Aulchenko, Yurii; Bakker, Stephan J. L.; Bandinelli, Stefania; Barroso, Ines; Beckmann, Jacques S.; Beilby, John P.; Bergman, Richard N.; Bergmann, Sven; Bis, Joshua C.; Boehnke, Michael; Bonnycastle, Lori L.; Bornstein, Stefan R.; Bots, Michiel L.; Bragg-Gresham, Jennifer L.; Brand, Stefan-Martin; Brand, Eva; Braund, Peter S.; Brown, Morris J.; Burton, Paul R.; Casas, Juan P.; Caulfield, Mark J.; Chakravarti, Aravinda; Chambers, John C.; Chandak, Giriraj R.; Chang, Yen-Pei C.; Charchar, Fadi J.; Chaturvedi, Nish; Shin Cho, Yoon; Clarke, Robert; Collins, Francis S.; Collins, Rory; Connell, John M.; Cooper, Jackie A.; Cooper, Matthew N.; Cooper, Richard S.; Corsi, Anna Maria; Dörr, Marcus; Dahgam, Santosh; Danesh, John; Smith, George Davey; Day, Ian N. M.; Deloukas, Panos; Denniff, Matthew; Dominiczak, Anna F.; Dong, Yanbin; Doumatey, Ayo; Elliott, Paul; Elosua, Roberto; Erdmann, Jeanette; Eyheramendy, Susana; Farrall, Martin; Fava, Cristiano; Forrester, Terrence; Fowkes, F. Gerald R.; Fox, Ervin R.; Frayling, Timothy M.; Galan, Pilar; Ganesh, Santhi K.; Garcia, Melissa; Gaunt, Tom R.; Glazer, Nicole L.; Go, Min Jin; Goel, Anuj; Grässler, Jürgen; Grobbee, Diederick E.; Groop, Leif; Guarrera, Simonetta; Guo, Xiuqing; Hadley, David; Hamsten, Anders; Han, Bok-Ghee; Hardy, Rebecca; Hartikainen, Anna-Liisa; Heath, Simon; Heckbert, Susan R.; Hedblad, Bo; Hercberg, Serge; Hernandez, Dena; Hicks, Andrew A.; Hilton, Gina; Hingorani, Aroon D.; Bolton, Judith A Hoffman; Hopewell, Jemma C.; Howard, Philip; Humphries, Steve E.; Hunt, Steven C.; Hveem, Kristian; Ikram, M. Arfan; Islam, Muhammad; Iwai, Naoharu; Jarvelin, Marjo-Riitta; Jackson, Anne U.; Jafar, Tazeen H.; Janipalli, Charles S.; Johnson, Toby; Kathiresan, Sekar; Khaw, Kay-Tee; Kim, Hyung-Lae; Kinra, Sanjay; Kita, Yoshikuni; Kivimaki, Mika; Kooner, Jaspal S.; Kumar, M. J. Kranthi; Kuh, Diana; Kulkarni, Smita R.; Kumari, Meena; Kuusisto, Johanna; Kuznetsova, Tatiana; Laakso, Markku; Laan, Maris; Laitinen, Jaana; Lakatta, Edward G.; Langefeld, Carl D.; Larson, Martin G.; Lathrop, Mark; Lawlor, Debbie A.; Lawrence, Robert W.; Lee, Jong-Young; Lee, Nanette R.; Levy, Daniel; Li, Yali; Longstreth, Will T.; Luan, Jian'an; Lucas, Gavin; Ludwig, Barbara; Mangino, Massimo; Mani, K. Radha; Marmot, Michael G.; Mattace-Raso, Francesco U. S.; Matullo, Giuseppe; McArdle, Wendy L.; McKenzie, Colin A.; Meitinger, Thomas; Melander, Olle; Meneton, Pierre; Meschia, James F.; Miki, Tetsuro; Milaneschi, Yuri; Mohlke, Karen L.; Mooser, Vincent; Morken, Mario A.; Morris, Richard W.; Mosley, Thomas H.; Najjar, Samer; Narisu, Narisu; Newton-Cheh, Christopher; Nguyen, Khanh-Dung Hoang; Nilsson, Peter; Nyberg, Fredrik; O'Donnell, Christopher J.; Ogihara, Toshio; Ohkubo, Takayoshi; Okamura, Tomonori; Ong, RickTwee-Hee; Ongen, Halit; Onland-Moret, N. Charlotte; O'Reilly, Paul F.; Org, Elin; Orru, Marco; Palmas, Walter; Palmen, Jutta; Palmer, Lyle J.; Palmer, Nicholette D.; Parker, Alex N.; Peden, John F.; Peltonen, Leena; Perola, Markus; Pihur, Vasyl; Platou, Carl G. P.; Plump, Andrew; Prabhakaran, Dorairajan; Psaty, Bruce M.; Raffel, Leslie J.; Rao, Dabeeru C.; Rasheed, Asif; Ricceri, Fulvio; Rice, Kenneth M.; Rosengren, Annika; Rotter, Jerome I.; Rudock, Megan E.; Sõber, Siim; Salako, Tunde; Saleheen, Danish; Salomaa, Veikko; Samani, Nilesh J.; Schwartz, Steven M.; Schwarz, Peter E. H.; Scott, Laura J.; Scott, James; Scuteri, Angelo; Sehmi, Joban S.; Seielstad, Mark; Seshadri, Sudha; Sharma, Pankaj; Shaw-Hawkins, Sue; Shi, Gang; Shrine, Nick R. G.; Sijbrands, Eric J. G.; Sim, Xueling; Singleton, Andrew; Sjögren, Marketa; Smith, Nicholas L.; Artigas, Maria Soler; Spector, Tim D.; Staessen, Jan A.; Stancakova, Alena; Steinle, Nanette I.; Strachan, David P.; Stringham, Heather M.; Sun, Yan V.; Swift, Amy J.; Tabara, Yasuharu; Tai, E-Shyong; Talmud, Philippa J.; Taylor, Andrew; Terzic, Janos; Thelle, Dag S.; Tobin, Martin D.; Tomaszewski, Maciej; Tripathy, Vikal; Tuomilehto, Jaakko; Tzoulaki, Ioanna; Uda, Manuela; Ueshima, Hirotsugu; Uiterwaal, Cuno S. P. M.; Umemura, Satoshi; van der Harst, Pim; van der Schouw, Yvonne T.; van Gilst, Wiek H.; Vartiainen, Erkki; Vasan, Ramachandran S.; Veldre, Gudrun; Verwoert, Germaine C.; Viigimaa, Margus; Vinay, D. G.; Vineis, Paolo; Voight, Benjamin F.; Vollenweider, Peter; Wagenknecht, Lynne E.; Wain, Louise V.; Wang, Xiaoling; Wang, Thomas J.; Wareham, Nicholas J.; Watkins, Hugh; Weder, Alan B.; Whincup, Peter H.; Wiggins, Kerri L.; Witteman, Jacqueline C. M.; Wong, Andrew; Wu, Ying; Yajnik, Chittaranjan S.; Yao, Jie; Young, J. H.; Zelenika, Diana; Zhai, Guangju; Zhang, Weihua; Zhang, Feng; Zhao, Jing Hua; Zhu, Haidong; Zhu, Xiaofeng; Zitting, Paavo; Zukowska-Szczechowska, Ewa; Okada, Yukinori; Wu, Jer-Yuarn; Gu, Dongfeng; Takeuchi, Fumihiko; Takahashi, Atsushi; Maeda, Shiro; Tsunoda, Tatsuhiko; Chen, Peng; Lim, Su-Chi; Wong, Tien-Yin; Liu, Jianjun; Young, Terri L.; Aung, Tin; Teo, Yik-Ying; Kim, Young Jin; Kang, Daehee; Chen, Chien-Hsiun; Tsai, Fuu-Jen; Chang, Li-Ching; Fann, S. -J. Cathy; Mei, Hao; Hixson, James E.; Chen, Shufeng; Katsuya, Tomohiro; Isono, Masato; Albrecht, Eva; Yamamoto, Kazuhiko; Kubo, Michiaki; Nakamura, Yusuke; Kamatani, Naoyuki; Kato, Norihiro; He, Jiang; Chen, Yuan-Tsong; Tanaka, Toshihiro; Reilly, Muredach P; Schunkert, Heribert; Assimes, Themistocles L.; Hall, Alistair; Hengstenberg, Christian; König, Inke R.; Laaksonen, Reijo; McPherson, Ruth; Thompson, John R.; Thorsteinsdottir, Unnur; Ziegler, Andreas; Absher, Devin; Chen, Li; Cupples13, L. Adrienne; Halperin, Eran; Li, Mingyao; Musunuru, Kiran; Preuss, Michael; Schillert, Arne; Thorleifsson, Gudmar; Wells, George A.; Holm, Hilma; Roberts, Robert; Stewart, Alexandre F. R.; Fortmann, Stephen; Go, Alan; Hlatky, Mark; Iribarren, Carlos; Knowles, Joshua; Myers, Richard; Quertermous, Thomas; Sidney, Steven; Risch, Neil; Tang, Hua; Blankenberg, Stefan; Schnabel, Renate; Sinning, Christoph; Lackner, Karl J.; Tiret, Laurence; Nicaud, Viviane; Cambien, Francois; Bickel, Christoph; Rupprecht, Hans J.; Perret, Claire; Proust, Carole; Münzel, Thomas F.; Barbalic, Maja; Chen, Ida Yii-Der; Demissie-Banjaw, Serkalem; Folsom, Aaron; Lumley, Thomas; Marciante, Kristin; Taylor, Kent D.; Volcik, Kelly; Gretarsdottir, Solveig; Gulcher, Jeffrey R.; Kong, Augustine; Stefansson, Kari; Thorgeirsson, Gudmundur; Andersen, Karl; Fischer, Marcus; Grosshennig, Anika; Linsel-Nitschke, Patrick; Stark, Klaus; Schreiber, Stefan; Aherrahrou, Zouhair; Bruse, Petra; Doering, Angela; Klopp, Norman; Diemert, Patrick; Loley, Christina; Medack, Anja; Nahrstedt, Janja; Peters, Annette; Wagner, Arnika K.; Willenborg, Christina; Böhm, Bernhard O.; Dobnig, Harald; Grammer, Tanja B.; Hoffmann, Michael M.; Meinitzer, Andreas; Winkelmann, Bernhard R.; Pilz, Stefan; Renner, Wilfried; Scharnagl, Hubert; Stojakovic, Tatjana; Tomaschitz, Andreas; Winkler, Karl; Guiducci, Candace; Burtt, Noel; Gabriel, Stacey B.; Dandona, Sonny; Jarinova, Olga; Qu, Liming; Wilensky, Robert; Matthai, William; Hakonarson, Hakon H.; Devaney, Joe; Burnett, Mary Susan; Pichard, Augusto D.; Kent, Kenneth M.; Satler, Lowell; Lindsay, Joseph M.; Waksman, Ron; Knouff, Christopher W.; Waterworth, Dawn M.; Walker, Max C.; Epstein, Stephen E.; Rader, Daniel J.; Nelson, Christopher P.; Wright, Benjamin J.; Balmforth, Anthony J.; Ball, Stephen G.; Loehr, Laura R.; Rosamond, Wayne D.; Benjamin, Emelia; Haritunians, Talin; Couper, David; Murabito, Joanne; Wang, Ying A.; Stricker, Bruno H.; Chang, Patricia P.; Willerson, James T.; Felix, Stephan B.; Watzinger, Norbert; Aragam, Jayashri; Zweiker, Robert; Lind, Lars; Rodeheffer, Richard J.; Greiser, Karin Halina; Deckers, Jaap W.; Stritzke, Jan; Ingelsson, Erik; Kullo, Iftikhar; Haerting, Johannes; Reffelmann, Thorsten; Redfield, Margaret M.; Werdan, Karl; Mitchell, Gary F.; Arnett, Donna K.; Gottdiener, John S.; Blettner, Maria; Friedrich, Nele; Kovacs, Peter; Wild, Philipp S.; Froguel, Philippe; Rettig, Rainer; Mägi, Reedik; Biffar, Reiner; Schmidt, Reinhold; Middelberg, Rita P. S.; Carroll, Robert J.; Penninx, Brenda W.; Scott, Rodney J.; Katz, Ronit; Sedaghat, Sanaz; Wild, Sarah H.; Kardia, Sharon L. R.; Ulivi, Sheila; Hwang, Shih-Jen; Enroth, Stefan; Kloiber, Stefan; Trompet, Stella; Stengel, Benedicte; Hancock, Stephen J.; Turner, Stephen T.; Rosas, Sylvia E.; Stracke, Sylvia; Harris, Tamara B.; Zeller, Tanja; Zemunik, Tatijana; Lehtimäki, Terho; Illig, Thomas; Aspelund, Thor; Nikopensius, Tiit; Esko, Tonu; Tanaka, Toshiko; Gyllensten, Ulf; Völker, Uwe; Emilsson, Valur; Vitart, Veronique; Aalto, Ville; Gudnason, Vilmundur; Chouraki, Vincent; Chen, Wei-Min; Igl, Wilmar; März, Winfried; Koenig, Wolfgang; Lieb, Wolfgang; Loos, Ruth J. F.; Liu, Yongmei; Snieder, Harold; Pramstaller, Peter P.; Parsa, Afshin; O'Connell, Jeffrey R.; Susztak, Katalin; Hamet, Pavel; Tremblay, Johanne; de Boer, Ian H.; Böger, Carsten A.; Goessling, Wolfram; Chasman, Daniel I.; Köttgen, Anna; Kao, W. H. Linda; Fox, Caroline S.

2016-01-01

Reduced glomerular filtration rate defines chronic kidney disease and is associated with cardiovascular and all-cause mortality. We conducted a meta-analysis of genome-wide association studies for estimated glomerular filtration rate (eGFR), combining data across 133,413 individuals with replication in up to 42,166 individuals. We identify 24 new and confirm 29 previously identified loci. Of these 53 loci, 19 associate with eGFR among individuals with diabetes. Using bioinformatics, we show that identified genes at eGFR loci are enriched for expression in kidney tissues and in pathways relevant for kidney development and transmembrane transporter activity, kidney structure, and regulation of glucose metabolism. Chromatin state mapping and DNase I hypersensitivity analyses across adult tissues demonstrate preferential mapping of associated variants to regulatory regions in kidney but not extra-renal tissues. These findings suggest that genetic determinants of eGFR are mediated largely through direct effects within the kidney and highlight important cell types and biological pathways. PMID:26831199

An optimal serum-free defined condition for in vitro culture of kidney organoids.

PubMed

Nishikawa, Masaki; Kimura, Hiroshi; Yanagawa, Naomi; Hamon, Morgan; Hauser, Peter; Zhao, Lifu; Jo, Oak D; Yanagawa, Norimoto

2018-07-02

Kidney organoid is an emerging topic of importance for research in kidney development and regeneration. Conventional culture systems for kidney organoids reported thus far use culture media containing serum, which may compromise our understanding and the potential clinical applicability of the organoid system. In our present study, we tested two serum-free culture conditions and compared their suitability for the maintenance and growth of kidney organoids in culture. One of the serum-free culture conditions was the combination of keratinocytes serum free medium (KSFM) with knockout serum replacement (KSR) (KSFM + KSR), and the other was the combination of knockout DMEM/F12 (KD/F12) and KSR (KD/F12 + KSR). With cell aggregates derived from E12.5 mouse embryonic kidneys, we found that KD/F12 + KSR was superior to KSFM + KSR in promoting the growth of the aggregate with expansion of Six2 + nephron progenitor cells (NPC) and elaborated ureteric branching morphogenesis. With KD/F12 + KSR, we found that lower concentrations of KSR at 5-10% were superior to a higher concentration (20%) in promoting the growth of aggregates without affecting the expression levels of NPC marker genes. We also found that NPC in aggregates retained their differentiation potential to develop nephron tubules through mesenchyme-to-epithelial transition (MET), after being maintained in culture under these conditions for up to 7 days. In conclusion, we have identified a defined serum-free culture condition suitable for the maintenance and growth of kidney organoids that retain the differentiation potential to develop nephron structures. This defined serum-free culture condition may serve as a useful platform for further investigation of kidney organoids in vitro. Copyright © 2018 Elsevier Inc. All rights reserved.

Kidney dendritic cells in acute and chronic renal disease.

PubMed

Hochheiser, Katharina; Tittel, André; Kurts, Christian

2011-06-01

Dendritic cells are not only the master regulators of adaptive immunity, but also participate profoundly in innate immune responses. Much has been learned about their basic immunological functions and their roles in various diseases. Comparatively little is still known about their role in renal disease, despite their obvious potential to affect immune responses in the kidney, and immune responses that are directed against renal components. Kidney dendritic cells form an abundant network in the renal tubulointerstitium and constantly survey the environment for signs of injury or infection, in order to alert the immune system to the need to initiate defensive action. Recent studies have identified a role for dendritic cells in several murine models of acute renal injury and chronic nephritis. Here we summarize the current knowledge on the role of kidney dendritic cells that has been obtained from the study of murine models of renal disease. © 2010 The Authors. Journal compilation © 2010 Blackwell Publishing Ltd.

Estimated Glomerular Filtration Rate; Laboratory Implementation and Current Global Status.

PubMed

Miller, W Greg; Jones, Graham R D

2018-01-01

In 2002, the Kidney Disease Outcomes Quality Initiative guidelines for identifying and treating CKD recommended that clinical laboratories report estimated glomerular filtration rate (eGFR) with every creatinine result to assist clinical practitioners to identify people with early-stage CKD. At that time, the original Modification of Diet in Renal Disease (MDRD) Study equation based on serum creatinine measurements was recommended for calculating eGFR. Because the MDRD Study equation was developed using a nonstandardized creatinine method, a Laboratory Working Group of the National Kidney Disease Education program was formed and implemented standardized calibration traceability for all creatinine methods from global manufacturers by approximately 2010. A modified MDRD Study equation for use with standardized creatinine was developed. The Chronic Kidney Disease Epidemiology Collaboration developed a new equation in 2009 that was more accurate than the MDRD Study equation at values above 60 mL/min/1.73 m 2 . As of 2017, reporting eGFR with creatinine is almost universal in many countries. A reference system for cystatin C became available in 2010, and manufacturers are in the process to standardize cystatin C assays. Equations for eGFR based on standardized cystatin C alone and with creatinine are now available from the Chronic Kidney Disease Epidemiology Collaboration and other groups. Copyright © 2017 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.

Identifying Outcomes that Are Important to Living Kidney Donors: A Nominal Group Technique Study.

PubMed

Hanson, Camilla S; Chapman, Jeremy R; Gill, John S; Kanellis, John; Wong, Germaine; Craig, Jonathan C; Teixeira-Pinto, Armando; Chadban, Steve J; Garg, Amit X; Ralph, Angelique F; Pinter, Jule; Lewis, Joshua R; Tong, Allison

2018-06-07

Living kidney donor candidates accept a range of risks and benefits when they decide to proceed with nephrectomy. Informed consent around this decision assumes they receive reliable data about outcomes they regard as critical to their decision making. We identified the outcomes most important to living kidney donors and described the reasons for their choices. Previous donors were purposively sampled from three transplant units in Australia (Sydney and Melbourne) and Canada (Vancouver). In focus groups using the nominal group technique, participants identified outcomes of donation, ranked them in order of importance, and discussed the reasons for their preferences. An importance score was calculated for each outcome. Qualitative data were analyzed thematically. Across 14 groups, 123 donors aged 27-78 years identified 35 outcomes. Across all participants, the ten highest ranked outcomes were kidney function (importance=0.40, scale 0-1), time to recovery (0.27), surgical complications (0.24), effect on family (0.22), donor-recipient relationship (0.21), life satisfaction (0.18), lifestyle restrictions (0.18), kidney failure (0.14), mortality (0.13), and acute pain/discomfort (0.12). Kidney function and kidney failure were more important to Canadian participants, compared with Australian donors. The themes identified included worthwhile sacrifice, insignificance of risks and harms, confidence and empowerment, unfulfilled expectations, and heightened susceptibility. Living kidney donors prioritized a range of outcomes, with the most important being kidney health and the surgical, lifestyle, functional, and psychosocial effects of donation. Donors also valued improvements to their family life and donor-recipient relationship. There were clear regional differences in the rankings. Copyright © 2018 by the American Society of Nephrology.

Apelin/APJ system: A novel potential therapy target for kidney disease.

PubMed

Huang, Zhen; Wu, Lele; Chen, Linxi

2018-05-01

Apelin is an endogenous ligand of seven-transmembrane G protein-coupled receptor APJ. Apelin and APJ are distributed in various tissues, including the heart, lung, kidney, and even in tumor tissues. Studies show that apelin mRNA is highly expressed in the inner stripe of kidney outer medulla, which plays an important role in process of water and sodium balance. Additionally, more studies also indicate that apelin/APJ system exerts a broad range of activities in kidney. Therefore, we review the role of apelin/APJ system in kidney diseases such as renal fibrosis, renal ischemia/reperfusion injury, diabetic nephropathy, polycystic kidney disease, and hemodialysis (HD). Apelin/APJ system can improve renal interstitial fibrosis by reducing the deposition of extracellular matrix. Apelin/APJ system significantly reduces renal ischemia/reperfusion injury by inhibiting renal cell death. Apelin/APJ system involves the progression of diabetic nephropathy (DN). Apelin/APJ system also predicts the process of polycystic kidney disease. Besides, apelin/APJ system prevents some dialysis complications in HD patients. And apelin/APJ system alleviates chronic kidney disease (CKD) by inhibiting vascular calcification (VC). Overall, apelin/APJ system plays diversified roles in kidney disease and may be a potential target for the treatment of kidney disease. © 2017 Wiley Periodicals, Inc.

Predicting kidney disease progression in patients with acute kidney injury after cardiac surgery.

PubMed

Mizuguchi, K Annette; Huang, Chuan-Chin; Shempp, Ian; Wang, Justin; Shekar, Prem; Frendl, Gyorgy

2018-06-01

The study objective was to identify patients who are likely to develop progressive kidney dysfunction (acute kidney disease) before their hospital discharge after cardiac surgery, allowing targeted monitoring of kidney function in this at-risk group with periodic serum creatinine measurements. Risks of progression to acute kidney disease (a state in between acute kidney injury and chronic kidney disease) were modeled from acute kidney injury stages (Kidney Disease: Improving Global Outcomes) in patients undergoing cardiac surgery. A modified Poisson regression with robust error variance was used to evaluate the association between acute kidney injury stages and the development of acute kidney disease (defined as doubling of creatinine 2-4 weeks after surgery) in this observational study. Acute kidney disease occurred in 4.4% of patients with no preexisting kidney disease and 4.8% of patients with preexisting chronic kidney disease. Acute kidney injury predicted development of acute kidney disease in a graded manner in which higher stages of acute kidney injury predicted higher relative risk of progressive kidney disease (area under the receiver operator characteristic curve = 0.82). This correlation persisted regardless of baseline kidney function (P < .001). Of note, development of acute kidney disease was associated with higher mortality and need for renal replacement therapy. The degree of acute kidney injury can identify patients who will have a higher risk of progression to acute kidney disease. These patients may benefit from close follow-up of renal function because they are at risk of progressing to chronic kidney disease or end-stage renal disease. Copyright © 2018 The American Association for Thoracic Surgery. Published by Elsevier Inc. All rights reserved.

Depth-section imaging of swine kidney by spectrally encoded microscopy

NASA Astrophysics Data System (ADS)

Liao, Jiuling; Gao, Wanrong

2016-10-01

The kidneys are essential regulatory organs whose main function is to regulate the balance of electrolytes in the blood, along with maintaining pH homeostasis. The study of the microscopic structure of the kidney will help identify kidney diseases associated with specific renal histology change. Spectrally encoded microscopy (SEM) is a new reflectance microscopic imaging technique in which a grating is used to illuminate different positions along a line on the sample with different wavelengths, reducing the size of system and imaging time. In this paper, a SEM device is described which is based on a super luminescent diode source and a home-built spectrometer. The lateral resolution was measured by imaging the USAF resolution target. The axial response curve was obtained as a reflect mirror was scanned through the focal plane axially. In order to test the feasibility of using SEM for depth-section imaging of an excised swine kidney tissue, the images of the samples were acquired by scanning the sample at 10 μm per step along the depth direction. Architectural features of the kidney tissue could be clearly visualized in the SEM images, including glomeruli and blood vessels. Results from this study suggest that SEM may be useful for locating regions with probabilities of kidney disease or cancer.

“Maybe They Don't Even Know That I Exist”: Challenges Faced by Family Members and Friends of Patients with Advanced Kidney Disease

PubMed Central

Szarka, Jackie; McFarland, Lynne V.; Vig, Elizabeth K.; Sudore, Rebecca L.; Crowley, Susan; Reinke, Lynn F.; Trivedi, Ranak; Taylor, Janelle S.

2017-01-01

Background and objectives Family members and friends of patients with advanced chronic illness are increasingly called on to assist with ever more complex medical care and treatment decisions arising late in the course of illness. Our goal was to learn about the experiences of family members and friends of patients with advanced kidney disease. Design, setting, participants, & measurements As part of a study intended to identify opportunities to enhance advance care planning, we conducted semistructured interviews at the Veterans Affairs Puget Sound Health Care System with 17 family members and friends of patients with advanced kidney disease. Interviews were conducted between April of 2014 and May of 2016 and were audiotaped, transcribed, and analyzed inductively using grounded theory to identify emergent themes. Results The following three themes emerged from interviews with patients’ family members and friends: (1) their roles in care and planning were fluid over the course of the patient’s illness, shaped by the patients’ changing needs and their readiness to involve those close to them; (2) their involvement in patients’ care was strongly shaped by health care system needs. Family and friends described filling gaps left by the health care system and how their involvement in care and decision-making was at times constrained and at other times expected by providers, depending on system needs; and (3) they described multiple sources of tension and conflict in their interactions with patients and the health care system, including instances of being pitted against the patient. Conclusions Interviews with family members and friends of patients with advanced kidney disease provide a window on the complex dynamics shaping their engagement in patients’ care, and highlight the potential value of offering opportunities for engagement throughout the course of illness. PMID:28356337

Kidney Paired Donation and the "Valuable Consideration" Problem: The Experiences of Australia, Canada, and the United States.

PubMed

Toews, Maeghan; Giancaspro, Mark; Richards, Bernadette; Ferrari, Paolo

2017-09-01

As organ donation rates remain unable to meet the needs of individuals waiting for transplants, it is necessary to identify reasons for this shortage and develop solutions to address it. The introduction of kidney paired donation (KPD) programs represents one such innovation that has become a valuable tool in donation systems around the world. Although KPD has been successful in increasing kidney donation and transplantation, there are lingering questions about its legality. Donation through KPD is done in exchange for-and with the expectation of-a reciprocal kidney donation and transplantation. It is this reciprocity that has caused concern about whether KPD complies with existing law. Organ donation systems around the world are almost universally structured to legally prohibit the commercial exchange of organs. Australia, Canada, and the United States have accomplished this goal by prohibiting the exchange of an organ for "valuable consideration," which is a legal term that has not historically been limited to monetary exchange. Whether or not KPD programs violate this legislative prohibition will depend on the specific legislative provision being considered, and the legal system and case law of the particular jurisdiction in question. This article compares the experiences of Australia, Canada, and the United States in determining the legality of KPD and highlights the need for legal clarity and flexibility as donation and transplantation systems continue to evolve.

Living Donor Kidney Transplantation: Overcoming Disparities in Live Kidney Donation in the US—Recommendations from a Consensus Conference

PubMed Central

Rodrigue, James R.; Kazley, Abby Swanson; Mandelbrot, Didier A.; Hays, Rebecca; LaPointe Rudow, Dianne

2015-01-01

Despite its superior outcomes relative to chronic dialysis and deceased donor kidney transplantation, live donor kidney transplantation (LDKT) is less likely to occur in minorities, older adults, and poor patients than in those who are white, younger, and have higher household income. In addition, there is considerable geographic variability in LDKT rates. Concomitantly, in recent years, the rate of living kidney donation (LKD) has stopped increasing and is declining, after decades of consistent growth. Particularly noteworthy is the decline in LKD among black, younger, male, and lower-income adults. The Live Donor Community of Practice within the American Society of Transplantation, with financial support from 10 other organizations, held a Consensus Conference on Best Practices in Live Kidney Donation in June 2014. The purpose of this meeting was to identify LKD best practices and knowledge gaps that might influence LDKT, with a focus on patient and donor education, evaluation efficiencies, disparities, and systemic barriers to LKD. In this article, we discuss trends in LDKT/LKD and emerging novel strategies for attenuating disparities, and we offer specific recommendations for future clinical practice, education, research, and policy from the Consensus Conference Workgroup focused on disparities. PMID:25883072

Endoplasmic Reticulum Stress in the Diabetic Kidney, the Good, the Bad and the Ugly.

PubMed

Cunard, Robyn

2015-04-20

Diabetic kidney disease is the leading worldwide cause of end stage kidney disease and a growing public health challenge. The diabetic kidney is exposed to many environmental stressors and each cell type has developed intricate signaling systems designed to restore optimal cellular function. The unfolded protein response (UPR) is a homeostatic pathway that regulates endoplasmic reticulum (ER) membrane structure and secretory function. Studies suggest that the UPR is activated in the diabetic kidney to restore normal ER function and viability. However, when the cell is continuously stressed in an environment that lies outside of its normal physiological range, then the UPR is known as the ER stress response. The UPR reduces protein synthesis, augments the ER folding capacity and downregulates mRNA expression of genes by multiple pathways. Aberrant activation of ER stress can also induce inflammation and cellular apoptosis, and modify signaling of protective processes such as autophagy and mTORC activation. The following review will discuss our current understanding of ER stress in the diabetic kidney and explore novel means of modulating ER stress and its interacting signaling cascades with the overall goal of identifying therapeutic strategies that will improve outcomes in diabetic nephropathy.

Identification of a novel AGXT gene mutation in primary hyperoxaluria after kidney transplantation failure.

PubMed

M'dimegh, Saoussen; Omezzine, Asma; Hamida-Rebai, Mériam Ben; Aquaviva-Bourdain, Cécile; M'barek, Ibtihel; Sahtout, Wissal; Zellama, Dorsaf; Souche, Geneviéve; Achour, Abdellatif; Abroug, Saoussen; Bouslama, Ali

2016-11-01

Primary hyperoxaluria is a genetic disorder in glyoxylate metabolism that leads to systemic overproduction of oxalate. Functional deficiency of alanine-glyoxylate aminotransferase in this disease leads to recurrent nephrolithiasis, nephrocalcinosis, systemic oxalosis, and kidney failure. The aim of this study was to determine the molecular etiology of kidney transplant loss in a young Tunisian individual. We present a young man with end-stage renal disease who received a kidney allograft and experienced early graft failure. There were no improvement in kidney function; he required hemodialysis and graft biopsy revealed calcium oxalate crystals, which raised suspicion of primary hyperoxaluria. Genetic study in the AGXT gene by PCR direct sequencing identified three missense changes in heterozygote state: the p. Gly190Arg mutation next to two other novels not previously described. The classification of the deleterious effect of the missense changes was developed using the summered results of four different mutation assessment algorithms, SIFT, PolyPhen, Mutation Taster, and Align-GVGD. This system classified the changes as polymorphism in one and as mutation in other. The patient was compound heterozygous mutations. Structural analysis showed that the novel mutation, p.Pro28Ser mutation, affects near the dimerization interface of AGT and positioned on binding site instead of the inhibitor, amino-oxyacetic acid (AOA). With the novel AGXT mutation, the mutational spectrum of this gene continues to broaden in our population. The diagnosis of PH1 was not recognized until after renal transplant with fatal consequences, which led us to confirm the importance of screening before planning for kidney transplantation in population with a relatively high frequency of AGXT mutation carriers. Copyright © 2016 Elsevier B.V. All rights reserved.

[Intrarenal smooth muscle: histology of a complex urodymamic machine].

PubMed

Arias, L F; Ortiz-Arango, N

2013-03-01

To know better the microscopic arrangement of the bundles of smooth muscle in the human renal parenchyma, their distribution and anatomical relationships, trying to make a reconstruction of this muscular system. Five adult human kidneys and one fetal kidney were processed "in toto" with cross sections every 300μm. In the histological sections we identify the smooth muscle fibers trying to determine its insertion, course and anatomical relationship with other structures of the kidney tissue. There are bundles of smooth muscle fibers of variable thickness parallel to the edges of the medullary pyramids, bundles that surrounding the medulla in a spiral course, and bundles that accompany arcuate vessels, the latter being the most abundant and easy to identify. These groups of muscle fibers do not have a precise or constant insertion site, their periodicity is not homogeneous and they are not a direct extension of the muscle of the renal pelvis, although some bundles are in contact with it. There are also unusual and inconstant small muscle fibers no associated to vessels in the interstitium of the cortex and, exceptionally, in the medulla. There is a complex microscopic system of smooth muscle fibers that partially surround the renal medulla and are related to renal pelvic muscles without a direct continuity with them. Although this small muscular system is under-recognized, could be very important in urodynamics. Copyright © 2012 AEU. Published by Elsevier Espana. All rights reserved.

SIX2 and BMP4 mutations associate with anomalous kidney development.

PubMed

Weber, Stefanie; Taylor, Jaclyn C; Winyard, Paul; Baker, Kari F; Sullivan-Brown, Jessica; Schild, Raphael; Knüppel, Tanja; Zurowska, Aleksandra M; Caldas-Alfonso, Alberto; Litwin, Mieczyslaw; Emre, Sevinc; Ghiggeri, Gian Marco; Bakkaloglu, Aysin; Mehls, Otto; Antignac, Corinne; Network, Escape; Schaefer, Franz; Burdine, Rebecca D

2008-05-01

Renal hypodysplasia (RHD) is characterized by reduced kidney size and/or maldevelopment of the renal tissue following abnormal organogenesis. Mutations in renal developmental genes have been identified in a subset of affected individuals. Here, we report the first mutations in BMP4 and SIX2 identified in patients with RHD. We detected 3 BMP4 mutations in 5 RHD patients, and 3 SIX2 mutations in 5 different RHD patients. Overexpression assays in zebrafish demonstrated that these mutations affect the function of Bmp4 and Six2 in vivo. Overexpression of zebrafish six2.1 and bmp4 resulted in dorsalization and ventralization, respectively, suggesting opposing roles in mesendoderm formation. When mutant constructs containing the identified human mutations were overexpressed instead, these effects were attenuated. Morpholino knockdown of bmp4 and six2.1 affected glomerulogenesis, suggesting specific roles for these genes in the formation of the pronephros. In summary, these studies implicate conserved roles for Six2 and Bmp4 in the development of the renal system. Defects in these proteins could affect kidney development at multiple stages, leading to the congenital anomalies observed in patients with RHD.

The absence of intrarenal ACE protects against hypertension

PubMed Central

Gonzalez-Villalobos, Romer A.; Janjoulia, Tea; Fletcher, Nicholas K.; Giani, Jorge F.; Nguyen, Mien T.X.; Riquier-Brison, Anne D.; Seth, Dale M.; Fuchs, Sebastien; Eladari, Dominique; Picard, Nicolas; Bachmann, Sebastian; Delpire, Eric; Peti-Peterdi, Janos; Navar, L. Gabriel; Bernstein, Kenneth E.; McDonough, Alicia A.

2013-01-01

Activation of the intrarenal renin-angiotensin system (RAS) can elicit hypertension independently from the systemic RAS. However, the precise mechanisms by which intrarenal Ang II increases blood pressure have never been identified. To this end, we studied the responses of mice specifically lacking kidney angiotensin-converting enzyme (ACE) to experimental hypertension. Here, we show that the absence of kidney ACE substantially blunts the hypertension induced by Ang II infusion (a model of high serum Ang II) or by nitric oxide synthesis inhibition (a model of low serum Ang II). Moreover, the renal responses to high serum Ang II observed in wild-type mice, including intrarenal Ang II accumulation, sodium and water retention, and activation of ion transporters in the loop of Henle (NKCC2) and distal nephron (NCC, ENaC, and pendrin) as well as the transporter activating kinases SPAK and OSR1, were effectively prevented in mice that lack kidney ACE. These findings demonstrate that ACE metabolism plays a fundamental role in the responses of the kidney to hypertensive stimuli. In particular, renal ACE activity is required to increase local Ang II, to stimulate sodium transport in loop of Henle and the distal nephron, and to induce hypertension. PMID:23619363

Technical Evaluation: Identification of Pathogenic Mutations in PKD1 and PKD2 in Patients with Autosomal Dominant Polycystic Kidney Disease by Next-Generation Sequencing and Use of a Comprehensive New Classification System.

PubMed

Kinoshita, Moritoshi; Higashihara, Eiji; Kawano, Haruna; Higashiyama, Ryo; Koga, Daisuke; Fukui, Takafumi; Gondo, Nobuhisa; Oka, Takehiko; Kawahara, Kozo; Rigo, Krisztina; Hague, Tim; Katsuragi, Kiyonori; Sudo, Kimiyoshi; Takeshi, Masahiko; Horie, Shigeo; Nutahara, Kikuo

2016-01-01

Genetic testing of PKD1 and PKD2 is expected to play an increasingly important role in determining allelic influences in autosomal dominant polycystic kidney disease (ADPKD) in the near future. However, to date, genetic testing is not commonly employed because it is expensive, complicated because of genetic heterogeneity, and does not easily identify pathogenic variants. In this study, we developed a genetic testing system based on next-generation sequencing (NGS), long-range polymerase chain reaction, and a new software package. The new software package integrated seven databases and provided access to five cloud-based computing systems. The database integrated 241 polymorphic nonpathogenic variants detected in 140 healthy Japanese volunteers aged >35 years, who were confirmed by ultrasonography as having no cysts in either kidney. Using this system, we identified 60 novel and 30 known pathogenic mutations in 101 Japanese patients with ADPKD, with an overall detection rate of 89.1% (90/101) [95% confidence interval (CI), 83.0%-95.2%]. The sensitivity of the system increased to 93.1% (94/101) (95% CI, 88.1%-98.0%) when combined with multiplex ligation-dependent probe amplification analysis, making it sufficient for use in a clinical setting. In 82 (87.2%) of the patients, pathogenic mutations were detected in PKD1 (95% CI, 79.0%-92.5%), whereas in 12 (12.8%) patients pathogenic mutations were detected in PKD2 (95% CI, 7.5%-21.0%); this is consistent with previously reported findings. In addition, we were able to reconfirm our pathogenic mutation identification results using Sanger sequencing. In conclusion, we developed a high-sensitivity NGS-based system and successfully employed it to identify pathogenic mutations in PKD1 and PKD2 in Japanese patients with ADPKD.

Provider Perspectives on Advance Care Planning for Patients with Kidney Disease: Whose Job Is It Anyway?

PubMed

O'Hare, Ann M; Szarka, Jackie; McFarland, Lynne V; Taylor, Janelle S; Sudore, Rebecca L; Trivedi, Ranak; Reinke, Lynn F; Vig, Elizabeth K

2016-05-06

There is growing interest in efforts to enhance advance care planning for patients with kidney disease. Our goal was to elicit the perspectives on advance care planning of multidisciplinary providers who care for patients with advanced kidney disease. Between April and December of 2014, we conducted semistructured interviews at the Department of Veterans Affairs Puget Sound Health Care System with 26 providers from a range of disciplines and specialties who care for patients with advanced kidney disease. Participants were asked about their perspectives and experiences related to advance care planning in this population. Interviews were audiotaped, transcribed, and analyzed inductively using grounded theory. The comments of providers interviewed for this study spoke to significant system-level barriers to supporting the process of advance care planning for patients with advanced kidney disease. We identified four overlapping themes: (1) medical care for this population is complex and fragmented across settings and providers and over time; (2) lack of a shared understanding and vision of advance care planning and its relationship with other aspects of care, such as dialysis decision making; (3) unclear locus of responsibility and authority for advance care planning; and (4) lack of active collaboration and communication around advance care planning among different providers caring for the same patients. The comments of providers who care for patients with advanced kidney disease spotlight both the need for and the challenges to interdisciplinary collaboration around advance care planning for this population. Systematic efforts at a variety of organizational levels will likely be needed to support teamwork around advance care planning among the different providers who care for patients with advanced kidney disease. Copyright © 2016 by the American Society of Nephrology.

21 CFR 876.5880 - Isolated kidney perfusion and transport system and accessories.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 21 Food and Drugs 8 2011-04-01 2011-04-01 false Isolated kidney perfusion and transport system and....5880 Isolated kidney perfusion and transport system and accessories. (a) Identification. An isolated kidney perfusion and transport system and accesssories is a device that is used to support a donated or a...

21 CFR 876.5880 - Isolated kidney perfusion and transport system and accessories.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Isolated kidney perfusion and transport system and....5880 Isolated kidney perfusion and transport system and accessories. (a) Identification. An isolated kidney perfusion and transport system and accesssories is a device that is used to support a donated or a...

Development of a Targeted Urine Proteome Assay for kidney diseases.

PubMed

Cantley, Lloyd G; Colangelo, Christopher M; Stone, Kathryn L; Chung, Lisa; Belcher, Justin; Abbott, Thomas; Cantley, Jennifer L; Williams, Kenneth R; Parikh, Chirag R

2016-01-01

Since human urine is the most readily available biofluid whose proteome changes in response to disease, it is a logical sample for identifying protein biomarkers for kidney diseases. Potential biomarkers were identified by using a multiproteomics workflow to compare urine proteomes of kidney transplant patients with immediate and delayed graft function. Differentially expressed proteins were identified, and corresponding stable isotope labeled internal peptide standards were synthesized for scheduled MRM. The Targeted Urine Proteome Assay (TUPA) was then developed by identifying those peptides for which there were at least two transitions for which interference in a urine matrix across 156 MRM runs was <30%. This resulted in an assay that monitors 224 peptides from 167 quantifiable proteins. TUPA opens the way for using a robust mass spectrometric technology, MRM, for quantifying and validating biomarkers from among 167 urinary proteins. This approach, while developed using differentially expressed urinary proteins from patients with delayed versus immediate graft function after kidney transplant, can be expanded to include differentially expressed urinary proteins in multiple kidney diseases. Thus, TUPA could provide a single assay to help diagnose, prognose, and manage many kidney diseases. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Epidemiologic insights into pediatric kidney stone disease.

PubMed

Matlaga, Brian R; Schaeffer, Anthony J; Novak, Thomas E; Trock, Bruce J

2010-12-01

The epidemiology of pediatric kidney stone has not yet been as rigorously defined as that of adult kidney stone disease. Herein, we review our recent epidemiologic works characterizing pediatric stone disease using the Kids' Inpatient Database (KID). Specifically we investigated the age and gender distribution of pediatric kidney stone disease, changes in disease prevalence over time, and medical comorbidities associated with this disorder. We identified patients by International Classification of Disease 9th Edition (ICD-9) codes for renal and ureteral calculi as the primary diagnosis. Medical comorbidities were identified using specific comorbidity software. Statistical comparisons between children with and without stone disease were performed. In the first decade of life, stone disease was more prevalent among males than females; however, in the second decade of life females were more commonly affected. Of note, there was a significant increase in treated stone disease across both genders between 1997 and 2003. We also found that the risk of kidney stone diagnosis in children younger than 6 years of age was significantly associated with hypertension and diabetes mellitus. The gender distribution among pediatric stone formers varies significantly by age, although overall females have a greater prevalence than males. There is also a strong association of stone disease and both diabetes and hypertension, although this was only observed in children less than 6 years of age. Taken all together, these findings suggest that urolithiasis in the young child is a complex systemic disease process.

Identification of aldo-keto reductase (AKR7A1) and glutathione S-transferase pi (GSTP1) as novel renal damage biomarkers following exposure to mercury.

PubMed

Shin, Y-J; Kim, K-A; Kim, E-S; Kim, J-H; Kim, H-S; Ha, M; Bae, O-N

2017-01-01

The kidney is one of the main targets for toxicity induced by xenobiotics. Sensitive detection of early impairment is critical to assess chemical-associated renal toxicity. The aim of this study was to identify potential nephrotoxic biomarkers in rat kidney tissues after exposure to mercury (Hg), a representative nephrotoxicant, and to evaluate these new biomarkers employing in vivo and in vitro systems. Mercuric chloride was administered orally to Sprague-Dawley rats for 2 weeks. Proteomic analysis revealed that aldo-keto reductase (AKR7A1) and glutathione S-transferase pi (GSTP1) were significantly elevated in kidney after Hg exposure. While the levels of conventional nephrotoxic clinical markers including blood urea nitrogen and serum creatinine were not elevated, the mRNA and protein levels of AKR7A1 and GSTP1 were increased upon Hg exposure in a dose-dependent manner. The increases in AKR7A1 and GSTP1 were also observed in rat kidneys after an extended exposure for 6 weeks to low-dose Hg. In in vitro rat kidney proximal tubular cells, changes in AKR7A1 and GSTP1 levels correlated well with the extent of cytotoxicity induced by Hg, cadmium, or cisplatin. AKR7A1 and GSTP1 were identified as new candidates for Hg-induced nephrotoxicity, suggesting that these biomarkers have potential for evaluating or predicting nephrotoxicity.

Familial Renal Cancer: Molecular Genetics and Surgical Management

PubMed Central

Barrisford, Glen W.; Singer, Eric A.; Rosner, Inger L.; Linehan, W. Marston; Bratslavsky, Gennady

2011-01-01

Familial renal cancer (FRC) is a heterogeneous disorder comprised of a variety of subtypes. Each subtype is known to have unique histologic features, genetic alterations, and response to therapy. Through the study of families affected by hereditary forms of kidney cancer, insights into the genetic basis of this disease have been identified. This has resulted in the elucidation of a number of kidney cancer gene pathways. Study of these pathways has led to the development of novel targeted molecular treatments for patients affected by systemic disease. As a result, the treatments for families affected by von Hippel-Lindau (VHL), hereditary papillary renal carcinoma (HPRC), hereditary leiomyomatosis renal cell carcinoma (HLRCC), and Birt-Hogg-Dubé (BHD) are rapidly changing. We review the genetics and contemporary surgical management of familial forms of kidney cancer. PMID:22312516

The Kallikrein-Kinin System: A Novel Mediator of IL-17-Driven Anti-Candida Immunity in the Kidney

PubMed Central

Ramani, Kritika; Garg, Abhishek V.; Jawale, Chetan V.; Jackson, Edwin K.; Shiva, Sruti S.; Horne, William; Kolls, Jay K.; Gaffen, Sarah L.; Biswas, Partha S.

2016-01-01

The incidence of life-threatening disseminated Candida albicans infections is increasing in hospitalized patients, with fatalities as high as 60%. Death from disseminated candidiasis in a significant percentage of cases is due to fungal invasion of the kidney, leading to renal failure. Treatment of candidiasis is hampered by drug toxicity, the emergence of antifungal drug resistance and lack of vaccines against fungal pathogens. IL-17 is a key mediator of defense against candidiasis. The underlying mechanisms of IL-17-mediated renal immunity have so far been assumed to occur solely through the regulation of antimicrobial mechanisms, particularly activation of neutrophils. Here, we identify an unexpected role for IL-17 in inducing the Kallikrein (Klk)-Kinin System (KKS) in C. albicans-infected kidney, and we show that the KKS provides significant renal protection in candidiasis. Microarray data indicated that Klk1 was upregulated in infected kidney in an IL-17-dependent manner. Overexpression of Klk1 or treatment with bradykinin rescued IL-17RA-/- mice from candidiasis. Therapeutic manipulation of IL-17-KKS pathways restored renal function and prolonged survival by preventing apoptosis of renal cells following C. albicans infection. Furthermore, combining a minimally effective dose of fluconazole with bradykinin markedly improved survival compared to either drug alone. These results indicate that IL-17 not only limits fungal growth in the kidney, but also prevents renal tissue damage and preserves kidney function during disseminated candidiasis through the KKS. Since drugs targeting the KKS are approved clinically, these findings offer potential avenues for the treatment of this fatal nosocomial infection. PMID:27814401

Proteomic analysis of the renal effects of simulated occupational jet fuel exposure.

PubMed

Witzmann, F A; Bauer, M D; Fieno, A M; Grant, R A; Keough, T W; Lacey, M P; Sun, Y; Witten, M L; Young, R S

2000-03-01

We analyzed protein expression in the cytosolic fraction prepared from whole kidneys in male Swiss-Webster mice exposed 1 h/day for five days to aerosolized JP-8 jet fuel at a concentration of 1000 mg/m3, simulating military occupational exposure. Kidney cytosol samples were solubilized and separated via large-scale, high-resolution two-dimensional electrophoresis (2-DE) and gel patterns scanned, digitized and processed for statistical analysis. Significant changes in soluble kidney proteins resulted from jet fuel exposure. Several of the altered proteins were identified by peptide mass finger-printing and related to ultrastructural abnormalities, altered protein processing, metabolic effects, and paradoxical stress protein/detoxification system responses. These results demonstrate a significant but comparatively moderate JP-8 effect on protein expression in the kidney and provide novel molecular evidence of JP-8 nephrotoxicity. Human risk is suggested by these data but conclusive assessment awaits a noninvasive search for biomarkers in JP-8 exposed humans.

Profiling of kidney vascular endothelial cell plasma membrane proteins by liquid chromatography-tandem mass spectrometry.

PubMed

Liu, Zan; Xu, Bo; Nameta, Masaaki; Zhang, Ying; Magdeldin, Sameh; Yoshida, Yutaka; Yamamoto, Keiko; Fujinaka, Hidehiko; Yaoita, Eishin; Tasaki, Masayuki; Nakagawa, Yuki; Saito, Kazuhide; Takahashi, Kota; Yamamoto, Tadashi

2013-06-01

Vascular endothelial cells (VECs) play crucial roles in physiological and pathologic conditions in tissues and organs. Most of these roles are related to VEC plasma membrane proteins. In the kidney, VECs are closely associated with structures and functions; however, plasma membrane proteins in kidney VECs remain to be fully elucidated. Rat kidneys were perfused with cationic colloidal silica nanoparticles (CCSN) to label the VEC plasma membrane. The CCSN-labeled plasma membrane fraction was collected by gradient ultracentrifugation. The VEC plasma membrane or whole-kidney lysate proteins were separated by sodium dodecyl sulfate polyacrylamide gel electrophoresis and digested with trypsin in gels for liquid chromatography-tandem mass spectrometry. Enrichment analysis was then performed. The VEC plasma membrane proteins were purified by the CCSN method with high yield (approximately 20 μg from 1 g of rat kidney). By Mascot search, 582 proteins were identified in the VEC plasma membrane fraction, and 1,205 proteins were identified in the kidney lysate. In addition to 16 VEC marker proteins such as integrin beta-1 and intercellular adhesion molecule-2 (ICAM-2), 8 novel proteins such as Deltex 3-like protein and phosphatidylinositol binding clathrin assembly protein (PICALM) were identified. As expected, many key functions of plasma membranes in general and of endothelial cells in particular (i.e., leukocyte adhesion) were significantly overrepresented in the proteome of CCSN-labeled kidney VEC fraction. The CCSN method is a reliable technique for isolation of VEC plasma membrane from the kidney, and proteomic analysis followed by bioinformatics revealed the characteristics of in vivo VECs in the kidney.

Scarcity discourses and their impacts on renal care policy, practices, and everyday experiences in rural British Columbia

PubMed Central

Brassolotto, Julia; Daly, Tamara

2017-01-01

Drawing from a qualitative case study in rural British Columbia, Canada, this paper examines the discourse of kidney scarcity and its impact on renal care policies and practices. Our findings suggest that at different levels of care, there are different discourses and treatment foci. We have identified three distinct scarcity discourses at work. At the macro policy level, the scarcity of transplantable kidneys is the dominant discourse. At the meso health care institution level, we witnessed a discourse regarding the scarcity of health care and human resources. At the micro community level, there was a discourse of the scarcity of health and life-sustaining resources. For each form of scarcity, particular responses are encouraged. At the macro level, renal care and transplant organizations emphasize the benefits of kidney transplantation and procuring more donors. At the meso level, participants from the regional health care system increasingly encourage home hemodialysis and patient-led care. At the micro level, community health care professionals push for rural renal patients to attend dialysis and maintain their care plans. This work contributes to critical, interdisciplinary organ transfer discourse by contextualizing kidney scarcity. It reveals the tension between these discourses and the implications of pursuing kidney donations without addressing the conditions in which individuals experience kidney failure. PMID:26854624

Results of kidney transplantation from high-terminal creatinine donors and the role of time-zero biopsy.

PubMed

Lin, N C; Yang, A H; King, K L; Wu, T H; Yang, W C; Loong, C C

2010-11-01

Deceased-donor kidney transplantation (DDKT) from high-terminal creatinine donors is associated with lower graft survival. These kidneys may be considered for discarding, worsening the organ shortage crisis. Using time-zero biopsy for histologic evaluation of these kidneys, we identified those organs eligible for transplantation, seeking to achieve better graft utility with comparable outcomes. From April 2004 to April 2008, 55 patients underwent DDKT. A time-zero biopsy was used to examine glomerulosclerosis, interstitial fibrosis, tubular atrophy, and arteriolar narrowing. A scoring system was used to determine a discard. Twenty-five patients received DDKT from donors whose terminal creatinine levels were >2.0 mg/dL (high terminal creatinine, HTC group) and 30 from donors whose terminal creatinine levels were <2.0 mg/dL (low terminal creatinine, LTC group). Patients who accepted kidneys from HTC donors had shorter waiting times (P = .011) but a higher incidence of delayed graft function after transplantation (P < .001). Nonetheless, 5-year graft survival rates were similar between the two groups. With a time-zero biopsy for histologic evaluation, kidneys recovered from high-terminal creatinine donors can be transplanted to overcome the organ shortage while achieving reasonable graft survival. Copyright © 2010 Elsevier Inc. All rights reserved.

The risk of thromboembolic events in kidney transplant patients.

PubMed

Verhave, Jacobien C; Tagalakis, Vicky; Suissa, Samy; Madore, François; Hébert, Marie-Josée; Cardinal, Héloïse

2014-06-01

Little is known about the risk of venous thrombosis following kidney transplant. To determine this we estimated the risk of thromboembolic events (TEs) in a cohort of consecutive patients who underwent kidney transplantation at a single tertiary care center over an 11-year period and calculated standardized incidence ratios (SIRs) for a first TE in kidney transplant recipients compared with the general population. We then performed a nested case-control study and compared patients with and without TEs to identify risk factors for thrombosis. Among 913 kidney transplant recipients (KTRs), 68 patients developed these events. The SIR for TEs in KTRs compared with the general population was 7.9 over the duration of follow-up. The risk was particularly higher in the first post-transplant year (SIR 26.1) but remained elevated afterward (SIR 5.2). Hospitalization, use of sirolimus, low hemoglobin level, and use of renin-angiotensin system inhibitors were independently associated with these events. When cases of TEs that occurred during hospitalization were excluded, the risk of these events remained elevated. The risk of TEs in KTRs was eightfold higher than in the general population but not fully explained by the increased risk associated with hospitalization. Our results underscore the important risk of thrombosis in patients who received a kidney transplant, making vigilance mandatory especially during hospitalization.

A Re-evaluation of Discarded Deceased Donor Kidneys in the UK: Are Usable Organs Still Being Discarded?

PubMed

Mittal, Shruti; Adamusiak, Anna; Horsfield, Catherine; Loukopoulos, Ioannis; Karydis, Nikolaos; Kessaris, Nicos; Drage, Martin; Olsburgh, Jonathon; Watson, Christopher Je; Callaghan, Chris J

2017-07-01

A significant proportion of procured deceased donor kidneys are subsequently discarded. The UK Kidney Fast-Track Scheme (KFTS) was introduced in 2012, enabling kidneys at risk of discard to be simultaneously offered to participating centers. We undertook an analysis of discarded kidneys to determine if unnecessary organ discard was still occurring since the KFTS was introduced. Between April and June 2015, senior surgeons independently inspected 31 consecutive discarded kidneys from throughout the United Kingdom. All kidneys were biopsied. Organs were categorized as usable, possibly usable pending histology, or not usable for implantation. After histology reports were available, final assessments of usability were made. There were 19 donors (6 donations after brain death, 13 donations after circulatory death), with a median (range) donor age of 67 (29-83) years and Kidney Donor Profile Index of 93 (19-100). Reasons for discard were variable. Only 3 discarded kidneys had not entered the KFTS. After initial assessment postdiscard, 11 kidneys were assessed as usable, with 9 kidneys thought to be possibly usable. Consideration of histological data reduced the number of kidneys thought usable to 10 (10/31; 32%). The KFTS scheme is successfully identifying organs at high risk of discard, though potentially transplantable organs are still being discarded. Analyses of discarded organs are essential to identify barriers to organ utilization and develop strategies to reduce unnecessary discard.

Dynamic MRI-based computer aided diagnostic systems for early detection of kidney transplant rejection: A survey

NASA Astrophysics Data System (ADS)

Mostapha, Mahmoud; Khalifa, Fahmi; Alansary, Amir; Soliman, Ahmed; Gimel'farb, Georgy; El-Baz, Ayman

2013-10-01

Early detection of renal transplant rejection is important to implement appropriate medical and immune therapy in patients with transplanted kidneys. In literature, a large number of computer-aided diagnostic (CAD) systems using different image modalities, such as ultrasound (US), magnetic resonance imaging (MRI), computed tomography (CT), and radionuclide imaging, have been proposed for early detection of kidney diseases. A typical CAD system for kidney diagnosis consists of a set of processing steps including: motion correction, segmentation of the kidney and/or its internal structures (e.g., cortex, medulla), construction of agent kinetic curves, functional parameter estimation, diagnosis, and assessment of the kidney status. In this paper, we survey the current state-of-the-art CAD systems that have been developed for kidney disease diagnosis using dynamic MRI. In addition, the paper addresses several challenges that researchers face in developing efficient, fast and reliable CAD systems for the early detection of kidney diseases.

Mononuclear phagocyte subpopulations in the mouse kidney.

PubMed

George, James F; Lever, Jeremie M; Agarwal, Anupam

2017-04-01

Mononuclear phagocytes are the most common cells in the kidney associated with immunity and inflammation. Although the presence of these cells in the kidney has been known for decades, the study of mononuclear phagocytes in the context of kidney function and dysfunction is still at an early stage. The purpose of this review is to summarize the present knowledge regarding classification of these cells in the mouse kidney and to identify relevant questions that would further advance the field and potentially lead to new opportunities for treatment of acute kidney injury and other kidney diseases.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wilhelmsen, Skadi; Janitzky, Andreas; Porsch, Markus

Standard treatment for upper urinary tract urothelial carcinoma (UUTUC) implies the radical removal of all urothelium-lined tissue, which requires nephroureterectomy with bladder cuff removal. We report on a patient with a rare coincidence of UUTUC and horseshoe kidney in whom a preoperative angiography helped to identify and subsequently embolize an abberant isthmic feeding artery, which was located in between both collecting systems. Ischemic discoloration of the isthmus area facilitated resection and no major blood loss occurred. Preoperative superselective embolization of the isthmus as the renal split area can be an effective tool to facilitate nephroureterectomy in the case of amore » horseshoe kidney.« less

Antibody-Mediated Rejection of the Kidney after Simultaneous Pancreas-Kidney Transplantation

PubMed Central

Pascual, Julio; Samaniego, Milagros D.; Torrealba, José R.; Odorico, Jon S.; Djamali, Arjang; Becker, Yolanda T.; Voss, Barbara; Leverson, Glen E.; Knechtle, Stuart J.; Sollinger, Hans W.; Pirsch, John D.

2008-01-01

The prevalence, risk factors, and outcome of antibody-mediated rejection (AMR) of the kidney after simultaneous pancreas-kidney transplantation are unknown. In 136 simultaneous pancreas-kidney recipients who were followed for an average of 3.1 yr, 21 episodes of AMR of the kidney allograft were identified. Eight episodes occurred early (≤90 d) after transplantation, and 13 occurred later. Histologic evidence of concomitant acute cellular rejection was noted in 12 cases; the other nine had evidence only of humoral rejection. In 13 cases, clinical rejection of the pancreas was diagnosed simultaneously, and two of these were biopsy proven and were positive for C4d immunostaining. Multivariate analysis identified only one significant risk factor: Female patients were three times more likely to experience AMR. Nearly all early episodes resolved with treatment and did not predict graft loss, but multivariate Cox models revealed that late AMR episodes more than tripled the risk for kidney and pancreas graft loss; therefore, new strategies are needed to prevent and to treat late AMR in simultaneous pancreas-kidney transplant recipients. PMID:18235091

Barriers to kidney transplants in Indonesia: a literature review.

PubMed

Bennett, P N; Hany, A

2009-03-01

People living with chronic kidney disease will require renal dialysis or a kidney transplant to maintain life. Although Indonesia has a developing healthcare industry, Indonesia's kidney transplant rates are lower than comparable nations. To explore the healthcare literature to identify barriers to kidney transplants in particular in relation to Indonesia. Healthcare databases were searched (CINAHL, Medline, EBSCOhostEJS, Blackwell Synergy, Web of Science, PubMed, Google Scholar and Proquest 5000) using the search terms: transplant, kidney disease, renal, dialysis, haemodialysis, Indonesia and nursing. The search was limited to English and Indonesian language data sources from 1997 to 2007. Reference lists of salient academic articles were hand searched. The results of our search identified six articles that met our criteria. Costs are the major barrier to kidney transplant in Indonesia, followed by cultural beliefs, perception of the law, lack of information and lack of infrastructure. In addition, kidney disease prevention strategies are required. There are many complex socio-economic, geographical, legal, cultural and religious factors that contribute to low kidney transplant rates in Indonesia. Although an increase in transplantation rates will require strategies from various agencies, healthcare professionals, including nurses, can play a role in overcoming some barriers. Community education programmes, improving their own education levels and by increasing empowerment in nursing we may contribute to improved kidney transplant rates in Indonesia.

Mechanisms of "kidney governing bones" theory in traditional Chinese medicine.

PubMed

Ju, Dahong; Liu, Meijie; Zhao, Hongyan; Wang, Jun

2014-09-01

Studies conducted by our group on the mechanism of "kidney governing bones" theory in traditional Chinese medicine (TCM) are reviewed in this paper. Conclusions can be summarized as follows. (1) Neuroendocrine-immune network (NIN)-osteoclast regulatory pathway OPG-RANKL-RANK is one of the mechanisms of "kidney governing bones." Although kidney-reinforcing therapy is regarded as one of the holistic regulatory mechanisms of the body, characteristic holistic regulation in TCM can be reflected through nonselective regulation of the NIN during kidney reinforcement therapy, which can be used to treat osteoporosis through microadjustments in the microenvironment of the bone marrow. (2) Marrow exhaustion in TCM, which is the state wherein lipocytes in the bone marrow increase whereas other cells decrease, serves as the pathogenesis of osteoporosis brought about by failure of the "kidney governing bones." (3) The kidney in TCM can be regarded as a complex system comprising multiple functional units in the body, including the unit "governing bones." Kidney deficiency refers to a deficiency in only one or more units of the kidney system and not the whole system itself, which explains the kidney-reinforcing effect of many herbs; some herbs can treat osteoporosis, but some cannot. Although both classified as kidney-reinforcing agents, the former can resolve failure of the "kidney governing bones" unit while the latter regulates the failure of other units in the kidney system. Despite the current understanding on "kidney governing bones" theory, the mechanism of "kidney governing bones" remains complicated and unresolved. Thus, further studies in this area are warranted.

The Full Spectrum of Clinical Ethical Issues in Kidney Failure. Findings of a Systematic Qualitative Review.

PubMed

Kahrass, Hannes; Strech, Daniel; Mertz, Marcel

2016-01-01

When treating patients with kidney failure, unavoidable ethical issues often arise. Current clinical practice guidelines some of them, but lack comprehensive information about the full range of relevant ethical issues in kidney failure. A systematic literature review of such ethical issues supports medical professionalism in nephrology, and offers a solid evidential base for efforts that aim to improve ethical conduct in health care. To identify the full spectrum of clinical ethical issues that can arise for patients with kidney failure in a systematic and transparent manner. A systematic review in Medline (publications in English or German between 2000 and 2014) and Google Books (with no restrictions) was conducted. Ethical issues were identified by qualitative text analysis and normative analysis. The literature review retrieved 106 references that together mentioned 27 ethical issues in clinical care of kidney failure. This set of ethical issues was structured into a matrix consisting of seven major categories and further first and second-order categories. The systematically-derived matrix helps raise awareness and understanding of the complexity of ethical issues in kidney failure. It can be used to identify ethical issues that should be addressed in specific training programs for clinicians, clinical practice guidelines, or other types of policies dealing with kidney failure.

The Full Spectrum of Clinical Ethical Issues in Kidney Failure. Findings of a Systematic Qualitative Review

PubMed Central

Kahrass, Hannes; Strech, Daniel; Mertz, Marcel

2016-01-01

Background When treating patients with kidney failure, unavoidable ethical issues often arise. Current clinical practice guidelines some of them, but lack comprehensive information about the full range of relevant ethical issues in kidney failure. A systematic literature review of such ethical issues supports medical professionalism in nephrology, and offers a solid evidential base for efforts that aim to improve ethical conduct in health care. Aim To identify the full spectrum of clinical ethical issues that can arise for patients with kidney failure in a systematic and transparent manner. Method A systematic review in Medline (publications in English or German between 2000 and 2014) and Google Books (with no restrictions) was conducted. Ethical issues were identified by qualitative text analysis and normative analysis. Results The literature review retrieved 106 references that together mentioned 27 ethical issues in clinical care of kidney failure. This set of ethical issues was structured into a matrix consisting of seven major categories and further first and second-order categories. Conclusions The systematically-derived matrix helps raise awareness and understanding of the complexity of ethical issues in kidney failure. It can be used to identify ethical issues that should be addressed in specific training programs for clinicians, clinical practice guidelines, or other types of policies dealing with kidney failure. PMID:26938863

Transcriptomic analysis on responses of the liver and kidney of finishing pigs fed cadmium contaminated rice.

PubMed

Xia, Yaoyao; Li, Jun; Ren, Wenkai; Feng, Zemeng; Huang, Ruilin; Yin, Yulong

2018-06-01

Cadmium (Cd) is a common harmful substance that has many deleterious effects on the liver and kidney. Most reports about Cd toxic studies focused on its inorganic status, whereas the toxicity of Cd in organic materials is less studied. Here, we performed RNA-seq to explore the influences of Cd contaminated rice on function of the liver and kidney of finishing pigs. The concentration of Cd in liver and kidney of pigs fed Cd contaminated rice increased by 4.00 and 2.94 times, respectively, compared to those in the control group. With transcriptomic analysis, approximately 4-6 × 10 7 clean reads were acquired. Five differently expressed genes (DEGs) were identified in the liver, and 12 DEGs in the kidney. SPHK2 was commonly down-regulated. No significantly enriched gene ontology (GO) terms were identified. By Kyoto encyclopaedia of genes and genomes (KEGG) enrichments, four pathways were identified in hepatic tissue, and five pathways in nephritic tissue. Intriguingly, two pathways (sphingolipid metabolism and VEGF signalling pathway) were altered both in the liver and kidney. Cd contaminated rice may cause liver and kidney damage and inflammation, or even lead to more severe harm to these tissues. © 2017 Society of Chemical Industry. © 2017 Society of Chemical Industry.

Recurrent AA Amyloidosis Combined With Chronic Active Antibody-mediated Rejection After Kidney Transplantation.

PubMed

Yeo, Min-Kyung; Ham, Young Rok; Choi, Song-Yi; Lee, Yong-Moon; Park, Moon Hyang; Suh, Kwang-Sun

2017-07-01

Kidney transplantation for amyloidosis remains a contentious issue. Recurrence of amyloidosis is one of the risks of transplantation. Chronic active antibody-mediated rejection is an important cause of chronic allograft dysfunction. A 47-year-old woman underwent kidney transplantation due to renal AA amyloidosis with unknown etiology. Six years posttransplantation, a kidney biopsy showed AA amyloidosis with chronic active antibody-mediated rejection. Donor-specific antibody class II was positive. The patient underwent intravenous plasmapheresis and treatment with rituximab and colchicine. The relationship between recurrence of amyloidosis and rejection was not obvious. Clinical characteristics of kidney transplantation for AA amyloidosis were subjected to literature review and 315 cases were identified. The incidence of amyloidosis recurrence and acute and chronic rejection rates were 15%, 15%, and 8%, respectively. Five-year patient and graft survival rates were 77% and 82%, respectively. Clinical courses of kidney transplantation in AA amyloidosis were, thus, identified.

Age at Immigration and Kidney Function among Self-Identified Healthy Africans in the United States.

PubMed

Ali, Mana; Mwendwa, Denée T; Sims, Regina; Ricks, Madia; Sumner, Anne E

2016-02-01

Kidney disease disparately affects those of African descent. Age trends have generally been established for kidney function in the overall US population, but the contribution of age at the time of immigration for African immigrants is unknown. To examine the independent and joint effects of age and age at the time of immigration, and kidney function. Estimated glomerular filtration rate (eGFR) was calculated for 93 African immigrants (60 % male; mean age = 33.5). Hierarchical regression and post hoc analyses revealed a significant age × age at the time of immigration interaction after accounting for traditional risk factors among those who immigrated at age ≤21. Younger age at the time of immigration to the US may exacerbate an inverse relationship between age and kidney function in a self-identified healthy African immigrant sample. Investigation of biopsychosocial factors associated with kidney health among African immigrants is warranted.

The renin-angiotensin-aldosterone system blockade in patients with advanced diabetic kidney disease.

PubMed

Bermejo, Sheila; García, Carles Oriol; Rodríguez, Eva; Barrios, Clara; Otero, Sol; Mojal, Sergi; Pascual, Julio; Soler, María José

Diabetic kidney disease is the leading cause of end-stage chronic kidney disease. The renin-angiotensin-aldosterone system (RAAS) blockade has been shown to slow the progression of diabetic kidney disease. Our objectives were: to study the percentage of patients with diabetic kidney disease treated with RAAS blockade, to determine its renal function, safety profile and assess whether its administration is associated with increased progression of CKD after 3 years of follow-up. Retrospective study. 197 diabetic kidney disease patients were included and divided into three groups according to the treatment: patients who had never received RAAS blockade (non-RAAS blockade), patients who at some point had received RAAS blockade (inconstant-RAAS blockade) and patients who received RAAS blockade (constant-RAAS blockade). Clinical characteristics and analytical variables such as renal function, electrolytes, glycosylated haemoglobin and glomerular filtration rate according to chronic kidney disease -EPI and MDRD formulas were assessed. We also studied their clinical course (baseline, 1 and 3 years follow-up) in terms of treatment group, survival, risk factors and renal prognosis. Non-RAAS blockade patients had worse renal function and older age (p<0.05) at baseline compared to RAAS blockade patients. Patients who received RAAS blockade were not found to have greater toxicity or chronic kidney disease progression and no differences in renal prognosis were identified. Mortality was higher in non-RAAS blockade patients, older patients and patients with worse renal function (p<0.05). In the multivariate analysis, older age and worse renal function were risk factors for mortality. Treatment with RAAS blockade is more common in diabetic kidney disease patients with eGFR≥30ml/min/1.73m 2 . In our study, there were no differences in the evolution of renal function between the three groups. Older age and worse renal function were associated with higher mortality in patients who did not receive RAAS blockade. Copyright © 2017 Sociedad Española de Nefrología. Published by Elsevier España, S.L.U. All rights reserved.

Early Outcomes of the New UK Deceased Donor Kidney Fast-Track Offering Scheme.

PubMed

Callaghan, Chris J; Mumford, Lisa; Pankhurst, Laura; Baker, Richard J; Bradley, J Andrew; Watson, Christopher J E

2017-12-01

The UK Kidney Fast-Track Scheme (KFTS) was introduced in 2012 to identify kidneys at high risk of discard and to rapidly facilitate transplantation. A retrospective analysis of kidneys transplanted through the KFTS was undertaken. UK Transplant Registry data were collected on deceased donor kidneys implanted between November 1, 2012, and April 30, 2015, (donation after brain death [DBD] donors) and March 1, 2013, and April 30, 2015 (donation after circulatory death [DCD] donors). Posttransplant outcomes included 1-year estimated glomerular filtration rate and death-censored graft survival (DCGS). Over the study period, 523 deceased donor kidneys were transplanted through the KFTS and 4174 via the standard National Kidney Allocation Scheme (NKAS). Kidneys in the KFTS were more likely to be from older diabetic donors, had a higher frequency of poor ex vivo perfusion, had longer cold ischemic times, and were transplanted into older recipients. One-year DCGS of KFTS and NKAS DBD donor kidneys was similar (94% vs 95%; P = 0.70), but for DCD donor kidneys, DCGS was lower in those allocated via the KFTS (91% versus 95%; P = 0.04). Median 1-year estimated glomerular filtration rate for DBD donor kidneys was lower in those allocated via the KFTS (49 vs 52 mL/min per 1.73 m; P = 0.01), but for DCD kidneys, there was no difference (45 vs 48 mL/min per 1.73 m; P = 0.10). Although KFTS kidneys have less favorable donor, graft, and recipient risk factors than NKAS kidneys, short-term graft and patient outcomes are acceptable. National schemes that identify and rapidly offer kidneys at high risk of discard may contribute to minimizing the unnecessary discard of organs.

Mononuclear phagocyte subpopulations in the mouse kidney

PubMed Central

George, James F.; Lever, Jeremie M.

2017-01-01

Mononuclear phagocytes are the most common cells in the kidney associated with immunity and inflammation. Although the presence of these cells in the kidney has been known for decades, the study of mononuclear phagocytes in the context of kidney function and dysfunction is still at an early stage. The purpose of this review is to summarize the present knowledge regarding classification of these cells in the mouse kidney and to identify relevant questions that would further advance the field and potentially lead to new opportunities for treatment of acute kidney injury and other kidney diseases. PMID:28100500

Perspectives of transplant physicians and surgeons on reimbursement, compensation, and incentives for living kidney donors.

PubMed

Tong, Allison; Chapman, Jeremy R; Wong, Germaine; Craig, Jonathan C

2014-10-01

The shortage of donors for organ transplantation has stimulated debate on financial incentives for living kidney donors. This study aims to describe the range of attitudes and opinions of transplant physicians on financial reimbursement, compensation, and incentives in living kidney donation. Qualitative study. 110 transplant nephrologists and surgeons from 12 countries across 43 transplantation units in Europe, Australasia, and North America. Face-to-face semistructured interviews were conducted. Transcripts were thematically analyzed. We identified 7 major themes. Prioritizing the removal of disincentives for living kidney donors was largely deemed acceptable. By contrast, provision of financial incentives raised concerns about undermining benevolence, compromising human dignity and value, and traversing market forces. Some contended that financial incentives potentially were legitimate if regulated, arguing that this would maximize utility in transplantation, but most also acknowledged the difficulty and that operational feasibility of a regulated system of financial incentivization may be limited. Participants were English speaking and from Western high-income countries; therefore, the transferability of our findings may be limited. Transplantation specialists believed that minimizing disincentives would support equity and justice in living kidney donation. Direct financial incentivization for living kidney donors, even in the context of a regulated market, was regarded by most as unjustified because of the potential moral consequences and uncertain feasibility. Removing financial disincentives and safeguarding the intrinsic volunteerism, value, and meaning of donation were viewed to uphold integrity in living kidney donation. Copyright © 2014 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.

Performance of Single-Use FlexorVue vs Reusable BoaVision Ureteroscope for Visualization of Calices and Stone Extraction in an Artificial Kidney Model.

PubMed

Schlager, Daniel; Hein, Simon; Obaid, Moaaz Abdulghani; Wilhelm, Konrad; Miernik, Arkadiusz; Schoenthaler, Martin

2017-11-01

To evaluate and compare Flexor ® Vue™, a semidisposable endoscopic deflection system with disposable ureteral sheath and reusable visualization source, and a nondisposable fiber optic ureteroscope in a standard in vitro setting. FlexorVue and a reusable fiber optic flexible ureteroscope were each tested in an artificial kidney model. The experimental setup included the visualization of colored pearls and the extraction of calculi with two different extraction devices (NCircle ® and NGage ® ). The procedures were performed by six experienced surgeons. Visualization time, access to calices, successful stone retraction, and time required were recorded. In addition, the surgeons' workload and subjective performance were determined according to the National Aeronautics and Space Administration-task load index (NASA-TLX). We referred to the Likert scale to assess maneuverability, handling, and image quality. Nearly all calices (99%) were correctly identified using the reusable scope, indicating full kidney access, whereas 74% of the calices were visualized using FlexorVue, of which 81% were correctly identified. Access to the lower poles of the kidney model was significantly less likely with the disposable device, and time to completion was significantly longer (755 s vs 153 s, p < 0.001). The stone clearance success rate with the disposable device was 23% using the NGage and 13% using the NCircle basket. Overall NASA-TLX scores were significantly higher using FlexorVue. The conventional reusable device also demonstrated superior maneuverability, handling, and image quality. FlexorVue offers a semidisposable deflecting endoscopic system allowing basic ureteroscopic and cystoscopic procedures. For its use as an addition or replacement for current reusable scopes, it requires substantial technical improvements.

Molecular mechanisms of acid-base sensing by the kidney.

PubMed

Brown, Dennis; Wagner, Carsten A

2012-05-01

A major function of the kidney is to collaborate with the respiratory system to maintain systemic acid-base status within limits compatible with normal cell and organ function. It achieves this by regulating the excretion and recovery of bicarbonate (mainly in the proximal tubule) and the secretion of buffered protons (mainly in the distal tubule and collecting duct). How proximal tubular cells and distal professional proton transporting (intercalated) cells sense and respond to changes in pH, bicarbonate, and CO(2) status is a question that has intrigued many generations of renal physiologists. Over the past few years, however, some candidate molecular pH sensors have been identified, including acid/alkali-sensing receptors (GPR4, InsR-RR), kinases (Pyk2, ErbB1/2), pH-sensitive ion channels (ASICs, TASK, ROMK), and the bicarbonate-stimulated adenylyl cyclase (sAC). Some acid-sensing mechanisms in other tissues, such as CAII-PDK2L1 in taste buds, might also have similar roles to play in the kidney. Finally, the function of a variety of additional membrane channels and transporters is altered by pH variations both within and outside the cell, and the expression of several metabolic enzymes are altered by acid-base status in parts of the nephron. Thus, it is possible that a master pH sensor will never be identified. Rather, the kidney seems equipped with a battery of molecules that scan the epithelial cell environment to mount a coordinated physiologic response that maintains acid-base homeostasis. This review collates current knowledge on renal acid-base sensing in the context of a whole organ sensing and response process.

Egg ovotransferrin-derived ACE inhibitory peptide IRW increases ACE2 but decreases proinflammatory genes expression in mesenteric artery of spontaneously hypertensive rats.

PubMed

Majumder, Kaustav; Liang, Guanxiang; Chen, Yanhong; Guan, LeLuo; Davidge, Sandra T; Wu, Jianping

2015-09-01

Egg ovotransferrin-derived angiotensin converting enzyme (ACE) inhibitory peptide IRW was previously shown to reduce blood pressure in spontaneously hypertensive rats through reduced vascular inflammation and increased nitric oxide-mediated vasorelaxation. The main objective of the present study was to investigate the molecular mechanism of this peptide through transcriptome analysis by RNAseq technique. Total RNA was extracted from kidney and mesenteric arteries; the RNAseq libraries (from untreated and IRW-treated groups) were constructed and subjected to sequence using HiSeq 2000 system (Illumina) system. A total of 12 764 and 13 352 genes were detected in kidney and mesenteric arteries, respectively. The differentially expressed (DE) genes between untreated and IRW-treated groups were identified and the functional analysis through ingenuity pathway analysis revealed a greater role of DE genes identified from mesenteric arteries than that of kidney in modulating various cardiovascular functions. Subsequent qPCR analysis further confirmed that IRW significantly increased the expression of ACE-2, ABCB-1, IRF-8, and CDH-1 while significantly decreased the expression ICAM-1 and VCAM-1 in mesenteric arteries. Our research showed for the first time that ACE inhibitory peptide IRW could contribute to its antihypertensive activity through increased ACE2 and decreased proinflammatory genes expression. © 2015 The Authors. Molecular Nutrition & Food Research published by Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Chronic kidney-disease screening service quality: questionnaire survey research evidence from Taichung City.

PubMed

Lin, Deng-Juin; Li, Ya-Hsin; Pai, Jar-Yuan; Sheu, Ing-Cheau; Glen, Robert; Chou, Ming-Jen; Lee, Ching-Yi

2009-12-19

Chronic kidney disease (CKD) is a serious public health problem in Taiwan and the world. The most effective, affordable treatments involve early prevention/detection/intervention, requiring screening. Successfully implementing CKD programs requires good patient participation, affected by patient perceptions of screening service quality. Service quality improvements can help make such programs more successful. Thus, good tools for assessing service quality perceptions are important. to investigate using a modified SERVQUAL questionnaire in assessing patient expectations, perceptions, and loyalty towards kidney disease screening service quality. 1595 kidney disease screening program patients in Taichung City were requested to complete and return a modified kidney disease screening SERVQUAL questionnaire. 1187 returned them. Incomplete ones (102) were culled and 1085 were chosen as effective for use. Paired t-tests, correlation tests, ANOVA, LSD test, and factor analysis identified the characteristics and factors of service quality. The paired t-test tested expectation score and perception score gaps. A structural equation modeling system examined satisfaction-based components' relationships. The effective response rate was 91.4%. Several methods verified validity. Cronbach's alpha on internal reliability was above 0.902. On patient satisfaction, expectation scores are high: 6.50 (0.82), but perception scores are significantly lower 6.14 (1.02). Older patients' perception scores are lower than younger patients'. Expectation and perception scores for patients with different types of jobs are significantly different. Patients higher on education have lower scores for expectation (r = -0.09) and perception (r = -0.26). Factor analysis identified three factors in the 22 item SERVQUAL form, which account for 80.8% of the total variance for the expectation scores and 86.9% of the total variance for the satisfaction scores. Expectation and perception score gaps in all 22 items are significant. The goodness-of-fit summary of the SEM results indicates that expectations and perceptions are positively correlated, perceptions and loyalty are positively correlated, but expectations and loyalty are not positively correlated. The results of this research suggest that the SERVQUAL instrument is a useful measurement tool in assessing and monitoring service quality in kidney disease screening services, enabling the staff to identify where service improvements are needed from the patients' perspectives.

Influence of CT-based depth correction of renal scintigraphy in evaluation of living kidney donors on side selection and postoperative renal function: is it necessary to know the relative renal function?

PubMed

Weinberger, Sarah; Klarholz-Pevere, Carola; Liefeldt, Lutz; Baeder, Michael; Steckhan, Nico; Friedersdorff, Frank

2018-03-22

To analyse the influence of CT-based depth correction in the assessment of split renal function in potential living kidney donors. In 116 consecutive living kidney donors preoperative split renal function was assessed using the CT-based depth correction. Influence on donor side selection and postoperative renal function of the living kidney donors were analyzed. Linear regression analysis was performed to identify predictors of postoperative renal function. A left versus right kidney depth variation of more than 1 cm was found in 40/114 donors (35%). 11 patients (10%) had a difference of more than 5% in relative renal function after depth correction. Kidney depth variation and changes in relative renal function after depth correction would have had influence on side selection in 30 of 114 living kidney donors. CT depth correction did not improve the predictability of postoperative renal function of the living kidney donor. In general, it was not possible to predict the postoperative renal function from preoperative total and relative renal function. In multivariate linear regression analysis, age and BMI were identified as most important predictors for postoperative renal function of the living kidney donors. Our results clearly indicate that concerning the postoperative renal function of living kidney donors, the relative renal function of the donated kidney seems to be less important than other factors. A multimodal assessment with consideration of all available results including kidney size, location of the kidney and split renal function remains necessary.

Urinary biomarkers may provide prognostic information for subclinical acute kidney injury after cardiac surgery.

PubMed

Albert, Christian; Albert, Annemarie; Kube, Johanna; Bellomo, Rinaldo; Wettersten, Nicholas; Kuppe, Hermann; Westphal, Sabine; Haase, Michael; Haase-Fielitz, Anja

2018-06-01

This study aimed to determine the biomarker-specific outcome patterns and short-and long-term prognosis of cardiac surgery-asoociated acute kidney injury (AKI) identified by standard criteria and/or urinary kidney biomarkers. Patients enrolled (N = 200), originated a German multicenter study (NCT00672334). Standard risk injury, failure, loss, and end-stage renal disease classification (RIFLE) criteria (including serum creatinine and urine output) and urinary kidney biomarker test result (neutrophil gelatinase-associated lipocalin, midkine, interleukin 6, and proteinuria) were used for diagnosis of postoperative AKI. Primary end point was acute renal replacement therapy or in-hospital mortality. Long-term end points among others included 5-year mortality. Patients with single-biomarker-positive subclinical AKI (RIFLE negative) were identified. We controlled for systemic inflammation using C-reactive protein test. Urinary biomarkers (neutrophil gelatinase-associated lipocalin, midkine, and interleukin 6) were identified as independent predictors of the primary end point. Neutrophil gelatinase-associated lipocalin, midkine, or interleukin 6 positivity or de novo/worsening proteinuria identified 21.1%, 16.9%, 30.5%, and 48.0% more cases, respectively, with likely subclinical AKI (biomarker positive/RIFLE negative) additionally to cases with RIFLE positivity alone. Patients with likely subclinical AKI (neutrophil gelatinase-associated lipocalin or interleukin 6 positive) had increased risk of primary end point (adjusted hazard ratio, 7.18; 95% confidence interval, 1.52-33.93 [P = .013] and hazard ratio, 6.27; 95% confidence interval, 1.12-35.21 [P = .037]), respectively. Compared with biomarker-negative/RIFLE-positive patients, neutrophil gelatinase-associated lipocalin positive/RIFLE-positive or midkine-positive/RIFLE-positive patients had increased risk of primary end point (odds ratio, 9.6; 95% confidence interval, 1.4-67.3 [P = .033] and odds ratio, 14.7; 95% confidence interval, 2.0-109.2 [P = .011], respectively). Three percent to 11% of patients appear to be influenced by single-biomarker-positive subclinical AKI. During follow-up, kidney biomarker-defined short-term outcomes appeared to translate into long-term outcomes. Urinary kidney biomarkers identified RIFLE-negative patients with high-risk subclinical AKI as well as a higher risk subgroup of patients among RIFLE-AKI-positive patients. These findings support the concept that urinary biomarkers define subclinical AKI and higher risk subpopulations with worse long-term prognosis among standard patients with AKI. Copyright © 2017 The American Association for Thoracic Surgery. All rights reserved.

[Health management system in outpatient follow-up of kidney transplantation patients].

PubMed

Zhang, Hong; Xie, Jinliang; Yao, Hui; Liu, Ling; Tan, Jianwen; Geng, Chunmi

2014-07-01

To develop a health management system for outpatient follow-up of kidney transplant patients. Access 2010 database software was used to establish the health management system for kidney transplantation patients in Windows XP operating system. Database management and post-operation follow-up of the kidney transplantation patients were realized through 6 function modules including data input, data query, data printing, questionnaire survey, data export, and follow-up management. The system worked stably and reliably, and the data input was easy and fast. The query, the counting and printing were convenient. Health management system for patients after kidney transplantation not only reduces the work pressure of the follow-up staff, but also improves the efficiency of outpatient follow-up.

Altered lipid metabolism in the aging kidney identified by three layered omic analysis

PubMed Central

Braun, Fabian; Rinschen, Markus M.; Bartels, Valerie; Frommolt, Peter; Habermann, Bianca; Hoeijmakers, Jan H.J.; Schumacher, Björn; Dollé, Martijn E.T.; Müller, Roman-Ulrich; Benzing, Thomas; Schermer, Bernhard; Kurschat, Christine E.

2016-01-01

Aging-associated diseases and their comorbidities affect the life of a constantly growing proportion of the population in developed countries. At the center of these comorbidities are changes of kidney structure and function as age-related chronic kidney disease predisposes to the development of cardiovascular diseases such as stroke, myocardial infarction or heart failure. To detect molecular mechanisms involved in kidney aging, we analyzed gene expression profiles of kidneys from adult and aged wild-type mice by transcriptomic, proteomic and targeted lipidomic methodologies. Interestingly, transcriptome and proteome analyses revealed differential expression of genes primarily involved in lipid metabolism and immune response. Additional lipidomic analyses uncovered significant age-related differences in the total amount of phosphatidylethanolamines, phosphatidylcholines and sphingomyelins as well as in subspecies of phosphatidylserines and ceramides with age. By integration of these datasets we identified Aldh1a1, a key enzyme in vitamin A metabolism specifically expressed in the medullary ascending limb, as one of the most prominent upregulated proteins in old kidneys. Moreover, ceramidase Asah1 was highly expressed in aged kidneys, consistent with a decrease in ceramide C16. In summary, our data suggest that changes in lipid metabolism are involved in the process of kidney aging and in the development of chronic kidney disease. PMID:26886165

Altered lipid metabolism in the aging kidney identified by three layered omic analysis.

PubMed

Braun, Fabian; Rinschen, Markus M; Bartels, Valerie; Frommolt, Peter; Habermann, Bianca; Hoeijmakers, Jan H J; Schumacher, Björn; Dollé, Martijn E T; Müller, Roman-Ulrich; Benzing, Thomas; Schermer, Bernhard; Kurschat, Christine E

2016-03-01

Aging-associated diseases and their comorbidities affect the life of a constantly growing proportion of the population in developed countries. At the center of these comorbidities are changes of kidney structure and function as age-related chronic kidney disease predisposes to the development of cardiovascular diseases such as stroke, myocardial infarction or heart failure. To detect molecular mechanisms involved in kidney aging, we analyzed gene expression profiles of kidneys from adult and aged wild-type mice by transcriptomic, proteomic and targeted lipidomic methodologies. Interestingly, transcriptome and proteome analyses revealed differential expression of genes primarily involved in lipid metabolism and immune response. Additional lipidomic analyses uncovered significant age-related differences in the total amount of phosphatidylethanolamines, phosphatidylcholines and sphingomyelins as well as in subspecies of phosphatidylserines and ceramides with age. By integration of these datasets we identified Aldh1a1, a key enzyme in vitamin A metabolism specifically expressed in the medullary ascending limb, as one of the most prominent upregulated proteins in old kidneys. Moreover, ceramidase Asah1 was highly expressed in aged kidneys, consistent with a decrease in ceramide C16. In summary, our data suggest that changes in lipid metabolism are involved in the process of kidney aging and in the development of chronic kidney disease.

Multiple New Loci Associated with Kidney Function and Chronic Kidney Disease: The CKDGen consortium

PubMed Central

Köttgen, Anna; Pattaro, Cristian; Böger, Carsten A.; Fuchsberger, Christian; Olden, Matthias; Glazer, Nicole L.; Parsa, Afshin; Gao, Xiaoyi; Yang, Qiong; Smith, Albert V.; O’Connell, Jeffrey R.; Li, Man; Schmidt, Helena; Tanaka, Toshiko; Isaacs, Aaron; Ketkar, Shamika; Hwang, Shih-Jen; Johnson, Andrew D.; Dehghan, Abbas; Teumer, Alexander; Paré, Guillaume; Atkinson, Elizabeth J.; Zeller, Tanja; Lohman, Kurt; Cornelis, Marilyn C.; Probst-Hensch, Nicole M.; Kronenberg, Florian; Tönjes, Anke; Hayward, Caroline; Aspelund, Thor; Eiriksdottir, Gudny; Launer, Lenore; Harris, Tamara B.; Rapmersaud, Evadnie; Mitchell, Braxton D.; Boerwinkle, Eric; Struchalin, Maksim; Cavalieri, Margherita; Singleton, Andrew; Giallauria, Francesco; Metter, Jeffery; de Boer, Ian; Haritunians, Talin; Lumley, Thomas; Siscovick, David; Psaty, Bruce M.; Zillikens, M. Carola; Oostra, Ben A.; Feitosa, Mary; Province, Michael; Levy, Daniel; de Andrade, Mariza; Turner, Stephen T.; Schillert, Arne; Ziegler, Andreas; Wild, Philipp S.; Schnabel, Renate B.; Wilde, Sandra; Muenzel, Thomas F.; Leak, Tennille S; Illig, Thomas; Klopp, Norman; Meisinger, Christa; Wichmann, H.-Erich; Koenig, Wolfgang; Zgaga, Lina; Zemunik, Tatijana; Kolcic, Ivana; Minelli, Cosetta; Hu, Frank B.; Johansson, Åsa; Igl, Wilmar; Zaboli, Ghazal; Wild, Sarah H; Wright, Alan F; Campbell, Harry; Ellinghaus, David; Schreiber, Stefan; Aulchenko, Yurii S; Rivadeneira, Fernando; Uitterlinden, Andre G; Hofman, Albert; Imboden, Medea; Nitsch, Dorothea; Brandstätter, Anita; Kollerits, Barbara; Kedenko, Lyudmyla; Mägi, Reedik; Stumvoll, Michael; Kovacs, Peter; Boban, Mladen; Campbell, Susan; Endlich, Karlhans; Völzke, Henry; Kroemer, Heyo K.; Nauck, Matthias; Völker, Uwe; Polasek, Ozren; Vitart, Veronique; Badola, Sunita; Parker, Alexander N.; Ridker, Paul M.; Kardia, Sharon L. R.; Blankenberg, Stefan; Liu, Yongmei; Curhan, Gary C.; Franke, Andre; Rochat, Thierry; Paulweber, Bernhard; Prokopenko, Inga; Wang, Wei; Gudnason, Vilmundur; Shuldiner, Alan R.; Coresh, Josef; Schmidt, Reinhold; Ferrucci, Luigi; Shlipak, Michael G.; van Duijn, Cornelia M.; Borecki, Ingrid; Krämer, Bernhard K.; Rudan, Igor; Gyllensten, Ulf; Wilson, James F.; Witteman, Jacqueline C.; Pramstaller, Peter P.; Rettig, Rainer; Hastie, Nick; Chasman, Daniel I.; Kao, W. H.; Heid, Iris M.; Fox, Caroline S.

2010-01-01

Chronic kidney disease (CKD) is a significant public health problem, and recent genetic studies have identified common CKD susceptibility variants. The CKDGen consortium performed a meta-analysis of genome-wide association data in 67,093 Caucasian individuals from 20 population-based studies to identify new susceptibility loci for reduced renal function, estimated by serum creatinine (eGFRcrea), cystatin C (eGFRcys), and CKD (eGFRcrea <60 ml/min/1.73m2; n = 5,807 CKD cases). Follow-up of the 23 genome-wide significant loci (p<5×10−8) in 22,982 replication samples identified 13 novel loci for renal function and CKD (in or near LASS2, GCKR, ALMS1, TFDP2, DAB2, SLC34A1, VEGFA, PRKAG2, PIP5K1B, ATXN2, DACH1, UBE2Q2, and SLC7A9) and 7 creatinine production and secretion loci (CPS1, SLC22A2, TMEM60, WDR37, SLC6A13, WDR72, BCAS3). These results further our understanding of biologic mechanisms of kidney function by identifying loci potentially influencing nephrogenesis, podocyte function, angiogenesis, solute transport, and metabolic functions of the kidney. PMID:20383146

ASIA syndrome, calcinosis cutis and chronic kidney disease following silicone injections. A case-based review.

PubMed

Barilaro, Giuseppe; Spaziani Testa, Claudia; Cacciani, Antonella; Donato, Giuseppe; Dimko, Mira; Mariotti, Amalia

2016-12-01

An immunologic adjuvant is a substance that enhances the antigen-specific immune response preferably without triggering one on its own. Silicone, a synthetic polymer used for reconstructive and cosmetic purposes, can cause, once injected, local and/or systemic reactions and trigger manifestations of autoimmunity, occasionally leading to an overt autoimmune disease. Siliconosis, calcinosis cutis with hypercalcemia and chronic kidney disease have all been reported in association with silicone injection. Here, we describe a case of autoimmune/auto-inflammatory syndrome induced by adjuvants, calcinosis cutis and chronic kidney disease after liquid silicone multiple injections in a young man who underwent a sex reassignment surgery, followed by a review of the literature. To our knowledge, this is the first report describing the concomitance of the three clinical conditions in the same patients. The link between silicone and the immune system is not completely understood yet and requires further reports and investigations with long-term data, in order to identify the main individual and genetical risk factors predisposing to the wide spectrum of the adjuvant-induced responses.

Outbreaks of phaeohyphomycosis in the chinook salmon (Oncorhynchus tshawytscha) caused by Phoma herbarum.

PubMed

Faisal, Mohamed; Elsayed, Ehab; Fitzgerald, Scott D; Silva, Victor; Mendoza, Leonel

2007-01-01

Phoma herbarum has been associated with two outbreaks of systemic mycosis in hatchery-reared chinook salmon (Oncorhynchus tshawytscha) fingerlings. Affected fish exhibited abnormal swimming behavior, exophthalmia, multiple rounded areas of muscle softening, protruded hemorrhagic vents, and abdominal swelling. In all affected fish, swimbladders were filled with whitish creamy viscous fungal mass, surrounded by dark red areas in swimbladder walls, kidneys, and musculature. Clinical and histopathological examinations suggest that the infection may have started primarily in the swimbladder and then spread to the kidneys, gastrointestinal tract, and surrounding musculature. Consistent microscopical findings included broad septate branched fungal hyaline hyphae, 5-12 microm in diameter within the swimbladder, stomach, and often within and adjacent to blood vessels. Profuse growths of woolly brown fungal colonies were obtained from swimbladders and kidneys on Sabouraud medium. On corn meal agar the formation of pycnidia, characteristic of Phoma spp., was detected within 10 days of incubation. Morphological and molecular analyses identified this fungus as Phoma herbarum. This report underscores systemic fungal infections as a threat to raceway-raised salmon.

Measuring glomerular number from kidney MRI images

NASA Astrophysics Data System (ADS)

Thiagarajan, Jayaraman J.; Natesan Ramamurthy, Karthikeyan; Kanberoglu, Berkay; Frakes, David; Bennett, Kevin; Spanias, Andreas

2016-03-01

Measuring the glomerular number in the entire, intact kidney using non-destructive techniques is of immense importance in studying several renal and systemic diseases. Commonly used approaches either require destruction of the entire kidney or perform extrapolation from measurements obtained from a few isolated sections. A recent magnetic resonance imaging (MRI) method, based on the injection of a contrast agent (cationic ferritin), has been used to effectively identify glomerular regions in the kidney. In this work, we propose a robust, accurate, and low-complexity method for estimating the number of glomeruli from such kidney MRI images. The proposed technique has a training phase and a low-complexity testing phase. In the training phase, organ segmentation is performed on a few expert-marked training images, and glomerular and non-glomerular image patches are extracted. Using non-local sparse coding to compute similarity and dissimilarity graphs between the patches, the subspace in which the glomerular regions can be discriminated from the rest are estimated. For novel test images, the image patches extracted after pre-processing are embedded using the discriminative subspace projections. The testing phase is of low computational complexity since it involves only matrix multiplications, clustering, and simple morphological operations. Preliminary results with MRI data obtained from five kidneys of rats show that the proposed non-invasive, low-complexity approach performs comparably to conventional approaches such as acid maceration and stereology.

Diabetic kidney disease.

PubMed

Thomas, Merlin C; Brownlee, Michael; Susztak, Katalin; Sharma, Kumar; Jandeleit-Dahm, Karin A M; Zoungas, Sophia; Rossing, Peter; Groop, Per-Henrik; Cooper, Mark E

2015-07-30

The kidney is arguably the most important target of microvascular damage in diabetes. A substantial proportion of individuals with diabetes will develop kidney disease owing to their disease and/or other co-morbidity, including hypertension and ageing-related nephron loss. The presence and severity of chronic kidney disease (CKD) identify individuals who are at increased risk of adverse health outcomes and premature mortality. Consequently, preventing and managing CKD in patients with diabetes is now a key aim of their overall management. Intensive management of patients with diabetes includes controlling blood glucose levels and blood pressure as well as blockade of the renin-angiotensin-aldosterone system; these approaches will reduce the incidence of diabetic kidney disease and slow its progression. Indeed, the major decline in the incidence of diabetic kidney disease (DKD) over the past 30 years and improved patient prognosis are largely attributable to improved diabetes care. However, there remains an unmet need for innovative treatment strategies to prevent, arrest, treat and reverse DKD. In this Primer, we summarize what is now known about the molecular pathogenesis of CKD in patients with diabetes and the key pathways and targets implicated in its progression. In addition, we discuss the current evidence for the prevention and management of DKD as well as the many controversies. Finally, we explore the opportunities to develop new interventions through urgently needed investment in dedicated and focused research. For an illustrated summary of this Primer, visit: http://go.nature.com/NKHDzg.

Effect of systemic administration of lipopolysaccharides derived from Porphyromonas gingivalis on gene expression in mice kidney.

PubMed

Harada, Fumiya; Uehara, Osamu; Morikawa, Tetsuro; Hiraki, Daichi; Onishi, Aya; Toraya, Seiko; Adhikari, Bhoj Raj; Takai, Rie; Yoshida, Koki; Sato, Jun; Nishimura, Michiko; Chiba, Itsuo; Wu, Ching Zong; Abiko, Yoshihiro

2018-01-31

Although an association between periodontitis and chronic kidney disease (CKD) has been suggested, the mechanism involved remains unclear. Herein, we examined the global gene expression profile in a mouse model that showed no acute inflammation in the kidney following stimulation with lipopolysaccharides (LPS) derived from Porphyromonas gingivalis (PG-LPS). The mice were injected with PG-LPS at a concentration of 5 mg/kg intraperitoneally, every 3 days, for 1 month. Microarray analysis was used to identify 10 genes with the highest expression levels in the kidney stimulated with PG-LPS. Among them, the functions of five genes (Saa3, Ticam2, Reg3b, Ocxt2a, and Xcr1) were known. The upregulation of these genes was confirmed by quantitative polymerase chain reaction assay. Furthermore, we examined whether the expression of these upregulated genes were altered in endothelial cells derived from the kidney, in vitro. The mRNA expression levels of all five genes were significantly higher in the experimental group than in the controls (no LPS stimulation; *p < 0.05). In conclusion, the responses noted in the kidney may have arisen mainly from the endothelial cells. Moreover, upregulation of the expression levels of Saa3, Ticam2, Reg3b, Ocxt2a, and Xcr1 may be associated with the pathogenesis of CKD.

Characteristics of renal papillae in kidney stone formers.

PubMed

Marien, Tracy P; Miller, Nicole L

2016-12-01

The mechanism of kidney stone formation is not well understood. In order to better understand the pathophysiology for specific kidney stone compositions and systemic diseases associated with kidney stones, endoscopic papillary mapping studies with concurrent biopsies have been conducted. This review will summarize the findings of these studies and proposed mechanisms for thirteen disease processes associated with kidney stones. A review of the literature was performed identifying thirteen studies that endoscopically mapped and biopsied renal papillae of different stone formers. These studies characterized renal papillae based on amount of Randall's plaque, Bellini's duct pathology, papillary contour changes, presence of attached stones, pitting, and frequently papillary and cortical biopsies. The groups studied and reviewed here are kidney stone formers who have a history of idiopathic calcium oxalate stone formation, cystinuria, brushite stones, gastric bypass, ileostomy, small bowel resection, primary hyperparathyroidism, distal renal tubular acidosis (dRTA), primary hyperoxaluria, idiopathic calcium phosphate stone formation, medullary sponge kidney (MSK), uric acid stones, and struvite stones. A proposed standardized scoring system for papillary pathology was also reviewed. The series showed various degrees and types of changes to the renal papillae and corresponding histopathologic changes for each type of stone former reviewed. Those with predominantly alone Randall's plaque pathology had less tissue damage versus those with extensive Bellini's duct lesions who had more interstitial fibrosis and cortical pathology. Randall's plaques are associated with stone formers who have low urinary volume, high urinary calcium, and acidic urine and thus are frequently seen in those with brushite stones, primary hyperparathyroidism, small bowel resection, and idiopathic calcium phosphate stone formers. Bellini's duct plugging and pathology is theorized to occur via free solution crystallization, ductal obstruction, inflammation, cellular injury, fibrosis, and acidification defects. Ureteroscopic manifestations of stone disease can vary from normal appearing papillae to significantly diseased appearing papillae. Some diseases have very characteristic papillary changes. Further studies are necessary to fully elucidate the mechanisms of stone formation in patients with nephrolithiasis.

[Proteomic analysis of myocardial hypertrophy induced by left kidney artery coarctation in rats].

PubMed

Lv, Yuan-yuan; Sun, Biao; Ma, Ji-zheng

2009-05-01

To identify the expression of proteins in cardiomyocytes in rats with left kidney artery coarctation. 16 male SD rats were separated into 2 groups (n=8): 2 kidney 1 Clip group (2K1C) and sham operation group (SO). The postoperational 8th week, after examination by normal doppler and tissue doppler echocardiography, the extracted proteins from cardiomyocytes were isolated by two-dimensional gel electrophoresis with staining. The gel images were acquired by scanner and 2-DE analysis software. Different spots observed on two 2D gels were selected and identified by matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF-MS). Overall, 21 protein spots showed significant difference, and 14 out of which were identified. Kidney artery coactation-induced cardiac hypertrophy displays different expression of proteins in cardiomyocytes.

Hispanic/Latino concerns about living kidney donation: a focus group study.

PubMed

Gordon, Elisa J; Mullee, Jack O; Ramirez, Daney I; MacLean, Jessica; Olivero, Maria; Feinglass, Joseph; Carney, Paula; O'Connor, Kate; Caicedo, Juan Carlos

2014-06-01

Given the shortage of kidneys for transplant, living kidney donation (LKD) is increasingly used to expand the organ donor pool. Although Hispanics/Latinos need disproportionately more kidney transplants, they receive a smaller proportion of living donor kidney transplants than other ethnic/racial groups. To assess Hispanics' awareness, perceptions, misconceptions, cultural beliefs, and values about and barriers to LKD. Nine focus groups were conducted with 76 adult Hispanics in Chicago, Illinois, between January and March 2012. Focus groups included kidney transplant recipients, living kidney donors, dialysis patients, and the general Hispanic public. Several themes emerged as perceived barriers to LKD. Many participants identified knowledge deficits about LKD, expressing uncertainty about the differences between LKD and deceased donation, and whether kidney disease simultaneously afflicts both kidneys. Many believed that donors experience dramatically shorter life expectancies, are unable to have children, and are more susceptible to kidney disease after donating. Recipients and donors reported that family members were involved in discussions about the donor's decision to donate, with some family members discouraging donation. Financial barriers cited included fear of becoming unable to work, losing one's job, or being unable to pay household bills while recovering. Participants also identified logistic barriers for undocumented immigrants (eg, the inability to obtain government insurance for transplant candidates and uncertainty about their eligibility to donate). Donors desired information about optimizing self-care to promote their remaining kidney's health. Culturally competent interventions are needed to redress Hispanics' knowledge deficits and misconceptions and reduce LKD disparities among Hispanics.

Autophagy and kidney inflammation

PubMed Central

Kimura, Tomonori; Isaka, Yoshitaka; Yoshimori, Tamotsu

2017-01-01

ABSTRACT Inflammation plays a pivotal role in pathophysiological processes of kidney diseases. Macroautophagy/autophagy plays multiple roles in inflammatory responses, and the regulation of inflammation by autophagy has great potential as a treatment for damaged kidneys. A growing body of evidence suggests autophagy protects kidney from versatile kidney inflammatory insults, including those that are acute, chronic, metabolic, and aging-related. It is noteworthy that, in kidney, mitophagy is active, and damaged lysosomes are removed by autophagy. In this mode, autophagy suppresses inflammation to protect the kidney. Systemic inflammation also affects the kidney via pro-inflammatory cytokines and infiltration of inflammatory cells, and autophagy also has a regulatory role in systemic inflammation. This review focuses on the roles of autophagy in kidney diseases and aging through inflammation, and discusses the potential usage of autophagy as an inflammatory modulator for the treatment of kidney diseases. PMID:28441075

Autophagy and kidney inflammation.

PubMed

Kimura, Tomonori; Isaka, Yoshitaka; Yoshimori, Tamotsu

2017-06-03

Inflammation plays a pivotal role in pathophysiological processes of kidney diseases. Macroautophagy/autophagy plays multiple roles in inflammatory responses, and the regulation of inflammation by autophagy has great potential as a treatment for damaged kidneys. A growing body of evidence suggests autophagy protects kidney from versatile kidney inflammatory insults, including those that are acute, chronic, metabolic, and aging-related. It is noteworthy that, in kidney, mitophagy is active, and damaged lysosomes are removed by autophagy. In this mode, autophagy suppresses inflammation to protect the kidney. Systemic inflammation also affects the kidney via pro-inflammatory cytokines and infiltration of inflammatory cells, and autophagy also has a regulatory role in systemic inflammation. This review focuses on the roles of autophagy in kidney diseases and aging through inflammation, and discusses the potential usage of autophagy as an inflammatory modulator for the treatment of kidney diseases.

Classical Renin-Angiotensin System in Kidney Physiology

PubMed Central

Sparks, Matthew A.; Crowley, Steven D.; Gurley, Susan B.; Mirotsou, Maria; Coffman, Thomas M.

2014-01-01

The renin-angiotensin system has powerful effects in control of the blood pressure and sodium homeostasis. These actions are coordinated through integrated actions in the kidney, cardio-vascular system and the central nervous system. Along with its impact on blood pressure, the renin-angiotensin system also influences a range of processes from inflammation and immune responses to longevity. Here, we review the actions of the “classical” renin-angiotensin system, whereby the substrate protein angiotensinogen is processed in a two-step reaction by renin and angiotensin converting enzyme, resulting in the sequential generation of angiotensin I and angiotensin II, the major biologically active renin-angiotensin system peptide, which exerts its actions via type 1 and type 2 angiotensin receptors. In recent years, several new enzymes, peptides, and receptors related to the renin-angiotensin system have been identified, manifesting a complexity that was previously unappreciated. While the functions of these alternative pathways will be reviewed elsewhere in this journal, our focus here is on the physiological role of components of the “classical” renin-angiotensin system, with an emphasis on new developments and modern concepts. PMID:24944035

The Genetic Landscape of Renal Complications in Type 1 Diabetes

PubMed Central

Sandholm, Niina; Van Zuydam, Natalie; Ahlqvist, Emma; Juliusdottir, Thorhildur; Deshmukh, Harshal A.; Rayner, N. William; Di Camillo, Barbara; Forsblom, Carol; Fadista, Joao; Ziemek, Daniel; Salem, Rany M.; Hiraki, Linda T.; Pezzolesi, Marcus; Trégouët, David; Dahlström, Emma; Valo, Erkka; Oskolkov, Nikolay; Ladenvall, Claes; Marcovecchio, M. Loredana; Cooper, Jason; Sambo, Francesco; Malovini, Alberto; Manfrini, Marco; McKnight, Amy Jayne; Lajer, Maria; Harjutsalo, Valma; Gordin, Daniel; Parkkonen, Maija; Lyssenko, Valeriya; McKeigue, Paul M.; Rich, Stephen S.; Brosnan, Mary Julia; Fauman, Eric; Bellazzi, Riccardo; Rossing, Peter; Hadjadj, Samy; Krolewski, Andrzej; Paterson, Andrew D.; Hirschhorn, Joel N.; Maxwell, Alexander P.; Cobelli, Claudio; Colhoun, Helen M.; Groop, Leif; McCarthy, Mark I.

2017-01-01

Diabetes is the leading cause of ESRD. Despite evidence for a substantial heritability of diabetic kidney disease, efforts to identify genetic susceptibility variants have had limited success. We extended previous efforts in three dimensions, examining a more comprehensive set of genetic variants in larger numbers of subjects with type 1 diabetes characterized for a wider range of cross-sectional diabetic kidney disease phenotypes. In 2843 subjects, we estimated that the heritability of diabetic kidney disease was 35% (P=6.4×10−3). Genome-wide association analysis and replication in 12,540 individuals identified no single variants reaching stringent levels of significance and, despite excellent power, provided little independent confirmation of previously published associated variants. Whole-exome sequencing in 997 subjects failed to identify any large-effect coding alleles of lower frequency influencing the risk of diabetic kidney disease. However, sets of alleles increasing body mass index (P=2.2×10−5) and the risk of type 2 diabetes (P=6.1×10−4) associated with the risk of diabetic kidney disease. We also found genome-wide genetic correlation between diabetic kidney disease and failure at smoking cessation (P=1.1×10−4). Pathway analysis implicated ascorbate and aldarate metabolism (P=9.0×10−6), and pentose and glucuronate interconversions (P=3.0×10−6) in pathogenesis of diabetic kidney disease. These data provide further evidence for the role of genetic factors influencing diabetic kidney disease in those with type 1 diabetes and highlight some key pathways that may be responsible. Altogether these results reveal important biology behind the major cause of kidney disease. PMID:27647854

NEK8 Links the ATR-regulated Replication Stress Response and S-phase CDK Activity to Renal Ciliopathies

PubMed Central

Choi, Hyo Jei Claudia; Lin, Jia-Ren; Vannier, Jean-Baptiste; Slaats, Gisela G.; Kile, Andrew C.; Paulsen, Renee D.; Manning, Danielle K.; Beier, David R.; Giles, Rachel H.; Boulton, Simon J.; Cimprich, Karlene A.

2013-01-01

Summary Renal ciliopathies are a leading cause of kidney failure, but their exact etiology is poorly understood. NEK8/NPHP9 is a ciliary kinase associated with two renal ciliopathies in humans and mice, nephronophthisis (NPHP) and polycystic kidney disease. Here, we identify NEK8 as a key effector of the ATR-mediated replication stress response. Cells lacking NEK8 form spontaneous DNA double-strand breaks (DSBs) which further accumulate when replication forks stall, and they exhibit reduced fork rates, unscheduled origin firing, and increased replication fork collapse. NEK8 suppresses DSB formation by limiting cyclin A-associated CDK activity. Strikingly, a mutation in NEK8 that is associated with renal ciliopathies affects its genome maintenance functions. Moreover, kidneys of NEK8 mutant mice accumulate DNA damage, and loss of NEK8 or replication stress similarly disrupts renal cell architecture in a 3D-culture system. Thus, NEK8 is a critical component of the DNA damage response that links replication stress with cystic kidney disorders. PMID:23973373

Outcome Measures Used to Report Kidney Function in Studies Investigating Surgical Management of Kidney Tumours: A Systematic Review.

PubMed

Ellis, Robert J; Cho, Yeoungjee; Del Vecchio, Sharon J; McStea, Megan; Morais, Christudas; Coombes, Jeff S; Wood, Simon T; Gobe, Glenda C; Francis, Ross S

2018-05-01

Most practice decisions relevant to preserving kidney function in patients managed surgically for kidney tumours are driven by observational studies. A wide range of outcome measures are used in these studies, which reduces comparability and increases the risk of reporting bias. To comprehensively and succinctly describe the outcomes used to evaluate kidney function in studies evaluating surgical management of kidney tumours. Electronic search of the PubMed database was conducted to identify studies with at least one measure of kidney function in patients managed surgically for kidney tumours, published between January 2000 and September 2017. Abstracts were initially screened for eligibility. Full texts of articles were then evaluated in more detail for inclusion. A narrative synthesis of the evidence was conducted. A total of 312 studies, involving 127905 participants, were included in this review. Most were retrospective (n=274) studies and conducted in a single centre (n=264). Overall, 78 unique outcome measures were identified, which were grouped into six outcome categories. Absolute postoperative kidney function (n=187), relative kidney function (n=181), and postoperative chronic kidney disease (n=131) were most frequently reported. Kidney function was predominantly quantified using estimated glomerular filtration rate or creatinine clearance (n=255), most using the modification of diet in renal disease equation (n=182). Only 70 studies provided rationale for specific outcome measures used. There is significant variability in the reporting and quantification of kidney function in studies evaluating patients managed surgically for kidney tumours. A standardised approach to measuring and reporting kidney function will increase the effectiveness of outcomes reported and improve relevance of research findings within a clinical context. Although we know that the removal of a kidney can reduce kidney function, clinical significance of various approaches is a matter of debate. This article demonstrates significant variability in the way kidney function was reported across all studies of patients with kidney cancer undergoing surgery, indicating a need for standardisation. Copyright © 2018 European Association of Urology. All rights reserved.

Kidney disease and obesity: epidemiology, mechanisms and treatment.

PubMed

Câmara, Niels Olsen Saraiva; Iseki, Kunitoshi; Kramer, Holly; Liu, Zhi-Hong; Sharma, Kumar

2017-03-01

The theme of World Kidney Day 2017 is 'kidney disease and obesity: healthy lifestyle for healthy kidneys'. To mark this event, Nature Reviews Nephrology invited five leading researchers to describe changes in the epidemiology of obesity-related kidney disease, advances in current understanding of the mechanisms and current approaches to the management of affected patients. The researchers also highlight new advances that could lead to the development of novel treatments and identify areas in which further basic and clinical studies are needed.

Carbamylated erythropoietin protects the kidneys from ischemia-reperfusion injury without stimulating erythropoiesis

DOE Office of Scientific and Technical Information (OSTI.GOV)

Imamura, Ryoichi; Isaka, Yoshitaka; Ichimaru, Naotsugu

Several studies have shown that erythropoietin (EPO) can protect the kidneys from ischemia-reperfusion injury and can raise the hemoglobin (Hb) concentration. Recently, the EPO molecule modified by carbamylation (CEPO) has been identified and was demonstrated to be able to protect several organs without increasing the Hb concentration. We hypothesized that treatment with CEPO would protect the kidneys from tubular apoptosis and inhibit subsequent tubulointerstitial injury without erythropoiesis. The therapeutic effect of CEPO was evaluated using a rat ischemia-reperfusion injury model. Saline-treated kidneys exhibited increased tubular apoptosis with interstitial expression of {alpha}-smooth muscle actin ({alpha}-SMA), while EPO treatment inhibited tubular apoptosismore » and {alpha}-SMA expression to some extent. On the other hand, CEPO-treated kidneys showed minimal tubular apoptosis with limited expression of {alpha}-SMA. Moreover, CEPO significantly promoted tubular epithelial cell proliferation without erythropoiesis. In conclusion, we identified a new therapeutic approach using CEPO to protect kidneys from ischemia-reperfusion injury.« less

The role of sympathetic nervous system in the progression of chronic kidney disease in the era of catheter based sympathetic renal denervation.

PubMed

Petras, Dimitrios; Koutroutsos, Konstantinos; Kordalis, Athanasios; Tsioufis, Costas; Stefanadis, Christodoulos

2013-08-01

The kidney has been shown to be critically involved as both trigger and target of sympathetic nervous system overactivity in both experimental and clinical studies. Renal injury and ischemia, activation of renin angiotensin system and dysfunction of nitric oxide system have been implicated in adrenergic activation from kidney. Conversely, several lines of evidence suggest that sympathetic overactivity, through functional and morphological alterations in renal physiology and structure, may contribute to kidney injury and chronic kidney disease progression. Pharmacologic modulation of sympathetic nervous system activity has been found to have a blood pressure independent renoprotective effect. The inadequate normalization of sympathoexcitation by pharmacologic treatment asks for novel treatment options. Catheter based renal denervation targets selectively both efferent and afferent renal nerves and functionally denervates the kidney providing blood pressure reduction in clinical trials and renoprotection in experimental models by ameliorating the effects of excessive renal sympathetic drive. This review will focus on the role of sympathetic overactivity in the pathogenesis of kidney injury and CKD progression and will speculate on the effect of renal denervation to these conditions.

Hydro-epidemiology of Chronic Kidney Disease(CKD) in Sri Lanka and Its Similarities to the CKD Epidemic in Meso-America.Sarath Gunatilake M.D, Dr. P.H, Professor, California State University, Long Beach California

NASA Astrophysics Data System (ADS)

Illangasekera, T.; Gunatilake, S.

2015-12-01

Over 2000 years ago Sri Lanka was known as the granary of the east. This distinction was achieved with a massive rice production aided by an efficient irrigation system. The basic structural unit of this irrigation system -with thousands of man-made lakes- was a large reservoir collecting rain water from tributaries and redistributing it to a cascade of rice paddy farms. The rice cultivation used organic fertilizer and natural pesticides made from ancient Ayurvedic recipes. The sociopolitical changes initiated in the county in 1977 resulted in a modernized agricultural economy with the renovation of the old irrigation system. Heavy use of pesticides, mostly Glyphosate (brand name "Round Up") with government subsidized cheap synthetic fertilizer (mostly triple phosphate) contaminated with heavy metals, including Arsenic and Cadmium, became a common practice. As a result, the shallow aquifers in the lowest lying areas, recharged by the irrigation water, was contaminated with Calcium, Magnesium phosphates, and the heavy metals, rendering the drinking water from shallow wells in these areas, extremely hard and unpalatable. The practice of drinking water from the shallow wells in low lying areas, most of which are abandoned now, and the use and spraying of pesticides particularly Glyphosate (often without proper personal protective equipment) have been identified in a case control study, as the main risk factors responsible for a massive epidemic of Chronic Kidney Disease (CKD) affecting 450,000 young farmers, resulting in 23,000 deaths. It is hypothesized that the Glyphosate chelates heavy metals delivering it to the kidney, with contaminated drinking water and food, causing progressive kidney damage. The same irrigation system that contributed to past prosperity has now become a scourge within the realm of a modernized agriculture. Climatic variations, global warming and severe dehydration also have been identified as contributory factors. Similar CKD epidemic killing thousands of sugar cane farmers, in Costa Rica, El Salvador and Nicaragua have been documented. The same risk factors (particularly the use of Glyphosate and dehydration) may be at play in these countries but at different levels of intensity.

Spectroscopic photoacoustics for assessing ischemic kidney damage

NASA Astrophysics Data System (ADS)

Berndl, Elizabeth S. L.; He, Xiaolin; Yuen, Darren A.; Kolios, Michael C.

2018-02-01

Ischemic reperfusion injuries (IRIs) are caused by return of blood to a tissue or organ after a period without oxygen or nutrients. Damage in the microvasculature causes an inflammatory response and heterogeneous scarring, which is associated with an increase in collagen in the extracellular matrix. Although most often associated with heart attacks and strokes, IRI also occurs when blood reperfuses a transplanted organ. Currently, monitoring for IRI is limited to biopsies, which are invasive and sample a limited area. In this work, we explored photoacoustic (PA) biomarkers of scarring. IRI events were induced in mice (n=2) by clamping the left renal artery, then re-establishing flow. At 53 days post-surgery, kidneys were saline perfused and cut in half laterally. One half was immediately imaged with a VevoX system (Fujifilm-VisualSonics, Toronto) in two near infrared ranges - 680 to 970 nm (NIR), and 1200 to 1350 nm (NIR II). The other half was decellularized and then imaged at NIR and NIR II. Regions of interest were manually identified and analyzed for each kidney. For both cellularized and decellularized samples, the PA signal ratio based on irradiation wavelengths of 715:930 nm was higher in damaged kidneys than for undamaged kidneys (p < 0.0001 for both). Damaged kidneys had ROIs with spectra indicating the presence of collagen in the NIR II range, while healthy kidneys did not. Collagen rich spectra were more apparent in decellularized kidneys, suggesting that in the cellularized samples, other components may be contributing to the signal. PA imaging using spectral ratios associated with collagen signatures may provide a non-invasive tool to determine areas of tissue damage due to IRIs.

Diuretic renography in hydronephrosis: delayed tissue tracer transit accompanies both functional decline and tissue reorganization.

PubMed

Schlotmann, Andreas; Clorius, John H; Rohrschneider, Wiltrud K; Clorius, Sandra N; Amelung, Folker; Becker, Kristianna

2008-07-01

The significance of delayed tissue tracer transit (TTT) of (99m)Tc-mercaptoacetyltriglycine ((99m)Tc-MAG3) has not been systematically evaluated in hydronephrosis. We sought to demonstrate that delayed TTT accompanies both functional decline and histomorphologic restructuring. Twenty 2- to 3-mo-old piglets with surgically induced partial unilateral ureteral stenosis were examined with magnetic resonance urography (MRU) to evaluate morphology and with (99m)Tc-MAG3 diuretic renography (DR) to determine single-kidney function (SKF), evaluate the response to furosemide stimulation (RFS), and assess TTT. All animals had DR and MRU before and after surgery and a third DR after surgery. Piglets were sacrificed after the final DR for renal histology. A total histologic score (THS) was generated. Preoperative DR demonstrated nonobstructive RFS, timely TTT, and balanced SKF in all 20 kidneys. After ureteral ligature, MRU demonstrated pelvic dilatation in all piglets. The postoperative DRs revealed 12 kidneys with delayed TTT in one or both follow-ups. In these 12 kidneys, the SKF declined from 51% +/- 4% to 18% +/- 14%, and the THS was 9.0 +/- 4.0. Three kidneys always had timely TTT, balanced SKF, and a THS of 1.8 +/- 0.3. The contralateral, nonoperated kidneys had timely TTT and a THS of 1.2 +/- 0.9. Postoperative scintigrams showed that 3 of 8 kidneys (38%) with an obstructive RFS had timely TTT, which demonstrates that TTT and RFS are not equivalent. In hydronephrosis, a delayed TTT of (99m)Tc-MAG3 accompanies both functional decline and histomorphologic restructuring in obstruction. According to the literature, a delayed TTT is determined by the filtration fraction of the kidneys and appears to identify an obstruction-mediated upregulated renin-angiotensin system.

CXC Chemokine Receptor 7 (CXCR7) Regulates CXCR4 Protein Expression and Capillary Tuft Development in Mouse Kidney

PubMed Central

Haege, Sammy; Mueller, Wiebke; Nietzsche, Sandor; Lupp, Amelie; Mackay, Fabienne; Schulz, Stefan; Stumm, Ralf

2012-01-01

Background The CXCL12/CXCR4 axis is involved in kidney development by regulating formation of the glomerular tuft. Recently, a second CXCL12 receptor was identified and designated CXCR7. Although it is established that CXCR7 regulates heart and brain development in conjunction with CXCL12 and CXCR4, little is known about the influence of CXCR7 on CXCL12 dependent kidney development. Methodology/Principal Findings We provided analysis of CXCR7 expression and function in the developing mouse kidney. Using in situ hybridization, we identified CXCR7 mRNA in epithelial cells including podocytes at all nephron stages up to the mature glomerulus. CXCL12 mRNA showed a striking overlap with CXCR7 mRNA in epithelial structures. In addition, CXCL12 was detected in stromal cells and the glomerular tuft. Expression of CXCR4 was complementary to that of CXCR7 as it occurred in mesenchymal cells, outgrowing ureteric buds and glomerular endothelial cells but not in podocytes. Kidney examination in CXCR7 null mice revealed ballooning of glomerular capillaries as described earlier for CXCR4 null mice. Moreover, we detected a severe reduction of CXCR4 protein but not CXCR4 mRNA within the glomerular tuft and in the condensed mesenchyme. Malformation of the glomerular tuft in CXCR7 null mice was associated with mesangial cell clumping. Conclusions/Significance We established that there is a similar glomerular pathology in CXCR7 and CXCR4 null embryos. Based on the phenotype and the anatomical organization of the CXCL12/CXCR4/CXCR7 system in the forming glomerulus, we propose that CXCR7 fine-tunes CXCL12/CXCR4 mediated signalling between podocytes and glomerular capillaries. PMID:22880115

CXC chemokine receptor 7 (CXCR7) regulates CXCR4 protein expression and capillary tuft development in mouse kidney.

PubMed

Haege, Sammy; Einer, Claudia; Thiele, Stefanie; Mueller, Wiebke; Nietzsche, Sandor; Lupp, Amelie; Mackay, Fabienne; Schulz, Stefan; Stumm, Ralf

2012-01-01

The CXCL12/CXCR4 axis is involved in kidney development by regulating formation of the glomerular tuft. Recently, a second CXCL12 receptor was identified and designated CXCR7. Although it is established that CXCR7 regulates heart and brain development in conjunction with CXCL12 and CXCR4, little is known about the influence of CXCR7 on CXCL12 dependent kidney development. We provided analysis of CXCR7 expression and function in the developing mouse kidney. Using in situ hybridization, we identified CXCR7 mRNA in epithelial cells including podocytes at all nephron stages up to the mature glomerulus. CXCL12 mRNA showed a striking overlap with CXCR7 mRNA in epithelial structures. In addition, CXCL12 was detected in stromal cells and the glomerular tuft. Expression of CXCR4 was complementary to that of CXCR7 as it occurred in mesenchymal cells, outgrowing ureteric buds and glomerular endothelial cells but not in podocytes. Kidney examination in CXCR7 null mice revealed ballooning of glomerular capillaries as described earlier for CXCR4 null mice. Moreover, we detected a severe reduction of CXCR4 protein but not CXCR4 mRNA within the glomerular tuft and in the condensed mesenchyme. Malformation of the glomerular tuft in CXCR7 null mice was associated with mesangial cell clumping. We established that there is a similar glomerular pathology in CXCR7 and CXCR4 null embryos. Based on the phenotype and the anatomical organization of the CXCL12/CXCR4/CXCR7 system in the forming glomerulus, we propose that CXCR7 fine-tunes CXCL12/CXCR4 mediated signalling between podocytes and glomerular capillaries.

Circulating nucleic acids as possible damage-associated molecular patterns in different stages of renal failure.

PubMed

Kocić, Gordana; Radenkovic, Sonja; Cvetkovic, Tatjana; Cencic, Avrelija; Carluccio, Francesco; Musovic, Dijana; Nikolić, Goran; Jevtović-Stoimenov, Tatjana; Sokolović, Dusan; Milojkovic, Boban; Basic, Jelena; Veljkovic, Andrej; Stojanović, Svetlana

2010-05-01

Chronic renal failure (CRF) is a condition associated with the risk of cardiovascular complications. Systemic inflammatory response, initiated by the pathogen-associated molecular-pattern (PAMP) molecules, exerts many similarities with the damage-associated molecular-pattern (DAMP) molecule-induced systemic response. Up to now, a number of DAMP molecules were identified. We hypothesized that the available circulating nucleic acids, acting as DAMPs, may modulate immunoinflammatory reaction in CRF. Patients with the different stages of chronic kidney disease, kidney transplantation, and patients on dialysis were included in the study. Obtained results about higher concentration of circulating ribonucleic acid (RNA), according to the stages of kidney diseases, may contribute to the hypothesis that damaged kidney tissue releases nucleic acids. Circulating RNAs expressed maximal absorbance peak at 270 nm in spectrophotometric scan analysis, which corresponded to polyC, compared to different standard samples. During in vitro conditions, by using the culture of human residential macrophages, circulating RNA isolated from patients with IV-V-stage renal diseases, patients on hemodialysis, and patients who underwent renal transplantation were able to significantly change signal transduction proteins related to inflammation and antiviral response. They significantly increased the intracellular concentration of active nuclear transcription factor nuclear factor kappa B (NF-kappaB), interferon regulatory factors (IRF)-3, and IRF-7 and significantly decreased melanoma differentiation-associated protein-5 (MDA-5) and p38. In this way, it seems that circulating RNA, acting as DAMP, may contribute to the mechanisms of additional inflammatory reaction, possible immune destruction, and decreased antiviral response, related to complications in kidney diseases.

Chronic treatment with atrial natriuretic peptide in spontaneously hypertensive rats: beneficial renal effects and sex differences.

PubMed

Romero, Mariana; Caniffi, Carolina; Bouchet, Gonzalo; Costa, María A; Elesgaray, Rosana; Arranz, Cristina; Tomat, Analía L

2015-01-01

The aim of this study was to investigate the effects of chronic treatment with atrial natriuretic peptide (ANP) on renal function, nitric oxide (NO) system, oxidative stress, collagen content and apoptosis in kidneys of spontaneously hypertensive rats (SHR), as well as sex-related differences in the response to the treatment. 10 week-old male and female SHR were infused with ANP (100 ng/h/rat) or saline (NaCl 0.9%) for 14 days (subcutaneous osmotic pumps). Systolic blood pressure (SBP) was recorded and diuresis and natriuresis were determined. After treatment, renal NO synthase (NOS) activity and eNOS expression were evaluated. Thiobarbituric acid-reactive substances (TBARS), glutathione concentration and glutathione peroxidase (GPx) and superoxide dismutase (SOD) activities were determined in the kidney. Collagen was identified in renal slices by Sirius red staining and apoptosis by Tunel assay. Female SHR showed lower SBP, oxidative stress, collagen content and apoptosis in kidney, and higher renal NOS activity and eNOS protein content, than males. ANP lowered SBP, increased diuresis, natriuresis, renal NOS activity and eNOS expression in both sexes. Renal response to ANP was more marked in females than in males. In kidney, ANP reduced TBARS, renal collagen content and apoptosis, and increased glutathione concentration and activity of GPx and SOD enzymes in both sexes. Female SHR exhibited less organ damage than males. Chronic ANP treatment would ameliorate hypertension and end-organ damage in the kidney by reducing oxidative stress, increasing NO-system activity, and diminishing collagen content and apoptosis, in both sexes.

Chronic Treatment with Atrial Natriuretic Peptide in Spontaneously Hypertensive Rats: Beneficial Renal Effects and Sex Differences

PubMed Central

Romero, Mariana; Caniffi, Carolina; Bouchet, Gonzalo; Costa, María A.; Elesgaray, Rosana; Arranz, Cristina; Tomat, Analía L.

2015-01-01

Objective The aim of this study was to investigate the effects of chronic treatment with atrial natriuretic peptide (ANP) on renal function, nitric oxide (NO) system, oxidative stress, collagen content and apoptosis in kidneys of spontaneously hypertensive rats (SHR), as well as sex-related differences in the response to the treatment. Methods 10 week-old male and female SHR were infused with ANP (100 ng/h/rat) or saline (NaCl 0.9%) for 14 days (subcutaneous osmotic pumps). Systolic blood pressure (SBP) was recorded and diuresis and natriuresis were determined. After treatment, renal NO synthase (NOS) activity and eNOS expression were evaluated. Thiobarbituric acid-reactive substances (TBARS), glutathione concentration and glutathione peroxidase (GPx) and superoxide dismutase (SOD) activities were determined in the kidney. Collagen was identified in renal slices by Sirius red staining and apoptosis by Tunel assay. Results Female SHR showed lower SBP, oxidative stress, collagen content and apoptosis in kidney, and higher renal NOS activity and eNOS protein content, than males. ANP lowered SBP, increased diuresis, natriuresis, renal NOS activity and eNOS expression in both sexes. Renal response to ANP was more marked in females than in males. In kidney, ANP reduced TBARS, renal collagen content and apoptosis, and increased glutathione concentration and activity of GPx and SOD enzymes in both sexes. Conclusions Female SHR exhibited less organ damage than males. Chronic ANP treatment would ameliorate hypertension and end-organ damage in the kidney by reducing oxidative stress, increasing NO-system activity, and diminishing collagen content and apoptosis, in both sexes. PMID:25774801

Lengths of nephron tubule segments and collecting ducts in the CD-1 mouse kidney: an ontogeny study.

PubMed

Walton, Sarah L; Moritz, Karen M; Bertram, John F; Singh, Reetu R

2016-11-01

The kidney continues to mature postnatally, with significant elongation of nephron tubules and collecting ducts to maintain fluid/electrolyte homeostasis. The aim of this project was to develop methodology to estimate lengths of specific segments of nephron tubules and collecting ducts in the CD-1 mouse kidney using a combination of immunohistochemistry and design-based stereology (vertical uniform random sections with cycloid arc test system). Lengths of tubules were determined at postnatal day 21 (P21) and 2 and 12 mo of age and also in mice fed a high-salt diet throughout adulthood. Immunohistochemistry was performed to identify individual tubule segments [aquaporin-1, proximal tubules (PT) and thin descending limbs of Henle (TDLH); uromodulin, distal tubules (DT); aquaporin-2, collecting ducts (CD)]. All tubular segments increased significantly in length between P21 and 2 mo of age (PT, 602% increase; DT, 200% increase; TDLH, 35% increase; CD, 53% increase). However, between 2 and 12 mo, a significant increase in length was only observed for PT (76% increase in length). At 12 mo of age, kidneys of mice on a high-salt diet demonstrated a 27% greater length of the TDLH, but no significant change in length was detected for PT, DT, and CD compared with the normal-salt group. Our study demonstrates an efficient method of estimating lengths of specific segments of the renal tubular system. This technique can be applied to examine structure of the renal tubules in combination with the number of glomeruli in the kidney in models of altered renal phenotype. Copyright © 2016 the American Physiological Society.

Renalase is a novel, soluble monoamine oxidase that regulates cardiac function and blood pressure

PubMed Central

Xu, Jianchao; Li, Guoyong; Wang, Peili; Velazquez, Heino; Yao, Xiaoqiang; Li, Yanyan; Wu, Yanling; Peixoto, Aldo; Crowley, Susan; Desir, Gary V.

2005-01-01

The kidney not only regulates fluid and electrolyte balance but also functions as an endocrine organ. For instance, it is the major source of circulating erythropoietin and renin. Despite currently available therapies, there is a marked increase in cardiovascular morbidity and mortality among patients suffering from end-stage renal disease. We hypothesized that the current understanding of the endocrine function of the kidney was incomplete and that the organ might secrete additional proteins with important biological roles. Here we report the identification of a novel flavin adenine dinucleotide–dependent amine oxidase (renalase) that is secreted into the blood by the kidney and metabolizes catecholamines in vitro (renalase metabolizes dopamine most efficiently, followed by epinephrine, and then norepinephrine). In humans, renalase gene expression is highest in the kidney but is also detectable in the heart, skeletal muscle, and the small intestine. The plasma concentration of renalase is markedly reduced in patients with end-stage renal disease, as compared with healthy subjects. Renalase infusion in rats caused a decrease in cardiac contractility, heart rate, and blood pressure and prevented a compensatory increase in peripheral vascular tone. These results identify renalase as what we believe to be a novel amine oxidase that is secreted by the kidney, circulates in blood, and modulates cardiac function and systemic blood pressure. PMID:15841207

The Adult Drosophila Malpighian Tubules Are Maintained by Pluripotent Stem Cells

PubMed Central

Singh, Shree Ram; Liu, Wei; Hou, Steven X.

2007-01-01

Summary All animals must excrete the waste products of metabolism. Excretion is performed by the kidney in vertebrates and by the Malpighian tubules in Drosophila. The mammalian kidney has an inherent ability for recovery and regeneration following ischemic injury. Stem cells and progenitor cells have been proposed to be responsible for repair and regeneration of injured renal tissue. In Drosophila, the Malpighian tubules are thought to be very stable, and no stem cells have been identified. We have identified pluripotent stem cells in the region of lower tubules and ureters of the Malpighian tubules. Using lineage tracing and molecular marker labeling, we demonstrated that several differentiated cells in the Malpighian tubules arise from the stem cells and an autocrine JAK-STAT signaling regulates the stem cells' self-renewal. Identifying adult kidney stem cells in Drosophila may provide important clues for understanding mammalian kidney repair and regeneration during injury. PMID:18371350

Acute kidney injury post-major orthopaedic surgery: A single-Centre case-control study.

PubMed

Ying, Tracey; Chan, Samantha; Lane, Stephen; Somerville, Christine

2018-02-01

To identify risk factors for acute kidney injury following major orthopaedic surgery. We included all patients undergoing major orthopaedic surgery at University Hospital Geelong between 2008 and 2014 in the study. Out of 2188 surgeries audited, we identified cases of acute kidney injury using the RIFLE criteria and matched those to controls 2:1 for age, sex, procedure and chronic kidney disease stage. We reviewed their records for risk factors of postoperative acute kidney injury, including medications such as gentamicin, diuretics, non-steroidal anti-inflammatory drugs and angiotensin-converting enzyme inhibitor or angiotensin receptor blocker use. We reviewed the patients' history of cardiovascular disease, chronic liver disease, hypertension and diabetes mellitus along with presence of sepsis and obesity. Associations of hypothetical risk factors were estimated using conditional logistic regression. We identified 164 cases of AKI in an elderly cohort (median age = 73 years). Controlling for baseline comorbidities, both diuretic and angiotensin-converting enzyme inhibitor or angiotensin receptor blocker use were found to be associated with a twofold risk of acute kidney injury (diuretic - OR 2.06 95% CI:1.30-3.26, P < 0.005, angiotensin-converting enzyme inhibitor or angiotensin receptor blocker use OR 2.09 95% CI:1.31-3.32, P < 0.005). A dose-effect model accounting for perioperative nonsteroidal anti-inflammatory drug administration demonstrated a linear relationship between the number of times these drugs were given and postoperative acute kidney injury risk (OR 1.35 95% CI:1.05-1.73, P = 0.02). We identified perioperative diuretics, non-steroidal anti-inflammatory drugs and angiotensin-converting enzyme inhibitor or angiotensin receptor blocker to be significantly associated with postoperative AKI. Further prospective studies are required to confirm this. © 2016 Asian Pacific Society of Nephrology.

Adenine phosphoribosyltransferase deficiency in the United Kingdom: two novel mutations and a cross-sectional survey

PubMed Central

Arenas-Hernandez, Monica; Escuredo, Emilia; Fairbanks, Lynette; Marinaki, Tony; Mapplebeck, Sarah; Sheaff, Michael; Almond, Michael K.

2016-01-01

Background Adenine phosphoribosyltransferase deficiency is an inborn error of metabolism that can cause kidney disease from crystalline nephropathy or kidney stones. Methods We present three cases from a single centre with varied presentations to illustrate how increasing awareness led to better patient identification. We then undertook a cross-sectional survey of all the patients identified from the Purine Research Laboratory in the UK since 1974. Results Our index case presented with recurrent nephrolithiasis and was diagnosed on stone analysis, the second case presented with acute kidney injury and the third case was identified from a biopsy undertaken for acute on chronic kidney injury. Genetic studies identified two novel mutations. Twenty patients were retrospectively identified. The mean age at diagnosis was 25 years (range 2–70); eight were <20 years, seven were 20–40 years and five were >40 years. Five of the 20 patients were deceased, 3 after end-stage renal disease (ESRD). Twelve have normal renal function, one had CKD stage 3, one had severe kidney disease and one was on dialysis. Conclusions Adenine phosphoribosyltransferase deficiency presents in a wide spectrum in all age groups. Patients can be completely asymptomatic and kidney disease may be incorrectly attributed to other conditions. Outcome is poor in late diagnosis and there is a high prevalence of ESRD. Patients with unexplained renal stone disease or deterioration in kidney function should be considered for screening. Identification and surveillance of patients in the UK can improve. There is now a rare disease registry with meetings organized that include patients, families and health care providers to improve awareness. PMID:27994857

The construction of a panel of serum amino acids for the identification of early chronic kidney disease patients.

PubMed

Li, Rui; Dai, Jinna; Kang, Hui

2018-03-01

Serum creatinine, urea, and cystatin-c are standardly used for the evaluation of renal function in the clinic. However, some patients have chronic kidney disease but still retain kidney function; a conventional serum index in these patients can be completely normal. Serum amino acid levels can reflect subtle changes in metabolism and are closely related to renal function. Here, we investigated how amino acids change as renal impairment increases. Subjects were divided into three groups by renal function glomerular filtration rate: healthy controls, patients with chronic kidney disease with normal kidney function, and patients with chronic kidney disease with decreased kidney function group. We identified 11 amino acids of interest using LC-MS/MS on MRM (+) mode. Statistical analysis indicated that alanine (ALA), valine (VAL), and tyrosine (TYR) decrease with renal function impairment, whereas phenylalanine (PHE) and citrulline (CIT) increase. We tried to construct a diagnostic model utilizing a combination of amino acids capable of identifying early chronic kidney disease patients. The accuracy, specificity, and sensitivity of the combining predictors were 86.9%, 84.6%, and 90.9%, respectively, which is superior to the reported values for serum creatinine, urea, and cystatin-c. Our data suggest that serum amino acid levels may supply important information for the early detection of chronic kidney disease. We are the first to establish a diagnostic model utilizing serum levels of multiple amino acids for the diagnosis of patients with early-stage chronic kidney disease. © 2017 Wiley Periodicals, Inc.

Kidney Involvement of Patients with Waldenström Macroglobulinemia and Other IgM-Producing B Cell Lymphoproliferative Disorders.

PubMed

Higgins, Larissa; Nasr, Samih H; Said, Samar M; Kapoor, Prashant; Dingli, David; King, Rebecca L; Rajkumar, S Vincent; Kyle, Robert A; Kourelis, Taxiarchis; Gertz, Morie A; Dispenzieri, Angela; Lacy, Martha Q; Buadi, Francis K; Ansell, Stephen M; Gonsalves, Wilson I; Thompson, Carrie A; Fervenza, Fernando C; Zand, Ladan; Hwa, Yi L; Jevremovic, Dragan; Shi, Min; Leung, Nelson

2018-05-30

Kidney involvement in Waldenström macroglobulinemia is less well described compared with kidney manifestations in multiple myeloma. Of the 1363 patients seen with Waldenström macroglobulinemia and other IgM-secreting B cell lymphoproliferative disorders seen at the Mayo Clinic between 1996 and 2015, 57 kidney biopsies were retrospectively studied. The biopsy findings were correlated with clinical, kidney, and hematologic characteristics. Criteria for inclusion were evidence of a monoclonal IgM protein and availability of a kidney and a bone marrow biopsy for review. Glomerular and tubulointerstitial pathologies were categorized according to whether they were related to the monoclonal IgM. Of the 57 patients identified, monoclonal gammopathy-related kidney lesions were identified in 82% (47 of 57 biopsies), whereas nonmonoclonal gammopathy-related kidney lesions were seen in 18% (ten of 57). Monoclonal gammopathy-related kidney lesions included monoclonal Ig-related amyloidosis ( n =19; 33%), nonamyloid glomerulopathy ( n =20, 35%), and tubulointerstitial nephropathies ( n =8; 14%). The most common monoclonal gammopathy-related kidney lesion was monoclonal Ig-related amyloidosis ( n =19; 33%) followed by cryoglobulinemic GN ( n =13; 28%). Lymphoma infiltration was the most common tubulointerstitial lesion ( n =4; 9%). The hematologic diagnosis was Waldenström macroglobulinemia in 74% ( n =42), monoclonal gammopathy of renal significance in 16% ( n =9), and marginal zone lymphoma ( n =2), chronic lymphocytic leukemia ( n =2), and low-grade B cell lymphoma ( n =2) in 4% each. Our study confirms a diverse variety of kidney lesions in patients with monoclonal IgM gammopathy. Copyright © 2018 by the American Society of Nephrology.

Duplex kidney: not just a drooping lily.

PubMed

Doery, Ashlea J; Ang, Eileen; Ditchfield, Michael R

2015-04-01

Duplex kidneys are common, mostly asymptomatic and of no clinical significance. However, they can be associated with significant pathology, often with long-term morbidity. There is minimal literature on the review of the duplex kidney, its associated anomalies and complications. The purpose of this paper is to review our experience of imaging the spectrum of abnormalities associated with duplex kidneys in the paediatric population and correlate this with contemporary literature. A retrospective review of the radiology database in a tertiary paediatric centre was performed. A word search of the Radiology Information System for 'duplex' of patients under the age of 16 was undertaken and limited to studies performed between 2006 and 2013. Two hundred seventy-four patients were identified (age range 0-16, median 3 years, gender 59.9% female) who had 836 studies: ultrasound 598/836 (71.6%), nuclear medicine 180/836 (21.5%), micturating cystourethrogram 52/836 (6.2%), MRI 5/836 (<1%) and CT scan 1/836 (<1%). Patients were categorised as duplex and no complication (151/274 = 55.1%), upper moiety obstruction, lower moiety reflux/scarring, multicystic dysplastic kidney, abnormal ureteric insertion and other pathology. Duplex kidneys are common and often not clinically significant. However, this study demonstrates almost 50% of paediatric patients investigated for duplex kidneys had complications requiring treatment. The most common complications were upper moiety obstruction associated with a ureterocele and lower moiety vesicoureteric reflux. Ultrasound was the most common modality for early detection of these complications. © 2015 The Royal Australian and New Zealand College of Radiologists.

Pre-operative renal volume predicts peak creatinine after congenital heart surgery in neonates.

PubMed

Carmody, J Bryan; Seckeler, Michael D; Ballengee, Cortney R; Conaway, Mark; Jayakumar, K Anitha; Charlton, Jennifer R

2014-10-01

Acute kidney injury is common in neonates following surgery for congenital heart disease. We conducted a retrospective analysis to determine whether neonates with smaller pre-operative renal volume were more likely to develop post-operative acute kidney injury. We conducted a retrospective review of 72 neonates who underwent congenital heart surgery for any lesion other than patent ductus arteriosus at our institution from January 2007 to December 2011. Renal volume was calculated by ultrasound using the prolate ellipsoid formula. The presence and severity of post-operative acute kidney injury was determined both by measuring the peak serum creatinine in the first 7 days post-operatively and by using the Acute Kidney Injury Network scoring system. Using a linear change point model, a threshold renal volume of 17 cm³ was identified. Below this threshold, there was an inverse linear relationship between renal volume and peak post-operative creatinine for all patients (p = 0.036) and the subgroup with a single morphologic right ventricle (p = 0.046). There was a non-significant trend towards more acute kidney injury using Acute Kidney Injury Network criteria in all neonates with renal volume ≤17 cm³ (p = 0.11) and in the subgroup with a single morphologic right ventricle (p = 0.17). Pre-operative renal volume ≤17 cm³ is associated with a higher peak post-operative creatinine and potentially greater risk for post-operative acute kidney injury for neonates undergoing congenital heart surgery. Neonates with a single right ventricle may be at higher risk.

The kidney cancer research priority-setting partnership: Identifying the top 10 research priorities as defined by patients, caregivers, and expert clinicians.

PubMed

Jones, Jennifer; Bhatt, Jaimin; Avery, Jonathan; Laupacis, Andreas; Cowan, Katherine; Basappa, Naveen; Basiuk, Joan; Canil, Christina; Al-Asaaed, Sohaib; Heng, Daniel; Wood, Lori; Stacey, Dawn; Kollmannsberger, Christian; Jewett, Michael A S

2017-12-01

It is critically important to define disease-specific research priorities to better allocate limited resources. There is growing recognition of the value of involving patients and caregivers, as well as expert clinicians in this process. To our knowledge, this has not been done this way for kidney cancer. Using the transparent and inclusive process established by the James Lind Alliance, the Kidney Cancer Research Network of Canada (KCRNC) sponsored a collaborative consensus-based priority-setting partnership (PSP) to identify research priorities in the management of kidney cancer. The final result was identification of 10 research priorities for kidney cancer, which are discussed in the context of current initiatives and gaps in knowledge. This process provided a systematic and effective way to collaboratively establish research priorities with patients, caregivers, and clinicians, and provides a valuable resource for researchers and funding agencies.

Building Chronic Kidney Disease Clinical Practice Guidelines Using the openEHR Guideline Definition Language.

PubMed

Lin, Ching-Heng; Lo, Ying-Chih; Hung, Pei-Yuan; Liou, Der-Ming

2016-12-07

As a result of the disease's high prevalence, chronic kidney disease (CKD) has become a global public health problem. A clinical decision support system that integrates with computer-interpretable guidelines (CIGs) should improve clinical outcomes and help to ensure patient safety. The openEHR guideline definition language (GDL) is a formal language used to represent CIGs. This study explores the feasibility of using a GDL approach for CKD; it also attempts to identify any potential gaps between the ideal concept and reality. Using the Kidney Disease Improving Global Outcomes (KDIGO) anemia guideline as material, we designed a development workflow in order to establish a series of GDL guidelines. Focus group discussions were conducted in order to identify important issues related to GDL implementation. Ten GDL guidelines and 37 archetypes were established using the KDIGO guideline document. For the focus group discussions, 16 clinicians and 22 IT experts were recruited and their perceptions, opinions and attitudes towards the GDL approach were explored. Both groups provided positive feedback regarding the GDL approach, but raised various concerns about GDL implementation. Based on the findings of this study, we identified some potential gaps that might exist during implementation between the GDL concept and reality. Three directions remain to be investigated in the future. Two of them are related to the openEHR GDL approach. Firstly, there is a need for the editing tool to be made more sophisticated. Secondly, there needs to be integration of the present approach into non openEHR-based hospital information systems. The last direction focuses on the applicability of guidelines and involves developing a method to resolve any conflicts that occur with insurance payment regulations.

Cross-platform single cell analysis of kidney development shows stromal cells express Gdnf.

PubMed

Magella, Bliss; Adam, Mike; Potter, Andrew S; Venkatasubramanian, Meenakshi; Chetal, Kashish; Hay, Stuart B; Salomonis, Nathan; Potter, S Steven

2018-02-01

The developing kidney provides a useful model for study of the principles of organogenesis. In this report we use three independent platforms, Drop-Seq, Chromium 10x Genomics and Fluidigm C1, to carry out single cell RNA-Seq (scRNA-Seq) analysis of the E14.5 mouse kidney. Using the software AltAnalyze, in conjunction with the unsupervised approach ICGS, we were unable to identify and confirm the presence of 16 distinct cell populations during this stage of active nephrogenesis. Using a novel integrative supervised computational strategy, we were able to successfully harmonize and compare the cell profiles across all three technological platforms. Analysis of possible cross compartment receptor/ligand interactions identified the nephrogenic zone stroma as a source of GDNF. This was unexpected because the cap mesenchyme nephron progenitors had been thought to be the sole source of GDNF, which is a key driver of branching morphogenesis of the collecting duct system. The expression of Gdnf by stromal cells was validated in several ways, including Gdnf in situ hybridization combined with immunohistochemistry for SIX2, and marker of nephron progenitors, and MEIS1, a marker of stromal cells. Finally, the single cell gene expression profiles generated in this study confirmed and extended previous work showing the presence of multilineage priming during kidney development. Nephron progenitors showed stochastic expression of genes associated with multiple potential differentiation lineages. Copyright © 2017 Elsevier Inc. All rights reserved.

User Requirements for a Chronic Kidney Disease Clinical Decision Support Tool to Promote Timely Referral.

PubMed

Gulla, Joy; Neri, Pamela M; Bates, David W; Samal, Lipika

2017-05-01

Timely referral of patients with CKD has been associated with cost and mortality benefits, but referrals are often done too late in the course of the disease. Clinical decision support (CDS) offers a potential solution, but interventions have failed because they were not designed to support the physician workflow. We sought to identify user requirements for a chronic kidney disease (CKD) CDS system to promote timely referral. We interviewed primary care physicians (PCPs) to identify data needs for a CKD CDS system that would encourage timely referral and also gathered information about workflow to assess risk factors for progression of CKD. Interviewees were general internists recruited from a network of 14 primary care clinics affiliated with Brigham and Women's Hospital (BWH). We then performed a qualitative analysis to identify user requirements and system attributes for a CKD CDS system. Of the 12 participants, 25% were women, the mean age was 53 (range 37-82), mean years in clinical practice was 27 (range 11-58). We identified 21 user requirements. Seven of these user requirements were related to support for the referral process workflow, including access to pertinent information and support for longitudinal co-management. Six user requirements were relevant to PCP management of CKD, including management of risk factors for progression, interpretation of biomarkers of CKD severity, and diagnosis of the cause of CKD. Finally, eight user requirements addressed user-centered design of CDS, including the need for actionable information, links to guidelines and reference materials, and visualization of trends. These 21 user requirements can be used to design an intuitive and usable CDS system with the attributes necessary to promote timely referral. Copyright © 2017 Elsevier B.V. All rights reserved.

RNA Sequencing Identifies Novel Translational Biomarkers of Kidney Fibrosis

PubMed Central

Craciun, Florin L.; Bijol, Vanesa; Ajay, Amrendra K.; Rao, Poornima; Kumar, Ramya K.; Hutchinson, John; Hofmann, Oliver; Joshi, Nikita; Luyendyk, James P.; Kusebauch, Ulrike; Moss, Christopher L.; Srivastava, Anand; Himmelfarb, Jonathan; Waikar, Sushrut S.; Moritz, Robert L.

2016-01-01

CKD is the gradual, asymptomatic loss of kidney function, but current tests only identify CKD when significant loss has already happened. Several potential biomarkers of CKD have been reported, but none have been approved for preclinical or clinical use. Using RNA sequencing in a mouse model of folic acid-induced nephropathy, we identified ten genes that track kidney fibrosis development, the common pathologic finding in patients with CKD. The gene expression of all ten candidates was confirmed to be significantly higher (approximately ten- to 150-fold) in three well established, mechanistically distinct mouse models of kidney fibrosis than in models of nonfibrotic AKI. Protein expression of these genes was also high in the folic acid model and in patients with biopsy-proven kidney fibrosis. mRNA expression of the ten genes increased with increasing severity of kidney fibrosis, decreased in response to therapeutic intervention, and increased only modestly (approximately two- to five-fold) with liver fibrosis in mice and humans, demonstrating specificity for kidney fibrosis. Using targeted selected reaction monitoring mass spectrometry, we detected three of the ten candidates in human urine: cadherin 11 (CDH11), macrophage mannose receptor C1 (MRC1), and phospholipid transfer protein (PLTP). Furthermore, urinary levels of each of these three proteins distinguished patients with CKD (n=53) from healthy individuals (n=53; P<0.05). In summary, we report the identification of urinary CDH11, MRC1, and PLTP as novel noninvasive biomarkers of CKD. PMID:26449608

A computer-aided diagnostic system for kidney disease

PubMed Central

Jahantigh, Farzad Firouzi; Malmir, Behnam; Avilaq, Behzad Aslani

2017-01-01

Background Disease diagnosis is complicated since patients may demonstrate similar symptoms but physician may diagnose different diseases. There are a few number of investigations aimed to create a fuzzy expert system, as a computer aided system for disease diagnosis. Methods In this research, a cross-sectional descriptive study conducted in a kidney clinic in Tehran, Iran in 2012. Medical diagnosis fuzzy rules applied, and a set of symptoms related to the set of considered diseases defined. The input case to be diagnosed defined by assigning a fuzzy value to each symptom and then three physicians asked about each suspected diseases. Then comments of those three physicians summarized for each disease. The fuzzy inference applied to obtain a decision fuzzy set for each disease, and crisp decision values attained to determine the certainty of existence for each disease. Results Results indicated that, in the diagnosis of seven cases of kidney disease by examining 21 indicators using fuzzy expert system, kidney stone disease with 63% certainty was the most probable, renal tubular was at the lowest level with 15%, and other kidney diseases were at the other levels. The most remarkable finding of this study was that results of kidney disease diagnosis (e.g., kidney stone) via fuzzy expert system were fully compatible with those of kidney physicians. Conclusion The proposed fuzzy expert system is a valid, reliable, and flexible instrument to diagnose several typical input cases. The developed system decreases the effort of initial physical checking and manual feeding of input symptoms. PMID:28392995

A computer-aided diagnostic system for kidney disease.

PubMed

Jahantigh, Farzad Firouzi; Malmir, Behnam; Avilaq, Behzad Aslani

2017-03-01

Disease diagnosis is complicated since patients may demonstrate similar symptoms but physician may diagnose different diseases. There are a few number of investigations aimed to create a fuzzy expert system, as a computer aided system for disease diagnosis. In this research, a cross-sectional descriptive study conducted in a kidney clinic in Tehran, Iran in 2012. Medical diagnosis fuzzy rules applied, and a set of symptoms related to the set of considered diseases defined. The input case to be diagnosed defined by assigning a fuzzy value to each symptom and then three physicians asked about each suspected diseases. Then comments of those three physicians summarized for each disease. The fuzzy inference applied to obtain a decision fuzzy set for each disease, and crisp decision values attained to determine the certainty of existence for each disease. Results indicated that, in the diagnosis of seven cases of kidney disease by examining 21 indicators using fuzzy expert system, kidney stone disease with 63% certainty was the most probable, renal tubular was at the lowest level with 15%, and other kidney diseases were at the other levels. The most remarkable finding of this study was that results of kidney disease diagnosis (e.g., kidney stone) via fuzzy expert system were fully compatible with those of kidney physicians. The proposed fuzzy expert system is a valid, reliable, and flexible instrument to diagnose several typical input cases. The developed system decreases the effort of initial physical checking and manual feeding of input symptoms.

Kidney Function After a Hypertensive Disorder of Pregnancy: A Longitudinal Study.

PubMed

Paauw, Nina D; van der Graaf, Anne Marijn; Bozoglan, Rita; van der Ham, David P; Navis, Gerjan; Gansevoort, Ron T; Groen, Henk; Lely, A Titia

2018-05-01

Registry-based studies report an increased risk for end-stage kidney disease after hypertensive disorders of pregnancy (HDPs). It is unclear whether HDPs lead to an increased incidence of chronic kidney disease (CKD) and/or progression of kidney function decline. Subanalysis of the Prevention of Renal and Vascular Endstage Disease (PREVEND) Study, a Dutch population-based cohort with follow-up of 5 visits approximately 3 years apart. Women without and with patient-reported HDPs (non-HDP, n=1,805; HDP, n=977) were identified. Mean age was 50 years at baseline and median follow-up was 11 years. An HDP. (1) The incidence of CKD using Cox regression and (2) the course of kidney function (estimated glomerular filtration rate [eGFR] and 24-hour albuminuria) over 5 visits using generalized estimating equation analysis adjusted for age, mean arterial pressure, and renin-angiotensin system (RAS) blockade. CKD was defined as eGFR<60mL/min/1.73m 2 and/or 24-hour albuminuria with albumin excretion > 30mg, and end-stage kidney disease was defined as receiving dialysis or kidney transplantation. During follow-up, none of the women developed end-stage renal disease and the incidence of CKD during follow-up was similar across HDP groups (HR, 1.04; 95% CI, 0.79-1.37; P=0.8). Use of RAS blockade was higher after HDP at all visits. During a median of 11 years, we observed a decrease in eGFR in both groups, with a slightly steeper decline in the HDP group (98±15 to 88±16 vs 99±17 to 91±15mL/min/1.73m 2 ; P group <0.01, P group*visit <0.05). The group effect remained significant after adjusting for mean arterial pressure, but disappeared after adjusting for RAS blockade. The 24-hour albuminuria did not differ between groups. No obstetric records available. HDPs defined by patient report rather than health records. HDPs did not detectably increase the incidence of CKD. During follow-up, we observed no differences in albuminuria, but observed a marginally lower eGFR after HDP that was no longer statistically significant after adjusting for the use of RAS blockers. In this population, we were unable to identify a significant risk for kidney function decline after patient-reported HDP. Copyright © 2017. Published by Elsevier Inc.

Immune System and Kidney Transplantation.

PubMed

Shrestha, Badri Man

2017-01-01

The immune system recognises a transplanted kidney as foreign body and mounts immune response through cellular and humoral mechanisms leading to acute or chronic rejection, which ultimately results in graft loss. Over the last five decades, there have been significant advances in the understanding of the immune responses to transplanted organs in both experimental and clinical transplant settings. Modulation of the immune response by using immunosuppressive agents has led to successful outcomes after kidney transplantation. The paper provides an overview of the general organisation and function of human immune system, immune response to kidney transplantation, and the current practice of immunosuppressive therapy in kidney transplantation in the United Kingdom.

Kidney disease models: tools to identify mechanisms and potential therapeutic targets

PubMed Central

Bao, Yin-Wu; Yuan, Yuan; Chen, Jiang-Hua; Lin, Wei-Qiang

2018-01-01

Acute kidney injury (AKI) and chronic kidney disease (CKD) are worldwide public health problems affecting millions of people and have rapidly increased in prevalence in recent years. Due to the multiple causes of renal failure, many animal models have been developed to advance our understanding of human nephropathy. Among these experimental models, rodents have been extensively used to enable mechanistic understanding of kidney disease induction and progression, as well as to identify potential targets for therapy. In this review, we discuss AKI models induced by surgical operation and drugs or toxins, as well as a variety of CKD models (mainly genetically modified mouse models). Results from recent and ongoing clinical trials and conceptual advances derived from animal models are also explored. PMID:29515089

Environmental pollution and kidney diseases.

PubMed

Xu, Xin; Nie, Sheng; Ding, Hanying; Hou, Fan Fan

2018-05-01

The burden of disease and death attributable to environmental pollution is becoming a public health challenge worldwide, especially in developing countries. The kidney is vulnerable to environmental pollutants because most environmental toxins are concentrated by the kidney during filtration. Given the high mortality and morbidity of kidney disease, environmental risk factors and their effect on kidney disease need to be identified. In this Review, we highlight epidemiological evidence for the association between kidney disease and environmental pollutants, including air pollution, heavy metal pollution and other environmental risk factors. We discuss the potential biological mechanisms that link exposure to environmental pollutants to kidney damage and emphasize the contribution of environmental pollution to kidney disease. Regulatory efforts should be made to control environmental pollution and limit individual exposure to preventable or avoidable environmental risk. Population studies with accurate quantification of environmental exposure in polluted regions, particularly in developing countries, might aid our understanding of the dose-response relationship between pollutants and kidney diseases.

Evolution of Acute Kidney Injury and Its Association With Systemic Hemodynamics in Children With Fluid-Refractory Septic Shock.

PubMed

Deep, Akash; Sagar, Hiremath; Goonasekera, Chulananda; Karthikeyan, Palaniswamy; Brierley, Joe; Douiri, Abdel

2018-07-01

There are no studies in pediatrics evaluating the progression of acute kidney injury in septic shock. We investigated the evolution of sepsis-associated acute kidney injury and its association with systemic hemodynamics in children with fluid-refractory septic shock. Prospective cohort study. PICU of a tertiary care hospital. All patients with fluid-refractory septic shock (n = 61) between September 2010 and February 2014. Hemodynamic variables using noninvasive ultrasound cardiac output monitor were measured at admission and 6 hourly thereafter till 48 hours. We used the Kidney Disease: Improving Global Outcomes criteria to define and stage acute kidney injury. Associations between various hemodynamic variables and development of acute kidney injury were evaluated. Severe acute kidney injury was defined as stage 2 or 3 acute kidney injury and was compared with no acute kidney injury or stage 1 acute kidney injury. Severe acute kidney injury developed in 29.5% (n = 18) of the 61 children with fluid-refractory septic shock, whereas 43 patients (70.49%) had either no or stage 1 acute kidney injury. Most patients who developed acute kidney injury did so within the first 48 hours of PICU admission. Severe acute kidney injury conferred a three-fold increased risk of death by day 28 (hazard ratio, 3.23; 95% CI, 1.52-6.67; p = 0.002), longer ICU stay, and increased duration of mechanical ventilation. Central venous pressure at presentation was higher in severe acute kidney injury by 5 cm H2O. Highest lactate in the first 24 hours of PICU admission, low diastolic blood pressure, low systemic vascular resistance index at admission were associated with severe acute kidney injury. This model reliably predicted stage 2/3 acute kidney injury by day 3 with area under the curve equals to 94%; 95% CI, 88.3-99.99. None of the other hemodynamic variables showed any association with severe acute kidney injury. Manifestations of sepsis-associated acute kidney injury often occur early after PICU admission and is associated with increased morbidity and mortality. There is a need to develop a predictive model in septic shock which could facilitate early detection of acute kidney injury.

Iron-Hepcidin Dysmetabolism, Anemia and Renal Hypoxia, Inflammation and Fibrosis in the Remnant Kidney Rat Model

PubMed Central

Garrido, Patrícia; Ribeiro, Sandra; Fernandes, João; Vala, Helena; Bronze-da-Rocha, Elsa; Rocha-Pereira, Petronila; Belo, Luís; Costa, Elísio; Santos-Silva, Alice; Reis, Flávio

2015-01-01

Anemia is a common complication of chronic kidney disease (CKD) that develops early and its severity increases as renal function declines. It is mainly due to a reduced production of erythropoietin (EPO) by the kidneys; however, there are evidences that iron metabolism disturbances increase as CKD progresses. Our aim was to study the mechanisms underlying the development of anemia of CKD, as well as renal damage, in the remnant kidney rat model of CKD induced by 5/6 nephrectomy. This model of CKD presented a sustained degree of renal dysfunction, with mild and advanced glomerular and tubulointerstitial lesions. Anemia developed 3 weeks after nephrectomy and persisted throughout the protocol. The remnant kidney was still able to produce EPO and the liver showed an increased EPO gene expression. In spite of the increased EPO blood levels, anemia persisted and was linked to low serum iron and transferrin levels, while serum interleukin (IL)-6 and high sensitivity C-reactive protein (hs-CRP) levels showed the absence of systemic inflammation. The increased expression of duodenal ferroportin favours iron absorption; however, serum iron is reduced which might be due to iron leakage through advanced kidney lesions, as showed by tubular iron accumulation. Our data suggest that the persistence of anemia may result from disturbances in iron metabolism and by an altered activity/function of EPO as a result of kidney cell damage and a local inflammatory milieu, as showed by the increased gene expression of different inflammatory proteins in the remnant kidney. In addition, this anemia and the associated kidney hypoxia favour the development of fibrosis, angiogenesis and inflammation that may underlie a resistance to EPO stimuli and reduced iron availability. These findings might contribute to open new windows to identify putative therapeutic targets for this condition, as well as for recombinant human EPO (rHuEPO) resistance, which occurs in a considerable percentage of CKD patients. PMID:25867633

Identifying and integrating consumer perspectives in clinical practice guidelines on autosomal-dominant polycystic kidney disease.

PubMed

Tong, Allison; Tunnicliffe, David J; Lopez-Vargas, Pamela; Mallett, Andrew; Patel, Chirag; Savige, Judy; Campbell, Katrina; Patel, Manish; Tchan, Michel C; Alexander, Stephen I; Lee, Vincent; Craig, Jonathan C; Fassett, Robert; Rangan, Gopala K

2016-02-01

This study aimed to identify consumer perspectives on topics and outcomes to integrate in the Kidney Health Australia Caring for Australasians with Renal Impairment (KHA-CARI) clinical practice guidelines on autosomal-dominant polycystic kidney disease (ADPKD). A workshop involving three concurrent focus groups with 18 consumers (patients with ADPKD (n = 15), caregivers (n = 3)) was convened. Guideline topics, interventions and outcomes were identified, and integrated into guideline development. Thematic analysis was used to analyse the reasons for their choices. Twenty-two priority topics were identified, with most focussed on non-pharmacological management (diet, fluid intake, physical activity, complementary medicine), pain management and psychosocial care (mental health, counselling, cognitive and behavioural training, education, support groups). They also identified 26 outcomes including quality of life (QoL), progression of kidney disease, kidney function, cyst growth and nephrotoxity. Almost all topics and outcomes suggested were identified by health professionals with the exception of five topics/outcomes. Six themes reflected reasons for their choices: clarifying ambiguities, resolving debilitating pain, concern for family, preparedness for the future, taking control and significance of impact. Although there was considerable concordance between the priority topics and outcomes of health professionals and consumers for guidelines of ADPKD, there was also important discordance with consumers focused on fewer issues, but particularly on lifestyle, psychosocial support, pain, and QoL and renal outcomes. Active consumer engagement in guidelines development can help to ensure the inclusion of patient-centred recommendations, which may lead to better management of disease progression, symptoms, complications, and psychosocial impact. © 2015 Asian Pacific Society of Nephrology.

Chronic kidney-disease screening service quality: questionnaire survey research evidence from Taichung city

PubMed Central

2009-01-01

Background Chronic kidney disease (CKD) is a serious public health problem in Taiwan and the world. The most effective, affordable treatments involve early prevention/detection/intervention, requiring screening. Successfully implementing CKD programs requires good patient participation, affected by patient perceptions of screening service quality. Service quality improvements can help make such programs more successful. Thus, good tools for assessing service quality perceptions are important. Aim: to investigate using a modified SERVQUAL questionnaire in assessing patient expectations, perceptions, and loyalty towards kidney disease screening service quality. Method 1595 kidney disease screening program patients in Taichung City were requested to complete and return a modified kidney disease screening SERVQUAL questionnaire. 1187 returned them. Incomplete ones (102) were culled and 1085 were chosen as effective for use. Paired t-tests, correlation tests, ANOVA, LSD test, and factor analysis identified the characteristics and factors of service quality. The paired t-test tested expectation score and perception score gaps. A structural equation modeling system examined satisfaction-based components' relationships. Results The effective response rate was 91.4%. Several methods verified validity. Cronbach's alpha on internal reliability was above 0.902. On patient satisfaction, expectation scores are high: 6.50 (0.82), but perception scores are significantly lower 6.14 (1.02). Older patients' perception scores are lower than younger patients'. Expectation and perception scores for patients with different types of jobs are significantly different. Patients higher on education have lower scores for expectation (r = -0.09) and perception (r = -0.26). Factor analysis identified three factors in the 22 item SERVQUAL form, which account for 80.8% of the total variance for the expectation scores and 86.9% of the total variance for the satisfaction scores. Expectation and perception score gaps in all 22 items are significant. The goodness-of-fit summary of the SEM results indicates that expectations and perceptions are positively correlated, perceptions and loyalty are positively correlated, but expectations and loyalty are not positively correlated. Conclusions The results of this research suggest that the SERVQUAL instrument is a useful measurement tool in assessing and monitoring service quality in kidney disease screening services, enabling the staff to identify where service improvements are needed from the patients' perspectives. PMID:20021684

SOS2 and ACP1 Loci Identified through Large-Scale Exome Chip Analysis Regulate Kidney Development and Function.

PubMed

Li, Man; Li, Yong; Weeks, Olivia; Mijatovic, Vladan; Teumer, Alexander; Huffman, Jennifer E; Tromp, Gerard; Fuchsberger, Christian; Gorski, Mathias; Lyytikäinen, Leo-Pekka; Nutile, Teresa; Sedaghat, Sanaz; Sorice, Rossella; Tin, Adrienne; Yang, Qiong; Ahluwalia, Tarunveer S; Arking, Dan E; Bihlmeyer, Nathan A; Böger, Carsten A; Carroll, Robert J; Chasman, Daniel I; Cornelis, Marilyn C; Dehghan, Abbas; Faul, Jessica D; Feitosa, Mary F; Gambaro, Giovanni; Gasparini, Paolo; Giulianini, Franco; Heid, Iris; Huang, Jinyan; Imboden, Medea; Jackson, Anne U; Jeff, Janina; Jhun, Min A; Katz, Ronit; Kifley, Annette; Kilpeläinen, Tuomas O; Kumar, Ashish; Laakso, Markku; Li-Gao, Ruifang; Lohman, Kurt; Lu, Yingchang; Mägi, Reedik; Malerba, Giovanni; Mihailov, Evelin; Mohlke, Karen L; Mook-Kanamori, Dennis O; Robino, Antonietta; Ruderfer, Douglas; Salvi, Erika; Schick, Ursula M; Schulz, Christina-Alexandra; Smith, Albert V; Smith, Jennifer A; Traglia, Michela; Yerges-Armstrong, Laura M; Zhao, Wei; Goodarzi, Mark O; Kraja, Aldi T; Liu, Chunyu; Wessel, Jennifer; Boerwinkle, Eric; Borecki, Ingrid B; Bork-Jensen, Jette; Bottinger, Erwin P; Braga, Daniele; Brandslund, Ivan; Brody, Jennifer A; Campbell, Archie; Carey, David J; Christensen, Cramer; Coresh, Josef; Crook, Errol; Curhan, Gary C; Cusi, Daniele; de Boer, Ian H; de Vries, Aiko P J; Denny, Joshua C; Devuyst, Olivier; Dreisbach, Albert W; Endlich, Karlhans; Esko, Tõnu; Franco, Oscar H; Fulop, Tibor; Gerhard, Glenn S; Glümer, Charlotte; Gottesman, Omri; Grarup, Niels; Gudnason, Vilmundur; Hansen, Torben; Harris, Tamara B; Hayward, Caroline; Hocking, Lynne; Hofman, Albert; Hu, Frank B; Husemoen, Lise Lotte N; Jackson, Rebecca D; Jørgensen, Torben; Jørgensen, Marit E; Kähönen, Mika; Kardia, Sharon L R; König, Wolfgang; Kooperberg, Charles; Kriebel, Jennifer; Launer, Lenore J; Lauritzen, Torsten; Lehtimäki, Terho; Levy, Daniel; Linksted, Pamela; Linneberg, Allan; Liu, Yongmei; Loos, Ruth J F; Lupo, Antonio; Meisinger, Christine; Melander, Olle; Metspalu, Andres; Mitchell, Paul; Nauck, Matthias; Nürnberg, Peter; Orho-Melander, Marju; Parsa, Afshin; Pedersen, Oluf; Peters, Annette; Peters, Ulrike; Polasek, Ozren; Porteous, David; Probst-Hensch, Nicole M; Psaty, Bruce M; Qi, Lu; Raitakari, Olli T; Reiner, Alex P; Rettig, Rainer; Ridker, Paul M; Rivadeneira, Fernando; Rossouw, Jacques E; Schmidt, Frank; Siscovick, David; Soranzo, Nicole; Strauch, Konstantin; Toniolo, Daniela; Turner, Stephen T; Uitterlinden, André G; Ulivi, Sheila; Velayutham, Dinesh; Völker, Uwe; Völzke, Henry; Waldenberger, Melanie; Wang, Jie Jin; Weir, David R; Witte, Daniel; Kuivaniemi, Helena; Fox, Caroline S; Franceschini, Nora; Goessling, Wolfram; Köttgen, Anna; Chu, Audrey Y

2017-03-01

Genome-wide association studies have identified >50 common variants associated with kidney function, but these variants do not fully explain the variation in eGFR. We performed a two-stage meta-analysis of associations between genotypes from the Illumina exome array and eGFR on the basis of serum creatinine (eGFRcrea) among participants of European ancestry from the CKDGen Consortium ( n Stage1 : 111,666; n Stage2 : 48,343). In single-variant analyses, we identified single nucleotide polymorphisms at seven new loci associated with eGFRcrea ( PPM1J , EDEM3, ACP1, SPEG, EYA4, CYP1A1 , and ATXN2L ; P Stage1 <3.7×10 -7 ), of which most were common and annotated as nonsynonymous variants. Gene-based analysis identified associations of functional rare variants in three genes with eGFRcrea, including a novel association with the SOS Ras/Rho guanine nucleotide exchange factor 2 gene, SOS2 ( P =5.4×10 -8 by sequence kernel association test). Experimental follow-up in zebrafish embryos revealed changes in glomerular gene expression and renal tubule morphology in the embryonic kidney of acp1- and sos2 -knockdowns. These developmental abnormalities associated with altered blood clearance rate and heightened prevalence of edema. This study expands the number of loci associated with kidney function and identifies novel genes with potential roles in kidney formation. Copyright © 2017 by the American Society of Nephrology.

Association between First Nations ethnicity and progression to kidney failure by presence and severity of albuminuria.

PubMed

Samuel, Susan M; Palacios-Derflingher, Luz; Tonelli, Marcello; Manns, Braden; Crowshoe, Lynden; Ahmed, Sofia B; Jun, Min; Saad, Nathalie; Hemmelgarn, Brenda R

2014-02-04

Despite a low prevalence of chronic kidney disease (estimated glomerular filtration rate [GFR]<60 mL/min per 1.73 m2), First Nations people have high rates of kidney failure requiring chronic dialysis or kidney transplantation. We sought to examine whether the presence and severity of albuminuria contributes to the progression of chronic kidney disease to kidney failure among First Nations people. We identified all adult residents of Alberta (age≥18 yr) for whom an outpatient serum creatinine measurement was available from May 1, 2002, to Mar. 31, 2008. We determined albuminuria using urine dipsticks and categorized results as normal (i.e., no albuminuria), mild, heavy or unmeasured. Our primary outcome was progression to kidney failure (defined as the need for chronic dialysis or kidney transplantation, or a sustained doubling of serum creatinine levels). We calculated rates of progression to kidney failure by First Nations status, by estimated GFR and by albuminuria category. We determined the relative hazard of progression to kidney failure for First Nations compared with non-First Nations participants by level of albuminuria and estimated GFR. Of the 1 816 824 participants we identified, 48 669 (2.7%) were First Nations. First Nations people were less likely to have normal albuminuria compared with non-First Nations people (38.7% v. 56.4%). Rates of progression to kidney failure were consistently 2- to 3-fold higher among First Nations people than among non-First Nations people, across all levels of albuminuria and estimated GFRs. Compared with non-First Nations people, First Nations people with an estimated GFR of 15.0-29.9 mL/min per 1.73 m2 had the highest risk of progression to kidney failure, with similar hazard ratios for those with normal and heavy albuminuria. Albuminuria confers a similar risk of progression to kidney failure for First Nations and non-First Nations people.

Urinary Virome Perturbations in Kidney Transplantation.

PubMed

Sigdel, Tara K; Mercer, Neil; Nandoe, Sharvin; Nicora, Carrie D; Burnum-Johnson, Kristin; Qian, Wei-Jun; Sarwal, Minnie M

2018-01-01

The human microbiome is important for health and plays a role in essential metabolic functions and protection from certain pathogens. Conversely, dysbiosis of the microbiome is seen in the context of various diseases. Recent studies have highlighted that a complex microbial community containing hundreds of bacteria colonizes the healthy urinary tract, but little is known about the human urinary viruses in health and disease. To evaluate the human urinary virome in the context of kidney transplantation (tx), variations in the composition of the urinary virome were evaluated in urine samples from normal healthy volunteers as well as patients with kidney disease after they had undergone kidney tx. Liquid chromatography-mass spectrometry/mass spectrometry analysis was undertaken on a selected cohort of 142 kidney tx patients and normal healthy controls, from a larger biobank of 770 kidney biopsy matched urine samples. In addition to analysis of normal healthy control urine, the cohort of kidney tx patients had biopsy confirmed phenotype classification, coincident with the urine sample analyzed, of stable grafts (STA), acute rejection, BK virus nephritis, and chronic allograft nephropathy. We identified 37 unique viruses, 29 of which are being identified for the first time in human urine samples. The composition of the human urinary virome differs in health and kidney injury, and the distribution of viral proteins in the urinary tract may be further impacted by IS exposure, diet and environmental, dietary, or cutaneous exposure to various insecticides and pesticides.

Molecular Diagnostics in Autosomal Dominant Polycystic Kidney Disease: Utility and Limitations

PubMed Central

Zhao, Xiao; Paterson, Andrew D.; Zahirieh, Alireza; He, Ning; Wang, Kairong; Pei, York

2008-01-01

Background and objectives: Gene-based mutation screening is now available and has the potential to provide diagnostic confirmation or exclusion of autosomal dominant polycystic kidney disease. This study illustrates its utility and limitations in the clinical setting. Design, setting, participants, & measurements: Using a molecular diagnostic service, genomic DNA of one affected individual from each study family was screened for pathologic PKD1 and PKD2 mutations. Bidirectional sequencing was performed to identify sequence variants in all exons and splice junctions of both genes and to confirm the specific mutations in other family members. In two multiplex families, microsatellite markers were genotyped at both PDK1 and PKD2 loci, and pair-wise and multipoint linkage analysis was performed. Results: Three of five probands studied were referred for assessment of renal cystic disease without a family history of autosomal dominant polycystic kidney disease, and two others were younger at-risk members of families with autosomal dominant polycystic kidney disease being evaluated as living-related kidney donors. Gene-based mutation screening identified pathogenic mutations that provided confirmation or exclusion of disease in three probands, but in the other two, only unclassified variants were identified. In one proband in which mutation screening was indeterminate, DNA linkage studies provided strong evidence for disease exclusion. Conclusions: Gene-based mutation screening or DNA linkage analysis should be considered in individuals in whom the diagnosis of autosomal dominant polycystic kidney disease is uncertain because of a lack of family history or equivocal imaging results and in younger at-risk individuals who are being evaluated as living-related kidney donors. PMID:18077784

Kidney transplantation from a mother with unrecognized Fabry disease to her son with low α-galactosidase A activity: A 14-year follow-up without enzyme replacement therapy.

PubMed

Odani, Keiko; Okumi, Masayoshi; Honda, Kazuho; Ishida, Hideki; Tanabe, Kazunari

2016-07-01

We report a case of kidney transplantation from mother to son, both of whom were likely to have had an unrecognized renal variant phenotype of Fabry disease. The patient was a 54-year-old man, with an unknown primary cause of end stage renal disease. He had no notable past medical history, other than end stage renal disease. He underwent living-related kidney transplantation from his mother at age 40 years. Foam cells in the glomeruli were identified on histology assessment of a 0-hour allograft biopsy, with zebra bodies identified in the glomerular visceral epithelial cells by electron microscopy. These findings were indicative of Fabry disease in the donated kidney. As a definitive diagnosis of Fabry's disease could not be confirmed, enzyme replacement therapy was not initiated. Thirteen years after kidney transplantation, the patient underwent left nephrectomy for a left renal tumour, with pathological findings of clear cell carcinoma, foam cells and zebra bodies in the native kidney. Detailed examinations identified low α-galactosidase A activity and mutation of the α-Gal A gene, confirming a diagnosis of a renal variant phenotype of Fabry disease. Histology of several allograft biopsies performed over the 14 years from the time of kidney transplantation revealed only moderate interstitial fibrosis and tubular atrophy, with no evidence of disease progression on electron microscopy, despite the presence of zebra bodies in the glomerular visceral epithelial cells. © 2016 Asian Pacific Society of Nephrology.

The morphology and treatment of coexisting ureteropelvic junction obstruction in lower moiety of duplex kidney.

PubMed

Liu, Wei; Zhang, Liujuan; Ma, Rui; Wu, Rongde

2016-10-01

Duplex kidney is a common congenital anomaly of the urinary tract, while ureteropelvic junction obstruction (UPJO) in lower unit of duplex kidney is rare. Surgical treatment can be challenging in such cases. The aim was to report our experience in managements of UPJO in lower moiety of duplex kidney. Among the pediatric patients with duplex system from 2007 to 2013, 7 children were diagnosed with UPJO in lower moiety. Their medical records were retrospectively analyzed, mainly focused on anatomic aspects and operation details. The lower pole UPJO associated with incomplete duplex systems were identified in 6 patients on the left side and 1 on the right side. Median patient age at surgery was 11 months (range 6-84 months). Prenatal hydronephrosis was detected in 4 patients, and 3 had intermittent abdominal pain. Hydronephrosis, thin parenchyma and presence of UPJO in lower moiety could be shown on computed tomography urogram (CTU). The ureters were fused in a "Y" shape without any dilation. Based on the length between UPJO to the confluence in retrograde ureteropyelography, patients were classified into group 1 (5 cases,≤3 cm) and group 2 (2 cases, >3 cm). In group 1, surgical procedure involved end-to-side pyeloureterostomy of the lower pelvis to the ureteral confluence in 4 cases and laparoscopic pyeloureterostomy in one case. The two patients in group 2 underwent laparoscopic pyeloplasty of lower moiety. In all of these patients hydronephrosis gradually improved and no complications were detected during follow-up. UPJO in a duplex kidney requires careful evaluation and treatment should be individualized. Ureteropyeloanastomosis is a feasible treatment for duplex kidneys associated to a functioning lower moiety with UPJO. With the technical improvements in laparoscopic pyeloplasty, this procedure can be performed using laparoscopy. Copyright © 2016 IJS Publishing Group Ltd. Published by Elsevier Ltd. All rights reserved.

Renal Dysfunction Induced by Kidney-Specific Gene Deletion of Hsd11b2 as a Primary Cause of Salt-Dependent Hypertension.

PubMed

Ueda, Kohei; Nishimoto, Mitsuhiro; Hirohama, Daigoro; Ayuzawa, Nobuhiro; Kawarazaki, Wakako; Watanabe, Atsushi; Shimosawa, Tatsuo; Loffing, Johannes; Zhang, Ming-Zhi; Marumo, Takeshi; Fujita, Toshiro

2017-07-01

Genome-wide analysis of renal sodium-transporting system has identified specific variations of Mendelian hypertensive disorders, including HSD11B2 gene variants in apparent mineralocorticoid excess. However, these genetic variations in extrarenal tissue can be involved in developing hypertension, as demonstrated in former studies using global and brain-specific Hsd11b2 knockout rodents. To re-examine the importance of renal dysfunction on developing hypertension, we generated kidney-specific Hsd11b2 knockout mice. The knockout mice exhibited systemic hypertension, which was abolished by reducing salt intake, suggesting its salt-dependency. In addition, we detected an increase in renal membrane expressions of cleaved epithelial sodium channel-α and T53-phosphorylated Na + -Cl - cotransporter in the knockout mice. Acute intraperitoneal administration of amiloride-induced natriuresis and increased urinary sodium/potassium ratio more in the knockout mice compared with those in the wild-type control mice. Chronic administration of amiloride and high-KCl diet significantly decreased mean blood pressure in the knockout mice, which was accompanied with the correction of hypokalemia and the resultant decrease in Na + -Cl - cotransporter phosphorylation. Accordingly, a Na + -Cl - cotransporter blocker hydrochlorothiazide significantly decreased mean blood pressure in the knockout mice. Chronic administration of mineralocorticoid receptor antagonist spironolactone significantly decreased mean blood pressure of the knockout mice along with downregulation of cleaved epithelial sodium channel-α and phosphorylated Na + -Cl - cotransporter expression in the knockout kidney. Our data suggest that kidney-specific deficiency of 11β-HSD2 leads to salt-dependent hypertension, which is attributed to mineralocorticoid receptor-epithelial sodium channel-Na + -Cl - cotransporter activation in the kidney, and provides evidence that renal dysfunction is essential for developing the phenotype of apparent mineralocorticoid excess. © 2017 American Heart Association, Inc.

The natural history of renal function after surgical management of renal cell carcinoma: Results from the Canadian Kidney Cancer Information System.

PubMed

Mason, Ross; Kapoor, Anil; Liu, Zhihui; Saarela, Olli; Tanguay, Simon; Jewett, Michael; Finelli, Antonio; Lacombe, Louis; Kawakami, Jun; Moore, Ronald; Morash, Christopher; Black, Peter; Rendon, Ricardo A

2016-11-01

Patients who undergo surgical management of renal cell carcinoma (RCC) are at risk for chronic kidney disease and its sequelae. This study describes the natural history of renal function after radical and partial nephrectomy and explores factors associated with postoperative decline in renal function. This is a multi-institutional cohort study of patients in the Canadian Kidney Cancer Information System who underwent partial or radical nephrectomy for RCC. Estimated glomerular filtration rate (eGFR) and stage of chronic kidney disease were determined preoperatively and at 3, 12, and 24 months postoperatively. Linear regression was used to determine the association between postoperative eGFR and type of surgery (radical vs. partial), duration of ischemia, ischemia type (warm vs. cold), and tumor size. With a median follow-up of 26 months, 1,379 patients were identified from the Canadian Kidney Cancer Information System database including 665 and 714 who underwent partial and radical nephrectomy, respectively. Patients undergoing radical nephrectomy had a lower eGFR (mean = 19ml/min/1.73m 2 lower) at 3, 12, and 24 months postoperatively (P<0.001). Decline in renal function occurred early and remained stable throughout follow-up. A lower preoperative eGFR and increasing age were also associated with a lower postoperative eGFR (P<0.01). Ischemia type and duration were not predictive of postoperative decline in eGFR (P>0.05). Severe renal failure (eGFR<30ml/min/1.73m 2 ) developed postoperatively in 12.5% and 4.1% of radical and partial nephrectomy patients, respectively (P<0.001). After the initial postoperative decline, renal function remains stable in patients undergoing surgery for RCC. Patients undergoing radical nephrectomy have a greater long-term reduction in renal function compared with those undergoing partial nephrectomy. Ischemia duration and type are not predictive of postoperative renal function when adhering to generally short ischemia durations. Copyright © 2016 Elsevier Inc. All rights reserved.

77 FR 26021 - Center for Scientific Review; Notice of Closed Meetings

Federal Register 2010, 2011, 2012, 2013, 2014

2012-05-02

... . Name of Committee: Digestive, Kidney and Urological Systems Integrated Review Group; Clinical... 20892, (301) 806-0009, [email protected] . Name of Committee: Digestive, Kidney and Urological Systems Integrated Review Group; Pathobiology of Kidney Disease Study Section. Date: June 4, 2012. Time: 8...

Epigenetics of kidney disease.

PubMed

Wanner, Nicola; Bechtel-Walz, Wibke

2017-07-01

DNA methylation and histone modifications determine renal programming and the development and progression of renal disease. The identification of the way in which the renal cell epigenome is altered by environmental modifiers driving the onset and progression of renal diseases has extended our understanding of the pathophysiology of kidney disease progression. In this review, we focus on current knowledge concerning the implications of epigenetic modifications during renal disease from early development to chronic kidney disease progression including renal fibrosis, diabetic nephropathy and the translational potential of identifying new biomarkers and treatments for the prevention and therapy of chronic kidney disease and end-stage kidney disease.

Simple ectopic kidney in three dogs.

PubMed

Choi, Jiyoung; Lee, Heechun; Lee, Youngwon; Choi, Hojung

2012-10-01

Simple ectopic kidney was diagnosed in three dogs by means of radiography and ultrasonography. A 2-year-old castrated male Schnauzer, a 13-year-old female Schnauzer and a 9-year-old male Jindo were referred with vomiting, hematuria and ocular discharge, respectively. In all three dogs, oval-shaped masses with soft tissue density were observed in the mid to caudal abdomen bilaterally or unilaterally, and kidney silhouettes were not identified at the proper anatomic places on abdominal radiographs. Ultrasonography confirmed the masses were malpositioned kidney. The ectopic kidneys had relatively small size, irregular shape and short ureter but showed normal function on excretory urography.

Photoacoustic imaging for assessing ischemic kidney damage in vivo

NASA Astrophysics Data System (ADS)

Berndl, Elizabeth S. L.; He, Xiaolin; Yuen, Darren A.; Kolios, Michael C.

2018-02-01

Ischemic reperfusion injuries (IRIs) occur after blood returns to a tissue or organ after a period without oxygen or nutrients, which causes an inflammatory response leading to heterogeneous scarring of the nearby tissue and vasculature. This is associated with long-term decreases blood flow, and necrosis. Although most commonly associated with heart attacks and strokes, IRIs are also a side effect of organ transplants, when the organ is reperfused in the recipient's body after being transported from the donor to the transplant hospital. Currently, the optimal method of monitoring for IRI is limited to biopsies, which are invasive and poorly monitor the spatial heterogeneity of the damage. To non-invasively identify changes in kidneys, the left renal artery in mice (n=3) was clamped for 45 minutes to create an IRI event. Both kidneys of each animal were monitored using photoacoustics (PA) with the VevoLAZR system (Fujifilm-VisualSonics, Toronto) three, four and eight weeks after surgery. IRI-treated kidneys show increased picosirius red staining, indicative of collagen (0.601 vs 0.042, p < 0.0001), decreased size as assessed by cross-sectional area (7.8 mm2 vs 35.9 mm2 , p < 0.0001), and decreased oxygen saturation (sO2; 62% vs 77%, p = 0.02). Analysis of the photoacoustic data shows that a two-point metric, the 715:930 nm ratio of the whole kidney (1.05 vs 0.57, p = 0.049) and the optical spectral slope (OSS) (0.8 * 10-3 vs 3.0 * 10-3, p = 0.013) are both able to differentiate between IRI-treated and healthy kidneys. These data suggest that photoacoustics can be used as a non-invasive method to observe in vivo changes in the kidney due to IRI.

Provider Perspectives on Advance Care Planning for Patients with Kidney Disease: Whose Job Is It Anyway?

PubMed Central

Szarka, Jackie; McFarland, Lynne V.; Taylor, Janelle S.; Sudore, Rebecca L.; Trivedi, Ranak; Reinke, Lynn F.; Vig, Elizabeth K.

2016-01-01

Background and objectives There is growing interest in efforts to enhance advance care planning for patients with kidney disease. Our goal was to elicit the perspectives on advance care planning of multidisciplinary providers who care for patients with advanced kidney disease. Design, setting, participants, & measurements Between April and December of 2014, we conducted semistructured interviews at the Department of Veterans Affairs Puget Sound Health Care System with 26 providers from a range of disciplines and specialties who care for patients with advanced kidney disease. Participants were asked about their perspectives and experiences related to advance care planning in this population. Interviews were audiotaped, transcribed, and analyzed inductively using grounded theory. Results The comments of providers interviewed for this study spoke to significant system–level barriers to supporting the process of advance care planning for patients with advanced kidney disease. We identified four overlapping themes: (1) medical care for this population is complex and fragmented across settings and providers and over time; (2) lack of a shared understanding and vision of advance care planning and its relationship with other aspects of care, such as dialysis decision making; (3) unclear locus of responsibility and authority for advance care planning; and (4) lack of active collaboration and communication around advance care planning among different providers caring for the same patients. Conclusions The comments of providers who care for patients with advanced kidney disease spotlight both the need for and the challenges to interdisciplinary collaboration around advance care planning for this population. Systematic efforts at a variety of organizational levels will likely be needed to support teamwork around advance care planning among the different providers who care for patients with advanced kidney disease. PMID:27084877

Concise Review: Kidney Generation with Human Pluripotent Stem Cells.

PubMed

Morizane, Ryuji; Miyoshi, Tomoya; Bonventre, Joseph V

2017-11-01

Chronic kidney disease (CKD) is a worldwide health care problem, resulting in increased cardiovascular mortality and often leading to end-stage kidney disease, where patients require kidney replacement therapies such as hemodialysis or kidney transplantation. Loss of functional nephrons contributes to the progression of CKD, which can be attenuated but not reversed due to inability to generate new nephrons in human adult kidneys. Human pluripotent stem cells (hPSCs), by virtue of their unlimited self-renewal and ability to differentiate into cells of all three embryonic germ layers, are attractive sources for kidney regenerative therapies. Recent advances in stem cell biology have identified key signals necessary to maintain stemness of human nephron progenitor cells (NPCs) in vitro, and led to establishment of protocols to generate NPCs and nephron epithelial cells from human fetal kidneys and hPSCs. Effective production of large amounts of human NPCs and kidney organoids will facilitate elucidation of developmental and pathobiological pathways, kidney disease modeling and drug screening as well as kidney regenerative therapies. We summarize the recent studies to induce NPCs and kidney cells from hPSCs, studies of NPC expansion from mouse and human embryonic kidneys, and discuss possible approaches in vivo to regenerate kidneys with cell therapies and the development of bioengineered kidneys. Stem Cells 2017;35:2209-2217. © 2017 AlphaMed Press.

USE OF qRTPCR TO IDENTIFY POTENTIAL BIOMARKERS OF BROMATE EXPOSURE IN F344 MALE RAT KIDNEYS

EPA Science Inventory

Potassium bromate (KBrO3) is a drinking water disinfection by-product that is nephrotoxic and carcinogenic. To identify potential biomarkers of carcinogenicity, male F344 rats were chronically exposed to a carcinogenic dose (400mg/l) of KBrO3 in their drinking water. Kidneys were...

Evaluation of normal findings using a detailed and focused technique for transcutaneous abdominal ultrasonography in the horse

PubMed Central

2014-01-01

Background Ultrasonography is an important diagnostic tool in the investigation of abdominal disease in the horse. Several factors may affect the ability to image different structures within the abdomen. The aim of the study was to describe the repeatability of identification of abdominal structures in normal horses using a detailed ultrasonographic examination technique and using a focused, limited preparation technique. Methods A detailed abdominal ultrasound examination was performed in five normal horses, repeated on five occasions (total of 25 examinations). The abdomen was divided into ten different imaging sites, and structures identified in each site were recorded. Five imaging sites were then selected for a single focused ultrasound examination in 20 normal horses. Limited patient preparation was performed. Structures were recorded as ‘identified’ if ultrasonographic features could be distinguished. The location of organs and their frequency of identification were recorded. Data from both phases were analysed to determine repeatability of identification of structures in each examination (irrespective of imaging site), and for each imaging site. Results Caecum, colon, spleen, liver and right kidney were repeatably identified using the detailed technique, and had defined locations. Large colon and right kidney were identified in 100% of examinations with both techniques. Liver, spleen, caecum, duodenum and other small intestine were identified more frequently with the detailed examination. Small intestine was most frequently identified in the ventral abdomen, its identification varied markedly within and between horses, and required repeated examinations in some horses. Left kidney could not be identified in every horse using either technique. Sacculated colon was identified in all ventral sites, and was infrequently identified in dorsal sites. Conclusions Caecum, sacculated large intestine, spleen, liver and right kidney were consistently identified with both techniques. There were some normal variations which should be considered when interpreting ultrasonographic findings in clinical cases: left kidney was not always identified, sacculated colon was occasionally identified in dorsal flank sites. Multiple imaging sites and repeated examinations may be required to identify small intestine. A focused examination identified most key structures, but has some limitations compared to a detailed examination. PMID:25238559

Acute Kidney Injury after Liver Transplantation.

PubMed

Durand, François; Francoz, Claire; Asrani, Sumeet K; Khemichian, Saro; Pham, Thomas A; Sung, Randall S; Genyk, Yuri S; Nadim, Mitra K

2018-05-29

Since the implementation of the MELD score-based allocation system, the number of transplant candidates with impaired renal function has increased. The aims of this review are to present new insights in the definitions and predisposing factors that result in acute kidney injury (AKI), and to propose guidelines for the prevention and treatment of post liver transplantation (LT) AKI. This review is based on both systematic review of relevant literature and expert opinion. Pretransplant AKI is associated with posttransplant morbidity, including prolonged post LT AKI which then predisposes to posttransplant chronic kidney disease (CKD). Prevention of posttransplant AKI is essential in the improvement of long term outcomes. Accurate assessment of baseline kidney function at evaluation is necessary, taking into account that serum creatinine overestimates glomerular filtration rate (GFR). New diagnostic criteria for AKI have been integrated with traditional approaches in patients with cirrhosis to potentially identify AKI earlier and improve outcomes. Delayed introduction or complete elimination of calcineurin inhibitors during the first weeks post LT in patients with early posttransplant AKI may improve GFR in high risk patients but with higher rates of rejection and more adverse events. Biomarkers may in the future provide diagnostic information such as etiology of AKI, and prognostic information on renal recovery post-LT, and potentially impact the decision for simultaneous liver-kidney transplantation. Overall, more attention should be paid to pretransplant and early posttransplant AKI to reduce the burden of late CKD.

Identifying potential kidney donors using social networking web sites.

PubMed

Chang, Alexander; Anderson, Emily E; Turner, Hang T; Shoham, David; Hou, Susan H; Grams, Morgan

2013-01-01

Social networking sites like Facebook may be a powerful tool for increasing rates of live kidney donation. They allow for wide dissemination of information and discussion and could lessen anxiety associated with a face-to-face request for donation. However, sparse data exist on the use of social media for this purpose. We searched Facebook, the most popular social networking site, for publicly available English-language pages seeking kidney donors for a specific individual, abstracting information on the potential recipient, characteristics of the page itself, and whether potential donors were tested. In the 91 pages meeting inclusion criteria, the mean age of potential recipients was 37 (range: 2-69); 88% were US residents. Other posted information included the individual's photograph (76%), blood type (64%), cause of kidney disease (43%), and location (71%). Thirty-two percent of pages reported having potential donors tested, and 10% reported receiving a live-donor kidney transplant. Those reporting donor testing shared more potential recipient characteristics, provided more information about transplantation, and had higher page traffic. Facebook is already being used to identify potential kidney donors. Future studies should focus on how to safely, ethically, and effectively use social networking sites to inform potential donors and potentially expand live kidney donation. © 2013 John Wiley & Sons A/S.

Identifying Potential Kidney Donors Using Social Networking Websites

PubMed Central

Chang, Alexander; Anderson, Emily E.; Turner, Hang T.; Shoham, David; Hou, Susan H.; Grams, Morgan

2013-01-01

Social networking sites like Facebook may be a powerful tool for increasing rates of live kidney donation. They allow for wide dissemination of information and discussion, and could lessen anxiety associated with a face-to-face request for donation. However, sparse data exist on the use of social media for this purpose. We searched Facebook, the most popular social networking site, for publicly available English-language pages seeking kidney donors for a specific individual, abstracting information on the potential recipient, characteristics of the page itself, and whether potential donors were tested. In the 91 pages meeting inclusion criteria, the mean age of potential recipients was 37 (range: 2–69); 88% were U.S. residents. Other posted information included the individual’s photograph (76%), blood type (64%), cause of kidney disease (43%), and location (71%). Thirty-two percent of pages reported having potential donors tested, and 10% reported receiving a live donor kidney transplant. Those reporting donor testing shared more potential recipient characteristics, provided more information about transplantation, and had higher page traffic. Facebook is already being used to identify potential kidney donors. Future studies should focus on how to safely, ethically, and effectively use social networking sites to inform potential donors and potentially expand live kidney donation. PMID:23600791

Patient attitudes toward mobile phone-based health monitoring: questionnaire study among kidney transplant recipients.

PubMed

McGillicuddy, John William; Weiland, Ana Katherine; Frenzel, Ronja Maximiliane; Mueller, Martina; Brunner-Jackson, Brenda Marie; Taber, David James; Baliga, Prabhakar Kalyanpur; Treiber, Frank Anton

2013-01-08

Mobile phone based remote monitoring of medication adherence and physiological parameters has the potential of improving long-term graft outcomes in the recipients of kidney transplants. This technology is promising as it is relatively inexpensive, can include intuitive software and may offer the ability to conduct close patient monitoring in a non-intrusive manner. This includes the optimal management of comorbidities such as hypertension and diabetes. There is, however, a lack of data assessing the attitudes of renal transplant recipients toward this technology, especially among ethnic minorities. To assess the attitudes of renal transplant recipients toward mobile phone based remote monitoring and management of their medical regimen; and to identify demographic or clinical characteristics that impact on this attitude. After a 10 minute demonstration of a prototype mobile phone based monitoring system, a 10 item questionnaire regarding attitude toward remote monitoring and the technology was administered to the participants, along with the 10 item Perceived Stress Scale and the 7 item Morisky Medication Adherence Scale. Between February and April 2012, a total of 99 renal transplant recipients were identified and agreed to participate in the survey. The results of the survey indicate that while 90% (87/97) of respondents own a mobile phone, only 7% (7/98) had any prior knowledge of mobile phone based remote monitoring. Despite this, the majority of respondents, 79% (78/99), reported a positive attitude toward the use of a prototype system if it came at no cost to themselves. Blacks were more likely than whites to own smartphones (43.1%, 28/65 vs 20.6%, 7/34; P=.03) and held a more positive attitude toward free use of the prototype system than whites (4.25±0.88 vs 3.76±1.07; P=.02). The data demonstrates that kidney transplant recipients have a positive overall attitude toward mobile phone based health technology (mHealth). Additionally, the data demonstrates that most kidney transplant recipients own and are comfortable using mobile phones and that many of these patients already own and use smart mobile phones. The respondents felt that mHealth offers an opportunity for improved self-efficacy and improved provider driven medical management. Respondents were comfortable with the idea of being monitored using mobile technology and are confident that their privacy can be protected. The small subset of kidney transplant recipients who are less interested in mHealth may be less technologically adept as reflected by their lower mobile phone ownership rates. As a whole, kidney transplant recipients are receptive to the technology and believe in its utility.

A new machine-learning method to prognosticate paraquat poisoned patients by combining coagulation, liver, and kidney indices.

PubMed

Hu, Lufeng; Li, Huaizhong; Cai, Zhennao; Lin, Feiyan; Hong, Guangliang; Chen, Huiling; Lu, Zhongqiu

2017-01-01

The prognosis of paraquat (PQ) poisoning is highly correlated to plasma PQ concentration, which has been identified as the most important index in PQ poisoning. This study investigated the predictive value of coagulation, liver, and kidney indices in prognosticating PQ-poisoning patients, when aligned with plasma PQ concentrations. Coagulation, liver, and kidney indices were first analyzed by variance analysis, receiver operating characteristic curves, and Fisher discriminant analysis. Then, a new, intelligent, machine learning-based system was established to effectively provide prognostic analysis of PQ-poisoning patients based on a combination of the aforementioned indices. In the proposed system, an enhanced extreme learning machine wrapped with a grey wolf-optimization strategy was developed to predict the risk status from a pool of 103 patients (56 males and 47 females); of these, 52 subjects were deceased and 51 alive. The proposed method was rigorously evaluated against this real-life dataset, in terms of accuracy, Matthews correlation coefficients, sensitivity, and specificity. Additionally, the feature selection was investigated to identify correlating factors for risk status. The results demonstrated that there were significant differences in the coagulation, liver, and kidney indices between deceased and surviving subjects (p<0.05). Aspartate aminotransferase, prothrombin time, prothrombin activity, total bilirubin, direct bilirubin, indirect bilirubin, alanine aminotransferase, urea nitrogen, and creatinine were the most highly correlated indices in PQ poisoning and showed statistical significance (p<0.05) in predicting PQ-poisoning prognoses. According to the feature selection, the most important correlated indices were found to be associated with aspartate aminotransferase, the aspartate aminotransferase to alanine ratio, creatinine, prothrombin time, and prothrombin activity. The method proposed here showed excellent results that were better than that produced based on blood-PQ concentration alone. These promising results indicated that the combination of these indices can provide a new avenue for prognosticating the outcome of PQ poisoning.

Aging changes in the kidneys and bladder

MedlinePlus

... fluid from the body. The kidneys also help control the body's chemical balance. The kidneys are part of the urinary system, which also includes the ureters, bladder, and urethra. Muscle ... bladder control. AGING CHANGES AND THEIR EFFECTS ON THE KIDNEYS ...

Early Diagnosis of Clear Cell Kidney Cancer via VHL/HIF Pathway Regulated-Circulating microRNA

DTIC Science & Technology

2016-05-01

Award Number: W81XWH-11-1-0715 TITLE: Early Diagnosis of Clear Cell Kidney Cancer via VHL/HIF Pathway-Regulated Circulating microRNA PRINCIPAL...TITLE AND SUBTITLE Sa. CONTRACT NUMBER Early Diagnosis of Clear Cell Kidney Cancer via VHL/HIF Pathway- Regulated Circulating microRNA Sb. GRANT NUMBER...panel of diagnostic miRNAs that are measurable in serum and will be able to identify kidney cancer in its earliest stages. We hypothesized that serum

Prevalence of kidney stones in the United States.

PubMed

Scales, Charles D; Smith, Alexandria C; Hanley, Janet M; Saigal, Christopher S

2012-07-01

The last nationally representative assessment of kidney stone prevalence in the United States occurred in 1994. After a 13-yr hiatus, the National Health and Nutrition Examination Survey (NHANES) reinitiated data collection regarding kidney stone history. Describe the current prevalence of stone disease in the United States, and identify factors associated with a history of kidney stones. A cross-sectional analysis of responses to the 2007-2010 NHANES (n=12 110). Self-reported history of kidney stones. Percent prevalence was calculated and multivariable models were used to identify factors associated with a history of kidney stones. The prevalence of kidney stones was 8.8% (95% confidence interval [CI], 8.1-9.5). Among men, the prevalence of stones was 10.6% (95% CI, 9.4-11.9), compared with 7.1% (95% CI, 6.4-7.8) among women. Kidney stones were more common among obese than normal-weight individuals (11.2% [95% CI, 10.0-12.3] compared with 6.1% [95% CI, 4.8-7.4], respectively; p<0.001). Black, non-Hispanic and Hispanic individuals were less likely to report a history of stone disease than were white, non-Hispanic individuals (black, non-Hispanic: odds ratio [OR]: 0.37 [95% CI, 0.28-0.49], p<0.001; Hispanic: OR: 0.60 [95% CI, 0.49-0.73], p<0.001). Obesity and diabetes were strongly associated with a history of kidney stones in multivariable models. The cross-sectional survey design limits causal inference regarding potential risk factors for kidney stones. Kidney stones affect approximately 1 in 11 people in the United States. These data represent a marked increase in stone disease compared with the NHANES III cohort, particularly in black, non-Hispanic and Hispanic individuals. Diet and lifestyle factors likely play an important role in the changing epidemiology of kidney stones. Published by Elsevier B.V.

Kidney transplantation in the elderly.

PubMed

Singh, Neeraj; Nori, Uday; Pesavento, Todd

2009-08-01

Recent outcome data, ongoing organ shortage and proposed changes in allocation policies are driving the need to review current practices and possible future course of kidney transplantation in the elderly patients. A proposed new kidney allocation system based on matching donor and recipient characteristics to enable 'age-matched' kidney allocation is currently being discussed in the USA. While this system benefits younger recipients, implications for elderly recipients receiving older grafts remain a matter of debate. Despite improved outcomes, there remain significant challenges to kidney transplantation in the elderly, including organ shortage, poor transplant rate, evolving allocation policies, high wait-list mortality and nonstandardized immunosuppression. Prospective studies are needed to evaluate the strategies to meet these challenges and to study the impact of proposed new allocation system.

Mechanisms of Acute Kidney Injury Induced by Experimental Lonomia obliqua Envenomation

PubMed Central

Berger, Markus; Santi, Lucélia; Beys-da-Silva, Walter O.; Oliveira, Fabrício Marcus Silva; Caliari, Marcelo Vidigal; Yates, John R.; Ribeiro, Maria Aparecida; Guimarães, Jorge Almeida

2015-01-01

Background Lonomia obliqua caterpillar envenomation causes acute kidney injury (AKI), which can be responsible for its deadly actions. This study evaluates the possible mechanisms involved in the pathogenesis of renal dysfunction. Methods To characterize L. obliqua venom effects we subcutaneously injected rats and examined renal functional, morphological and biochemical parameters at several time points. We also performed discovery based proteomic analysis to measure protein expression to identify molecular pathways of renal disease. Results L. obliqua envenomation causes acute tubular necrosis, which is associated with renal inflammation; formation of hematic casts, resulting from intravascular hemolysis; increase in vascular permeability and fibrosis. The dilation of Bowman’s space and glomerular tuft is related to fluid leakage and intra-glomerular fibrin deposition, respectively, since tissue factor procoagulant activity increases in the kidney. Systemic hypotension also contributes to these alterations and to the sudden loss of basic renal functions, including filtration and excretion capacities, urinary concentration and maintenance of fluid homeostasis. In addition, envenomed kidneys increases expression of proteins involved in cell stress, inflammation, tissue injury, heme-induced oxidative stress, coagulation and complement system activation. Finally, the localization of the venom in renal tissue agrees with morphological and functional alterations, suggesting also a direct nephrotoxic activity. Conclusions Mechanisms of L. obliqua-induced AKI are complex involving mainly glomerular and tubular functional impairment and vascular alterations. These results are important to understand the mechanisms of renal injury and may suggest more efficient ways to prevent or attenuate the pathology of Lonomia’s envenomation. PMID:24798088

A multimodal imaging framework for enhanced robot-assisted partial nephrectomy guidance

NASA Astrophysics Data System (ADS)

Halter, Ryan J.; Wu, Xiaotian; Hartov, Alex; Seigne, John; Khan, Shadab

2015-03-01

Robot-assisted laparoscopic partial nephrectomies (RALPN) are performed to treat patients with locally confined renal carcinoma. There are well-documented benefits to performing partial (opposed to radical) kidney resections and to using robot-assisted laparoscopic (opposed to open) approaches. However, there are challenges in identifying tumor margins and critical benign structures including blood vessels and collecting systems during current RALPN procedures. The primary objective of this effort is to couple multiple image and data streams together to augment visual information currently provided to surgeons performing RALPN and ultimately ensure complete tumor resection and minimal damage to functional structures (i.e. renal vasculature and collecting systems). To meet this challenge we have developed a framework and performed initial feasibility experiments to couple pre-operative high-resolution anatomic images with intraoperative MRI, ultrasound (US) and optical-based surface mapping and kidney tracking. With these registered images and data streams, we aim to overlay the high-resolution contrast-enhanced anatomic (CT or MR) images onto the surgeon's view screen for enhanced guidance. To date we have integrated the following components of our framework: 1) a method for tracking an intraoperative US probe to extract the kidney surface and a set of embedded kidney markers, 2) a method for co-registering intraoperative US scans with pre-operative MR scans, and 3) a method for deforming pre-op scans to match intraoperative scans. These components have been evaluated through phantom studies to demonstrate protocol feasibility.

Unrecognized Fibrinogen A α-Chain Amyloidosis: Results From Targeted Genetic Testing.

PubMed

Tavares, Isabel; Oliveira, João Paulo; Pinho, Ana; Moreira, Luciana; Rocha, Liliana; Santos, Josefina; Pinheiro, Joaquim; Costa, Paulo Pinho; Lobato, Luísa

2017-08-01

Fibrinogen A α-chain (AFib) amyloidosis results from autosomal-dominant mutations in the gene encoding AFib (FGA). Patients with this disorder typically present with proteinuria. Isolated cases of AFib amyloidosis, carrying the FGA p.Glu545Val variant, were identified in the district of Braga, in northwest Portugal. This observation led us to hypothesize that this disorder might be an unrecognized cause of kidney disease in that region and prompted us to carry out targeted genetic testing for the p.Glu545Val variant in the local hemodialysis population and family members of identified cases. Case series. 3 groups of participants: (1) kidney biopsy registry, n=4; (2) hemodialysis facility, n=122 of 267 patients; and (3) genetically at-risk individuals; n=69 of 167 family members. Kidney disease, kidney disease progression, and survival. The p.Glu545Val variant was identified in all 4 patients of the biopsy registry, 12 of 122 (9.8%) hemodialysis patients tested, and 34 of 69 (49%) relatives tested. These 50 cases belonged to 13 unrelated families with kidney disease or amyloidosis identified in 61% of probands. 35 individuals presented with hypertension at a mean of 51.0±10.4 years. Of these, 30 developed kidney disease at a mean of 56.7±12.0 years, and 21 initiated dialysis therapy at a mean of 61.4±11.3 years. Heart, liver, spleen, colon, and ileum were involved along the progression of the disease. Kidney disease was formerly attributed to hypertension in 25% of patients with AFib amyloidosis undergoing hemodialysis. Retrospective data collection for patients with amyloidosis previously diagnosed. AFib amyloidosis appears to be an under-recognized disorder in Braga, Portugal, where we found a high frequency of the FGA p.Glu545Val variant. Due to the nonspecific nature of its major clinical features, the diagnosis of AFib amyloidosis should have a high index of suspicion, particularly in populations in which hypertension is prevalent. Copyright © 2017 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.

A critical assessment on kidney allocation systems.

PubMed

Formica, Richard N

2017-01-01

The kidney allocation system that took effect on December 4, 2014 represents a significant improvement over the prior approach. It seeks to improve outcomes by longevity matching - pairing kidneys expected to function the longest with recipients expected to live the longest. It addresses the biological barriers faced by highly sensitized patients in an evidence based fashion and it begins to introduce the concept of medical need into kidney allocation by crediting time from the starting dialysis to a patient's waiting time. Additionally, it adds a more granular and continuous approach to classifying deceased donor kidneys through the kidney donor profile index and moves away from the dichotomous and flawed, standard criteria/extended criteria approach to allocating kidneys. Despite these changes, access to kidney transplantation across the age spectrum has remained intact and equitable. However even with these numerous positive improvements the system is not without its flaws. The increased sharing and by extension shipping of kidneys have created logistical challenges for organ procurement organizations and transplant centers. Early results seem to indicate that there have been an increase in cold ischemic time, an increase in delayed graft function and an increase in organ discard rate. There is also a reduced offer rate for children and while not a statistically significant decline in the number of transplants, it is a trend that requires close monitoring. Finally, the new kidney allocation system has done nothing to address the glaring deficiencies in the multi-organ allocation practices, all of which include a kidney, in the United States. Therefore despite the improvements made in kidney allocation, there is work yet to be done to ensure that the allocation of life saving and life prolonging organs for transplantation is done in a fashion consistent with ethical principles, based on science and free from local self interest so that this national resource is used for the betterment of the population it is meant to serve. Copyright © 2016. Published by Elsevier Inc.

Chronic kidney disease of nontraditional etiology in Central America: a provisional epidemiologic case definition for surveillance and epidemiologic studies.

PubMed

Lozier, Matthew; Turcios-Ruiz, Reina Maria; Noonan, Gary; Ordunez, Pedro

2016-11-01

SYNOPSIS Over the last two decades, experts have reported a rising number of deaths caused by chronic kidney disease (CKD) along the Pacific coast of Central America, from southern Mexico to Costa Rica. However, this specific disease is not associated with traditional causes of CKD, such as aging, diabetes, or hypertension. Rather, this disease is a chronic interstitial nephritis termed chronic kidney disease of nontraditional etiology (CKDnT). According to the Pan American Health Organization (PAHO) mortality database, there are elevated rates of deaths related to kidney disease in many of these countries, with the highest rates being reported in El Salvador and Nicaragua. This condition has been identified in certain agricultural communities, predominantly among male farmworkers. Since CKD surveillance systems in Central America are under development or nonexistent, experts and governmental bodies have recommended creating standardized case definitions for surveillance purposes to monitor and characterize this epidemiological situation. A group of experts from Central American ministries of health, the U.S. Centers for Disease Control and Prevention (CDC), and PAHO held a workshop in Guatemala to discuss CKDnT epidemiologic case definitions. In this paper, we propose that CKD in general be identified by the standard definition internationally accepted and that a suspect case of CKDnT be defined as a person age < 60 years with CKD, without type 1 diabetes mellitus, hypertensive diseases, and other well-known causes of CKD. A probable case of CKDnT is defined as a suspect case with the same findings confirmed three or more months later.

Should We Formulate an Incentivized Model Facilitating Kidney Donation from Living Donors? A Focus on Turkey's Current System.

PubMed

Avci, Ercan

2018-04-23

Kidney transplantation is a lifesaving medical treatment. However, very high demand for kidneys with low kidney donation causes a black market that exploits patients' desperation and donors' vulnerability. The current kidney donation programs fail to produce promising results to avoid illegal and unethical kidney trafficking and commercialism. Even though the primary goal of kidney donation is to increase the number of deceased organ donations, in some countries, like Turkey, due to religious or cultural concerns, it is impossible to supply adequate deceased kidney donations. In this view, the aim of this paper is to examine kidney trafficking in the scope of Turkey's current organ donation system and propose a new model, named the Incentivized Kidney Donation Model (IKDM), to increase kidney donation from living donors. The model encompasses the following benefits offered to kidney donors; lifetime health insurance, exemptions from copayments/contribution shares, priority when receiving an organ, priority when finding a job, income tax exemptions for salaried employees, and free or discounted public utilities. This normative model has the potential to promote donors' altruistic acts as well as the solidarity and loyalty among members of a society without violating ethical values and internationally accepted principles. © 2018 John Wiley & Sons Ltd.

Using Patient-Reported Outcome Measures (PROMs) to promote quality of care and safety in the management of patients with Advanced Chronic Kidney disease (PRO-trACK project): a mixed-methods project protocol.

PubMed

Aiyegbusi, Olalekan Lee; Kyte, Derek; Cockwell, Paul; Marshall, Tom; Dutton, Mary; Slade, Anita; Marklew, Neil; Price, Gary; Verdi, Rav; Waters, Judi; Sharpe, Keeley; Calvert, Melanie

2017-06-30

Advanced chronic kidney disease (CKD) has a major effect on the quality of life and health status of patients and requires accurate and responsive management. The use of electronic patient-reported outcome measures (ePROMs) could assist patients with advanced pre-dialysis CKD, and the clinicians responsible for their care, by identifying important changes in symptom burden in real time. We report the protocol for 'Using Patient-Reported Outcome measures (PROMs) to promote quality of care and safety in the management of patients with Advanced Chronic Kidney Disease' (PRO-trACK) project, which will explore the feasibility and validity of an ePROM system for use in patients with advanced CKD. The project will use a mixed-methods approach in three studies: (1) usability testing of the ePROM system involving up to 30 patients and focusing on acceptability and technical performance/stability; (2) ascertaining the views of patient and clinician stakeholders on the optimal use and administration of the CKD ePROM system-this will involve qualitative face-to-face/telephone interviewing with up to 30 patients or until saturation is achieved, focus groups with up to 15 clinical staff, management and IT team members; (3) psychometric assessment of the system, within a cohort of at least 180 patients with advanced CKD, to establish the measurement properties of the ePROM. This project was approved by the West Midlands Edgbaston Research Ethics Committee (Reference 17/WM/0010) and received Health Research Authority (HRA) approval on 24 February 2017.The findings from this project will be provided to clinicians at the Department of Renal Medicine, Queen Elizabeth Hospitals, Birmingham (QEHB), NHS England, presented at conferences and to the Kidney Patients' Association, British Kidney Patient Association and the British Renal Society. Articles based on the findings will be written and submitted for publication in peer-reviewed journals. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Assessing barriers to adherence in routine clinical care for pediatric kidney transplant patients.

PubMed

Varnell, Charles D; Rich, Kristin L; Nichols, Melissa; Dahale, Devesh; Goebel, Jens W; Pai, Ahna L H; Hooper, David K; Modi, Avani C

2017-11-01

Patient-identified barriers to immunosuppressive medications are associated with poor adherence and negative clinical outcomes in transplant patients. Assessment of adherence barriers is not part of routine post-transplant care, and studies regarding implementing such a process in a reliable way are lacking. Using the Model for Improvement and PDSA cycles, we implemented a system to identify adherence barriers, including patient-centered design of a barriers assessment tool, identification of eligible patients, clear roles for clinic staff, and creating a culture of non-judgmental discussion around adherence. We performed time-series analysis of our process measure. Secondary analyses examined the endorsement and concordance of adherence barriers between patient-caregiver dyads. After three methods of testing, the most reliable delivery system was an EHR-integrated tablet that alerted staff of patient eligibility for assessment. Barriers were endorsed by 35% of caregivers (n=85) and 43% of patients (n=60). The most frequently patient-endorsed barriers were forgetting, poor taste, and side effects. Caregivers endorsed forgetting and side effects. Concordance between patient-caregiver dyads was fair (k=0.299). Standardized adherence barriers assessment is feasible in the clinical care of pediatric kidney transplant patients. Features necessary for success included automation, redundant systems with designated staff to identify and mitigate failures, aligned reporting structures, and reliable measurement approaches. Future studies will examine whether barriers predict clinical outcomes (eg, organ rejection, graft loss). © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Kidneys at Higher Risk of Discard: Expanding the Role of Dual Kidney Transplantation

PubMed Central

Tanriover, B.; Mohan, S.; Cohen, D. J.; Radhakrishnan, J.; Nickolas, T. L.; Stone, P. W.; Tsapepas, D. S.; Crew, R. J.; Dube, G. K.; Sandoval, P. R.; Samstein, B.; Dogan, E.; Gaston, R. S.; Tanriover, J. N.; Ratner, L. E.; Hardy, M. A.

2014-01-01

Half of the recovered expanded criteria donor (ECD) kidneys are discarded in the United States. A new kidney allocation system offers kidneys at higher risk of discard, Kidney Donor Profile Index (KDPI) >85%, to a wider geographic area to promote broader sharing and expedite utilization. Dual kidney transplantation (DKT) based on the KDPI is a potential option to streamline allocation of kidneys which otherwise would have been discarded. To assess the clinical utility of the KDPI in kidneys at higher risk of discard, we analyzed the OPTN/UNOS Registry that included the deceased donor kidneys recovered between 2002 and 2012. The primary outcomes were allograft survival, patient survival and discard rate based on different KDPI categories (<80%, 80–90% and >90%). Kidneys with KDPI >90% were associated with increased odds of discard (OR = 1.99, 95% CI 1.74–2.29) compared to ones with KDPI <80%. DKTs of KDPI >90% were associated with lower overall allograft failure (HR = 0.74, 95% CI 0.62–0.89) and better patient survival (HR = 0.79, 95% CI 0.64–0.98) compared to single ECD kidneys with KDPI >90%. Kidneys at higher risk of discard may be offered in the up-front allocation system as a DKT. Further modeling and simulation studies are required to determine a reasonable KDPI cutoff percentile. PMID:24472195

Polycystic kidney disease at Howard University Hospital.

PubMed

Hosten, A O; Cummings, Y

1977-08-01

Adult polycystic kidney disease treatment at Howard University Hospital is summarized. The cases are taken from autopsies performed between January 1955 and November 1975 and from the Hospital's dialysis population. Polycystic kidney disease was identified in six adults and four infants. Only two dialysis patients were clinically thought to have the disease. A review of the major clinical features of the disease is presented.

Systems toxicology of chemically induced liver and kidney injuries: histopathology‐associated gene co‐expression modules

PubMed Central

Te, Jerez A.; AbdulHameed, Mohamed Diwan M.

2016-01-01

Abstract Organ injuries caused by environmental chemical exposures or use of pharmaceutical drugs pose a serious health risk that may be difficult to assess because of a lack of non‐invasive diagnostic tests. Mapping chemical injuries to organ‐specific histopathology outcomes via biomarkers will provide a foundation for designing precise and robust diagnostic tests. We identified co‐expressed genes (modules) specific to injury endpoints using the Open Toxicogenomics Project‐Genomics Assisted Toxicity Evaluation System (TG‐GATEs) – a toxicogenomics database containing organ‐specific gene expression data matched to dose‐ and time‐dependent chemical exposures and adverse histopathology assessments in Sprague–Dawley rats. We proposed a protocol for selecting gene modules associated with chemical‐induced injuries that classify 11 liver and eight kidney histopathology endpoints based on dose‐dependent activation of the identified modules. We showed that the activation of the modules for a particular chemical exposure condition, i.e., chemical‐time‐dose combination, correlated with the severity of histopathological damage in a dose‐dependent manner. Furthermore, the modules could distinguish different types of injuries caused by chemical exposures as well as determine whether the injury module activation was specific to the tissue of origin (liver and kidney). The generated modules provide a link between toxic chemical exposures, different molecular initiating events among underlying molecular pathways and resultant organ damage. Published 2016. This article is a U.S. Government work and is in the public domain in the USA. Journal of Applied Toxicology published by John Wiley & Sons, Ltd. PMID:26725466

Pericytes in kidney fibrosis.

PubMed

Ren, Shuyu; Duffield, Jeremy S

2013-07-01

Pericytes and perivascular fibroblasts have emerged as poorly appreciated yet extensive populations of mesenchymal cells in the kidney that play important roles in homeostasis and responses to injury. This review will update readers on the evolving understanding of the biology of these cells. Fate mapping has identified pericytes and perivascular fibroblasts as the major source of pathological fibrillar matrix-forming cells in interstitial kidney disease. In other organs similar cells have been described and independent fate mapping indicates that pericytes or perivascular cells are myofibroblast progenitors in multiple organs. Over the last year, new insights into the function of pericytes in kidney homeostasis has been uncovered and new molecular pathways that regulate detachment and their transdifferentiation into pathological myofibroblasts, including Wingless/Int, ephrin, transforming growth factor β, platelet derived growth factor, and Hedgehog signaling pathways, have been reported. In addition provocative studies indicate that microRNAs, which regulate posttranscriptional gene expression, may also play important roles in their transdifferentiation. Pericytes and perivascular fibroblasts are the major source of pathological collagen fiber-forming cells in interstitial kidney diseases. New avenues of research into their activation and differentiation has identified new drug candidates for the treatment of interstitial kidney disease.

Challenge with 17alpha-ethinylestradiol (EE2) during early development persistently impairs growth, differentiation, and local expression of IGF-I and IGF-II in immune organs of tilapia.

PubMed

Shved, Natallia; Berishvili, Giorgi; Häusermann, Eliane; D'Cotta, Helena; Baroiller, Jean-François; Eppler, Elisabeth

2009-03-01

The enormous expansion of world-wide aquaculture has led to increasing interest in the regulation of fish immune system. Estrogen has recently been shown to inhibit the endocrine (liver-derived) and autocrine/paracrine local insulin-like growth factor-I system in fish. In order to address the potential actions of estrogen on the IGF system in immune organs, tilapia were fed with 17alpha-ethinylestradiol (EE2)-enriched food from 10 to 40 days post fertilization (DPF) to induce functional feminization, an approach commonly used in aquaculture. EE2-treated and control fish were sampled at 75 and 165 DPF. The expression levels of ER-alpha, IGF-I, IGF-II and growth hormone receptor (GH-R) mRNA in spleen and head kidney were determined by real-time PCR and the expressing sites of IGF-I mRNA identified by in situ hybridisation. Ratios of spleen length and weight to body length and weight were determined. At 165 DPF, the length (4.9% vs. 7.6%) and weight (0.084% vs. 0.132%) ratios were significantly lowered in EE2-treated fish and number and size of the melanomacrophage centres were considerably reduced. At 75 DPF, both in spleen and head kidney of EE2-treated fish the expression levels of IGF-I and IGF-II mRNA were markedly diminished. The suppression was more pronounced for IGF-I (spleen: -12.071-fold; head kidney: -8.413-fold) than for IGF-II (spleen: -4.102-fold; head kidney: -1.342-fold). In agreement, clearly fewer leucocytes and macrophages in head kidney and spleen of EE2-treated fish contained IGF-I mRNA as shown by in situ hybridisation. ER-alpha mRNA expression in spleen was increased at 75 DPF but unchanged in head kidney. GH-R gene expression showed a mild upregulation at 165 DPF in both tissues. Thus, exposure to EE2 during early development affected distinctly the IGF system in tilapia immune organs. It led to lasting impairment of spleen growth and differentiation that can be attributed to an interaction of EE2 with IGF-I and, less pronouncedly, IGF-II. Especially, the impairment of spleen and melanomacrophage centres might interfere with the antigen presentation capacity of the immune system and, thus, alter susceptibility to infection.

Dact2 is expressed in the developing ureteric bud/collecting duct system of the kidney and controls morphogenetic behavior of collecting duct cells.

PubMed

Lee, Wen-Chin; Hough, Melinda T; Liu, Weijia; Ekiert, Robert; Lindström, Nils O; Hohenstein, Peter; Davies, Jamie A

2010-10-01

The overall pattern of the developing kidney is set in large part by the developing ureteric bud/collecting duct system, and dysgenesis of this system accounts for a variety of clinically significant renal diseases. Understanding how the behavior of cells in the developing ureteric bud/collecting duct is controlled is therefore important to understanding the normal and abnormal kidney. Dact proteins have recently been identified as cytoplasmic regulators of intracellular signaling. Dact1 inhibits Wnt signaling, and Dact2 inhibits transforming growth factor (TGF)-β signaling. Here, we report that Dact2 is expressed in developing and adult mouse kidneys, specifically in the ureteric bud/collecting duct epithelium, a structure whose morphogenesis is controlled partially by TGF-β. When small interfering RNA is used to knock down Dact2 expression in collecting duct cells, they show some constitutive phospho-Smad2, undetectable in controls, and elevated phospho-Smad2 in response to TGF-β. They also show defective migration and, in a monolayer wound-healing assay, they fail to assemble a leading edge "cable" of actomyosin and advance instead as a disorganized mass of lamellipodium-bearing cells. This effect is seriously exacerbated by exogenous TGF-β, although control cells tolerate it well. In three-dimensional culture, Dact2 knockdown cells form cysts and branching tubules, but the outlines of the cysts made by knockdown cells are ragged rather than smooth and the branching tubules are decorated with many fine spikes not seen in controls. These data suggest Dact2 plays a role in regulating morphogenesis by renal collecting duct cells, probably by protecting cells from overly strong TGF-β pathway activation.

Systemic molecular and cellular changes induced in rats upon inhalation of JP-8 petroleum fuel vapor.

PubMed

Hanas, Jay S; Bruce Briggs, G; Lerner, Megan R; Lightfoot, Stan A; Larabee, Jason L; Karsies, Todd J; Epstein, Robert B; Hanas, Rushie J; Brackett, Daniel J; Hocker, James R

2010-05-01

Limited information is available regarding systemic changes in mammals associated with exposures to petroleum/hydrocarbon fuels. In this study, systemic toxicity of JP-8 jet fuel was observed in a rat inhalation model at different JP-8 fuel vapor concentrations (250, 500, or 1000 mg/m(3), for 91 days). Gel electrophoresis and mass spectrometry sequencing identified the alpha-2 microglobulin protein to be elevated in rat kidney in a JP-8 dose-dependent manner. Western blot analysis of kidney and lung tissue extracts revealed JP-8 dependent elevation of inducible heat shock protein 70 (HSP70). Tissue changes were observed histologically (hematoxylin and eosin staining) in liver, kidney, lung, bone marrow, and heart, and more prevalently at medium or high JP-8 vapor phase exposures (500-1000 mg/m(3)) than at low vapor phase exposure (250 mg/m(3)) or non-JP-8 controls. JP-8 fuel-induced liver alterations included dilated sinusoids, cytoplasmic clumping, and fat cell deposition. Changes to the kidneys included reduced numbers of nuclei, and cytoplasmic dumping in the lumen of proximal convoluted tubules. JP-8 dependent lung alterations were edema and dilated alveolar capillaries, which allowed clumping of red blood cells (RBCs). Changes in the bone marrow in response to JP-8 included reduction of fat cells and fat globules, and cellular proliferation (RBCs, white blood cells-WBCs, and megakaryocytes). Heart tissue from JP-8 exposed animals contained increased numbers of inflammatory and fibroblast cells, as well as myofibril scarring. cDNA array analysis of heart tissue revealed a JP-8 dependent increase in atrial natriuretic peptide precursor mRNA and a decrease in voltage-gated potassium (K+) ion channel mRNA.

Is there a differential strength of specific HLA mismatches in kidney transplants?

PubMed

Sasaki, N; Idica, A; Terasaki, P

2008-05-01

In this article we attempted to identify whether there is a specific mismatched antigen that might be detrimental to kidney transplant outcome. The frequency of function versus failure of transplant cases was tallied within subpopulations among a subset of the 2006 United Network for Organ Sharing transplant dataset. We examined 7998 cadaveric and 11,420 living donor kidney transplants that were mismatched for a single class I antigen. When tested by five different criteria, the results were relatively similar for the HLA class I, A- and B-locus mismatches. HLA A1 was identified as the single most dominant immunogenic mismatch. However, when the P values were multiplied by 68, the number of comparisons, A1 was only marginally significant. We concluded that at least for class I specificities, the 68 specificities were about equal immunogenicity in kidney transplantation.

Renal Parenchymal Area Growth Curves for Children 0 to 10 Months Old.

PubMed

Fischer, Katherine; Li, Chunming; Wang, Huixuan; Song, Yihua; Furth, Susan; Tasian, Gregory E

2016-04-01

Low renal parenchymal area, which is the gross area of the kidney in maximal longitudinal length minus the area of the collecting system, has been associated with increased risk of end stage renal disease during childhood in boys with posterior urethral valves. To our knowledge normal values do not exist. We aimed to increase the clinical usefulness of this measure by defining normal renal parenchymal area during infancy. In a cross-sectional study of children with prenatally detected mild unilateral hydronephrosis who were evaluated between 2000 and 2012 we measured the renal parenchymal area of normal kidney(s) opposite the kidney with mild hydronephrosis. Measurement was done with ultrasound from birth to post-gestational age 10 months. We used the LMS method to construct unilateral, bilateral, side and gender stratified normalized centile curves. We determined the z-score and the centile of a total renal parenchymal area of 12.4 cm(2) at post-gestational age 1 to 2 weeks, which has been associated with an increased risk of kidney failure before age 18 years in boys with posterior urethral valves. A total of 975 normal kidneys of children 0 to 10 months old were used to create renal parenchymal area centile curves. At the 97th centile for unilateral and single stratified curves the estimated margin of error was 4.4% to 8.8%. For bilateral and double stratified curves the estimated margin of error at the 97th centile was 6.6% to 13.2%. Total renal parenchymal area less than 12.4 cm(2) at post-gestational age 1 to 2 weeks had a z-score of -1.96 and fell at the 3rd percentile. These normal renal parenchymal area curves may be used to track kidney growth in infants and identify those at risk for chronic kidney disease progression. Copyright © 2016 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

Local television news reporting of kidney disease.

PubMed

Jaffery, Jonathan B; Jacobson, Lynn M; Goldstein, Kenneth M; Pribble, James M

2006-12-01

Local television is the primary news source for the majority of Americans. This study aims to describe how local news reports on kidney disease. Using our searchable database of health-related late local news segments from 2002, we identified stories with the key words kidney, hypertension, blood pressure, or diabetes. This database is a representative sample of the late local news on 122 stations in the 50 largest US media markets, comprising 60% of the population. The content of each identified story was reviewed to determine whether it mentioned: (1) chronic kidney disease (CKD), (2) screening for kidney disease, or (3) kidney disease as a potential complication (for blood pressure- or diabetes-related stories). Only 2 of 1,799 database news stories (0.11%) included "kidney" as a summary key word; neither referred to CKD, screening, or complications of other diseases. Of 19 stories about hypertension or blood pressure (1.06% of all stories) and the 14 stories about diabetes (0.78% of all stories), none mentioned these criteria. Despite efforts to increase public awareness of and screening for CKD, local television news (the most important news source for a majority of Americans) did little to help achieve these goals. Further work will be needed to confirm whether this paucity of coverage varies over time and determine why so little attention is given to CKD. Educating physicians and public relations personnel who advocate for kidney disease about journalists' needs may be an important step to help advance public awareness of CKD.

Lipoxins Regulate the Early Growth Response-1 Network and Reverse Diabetic Kidney Disease.

PubMed

Brennan, Eoin P; Mohan, Muthukumar; McClelland, Aaron; Tikellis, Christos; Ziemann, Mark; Kaspi, Antony; Gray, Stephen P; Pickering, Raelene; Tan, Sih Min; Ali-Shah, Syed Tasadaque; Guiry, Patrick J; El-Osta, Assam; Jandeleit-Dahm, Karin; Cooper, Mark E; Godson, Catherine; Kantharidis, Phillip

2018-05-01

Background The failure of spontaneous resolution underlies chronic inflammatory conditions, including microvascular complications of diabetes such as diabetic kidney disease. The identification of endogenously generated molecules that promote the physiologic resolution of inflammation suggests that these bioactions may have therapeutic potential in the context of chronic inflammation. Lipoxins (LXs) are lipid mediators that promote the resolution of inflammation. Methods We investigated the potential of LXA 4 and a synthetic LX analog (Benzo-LXA 4 ) as therapeutics in a murine model of diabetic kidney disease, ApoE -/- mice treated with streptozotocin. Results Intraperitoneal injection of LXs attenuated the development of diabetes-induced albuminuria, mesangial expansion, and collagen deposition. Notably, LXs administered 10 weeks after disease onset also attenuated established kidney disease, with evidence of preserved kidney function. Kidney transcriptome profiling defined a diabetic signature (725 genes; false discovery rate P ≤0.05). Comparison of this murine gene signature with that of human diabetic kidney disease identified shared renal proinflammatory/profibrotic signals (TNF- α , IL-1 β , NF- κ B). In diabetic mice, we identified 20 and 51 transcripts regulated by LXA 4 and Benzo-LXA 4 , respectively, and pathway analysis identified established (TGF- β 1, PDGF, TNF- α , NF- κ B) and novel (early growth response-1 [EGR-1]) networks activated in diabetes and regulated by LXs. In cultured human renal epithelial cells, treatment with LXs attenuated TNF- α -driven Egr-1 activation, and Egr-1 depletion prevented cellular responses to TGF- β 1 and TNF- α Conclusions These data demonstrate that LXs can reverse established diabetic complications and support a therapeutic paradigm to promote the resolution of inflammation. Copyright © 2018 by the American Society of Nephrology.

d-Limonene-induced male rat-specific nephrotoxicity: Evaluation of the association between d-limonene and alpha 2u-globulin

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lehman-McKeeman, L.D.; Rodriguez, P.A.; Takigiku, R.

1989-06-15

d-Limonene is a naturally occurring monoterpene, which when dosed orally, causes a male rat-specific nephrotoxicity manifested acutely as the exacerbation of protein droplets in proximal tubule cells. Experiments were conducted to examine the retention of (/sup 14/C)d-limonene in male and female rat kidney, to determine whether d-limonene or one or more of its metabolites associates with the male rat-specific protein, alpha 2u-globulin, and if so, to identify the bound material. The results indicated that, 24 hr after oral administration of 3 mmol d-limonene/kg, the renal concentration of d-limonene equivalents was approximately 2.5 times higher in male rats than in femalemore » rats. Equilibrium dialysis in the presence or absence of sodium dodecyl sulfate indicated that approximately 40% of the d-limonene equivalents in male rat kidney associated with proteins in a reversible manner, whereas no significant association was observed between d-limonene equivalents and female rat kidney proteins. Association between d-limonene and male rat kidney proteins was characterized by high-performance gel filtration and reverse-phase chromatography. Gel filtration HPLC indicated that d-limonene in male rat kidney is associated with a protein fraction having a molecular weight of approximately 20,000. Separation of alpha 2u-globulin from other kidney proteins by reverse-phase HPLC indicated that d-limonene associated with a protein present only in male rat kidney which was definitively identified as alpha 2u-globulin by amino acid sequencing. The major metabolite associated with alpha 2u-globulin was d-limonene-1,2-oxide. Parent d-limonene was also identified as a minor component in the alpha 2u-globulin fraction.« less

Changing Needs for Information and Support in an Online System for Parents of Children With Kidney Disease

PubMed Central

Pinsk, Maury; Nicholas, David

2017-01-01

Background: Pediatric chronic kidney disease is psychologically, financially, and physically demanding on parents providing care. Parents often feel isolated because of the rarity of the condition, and geographic isolation often compounds this perception in Canada. Many parents seek assistance online for both information and social support. Objective: This study examines an online portal, titled “Ability Online,” which was designed to provide support and information to a diverse group of parents using chat facilities, bulletin boards, and e-mail. Specifically, we sought to identify how the technologies offered in this system related to the support and information seeking needs for parents. Secondary aims of determining possible reasons for attrition over time were explored as well. Design: Mixed methodology sequential exploratory design using the qualitative methodology of descriptive interpretation. Setting: Telephone interviews. Patients: Twenty parents of pediatric patients with chronic kidney disease from four Canadian centers who engaged in an online social support system “Ability Online.” Measurements: Interview transcripts generated from 20 taped phone conversations were reviewed from parents who engaged in the online system, and the themes derived from these transcripts served to generate semistructured interview questions that focused on their use of, and perceived benefit from, this technology for social support. Follow-up telephone interviews were then conducted with a 6-person subset of the original group in an effort to further define the impact of technology on their experience. This same smaller cohort provided data on social supports, caregiver satisfaction, and caregiver stress. Results: Many parents experience a progression through which their needs for knowledge and support change over time. Specifically, parents describe a transition from pure information seeking, to seeking parental interaction, mutual support and collaboration, and ultimately to advocacy. Parents described how technology could be used to address those needs. Limitations: Our cohort was slightly more educated and representative of more urban populations than published data reflecting the population of North American pediatric patients living with kidney disease. Conclusions: Our data suggest themes of technology use influencing the goals of online support seeking. While our findings are preliminary, further study may inform Web designers to identify the changing needs of participants in designing such online support networks, and minimize the reasons that participants fail to adopt, or terminate their online experiences. PMID:28717515

Inflammation in renal atherosclerotic disease.

PubMed

Udani, Suneel M; Dieter, Robert S

2008-07-01

The study of renal atherosclerotic disease has conventionally focused on the diagnosis and management of renal artery stenosis. With the increased understanding of atherosclerosis as a systemic inflammatory process, there has been increased interest in vascular biology at the microvasculature level. While different organ beds share some features, the inflammation and injury in the microvasculature of the kidney has unique elements as well. Understanding of the pathogenesis yields a better understanding of the clinical manifestations of renal atherosclerotic disease, which can be very subtle. Furthermore, identifying the molecular mechanisms responsible for the progression of kidney damage can also direct clinicians and scientists toward targeted therapies. Existing therapies used to treat atherosclerotic disease in other vascular beds may also play a role in the treatment of renal atherosclerotic disease.

Isolation and characterizations of oxalate-binding proteins in the kidney

DOE Office of Scientific and Technical Information (OSTI.GOV)

Roop-ngam, Piyachat; Chaiyarit, Sakdithep; Pongsakul, Nutkridta

Highlights: Black-Right-Pointing-Pointer The first large-scale characterizations of oxalate-binding kidney proteins. Black-Right-Pointing-Pointer The recently developed oxalate-conjugated EAH Sepharose 4B beads were applied. Black-Right-Pointing-Pointer 38 forms of 26 unique oxalate-binding kidney proteins were identified. Black-Right-Pointing-Pointer 25/26 (96%) of identified proteins had 'L-x(3,5)-R-x(2)-[AGILPV]' domain. -- Abstract: Oxalate-binding proteins are thought to serve as potential modulators of kidney stone formation. However, only few oxalate-binding proteins have been identified from previous studies. Our present study, therefore, aimed for large-scale identification of oxalate-binding proteins in porcine kidney using an oxalate-affinity column containing oxalate-conjugated EAH Sepharose 4B beads for purification followed by two-dimensional gel electrophoresis (2-DE) tomore » resolve the recovered proteins. Comparing with those obtained from the controlled column containing uncoupled EAH-Sepharose 4B (to subtract the background of non-specific bindings), a total of 38 protein spots were defined as oxalate-binding proteins. These protein spots were successfully identified by quadrupole time-of-flight mass spectrometry (MS) and/or tandem MS (MS/MS) as 26 unique proteins, including several nuclear proteins, mitochondrial proteins, oxidative stress regulatory proteins, metabolic enzymes and others. Identification of oxalate-binding domain using the PRATT tool revealed 'L-x(3,5)-R-x(2)-[AGILPV]' as a functional domain responsible for oxalate-binding in 25 of 26 (96%) unique identified proteins. We report herein, for the first time, large-scale identification and characterizations of oxalate-binding proteins in the kidney. The presence of positively charged arginine residue in the middle of this functional domain suggested its significance for binding to the negatively charged oxalate. These data will enhance future stone research, particularly on stone modulators.« less

Apolipoprotein L1 and Chronic Kidney Disease Risk in Young Potential Living Kidney Donors.

PubMed

Locke, Jayme E; Sawinski, Deirdre; Reed, Rhiannon D; Shelton, Brittany; MacLennan, Paul A; Kumar, Vineeta; Mehta, Shikha; Mannon, Roslyn B; Gaston, Robert; Julian, Bruce A; Carr, John J; Terry, James G; Kilgore, Meredith; Massie, Allan B; Segev, Dorry L; Lewis, Cora E

2018-06-01

The aim of this study was to develop a novel chronic kidney disease (CKD) risk prediction tool for young potential living kidney donors. Living kidney donor selection practices have evolved from examining individual risk factors to a risk calculator incorporating multiple characteristics. Owing to limited long-term data and lack of genetic information, current risk tools lack precision among young potential living kidney donors, particularly African Americans (AAs). We identified a cohort of young adults (18-30 years) with no absolute contraindication to kidney donation from the longitudinal cohort study Coronary Artery Risk Development in Young Adults. Risk associations for CKD (estimated glomerular filtration rate <60 mL/min/1.73 m) were identified and assigned weighted points to calculate risk scores. A total of 3438 healthy adults were identified [mean age 24.8 years; 48.3% AA; median follow-up 24.9 years (interquartile range: 24.5-25.2)]. For 18-year olds, 25-year projected CKD risk varied by ethnicity and sex even without baseline clinical and genetic abnormalities; risk was 0.30% for European American (EA) women, 0.52% for EA men, 0.52% for AA women, 0.90% for AA men. Among 18-year-old AAs with apolipoprotein L1 gene (APOL1) renal-risk variants without baseline abnormalities, 25-year risk significantly increased: 1.46% for women and 2.53% for men; among those with 2 APOL1 renal-risk variants and baseline abnormalities, 25-year risk was higher: 2.53% to 6.23% for women and 4.35% to 10.58% for men. Young AAs were at highest risk for CKD, and APOL1 renal-risk variants drove some of this risk. Understanding the genetic profile of young AA potential living kidney donors in the context of baseline health characteristics may help to inform candidate selection and counseling.

Predictors of liver donation without kidney recovery in a cohort of expanded criteria donors: identifying opportunities to improve expanded criteria donor kidney utilization.

PubMed

White, S L; Leichtman, A B; O'Connor, K; Lipkowitz, G; Pietroski, R; Stoff, J S; Luskin, R S; Belcher, J; Meyer, K; Merion, R M; Port, F K; Delmonico, F L

2012-09-01

To maximize deceased donation, it is necessary to facilitate organ recovery from expanded criteria donors (ECDs). Utilization of donors meeting the kidney definition for ECDs increases access to kidney transplantation and reduces waiting times; however, ECDs often do not proceed to kidney recovery. Based on a prospective study of three Organ Procurement Organizations in the United States, we describe the characteristics of donors meeting the Organ Procurement and Transplant Network (OPTN) ECD kidney definition (donor age 60+ or donor age 50-60 years with two of the following: final serum creatinine > 1.5 mg/dL, history of hypertension, or death from cerebral vascular accident) who donated a liver without kidney recovery. ECDs with organs recovered between February 2003 and September 2005 by New England Organ Bank, Gift of Life Michigan, and LifeChoice Donor Services were studied (n = 324). All donors were declared dead by neurological criteria. Data on a wide range of donor characteristics were collected, including donor demographics, medical history, cause of death, donor status during hospitalization, serological status, and donor kidney quality. Logistic regression models were used to identify donor characteristics predictive of liver-alone donation. Seventy-four of the 324 donors fulfilling the ECD definition for kidneys donated a liver alone (23%). History of diabetes, final serum creatinine > 1.5 mg/dL, age 70+, and presence of proteinuria were associated with liver-alone donation in univariate models. On multivariate analysis, only final serum creatinine > 1.5 mg/dL and age 70+ were independently predictive of liver donation alone. Older age and elevated serum creatinine may be perceived as stronger contraindications to kidney donation than the remaining elements of the ECD definition. It is likely that at least a proportion of these liver-alone donors represent missed opportunities for kidney transplantation. Copyright © 2012 Elsevier Inc. All rights reserved.

Studying Kidney Disease Using Tissue and Genome Engineering in Human Pluripotent Stem Cells.

PubMed

Garreta, Elena; González, Federico; Montserrat, Núria

2018-01-01

Kidney morphogenesis and patterning have been extensively studied in animal models such as the mouse and zebrafish. These seminal studies have been key to define the molecular mechanisms underlying this complex multistep process. Based on this knowledge, the last 3 years have witnessed the development of a cohort of protocols allowing efficient differentiation of human pluripotent stem cells (hPSCs) towards defined kidney progenitor populations using two-dimensional (2D) culture systems or through generating organoids. Kidney organoids are three-dimensional (3D) kidney-like tissues, which are able to partially recapitulate kidney structure and function in vitro. The current possibility to combine state-of-the art tissue engineering with clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated systems 9 (Cas9)-mediated genome engineering provides an unprecedented opportunity for studying kidney disease with hPSCs. Recently, hPSCs with genetic mutations introduced through CRISPR/Cas9-mediated genome engineering have shown to produce kidney organoids able to recapitulate phenotypes of polycystic kidney disease and glomerulopathies. This mini review provides an overview of the most recent advances in differentiation of hPSCs into kidney lineages, and the latest implementation of the CRISPR/Cas9 technology in the organoid setting, as promising platforms to study human kidney development and disease. © 2017 S. Karger AG, Basel.

Development and validation of an electronic phenotyping algorithm for chronic kidney disease

PubMed Central

Nadkarni, Girish N; Gottesman, Omri; Linneman, James G; Chase, Herbert; Berg, Richard L; Farouk, Samira; Nadukuru, Rajiv; Lotay, Vaneet; Ellis, Steve; Hripcsak, George; Peissig, Peggy; Weng, Chunhua; Bottinger, Erwin P

2014-01-01

Twenty-six million Americans are estimated to have chronic kidney disease (CKD) with increased risk for cardiovascular disease and end stage renal disease. CKD is frequently undiagnosed and patients are unaware, hampering intervention. A tool for accurate and timely identification of CKD from electronic medical records (EMR) could improve healthcare quality and identify patients for research. As members of eMERGE (electronic medical records and genomics) Network, we developed an automated phenotyping algorithm that can be deployed to identify rapidly diabetic and/or hypertensive CKD cases and controls in health systems with EMRs It uses diagnostic codes, laboratory results, medication and blood pressure records, and textual information culled from notes. Validation statistics demonstrated positive predictive values of 96% and negative predictive values of 93.3. Similar results were obtained on implementation by two independent eMERGE member institutions. The algorithm dramatically outperformed identification by ICD-9-CM codes with 63% positive and 54% negative predictive values, respectively. PMID:25954398

Inflammatory and fibrotic proteins proteomically identified as key protein constituents in urine and stone matrix of patients with kidney calculi.

PubMed

Boonla, Chanchai; Tosukhowong, Piyaratana; Spittau, Björn; Schlosser, Andreas; Pimratana, Chaowat; Krieglstein, Kerstin

2014-02-15

To uncover whether urinary proteins are incorporated into stones, the proteomic profiles of kidney stones and urine collected from the same patients have to be explored. We employed 1D-PAGE and nanoHPLC-ESI-MS/MS to analyze the proteomes of kidney stone matrix (n=16), nephrolithiatic urine (n=14) and healthy urine (n=3). We identified 62, 66 and 22 proteins in stone matrix, nephrolithiatic urine and healthy urine, respectively. Inflammation- and fibrosis-associated proteins were frequently detected in the stone matrix and nephrolithiatic urine. Eighteen proteins were exclusively found in the stone matrix and nephrolithiatic urine, considered as candidate biomarkers for kidney stone formation. S100A8 and fibronectin, representatives of inflammation and fibrosis, respectively, were up-regulated in nephrolithiasis renal tissues. S100A8 was strongly expressed in infiltrated leukocytes. Fibronectin was over-expressed in renal tubular cells. S100A8 and fibronectin were immunologically confirmed to exist in nephrolithiatic urine and stone matrix, but in healthy urine they were undetectable. Conclusion, both kidney stones and urine obtained from the same patients greatly contained inflammatory and fibrotic proteins. S100A8 and fibronectin were up-regulated in stone-baring kidneys and nephrolithiatic urine. Therefore, inflammation and fibrosis are suggested to be involved in the formation of kidney calculi. Copyright © 2013 Elsevier B.V. All rights reserved.

Volumetric Nephrogram Represents Renal Function and Complements Aortic Anatomic Severity Grade in Predicting EVAR Outcomes.

PubMed

Balceniuk, Mark D; Trakimas, Lauren; Aghaie, Claudia; Mix, Doran; Rasheed, Khurram; Seaman, Matthew; Ellis, Jennifer; Glocker, Roan; Doyle, Adam; Stoner, Michael C

2018-07-01

Chronic kidney disease (CKD) is a predictor of poor outcomes for patients undergoing endovascular aortic aneurysm repair (EVAR). Anatomic severity grade (ASG) represents a quantitative mechanism for assessing anatomical suitability for endovascular aortic repair. Anatomic severity grade has been correlated with repair outcomes and resource utilization. The purpose of this study was to identify a novel renal perfusion metric as a way to assist ASG with predicting EVAR outcomes. Retrospective review of a prospectively maintained database identified elective infrarenal aortic aneurysm repair cases. Anatomic grading was undertaken by independent reviewers. Using volumetric software, kidney volume, and a novel measure of kidney functional volume, the volumetric nephrogram (VN) was recorded. Systematic evaluation of the relationship of kidney volume and VN to CKD and ASG was undertaken using linear regression and receiver-operator statistical tools. A total of 386 cases with patient and anatomic data were identified and graded. Mean age was 72.9 ± 0.4 years. Renal volume <281 mL correlated with CKD (area under the curve [AUC] = .708; P ≤ .0001). Volumetric nephrogram <22.5 HU·L correlated with CKD (AUC = 0.764; P ≤ .0001). High (≥15) ASG scores correlated with both renal volume (AUC = .628; P ≤ .0001) and VN (AUC = .628; P ≤ .0001). Regression analysis demonstrated a strong, inverse relationship between ASG and VN ( R 2 = .95). These data demonstrate that VN is a strong predictor of CKD in a large database of patients undergoing elective aneurysm repair. We demonstrate an inverse relationship between renal function and ASG that has not been previously described in the literature. Additionally, we have shown that VN complements ASG as a model of overall cardiovascular health and atherosclerotic burden. Outcomes in patients with poor renal function may be related to anatomical issues in addition to well-described systemic ramifications.

Integration of genome-wide association studies with biological knowledge identifies six novel genes related to kidney function.

PubMed

Chasman, Daniel I; Fuchsberger, Christian; Pattaro, Cristian; Teumer, Alexander; Böger, Carsten A; Endlich, Karlhans; Olden, Matthias; Chen, Ming-Huei; Tin, Adrienne; Taliun, Daniel; Li, Man; Gao, Xiaoyi; Gorski, Mathias; Yang, Qiong; Hundertmark, Claudia; Foster, Meredith C; O'Seaghdha, Conall M; Glazer, Nicole; Isaacs, Aaron; Liu, Ching-Ti; Smith, Albert V; O'Connell, Jeffrey R; Struchalin, Maksim; Tanaka, Toshiko; Li, Guo; Johnson, Andrew D; Gierman, Hinco J; Feitosa, Mary F; Hwang, Shih-Jen; Atkinson, Elizabeth J; Lohman, Kurt; Cornelis, Marilyn C; Johansson, Asa; Tönjes, Anke; Dehghan, Abbas; Lambert, Jean-Charles; Holliday, Elizabeth G; Sorice, Rossella; Kutalik, Zoltan; Lehtimäki, Terho; Esko, Tõnu; Deshmukh, Harshal; Ulivi, Sheila; Chu, Audrey Y; Murgia, Federico; Trompet, Stella; Imboden, Medea; Coassin, Stefan; Pistis, Giorgio; Harris, Tamara B; Launer, Lenore J; Aspelund, Thor; Eiriksdottir, Gudny; Mitchell, Braxton D; Boerwinkle, Eric; Schmidt, Helena; Cavalieri, Margherita; Rao, Madhumathi; Hu, Frank; Demirkan, Ayse; Oostra, Ben A; de Andrade, Mariza; Turner, Stephen T; Ding, Jingzhong; Andrews, Jeanette S; Freedman, Barry I; Giulianini, Franco; Koenig, Wolfgang; Illig, Thomas; Meisinger, Christa; Gieger, Christian; Zgaga, Lina; Zemunik, Tatijana; Boban, Mladen; Minelli, Cosetta; Wheeler, Heather E; Igl, Wilmar; Zaboli, Ghazal; Wild, Sarah H; Wright, Alan F; Campbell, Harry; Ellinghaus, David; Nöthlings, Ute; Jacobs, Gunnar; Biffar, Reiner; Ernst, Florian; Homuth, Georg; Kroemer, Heyo K; Nauck, Matthias; Stracke, Sylvia; Völker, Uwe; Völzke, Henry; Kovacs, Peter; Stumvoll, Michael; Mägi, Reedik; Hofman, Albert; Uitterlinden, Andre G; Rivadeneira, Fernando; Aulchenko, Yurii S; Polasek, Ozren; Hastie, Nick; Vitart, Veronique; Helmer, Catherine; Wang, Jie Jin; Stengel, Bénédicte; Ruggiero, Daniela; Bergmann, Sven; Kähönen, Mika; Viikari, Jorma; Nikopensius, Tiit; Province, Michael; Ketkar, Shamika; Colhoun, Helen; Doney, Alex; Robino, Antonietta; Krämer, Bernhard K; Portas, Laura; Ford, Ian; Buckley, Brendan M; Adam, Martin; Thun, Gian-Andri; Paulweber, Bernhard; Haun, Margot; Sala, Cinzia; Mitchell, Paul; Ciullo, Marina; Kim, Stuart K; Vollenweider, Peter; Raitakari, Olli; Metspalu, Andres; Palmer, Colin; Gasparini, Paolo; Pirastu, Mario; Jukema, J Wouter; Probst-Hensch, Nicole M; Kronenberg, Florian; Toniolo, Daniela; Gudnason, Vilmundur; Shuldiner, Alan R; Coresh, Josef; Schmidt, Reinhold; Ferrucci, Luigi; Siscovick, David S; van Duijn, Cornelia M; Borecki, Ingrid B; Kardia, Sharon L R; Liu, Yongmei; Curhan, Gary C; Rudan, Igor; Gyllensten, Ulf; Wilson, James F; Franke, Andre; Pramstaller, Peter P; Rettig, Rainer; Prokopenko, Inga; Witteman, Jacqueline; Hayward, Caroline; Ridker, Paul M; Parsa, Afshin; Bochud, Murielle; Heid, Iris M; Kao, W H Linda; Fox, Caroline S; Köttgen, Anna

2012-12-15

In conducting genome-wide association studies (GWAS), analytical approaches leveraging biological information may further understanding of the pathophysiology of clinical traits. To discover novel associations with estimated glomerular filtration rate (eGFR), a measure of kidney function, we developed a strategy for integrating prior biological knowledge into the existing GWAS data for eGFR from the CKDGen Consortium. Our strategy focuses on single nucleotide polymorphism (SNPs) in genes that are connected by functional evidence, determined by literature mining and gene ontology (GO) hierarchies, to genes near previously validated eGFR associations. It then requires association thresholds consistent with multiple testing, and finally evaluates novel candidates by independent replication. Among the samples of European ancestry, we identified a genome-wide significant SNP in FBXL20 (P = 5.6 × 10(-9)) in meta-analysis of all available data, and additional SNPs at the INHBC, LRP2, PLEKHA1, SLC3A2 and SLC7A6 genes meeting multiple-testing corrected significance for replication and overall P-values of 4.5 × 10(-4)-2.2 × 10(-7). Neither the novel PLEKHA1 nor FBXL20 associations, both further supported by association with eGFR among African Americans and with transcript abundance, would have been implicated by eGFR candidate gene approaches. LRP2, encoding the megalin receptor, was identified through connection with the previously known eGFR gene DAB2 and extends understanding of the megalin system in kidney function. These findings highlight integration of existing genome-wide association data with independent biological knowledge to uncover novel candidate eGFR associations, including candidates lacking known connections to kidney-specific pathways. The strategy may also be applicable to other clinical phenotypes, although more testing will be needed to assess its potential for discovery in general.

Integration of genome-wide association studies with biological knowledge identifies six novel genes related to kidney function

PubMed Central

Chasman, Daniel I.; Fuchsberger, Christian; Pattaro, Cristian; Teumer, Alexander; Böger, Carsten A.; Endlich, Karlhans; Olden, Matthias; Chen, Ming-Huei; Tin, Adrienne; Taliun, Daniel; Li, Man; Gao, Xiaoyi; Gorski, Mathias; Yang, Qiong; Hundertmark, Claudia; Foster, Meredith C.; O'Seaghdha, Conall M.; Glazer, Nicole; Isaacs, Aaron; Liu, Ching-Ti; Smith, Albert V.; O'Connell, Jeffrey R.; Struchalin, Maksim; Tanaka, Toshiko; Li, Guo; Johnson, Andrew D.; Gierman, Hinco J.; Feitosa, Mary F.; Hwang, Shih-Jen; Atkinson, Elizabeth J.; Lohman, Kurt; Cornelis, Marilyn C.; Johansson, Åsa; Tönjes, Anke; Dehghan, Abbas; Lambert, Jean-Charles; Holliday, Elizabeth G.; Sorice, Rossella; Kutalik, Zoltan; Lehtimäki, Terho; Esko, Tõnu; Deshmukh, Harshal; Ulivi, Sheila; Chu, Audrey Y.; Murgia, Federico; Trompet, Stella; Imboden, Medea; Coassin, Stefan; Pistis, Giorgio; Harris, Tamara B.; Launer, Lenore J.; Aspelund, Thor; Eiriksdottir, Gudny; Mitchell, Braxton D.; Boerwinkle, Eric; Schmidt, Helena; Cavalieri, Margherita; Rao, Madhumathi; Hu, Frank; Demirkan, Ayse; Oostra, Ben A.; de Andrade, Mariza; Turner, Stephen T.; Ding, Jingzhong; Andrews, Jeanette S.; Freedman, Barry I.; Giulianini, Franco; Koenig, Wolfgang; Illig, Thomas; Meisinger, Christa; Gieger, Christian; Zgaga, Lina; Zemunik, Tatijana; Boban, Mladen; Minelli, Cosetta; Wheeler, Heather E.; Igl, Wilmar; Zaboli, Ghazal; Wild, Sarah H.; Wright, Alan F.; Campbell, Harry; Ellinghaus, David; Nöthlings, Ute; Jacobs, Gunnar; Biffar, Reiner; Ernst, Florian; Homuth, Georg; Kroemer, Heyo K.; Nauck, Matthias; Stracke, Sylvia; Völker, Uwe; Völzke, Henry; Kovacs, Peter; Stumvoll, Michael; Mägi, Reedik; Hofman, Albert; Uitterlinden, Andre G.; Rivadeneira, Fernando; Aulchenko, Yurii S.; Polasek, Ozren; Hastie, Nick; Vitart, Veronique; Helmer, Catherine; Wang, Jie Jin; Stengel, Bénédicte; Ruggiero, Daniela; Bergmann, Sven; Kähönen, Mika; Viikari, Jorma; Nikopensius, Tiit; Province, Michael; Ketkar, Shamika; Colhoun, Helen; Doney, Alex; Robino, Antonietta; Krämer, Bernhard K.; Portas, Laura; Ford, Ian; Buckley, Brendan M.; Adam, Martin; Thun, Gian-Andri; Paulweber, Bernhard; Haun, Margot; Sala, Cinzia; Mitchell, Paul; Ciullo, Marina; Kim, Stuart K.; Vollenweider, Peter; Raitakari, Olli; Metspalu, Andres; Palmer, Colin; Gasparini, Paolo; Pirastu, Mario; Jukema, J. Wouter; Probst-Hensch, Nicole M.; Kronenberg, Florian; Toniolo, Daniela; Gudnason, Vilmundur; Shuldiner, Alan R.; Coresh, Josef; Schmidt, Reinhold; Ferrucci, Luigi; Siscovick, David S.; van Duijn, Cornelia M.; Borecki, Ingrid B.; Kardia, Sharon L.R.; Liu, Yongmei; Curhan, Gary C.; Rudan, Igor; Gyllensten, Ulf; Wilson, James F.; Franke, Andre; Pramstaller, Peter P.; Rettig, Rainer; Prokopenko, Inga; Witteman, Jacqueline; Hayward, Caroline; Ridker, Paul M; Parsa, Afshin; Bochud, Murielle; Heid, Iris M.; Kao, W.H. Linda; Fox, Caroline S.; Köttgen, Anna

2012-01-01

In conducting genome-wide association studies (GWAS), analytical approaches leveraging biological information may further understanding of the pathophysiology of clinical traits. To discover novel associations with estimated glomerular filtration rate (eGFR), a measure of kidney function, we developed a strategy for integrating prior biological knowledge into the existing GWAS data for eGFR from the CKDGen Consortium. Our strategy focuses on single nucleotide polymorphism (SNPs) in genes that are connected by functional evidence, determined by literature mining and gene ontology (GO) hierarchies, to genes near previously validated eGFR associations. It then requires association thresholds consistent with multiple testing, and finally evaluates novel candidates by independent replication. Among the samples of European ancestry, we identified a genome-wide significant SNP in FBXL20 (P = 5.6 × 10−9) in meta-analysis of all available data, and additional SNPs at the INHBC, LRP2, PLEKHA1, SLC3A2 and SLC7A6 genes meeting multiple-testing corrected significance for replication and overall P-values of 4.5 × 10−4–2.2 × 10−7. Neither the novel PLEKHA1 nor FBXL20 associations, both further supported by association with eGFR among African Americans and with transcript abundance, would have been implicated by eGFR candidate gene approaches. LRP2, encoding the megalin receptor, was identified through connection with the previously known eGFR gene DAB2 and extends understanding of the megalin system in kidney function. These findings highlight integration of existing genome-wide association data with independent biological knowledge to uncover novel candidate eGFR associations, including candidates lacking known connections to kidney-specific pathways. The strategy may also be applicable to other clinical phenotypes, although more testing will be needed to assess its potential for discovery in general. PMID:22962313

Setting Research Priorities for Kidney Cancer.

PubMed

Jones, Jennifer M; Bhatt, Jaimin; Avery, Jonathan; Laupacis, Andreas; Cowan, Katherine; Basappa, Naveen S; Basiuk, Joan; Canil, Christina; Al-Asaaed, Sohaib; Heng, Daniel Y C; Wood, Lori; Stacey, Dawn; Kollmannsberger, Christian; Jewett, Michael A S

2017-12-01

Defining disease-specific research priorities in cancer can facilitate better allocation of limited resources. Involving patients and caregivers as well as expert clinicians in this process is of value. We undertook this approach for kidney cancer as an example. The Kidney Cancer Research Network of Canada sponsored a collaborative consensus-based priority-setting partnership that identified ten research priorities in the management of kidney cancer. These are discussed in the context of current initiatives and gaps in knowledge. Copyright © 2017 European Association of Urology. Published by Elsevier B.V. All rights reserved.

Effect of Long-Term Systolic Blood Pressure Trajectory on Kidney Damage in the Diabetic Population: A Prospective Study in a Community-Based Chinese Cohort.

PubMed

Li, Jian-Chao; Tian, Jun; Wu, Shou-Ling; Wang, Zhi-Jun; Zhang, Xiao-Fei; Jia, Dao; Ding, Rong-Jing; Xiao, Xiong-Fu; Fan, Yu-Bo; Hu, Da-Yi

2018-05-20

Previous studies have shown that hypertension is an important factor contributing to the occurrence and progression of diabetic kidney damage. However, the relationship between the patterns of blood pressure (BP) trajectory and kidney damage in the diabetic population remains unclear. This prospective study investigated the effect of long-term systolic BP (SBP) trajectory on kidney damage in the diabetic population based on an 8-year follow-up community-based cohort. This study included 4556 diabetic participants among 101,510 participants. BP, estimated glomerular filtration rate (eGFR), and urinary protein were measured every 2 years from 2006 to 2014. SBP trajectory was identified by the censored normal modeling. Five discrete SBP trajectories were identified according to SBP range and the changing pattern over time. Kidney damage was evaluated through eGFR and urinary protein value. A multivariate logistic regression model was used to analyze the influence of different SBP trajectory groups on kidney damage. We identified five discrete SBP trajectories: low-stable group (n = 864), moderate-stable group (n = 1980), moderate increasing group (n = 609), elevated decreasing group, (n = 679), and elevated stable group (n = 424). The detection rate of kidney damage in the low-stable group (SBP: 118-124 mmHg) was the lowest among the five groups. The detection rate of each kidney damage index was higher in the elevated stable group (SBP: 159-172 mmHg) compared with the low-stable group. For details, the gap was 4.14 (11.6% vs. 2.8%) in eGFR <60 ml·min -1 ·1.73 m -2 and 3.66 (17.2% vs. 4.7%), 3.38 (25.0% vs. 7.4%), and 1.8 (10.6% vs. 5.9%) times in positive urinary protein, eGFR <60 ml·min -1 ·1.73 m -2 and/or positive urinary protein, and eGFR decline ≥30%, respectively (P < 0.01). An elevated stable SBP trajectory is an independent risk factor for kidney damage in the diabetic population.

Measurement of bio-impedance with a smart needle to confirm percutaneous kidney access.

PubMed

Hernandez, D J; Sinkov, V A; Roberts, W W; Allaf, M E; Patriciu, A; Jarrett, T W; Kavoussi, L R; Stoianovici, D

2001-10-01

The traditional method of percutaneous renal access requires freehand needle placement guided by C-arm fluoroscopy, ultrasonography, or computerized tomography. This approach provides limited objective means for verifying successful access. We developed an impedance based percutaneous Smart Needle system and successfully used it to confirm collecting system access in ex vivo porcine kidneys. The Smart Needle consists of a modified 18 gauge percutaneous access needle with the inner stylet electrically insulated from the outer sheath. Impedance is measured between the exposed stylet tip and sheath using Model 4275 LCR meter (Hewlett-Packard, Sunnyvale, California). An ex vivo porcine kidney was distended by continuous gravity infusion of 100 cm. water saline from a catheter passed through the parenchyma into the collecting system. The Smart Needle was gradually inserted into the kidney to measure depth precisely using a robotic needle placement system, while impedance was measured continuously. The Smart Needle was inserted 4 times in each of 4 kidneys. When the needle penetrated the distended collecting system in 11 of 16 attempts, a characteristic sharp drop in resistivity was noted from 1.9 to 1.1 ohm m. Entry into the collecting system was confirmed by removing the stylet and observing fluid flow from the sheath. This characteristic impedance change was observed only at successful entry into the collecting system. A characteristic sharp drop in impedance signifies successful entry into the collecting system. The Smart Needle system may prove useful for percutaneous kidney access.

Effects of pituitary adenylate cyclase activating polypeptide in the urinary system, with special emphasis on its protective effects in the kidney.

PubMed

Reglodi, Dora; Kiss, Peter; Horvath, Gabriella; Lubics, Andrea; Laszlo, Eszter; Tamas, Andrea; Racz, Boglarka; Szakaly, Peter

2012-04-01

Pituitary adenylate cyclase activating polypeptide (PACAP) is a widespread neuropeptide with diverse effects in the nervous system and peripheral organs. One of the most well-studied effects of PACAP is its cytoprotective action, against different harmful stimuli in a wide variety of cells and tissues. PACAP occurs in the urinary system, from the kidney to the lower urinary tract. The present review focuses on the nephroprotective effects of PACAP and summarizes data obtained regarding the protective effects of PACAP in different models of kidney pathologies. In vitro data show that PACAP protects tubular cells against oxidative stress, myeloma light chain, cisplatin, cyclosporine-A and hypoxia. In vivo data provide evidence for its protective effects in ischemia/reperfusion, cisplatin, cyclosporine-A, myeloma kidney injury, diabetic nephropathy and gentamicin-induced kidney damage. Results accumulated on the renoprotective effects of PACAP suggest that PACAP is an emerging candidate for treatment of human kidney pathologies. Copyright © 2011 Elsevier Ltd. All rights reserved.

Risk Factors for Progression of Chronic Kidney Disease

PubMed Central

Staples, Amy; Wong, Craig

2010-01-01

Purpose of Review Provides an overview of the identified risk factors for chronic kidney disease (CKD) progression emphasizing the pediatric population. Recent findings Over the past ten years, there have been significant changes to our understanding and study of pre-terminal kidney failure. Recent refinements in the measurement of glomerular filtration rate (GFR) and GFR estimating equations are important tools for identification and association of risk factors for CKD progression in children. In pediatric CKD, lower level of kidney function at presentation, higher levels of proteinuria, and hypertension are known markers for a more rapid decline in GFR. Anemia and other reported risk factors from the pre-genomic era have need for further study and validation. Genome-wide association studies have identified genetic loci which have provided novel genetic risk factors for CKD progression. Summary With cohort studies of children with CKD becoming mature, they have started to yield important refinements to the assessment of CKD progression. While many of the traditional risk factors for renal progression will certainly be assessed, such cohorts will be important for evaluating novel risk factors identified by genome-wide studies. PMID:20090523

Black Americans' Perspectives of Barriers and Facilitators of Community Screening for Kidney Disease.

PubMed

Umeukeje, Ebele M; Wild, Marcus G; Maripuri, Saugar; Davidson, Teresa; Rutherford, Margaret; Abdel-Kader, Khaled; Lewis, Julia; Wilkins, Consuelo H; Cavanaugh, Kerri

2018-04-06

Incidence of ESKD is three times higher in black Americans than in whites, and CKD prevalence continues to rise among black Americans. Community-based kidney disease screening may increase early identification and awareness of black Americans at risk, but it is challenging to implement. This study aimed to identify participants' perspectives of community kidney disease screening. The Health Belief Model provides a theoretic framework for conceptualization of these perspectives and optimization of community kidney disease screening activities. Researchers in collaboration with the Tennessee Kidney Foundation conducted three focus groups of adults in black American churches in Nashville, Tennessee. Questions examined views on CKD information, access to care, and priorities of kidney disease health. Content analysis was used. Guided by the Health Belief Model, a priori themes were generated, and additional themes were derived from the data using an inductive approach. Thirty-two black Americans completed the study in 2014. Participants were mostly women (79%) with a mean age of 56 years old (range, 24-78). Two major categories of barriers to kidney disease screening were identified: ( 1 ) participant factors, including limited kidney disease knowledge, spiritual/religious beliefs, emotions, and culture of the individual; and ( 2 ) logistic factors, including lack of convenience and incentives and poor advertisement. Potential facilitators of CKD screening included provision of CKD education, convenience of screening activities, and use of culturally sensitive and enhanced communication strategies. Program recommendations included partnering with trusted community members, selecting convenient locations, tailored advertising, and provision of compensation. Findings of this study suggest that provider-delivered culturally sensitive education and stakeholder engagement are critical to increase trust, decrease fear, and maximize participation and early identification of kidney disease among black Americans considering community screening. Copyright © 2018 by the American Society of Nephrology.

Monoallelic Mutations to DNAJB11 Cause Atypical Autosomal-Dominant Polycystic Kidney Disease.

PubMed

Cornec-Le Gall, Emilie; Olson, Rory J; Besse, Whitney; Heyer, Christina M; Gainullin, Vladimir G; Smith, Jessica M; Audrézet, Marie-Pierre; Hopp, Katharina; Porath, Binu; Shi, Beili; Baheti, Saurabh; Senum, Sarah R; Arroyo, Jennifer; Madsen, Charles D; Férec, Claude; Joly, Dominique; Jouret, François; Fikri-Benbrahim, Oussamah; Charasse, Christophe; Coulibaly, Jean-Marie; Yu, Alan S; Khalili, Korosh; Pei, York; Somlo, Stefan; Le Meur, Yannick; Torres, Vicente E; Harris, Peter C

2018-05-03

Autosomal-dominant polycystic kidney disease (ADPKD) is characterized by the progressive development of kidney cysts, often resulting in end-stage renal disease (ESRD). This disorder is genetically heterogeneous with ∼7% of families genetically unresolved. We performed whole-exome sequencing (WES) in two multiplex ADPKD-like pedigrees, and we analyzed a further 591 genetically unresolved, phenotypically similar families by targeted next-generation sequencing of 65 candidate genes. WES identified a DNAJB11 missense variant (p.Pro54Arg) in two family members presenting with non-enlarged polycystic kidneys and a frameshifting change (c.166_167insTT) in a second family with small renal and liver cysts. DNAJB11 is a co-factor of BiP, a key chaperone in the endoplasmic reticulum controlling folding, trafficking, and degradation of secreted and membrane proteins. Five additional multigenerational families carrying DNAJB11 mutations were identified by the targeted analysis. The clinical phenotype was consistent in the 23 affected members, with non-enlarged cystic kidneys that often evolved to kidney atrophy; 7 subjects reached ESRD from 59 to 89 years. The lack of kidney enlargement, histologically evident interstitial fibrosis in non-cystic parenchyma, and recurring episodes of gout (one family) suggested partial phenotypic overlap with autosomal-dominant tubulointerstitial diseases (ADTKD). Characterization of DNAJB11-null cells and kidney samples from affected individuals revealed a pathogenesis associated with maturation and trafficking defects involving the ADPKD protein, PC1, and ADTKD proteins, such as UMOD. DNAJB11-associated disease is a phenotypic hybrid of ADPKD and ADTKD, characterized by normal-sized cystic kidneys and progressive interstitial fibrosis resulting in late-onset ESRD. Copyright © 2018 American Society of Human Genetics. Published by Elsevier Inc. All rights reserved.

Predictive features of chronic kidney disease in atypical haemolytic uremic syndrome

PubMed Central

Jamme, Matthieu; Raimbourg, Quentin; Chauveau, Dominique; Seguin, Amélie; Presne, Claire; Perez, Pierre; Gobert, Pierre; Wynckel, Alain; Provôt, François; Delmas, Yahsou; Mousson, Christiane; Servais, Aude; Vrigneaud, Laurence; Veyradier, Agnès

2017-01-01

Chronic kidney disease (CKD) is a frequent and serious complication of atypical haemolytic uremic syndrome (aHUS). We aimed to develop a simple accurate model to predict the risk of renal dysfunction in aHUS based on clinical and biological features available at hospital admission. Renal function at 1-year follow-up, based on an estimated glomerular filtration rate < 60mL/min/1.73m2 as assessed by the Modification of Diet in Renal Disease equation, was used as an indicator of significant CKD. Prospectively collected data from a cohort of 156 aHUS patients who did not receive eculizumab were used to identify predictors of CKD. Covariates associated with renal impairment were identified by multivariate analysis. The model performance was assessed and a scoring system for clinical practice was constructed from the regression coefficient. Multivariate analyses identified three predictors of CKD: a high serum creatinine level, a high mean arterial pressure and a mildly decreased platelet count. The prognostic model had a good discriminative ability (area under the curve = .84). The scoring system ranged from 0 to 5, with corresponding risks of CKD ranging from 18% to 100%. This model accurately predicts development of 1-year CKD in patients with aHUS using clinical and biological features available on admission. After further validation, this model may assist in clinical decision making. PMID:28542627

Model systems for the study of kidney development: use of the pronephros in the analysis of organ induction and patterning.

PubMed

Vize, P D; Seufert, D W; Carroll, T J; Wallingford, J B

1997-08-15

Most vertebrate organs, once formed, continue to perform the function for which they were generated until the death of the organism. The kidney is a notable exception to this rule. Vertebrates, even those that do not undergo metamorphosis, utilize a progression of more complex kidneys as they grow and develop. This is presumably due to the changing conditions to which the organism must respond to retain what Homer Smith referred to as our physiological freedom. To quote, "Recognizing that we have the kind of blood we have because we have the kind of kidneys we have, we must acknowledge that our kidneys constitute the major foundation of our physiological freedom. Only because they work the way they do has it become possible for us to have bones, muscles, glands, and brains. Superficially, it might be said that the function of the kidneys is to make urine; but in a more considered view one can say that the kidneys make the stuff of philosophy itself" ("From Fish to Philosopher," Little, Brown and Co., Boston, 1953). Different kidneys are used to make the stuff of philosophy at different stages of development depending on the age and needs of the organism, rather than the usual approach of simply making embryonic organs larger as the animal grows. Although evolution has provided the higher vertebrates with complex adult kidneys, they continue to utilize simple kidneys in embryogenesis. In lower vertebrates with simple adult kidneys, even more simple versions are used during early developmental stages. In this review the anatomy, development, and gene expression patterns of the embryonic kidney, the pronephros, will be described and compared to the more complex kidney forms. Despite some differences in anatomy, similar developmental pathways seem to be responsible for the induction and the response to induction in both evanescent and permanent kidney forms. Gene expression patterns can, therefore, be added to the morphological and functional data indicating that all forms of the kidney are closely related structures. Given the similarities between the development of simple and complex kidneys, the embryonic kidneys may be an ideal model system in which to investigate the genesis of multicomponent organ systems.

Trimethoprim use for urinary tract infection and risk of adverse outcomes in older patients: cohort study

PubMed Central

Crellin, Elizabeth; Leyrat, Clémence; Nitsch, Dorothea; Douglas, Ian J; Root, Adrian; Williamson, Elizabeth; Smeeth, Liam; Tomlinson, Laurie A

2018-01-01

Abstract Objective To determine if trimethoprim use for urinary tract infection (UTI) is associated with an increased risk of acute kidney injury, hyperkalaemia, or sudden death in the general population. Design Cohort study. Setting UK electronic primary care records from practices contributing to the Clinical Practice Research Datalink linked to the Hospital Episode Statistics database. Participants Adults aged 65 and over with a prescription for trimethoprim, amoxicillin, cefalexin, ciprofloxacin, or nitrofurantoin prescribed up to three days after a primary care diagnosis of UTI between April 1997 and September 2015. Main outcome measures The outcomes were acute kidney injury, hyperkalaemia, and death within 14 days of a UTI treated with antibiotics. Results Among a cohort of 1 191 905 patients aged 65 and over, 178 238 individuals were identified with at least one UTI treated with antibiotics, comprising a total of 422 514 episodes of UTIs treated with antibiotics. The odds of acute kidney injury in the 14 days following antibiotic initiation were higher following trimethoprim (adjusted odds ratio 1.72, 95% confidence interval 1.31 to 2.24) and ciprofloxacin (1.48, 1.03 to 2.13) compared with amoxicillin. The odds of hyperkalaemia in the 14 days following antibiotic initiation were only higher following trimethoprim (2.27, 1.49 to 3.45) compared with amoxicillin. However, the odds of death within the 14 days following antibiotic initiation were not higher with trimethoprim than with amoxicillin: in the whole population the adjusted odds ratio was 0.90 (95% confidence interval 0.76 to 1.07) while among users of renin-angiotensin system blockers the odds of death within 14 days of antibiotic initiation was 1.12 (0.80 to 1.57). The results suggest that, for 1000 UTIs treated with antibiotics among people 65 and over, treatment with trimethoprim instead of amoxicillin would result in one to two additional cases of hyperkalaemia and two admissions with acute kidney injury, regardless of renin-angiotensin system blockade. However, for people taking renin-angiotensin system blockers and spironolactone treatment with trimethoprim instead of amoxicillin there were 18 additional cases of hyperkalaemia and 11 admissions with acute kidney injury. Conclusion Trimethoprim is associated with a greater risk of acute kidney injury and hyperkalaemia compared with other antibiotics used to treat UTIs, but not a greater risk of death. The relative risk increase is similar across population groups, but the higher baseline risk among those taking renin-angiotensin system blockers and potassium-sparing diuretics translates into higher absolute risks of acute kidney injury and hyperkalaemia in these groups. PMID:29438980

1000 Genomes-based meta-analysis identifies 10 novel loci for kidney function

PubMed Central

Gorski, Mathias; van der Most, Peter J.; Teumer, Alexander; Chu, Audrey Y.; Li, Man; Mijatovic, Vladan; Nolte, Ilja M.; Cocca, Massimiliano; Taliun, Daniel; Gomez, Felicia; Li, Yong; Tayo, Bamidele; Tin, Adrienne; Feitosa, Mary F.; Aspelund, Thor; Attia, John; Biffar, Reiner; Bochud, Murielle; Boerwinkle, Eric; Borecki, Ingrid; Bottinger, Erwin P.; Chen, Ming-Huei; Chouraki, Vincent; Ciullo, Marina; Coresh, Josef; Cornelis, Marilyn C.; Curhan, Gary C.; d’Adamo, Adamo Pio; Dehghan, Abbas; Dengler, Laura; Ding, Jingzhong; Eiriksdottir, Gudny; Endlich, Karlhans; Enroth, Stefan; Esko, Tõnu; Franco, Oscar H.; Gasparini, Paolo; Gieger, Christian; Girotto, Giorgia; Gottesman, Omri; Gudnason, Vilmundur; Gyllensten, Ulf; Hancock, Stephen J.; Harris, Tamara B.; Helmer, Catherine; Höllerer, Simon; Hofer, Edith; Hofman, Albert; Holliday, Elizabeth G.; Homuth, Georg; Hu, Frank B.; Huth, Cornelia; Hutri-Kähönen, Nina; Hwang, Shih-Jen; Imboden, Medea; Johansson, Åsa; Kähönen, Mika; König, Wolfgang; Kramer, Holly; Krämer, Bernhard K.; Kumar, Ashish; Kutalik, Zoltan; Lambert, Jean-Charles; Launer, Lenore J.; Lehtimäki, Terho; de Borst, Martin; Navis, Gerjan; Swertz, Morris; Liu, Yongmei; Lohman, Kurt; Loos, Ruth J. F.; Lu, Yingchang; Lyytikäinen, Leo-Pekka; McEvoy, Mark A.; Meisinger, Christa; Meitinger, Thomas; Metspalu, Andres; Metzger, Marie; Mihailov, Evelin; Mitchell, Paul; Nauck, Matthias; Oldehinkel, Albertine J.; Olden, Matthias; WJH Penninx, Brenda; Pistis, Giorgio; Pramstaller, Peter P.; Probst-Hensch, Nicole; Raitakari, Olli T.; Rettig, Rainer; Ridker, Paul M.; Rivadeneira, Fernando; Robino, Antonietta; Rosas, Sylvia E.; Ruderfer, Douglas; Ruggiero, Daniela; Saba, Yasaman; Sala, Cinzia; Schmidt, Helena; Schmidt, Reinhold; Scott, Rodney J.; Sedaghat, Sanaz; Smith, Albert V.; Sorice, Rossella; Stengel, Benedicte; Stracke, Sylvia; Strauch, Konstantin; Toniolo, Daniela; Uitterlinden, Andre G.; Ulivi, Sheila; Viikari, Jorma S.; Völker, Uwe; Vollenweider, Peter; Völzke, Henry; Vuckovic, Dragana; Waldenberger, Melanie; Jin Wang, Jie; Yang, Qiong; Chasman, Daniel I.; Tromp, Gerard; Snieder, Harold; Heid, Iris M.; Fox, Caroline S.; Köttgen, Anna; Pattaro, Cristian; Böger, Carsten A.; Fuchsberger, Christian

2017-01-01

HapMap imputed genome-wide association studies (GWAS) have revealed >50 loci at which common variants with minor allele frequency >5% are associated with kidney function. GWAS using more complete reference sets for imputation, such as those from The 1000 Genomes project, promise to identify novel loci that have been missed by previous efforts. To investigate the value of such a more complete variant catalog, we conducted a GWAS meta-analysis of kidney function based on the estimated glomerular filtration rate (eGFR) in 110,517 European ancestry participants using 1000 Genomes imputed data. We identified 10 novel loci with p-value < 5 × 10−8 previously missed by HapMap-based GWAS. Six of these loci (HOXD8, ARL15, PIK3R1, EYA4, ASTN2, and EPB41L3) are tagged by common SNPs unique to the 1000 Genomes reference panel. Using pathway analysis, we identified 39 significant (FDR < 0.05) genes and 127 significantly (FDR < 0.05) enriched gene sets, which were missed by our previous analyses. Among those, the 10 identified novel genes are part of pathways of kidney development, carbohydrate metabolism, cardiac septum development and glucose metabolism. These results highlight the utility of re-imputing from denser reference panels, until whole-genome sequencing becomes feasible in large samples. PMID:28452372

1000 Genomes-based meta-analysis identifies 10 novel loci for kidney function.

PubMed

Gorski, Mathias; van der Most, Peter J; Teumer, Alexander; Chu, Audrey Y; Li, Man; Mijatovic, Vladan; Nolte, Ilja M; Cocca, Massimiliano; Taliun, Daniel; Gomez, Felicia; Li, Yong; Tayo, Bamidele; Tin, Adrienne; Feitosa, Mary F; Aspelund, Thor; Attia, John; Biffar, Reiner; Bochud, Murielle; Boerwinkle, Eric; Borecki, Ingrid; Bottinger, Erwin P; Chen, Ming-Huei; Chouraki, Vincent; Ciullo, Marina; Coresh, Josef; Cornelis, Marilyn C; Curhan, Gary C; d'Adamo, Adamo Pio; Dehghan, Abbas; Dengler, Laura; Ding, Jingzhong; Eiriksdottir, Gudny; Endlich, Karlhans; Enroth, Stefan; Esko, Tõnu; Franco, Oscar H; Gasparini, Paolo; Gieger, Christian; Girotto, Giorgia; Gottesman, Omri; Gudnason, Vilmundur; Gyllensten, Ulf; Hancock, Stephen J; Harris, Tamara B; Helmer, Catherine; Höllerer, Simon; Hofer, Edith; Hofman, Albert; Holliday, Elizabeth G; Homuth, Georg; Hu, Frank B; Huth, Cornelia; Hutri-Kähönen, Nina; Hwang, Shih-Jen; Imboden, Medea; Johansson, Åsa; Kähönen, Mika; König, Wolfgang; Kramer, Holly; Krämer, Bernhard K; Kumar, Ashish; Kutalik, Zoltan; Lambert, Jean-Charles; Launer, Lenore J; Lehtimäki, Terho; de Borst, Martin; Navis, Gerjan; Swertz, Morris; Liu, Yongmei; Lohman, Kurt; Loos, Ruth J F; Lu, Yingchang; Lyytikäinen, Leo-Pekka; McEvoy, Mark A; Meisinger, Christa; Meitinger, Thomas; Metspalu, Andres; Metzger, Marie; Mihailov, Evelin; Mitchell, Paul; Nauck, Matthias; Oldehinkel, Albertine J; Olden, Matthias; Wjh Penninx, Brenda; Pistis, Giorgio; Pramstaller, Peter P; Probst-Hensch, Nicole; Raitakari, Olli T; Rettig, Rainer; Ridker, Paul M; Rivadeneira, Fernando; Robino, Antonietta; Rosas, Sylvia E; Ruderfer, Douglas; Ruggiero, Daniela; Saba, Yasaman; Sala, Cinzia; Schmidt, Helena; Schmidt, Reinhold; Scott, Rodney J; Sedaghat, Sanaz; Smith, Albert V; Sorice, Rossella; Stengel, Benedicte; Stracke, Sylvia; Strauch, Konstantin; Toniolo, Daniela; Uitterlinden, Andre G; Ulivi, Sheila; Viikari, Jorma S; Völker, Uwe; Vollenweider, Peter; Völzke, Henry; Vuckovic, Dragana; Waldenberger, Melanie; Jin Wang, Jie; Yang, Qiong; Chasman, Daniel I; Tromp, Gerard; Snieder, Harold; Heid, Iris M; Fox, Caroline S; Köttgen, Anna; Pattaro, Cristian; Böger, Carsten A; Fuchsberger, Christian

2017-04-28

HapMap imputed genome-wide association studies (GWAS) have revealed >50 loci at which common variants with minor allele frequency >5% are associated with kidney function. GWAS using more complete reference sets for imputation, such as those from The 1000 Genomes project, promise to identify novel loci that have been missed by previous efforts. To investigate the value of such a more complete variant catalog, we conducted a GWAS meta-analysis of kidney function based on the estimated glomerular filtration rate (eGFR) in 110,517 European ancestry participants using 1000 Genomes imputed data. We identified 10 novel loci with p-value < 5 × 10 -8 previously missed by HapMap-based GWAS. Six of these loci (HOXD8, ARL15, PIK3R1, EYA4, ASTN2, and EPB41L3) are tagged by common SNPs unique to the 1000 Genomes reference panel. Using pathway analysis, we identified 39 significant (FDR < 0.05) genes and 127 significantly (FDR < 0.05) enriched gene sets, which were missed by our previous analyses. Among those, the 10 identified novel genes are part of pathways of kidney development, carbohydrate metabolism, cardiac septum development and glucose metabolism. These results highlight the utility of re-imputing from denser reference panels, until whole-genome sequencing becomes feasible in large samples.

Relation between Kidney Length and Cardiovascular and Renal Risk in High-Risk Patients

PubMed Central

van der Sande, Nicolette G.C.; Visseren, Frank L.J.; van der Graaf, Yolanda; Nathoe, Hendrik M.; de Borst, Gert Jan; Leiner, Tim

2017-01-01

Background and objectives Kidney length is often measured during routine abdominal ultrasonography and may be of use to identify patients at high vascular and renal risk. We aimed to explore patient characteristics related to kidney length, from which reference values were derived, and evaluate the relationship between kidney length and the risk of cardiovascular events and ESRD in high-risk patients. Design, setting, participants, & measurements The study population consisted of 10,251 patients with clinical manifest arterial disease or vascular risk factors included in the Second Manifestations of ARTerial disease (SMART) Study cohort between 1996 and 2014. Linear regression was used to explore patient characteristics of kidney length. The relationship between kidney length and cardiovascular events (myocardial infarction, stroke, and cardiovascular mortality), all-cause mortality, and ESRD was analyzed using Cox regression. Kidney length was analyzed in tertiles, using the second tertile as the reference category. Results Kidney length was strongly correlated with body surface area (2.04 mm; 95% confidence interval [95% CI], 1.95 to 2.13 per 0.1 m2 increase) and eGFR (1.62 mm; 95% CI, 1.52 to 1.73 per 10 ml/min per 1.73 m2 increase). During the median follow-up of 6.3 years, 1317 patients experienced a cardiovascular event, including 711 myocardial infarctions, 369 strokes, and 735 vascular cause deaths. A total of 1462 patients died of any cause and 52 patients developed ESRD. Irrespective of eGFR, patients in the third tertile of kidney length (11.7–16.1 cm) were at higher risk of cardiovascular mortality (hazard ratio, 1.33; 95% CI, 1.05 to 1.67) and cardiovascular events (hazard ratio, 1.28; 95% CI, 1.09 to 1.50). Patients in the first tertile of kidney length (7.8–10.8 cm) were not at higher risk of cardiovascular adverse events. Conclusions Large kidney length is related to higher risk of cardiovascular events and mortality in high-risk patients, irrespective of eGFR. Kidney length may serve as a clinical marker to further identify patients at high cardiovascular risk. PMID:28487344

Relation between Kidney Length and Cardiovascular and Renal Risk in High-Risk Patients.

PubMed

van der Sande, Nicolette G C; Visseren, Frank L J; van der Graaf, Yolanda; Nathoe, Hendrik M; de Borst, Gert Jan; Leiner, Tim; Blankestijn, Peter J

2017-06-07

Kidney length is often measured during routine abdominal ultrasonography and may be of use to identify patients at high vascular and renal risk. We aimed to explore patient characteristics related to kidney length, from which reference values were derived, and evaluate the relationship between kidney length and the risk of cardiovascular events and ESRD in high-risk patients. The study population consisted of 10,251 patients with clinical manifest arterial disease or vascular risk factors included in the Second Manifestations of ARTerial disease (SMART) Study cohort between 1996 and 2014. Linear regression was used to explore patient characteristics of kidney length. The relationship between kidney length and cardiovascular events (myocardial infarction, stroke, and cardiovascular mortality), all-cause mortality, and ESRD was analyzed using Cox regression. Kidney length was analyzed in tertiles, using the second tertile as the reference category. Kidney length was strongly correlated with body surface area (2.04 mm; 95% confidence interval [95% CI], 1.95 to 2.13 per 0.1 m 2 increase) and eGFR (1.62 mm; 95% CI, 1.52 to 1.73 per 10 ml/min per 1.73 m 2 increase). During the median follow-up of 6.3 years, 1317 patients experienced a cardiovascular event, including 711 myocardial infarctions, 369 strokes, and 735 vascular cause deaths. A total of 1462 patients died of any cause and 52 patients developed ESRD. Irrespective of eGFR, patients in the third tertile of kidney length (11.7-16.1 cm) were at higher risk of cardiovascular mortality (hazard ratio, 1.33; 95% CI, 1.05 to 1.67) and cardiovascular events (hazard ratio, 1.28; 95% CI, 1.09 to 1.50). Patients in the first tertile of kidney length (7.8-10.8 cm) were not at higher risk of cardiovascular adverse events. Large kidney length is related to higher risk of cardiovascular events and mortality in high-risk patients, irrespective of eGFR. Kidney length may serve as a clinical marker to further identify patients at high cardiovascular risk. Copyright © 2017 by the American Society of Nephrology.

The need for kidney transplantation in low- and middle-income countries in 2012: an epidemiological perspective.

PubMed

Muralidharan, Aditya; White, Sarah

2015-03-01

Epidemiological and demographic transitions are shifting the burden of modifiable risk factors for chronic and end-stage kidney disease to low- and middle-income countries (LMIC). This shifting burden of disease--combined with economic transitions and health system reforms--has led to the rapid growth of dialysis populations in LMIC including Malaysia, Tunisia, Turkey, Chile, Mexico, and Uruguay. Yet, compared to 1.5 million on dialysis in LMIC, only approximately 33,000 kidney transplants were performed in 2012. Reasons include health system factors (personnel, infrastructure, system coordination, and financing) and cultural factors (public and professional attitudes and the legal environment). The size of the dialysis populations, however, is generally a poor indicator of the potential need for kidney transplantation in LMIC. Population needs for kidney transplantation should instead be assessed based on the epidemiology of the actual underlying burden of disease (both treated and untreated), and the costs and benefits of treatment as well as prevention strategies relative to existing service provision. Here, we review current data on the global burden of end-stage kidney disease and the distribution of major risk factors, and compare this to access to kidney transplantation in 2012.

The experiences of commercial kidney donors: thematic synthesis of qualitative research.

PubMed

Tong, Allison; Chapman, Jeremy R; Wong, Germaine; Cross, Nicholas B; Batabyal, Pikli; Craig, Jonathan C

2012-11-01

Commercial transplantation has expanded because of the shortage of kidneys for transplantation. This study aims to synthesize qualitative studies on the experiences and perspectives of living commercial kidney donors. We conducted a comprehensive literature search in electronic databases to April 2011 and consulted experts to identify unpublished studies. Thematic synthesis was used to analyze the findings. Seven studies involving over 676 commercial kidney donors were included. Three major themes were identified: desperation (the participants' decision to sell their kidney was forced by poverty, debt, or to fulfill a family obligation); despair (destroyed body integrity, shame and secrecy, dehumanized and dispirited, loss of livelihood, heightened sense of vulnerability, disappointment, and regret); and debasement (deception by brokers and recipients, victimized by the hospital, stigmatized by community, and rejected by family). Commercial kidney transplantation is reported to result in ramifications for the donors' mental, physical, and social well-being. Not only do they remain in poverty, they lose dignity, sense of purpose, respect, relationships, and livelihood. Review of this published literature supports the need for effective implementation of the WHO guiding principles and legislated regulation to deter potential recipients and healthcare providers from pursuing commercial transplantation. © 2012 The Authors. Transplant International © 2012 European Society for Organ Transplantation.

Common variants in Mendelian kidney disease genes and their association with renal function.

PubMed

Parsa, Afshin; Fuchsberger, Christian; Köttgen, Anna; O'Seaghdha, Conall M; Pattaro, Cristian; de Andrade, Mariza; Chasman, Daniel I; Teumer, Alexander; Endlich, Karlhans; Olden, Matthias; Chen, Ming-Huei; Tin, Adrienne; Kim, Young J; Taliun, Daniel; Li, Man; Feitosa, Mary; Gorski, Mathias; Yang, Qiong; Hundertmark, Claudia; Foster, Meredith C; Glazer, Nicole; Isaacs, Aaron; Rao, Madhumathi; Smith, Albert V; O'Connell, Jeffrey R; Struchalin, Maksim; Tanaka, Toshiko; Li, Guo; Hwang, Shih-Jen; Atkinson, Elizabeth J; Lohman, Kurt; Cornelis, Marilyn C; Johansson, Asa; Tönjes, Anke; Dehghan, Abbas; Couraki, Vincent; Holliday, Elizabeth G; Sorice, Rossella; Kutalik, Zoltan; Lehtimäki, Terho; Esko, Tõnu; Deshmukh, Harshal; Ulivi, Sheila; Chu, Audrey Y; Murgia, Federico; Trompet, Stella; Imboden, Medea; Kollerits, Barbara; Pistis, Giorgio; Harris, Tamara B; Launer, Lenore J; Aspelund, Thor; Eiriksdottir, Gudny; Mitchell, Braxton D; Boerwinkle, Eric; Schmidt, Helena; Hofer, Edith; Hu, Frank; Demirkan, Ayse; Oostra, Ben A; Turner, Stephen T; Ding, Jingzhong; Andrews, Jeanette S; Freedman, Barry I; Giulianini, Franco; Koenig, Wolfgang; Illig, Thomas; Döring, Angela; Wichmann, H-Erich; Zgaga, Lina; Zemunik, Tatijana; Boban, Mladen; Minelli, Cosetta; Wheeler, Heather E; Igl, Wilmar; Zaboli, Ghazal; Wild, Sarah H; Wright, Alan F; Campbell, Harry; Ellinghaus, David; Nöthlings, Ute; Jacobs, Gunnar; Biffar, Reiner; Ernst, Florian; Homuth, Georg; Kroemer, Heyo K; Nauck, Matthias; Stracke, Sylvia; Völker, Uwe; Völzke, Henry; Kovacs, Peter; Stumvoll, Michael; Mägi, Reedik; Hofman, Albert; Uitterlinden, Andre G; Rivadeneira, Fernando; Aulchenko, Yurii S; Polasek, Ozren; Hastie, Nick; Vitart, Veronique; Helmer, Catherine; Wang, Jie Jin; Stengel, Bénédicte; Ruggiero, Daniela; Bergmann, Sven; Kähönen, Mika; Viikari, Jorma; Nikopensius, Tiit; Province, Michael; Colhoun, Helen; Doney, Alex; Robino, Antonietta; Krämer, Bernhard K; Portas, Laura; Ford, Ian; Buckley, Brendan M; Adam, Martin; Thun, Gian-Andri; Paulweber, Bernhard; Haun, Margot; Sala, Cinzia; Mitchell, Paul; Ciullo, Marina; Vollenweider, Peter; Raitakari, Olli; Metspalu, Andres; Palmer, Colin; Gasparini, Paolo; Pirastu, Mario; Jukema, J Wouter; Probst-Hensch, Nicole M; Kronenberg, Florian; Toniolo, Daniela; Gudnason, Vilmundur; Shuldiner, Alan R; Coresh, Josef; Schmidt, Reinhold; Ferrucci, Luigi; van Duijn, Cornelia M; Borecki, Ingrid; Kardia, Sharon L R; Liu, Yongmei; Curhan, Gary C; Rudan, Igor; Gyllensten, Ulf; Wilson, James F; Franke, Andre; Pramstaller, Peter P; Rettig, Rainer; Prokopenko, Inga; Witteman, Jacqueline; Hayward, Caroline; Ridker, Paul M; Bochud, Murielle; Heid, Iris M; Siscovick, David S; Fox, Caroline S; Kao, W Linda; Böger, Carsten A

2013-12-01

Many common genetic variants identified by genome-wide association studies for complex traits map to genes previously linked to rare inherited Mendelian disorders. A systematic analysis of common single-nucleotide polymorphisms (SNPs) in genes responsible for Mendelian diseases with kidney phenotypes has not been performed. We thus developed a comprehensive database of genes for Mendelian kidney conditions and evaluated the association between common genetic variants within these genes and kidney function in the general population. Using the Online Mendelian Inheritance in Man database, we identified 731 unique disease entries related to specific renal search terms and confirmed a kidney phenotype in 218 of these entries, corresponding to mutations in 258 genes. We interrogated common SNPs (minor allele frequency >5%) within these genes for association with the estimated GFR in 74,354 European-ancestry participants from the CKDGen Consortium. However, the top four candidate SNPs (rs6433115 at LRP2, rs1050700 at TSC1, rs249942 at PALB2, and rs9827843 at ROBO2) did not achieve significance in a stage 2 meta-analysis performed in 56,246 additional independent individuals, indicating that these common SNPs are not associated with estimated GFR. The effect of less common or rare variants in these genes on kidney function in the general population and disease-specific cohorts requires further research.

Calcium Oxalate Accumulation in Malpighian Tubules of Silkworm (Bombyx mori)

NASA Astrophysics Data System (ADS)

Wyman, Aaron J.; Webb, Mary Alice

2007-04-01

Silkworm provides an ideal model system for study of calcium oxalate crystallization in kidney-like organs, called Malpighian tubules. During their growth and development, silkworm larvae accumulate massive amounts of calcium oxalate crystals in their Malpighian tubules with no apparent harm to the organism. This manuscript reports studies of crystal structure in the tubules along with analyses identifying molecular constituents of tubule exudate.

21 CFR 866.5320 - Properdin factor B immuno-logical test system.

Code of Federal Regulations, 2011 CFR

2011-04-01

... factor B aids in the diagnosis of several kidney diseases, e.g., chronic glomerulonephritis (inflammation of the glomeruli of the kidney), lupus nephritis (kidney disease associated with a multisystem...

American Kidney Fund

MedlinePlus

... Carolyn Wilson Scholarship Program Grants Managements System (GMS) Login Education & Research Patient webinars Become a kidney health ... Blog Newsroom Contact Us HelpLine En Español GMS Login Give Monthly Give In Honor Donate Kidney Disease ...

Tests for Kidney Health

MedlinePlus

... Carolyn Wilson Scholarship Program Grants Managements System (GMS) Login Education & Research Webinars Become a Kidney Health Coach ... Blog Newsroom Contact Us HelpLine En Español GMS Login Give Monthly Give In Honor Donate Kidney Disease ...

Mining the human urine proteome for monitoring renal transplant injury

DOE Office of Scientific and Technical Information (OSTI.GOV)

Sigdel, Tara K.; Gao, Yuqian; He, Jintang

The human urinary proteome reflects systemic and inherent renal injury perturbations and can be analyzed to harness specific biomarkers for different kidney transplant injury states. 396 unique urine samples were collected contemporaneously with an allograft biopsy from 396 unique kidney transplant recipients. Centralized, blinded histology on the graft was used to classify matched urine samples into categories of acute rejection (AR), chronic allograft nephropathy (CAN), BK virus nephritis (BKVN), and stable graft (STA). Liquid chromatography–mass spectrometry (LC-MS) based proteomics using iTRAQ based discovery (n=108) and global label-free LC-MS analyses of individual samples (n=137) for quantitative proteome assessment were used inmore » the discovery step. Selected reaction monitoring (SRM) was applied to identify and validate minimal urine protein/peptide biomarkers to accurately segregate organ injury causation and pathology on unique urine samples (n=151). A total of 958 proteins were initially quantified by iTRAQ, 87% of which were also identified among 1574 urine proteins detected in LC-MS validation. 103 urine proteins were significantly (p<0.05) perturbed in injury and enriched for humoral immunity, complement activation, and lymphocyte trafficking. A set of 131 peptides corresponding to 78 proteins were assessed by SRM for their significance in an independent sample cohort. A minimal set of 35 peptides mapping to 33 proteins, were modeled to segregate different injury groups (AUC =93% for AR, 99% for CAN, 83% for BKVN). Urinary proteome discovery and targeted validation identified urine protein fingerprints for non-invasive differentiation of kidney transplant injuries, thus opening the door for personalized immune risk assessment and therapy.« less

Influence of low-level laser radiation on kidney functions

NASA Astrophysics Data System (ADS)

Koultchavenia, Ekaterina V.

1998-12-01

Most of all renal diseases are accompanied by lowering of kidney functions. That makes the quality of the treatment worse. On an example 69 patients receiving Low-Level Laser Therapy (LLLT), the influence of the laser radiation on a contracting system of blood, on current of an active and inactive tubercular inflammation and on partial functions of kidneys were investigated. Is established, that LLLT does not render influence to a contracting system; promotes stopping of unspecific and moderate peaking of a specific inflammation of kidneys. Is proved, that after a rate of laserotherapy the improving of a blood micricirculation in kidney occurs in 57.9% of patients; a secretion - in 63.1% of the patients; a stimulation of urodynamic is fixed in 79% of cases. Magnification of diuresis, improving filtration and concentration functions of kidneys also is marked.

Differences in access to kidney transplantation between Hispanic and non-Hispanic whites by geographic location in the United States.

PubMed

Arce, Cristina M; Goldstein, Benjamin A; Mitani, Aya A; Lenihan, Colin R; Winkelmayer, Wolfgang C

2013-12-01

Hispanic patients undergoing chronic dialysis are less likely to receive a kidney transplant compared with non-Hispanic whites. This study sought to elucidate disparities in the path to receipt of a deceased donor transplant between Hispanic and non-Hispanic whites. Using the US Renal Data System, 417,801 Caucasians who initiated dialysis between January 1, 1995 and December 31, 2007 with follow-up through 2008 were identified. This study investigated time from first dialysis to first kidney transplantation, time from first dialysis to waitlisting, and time from waitlisting to kidney transplantation. Multivariable Cox regression estimated cause-specific hazard ratios (HRCS) and subdistribution (competing risk) hazard ratios (HRSD) for Hispanics versus non-Hispanic whites. Hispanics experienced lower adjusted rates of deceased donor kidney transplantation than non-Hispanic whites (HRCS, 0.77; 95% confidence interval [95% CI], 0.75 to 0.80) measured from dialysis initiation. No meaningful differences were found in time from dialysis initiation to placement on the transplant waitlist. Once waitlisted, Hispanics had lower adjusted rates of deceased donor kidney transplantation (HRCS, 0.66; 95% CI, 0.64 to 0.68), and the association attenuated once accounting for competing risks (HRSD, 0.79; 95% CI, 0.77 to 0.81). Additionally controlling for blood type and organ procurement organization further reduced the disparity (HRSD, 0.99; 95% CI, 0.96 to 1.02). After accounting for geographic location and controlling for competing risks (e.g., Hispanic survival advantage), the disparity in access to deceased donor transplantation was markedly attenuated among Hispanics compared with non-Hispanic whites. To overcome the geographic disparities that Hispanics encounter in the path to transplantation, organ allocation policy revisions are needed to improve donor organ equity.

Dialysis-treated end-stage kidney disease in Libya: epidemiology and risk factors.

PubMed

Goleg, Fathea Abobker; Kong, Norella Chiew-Tong; Sahathevan, Ramesh

2014-08-01

End-stage kidney disease (ESKD) is now a worldwide pandemic. In concert with this, ESKD in Libya has also increased exponentially in recent decades. This review aims to define the magnitude of and risks for this ESKD epidemic among Libyans as there is a dearth of published data on this subject. A systematic review was conducted by searching PubMed, EMBASE and Google scholar databases to identify all relevant papers published in English from 2003 to 2012, using the following keywords: end stage, terminal, chronic, renal, kidney, risk factors, Arab, North Africa and Libya. In 2003, the reported incidence of ESKD and prevalence of dialysis-treated ESKD in Libya were the same at 200 per million population (pmp). In 2007, the prevalence of dialysis-treated ESKD was 350 pmp, but the true incidence of ESKD was not available. The most recent published WHO data in 2012 showed the incidence of dialysis-treated ESKD had risen to 282 pmp and the prevalence of dialysis-treated ESKD had reached 624 pmp. The leading causes of ESKD were diabetic kidney disease (26.5 %), chronic glomerulonephritis (21.1 %), hypertensive nephropathy (14.6 %) and congenital/hereditary disease (12.3 %). The total number of dialysis centers was 40 with 61 nephrologists. Nephrologist/internist to patient ratio was 1:40, and nurse to patient ratio was 1:3.7. Only 135 living-related kidney transplants had been performed between 2004 and 2007. There were no published data on most macroeconomic and renal service factors. ESKD is a major public health problem in Libya with diabetic kidney disease and chronic glomerulonephritis being the leading causes. The most frequent co-morbidities were hypertension, obesity and the metabolic syndrome. In addition to provision of RRT, preventive strategies are also urgently needed for a holistic integrated renal care system.

A novel mutation causing nephronophthisis in the Lewis polycystic kidney rat localises to a conserved RCC1 domain in Nek8

PubMed Central

2012-01-01

Background Nephronophthisis (NPHP) as a cause of cystic kidney disease is the most common genetic cause of progressive renal failure in children and young adults. NPHP is characterized by abnormal and/or loss of function of proteins associated with primary cilia. Previously, we characterized an autosomal recessive phenotype of cystic kidney disease in the Lewis Polycystic Kidney (LPK) rat. Results In this study, quantitative trait locus analysis was used to define a ~1.6Mbp region on rat chromosome 10q25 harbouring the lpk mutation. Targeted genome capture and next-generation sequencing of this region identified a non-synonymous mutation R650C in the NIMA (never in mitosis gene a)- related kinase 8 ( Nek8) gene. This is a novel Nek8 mutation that occurs within the regulator of chromosome condensation 1 (RCC1)-like region of the protein. Specifically, the R650C substitution is located within a G[QRC]LG repeat motif of the predicted seven bladed beta-propeller structure of the RCC1 domain. The rat Nek8 gene is located in a region syntenic to portions of human chromosome 17 and mouse 11. Scanning electron microscopy confirmed abnormally long cilia on LPK kidney epithelial cells, and fluorescence immunohistochemistry for Nek8 protein revealed altered cilia localisation. Conclusions When assessed relative to other Nek8 NPHP mutations, our results indicate the whole propeller structure of the RCC1 domain is important, as the different mutations cause comparable phenotypes. This study establishes the LPK rat as a novel model system for NPHP and further consolidates the link between cystic kidney disease and cilia proteins. PMID:22899815

Mathematical Model of Ammonia Handling in the Rat Renal Medulla

PubMed Central

Noiret, Lorette; Baigent, Stephen; Jalan, Rajiv; Thomas, S. Randall

2015-01-01

The kidney is one of the main organs that produces ammonia and release it into the circulation. Under normal conditions, between 30 and 50% of the ammonia produced in the kidney is excreted in the urine, the rest being absorbed into the systemic circulation via the renal vein. In acidosis and in some pathological conditions, the proportion of urinary excretion can increase to 70% of the ammonia produced in the kidney. Mechanisms regulating the balance between urinary excretion and renal vein release are not fully understood. We developed a mathematical model that reflects current thinking about renal ammonia handling in order to investigate the role of each tubular segment and identify some of the components which might control this balance. The model treats the movements of water, sodium chloride, urea, NH3 and NH4+, and non-reabsorbable solute in an idealized renal medulla of the rat at steady state. A parameter study was performed to identify the transport parameters and microenvironmental conditions that most affect the rate of urinary ammonia excretion. Our results suggest that urinary ammonia excretion is mainly determined by those parameters that affect ammonia recycling in the loops of Henle. In particular, our results suggest a critical role for interstitial pH in the outer medulla and for luminal pH along the inner medullary collecting ducts. PMID:26280830

A major X-linked locus affects kidney function in mice

PubMed Central

Leduc, Magalie S.; Savage, Holly S.; Stearns, Timothy M.; Cario, Clinton L.; Walsh, Kenneth A.; Paigen, Beverly; Berndt, Annerose

2012-01-01

Chronic kidney disease is a common disease with increasing prevalence in the western population. One common reason for chronic kidney failure is diabetic nephropathy. Diabetic nephropathy and hyperglycemia are characteristics of the mouse inbred strain KK/HlJ, which is predominantly used as a model for metabolic syndrome due to its inherited glucose intolerance and insulin resistance. We used KK/HlJ, an albuminuria-sensitive strain, and C57BL/6J, an albuminuria-resistant strain, to perform a quantitative trait locus (QTL) cross to identify the genetic basis for chronic kidney failure. Albumin-creatinine-ratio (ACR) was measured in 130 F2 male offspring. One significant QTL was identified on chromosome (Chr) X and four suggestive QTLs were found on Chrs 6, 7, 12, and 13. Narrowing of the QTL region was focused on the X-linked QTL and performed by incorporating genotype and expression analyses for genes located in the region. From the 485 genes identified in the X-linked QTL region, a few candidate genes were identified using a combination of bioinformatic evidence based on genomic comparison of the parental strains and known function in urine homeostasis. Finally, this study demonstrates the significance of the X chromosome in the genetic determination of albuminuria. PMID:23011808

Heritability of Measures of Kidney Disease Among Zuni Indians: The Zuni Kidney Project

PubMed Central

MacCluer, Jean W.; Scavini, Marina; Shah, Vallabh O.; Cole, Shelley A.; Laston, Sandra L.; Voruganti, V. Saroja; Paine, Susan S.; Eaton, Alfred J.; Comuzzie, Anthony G.; Tentori, Francesca; Pathak, Dorothy R.; Bobelu, Arlene; Bobelu, Jeanette; Ghahate, Donica; Waikaniwa, Mildred; Zager, Philip G.

2010-01-01

Background The long-term goal of the GKDZI (Genetics of Kidney Disease in Zuni Indians) Study is to identify genes, environmental factors, and genetic-environmental interactions that modulate susceptibility to renal disease and intermediate phenotypes. Study Design A community-based participatory research approach was used to recruit family members of individuals with kidney disease. Setting & Participants The study was conducted in the Zuni Indians, a small endogamous tribe located in rural New Mexico. We recruited members of extended families, ascertained through a proband with kidney disease and at least 1 sibling with kidney disease. 821 participants were recruited, comprising 7,702 relative pairs. Predictor Outcomes & Measurements Urine albumin-creatinine ratio (UACR) and hematuria were determined in 3 urine samples and expressed as a true ratio. Glomerular filtration rate (GFR) was estimated using the Modification of Diet in Renal Disease (MDRD) Study equation modified for American Indians. Probands were considered to have kidney disease if UACR was ≥0.2 in 2 or more of 3 spot urine samples or estimated GFR was decreased according to the CRIC (Chronic Renal Insufficiency Cohort) Study criteria. Results Kidney disease was identified in 192 participants (23.4%). There were significant heritabilities for estimated GFR, UACR, serum creatinine, serum urea nitrogen, and uric acid and a variety of phenotypes related to obesity, diabetes, and cardiovascular disease. There were significant genetic correlations of some kidney-related phenotypes with these other phenotypes. Limitations Limitations include absence of renal biopsy, possible misclassification bias, lack of direct GFR measurements, and failure to include all possible environmental interactions. Conclusions Many phenotypes related to kidney disease showed significant heritabilities in Zuni Indians, and there were significant genetic correlations with phenotypes related to obesity, diabetes, and cardiovascular disease. The study design serves as a paradigm for the conduct of research in relatively isolated, endogamous, underserved populations. PMID:20646805

Robotics applied in laparoscopic kidney surgery: the Yonsei University experience of 127 cases.

PubMed

Lorenzo, Enrique Ian S; Jeong, Wooju; Oh, Cheol Kyu; Chung, Byung Ha; Choi, Young Deuk; Rha, Koon Ho

2011-01-01

We report our experience on 127 kidney surgeries with the da Vinci surgical system and show the feasibility of a robotics application in a variety of kidney surgeries by both a laparoscopically-trained and a laparoscopically-naïve surgeon. Clinical data of patients who underwent kidney surgery with the da Vinci surgical system from September 2006 to April 2009 were reviewed. Data acquired from medical records included patient demographics, operative time, estimated blood loss (EBL), incidence of intraoperative complication, duration of hospital stay, blood transfusion rate, oncological outcomes, and follow-up results. One-hundred twenty-seven kidney surgeries have been conducted with the da Vinci surgical system at our institution. Three urologists--1 with formal endourology training, 1 with laparoscopic experience, and 1 laparoscopically naïve--have used it for a variety of procedures involving the kidney. The cases include 65 partial nephrectomies (RPN), 38 radical nephrectomies (RRN), and 24 nephroureterectomies with bladder cuff (RNU). Results on operative time, EBL, incidence of intraoperative injury, duration of hospital stay, and blood transfusion rate are comparable with contemporary studies. Robotics application in kidney surgery is a viable option for various procedures. Our experience shows it can be safely and effectively conducted by both laparoscopically-trained and laparoscopically-naïve surgeons once they are accustomed to the robotics system. Copyright © 2011 Elsevier Inc. All rights reserved.

Generalization of Associations of Kidney-Related Genetic Loci to American Indians

PubMed Central

Haack, Karin; Almasy, Laura; Laston, Sandra; Lee, Elisa T.; Best, Lyle G.; Fabsitz, Richard R.; MacCluer, Jean W.; Howard, Barbara V.; Umans, Jason G.; Cole, Shelley A.

2014-01-01

Summary Background and objectives CKD disproportionally affects American Indians, who similar to other populations, show genetic susceptibility to kidney outcomes. Recent studies have identified several loci associated with kidney traits, but their relevance in American Indians is unknown. Design, setting, participants, & measurements This study used data from a large, family-based genetic study of American Indians (the Strong Heart Family Study), which includes 94 multigenerational families enrolled from communities located in Oklahoma, the Dakotas, and Arizona. Individuals were recruited from the Strong Heart Study, a population-based study of cardiovascular disease in American Indians. This study selected 25 single nucleotide polymorphisms in 23 loci identified from recently published kidney-related genome-wide association studies in individuals of European ancestry to evaluate their associations with kidney function (estimated GFR; individuals 18 years or older, up to 3282 individuals) and albuminuria (urinary albumin to creatinine ratio; n=3552) in the Strong Heart Family Study. This study also examined the association of single nucleotide polymorphisms in the APOL1 region with estimated GFR in 1121 Strong Heart Family Study participants. GFR was estimated using the abbreviated Modification of Diet in Renal Disease Equation. Additive genetic models adjusted for age and sex were used. Results This study identified significant associations of single nucleotide polymorphisms with estimated GFR in or nearby PRKAG2, SLC6A13, UBE2Q2, PIP5K1B, and WDR72 (P<2.1 × 10-3 to account for multiple testing). Single nucleotide polymorphisms in these loci explained 2.2% of the estimated GFR total variance and 2.9% of its heritability. An intronic variant of BCAS3 was significantly associated with urinary albumin to creatinine ratio. APOL1 single nucleotide polymorphisms were not associated with estimated GFR in a single variant test or haplotype analyses, and the at-risk variants identified in individuals with African ancestry were not detected in DNA sequencing of American Indians. Conclusion This study extends the genetic associations of loci affecting kidney function to American Indians, a population at high risk of kidney disease, and provides additional support for a potential biologic relevance of these loci across ancestries. PMID:24311711

Use of Readily Accessible Inflammatory Markers to Predict Diabetic Kidney Disease.

PubMed

Winter, Lauren; Wong, Lydia A; Jerums, George; Seah, Jas-Mine; Clarke, Michele; Tan, Sih Min; Coughlan, Melinda T; MacIsaac, Richard J; Ekinci, Elif I

2018-01-01

Diabetic kidney disease is a common complication of type 1 and type 2 diabetes and is the primary cause of end-stage renal disease in developed countries. Early detection of diabetic kidney disease will facilitate early intervention aimed at reducing the rate of progression to end-stage renal disease. Diabetic kidney disease has been traditionally classified based on the presence of albuminuria. More recently estimated glomerular filtration rate has also been incorporated into the staging of diabetic kidney disease. While albuminuric diabetic kidney disease is well described, the phenotype of non-albuminuric diabetic kidney disease is now widely accepted. An association between markers of inflammation and diabetic kidney disease has previously been demonstrated. Effector molecules of the innate immune system including C-reactive protein, interleukin-6, and tumor necrosis factor-α are increased in patients with diabetic kidney disease. Furthermore, renal infiltration of neutrophils, macrophages, and lymphocytes are observed in renal biopsies of patients with diabetic kidney disease. Similarly high serum neutrophil and low serum lymphocyte counts have been shown to be associated with diabetic kidney disease. The neutrophil-lymphocyte ratio is considered a robust measure of systemic inflammation and is associated with the presence of inflammatory conditions including the metabolic syndrome and insulin resistance. Cross-sectional studies have demonstrated a link between high levels of the above inflammatory biomarkers and diabetic kidney disease. Further longitudinal studies will be required to determine if these readily available inflammatory biomarkers can accurately predict the presence and prognosis of diabetic kidney disease, above and beyond albuminuria, and estimated glomerular filtration rate.

Chronic kidney disease in an Aboriginal population: A nurse practitioner-led approach to management.

PubMed

Barrett, Elizabeth; Salem, Lesley; Wilson, Sue; O'Neill, Claire; Davis, Kathleen; Bagnulo, Sharif

2015-12-01

Chronic kidney disease (CKD) is a significant health problem impacting Australia's Aboriginal and Torres Strait Islander population. After age adjustment, the prevalence of kidney disease is 3.7 times higher in Aboriginal people and 7.3 times higher for end-stage kidney disease compared with the wider population. Yet at an Aboriginal Community Controlled Health Service (ACCHS) with a significant patient population, fewer than expected numbers of Aboriginal patients were identified with CKD. The ACCHS engaged a nurse practitioner to lead a systematic approach to the identification and treatment of CKD. This nurse practitioner-led approach to CKD was developed and implemented at a rural NSW ACCHS, with the support of a partnership formed between the nurse practitioner, the ACCHS, a nephrologist from a referral hospital and a statewide NGO. The primary measure for improvement has been to identify and stage patients with CKD and establish management plans as appropriate. This nurse-led project was established to: (i) identify patients with CKD; (ii) provide access for CKD patients to appropriate services; (iii) commence pharmacological and non-pharmacological strategies that enable remission or regression of CKD; and (iv) educate practice GPs and other staff members on CKD clinical guidelines and best practice. The CKD project has improved access to essential health care for vulnerable and at-risk populations, with 187 patients to date having been identified with kidney disease and staged for its severity. The need for strong multi-disciplinary teamwork has been demonstrated with good communication strategies implemented. © 2015 National Rural Health Alliance Inc.

Chronic Kidney Disease in Kidney Stone Formers

PubMed Central

Krambeck, Amy E.; Lieske, John C.

2011-01-01

Summary Recent population studies have found symptomatic kidney stone formers to be at increased risk for chronic kidney disease (CKD). Although kidney stones are not commonly identified as the primary cause of ESRD, they still may be important contributing factors. Paradoxically, CKD can be protective against forming kidney stones because of the substantial reduction in urine calcium excretion. Among stone formers, those with rare hereditary diseases (cystinuria, primary hyperoxaluria, Dent disease, and 2,8 dihydroxyadenine stones), recurrent urinary tract infections, struvite stones, hypertension, and diabetes seem to be at highest risk for CKD. The primary mechanism for CKD from kidney stones is usually attributed to an obstructive uropathy or pyelonephritis, but crystal plugs at the ducts of Bellini and parenchymal injury from shockwave lithotripsy may also contribute. The historical shift to less invasive surgical management of kidney stones has likely had a beneficial impact on the risk for CKD. Among potential kidney donors, past symptomatic kidney stones but not radiographic stones found on computed tomography scans were associated with albuminuria. Kidney stones detected by ultrasound screening have also been associated with CKD in the general population. Further studies that better classify CKD, better characterize stone formers, more thoroughly address potential confounding by comorbidities, and have active instead of passive follow-up to avoid detection bias are needed. PMID:21784825

Assessing the likely harms to kidney vendors in regulated organ markets.

PubMed

Koplin, Julian

2014-01-01

Advocates of paid living kidney donation frequently argue that kidney sellers would benefit from paid donation under a properly regulated kidney market. The poor outcomes experienced by participants in existing markets are often entirely attributed to harmful black-market practices. This article reviews the medical and anthropological literature on the physical, psychological, social, and financial harms experienced by vendors under Iran's regulated system of donor compensation and black markets throughout the world and argues that this body of research not only documents significant harms to vendors, but also provides reasons to believe that such harms would persist under a regulated system. This does not settle the question of whether or not a regulated market should be introduced, but it does strengthen the case against markets in kidneys while suggesting that those advocating such a system cannot appeal to the purported benefits to vendors to support their case.

Why do we have the kidney allocation system we have today? A history of the 2014 kidney allocation system.

PubMed

Stegall, Mark D; Stock, Peter G; Andreoni, Kenneth; Friedewald, John J; Leichtman, Alan B

2017-01-01

"Those who do not know the past are destined to repeat it". The current system for the allocation of deceased donor kidneys that was implemented in December 2014 (termed the kidney allocation system (KAS)) was the culmination of a decade-long process. Thus, many people involved in transplantation today may not be aware of the underlying concepts and early debates that resulted in KAS. Others who were involved might not remember the details (or have chosen to forget). The goal of this manuscript is to outline the history of the process in order to shed light on why KAS has its current format. Copyright © 2016 American Society for Histocompatibility and Immunogenetics. Published by Elsevier Inc. All rights reserved.

Benefits of a transfer clinic in adolescent and young adult kidney transplant patients.

PubMed

McQuillan, Rory F; Toulany, Alene; Kaufman, Miriam; Schiff, Jeffrey R

2015-01-01

Adolescent and young adult kidney transplant recipients have worse graft outcomes than older and younger age groups. Difficulties in the process of transition, defined as the purposeful, planned movement of adolescents with chronic health conditions from child to adult-centered health care systems, may contribute to this. Improving the process of transition may improve adherence post-transfer to adult care services. The purpose of this study is to investigate whether a kidney transplant transfer clinic for adolescent and young adult kidney transplant recipients transitioning from pediatric to adult care improves adherence post-transfer. We developed a joint kidney transplant transfer clinic between a pediatric kidney transplant program, adult kidney transplant program, and adolescent medicine at two academic health centers. The transfer clinic facilitated communication between the adult and pediatric transplant teams, a face-to-face meeting of the patient with the adult team, and a meeting with the adolescent medicine physician. We compared the outcomes of 16 kidney transplant recipients transferred before the clinic was established with 16 patients who attended the clinic. The primary outcome was a composite measure of non-adherence. Non-adherence was defined as either self-reported medication non-adherence or displaying two of the following three characteristics: non-attendance at clinic, non-attendance for blood work appointments, or undetectable calcineurin inhibitor levels within 1 year post-transfer. The two groups were similar at baseline, with non-adherence identified in 43.75 % of patients. Non-adherent behavior in the year post-transfer, which included missing clinic visits, missing regular blood tests, and undetectable calcineurin inhibitor levels, was significantly lower in the cohort which attended the transfer clinic (18.8 versus 62.5 %, p = 0.03). The median change in estimated glomerular filtration rate (eGFR) in the year following transfer was smaller in the group that attended the transition clinic (-0.9 ± 13.2 ml/min/1.73 m(2)) compared to those who did not (-12.29 ± 14.9 ml/min/1.73 m(2)), p = 0.045. Attendance at a single kidney transplant transfer clinic was associated with improved adherence and renal function in the year following transfer to adult care. If these changes are sustained, they may improve long-term graft outcomes for adolescent kidney transplant recipients.

Dual Kidney Transplantation Offers a Valuable Source for Kidneys With Good Functional Outcome.

PubMed

Khalid, U; Asderakis, A; Rana, T; Szabo, L; Chavez, R; Ilham, M A; Ablorsu, E

2016-01-01

Reasons for declining kidney donors are older age, with or without, hypertension, kidney dysfunction, and diabetes. Implantation of both kidneys into a single recipient from such donors may improve their acceptability and outcome. Patients who underwent dual kidney transplantation (DKT) between June 2010 and May 2014 were identified from a prospectively maintained database. Single kidney transplantations (SKT) with matching donor criteria were also identified. Donors considered for DKT were the following: DBDs >70 years of age with diabetes and/or hypertension; DCDs >65 years of age with diabetes and/or hypertension; and DCDs >70 years of age. Over a 4-year period, 34 patients underwent adult DKT, and 51, with matching donor criteria, underwent SKT. The median estimated glomerular filtration rate (eGFR) at 12 and 36 months of DKT was 49 (range, 5-79) and 42 (range, 15-85) mL/min compared with SKT of 35 (range, 10-65) and 32 (range, 6-65), respectively. The 1-year graft survival for DKT and SKT was 88% and 96% (P = .52), and patient survival was 94% and 98%, respectively (P = .12). Median hospital stay, intensive care unit admission, and wound complications were more frequent in the DKT group. Graft function following DKT is significantly better compared with matched criteria SKT; graft and patient survival are similar. There is an increased rate of complications following DKT, with longer hospital stay and ICU admission. Copyright © 2016 Elsevier Inc. All rights reserved.

Diabetic Kidney Disease: A Syndrome Rather Than a Single Disease

PubMed Central

Piccoli, Giorgina B.; Grassi, Giorgio; Cabiddu, Gianfranca; Nazha, Marta; Roggero, Simona; Capizzi, Irene; De Pascale, Agostino; Priola, Adriano M.; Di Vico, Cristina; Maxia, Stefania; Loi, Valentina; Asunis, Anna M.; Pani, Antonello; Veltri, Andrea

2015-01-01

The term "diabetic kidney" has recently been proposed to encompass the various lesions, involving all kidney structures that characterize protean kidney damage in patients with diabetes. While glomerular diseases may follow the stepwise progression that was described several decades ago, the tenet that proteinuria identifies diabetic nephropathy is disputed today and should be limited to glomerular lesions. Improvements in glycemic control may have contributed to a decrease in the prevalence of glomerular lesions, initially described as hallmarks of diabetic nephropathy, and revealed other types of renal damage, mainly related to vasculature and interstitium, and these types usually present with little or no proteinuria. Whilst glomerular damage is the hallmark of microvascular lesions, ischemic nephropathies, renal infarction, and cholesterol emboli syndrome are the result of macrovascular involvement, and the presence of underlying renal damage sets the stage for acute infections and drug-induced kidney injuries. Impairment of the phagocytic response can cause severe and unusual forms of acute and chronic pyelonephritis. It is thus concluded that screening for albuminuria, which is useful for detecting "glomerular diabetic nephropathy", does not identify all potential nephropathies in diabetes patients. As diabetes is a risk factor for all forms of kidney disease, diagnosis in diabetic patients should include the same combination of biochemical, clinical, and imaging tests as employed in non-diabetic subjects, but with the specific consideration that chronic kidney disease (CKD) may develop more rapidly and severely in diabetic patients. PMID:26676663

High-Throughput Screening Enhances Kidney Organoid Differentiation from Human Pluripotent Stem Cells and Enables Automated Multidimensional Phenotyping.

PubMed

Czerniecki, Stefan M; Cruz, Nelly M; Harder, Jennifer L; Menon, Rajasree; Annis, James; Otto, Edgar A; Gulieva, Ramila E; Islas, Laura V; Kim, Yong Kyun; Tran, Linh M; Martins, Timothy J; Pippin, Jeffrey W; Fu, Hongxia; Kretzler, Matthias; Shankland, Stuart J; Himmelfarb, Jonathan; Moon, Randall T; Paragas, Neal; Freedman, Benjamin S

2018-05-15

Organoids derived from human pluripotent stem cells are a potentially powerful tool for high-throughput screening (HTS), but the complexity of organoid cultures poses a significant challenge for miniaturization and automation. Here, we present a fully automated, HTS-compatible platform for enhanced differentiation and phenotyping of human kidney organoids. The entire 21-day protocol, from plating to differentiation to analysis, can be performed automatically by liquid-handling robots, or alternatively by manual pipetting. High-content imaging analysis reveals both dose-dependent and threshold effects during organoid differentiation. Immunofluorescence and single-cell RNA sequencing identify previously undetected parietal, interstitial, and partially differentiated compartments within organoids and define conditions that greatly expand the vascular endothelium. Chemical modulation of toxicity and disease phenotypes can be quantified for safety and efficacy prediction. Screening in gene-edited organoids in this system reveals an unexpected role for myosin in polycystic kidney disease. Organoids in HTS formats thus establish an attractive platform for multidimensional phenotypic screening. Copyright © 2018 Elsevier Inc. All rights reserved.

Association between chronic kidney disease and urinary calculus by stone location: a population-based study.

PubMed

Keller, Joseph J; Chen, Yi-Kuang; Lin, Herng-Ching

2012-12-01

Study Type--Disease prevalence study (cohort design) Level of Evidence 2a. What's known on the subject? and What does the study add? Several studies have estimated the potential association of urinary calculus (UC) with chronic kidney disease (CKD). However, previous literature focusing on this issue tended to evaluate the impact of kidney stones alone on incident CKD, with no studies having been conducted investigating the association between CKD and stone formation in other portions of the urological system. We found that patients with CKD were consistently more likely than comparison subjects to have been previously diagnosed with kidney calculus (odds ratio [OR] 2.10, 95% confidence interval [CI] 1.95-2.27), ureter calculus (OR 1.68, 95% CI 1.51-1.85), bladder calculus (OR 1.49, 95% CI 1.13-1.98), and unspecified calculus (OR 1.89, 95% CI 1.74-2.06). We concluded that there was an association between CKD and UC regardless of stone location. • To explore the association of chronic kidney disease (CKD) with prior kidney calculus, ureter calculus, and bladder calculus using a population-based dataset in Taiwan. Several studies have estimated the potential association of urinary calculus (UC) with CKD. However, previous literature focusing on this issue tended to evaluate the impact of kidney stones alone on incident CKD, with no studies having been conducted investigating the association between CKD and stone formation in other portions of the urological system. • We identified 21,474 patients who received their first-time diagnosis of CKD between 2001 and 2009. • The 21,474 controls were frequency-matched with cases for sex, age group, and index year. • We used conditional logistic regression analyses to compute the odds ratio (OR) and corresponding 95% confidence interval (CI) as an estimation of association between CKD and having been previously diagnosed with UC. • The results show that compared with controls, the OR of prior UC for cases was 1.91 (95% CI 1.81-2.01, P < 0.001) after adjusting for potential confounders. • Furthermore, cases were consistently more likely than controls to have been previously diagnosed with kidney calculus (OR 2.10, 95% CI 1.95-2.27), ureter calculus (OR 1.68, 95% CI 1.51-1.85), bladder calculus (OR 1.49, 95% CI 1.13-1.98), and unspecified UC (OR 1.89, 95% CI 1.74-2.06). • We concluded that there was an association between ckd and UC regardless of stone location. © 2012 BJU INTERNATIONAL.

CCKB/gastrin receptors mediate changes in sodium and potassium absorption in the isolated perfused rat kidney.

PubMed

von Schrenck, T; Ahrens, M; de Weerth, A; Bobrowski, C; Wolf, G; Jonas, L; Jocks, T; Schulz, M; Bläker, M; Neumaier, M; Stahl, R A

2000-09-01

To evaluate the function of cholecystokinin B (CCKB)/gastrin receptors in the rat kidney, we identified the receptors by Northern blot and localized the receptors by immunohistochemistry. The functional effects of gastrin were studied under standardized in vitro conditions using the isolated perfused kidney. Rat kidneys were mounted in an organ bath by attaching the renal artery to a perfusion system. A catheter was inserted into the renal vein and the ureter to collect samples that were analyzed for the concentrations of electrolytes. After a preperfusion period, gastrin-17-I was given via the renal artery (10-8 to 10-6 mol/L). Subsequently, hemodynamic parameters (for example, perfusate flow) and changes in sodium and potassium absorption were determined. All data were subjected to a nonparametric analysis of variance and, in case of significant results, to subsequent paired comparisons by the a posteriori Wilcoxon test. Northern blot analysis detected CCKB receptor transcripts in total RNA isolated from kidneys. Immunohistochemistry localized CCKB receptors on tubules and collecting duct cells. Compared with controls, gastrin (10-6 mol/L) caused a decrease in the fractional sodium reabsorption (basal 80%, 10 minutes after application of gastrin 71%, after 20 minutes 62%, P < 0.05). This effect was inhibited by the CCKB receptor antagonist L-365,260. Gastrin decreased urinary potassium excretion at 10-8 and 10-6 mol/L [maximal decrease at 10-6 mol/L from baseline values (100%) to 49% after 10 minutes and to 69% after 20 minutes, P < 0.05, N = 6]. This effect was also abolished by the CCKB receptor antagonist L-365,260. Gastrin (10-6 mol/L) reduced perfusate flow by 31% (P < 0.05). CCKB receptors are expressed in the rat kidney on tubules and collecting ducts. These receptors mediate changes in renal potassium and sodium absorption. In addition, gastrin causes a decrease in perfusate flow, indicating that CCKB receptors might also modulate vascular resistance in the kidney.

Mitogen-Activated Protein Kinase 14 Promotes AKI

PubMed Central

Husi, Holger; Gonzalez-Lafuente, Laura; Valiño-Rivas, Lara; Fresno, Manuel; Sanz, Ana Belen; Mullen, William; Albalat, Amaya; Mezzano, Sergio; Vlahou, Tonia; Mischak, Harald

2017-01-01

An improved understanding of pathogenic pathways in AKI may identify novel therapeutic approaches. Previously, we conducted unbiased liquid chromatography-tandem mass spectrometry–based protein expression profiling of the renal proteome in mice with acute folate nephropathy. Here, analysis of the dataset identified enrichment of pathways involving NFκB in the kidney cortex, and a targeted data mining approach identified components of the noncanonical NFκB pathway, including the upstream kinase mitogen-activated protein kinase kinase kinase 14 (MAP3K14), the NFκB DNA binding heterodimer RelB/NFκB2, and proteins involved in NFκB2 p100 ubiquitination and proteasomal processing to p52, as upregulated. Immunohistochemistry localized MAP3K14 expression to tubular cells in acute folate nephropathy and human AKI. In vivo, kidney expression levels of NFκB2 p100 and p52 increased rapidly after folic acid injection, as did DNA binding of RelB and NFκB2, detected in nuclei isolated from the kidneys. Compared with wild-type mice, MAP3K14 activity–deficient aly/aly (MAP3K14aly/aly) mice had less kidney dysfunction, inflammation, and apoptosis in acute folate nephropathy and less kidney dysfunction and a lower mortality rate in cisplatin-induced AKI. The exchange of bone marrow between wild-type and MAP3K14aly/aly mice did not affect the survival rate of either group after folic acid injection. In cultured tubular cells, MAP3K14 small interfering RNA targeting decreased inflammation and cell death. Additionally, cell culture and in vivo studies identified the chemokines MCP-1, RANTES, and CXCL10 as MAP3K14 targets in tubular cells. In conclusion, MAP3K14 promotes kidney injury through promotion of inflammation and cell death and is a promising novel therapeutic target. PMID:27620989

77 FR 30540 - Center for Scientific Review Notice of Closed Meetings

Federal Register 2010, 2011, 2012, 2013, 2014

2012-05-23

... Committee: Center for Scientific Review Special Emphasis Panel; Drug Discovery for the Nervous System...: Digestive, Kidney and Urological Systems Integrated Review Group; Kidney Molecular Biology and Genitourinary...

Belatacept Injection

MedlinePlus

... rejection (attack of a transplanted organ by the immune system of a person receiving the organ) of kidney ... It works by decreasing the activity of the immune system to prevent it from attacking the transplanted kidney.

The Promise of Mesenchymal Stem Cell Therapy for Diabetic Kidney Disease.

PubMed

Griffin, Tomás P; Martin, William Patrick; Islam, Nahidul; O'Brien, Timothy; Griffin, Matthew D

2016-05-01

Diabetes mellitus (DM) commonly leads to progressive chronic kidney disease despite current best medical practice. The pathogenesis of diabetic kidney disease (DKD) involves a complex network of primary and secondary mechanisms with both intra-renal and systemic components. Apart from inhibition of the renin angiotensin aldosterone system, targeting individual pathogenic mediators with drug therapy has not, thus far, been proven to have high clinical value. Stem or progenitor cell therapies offer an alternative strategy for modulating complex disease processes through suppressing multiple pathogenic pathways and promoting pro-regenerative mechanisms. Mesenchymal stem cells (MSCs) have shown particular promise based on their accessibility from adult tissues and their diverse mechanisms of action including secretion of paracrine anti-inflammatory and cyto-protective factors. In this review, the progress toward clinical translation of MSC therapy for DKD is critically evaluated. Results from animal models suggest distinct potential for systemic MSC infusion to favourably modulate DKD progression. However, only a few early phase clinical trials have been initiated and efficacy in humans remains to be proven. Key knowledge gaps and research opportunities exist in this field. These include the need to gain greater understanding of in vivo mechanism of action, to identify quantifiable biomarkers of response to therapy and to define the optimal source, dose and timing of MSC administration. Given the rising prevalence of DM and DKD worldwide, continued progress toward harnessing the inherent regenerative functions of MSCs and other progenitor cells for even a subset of those affected has potential for profound societal benefits.

Plasma Kallikrein-Kinin system mediates immune-mediated renal injury in trichloroethylene-sensitized mice.

PubMed

Wang, Hui; Zhang, Jia-Xiang; Ye, Liang-Ping; Li, Shu-Long; Wang, Feng; Zha, Wan-Sheng; Shen, Tong; Wu, Changhao; Zhu, Qi-Xing

2016-07-01

Trichloroethylene (TCE) is a major environmental pollutant. An immunological response is a newly-recognized mechanism for TCE-induced kidney damage. However, the role of the plasma kallikrein-kinin system (KKS) in immune-mediated kidney injury has never been examined. This study aimed to explore the role of the key components of the KKS, i.e. plasma kallikrein (PK), bradykinin (BK) and its receptors B1R and B2R, in TCE-induced kidney injury. A mouse model of skin sensitization was used to explore the mechanism of injury with or without a PK inhibitor PKSI. Kidney function was evaluated by measuring blood urea nitrogen (BUN) and creatinine (Cr) in conjunction with histopathologic characterization. Plasma BK was determined by ELISA; Renal C5b-9 membrane attack complex was evaluated by immunohistochemistry. Expression of BK and PK in the kidney was detected by immunofluorescence. mRNA and protein levels of B1R and B2R were assessed by real-time qPCR and Western blot. As expected, numerous inflammatory cell infiltration and tubular epithelial cell vacuolar degeneration were observed in TCE-sensitized mice. Moreover, serum BUN and Cr and plasma BK were increased. In addition, deposition of BK, PK and C5b-9 were observed and B1R and B2R mRNA and proteins levels were up-regulated. Pre-treatment with PKSI, a highly selective inhibitor of PK, alleviated TCE-induced renal damage. In addition, PKSI attenuated TCE-induced up-regulation of BK, PK and its receptors and C5b-9. These results provided the first evidence that activation of the KKS contributed to immune-mediated renal injury induced by TCE and also helped to identify the KKS as a potential therapeutic target for mitigating chemical sensitization-induced renal damage.

Profile, risk factors and outcome of acute kidney injury in paediatric acute-on-chronic liver failure.

PubMed

Lal, Bikrant B; Alam, Seema; Sood, Vikrant; Rawat, Dinesh; Khanna, Rajeev

2018-01-11

There are no studies on acute kidney injury in paediatric acute-on-chronic liver failure. This study was planned with aim to describe the clinical presentation and outcome of acute kidney injury among paediatric acute-on-chronic liver failure patients. Data of all children 1-18 years of age presenting with acute chronic liver failure (Asia pacific association for the study of the liver definition) was reviewed. Acute kidney injury was defined as per Kidney Diseases-Improving Global Outcomes guidelines. Poor outcome was defined as death or need for liver transplant within 3 months of development of acute kidney injury. A total of 84 children with acute-on-chronic liver failure were presented to us in the study period. Acute kidney injury developed in 22.6% of patients with acute-on-chronic liver failure. The median duration from acute-on-chronic liver failure to development of acute kidney injury was 4 weeks (Range: 2-10 weeks). The causes of acute kidney injury were hepatorenal syndrome (31.6%), sepsis (31.6%), nephrotoxic drugs (21%), dehydration (10.5%) and bile pigment related acute tubular necrosis in one patient. On univariate analysis, higher baseline bilirubin, higher international normalized ratio, higher paediatric end stage liver disease, presence of systemic inflammatory response syndrome and presence of spontaneous bacterial peritonitis had significant association with presence of acute kidney injury. On logistic regression analysis, presence of systemic inflammatory response syndrome (adjusted OR: 8.659, 95% CI: 2.18-34.37, P = .002) and higher baseline bilirubin (adjusted OR: 1.07, 95% CI: 1.008-1.135, P = .025) were independently associated with presence of acute kidney injury. Of the patients with acute kidney injury, 5(26.3%) survived with native liver, 10(52.6%) died and 4 (21.1%) underwent liver transplantation. Acute kidney injury developed in 22.6% of children with acute-on-chronic liver failure. Bilirubin more than 17.7 mg/dL and presence of systemic inflammatory response syndrome were high risk factors for acute kidney injury. Development of acute kidney injury in a child with acute-on-chronic liver failure suggests poor outcome and need for early intervention. © 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

[Establishment of systemic lupus erythematosus-like murine model with Sm mimotope].

PubMed

Xie, Hong-Fu; Feng, Hao; Zeng, Hai-Yan; Li, Ji; Shi, Wei; Yi, Mei; Wu, Bin

2007-04-01

To establish systemic lupus erythematosus (SLE) -like murine model by immunizing BALB/C mice with Sm mimotope. Sm mimotope was identified by screening a 12-mer random peptide library with monoclonal anti-Smith antibody. Sm mimotope was initially defined with sandwich ELISA, DNA sequencing, and deduced amino acid sequence; and BALB/C mice were subcutaneously injected with mixture phages clones. Sera Sm antibody, anti-double stranded DNA (dsDNA) antibody, and antinuclear antibody (ANA) of mice were detected using direct immunofluorescence; kidney histological changes were examined by HE staining. Five randomly selected peptides were sequenced and the amino acid sequences IR, SQ, and PP were detected in a higher frequency. High-titer IgG autoantibodies of dsDNA, Sm, and ANA in the sera of experiment group were detected by ELISA 28 days after having been immunized by Sm mimotope. Proteinuria was detected 33 days later; immune complex and nephritis were observed in kidney specimens. SLE-like murine model can be successfully induced by Sm phage mimotope.

Constructing kidney-like tissues from cells based on programs for organ development: toward a method of in vitro tissue engineering of the kidney.

PubMed

Rosines, Eran; Johkura, Kohei; Zhang, Xing; Schmidt, Heidi J; Decambre, Marvalyn; Bush, Kevin T; Nigam, Sanjay K

2010-08-01

The plausibility of constructing vascularized three-dimensional (3D) kidney tissue from cells was investigated. The kidney develops from mutual inductive interactions between cells of the ureteric bud (UB), derived from the Wolffian duct (WD), and the metanephric mesenchyme (MM). We found that isolated MMs were capable of inducing branching morphogenesis of the WD (an epithelial tube) in recombination cultures; suggesting that the isolated MM retains inductive capacity for WD-derived epithelial tubule cells other than those from the UB. Hanging drop aggregates of embryonic and adult renal epithelial cells from UB and mouse inner medullary collecting duct cell (IMCD) lines, which are ultimately of WD origin, were capable of inducing MM epithelialization and tubulogenesis with apparent connections (UB cells) and collecting duct-like tubules with lumens (IMCD). This supports the view that the collecting system can be constructed from certain epithelial cells (those ultimately of WD origin) when stimulated by MM. Although the functions of the MM could not be replaced by cultured mesenchymal cells, primary MM cells and one MM-derived cell line (BSN) produced factors that stimulate UB branching morphogenesis, whereas another, rat inducible metanephric mesenchyme (RIMM-18), supported WD budding as a feeder layer. This indicates that some MM functions can be recapitulated by cells. Although engineering of a kidney-like tissue from cultured cells alone remains to be achieved, these results suggest the feasibility of such an approach following the normal developmental progression of the UB and MM. Consistent with this notion, implants of kidney-like tissues constructed in vitro from recombinations of the UB and MM survived for over 5 weeks and achieved an apparently host-derived glomerular vasculature. Lastly, we addressed the issue of optimal macro- and micro-patterning of kidney-like tissue, which might be necessary for function of an organ assembled using a tissue engineering approach. To identify suitable conditions, 3D reconstructions of HoxB7-green fluorescent protein mouse rudiments (E12) cultured on a filter or suspended in a collagen gel (type I or type IV) revealed that type IV collagen 3D culture supports the deepest tissue growth (600 +/- 8 microm) and the largest kidney volume (0.22 +/- 0.02 mm(3)), and enabled the development of an umbrella-shaped collecting system such as occurs in vivo. Taken together with prior work (Rosines et al., 2007; Steer et al., 2002), these results support the plausibility of a developmental strategy for constructing and propagating vascularized 3D kidney-like tissues from recombinations of cultured renal progenitor cells and/or primordial tissue.

Long noncoding RNA Hoxb3os is dysregulated in autosomal dominant polycystic kidney disease and regulates mTOR signaling.

PubMed

Aboudehen, Karam; Farahani, Shayan; Kanchwala, Mohammed; Chan, Siu Chiu; Avdulov, Svetlana; Mickelson, Alan; Lee, Dayeon; Gearhart, Micah D; Patel, Vishal; Xing, Chao; Igarashi, Peter

2018-06-15

Autosomal dominant polycystic kidney disease (ADPKD) is a debilitating disease that is characterized by the accumulation of numerous fluid-filled cysts in the kidney. ADPKD is primarily caused by mutations in two genes, PKD1 and PKD2 Long noncoding RNAs (lncRNA), defined by a length >200 nucleotides and absence of a long ORF, have recently emerged as epigenetic regulators of development and disease; however, their involvement in PKD has not been explored previously. Here, we performed deep RNA-Seq to identify lncRNAs that are dysregulated in two orthologous mouse models of ADPKD (kidney-specific Pkd1 and Pkd2 mutant mice). We identified a kidney-specific, evolutionarily conserved lncRNA called Hoxb3os that was down-regulated in cystic kidneys from Pkd1 and Pkd2 mutant mice. The human ortholog HOXB3-AS1 was down-regulated in cystic kidneys from ADPKD patients. Hoxb3os was highly expressed in renal tubules in adult WT mice, whereas its expression was lost in the cyst epithelium of mutant mice. To investigate the function of Hoxb3os , we utilized CRISPR/Cas9 to knock out its expression in mIMCD3 cells. Deletion of Hoxb3os resulted in increased phosphorylation of mTOR and its downstream targets, including p70 S6 kinase, ribosomal protein S6, and the translation repressor 4E-BP1. Consistent with activation of mTORC1 signaling, Hoxb3os mutant cells displayed increased mitochondrial respiration. The Hoxb3os mutant phenotype was partially rescued upon re-expression of Hoxb3os in knockout cells. These findings identify Hoxb3os as a novel lncRNA that is down-regulated in ADPKD and regulates mTOR signaling and mitochondrial respiration. © 2018 Aboudehen et al.

Purification and Immunobiochemical Characterization of a 31 kDa Cross-Reactive Allergen from Phaseolus vulgaris (Kidney Bean)

PubMed Central

Kasera, Ramkrashan; Singh, Anand Bahadur; Lavasa, Shakuntala; Nagendra, Komarla; Arora, Naveen

2013-01-01

Background Legumes are a rich source of proteins but are also potential elicitors of IgE-mediated food allergy. This study aimed to isolate and characterize a major allergen of Phaseolus vulgaris (kidney bean) and determine its allergenicity. Methodology Kidney bean allergen was purified using Q Sepharose column (anion exchanger) and eluates with high intensity were pooled to purify protein using Superdex 75 (gel filtration) and C18 column (RP-HPLC). Patients with history of kidney bean allergy were skin prick tested (SPT) with crude kidney bean extract and the purified protein. Specific IgE was estimated in sera by enzyme-linked immunosorbent assay (ELISA). Characterization of purified protein and its cross-reactivity was investigated by immunobiochemical methods. Identification of purified protein was carried out by tandem mass spectrometry. Principal Findings Purified protein appeared as a single band at 31 kDa on SDS-PAGE and showed IgE binding to 88% patients’ sera by ELISA and immunoblotting. SPT with purified protein identified 78% hypersensitive patients of kidney bean. Significant release of histamine from sensitized basophils was observed after challenge with purified protein. PAS staining suggested it to be a glycoprotein, but no change in IgE binding was observed after periodate oxidation. The 31 kDa protein remained stable for 60 min on incubation with pepsin. The purified protein had high allergenic potential since it required only 102 ng of self protein for 50% IgE inhibition. Mass spectrometric analysis identified it as Phytohemagglutinin. It also showed hemagglutination with human RBCs. Cross-reactivity was observed with peanut and black gram with IC50 of 185 and 228 ng respectively. Conclusion/Significance A 31 kDa major allergen of kidney bean was purified and identified as phytohemagglutinin with cross-reactivity to peanut and black gram. PMID:23671655

C-kit+ cells isolated from developing kidneys are a novel population of stem cells with regenerative potential

PubMed Central

Rangel, Erika B; Gomes, Samirah A; Dulce, Raul A; Premer, Courtney; Rodrigues, Claudia O; Kanashiro-Takeuchi, Rosemeire M; Oskouei, Behzad; Carvalho, Decio A; Ruiz, Phillip; Reiser, Jochen; Hare, Joshua M

2013-01-01

The presence of tissue specific precursor cells is an emerging concept in organ formation and tissue homeostasis. Several progenitors are described in the kidneys. However, their identity as a true stem cell remains elusive. Here, we identify a neonatal kidney-derived c-kit+ cell population that fulfills all of the criteria as a stem cell. These cells were found in the thick ascending limb of Henle's loop and exhibited clonogenicity, self-renewal, and multipotentiality with differentiation capacity into mesoderm and ectoderm progeny. Additionally, c-kit+ cells formed spheres in nonadherent conditions when plated at clonal density and expressed markers of stem cells, progenitors, and differentiated cells. Ex-vivo expanded c-kit+ cells integrated into several compartments of the kidney, including tubules, vessels, and glomeruli, and contributed to functional and morphological improvement of the kidney following acute ischemia-reperfusion injury in rats. Together these findings document a novel neonatal rat kidney c-kit+ stem cell population that can be isolated, expanded, cloned, differentiated, and employed for kidney repair following acute kidney injury. These cells have important biological and therapeutic implications. PMID:23733311

Effects of Single and Combined Losartan and Tempol Treatments on Oxidative Stress, Kidney Structure and Function in Spontaneously Hypertensive Rats with Early Course of Proteinuric Nephropathy.

PubMed

Karanovic, Danijela; Grujic-Milanovic, Jelica; Miloradovic, Zoran; Ivanov, Milan; Jovovic, Djurdjica; Vajic, Una-Jovana; Zivotic, Maja; Markovic-Lipkovski, Jasmina; Mihailovic-Stanojevic, Nevena

2016-01-01

Oxidative stress has been widely implicated in both hypertension and chronic kidney disease (CKD). Hypertension is a major risk factor for CKD progression. In the present study we have investigated the effects of chronic single tempol (membrane-permeable radical scavenger) or losartan (angiotensin II type 1 receptor blocker) treatment, and their combination on systemic oxidative status (plasma thiobarbituric acid-reactive substances (pTBARS) production, plasma antioxidant capacity (2,2'-azino-bis(3-ethylbenzothiazoline-6-sulphonic acid, pABTS), erythrocyte antioxidant enzymes activities) and kidney oxidative stress (kTBARS, kABTS, kidney antioxidant enzymes activities), kidney function and structure in spontaneously hypertensive rats (SHR) with the early course of adriamycin-induced nephropathy. Adult SHR were divided into five groups. The control group received vehicle, while the other groups received adriamycin (2 mg/kg, i.v.) twice in a 21-day interval, followed by vehicle, losartan (L,10 mg/kg/day), tempol (T,100 mg/kg/day) or combined T+L treatment (by gavage) during a six-week period. Adriamycin significantly increased proteinuria, plasma lipid peroxidation, kidney protein oxidation, nitrite excretion, matrix metalloproteinase-1 (MMP-1) protein expression and nestin immunostaining in the kidney. Also, it decreased kidney antioxidant defense, kidney NADPH oxidase 4 (kNox4) protein expression and abolished anti-inflammatory response due to significant reduction of kidney NADPH oxidase 2 (kNox2) protein expression in SHR. All treatments reduced protein-to-creatinine ratio (marker of proteinuria), pTBARS production, kidney protein carbonylation, nitrite excretion, increased antioxidant capacity and restored kidney nestin expression similar to control. Both single treatments significantly improved systemic and kidney antioxidant defense, bioavailability of renal nitric oxide, reduced kMMP-1 protein expression and renal injury, thus retarded CKD progression. Losartan improved blood pressure, as well as tubular injury and restored anti-inflammatory defense by reverting kNox2 expression to the control level. Interestingly, tempol was more successful in reducing systemic oxidative stress, proteinuria, kMMP-1 and glomerulosclerosis. However, combined treatment failed to overcome the beneficial effects of single treatments in slowing down the progression of ADR-induced nephropathy in SHR.

21 CFR 866.5320 - Properdin factor B immuno-logical test system.

Code of Federal Regulations, 2010 CFR

2010-04-01

... of the glomeruli of the kidney), lupus nephritis (kidney disease associated with a multisystem autoimmune disease, systemic lupus erythematosus), as well as several skin diseases, e.g., dermititis...

Clinical Course of a Patient With Kidney Failure Due to Isolated Bilateral Renal Extramedullary Plasmacytomas.

PubMed

Lawrence, Braden J; Petersen, Emily L; Riches, Wayne G; Pfeiffer, David C

2018-06-06

Plasmacytomas are rare immunoproliferative monoclonal plasma cell diseases of lymphoid lineage that may present in an isolated or systemic manner. Systemic involvement is much more common than occurrences isolated to a particular organ, and for this reason, it is imperative to rule out systemic involvement for osseous and nonosseous isolated neoplasms. These neoplasms present unique challenges due to their location, extent of involvement, vague presentation, and dearth of treatment protocol. We report the case of a 69-year-old man who developed chronic kidney disease stage 4 between 2009 and 2012. Precipitous kidney failure, anorexia, fatigue, and flank pain necessitated clinical follow-up that ultimately led to thorough imaging and bilateral kidney biopsy. Protein electrophoresis, immunohistochemistry, and immunofluorescence were all consistent with bilateral renal extramedullary plasmacytomas. Treatment recommendations are often limited to prior case successes; however, chemotherapy, radiation, and surgery are the mainstay of treatment. Although surgery or combined therapy provides the best results for patients, such options are unfeasible with bilateral kidney involvement. Therefore, a chemotherapy regimen, similar to that for multiple myeloma, was determined to be most reasonable. Treatment consisted of 4 cycles of a bortezomib, cyclophosphamide, and dexamethasone regimen. Three months following chemotherapy, kidney function returned to baseline levels. Copyright © 2018 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.

Knowledge-based segmentation of pediatric kidneys in CT for measuring parenchymal volume

NASA Astrophysics Data System (ADS)

Brown, Matthew S.; Feng, Waldo C.; Hall, Theodore R.; McNitt-Gray, Michael F.; Churchill, Bernard M.

2000-06-01

The purpose of this work was to develop an automated method for segmenting pediatric kidneys in contrast-enhanced helical CT images and measuring the volume of the renal parenchyma. An automated system was developed to segment the abdomen, spine, aorta and kidneys. The expected size, shape, topology an X-ray attenuation of anatomical structures are stored as features in an anatomical model. These features guide 3-D threshold-based segmentation and then matching of extracted image regions to anatomical structures in the model. Following segmentation, the kidney volumes are calculated by summing included voxels. To validate the system, the kidney volumes of 4 swine were calculated using our approach and compared to the 'true' volumes measured after harvesting the kidneys. Automated volume calculations were also performed retrospectively in a cohort of 10 children. The mean difference between the calculated and measured values in the swine kidneys was 1.38 (S.D. plus or minus 0.44) cc. For the pediatric cases, calculated volumes ranged from 41.7 - 252.1 cc/kidney, and the mean ratio of right to left kidney volume was 0.96 (S.D. plus or minus 0.07). These results demonstrate the accuracy of the volumetric technique that may in the future provide an objective assessment of renal damage.

Monitoring Lead (Pb) Pollution and Identifying Pb Pollution Sources in Japan Using Stable Pb Isotope Analysis with Kidneys of Wild Rats.

PubMed

Nakata, Hokuto; Nakayama, Shouta M M; Oroszlany, Balazs; Ikenaka, Yoshinori; Mizukawa, Hazuki; Tanaka, Kazuyuki; Harunari, Tsunehito; Tanikawa, Tsutomu; Darwish, Wageh Sobhy; Yohannes, Yared B; Saengtienchai, Aksorn; Ishizuka, Mayumi

2017-01-10

Although Japan has been considered to have little lead (Pb) pollution in modern times, the actual pollution situation is unclear. The present study aims to investigate the extent of Pb pollution and to identify the pollution sources in Japan using stable Pb isotope analysis with kidneys of wild rats. Wild brown ( Rattus norvegicus , n = 43) and black ( R. rattus , n = 98) rats were trapped from various sites in Japan. Mean Pb concentrations in the kidneys of rats from Okinawa (15.58 mg/kg, dry weight), Aichi (10.83), Niigata (10.62), Fukuoka (8.09), Ibaraki (5.06), Kyoto (4.58), Osaka (4.57), Kanagawa (3.42), and Tokyo (3.40) were above the threshold (2.50) for histological kidney changes. Similarly, compared with the previous report, it was regarded that even structural and functional kidney damage as well as neurotoxicity have spread among rats in Japan. Additionally, the possibility of human exposure to a high level of Pb was assumed. In regard to stable Pb isotope analysis, distinctive values of stable Pb isotope ratios (Pb-IRs) were detected in some kidney samples with Pb levels above 5.0 mg/kg. This result indicated that composite factors are involved in Pb pollution. However, the identification of a concrete pollution source has not been accomplished due to limited differences among previously reported values of Pb isotope composition in circulating Pb products. Namely, the current study established the limit of Pb isotope analysis for source identification. Further detailed research about monitoring Pb pollution in Japan and the demonstration of a novel method to identify Pb sources are needed.

Monitoring Lead (Pb) Pollution and Identifying Pb Pollution Sources in Japan Using Stable Pb Isotope Analysis with Kidneys of Wild Rats

PubMed Central

Nakata, Hokuto; Nakayama, Shouta M. M.; Oroszlany, Balazs; Ikenaka, Yoshinori; Mizukawa, Hazuki; Tanaka, Kazuyuki; Harunari, Tsunehito; Tanikawa, Tsutomu; Darwish, Wageh Sobhy; Yohannes, Yared B.; Saengtienchai, Aksorn; Ishizuka, Mayumi

2017-01-01

Although Japan has been considered to have little lead (Pb) pollution in modern times, the actual pollution situation is unclear. The present study aims to investigate the extent of Pb pollution and to identify the pollution sources in Japan using stable Pb isotope analysis with kidneys of wild rats. Wild brown (Rattus norvegicus, n = 43) and black (R. rattus, n = 98) rats were trapped from various sites in Japan. Mean Pb concentrations in the kidneys of rats from Okinawa (15.58 mg/kg, dry weight), Aichi (10.83), Niigata (10.62), Fukuoka (8.09), Ibaraki (5.06), Kyoto (4.58), Osaka (4.57), Kanagawa (3.42), and Tokyo (3.40) were above the threshold (2.50) for histological kidney changes. Similarly, compared with the previous report, it was regarded that even structural and functional kidney damage as well as neurotoxicity have spread among rats in Japan. Additionally, the possibility of human exposure to a high level of Pb was assumed. In regard to stable Pb isotope analysis, distinctive values of stable Pb isotope ratios (Pb-IRs) were detected in some kidney samples with Pb levels above 5.0 mg/kg. This result indicated that composite factors are involved in Pb pollution. However, the identification of a concrete pollution source has not been accomplished due to limited differences among previously reported values of Pb isotope composition in circulating Pb products. Namely, the current study established the limit of Pb isotope analysis for source identification. Further detailed research about monitoring Pb pollution in Japan and the demonstration of a novel method to identify Pb sources are needed. PMID:28075384

Selenium-binding protein 1: a sensitive urinary biomarker to detect heavy metal-induced nephrotoxicity.

PubMed

Lee, Eui Kyung; Shin, Young-Jun; Park, Eun Young; Kim, Nam Deuk; Moon, Aree; Kwack, Seung Jun; Son, Ji Yeon; Kacew, Sam; Lee, Byung Mu; Bae, Ok-Nam; Kim, Hyung Sik

2017-04-01

Identifying novel biomarkers to detect nephrotoxicity is clinically important. Here, we attempted to identify new biomarkers for mercury-induced nephrotoxicity and compared their sensitivity to that of traditional biomarkers in animal models. Comparative proteomics analysis was performed in kidney tissues of Sprague-Dawley rats after oral treatment with HgCl 2 (0.1, 1, or 5 mg/kg/day) for 21 days. Kidney cortex tissues were analyzed by two-dimensional gel electrophoresis/matrix-assisted laser desorption/ionization, and differentially expressed proteins were identified. The corresponding spots were quantitated by RT-PCR. Selenium-binding protein 1 (SBP1) was found to be the most markedly upregulated protein in the kidney cortex of rats after HgCl 2 administration. However, blood urea nitrogen, serum creatinine, and glucose levels increased significantly only in the 1 or 5 mg/kg HgCl 2 -treated groups. A number of urinary excretion proteins, including kidney injury molecule-1, clusterin, monocyte chemoattractant protein-1, and β-microglobulin, increased dose-dependently. Histopathological examination revealed severe proximal tubular damage in high-dose (5 mg/kg) HgCl 2 -exposed groups. In addition, urinary excretion of SBP1 significantly increased in a dose-dependent manner. To confirm the critical role of SBP1 as a biomarker for nephrotoxicity, normal kidney proximal tubular cells were treated with HgCl 2 , CdCl 2 , or cisplatin for 24 h. SBP1 levels significantly increased in conditioned media exposed to nephrotoxicants, but decreased in cell lysates. Our investigations suggest that SBP1 may play a critical role in the pathological processes underlying chemical-induced nephrotoxicity. Thus, urinary excretion of SBP1 might be a sensitive and specific biomarker to detect early stages of kidney injury.

The case for living kidney sales: rationale, objections and concerns.

PubMed

Matas, Arthur J

2004-12-01

Currently, potential kidney transplant candidates are dying on the waiting list. One potential solution would be a regulated system of living kidney sales (with safeguards to protect the vendor). Potential objections and practical concerns are discussed.

Kidney biopsy

MedlinePlus

... normal structure. What Abnormal Results Mean An abnormal result means there are changes in the kidney tissue. This may be due to: Infection Poor blood flow through the kidney Connective tissue diseases such as systemic lupus erythematosus Other diseases that may be affecting the ...

Application of small RNA sequencing to identify microRNAs in acute kidney injury and fibrosis

DOE Office of Scientific and Technical Information (OSTI.GOV)

Pellegrini, Kathryn L.

Establishing a microRNA (miRNA) expression profile in affected tissues provides an important foundation for the discovery of miRNAs involved in the development or progression of pathologic conditions. We conducted small RNA sequencing to generate a temporal profile of miRNA expression in the kidneys using a mouse model of folic acid-induced (250 mg/kg i.p.) kidney injury and fibrosis. From the 103 miRNAs that were differentially expressed over the time course (> 2-fold, p < 0.05), we chose to further investigate miR-18a-5p, which is expressed during the acute stage of the injury; miR-132-3p, which is upregulated during transition between acute and fibroticmore » injury; and miR-146b-5p, which is highly expressed at the peak of fibrosis. Using qRT-PCR, we confirmed the increased expression of these candidate miRNAs in the folic acid model as well as in other established mouse models of acute injury (ischemia/reperfusion injury) and fibrosis (unilateral ureteral obstruction). In situ hybridization confirmed high expression of miR-18a-5p, miR-132-3p and miR-146b-5p throughout the kidney cortex in mice and humans with severe kidney injury or fibrosis. When primary human proximal tubular epithelial cells were treated with model nephrotoxicants such as cadmium chloride (CdCl{sub 2}), arsenic trioxide, aristolochic acid (AA), potassium dichromate (K{sub 2}Cr{sub 2}O{sub 7}) and cisplatin, miRNA-132-3p was upregulated 4.3-fold after AA treatment and 1.5-fold after K{sub 2}Cr{sub 2}O{sub 7} and CdCl{sub 2} treatment. These results demonstrate the application of temporal small RNA sequencing to identify miR-18a, miR-132 and miR-146b as differentially expressed miRNAs during distinct phases of kidney injury and fibrosis progression. - Highlights: • We used small RNA sequencing to identify differentially expressed miRNAs in kidney. • Distinct patterns were found for acute injury and fibrotic stages in the kidney. • Upregulation of miR-18a, -132 and -146b was confirmed in mice and human kidneys.« less

Acute Kidney Injury in Patients on SGLT2 Inhibitors: A Propensity-Matched Analysis.

PubMed

Nadkarni, Girish N; Ferrandino, Rocco; Chang, Alexander; Surapaneni, Aditya; Chauhan, Kinsuk; Poojary, Priti; Saha, Aparna; Ferket, Bart; Grams, Morgan E; Coca, Steven G

2017-11-01

Sodium-glucose cotransporter-2 (SGLT2) inhibitors are new medications that improve cardiovascular and renal outcomes in patients with type 2 diabetes (T2D). However, the Food and Drug Administration has issued alerts regarding increased acute kidney injury (AKI) risk with canagliflozin and dapagliflozin. We aimed to assess the real-world risk of AKI in new SGLT2 inhibitor users in two large health care utilization cohorts of patients with T2D. We used longitudinal data from the Mount Sinai chronic kidney disease registry and the Geisinger Health System cohort. We selected SGLT inhibitor users and nonusers (patients with T2D without SGLT2 inhibitor prescription). We determined AKI by the KDIGO (Kidney Disease: Improving Global Outcomes) definition (AKI KDIGO ). We performed 1:1 nearest-neighbor propensity matching and calculated unadjusted hazard ratios (HRs) and adjusted HRs (aHRs; accounting for covariates poorly balanced) for AKI in primary and sensitivity analyses. We identified 377 SGLT2 inhibitor users and 377 nonusers in the Mount Sinai cohort, of whom 3.8 and 9.7%, respectively, had an AKI KDIGO event over a median follow-up time of 14 months. The unadjusted hazards of AKI KDIGO were 60% lower in users (HR 0.4 [95% CI 0.2-0.7]; P = 0.01), which was unchanged (aHR 0.4 [95% CI 0.2-0.7]; P = 0.004) postadjustment. Similarly, we identified 1,207 SGLT2 inhibitor users and 1,207 nonusers in the Geisinger cohort, of whom 2.2 and 4.6% had an AKI KDIGO event. AKI KDIGO unadjusted hazards were lower in users (HR 0.5 [95% CI 0.3-0.8]; P < 0.01) with modest attenuation postadjustment for covariates (aHR 0.6 [95% CI 0.4-1.1]; P = 0.09). These estimates did not qualitatively change across several sensitivity analyses. Our findings do not suggest an increased risk of AKI associated with SGLT2 inhibitor use in patients with T2D in two large health systems. © 2017 by the American Diabetes Association.

Of Inflammasomes and Alarmins: IL-1β and IL-1α in Kidney Disease

PubMed Central

2016-01-01

Kidney injury implies danger signaling and a response by the immune system. The inflammasome is a central danger recognition platform that triggers local and systemic inflammation. In immune cells, inflammasome activation causes the release of mature IL-1β and of the alarmin IL-1α. Dying cells release IL-1α also, independently of the inflammasome. Both IL-1α and IL-1β ligate the same IL-1 receptor (IL-1R) that is present on nearly all cells inside and outside the kidney, further amplifying cytokine and chemokine release. Thus, the inflammasome-IL-1α/IL-β-IL-1R system is a central element of kidney inflammation and the systemic consequences. Seminal discoveries of recent years have expanded this central paradigm of inflammation. This review gives an overview of arising concepts of inflammasome and IL-1α/β regulation in renal cells and in experimental kidney disease models. There is a pipeline of compounds that can interfere with the inflammasome-IL-1α/IL-β-IL-1R system, ranging from recently described small molecule inhibitors of NLRP3, a component of the inflammasome complex, to regulatory agency–approved IL-1–neutralizing biologic drugs. Based on strong theoretic and experimental rationale, the potential therapeutic benefits of using such compounds to block the inflammasome-IL-1α/IL-β-IL-1R system in kidney disease should be further explored. PMID:27516236

Racial Differences in Estimated GFR Decline, ESRD, and Mortality in an Integrated Health System

PubMed Central

Derose, Stephen F.; Rutkowski, Mark P.; Crooks, Peter W.; Shi, Jiaxiao M.; Wang, Jean; Kalantar-Zadeh, Kamyar; Kovesdy, Csaba P.; Levin, Nathan W.; Jacobsen, Steven J.

2013-01-01

Background Current evidence does not clearly identify the contribution of kidney function decline and mortality to racial disparities in ESRD incidence. We used observed eGFR to project the time of onset of kidney failure and examined mortality to better understand these racial disparities. Study Design Retrospective cohort. Setting & Participants Adult members of Kaiser Permanente Southern California from 2003–2009 with >2 serum creatinine tests and >180 days between tests: 526,498 whites, 350,919 Hispanics, 136,923 blacks, and 105,476 Asians. Predictor Race/ethnicity. Outcomes ESRD (dialysis, transplantation); mortality. Measurements eGFR decline was modeled using linear regression. Kidney failure was projected based on predicted eGFR <15 mL/min/1.73m2 at specified times. Racial differences in projected kidney failure and mortality among those with projected kidney failure were estimated with adjustment for age, sex, and entry eGFR. Results Blacks had more extreme rates of eGFR decline (1st percentile, −23.6 mL/min/1.73m2 per year), followed by Hispanics (−20.9 mL/min/1.73m2 per year), whites (−20.1 mL/min/1.73m2 per year), and Asians (−17.6 mL/min/1.73m2 per year; P<0.001). There were 25,065 white, 11,368 Hispanic, 6,785 black, and 3,176 Asians with projected kidney failure during the study period. The ORs for projected kidney failure vs. whites during CKD stages 3 and 4 were 1.54 (95% CI, 1.46–1.62) in blacks, 1.49 (95% CI, 1.42–1.56) in Hispanics, and 1.41 (95% CI, 1.32–1.51) in Asians. Among those with projected kidney failure, the HRs of death vs. whites during CKD stages 3 and 4 were 0.82 (95% CI, 0.77–0.88) in blacks, 0.67 (95% CI, 0.63–0.72) in Hispanics, and 0.58 (95% CI, 0.52–0.65) in Asians. Limitations Results may not generalize to the uninsured or subgroups within a race. Projected kidney failure was based on linear trends from clinically obtained eGFR. Conclusions We found more extreme rates of eGFR decline in blacks. Projected kidney failure during CKD stages 3 and 4 was high in blacks, Hispanics, and Asians relative to whites. Mortality among those with projected kidney failure was highest in whites. Differences in eGFR decline and mortality contributed to racial disparities in ESRD incidence. PMID:23499049

Overcoming Barriers in Kidney Health-Forging a Platform for Innovation.

PubMed

Linde, Peter G; Archdeacon, Patrick; Breyer, Matthew D; Ibrahim, Tod; Inrig, Jula K; Kewalramani, Reshma; Lee, Celeste Castillo; Neuland, Carolyn Y; Roy-Chaudhury, Prabir; Sloand, James A; Meyer, Rachel; Smith, Kimberly A; Snook, Jennifer; West, Melissa; Falk, Ronald J

2016-07-01

Innovation in kidney diseases is not commensurate with the effect of these diseases on human health and mortality or innovation in other key therapeutic areas. A primary cause of the dearth in innovation is that kidney diseases disproportionately affect a demographic that is largely disenfranchised, lacking sufficient advocacy, public attention, and funding. A secondary and likely consequent cause is that the existing infrastructure supporting nephrology research pales in comparison with those for other internal medicine specialties, especially cardiology and oncology. Citing such inequities, however, is not enough. Changing the status quo will require a coordinated effort to identify and redress the existing deficits. Specifically, these deficits relate to the need to further develop and improve the following: understanding of the disease mechanisms and pathophysiology, patient engagement and activism, clinical trial infrastructure, and investigational clinical trial designs as well as coordinated efforts among critical stakeholders. This paper identifies potential solutions to these barriers, some of which are already underway through the Kidney Health Initiative. The Kidney Health Initiative is unique and will serve as a current and future platform from which to overcome these barriers to innovation in nephrology. Copyright © 2016 by the American Society of Nephrology.

A proposed new classification for the renal collecting system of cattle.

PubMed

Pereira-Sampaio, Marco A; Bagetti Filho, Helio J S; Carvalho, Francismar S; Sampaio, Francisco J B; Henry, Robert W

2010-11-01

To evaluate the intrarenal anatomy of kidneys obtained from cattle and to propose a new classification for the renal collecting system of cattle. 37 kidneys from 20 adult male mixed-breed cattle. Intrarenal anatomy was evaluated by the use of 3-D endocasts made of the kidneys. The number of renal lobes and minor renal calyces in each kidney and each renal region (cranial pole, caudal pole, and hilus) was quantified. The renal pelvis was evident in all casts and was classified into 2 types (nondilated [28/37 {75.7%}] or dilated [9/37 {24.3%}]). All casts had a major renal calyx associated with the cranial pole and the caudal pole. The number of minor renal calices per kidney ranged from 13 to 64 (mean, 22.7). There was a significant correlation between the number of renal lobes and the number of minor renal calices for the entire kidney, the cranial pole region, and the hilus region; however, there was not a similar significant correlation for the caudal pole region. Major and minor renal calices were extremely narrow, compared with major and minor renal calices in pigs and humans. The renal collecting system of cattle, with a renal pelvis and 2 major renal calices connected to several minor renal calices by an infundibulum, differed substantially from the renal collecting system of pigs and humans. From a morphological standpoint, the kidneys of cattle were not suitable for use as a model in endourologic research and training.

Inflammation and hypoxia in the kidney: friends or foes?

PubMed

Haase, Volker H

2015-08-01

Hypoxic injury is commonly associated with inflammatory-cell infiltration, and inflammation frequently leads to the activation of cellular hypoxia response pathways. The molecular mechanisms underlying this cross-talk during kidney injury are incompletely understood. Yamaguchi and colleagues identify CCAAT/enhancer-binding protein δ as a cytokine- and hypoxia-regulated transcription factor that fine-tunes hypoxia-inducible factor-1 signaling in renal epithelial cells and thus provide a novel molecular link between hypoxia and inflammation in kidney injury.

Evolutionary trade-offs in kidney injury and repair.

PubMed

Lei, Yutian; Anders, Hans-Joachim

2017-11-01

Evolutionary medicine has proven helpful to understand the origin of human disease, e.g. in identifying causal roles of recent environmental changes impacting on human physiology (environment-phenotype mismatch). In contrast, diseases affecting only a limited number of members of a species often originate from evolutionary trade-offs for usually physiologic adaptations assuring reproductive success in the context of extrinsic threats. For example, the G1 and G2 variants of the APOL1 gene supporting control of Trypanosoma infection come with the trade-off that they promote the progression of kidney disease. In this review we extend the concept of evolutionary nephrology by discussing how the physiologic adaptations (danger responses) to tissue injury create evolutionary trade-offs that drive histopathological changes underlying acute and chronic kidney diseases. The evolution of multicellular organisms positively selected a number of danger response programs for their overwhelming benefits in assuring survival such as clotting, inflammation, epithelial healing and mesenchymal healing, i.e. fibrosis and sclerosis. Upon kidney injury these danger programs often present as pathomechanisms driving persistent nephron loss and renal failure. We explore how classic kidney disease entities involve insufficient or overshooting activation of these danger response programs for which the underlying genetic basis remains largely to be defined. Dissecting the causative and hierarchical relationships between danger programs should help to identify molecular targets to control kidney injury and to improve disease outcomes.

Common Variants in Mendelian Kidney Disease Genes and Their Association with Renal Function

PubMed Central

Fuchsberger, Christian; Köttgen, Anna; O’Seaghdha, Conall M.; Pattaro, Cristian; de Andrade, Mariza; Chasman, Daniel I.; Teumer, Alexander; Endlich, Karlhans; Olden, Matthias; Chen, Ming-Huei; Tin, Adrienne; Kim, Young J.; Taliun, Daniel; Li, Man; Feitosa, Mary; Gorski, Mathias; Yang, Qiong; Hundertmark, Claudia; Foster, Meredith C.; Glazer, Nicole; Isaacs, Aaron; Rao, Madhumathi; Smith, Albert V.; O’Connell, Jeffrey R.; Struchalin, Maksim; Tanaka, Toshiko; Li, Guo; Hwang, Shih-Jen; Atkinson, Elizabeth J.; Lohman, Kurt; Cornelis, Marilyn C.; Johansson, Åsa; Tönjes, Anke; Dehghan, Abbas; Couraki, Vincent; Holliday, Elizabeth G.; Sorice, Rossella; Kutalik, Zoltan; Lehtimäki, Terho; Esko, Tõnu; Deshmukh, Harshal; Ulivi, Sheila; Chu, Audrey Y.; Murgia, Federico; Trompet, Stella; Imboden, Medea; Kollerits, Barbara; Pistis, Giorgio; Harris, Tamara B.; Launer, Lenore J.; Aspelund, Thor; Eiriksdottir, Gudny; Mitchell, Braxton D.; Boerwinkle, Eric; Schmidt, Helena; Hofer, Edith; Hu, Frank; Demirkan, Ayse; Oostra, Ben A.; Turner, Stephen T.; Ding, Jingzhong; Andrews, Jeanette S.; Freedman, Barry I.; Giulianini, Franco; Koenig, Wolfgang; Illig, Thomas; Döring, Angela; Wichmann, H.-Erich; Zgaga, Lina; Zemunik, Tatijana; Boban, Mladen; Minelli, Cosetta; Wheeler, Heather E.; Igl, Wilmar; Zaboli, Ghazal; Wild, Sarah H.; Wright, Alan F.; Campbell, Harry; Ellinghaus, David; Nöthlings, Ute; Jacobs, Gunnar; Biffar, Reiner; Ernst, Florian; Homuth, Georg; Kroemer, Heyo K.; Nauck, Matthias; Stracke, Sylvia; Völker, Uwe; Völzke, Henry; Kovacs, Peter; Stumvoll, Michael; Mägi, Reedik; Hofman, Albert; Uitterlinden, Andre G.; Rivadeneira, Fernando; Aulchenko, Yurii S.; Polasek, Ozren; Hastie, Nick; Vitart, Veronique; Helmer, Catherine; Wang, Jie Jin; Stengel, Bénédicte; Ruggiero, Daniela; Bergmann, Sven; Kähönen, Mika; Viikari, Jorma; Nikopensius, Tiit; Province, Michael; Colhoun, Helen; Doney, Alex; Robino, Antonietta; Krämer, Bernhard K.; Portas, Laura; Ford, Ian; Buckley, Brendan M.; Adam, Martin; Thun, Gian-Andri; Paulweber, Bernhard; Haun, Margot; Sala, Cinzia; Mitchell, Paul; Ciullo, Marina; Vollenweider, Peter; Raitakari, Olli; Metspalu, Andres; Palmer, Colin; Gasparini, Paolo; Pirastu, Mario; Jukema, J. Wouter; Probst-Hensch, Nicole M.; Kronenberg, Florian; Toniolo, Daniela; Gudnason, Vilmundur; Shuldiner, Alan R.; Coresh, Josef; Schmidt, Reinhold; Ferrucci, Luigi; van Duijn, Cornelia M.; Borecki, Ingrid; Kardia, Sharon L.R.; Liu, Yongmei; Curhan, Gary C.; Rudan, Igor; Gyllensten, Ulf; Wilson, James F.; Franke, Andre; Pramstaller, Peter P.; Rettig, Rainer; Prokopenko, Inga; Witteman, Jacqueline; Hayward, Caroline; Ridker, Paul M.; Bochud, Murielle; Heid, Iris M.; Siscovick, David S.; Fox, Caroline S.; Kao, W. Linda; Böger, Carsten A.

2013-01-01

Many common genetic variants identified by genome-wide association studies for complex traits map to genes previously linked to rare inherited Mendelian disorders. A systematic analysis of common single-nucleotide polymorphisms (SNPs) in genes responsible for Mendelian diseases with kidney phenotypes has not been performed. We thus developed a comprehensive database of genes for Mendelian kidney conditions and evaluated the association between common genetic variants within these genes and kidney function in the general population. Using the Online Mendelian Inheritance in Man database, we identified 731 unique disease entries related to specific renal search terms and confirmed a kidney phenotype in 218 of these entries, corresponding to mutations in 258 genes. We interrogated common SNPs (minor allele frequency >5%) within these genes for association with the estimated GFR in 74,354 European-ancestry participants from the CKDGen Consortium. However, the top four candidate SNPs (rs6433115 at LRP2, rs1050700 at TSC1, rs249942 at PALB2, and rs9827843 at ROBO2) did not achieve significance in a stage 2 meta-analysis performed in 56,246 additional independent individuals, indicating that these common SNPs are not associated with estimated GFR. The effect of less common or rare variants in these genes on kidney function in the general population and disease-specific cohorts requires further research. PMID:24029420

Hydrogen Sulfide in Renal Physiology and Disease.

PubMed

Feliers, Denis; Lee, Hak Joo; Kasinath, Balakuntalam S

2016-11-01

Hydrogen sulfide (H2S) has only recently gained recognition for its physiological effects. It is synthesized widely in the mammalian tissues and regulates several biologic processes ranging from development, angiogenesis, neurotransmission to protein synthesis. Recent Advances: The aim of this review is to critically evaluate the evidence for a role for H2S in kidney function and disease. H2S regulates fundamental kidney physiologic processes such as glomerular filtration and sodium reabsorption. In kidney disease states H2S appears to play a complex role in a context-dependent manner. In some disease states such as ischemia-reperfusion and diabetic kidney disease it can serve as an agent that ameliorates kidney injury. In other diseases such as cis-platinum-induced kidney disease it may mediate kidney injury although more investigation is needed. Recent studies have revealed that the actions of nitric oxide and H2S may be integrated in kidney cells. Further studies are needed to understand the full impact of H2S on kidney physiology. As it is endowed with the properties of regulating blood flow, oxidative stress, and inflammation, H2S should be investigated for its role in inflammatory and toxic diseases of the kidney. Such in-depth exploration may identify specific kidney diseases in which H2S may constitute a unique target for therapeutic intervention. Antioxid. Redox Signal. 25, 720-731.

[The occurrence of dioctophymosis in dogs from Municipality of Cachoeiro do Itapemirim in the State of Espírito Santo, Brazil, from May to December of 2004].

PubMed

Pereira, Bruna J; Girardelli, Giovani L; Trivilin, Leonardo O; Lima, Vanessa R; Nunes, Louisiane de C; Martins, Isabella V F

2006-01-01

Dioctophyma renale is frequently observed in dogs from rural areas. From a total of 67 necropsies carried out from May to December of 2004, 56 were dogs, which came from the minicipality of Cachoeiro do Itapemirim, two animals parasited for D. renale. In one of these animals in a mass of epiplon a nematode female of 15 cm of length was found in ectopic position. The right kidney was atrophic and with the presence of 2 females (58 and 50 cm) and 2 males (21 cm each). In the second animal, the kidneys were morphologically different. The left kidney was presented hypertrophic, while right kidney was observed a female with 45 cm. The recovered helminths were identified and fixed in AFA. During the ovariectomy of a dog of the same region a male nematode of approximately 20 cm was found in site the abdominal cavity. All of them were identified as D. renale.

The systemic nature of CKD.

PubMed

Zoccali, Carmine; Vanholder, Raymond; Massy, Ziad A; Ortiz, Alberto; Sarafidis, Pantelis; Dekker, Friedo W; Fliser, Danilo; Fouque, Denis; Heine, Gunnar H; Jager, Kitty J; Kanbay, Mehmet; Mallamaci, Francesca; Parati, Gianfranco; Rossignol, Patrick; Wiecek, Andrzej; London, Gerard

2017-06-01

The accurate definition and staging of chronic kidney disease (CKD) is one of the major achievements of modern nephrology. Intensive research is now being undertaken to unravel the risk factors and pathophysiologic underpinnings of this disease. In particular, the relationships between the kidney and other organs have been comprehensively investigated in experimental and clinical studies in the last two decades. Owing to technological and analytical limitations, these links have been studied with a reductionist approach focusing on two organs at a time, such as the heart and the kidney or the bone and the kidney. Here, we discuss studies that highlight the complex and systemic nature of CKD. Energy balance, innate immunity and neuroendocrine signalling are highly integrated biological phenomena. The diseased kidney disrupts such integration and generates a high-risk phenotype with a clinical profile encompassing inflammation, protein-energy wasting, altered function of the autonomic and central nervous systems and cardiopulmonary, vascular and bone diseases. A systems biology approach to CKD using omics techniques will hopefully enable in-depth study of the pathophysiology of this systemic disease, and has the potential to unravel critical pathways that can be targeted for CKD prevention and therapy.

Association between Organ Procurement Organization Social Network Centrality and Kidney Discard and Transplant Outcomes1

PubMed Central

Butala, Neel M.; King, Marissa D.; Reitsma, William; Formica, Richard N.; Abt, Peter L.; Reese, Peter P.; Parikh, Chirag R.

2015-01-01

Background Given growth in kidney transplant waitlists and discard rates, donor kidney acceptance is an important problem. We used network analysis to examine whether organ procurement organization (OPO) network centrality affects discard and outcomes. Methods We identified 106,160 deceased-donor kidneys recovered for transplant from 2000–2010 in SRTR. We constructed the transplant network by year with each OPO representing a node and each kidney-sharing relationship between OPOs representing a directed tie between nodes. Primary exposures were the number of different OPOs to which an OPO has given a kidney or from which an OPO has received a kidney in year preceding procurement year. Primary outcomes were discard, cold-ischemia time, delayed graft function, and 1-year graft loss. We used multivariable regression, restricting analysis to the 50% of OPOs with highest discard and stratifying remaining OPOs by kidney volume. Models controlled for kidney donor risk index, waitlist time, and kidney pumping. Results An increase in one additional OPO to which a kidney was given by a procuring OPO in a year was associated with 1.4% lower likelihood of discard for a given kidney (odds ratio, 0.986; 95% confidence interval, 0.974-0.998) among OPOs procuring high kidney volume, but 2% higher likelihood of discard (OR:1.021, CI:1.006, 1.037) among OPOs procuring low kidney volume, with mixed associations with recipient outcomes. Conclusions Our study highlights the value of network analysis in revealing how broader kidney sharing is associated with levels of organ acceptance. We conclude interventions to promote broader inter-OPO sharing could be developed to reduce discard for a subset of OPOs. PMID:26102610

Is Fibroblast growth factor 23 the leading cause of increased mortality among chronic kidney disease patients? A narrative review.

PubMed

Sharaf El Din, Usama A; Salem, Mona M; Abdulazim, Dina O

2017-05-01

The death rate among chronic kidney disease patients is the highest compared to other chronic diseases. 60% of these fatalities are cardiovascular. Cardiovascular calcifications and chronic inflammation affect almost all chronic kidney disease patients and are associated with cardiovascular mortality. Fibroblast growth factor 23 is associated with vascular calcification. Systemic inflammation in chronic kidney disease patients is multifactorial. The role of systemic inflammation in the pathogenesis of vascular calcification was recently reappraised. Fibroblast growth factor 23 was accused as a direct stimulus of left ventricular hypertrophy, uremic inflammation, and impaired neutrophil function. This review will discuss the underlying mechanisms that underlie the link between Fibroblast growth factor 23 and increased mortality encountered among chronic kidney disease patients.

A roadmap for the genetic analysis of renal aging

PubMed Central

Noordmans, Gerda A; Hillebrands, Jan-Luuk; van Goor, Harry; Korstanje, Ron

2015-01-01

Several studies show evidence for the genetic basis of renal disease, which renders some individuals more prone than others to accelerated renal aging. Studying the genetics of renal aging can help us to identify genes involved in this process and to unravel the underlying pathways. First, this opinion article will give an overview of the phenotypes that can be observed in age-related kidney disease. Accurate phenotyping is essential in performing genetic analysis. For kidney aging, this could include both functional and structural changes. Subsequently, this article reviews the studies that report on candidate genes associated with renal aging in humans and mice. Several loci or candidate genes have been found associated with kidney disease, but identification of the specific genetic variants involved has proven to be difficult. CUBN, UMOD, and SHROOM3 were identified by human GWAS as being associated with albuminuria, kidney function, and chronic kidney disease (CKD). These are promising examples of genes that could be involved in renal aging, and were further mechanistically evaluated in animal models. Eventually, we will provide approaches for performing genetic analysis. We should leverage the power of mouse models, as testing in humans is limited. Mouse and other animal models can be used to explain the underlying biological mechanisms of genes and loci identified by human GWAS. Furthermore, mouse models can be used to identify genetic variants associated with age-associated histological changes, of which Far2, Wisp2, and Esrrg are examples. A new outbred mouse population with high genetic diversity will facilitate the identification of genes associated with renal aging by enabling high-resolution genetic mapping while also allowing the control of environmental factors, and by enabling access to renal tissues at specific time points for histology, proteomics, and gene expression. PMID:26219736

Follow-up imaging of the urinary tract in spinal injury patients: is a KUB necessary with every ultrasound?

PubMed

Tins, B; Teo, H-G; Popuri, R; Cassar-Pullicino, V; Tyrrell, P

2005-04-01

Prospective study of 100 consecutive patients. To evaluate the diagnostic usefulness of the urinary tract (KUB) radiograph routinely performed as part of spinal injury patient urinary tract screening with ultrasound (US) and the KUB radiograph. Orthopaedic and District General Hospital with spinal injuries unit, UK. Prospective study of the urinary tract of 100 consecutive routine follow-up spinal injury patients with KUB (kidneys, ureters, bladder) radiograph and US of the urinary tract. The percentage of the visualised area of kidneys and urinary bladder and relevant abnormal findings were recorded. Relevant patient history was recorded. In all, 80 men 20 women were examined (average age 46 years, average time since injury 11 years). A total of 199 kidneys and 99 urinary bladders were examined. On average, less than 50% of the renal area and about 70-75% of the urinary bladder area were visualised. Five patients had renal stones identified on the KUB radiograph, and of these two were seen on US. There were no stones seen on US only. The patient history was not helpful to identify patients with renal stones. Significant further renal abnormalities were identified with US in 14 patients, and with the KUB radiograph in 0 patients. Significant urinary bladder abnormalities were identified with US in 20 patients, and with the KUB radiograph in 0 patients. On average, less than 50% of the kidney area is visualised on the KUB due to overlying bowel markings making the KUB radiograph a poor tool to assess the kidneys. The KUB radiograph and US are poor tools to assess urinary tract stones. In the absence of a therapeutic consequence, the KUB radiograph does not seem justified in the routine follow-up of the urinary tract in spinal injury patients.

Synthetic marijuana and acute kidney injury: an unforeseen association.

PubMed

Kazory, Amir; Aiyer, Ravi

2013-06-01

Synthetic cannabinoids (SCs) have emerged as drugs of abuse with increasing popularity among young adults. The potential renal complication related to the abuse of SC was not recognized until recently. Here, we present a case of severe acute kidney injury (AKI) that developed after inhalation of SC in an otherwise healthy young patient. A kidney biopsy revealed severe acute tubular necrosis, and supportive management resulted in the recovery of the kidney function. Herein, we briefly summarize the only two previous reports (a total of 21 cases) on the association between SC abuse and renal dysfunction and identify the common aspects in all observations.

Effect of Chronic Kidney Diseases on Mortality among Digoxin Users Treated for Non-Valvular Atrial Fibrillation: A Nationwide Register-Based Retrospective Cohort Study.

PubMed

Sessa, Maurizio; Mascolo, Annamaria; Andersen, Mikkel Porsborg; Rosano, Giuseppe; Rossi, Francesco; Capuano, Annalisa; Torp-Pedersen, Christian

2016-01-01

This study investigated the impact of chronic kidney disease on all-causes and cardiovascular mortality in patients with atrial fibrillation treated with digoxin. All patients with non-valvular atrial fibrillation and/or atrial flutter as hospitalization diagnosis from January 1, 1997 to December 31, 2012 were identified in Danish nationwide administrative registries. Cox proportional hazard model was used to compare the adjusted risk of all-causes and cardiovascular mortality among patients with and without chronic kidney disease and among patients with different chronic kidney disease stages within 180 days and 2 years from the first digoxin prescription. We identified 37,981 patients receiving digoxin; 1884 patients had the diagnosis of chronic kidney disease. Cox regression analysis showed no statistically significant differences in all-causes (Hazard Ratio, HR 0.89; 95% confident interval, CI 0.78-1.03) and cardiovascular mortality (HR 0.88; 95%CI 0.74-1.05) among patients with and without chronic kidney disease within 180 days of follow-up period. No statistically significant differences was found using a 2 years follow-up period neither for all causes mortality (HR 0.90; 95%CI 0.79-1.03), nor for cardiovascular mortality (HR 0.87; 95%CI 0.74-1.02). No statistically significant differences was found comparing patients with and without estimated Glomerular Filtration Rate <30ml/min/1.73m2 and patients with different stages of chronic kidney disease, for all-causes and cardiovascular mortality within 180 days and 2 years from the first digoxin prescription. This study suggest no direct effect of chronic kidney disease and chronic kidney disease stages on all-causes and cardiovascular mortality within both 180 days and 2 years from the first digoxin prescription in patients treatment-naïve with digoxin for non-valvular atrial fibrillation.

Kidney Transplant Access in the Southeast: View From the Bottom

PubMed Central

Patzer, R. E.; Pastan, S. O.

2014-01-01

The Southeastern region of the United States has the highest burden of end-stage renal disease (ESRD) but the lowest rates of kidney transplantation in the nation. There are many patient-, dialysis facility–, ESRD Network– and health system–level barriers that contribute to this regional disparity. Compared to the rest of the nation, the Southeast has a larger population of African-Americans and higher poverty, as well as more prevalent ESRD risk factors including hypertension, obesity and diabetes. Dialysis facilities—where ESRD patients receive the majority of their healthcare—play an important role in transplant access. Identifying characteristics of individual dialysis units with low rates of kidney transplantation, such as understaffing or for-profit status, can help identify targets for quality improvement initiatives. Geographic differences across the country can identify opportunities to increase funding for healthcare resources in proportion to patient and disease burden. Focusing interventions among dialysis facilities with the lowest transplant rates within the Southeast, such as provider and patient education, has the potential to increase referrals for kidney transplantation, leading to higher rates of kidney transplants in this region. Referral for transplantation should be measured on a national level to monitor disparities in early access to transplantation. Transplant centers have an obligation to assist under-served populations in ensuring equity in access to services. Policies that improve access to care for patients, such as the Affordable Care Act and Medicaid expansion, are particularly important for Southern states and may alleviate geographic disparities. PMID:24891223

A priori and a posteriori approaches for finding genes of evolutionary interest in non-model species: osmoregulatory genes in the kidney transcriptome of the desert rodent Dipodomys spectabilis (banner-tailed kangaroo rat).

PubMed

Marra, Nicholas J; Eo, Soo Hyung; Hale, Matthew C; Waser, Peter M; DeWoody, J Andrew

2012-12-01

One common goal in evolutionary biology is the identification of genes underlying adaptive traits of evolutionary interest. Recently next-generation sequencing techniques have greatly facilitated such evolutionary studies in species otherwise depauperate of genomic resources. Kangaroo rats (Dipodomys sp.) serve as exemplars of adaptation in that they inhabit extremely arid environments, yet require no drinking water because of ultra-efficient kidney function and osmoregulation. As a basis for identifying water conservation genes in kangaroo rats, we conducted a priori bioinformatics searches in model rodents (Mus musculus and Rattus norvegicus) to identify candidate genes with known or suspected osmoregulatory function. We then obtained 446,758 reads via 454 pyrosequencing to characterize genes expressed in the kidney of banner-tailed kangaroo rats (Dipodomys spectabilis). We also determined candidates a posteriori by identifying genes that were overexpressed in the kidney. The kangaroo rat sequences revealed nine different a priori candidate genes predicted from our Mus and Rattus searches, as well as 32 a posteriori candidate genes that were overexpressed in kidney. Mutations in two of these genes, Slc12a1 and Slc12a3, cause human renal diseases that result in the inability to concentrate urine. These genes are likely key determinants of physiological water conservation in desert rodents. Copyright © 2012 Elsevier Inc. All rights reserved.

New Organ Allocation System for Combined Liver-Kidney Transplants and the Availability of Kidneys for Transplant to Patients with Stage 4-5 CKD.

PubMed

Asch, William S; Bia, Margaret J

2017-05-08

A new proposal has been created for establishing medical criteria for organ allocation in recipients receiving simultaneous liver-kidney transplants. In this article, we describe the new policy, elaborate on the points of greatest controversy, and offer a perspective on the policy going forward. Although we applaud the fact that simultaneous liver-kidney transplant activity will now be monitored and appreciate the creation of medical criteria for allocation in simultaneous liver-kidney transplants, we argue that some of the criteria proposed, especially those for allocating a kidney to a liver recipient with AKI, are too liberal. We call on the nephrology community to follow the consequences of this new policy and push for a re-examination of the longstanding policy of allocating kidneys to multiorgan transplant recipients before all other candidates. The charge to protect our system of equitable organ allocation is very challenging, but it is a challenge that we must embrace. Copyright © 2017 by the American Society of Nephrology.

Candidacy for Kidney Transplantation of Older Adults

PubMed Central

Grams, Morgan E.; Kucirka, Lauren M.; Hanrahan, Colleen F.; Montgomery, Robert A.; Massie, Allan B.; Segev, Dorry L.

2013-01-01

OBJECTIVES To develop a prediction model for kidney transplantation (KT) outcomes specific to older adults with end-stage renal disease (ESRD) and to use this model to estimate the number of excellent older KT candidates who lack access to KT. DESIGN Secondary analysis of data collected by the United Network for Organ Sharing and U.S. Renal Disease System. SETTING Retrospective analysis of national registry data. PARTICIPANTS Model development: Medicare-primary older recipients (aged ≥ 65) of a first KT between 1999 and 2006 (N = 6,988). Model application: incident Medicare-primary older adults with ESRD between 1999 and 2006 without an absolute or relative contraindication to transplantation (N = 128,850). MEASUREMENTS Comorbid conditions were extracted from U.S. Renal Disease System Form 2728 data and Medicare claims. RESULTS The prediction model used 19 variables to estimate post-KT outcome and showed good calibration (Hosmer–Lemeshow P = .44) and better prediction than previous population-average models (P < .001). Application of the model to the population with incident ESRD identified 11,756 excellent older transplant candidates (defined as >87% predicted 3-year post-KT survival, corresponding to the top 20% of transplanted older adults used in model development), of whom 76.3% (n = 8,966) lacked access. It was estimated that 11% of these candidates would have identified a suitable live donor had they been referred for KT. CONCLUSION A risk-prediction model specific to older adults can identify excellent KT candidates. Appropriate referral could result in significantly greater rates of KT in older adults. PMID:22239290

Recent advances in kidney transplantation: a viewpoint from the Descartes advisory board.

PubMed

Abramowicz, Daniel; Oberbauer, Rainer; Heemann, Uwe; Viklicky, Ondrej; Peruzzi, Licia; Mariat, Christophe; Crespo, Marta; Budde, Klemens; Oniscu, Gabriel C

2018-01-12

Transplantation medicine is a rapidly evolving field. Keeping afloat of the published literature to offer the best clinical care to our patients is a daunting task. As part of its educational mission, the Descartes advisory board identified seven topics in kidney transplantation where there has been substantial progresses over the last years: kidney allocation within Eurotransplant; kidney exchange strategies; kidney machine perfusion strategies; the changing landscape of anti-human leukocyte antigen (HLA) antibodies; the new immunosuppressive drugs in the pipeline; strategies for immunosuppression minimization; and the continuous enigma of focal segmental glomerular sclerosis recurrence after transplantation. Here, we have summarized the main knowledge and the main challenges of these seven topics with the aim to provide transplant professionals at large with key bullet points to successfully understand these new concepts.

Perioperative Acute Kidney Injury: Prevention, Early Recognition, and Supportive Measures.

PubMed

Romagnoli, Stefano; Ricci, Zaccaria; Ronco, Claudio

2018-06-26

Acute kidney injury (AKI) is a frequent complication of both cardiac and major non-cardiac surgery. AKI is independently associated with morbidity, mortality, and long-term adverse events including chronic kidney disease in postsurgical patients. Since specific treatment options for kidney failure are very limited, early identification, diagnosis, and renal support strategies are key steps to improve patients' outcome. According to current Kidney Disease: Improving Global Outcomes (KDIGO) guidelines, AKI diagnosis is based on 2 functional markers, serum creatinine increase and urine output decrease, that are not renal-specific and have important limitations. However, preoperative risk stratification for postoperative AKI and/or early diagnosis after surgery could be the best way to apply preventive or timely supportive therapeutic measures. Clinical prediction scores, renal functional reserve assessment, and new biomarkers of kidney stress (suppression of tumorigenicity-2, insulin-like growth factor binding protein-7, tissue inhibitor metalloproteinase-2) may help the clinicians to identify patients at risk of AKI and that could benefit from the application of nephroprotective bundles suggested by the KDIGO guidelines. In severe AKI patients with oligoanuria and fluid accumulation, renal replacement therapy is the only supportive measure even if mode and timing remain open to investigation. Key messages: Perioperative AKI is an important and underdiagnosed complication. Identifying patients at high risk of AKI and diagnosing AKI early are major goals. Preventive interventions are mainly based on the KDIGO guidelines and bundles. Furthermore, a personalized multidisciplinary approach should always be considered to minimize the progression of disease and the complications related to kidney damage. © 2018 S. Karger AG, Basel.

A protein with anion exchange properties found in the kidney proximal tubule.

PubMed

Soleimani, M; Bizal, G L; Anderson, C C

1993-09-01

One important mechanism for reabsorption of chloride in the kidney proximal tubule involves anion exchange of chloride for a base. Anion exchange transport systems in general demonstrate sensitivity to inhibition by disulfonic stilbenes, probenecid, furosemide, and the arginyl amino group modifier phenylglyoxal. Using disulfonic stilbene affinity chromatography, we have identified and partially purified a protein with anion exchanger properties in luminal membrane vesicles isolated from rabbit kidney cortex. This protein has a molecular weight of 162 kD. The binding of the 162 kD protein to the stilbene affinity matrix is inhibited by disulfonic stilbenes, probenecid, furosemide, and phenylglyoxal. Reconstitution of the proteins eluted from the affinity matrix into liposomes demonstrates anion exchange activity as assayed by radiolabeled chloride influx. Deletion of the 162 kD protein from the eluted mixture by probenecid diminishes the anion exchanger activity in the reconstituted liposomes. Further purification of the disulfonic stilbene column eluant by Econo-Pac Q ion exchange chromatography resulted in significant enrichment in 162 kD protein abundance and also anion exchange activity in reconstituted liposomes. The results of the above experiments strongly suggest that the 162 kD protein is an anion exchanger. Insight into the functional and molecular characteristics of this protein should provide important information about the mechanism(s) of chloride reabsorption in the kidney proximal tubule.

Transcriptome analysis of grey mullet (Mugil cephalus) after challenge with Lactococcus garvieae.

PubMed

Byadgi, Omkar; Chen, Yao-Chung; Barnes, Andrew C; Tsai, Ming-An; Wang, Pei-Chyi; Chen, Shih-Chu

2016-11-01

Grey mullet (Mugil cephalus) is an economically important fish species in Taiwan mariculture industry. Moreover, grey mullet are common hosts of a bacterial infection by Lactococcus garvieae. However, until now the information related to the immune system of grey mullet is unclear. Therefore, to understand the molecular basis underlying the host immune response to L. garvieae infection, Illumina HiSeq™ 2000 was used to analyse the head kidney and spleen transcriptome of infected grey mullet. De novo assembly of paired-end reads yielded 55,203 unigenes. Comparative analysis of the expression profiles between bacterial challenge fish and control fish identified a total of 7192 from head kidney and 7280 in spleen differentially expressed genes (P < 0.05), including 4211 upregulated genes and 2981 downregulated genes in head kidney, while in spleen 3598 genes were upregulated and 3682 downregulated. A significant enrichment analysis of these differentially expressed genes (DEG) in spleen and head kidney revealed major immune-related pathways, including complement and coagulation cascades, Toll-like receptor signalling, and antigen processing and presentation. Moreover, selected DEGs were validated using qPCR. Altogether, the results obtained on immune-related genes may allow for a better understanding of immunity in grey mullet to Lactococcus garvieae, carrying out detailed functional analysis of these genes and developing strategies for efficient immune protection against infections in grey mullet. Crown Copyright © 2016. Published by Elsevier Ltd. All rights reserved.

Cross-study and cross-omics comparisons of three nephrotoxic compounds reveal mechanistic insights and new candidate biomarkers

DOE Office of Scientific and Technical Information (OSTI.GOV)

Matheis, Katja A., E-mail: katja.matheis@boehringer-ingelheim.com; Com, Emmanuelle; High-Throughput Proteomics Core Facility OUEST-genopole

2011-04-15

The European InnoMed-PredTox project was a collaborative effort between 15 pharmaceutical companies, 2 small and mid-sized enterprises, and 3 universities with the goal of delivering deeper insights into the molecular mechanisms of kidney and liver toxicity and to identify mechanism-linked diagnostic or prognostic safety biomarker candidates by combining conventional toxicological parameters with 'omics' data. Mechanistic toxicity studies with 16 different compounds, 2 dose levels, and 3 time points were performed in male Crl: WI(Han) rats. Three of the 16 investigated compounds, BI-3 (FP007SE), Gentamicin (FP009SF), and IMM125 (FP013NO), induced kidney proximal tubule damage (PTD). In addition to histopathology and clinicalmore » chemistry, transcriptomics microarray and proteomics 2D-DIGE analysis were performed. Data from the three PTD studies were combined for a cross-study and cross-omics meta-analysis of the target organ. The mechanistic interpretation of kidney PTD-associated deregulated transcripts revealed, in addition to previously described kidney damage transcript biomarkers such as KIM-1, CLU and TIMP-1, a number of additional deregulated pathways congruent with histopathology observations on a single animal basis, including a specific effect on the complement system. The identification of new, more specific biomarker candidates for PTD was most successful when transcriptomics data were used. Combining transcriptomics data with proteomics data added extra value.« less

Quantitative Enzymatic and Immunologic Histophotometry of Diseased Human Kid-Ney Tissues Using Tv-Camera and Computer Assisted Image Processing Systems.

NASA Astrophysics Data System (ADS)

Heinert, G.; Mondorf, W.

1982-11-01

High speed image processing was used to analyse morphologic and metabolic characteristics of clinically relevant kidney tissue alterations.Qualitative computer-assisted histophotometry was performed to measure alterations in levels of the enzymes alkaline phosphatase (Ap),alanine aminopeptidase (AAP),g-glutamyltranspepti-dase (GGTP) and A-glucuronidase (B-G1) and AAP and GGTP immunologically determined in prepared renal and cancer tissue sections. A "Mioro-Videomat 2" image analysis system with a "Tessovar" macroscope,a computer-assisted "Axiomat" photomicroscope and an "Interactive Image Analysis System (IBAS)" were employed for analysing changes in enzyme activities determined by changes in absorbance or transmission.Diseased kidney as well as renal neoplastic tissues could be distinguished by significantly (wilcoxon test,p<0,05) decreased enzyme concentrations as compared to those found in normal human kidney tissues.This image analysis techniques might be of potential use in diagnostic and prognostic evaluation of renal cancer and diseased kidney tissues.

Pathogenesis of Chronic Cardiorenal Syndrome: Is There a Role for Oxidative Stress?

PubMed Central

Rubattu, Speranza; Mennuni, Silvia; Testa, Marco; Mennuni, Mara; Pierelli, Giorgia; Pagliaro, Beniamino; Gabriele, Erica; Coluccia, Roberta; Autore, Camillo; Volpe, Massimo

2013-01-01

Cardiorenal syndrome is a frequently encountered clinical condition when the dysfunction of either the heart or kidneys amplifies the failure progression of the other organ. Complex biochemical, hormonal and hemodynamic mechanisms underlie the development of cardiorenal syndrome. Both in vitro and experimental studies have identified several dysregulated pathways in heart failure and in chronic kidney disease that lead to increased oxidative stress. A decrease in mitochondrial oxidative metabolism has been reported in cardiomyocytes during heart failure. This is balanced by a compensatory increase in glucose uptake and glycolysis with consequent decrease in myocardial ATP content. In the kidneys, both NADPH oxidase and mitochondrial metabolism are important sources of TGF-β1-induced cellular ROS. NOX-dependent oxidative activation of transcription factors such as NF-kB and c-jun leads to increased expression of renal target genes (phospholipaseA2, MCP-1 and CSF-1, COX-2), thus contributing to renal interstitial fibrosis and inflammation. In the present article, we postulate that, besides contributing to both cardiac and renal dysfunction, increased oxidative stress may also play a crucial role in cardiorenal syndrome development and progression. In particular, an imbalance between the renin-angiotensin-aldosterone system, the sympathetic nervous system, and inflammation may favour cardiorenal syndrome through an excessive oxidative stress production. This article also discusses novel therapeutic strategies for their potential use in the treatment of patients affected by cardiorenal syndrome. PMID:24264044

The Immune System in Hypertension

ERIC Educational Resources Information Center

Trott, Daniel W.; Harrison, David G.

2014-01-01

While hypertension has predominantly been attributed to perturbations of the vasculature, kidney, and central nervous system, research for almost 50 yr has shown that the immune system also contributes to this disease. Inflammatory cells accumulate in the kidneys and vasculature of humans and experimental animals with hypertension and likely…

Analysis of the Results of ABO-Incompatible Kidney Transplantation: In Comparison with ABO-Compatible Kidney Transplantation

PubMed Central

Jeon, Byung Joo; Seong, Youl Keun; Han, Bo Hyun

2010-01-01

Purpose The number of patients waiting for kidney transplantation is incessantly increasing, but the number of cadaveric kidney transplantations or ABO-compatible donors is so insufficient that ABO-incompatible kidney transplantation is being performed as an alternative. There are overseas studies and research showing that the 5-year survival rate and 5-year graft survival rate of ABO-incompatible kidney transplantation are not much different from those of ABO-compatible kidney transplantation. However, domestic research on the subject is rare. Therefore, we report the results of 22 ABO-incompatible kidney transplantation cases performed in our hospital. Materials and Methods This research was from 22 patients in our hospital who underwent ABO-incompatible kidney transplantation from 15 February 2007 to 20 May 2010. Results As yet, there have been no donor graft losses and no deaths after transplantation. The results of the two groups were analyzed by analysis of covariance of the creatinine value of the recipients at 6 months after the operation, corrected for the preoperative value in order to statistically identify whether there were differences in renal function after the operation between ABO-compatible and ABO-incompatible kidney transplantation. The results of the analysis of covariance showed no statistical difference in renal function after the operation between the two groups. Conclusions Even though there were not many cases, our initial results for ABO-incompatible kidney transplantation were positive. Considering the increasing number of patients waiting for kidney transplantation, longer-term domestic research studies of ABO-incompatible kidney transplantation are necessary. PMID:21221208

Utilization of Deceased Donor Kidneys to Initiate Living Donor Chains.

PubMed

Melcher, M L; Roberts, J P; Leichtman, A B; Roth, A E; Rees, M A

2016-05-01

We propose that some deceased donor (DD) kidneys be allocated to initiate nonsimultaneous extended altruistic donor chains of living donor (LD) kidney transplants to address, in part, the huge disparity between patients on the DD kidney waitlist and available donors. The use of DD kidneys for this purpose would benefit waitlisted candidates in that most patients enrolled in kidney paired donation (KPD) systems are also waitlisted for a DD kidney transplant, and receiving a kidney through the mechanism of KPD will decrease pressure on the DD pool. In addition, a LD kidney usually provides survival potential equal or superior to that of DD kidneys. If KPD chains that are initiated by a DD can end in a donation of an LD kidney to a candidate on the DD waitlist, the quality of the kidney allocated to a waitlisted patient is likely to be improved. We hypothesize that a pilot program would show a positive impact on patients of all ethnicities and blood types. © Copyright 2016 The American Society of Transplantation and the American Society of Transplant Surgeons.

[Efficiency of Brazilian States and the Federal District in the public kidney transplant system based on DEA (Data Envelopment Analysis) and the Malmquist index].

PubMed

Costa, Cassia Kely Favoretto; Balbinotto Neto, Giácomo; Sampaio, Luciano Menezes Bezerra

2014-08-01

The objective of this study was to evaluate the efficiency of Brazilian States and the Federal District in the public kidney transplant system and their productivity trends from 2006 to 2011. The authors used Data Envelopment Analysis (DEA) with slack and the Malmquist index with slack. Inputs included spending on hospital services and health professionals in the system. The output was the number of kidney transplants performed in each State. The data showed a significant discrepancy between States in the number of kidney transplants. The transplant system's inefficiency may result from inadequate management, failure to comply with national guidelines, inactive hospital transplant committees, and overburdened hospital staff. Institutional changes promoted by the Brazilian Ministry of Health (procedures improvement and standardization) failed to increase productivity in most States during this period.

Gene-Trap Mutagenesis Identifies Mammalian Genes Contributing to Intoxication by Clostridium perfringens ε-Toxin

PubMed Central

Ivie, Susan E.; Fennessey, Christine M.; Sheng, Jinsong; Rubin, Donald H.; McClain, Mark S.

2011-01-01

The Clostridium perfringens ε-toxin is an extremely potent toxin associated with lethal toxemias in domesticated ruminants and may be toxic to humans. Intoxication results in fluid accumulation in various tissues, most notably in the brain and kidneys. Previous studies suggest that the toxin is a pore-forming toxin, leading to dysregulated ion homeostasis and ultimately cell death. However, mammalian host factors that likely contribute to ε-toxin-induced cytotoxicity are poorly understood. A library of insertional mutant Madin Darby canine kidney (MDCK) cells, which are highly susceptible to the lethal affects of ε-toxin, was used to select clones of cells resistant to ε-toxin-induced cytotoxicity. The genes mutated in 9 surviving resistant cell clones were identified. We focused additional experiments on one of the identified genes as a means of validating the experimental approach. Gene expression microarray analysis revealed that one of the identified genes, hepatitis A virus cellular receptor 1 (HAVCR1, KIM-1, TIM1), is more abundantly expressed in human kidney cell lines than it is expressed in human cells known to be resistant to ε-toxin. One human kidney cell line, ACHN, was found to be sensitive to the toxin and expresses a larger isoform of the HAVCR1 protein than the HAVCR1 protein expressed by other, toxin-resistant human kidney cell lines. RNA interference studies in MDCK and in ACHN cells confirmed that HAVCR1 contributes to ε-toxin-induced cytotoxicity. Additionally, ε-toxin was shown to bind to HAVCR1 in vitro. The results of this study indicate that HAVCR1 and the other genes identified through the use of gene-trap mutagenesis and RNA interference strategies represent important targets for investigation of the process by which ε-toxin induces cell death and new targets for potential therapeutic intervention. PMID:21412435

Gene-trap mutagenesis identifies mammalian genes contributing to intoxication by Clostridium perfringens ε-toxin.

PubMed

Ivie, Susan E; Fennessey, Christine M; Sheng, Jinsong; Rubin, Donald H; McClain, Mark S

2011-03-11

The Clostridium perfringens ε-toxin is an extremely potent toxin associated with lethal toxemias in domesticated ruminants and may be toxic to humans. Intoxication results in fluid accumulation in various tissues, most notably in the brain and kidneys. Previous studies suggest that the toxin is a pore-forming toxin, leading to dysregulated ion homeostasis and ultimately cell death. However, mammalian host factors that likely contribute to ε-toxin-induced cytotoxicity are poorly understood. A library of insertional mutant Madin Darby canine kidney (MDCK) cells, which are highly susceptible to the lethal affects of ε-toxin, was used to select clones of cells resistant to ε-toxin-induced cytotoxicity. The genes mutated in 9 surviving resistant cell clones were identified. We focused additional experiments on one of the identified genes as a means of validating the experimental approach. Gene expression microarray analysis revealed that one of the identified genes, hepatitis A virus cellular receptor 1 (HAVCR1, KIM-1, TIM1), is more abundantly expressed in human kidney cell lines than it is expressed in human cells known to be resistant to ε-toxin. One human kidney cell line, ACHN, was found to be sensitive to the toxin and expresses a larger isoform of the HAVCR1 protein than the HAVCR1 protein expressed by other, toxin-resistant human kidney cell lines. RNA interference studies in MDCK and in ACHN cells confirmed that HAVCR1 contributes to ε-toxin-induced cytotoxicity. Additionally, ε-toxin was shown to bind to HAVCR1 in vitro. The results of this study indicate that HAVCR1 and the other genes identified through the use of gene-trap mutagenesis and RNA interference strategies represent important targets for investigation of the process by which ε-toxin induces cell death and new targets for potential therapeutic intervention.

Chinese herbal medicines and chronic kidney disease: a positive outcome in a large patient study in Taiwan.

PubMed

Gobe, Glenda C; Shen, Kunyu

2015-12-01

The worth of traditional Chinese herbal medicines for chronic kidney disease (CKD) patients remains in debate. Lin et al. used a research database in Taiwan to identify almost 25,000 stage 3-5 newly diagnosed CKD patients who, after diagnosis, did or did not use prescribed Chinese herbal medicines for CKD. Reduced risk of end-stage kidney disease from specific traditional medicines warrants reflection on a CKD therapy resource that is largely ignored by Western medicine.

Congenital anatomic variants of the kidney and ureter: a pictorial essay.

PubMed

Srinivas, M R; Adarsh, K M; Jeeson, Riya; Ashwini, C; Nagaraj, B R

2016-03-01

Congenital renal parenchymal and pelvicalyceal abnormalities have a wide spectrum. Most of them are asymptomatic, like that of ectopia, cross fused kidney, horseshoe kidney, etc., while a few of them become complicated, leading to renal failure and death. It is very important for the radiologist to identify these anatomic variants and guide the clinicians for surgical and therapeutic procedures. Cross-sectional imaging with a volume rendered technique/maximum intensity projection has overcome ultrasonography and IVU for identification and interpretation of some of these variants.

SERS-Based Prognosis of Kidney Transplant Outcome

NASA Astrophysics Data System (ADS)

Chi, Jingmao

Kidney transplant is the predominant procedure of all organ transplants around the world. The number of patients on the waiting list for a kidney is growing rapidly, yet the number of donations does not keep up with the fast-growing need. This thesis focuses on the surface-enhanced Raman scattering (SERS) analysis of urine samples for prognosis of kidney transplant outcome, which can potentially let patients have a more timely treatment as well as expand the organ pool for transplant. We have observed unique SERS spectral features from urine samples of kidney transplant recipients that have strong associations with the kidney acute rejection (AR) based on the analysis of urine one day after the transplant. Our ability to provide an early prognosis of transplant outcome is a significant advance over the current gold standard of clinical diagnosis, which occurs weeks or months after the surgical procedure. The SERS analysis has also been applied to urine samples from deceased kidney donors. Excellent classification ability was achieved when the enhanced PCA-LDA analysis was used to classify and identify urine samples from different cases. The sensitivity of the acute tubular necrosis (ATN) class is more than 90%, which can indicate the usable kidneys in the high failure risk category. This analysis can help clinicians identify usable kidneys which would be discarded using conventional clinic methods as high failure risk. To investigate the biomarkers that cause the unique SERS features, an HPLC-SERS-MS approach was established. The high-performance liquid chromatography (HPLC) was used to separate the urinary components to reduce the sample complexity. The mass spectrometry (MS) was used to determine the formulas and the structures of the biomarkers. The presence of 1-methyl-2-pyrrolidone (NMP) and adenine in urine samples were confirmed by both MS and SERS analysis. Succinylmonocholine, a metabolite of suxamethonium, has a potential to be the biomarker that causes the unique SERS spectral features that indicate kidney AR. By integrating SERS analysis with statistical and chemical analysis and with the promising outcomes, this research has made a significant contribution in exploring the frontier of SERS analysis in biomedical sensing and diagnosis.

Physiological and molecular effects of interleukin-18 administration on the mouse kidney.

PubMed

Yamanishi, Kyosuke; Mukai, Keiichiro; Hashimoto, Takuya; Ikubo, Kaoru; Nakasho, Keiji; El-Darawish, Yosif; Li, Wen; Okuzaki, Daisuke; Watanabe, Yuko; Hayakawa, Tetsu; Nojima, Hiroshi; Yamanishi, Hiromichi; Okamura, Haruki; Matsunaga, Hisato

2018-03-07

The cytokine interleukin-18 was originally identified as an interferon-γ-inducing proinflammatory factor; however, there is increasing evidence to suggest that it has non-immunological effects on physiological functions. We previously investigated the potential pathophysiological relationship between interleukin-18 and dyslipidemia, non-alcoholic fatty liver disease, and non-alcoholic steatohepatitis, and suggested interleukin-18 as a possible novel treatment for not only these diseases but also for cancer immunotherapy. Before clinical application, the effects of interleukin-18 on the kidney need to be determined. In the current study, we examined the kidney of interleukin-18 knockout (Il18 -/- ) mice and the effects of interleukin-18 on the kidney following intravenous administration of recombinant interleukin-18. Il18 -/- male mice were generated on the C57Bl/6 background and littermate C57Bl/6 Il18 +/+ male mice were used as controls. To assess kidney damage, serum creatinine and blood urea nitrogen levels were measured and histopathological analysis was performed. For molecular analysis, microarray and quantitative reverse transcription PCR was performed using mice 6 and 12 weeks old. To evaluate the short- and long-term effects of interleukin-18 on the kidney, recombinant interleukin-18 was administered for 2 and 12 weeks, respectively. Compared with Il18 +/+ mice, Il18 -/- mice developed kidney failure in their youth-6 weeks of age, but the condition was observed to improve as the mice aged, even though dyslipidemia, arteriosclerosis, and higher insulin resistance occurred. Analyses of potential molecular mechanisms involved in the onset of early kidney failure in Il18 -/- mice identified a number of associated genes, such as Itgam, Nov, and Ppard. Intravenous administration of recombinant interleukin-18 over both the short and long term showed no effects on the kidney despite significant improvement in metabolic diseases. Short- and long-term administration of interleukin-18 appeared to have no adverse effects on the kidney in these mice, suggesting that administration may be a safe and novel treatment for metabolic diseases and cancer.

Mesenchymal Stem Cell-Based Therapy for Kidney Disease: A Review of Clinical Evidence

PubMed Central

2016-01-01

Mesenchymal stem cells form a population of self-renewing, multipotent cells that can be isolated from several tissues. Multiple preclinical studies have demonstrated that the administration of exogenous MSC could prevent renal injury and could promote renal recovery through a series of complex mechanisms, in particular via immunomodulation of the immune system and release of paracrine factors and microvesicles. Due to their therapeutic potentials, MSC are being evaluated as a possible player in treatment of human kidney disease, and an increasing number of clinical trials to assess the safety, feasibility, and efficacy of MSC-based therapy in various kidney diseases have been proposed. In the present review, we will summarize the current knowledge on MSC infusion to treat acute kidney injury, chronic kidney disease, diabetic nephropathy, focal segmental glomerulosclerosis, systemic lupus erythematosus, and kidney transplantation. The data obtained from these clinical trials will provide further insight into safety, feasibility, and efficacy of MSC-based therapy in renal pathologies and allow the design of consensus protocol for clinical purpose. PMID:27721835

Cardio-renal syndromes: from foggy bottoms to sunny hills.

PubMed

Ronco, Claudio

2011-11-01

"Cardio-renal syndromes" (CRS) are disorders of the heart and kidneys whereby acute or chronic dysfunction in one organ may induce acute or chronic dysfunction of the other. The current definition has been expanded into five subtypes whose etymology reflects the primary and secondary pathology, the time-frame and simultaneous cardiac and renal co-dysfunction secondary to systemic disease: CRS type I: acute worsening of heart function (AHF-ACS) leading to kidney injury and/or dysfunction. CRS type II: chronic abnormalities in heart function (CHF-CHD) leading to kidney injury or dysfunction. CRS type III: acute worsening of kidney function (AKI) leading to heart injury and/or dysfunction. CRS type IV: chronic kidney disease (CKD) leading to heart injury, disease and/or dysfunction. CRS type V: systemic conditions leading to simultaneous injury and/or dysfunction of heart and kidney. These different subtypes may have a different pathophysiological mechanism and they may represent separate entities in terms of prevention and therapy.

Enhancing effect of Fe2+ on the formaldehyde production from trimethylamine N-oxide decomposition catalyzed by the extract of Harpadon nehereus kidney

NASA Astrophysics Data System (ADS)

Sun, Yong; Zhou, Deqing; Zhao, Feng

2011-03-01

The effects of Fe2+ on the trimethylamine N-oxide (TMAO) demethylating activity of the Harpadon nehereus kidney extract were studied in this research. The activity of the kidney extract was presumably inhibited by ethylene diamine tetra-acetic acid (EDTA), which indicates that the kidney extract contains an enzyme or enzyme system with metal cations as activator. Activity of the kidney extract was enhanced significantly when Fe2+ was added into the model system in vitro. As the concentration of Fe2+ increased, the decomposing rate of TMAO increased rapidly until TMAO decomposed completely. The activity of the kidney extract was also enhanced by reductant such as ascorbic acid. Inductively Coupled Plasma-Atomic Emission Spectrometry (ICP-AES) was employed to determine the content of total iron in a number of fishery products. Significant positive correlation between the contents of total iron and endogenous formaldehyde (FA) was found, especially in marine products.

Analysis of Urinary Calculi Using Infrared Spectroscopic Imaging

NASA Astrophysics Data System (ADS)

Sablinskas, Valdas; Lesciute, Daiva; Hendrixson, Vaiva

2009-06-01

Kidney stone disease is a cosmopolitan disease, occurring in both industrialized and developing countries and mainly affecting adults aged 2060 years. The formation of kidney stones is a process that includes many factors. Its primary and contributing pathogenic factors are genetic, nutritional and environmental, but also include personal habits. Information about the chemical structure of kidney stones is of great importance to the treatment of the kidney diseases. The usefulness of such information was first recognized in early 1950s. Analysis of urinary stones by various chemical methods, polarization microscopy, x-ray diffraction, porosity determination, solid phase NMR, and thermo analytical procedures have been widely used. Unfortunately, no one method is sufficient to provide all the clinically useful information about the structure and composition of the stones. Infrared spectroscopy can be considered a relatively new method of kidney stone analysis. It allows to identify any organic or inorganic molecules the constituents of kidney stones. So far this method had never been used to collect information about kidney stone component patterns in Lithuania. Since no epidemiological studies have been performed in this field, the medical treatment of kidney stone disease is empirical and often ineffective in hospitals around the country. The aim of this paper is to present some results of analysis of kidney stones extracted from local patients using FTIR spectroscopical microscopy.

Kidneys for sale: who disapproves, and why?

PubMed

Leider, S; Roth, A E

2010-05-01

The shortage of transplant kidneys has spurred debate about legalizing monetary payments to donors to increase the number of available kidneys. However, buying and selling organs faces widespread disapproval. We survey a representative sample of Americans to assess disapproval for several forms of kidney market, and to understand why individuals disapprove by identifying factors that predict disapproval, including disapproval of markets for other body parts, dislike of increased scope for markets and distrust of markets generally. Our results suggest that while the public is potentially receptive to compensating kidney donors, among those who oppose it, general disapproval toward certain kinds of transactions is at least as important as concern about specific policy details. Between 51% and 63% of respondents approve of the various potential kidney markets we investigate, and between 42% and 58% want such markets to be legal. A total of 38% of respondents disapprove of at least one market. Respondents who distrust markets generally are not more disapproving of kidney markets; however we find significant correlations between kidney market disapproval and attitudes reflecting disapproval toward certain transactions-including both other body markets and market encroachment into traditionally nonmarket exchanges, such as food preparation.

A serine protease inhibitor attenuates aldosterone-induced kidney injuries via the suppression of plasmin activity.

PubMed

Kakizoe, Yutaka; Miyasato, Yoshikazu; Onoue, Tomoaki; Nakagawa, Terumasa; Hayata, Manabu; Uchimura, Kohei; Morinaga, Jun; Mizumoto, Teruhiko; Adachi, Masataka; Miyoshi, Taku; Sakai, Yoshiki; Tomita, Kimio; Mukoyama, Masashi; Kitamura, Kenichiro

2016-10-01

Emerging evidence has suggested that aldosterone has direct deleterious effects on the kidney independently of its hemodynamic effects. However, the detailed mechanisms of these direct effects remain to be elucidated. We have previously reported that camostat mesilate (CM), a synthetic serine protease inhibitor, attenuated kidney injuries in Dahl salt-sensitive rats, remnant kidney rats, and unilateral ureteral obstruction rats, suggesting that some serine proteases would be involved in the pathogenesis of kidney injuries. The current study was conducted to investigate the roles of serine proteases and the beneficial effects of CM in aldosterone-related kidney injuries. We observed a serine protease that was activated by aldosterone/salt in rat kidney lysate, and identified it as plasmin with liquid chromatography-tandem mass spectrometry. Plasmin increased pro-fibrotic and inflammatory gene expressions in rat renal fibroblast cells. CM inhibited the protease activity of plasmin and suppressed cell injury markers induced by plasmin in the fibroblast cells. Furthermore, CM ameliorated glomerulosclerosis and interstitial fibrosis in the kidney of aldosterone/salt-treated rats. Our findings indicate that plasmin has important roles in kidney injuries that are induced by aldosterone/salt, and that serine protease inhibitor could provide a new strategy for the treatment of aldosterone-associated kidney diseases in humans. Copyright © 2016 The Authors. Production and hosting by Elsevier B.V. All rights reserved.

Effects of Single and Combined Losartan and Tempol Treatments on Oxidative Stress, Kidney Structure and Function in Spontaneously Hypertensive Rats with Early Course of Proteinuric Nephropathy

PubMed Central

Grujic-Milanovic, Jelica; Miloradovic, Zoran; Ivanov, Milan; Jovovic, Djurdjica; Vajic, Una-Jovana; Zivotic, Maja; Markovic-Lipkovski, Jasmina; Mihailovic-Stanojevic, Nevena

2016-01-01

Oxidative stress has been widely implicated in both hypertension and chronic kidney disease (CKD). Hypertension is a major risk factor for CKD progression. In the present study we have investigated the effects of chronic single tempol (membrane-permeable radical scavenger) or losartan (angiotensin II type 1 receptor blocker) treatment, and their combination on systemic oxidative status (plasma thiobarbituric acid-reactive substances (pTBARS) production, plasma antioxidant capacity (2,2'-azino-bis(3-ethylbenzothiazoline-6-sulphonic acid, pABTS), erythrocyte antioxidant enzymes activities) and kidney oxidative stress (kTBARS, kABTS, kidney antioxidant enzymes activities), kidney function and structure in spontaneously hypertensive rats (SHR) with the early course of adriamycin-induced nephropathy. Adult SHR were divided into five groups. The control group received vehicle, while the other groups received adriamycin (2 mg/kg, i.v.) twice in a 21-day interval, followed by vehicle, losartan (L,10 mg/kg/day), tempol (T,100 mg/kg/day) or combined T+L treatment (by gavage) during a six-week period. Adriamycin significantly increased proteinuria, plasma lipid peroxidation, kidney protein oxidation, nitrite excretion, matrix metalloproteinase-1 (MMP-1) protein expression and nestin immunostaining in the kidney. Also, it decreased kidney antioxidant defense, kidney NADPH oxidase 4 (kNox4) protein expression and abolished anti-inflammatory response due to significant reduction of kidney NADPH oxidase 2 (kNox2) protein expression in SHR. All treatments reduced protein-to-creatinine ratio (marker of proteinuria), pTBARS production, kidney protein carbonylation, nitrite excretion, increased antioxidant capacity and restored kidney nestin expression similar to control. Both single treatments significantly improved systemic and kidney antioxidant defense, bioavailability of renal nitric oxide, reduced kMMP-1 protein expression and renal injury, thus retarded CKD progression. Losartan improved blood pressure, as well as tubular injury and restored anti-inflammatory defense by reverting kNox2 expression to the control level. Interestingly, tempol was more successful in reducing systemic oxidative stress, proteinuria, kMMP-1 and glomerulosclerosis. However, combined treatment failed to overcome the beneficial effects of single treatments in slowing down the progression of ADR-induced nephropathy in SHR. PMID:27560781

Cardiac surgery-associated acute kidney injury.

PubMed

Vives, Marc; Wijeysundera, Duminda; Marczin, Nandor; Monedero, Pablo; Rao, Vivek

2014-05-01

Acute kidney injury develops in up to 30% of patients who undergo cardiac surgery, with up to 3% of patients requiring dialysis. The requirement for dialysis after cardiac surgery is associated with an increased risk of infection, prolonged stay in critical care units and long-term need for dialysis. The development of acute kidney injury is independently associated with substantial short- and long-term morbidity and mortality. Its pathogenesis involves multiple pathways. Haemodynamic, inflammatory, metabolic and nephrotoxic factors are involved and overlap each other leading to kidney injury. Clinical studies have identified predictors for cardiac surgery-associated acute kidney injury that can be used effectively to determine the risk for acute kidney injury in patients undergoing cardiac surgery. High-risk patients can be targeted for renal protective strategies. Nonetheless, there is little compelling evidence from randomized trials supporting specific interventions to protect or prevent acute kidney injury in cardiac surgery patients. Several strategies have shown some promise, including less invasive procedures in those at greatest risk, natriuretic peptide, fenoldopam, preoperative hydration, preoperative optimization of anaemia and postoperative early use of renal replacement therapy. The efficacy of larger-scale trials remains to be confirmed.

Mechanisms by Which Dehydration May Lead to Chronic Kidney Disease.

PubMed

Roncal-Jimenez, C; Lanaspa, M A; Jensen, T; Sanchez-Lozada, L G; Johnson, R J

2015-01-01

Dehydration, a condition that characterizes excessive loss of body water, is well known to be associated with acute renal dysfunction; however, it has largely been considered reversible and to be associated with no long-term effects on the kidney. Recently, an epidemic of chronic kidney disease has emerged in Central America in which the major risk factor seems to be recurrent heat-associated dehydration. This has led to studies investigating whether recurrent dehydration may lead to permanent kidney damage. Three major potential mechanisms have been identified, including the effects of vasopressin on the kidney, the activation of the aldose reductase-fructokinase pathway, and the effects of chronic hyperuricemia. The discovery of these pathways has also led to the recognition that mild dehydration may be a risk factor in progression of all types of chronic kidney diseases. Furthermore, there is some evidence that increasing hydration, particularly with water, may actually prevent CKD. Thus, a whole new area of investigation is developing that focuses on the role of water and osmolarity and their influence on kidney function and health. © 2015 S. Karger AG, Basel.

Safe and ethical living kidney donation in Qatar: A national health system's approach.

PubMed

Asim, Muhammad; Al-Maslamani, Yousuf; Al-Malki, Hassan

2017-01-01

The increasing incidence of end-stage kidney disease in Qatar has led to growing demand for donor kidneys. The deceased donor kidney program has yet to achieve its full potential; hence, living kidney donation has been widely adopted as an appropriate alternative. The reliance on living kidney donors however, raises a number of social, ethical, and legal concerns surrounding informed consent, voluntarism, psychosocial evaluation, perioperative care, and long-term follow-up of living kidney donors. Many of these concerns become heightened in a multicultural, multilingual society within a Gulf country such as Qatar. This article provides an insight into the challenges that living kidney donation poses in a multiethnic society with significant socioeconomic divides. It also discusses the remedial measures that the Qatari government, healthcare authorities, and transplant community have adopted to address these issues.

Safe and ethical living kidney donation in Qatar: A national health system's approach

PubMed Central

Asim, Muhammad; Al-Maslamani, Yousuf; Al-Malki, Hassan

2017-01-01

The increasing incidence of end-stage kidney disease in Qatar has led to growing demand for donor kidneys. The deceased donor kidney program has yet to achieve its full potential; hence, living kidney donation has been widely adopted as an appropriate alternative. The reliance on living kidney donors however, raises a number of social, ethical, and legal concerns surrounding informed consent, voluntarism, psychosocial evaluation, perioperative care, and long-term follow-up of living kidney donors. Many of these concerns become heightened in a multicultural, multilingual society within a Gulf country such as Qatar. This article provides an insight into the challenges that living kidney donation poses in a multiethnic society with significant socioeconomic divides. It also discusses the remedial measures that the Qatari government, healthcare authorities, and transplant community have adopted to address these issues. PMID:28795019

Microarray identification of novel genes downstream of Six1, a critical factor in cranial placode, somite and kidney development

PubMed Central

Yan, Bo; Neilson, Karen M.; Ranganathan, Ramya; Maynard, Thomas; Streit, Andrea; Moody, Sally A.

2014-01-01

Background Six1 plays an important role in the development of several vertebrate organs, including cranial sensory placodes, somites and kidney. Although Six1 mutations cause one form of Branchio-Otic Syndrome (BOS), the responsible gene in many patients has not been identified; genes that act downstream of Six1 are potential BOS candidates. Results We sought to identify novel genes expressed during placode, somite and kidney development by comparing gene expression between control and Six1-expressing ectodermal explants. The expression patterns of 19 of the significantly up-regulated and 11 of the significantly down-regulated genes were assayed from cleavage to larval stages. 28/30 genes are expressed in the otocyst, a structure that is functionally disrupted in BOS, and 26/30 genes are expressed in the nephric mesoderm, a structure that is functionally disrupted in the related Branchio-Otic-Renal (BOR) syndrome. We also identified the chick homologues of 5 genes and show that they have conserved expression patterns. Conclusions Of the 30 genes selected for expression analyses, all are expressed at many of the developmental times and appropriate tissues to be regulated by Six1. Many have the potential to play a role in the disruption of hearing and kidney function seen in BOS/BOR patients. PMID:25403746

Isozyme-specific comprehensive characterization of transglutaminase-crosslinked substrates in kidney fibrosis.

PubMed

Tatsukawa, Hideki; Otsu, Risa; Tani, Yuji; Wakita, Ryosuke; Hitomi, Kiyotaka

2018-05-09

Chronic kidney disease is characterized by prolonged decline in renal function, excessive accumulation of ECM, and progressive tissue fibrosis. Transglutaminase (TG) is a crosslinking enzyme that catalyzes the formation of covalent bonds between glutamine and lysine residues, and is involved in the induction of renal fibrosis via the stabilization of ECM and the activation of TGF-β1. Despite the accumulating evidences indicating that TG2 is a key enzyme in fibrosis, genetic knockout of TG2 reduced by only 50% the elevated protein crosslinking and fibrous protein in renal fibrosis model, whereas treatment with TG inhibitor almost completely reduced these levels. Here, we also clarified the distributions of TG isozymes and their in situ activities and identified the isozyme-specific crosslinked substrates for both TG1 and TG2 in fibrotic kidney. We found that TG1 activity was markedly enhanced in renal tubular epithelium and interstitial areas, whereas TG2 activity increased only in the extracellular space. In total, 47 and 67 possible candidates were identified as TG1 and TG2 substrates, respectively, only in fibrotic kidney. Among them, several possible substrates related to renal disease and fibrosis were identified. These findings provide novel insights into the mechanisms of renal fibrosis through the targeting of isozyme-specific TG substrates.

Abdominal ultrasound

MedlinePlus

... inflammation in pancreas) Spleen enlargement ( splenomegaly ) Portal hypertension Liver tumors Obstruction of bile ... Digestive system Kidney anatomy Ultrasound in pregnancy Kidney - blood and urine flow ...

Awareness level of kidney functions and diseases among adults in a Nigerian population

PubMed Central

Okwuonu, C. G.; Chukwuonye, I. I.; Ogah, S. O.; Abali, C.; Adejumo, O. A.; Oviasu, E.

2015-01-01

The prevalence of kidney diseases is on the increase in Nigeria. The cost of its management is far beyond the reach of an average patient. Prevention is thus of paramount importance and awareness of kidney diseases will help in its prevention. The aim of this study is to assess the level of awareness of kidney functions and diseases among adults in a Nigerian population. A semi-structured, researcher – administered questionnaire was the tool for data collection. Four hundred and thirty-five questionnaires were analyzed. There were 160 males (36.8%) and 275 females (63.2%). The mean age was 42.8 ± 14 years with a range of 18–78 years. Among these, 82.1% were aware of the kidneys' involvement in waste removal from the body through urine while 36% and 29% were aware of kidneys' role in blood pressure regulation and blood production, respectively. Only 26.6% correctly identified at least two basic functions of the kidneys. Also, 32.6% of the respondents were aware of at least three common causes of kidney diseases in our environment. Majority of the respondents (70.7%) did not know that kidney diseases could be inherited. Furthermore, belief in alternative therapy for kidney disease was documented in 83.2%, while unawareness of dialysis as a treatment modality was recorded in 68% of the respondents. The awareness of kidney functions and diseases among the population is poor. Measures are needed to improve this to stem the rising prevalence of chronic kidney disease in Nigeria. PMID:26060365

Conserved and Divergent Features of Human and Mouse Kidney Organogenesis.

PubMed

Lindström, Nils O; McMahon, Jill A; Guo, Jinjin; Tran, Tracy; Guo, Qiuyu; Rutledge, Elisabeth; Parvez, Riana K; Saribekyan, Gohar; Schuler, Robert E; Liao, Christopher; Kim, Albert D; Abdelhalim, Ahmed; Ruffins, Seth W; Thornton, Matthew E; Basking, Laurence; Grubbs, Brendan; Kesselman, Carl; McMahon, Andrew P

2018-03-01

Human kidney function is underpinned by approximately 1,000,000 nephrons, although the number varies substantially, and low nephron number is linked to disease. Human kidney development initiates around 4 weeks of gestation and ends around 34-37 weeks of gestation. Over this period, a reiterative inductive process establishes the nephron complement. Studies have provided insightful anatomic descriptions of human kidney development, but the limited histologic views are not readily accessible to a broad audience. In this first paper in a series providing comprehensive insight into human kidney formation, we examined human kidney development in 135 anonymously donated human kidney specimens. We documented kidney development at a macroscopic and cellular level through histologic analysis, RNA in situ hybridization, immunofluorescence studies, and transcriptional profiling, contrasting human development (4-23 weeks) with mouse development at selected stages (embryonic day 15.5 and postnatal day 2). The high-resolution histologic interactive atlas of human kidney organogenesis generated can be viewed at the GUDMAP database (www.gudmap.org) together with three-dimensional reconstructions of key components of the data herein. At the anatomic level, human and mouse kidney development differ in timing, scale, and global features such as lobe formation and progenitor niche organization. The data also highlight differences in molecular and cellular features, including the expression and cellular distribution of anchor gene markers used to identify key cell types in mouse kidney studies. These data will facilitate and inform in vitro efforts to generate human kidney structures and comparative functional analyses across mammalian species. Copyright © 2018 by the American Society of Nephrology.

Diabetes and Kidney Disease in American Indians: Potential Role of Sugar-Sweetened Beverages.

PubMed

Yracheta, Joseph M; Lanaspa, Miguel A; Le, MyPhuong T; Abdelmalak, Manal F; Alfonso, Javier; Sánchez-Lozada, Laura G; Johnson, Richard J

2015-06-01

Since the early 20th century, a marked increase in obesity, diabetes, and chronic kidney disease has occurred in the American Indian population, especially the Pima Indians of the Southwest. Here, we review the current epidemic and attempt to identify remediable causes. A search was performed using PubMed and the search terms American Indian and obesity, American Indian and diabetes, American Indian and chronic kidney disease, and American Indian and sugar or fructose, Native American, Alaska Native, First Nations, Aboriginal, Amerind, and Amerindian for American Indian for articles linking American Indians with diabetes, obesity, chronic kidney disease, and sugar; additional references were identified in these publications traced to 1900 and articles were reviewed if they were directly discussing these topics. Multiple factors are involved in the increased risk for diabetes and kidney disease in the American Indian population, including poverty, overnutrition, poor health care, high intake of sugar, and genetic mechanisms. Genetic factors may be especially important in the Pima, as historical records suggest that this group was predisposed to obesity before exposure to Western culture and diet. Exposure to sugar-sweetened beverages may also be involved in the increased risk for chronic kidney disease. In these small populations in severe health crisis, we recommend further studies to investigate the role of excess added sugar, especially sugar-sweetened beverages, as a potentially remediable risk factor. Copyright © 2015 Mayo Foundation for Medical Education and Research. Published by Elsevier Inc. All rights reserved.

Acute Kidney Injury and Bisphosphonate Use in Cancer: A Report From the Research on Adverse Drug Events and Reports (RADAR) Project

PubMed Central

Edwards, Beatrice J.; Usmani, Sarah; Raisch, Dennis W.; McKoy, June M.; Samaras, Athena T.; Belknap, Steven M.; Trifilio, Steven M.; Hahr, Allison; Bunta, Andrew D.; Abu-Alfa, Ali; Langman, Craig B.; Rosen, Steve T.; West, Dennis P.

2013-01-01

Purpose: To determine whether acute kidney injury (AKI) is identified within the US Food and Drug Administration's Adverse Events and Reporting System (FDA AERS) as an adverse event resulting from bisphosphonate (BP) use in cancer therapy. Methods: A search of the FDA AERS records from January 1998 through June 2009 was performed; search terms were “renal problems” and all drug names for BPs. The search resulted in 2,091 reports. We analyzed for signals of disproportional association by calculating the proportional reporting ratio for zoledronic acid (ZOL) and pamidronate. Literature review of BP-associated renal injury within the cancer setting was conducted. Results: Four hundred eighty cases of BP-associated acute kidney injury (AKI) were identified in patients with cancer. Two hundred ninety-eight patients (56%) were female; mean age was 66 ± 10 years. Multiple myeloma (n = 220, 46%), breast cancer (n = 98, 20%), and prostate cancer (n = 24, 5%) were identified. Agents included ZOL (n = 411, 87.5%), pamidronate (n = 8, 17%), and alendronate (n = 36, 2%). Outcomes included hospitalization (n = 304, 63.3%) and death (n = 68, 14%). The proportional reporting ratio for ZOL was 1.22 (95% CI, 1.13 to 1.32) and for pamidronate was 1.55 (95% CI, 1.25 to 1.65), reflecting a nonsignificant safety signal for both drugs. Conclusion: AKI was identified in BP cancer clinical trials, although a safety signal for BPs and AKI within the FDA AERS was not detected. Our findings may be attributed, in part, to clinicians who believe that AKI occurs infrequently; ascribe the AKI to underlying premorbid disease, therapy, or cancer progression; or consider that AKI is a known adverse drug reaction of BPs and thus under-report AKI to the AERS. PMID:23814519

Polythelia and associated conditions.

PubMed

Pellegrini, J R; Wagner, R F

1983-09-01

Polythelia (congenital supernumerary nipples) is a marker for more serious anomalies of the urinary and cardiovascular systems. It is associated with obstructive abnormalities of the kidney or the renal collecting system, renal agenesis, renal cell carcinoma, supernumerary kidneys, cardiac conduction disturbances and congenital heart disease.

Kidney Transplant Rejection and Tissue Injury by Gene Profiling of Biopsies and Peripheral Blood Lymphocytes

PubMed Central

Flechner, Stuart M.; Kurian, Sunil M.; Head, Steven R.; Sharp, Starlette M.; Whisenant, Thomas C.; Zhang, Jie; Chismar, Jeffrey D.; Horvath, Steve; Mondala, Tony; Gilmartin, Timothy; Cook, Daniel J.; Kay, Steven A.; Walker, John R.; Salomon, Daniel R.

2007-01-01

A major challenge for kidney transplantation is balancing the need for immunosuppression to prevent rejection, while minimizing drug-induced toxicities. We used DNA microarrays (HG-U95Av2 GeneChips, Affymetrix) to determine gene expression profiles for kidney biopsies and peripheral blood lymphocytes (PBLs) in transplant patients including normal donor kidneys, well-functioning transplants without rejection, kidneys undergoing acute rejection, and transplants with renal dysfunction without rejection. We developed a data analysis schema based on expression signal determination, class comparison and prediction, hierarchical clustering, statistical power analysis and real-time quantitative PCR validation. We identified distinct gene expression signatures for both biopsies and PBLs that correlated significantly with each of the different classes of transplant patients. This is the most complete report to date using commercial arrays to identify unique expression signatures in transplant biopsies distinguishing acute rejection, acute dysfunction without rejection and well-functioning transplants with no rejection history. We demonstrate for the first time the successful application of high density DNA chip analysis of PBL as a diagnostic tool for transplantation. The significance of these results, if validated in a multicenter prospective trial, would be the establishment of a metric based on gene expression signatures for monitoring the immune status and immunosuppression of transplanted patients. PMID:15307835

Comparison of microbial growth inhibition screening assays with high-pressure liquid chromatography for detection of experimentally incurred penicillin G residues in calves.

PubMed

Musser, Jeffrey M B; Anderson, Kevin L; Boison, Joe O

2002-01-01

Twelve calves were fed milk replacer containing 3.33 ppm penicillin G for one feeding, and 12 calves were fed the medicated milk replacer once daily at a rate of 12% of their body weight for 14 days. Two calves served as controls. Calves were slaughtered 4 to 13 hours after being fed. Kidney, liver, muscle, and urine samples were assayed for penicillin by high-pressure liquid chromatography (HPLC). Penicillin G was not detected in any muscle samples and concentrations of penicillin exceeded the tolerance level (0.05 microg/g) in kidney or liver tissue from 13 of 24 treated-calf carcasses examined by HPLC. The Live Animal Swab Test identified all 13 carcasses with violative drug residues. Using kidney as the test matrix, the Swab Test on Premises identified 10 of 13 carcasses with violative drug residues, while the Calf Antibiotic Sulfa Test identified seven of 13 carcasses with violative residues.

Risk factors for acute kidney injury after partial hepatectomy

PubMed Central

Bredt, Luis Cesar; Peres, Luis Alberto Batista

2017-01-01

AIM To identify risk factors for the occurrence of acute kidney injury (AKI) in the postoperative period of partial hepatectomies. METHODS Retrospective analysis of 446 consecutive resections in 405 patients, analyzing clinical characteristics, preoperative laboratory data, intraoperative data, and postoperative laboratory data and clinical evolution. Adopting the International Club of Ascites criteria for the definition of AKI, potential predictors of AKI by logistic regression were identified. RESULTS Of the total 446 partial liver resections, postoperative AKI occurred in 80 cases (17.9%). Identified predictors of AKI were: Non-dialytic chronic kidney injury (CKI), biliary obstruction, the Model for End-Stage Liver Disease (MELD) score, the extent of hepatic resection, the occurrence of intraoperative hemodynamic instability, post-hepatectomy haemorrhage, and postoperative sepsis. CONCLUSION The MELD score, the presence of non-dialytic CKI and biliary obstruction in the preoperative period, and perioperative hemodynamics instability, bleeding, and sepsis are risk factors for the occurrence of AKI in patients that underwent partial hepatectomy. PMID:28706580

Kidney Transplant Candidates’ Views of the Transplant Allocation System

PubMed Central

Louis, Okiki N; Sankar, Pamela; Ubel, Peter A

1997-01-01

OBJECTIVE The point system used to distribute scarce transplantable kidneys places great emphasis on antigen matching. This contributes to increased waiting times for African Americans, who have a disproportionate share of rare antigens. We conducted a pilot study to explore the understanding and attitudes of kidney transplant candidates toward the way the transplant allocation system trades off between antigen matching and waiting time. MEASUREMENTS MAIN RESULTS We performed semi-structured interviews of a convenience sample of 33 patients awaiting transplants in Philadelphia and its surrounding suburbs. Patients had a number of misconceptions about the transplant allocation system. Many incorrectly thought, for example, that quality of life and financial status influence which patients on the waiting list receive available organs. Despite these and other misconceptions, the majority of patients thought the allocation system was fair. However, many African Americans thought the system was biased against them because of their race. After hearing about how the transplant system factors antigen matching and waiting time into organ allocation, the majority of subjects still felt the system was fair. After hearing that the emphasis on antigen matching causes African Americans to wait twice as long as whites, a larger number of subjects thought the system was unfair. Nevertheless, few thought the system should be changed. Even African American patients who felt the system was unfair still approved of the emphasis on antigen matching out of a desire to have a successful kidney transplant. CONCLUSIONS We found that most of the interviewed patients awaiting kidney transplant thought the system should continue to emphasize antigen matching. Although attitudes toward the allocation system differed by race, with African American patients more suspicious of the system, the importance patients placed on antigen matching did not appear to differ by race. PMID:9276653

Utility of applying quality assessment tools for kidneys with KDPI ≥80

PubMed Central

Doshi, Mona D.; Reese, Peter P.; Hall, Isaac E.; Schröppel, Bernd; Ficek, Joseph; Formica, Richard N.; Weng, Francis L.; Hazs, Rick D.; Philbrook, Heather Thiessen; Parikh, Chirag

2016-01-01

Background Kidneys with “high” kidney donor profile index (KDPI) are often biopsied and pumped, yet frequently discarded. Methods In this multicenter study, we describe the characteristics and outcomes of kidneys with KDPI ≥80 that were procured from 338 deceased donors. We excluded donors with anatomical kidney abnormalities. Results Donors were categorized by the number of kidneys discarded: 1) none (n=154, 46%), 2) 1 discarded and 1 transplanted (n=48, 14%), 3) both discarded (n=136, 40%). Donors in group 3 were older, more often white, and had higher terminal creatinine and KDPI than group 1 (all p<0.05). Biopsy was performed in 92% of all kidneys, and 47% were pumped. Discard was associated with biopsy findings and 1st hour renal resistance. Kidney injury biomarker levels (NGAL, IL-18, and KIM-1 measured from donor urine at procurement and from perfusate soon after pump perfusion) were not different between groups. There was no significant difference in 1-year estimated glomerular filtration rate (eGFR) or graft failure between groups 1 and 2 (41.5±18 vs. 41.4±22 mL/min/1.73m2; p=0.97 and 9% vs. 10%; p=0.76). Conclusions Kidneys with KDPI ≥80 comprise the most resource consuming fraction of our donor kidney pool and have the highest rates of discard. Our data suggest that some discarded kidneys with KDPI ≥80 are viable; however, current tools and urine- and perfusate-biomarkers to identify these viable kidneys are not satisfactory. We need better methods to assess viability of kidneys with high KDPI. PMID:27490414

Diuretic renography in hydronephrosis: renal tissue tracer transit predicts functional course and thereby need for surgery.

PubMed

Schlotmann, Andreas; Clorius, John H; Clorius, Sandra N

2009-10-01

The recognition of those hydronephrotic kidneys which require therapy to preserve renal function remains difficult. We retrospectively compared the 'tissue tracer transit' (TTT) of (99m)Tc-mercaptoacetyltriglycine ((99m)Tc-MAG(3)) with 'response to furosemide stimulation' (RFS) and with 'single kidney function < 40%' (SKF < 40%) to predict functional course and thereby need for surgery. Fifty patients with suspected unilateral obstruction and normal contralateral kidney had 115 paired (baseline/follow-up) (99m)Tc-MAG(3) scintirenographies. Three predictions of the functional development were derived from each baseline examination: the first based on TTT (visually assessed), the second on RFS and the third on SKF < 40%. Each prediction also considered whether the patient had surgery. Possible predictions were 'better', 'worse' or 'stable' function. A comparison of SKF at baseline and follow-up verified the predictions. The frequency of correct predictions for functional improvement following surgery was 8 of 10 kidneys with delayed TTT, 9 of 22 kidneys with obstructive RFS and 9 of 21 kidneys with SKF < 40%; for functional deterioration without surgery it was 2 of 3 kidneys with delayed TTT, 3 of 20 kidneys with obstructive RFS and 3 of 23 kidneys with SKF < 40%. Without surgery 67 of 70 kidneys with timely TTT maintained function. Without surgery 0 of 9 kidneys with timely TTT but obstructive RFS and only 1 of 16 kidneys with timely TTT but SKF < 40% lost function. Delayed TTT appears to identify the need for therapy to preserve function of hydronephrotic kidneys, while timely TTT may exclude risk even in the presence of an obstructive RFS or SKF < 40%.

Improving Global Kidney Health: International Society of Nephrology Initiatives and the Global Kidney Health Atlas.

PubMed

Levin, Adeera

2018-01-01

Chronic Kidney Disease (CKD) is a major public health problem and is increasingly being recognized as an important driver of costs in all health care systems. The diversity of outcomes for people living with CKD is in part due to variability in biology, access to care, environmental factors, and health care system differences. The International Society of Nephrology (ISN), working in collaboration with its partners, has evolved into a philanthropic organization, from a traditional medical society, committed to a vision that sees "a future where all people have access to sustainable kidney health". A set of activities, including a Global Kidney Health Summit, the Global Kidney Health Atlas, and a Global Kidney Health Policy Forum, which has formed the basis of a multi-stakeholder engagement process, building on a solid base of ISN programs and educational activities, is described. Through building awareness and increasing capacity to conduct research, the international community will build a more solid foundation on which to advocate for sustainable, ethical solutions to the problem of kidney disease throughout the world. The ISN aims to improve kidney health worldwide through a variety of diverse activities addressing education, advocacy, and research. Collaboration with partners within and outside the medical community is key in achieving this goal. Key Messages: Kidney disease is an important public health problem and is driven by genetic, environmental, and socioeconomic factors. Through active collaboration with diverse partners, the international community is striving for sustainable kidney health and aims to achieve this through coordinated work in a variety of spheres. © 2018 The Author(s) Published by S. Karger AG, Basel.

Dietary vitamin C and E modulates oxidative stress induced-kidney and lens injury in diabetic aged male rats through modulating glucose homeostasis and antioxidant systems.

PubMed

Özkaya, Dilek; Naziroğlu, Mustafa; Armağan, Abdullah; Demirel, Alpay; Köroglu, Banu Kale; Çolakoğlu, Neriman; Kükner, Aysel; Sönmez, Tolga Taha

2011-06-01

Diabetes induces oxidative stress in aged human and rat, although daily supplementation of vitamins C and E (VCE) can be beneficial to aged diabetic rats by reducing free radical production. The aim of the present study was to evaluate whether dietary VCE supplementation relieves oxidative stress in streptozotocin (STZ)-induced diabetic in aged rats. Thirty aged rats were randomly divided into three groups. The first group was used as a control. The second group was made diabetic using a single dose of intraperitoneal STZ. VCE-supplemented feed was given to aged diabetic rats constituting the third group. On the 21st day of the experiment, blood, lens and kidney samples were taken from all animals. Glutathione peroxidase (GSH-Px) activity in lens and kidney, reduced glutathione (GSH), vitamin E and β-carotene concentrations in kidney were lower in the diabetic group than in the control whereas plasma glucose, urea and creatinine, and kidney and lens peroxidation (LP) levels were higher in the diabetic group than in the control. However, kidney and lens LP levels, and plasma glucose, urea and creatinine values were decreased by VCE supplementation. Lens and kidney GSH-Px activity, kidney GSH, vitamin E and β-carotene concentrations and erythrocyte counts were increased by VCE treatment. Kidney weights, vitamin A, haemoglobin, hematocrit, leukocyte and platelets values were not changed by diabetes and/or VCE supplementation. VCE ameliorated also diabetes-induced histopathological changes in kidney. In conclusion, we observed that VCE supplementation is beneficial towards kidney and lens of aged diabetic rats by modulating oxidative and antioxidant systems. Copyright © 2011 John Wiley & Sons, Ltd.

Human kidney proximal tubule cells are vulnerable to the effects of Rauwolfia serpentina.

PubMed

Mossoba, Miriam E; Flynn, Thomas J; Vohra, Sanah; Wiesenfeld, Paddy L; Sprando, Robert L

2015-12-01

Rauwolfia serpentina (or Snake root plant) is a botanical dietary supplement marketed in the USA for maintaining blood pressure. Very few studies have addressed the safety of this herb, despite its wide availability to consumers. Its reported pleiotropic effects underscore the necessity for evaluating its safety. We used a human kidney cell line to investigate the possible negative effects of R. serpentina on the renal system in vitro, with a specific focus on the renal proximal tubules. We evaluated cellular and mitochondrial toxicity, along with a variety of other kidney-specific toxicology biomarkers. We found that R. serpentina was capable of producing highly detrimental effects in our in vitro renal cell system. These results suggest more studies are needed to investigate the safety of this dietary supplement in both kidney and other target organ systems.

Evidence suggesting a genetic contribution to kidney stone in northeastern Thai population.

PubMed

Sritippayawan, Suchai; Borvornpadungkitti, Sombat; Paemanee, Atchara; Predanon, Chagkrapan; Susaengrat, Wattanachai; Chuawattana, Duangporn; Sawasdee, Nunghathai; Nakjang, Sirintra; Pongtepaditep, Suttikarn; Nettuwakul, Choochai; Rungroj, Nanyawan; Vasuvattakul, Somkiat; Malasit, Prida; Yenchitsomanus, Pa-thai

2009-06-01

Genetic factor may play a role in the pathogenesis of kidney stone that is found in the northeastern (NE) Thai population. Herein, we report initial evidence suggesting genetic contribution to the disease in this population. We examined 1,034 subjects including 135 patients with kidney stone, 551 family members, and 348 villagers by radiography of kidney-ureter-bladder (KUB) and other methods, and also analyzed stones removed by surgical operations. One hundred and sixteen of 551 family members (21.05%) and 23 of the 348 villagers (6.61%) were affected with kidney stone. The relative risk (lambda(R)) of the disease among family members was 3.18. Calcium stones (whewellite, dahllite, and weddellite) were observed in about 88% of stones analyzed. Our data indicate familial aggregation of kidney stone in this population supporting that genetic factor should play some role in its pathogenesis. Genetic and genomic studies will be conducted to identify the genes associated with the disease.

Novel pathologic scoring tools predict end-stage kidney disease in light chain (AL) amyloidosis.

PubMed

Rubinstein, Samuel; Cornell, Robert F; Du, Liping; Concepcion, Beatrice; Goodman, Stacey; Harrell, Shelton; Horst, Sara; Lenihan, Daniel; Slosky, David; Fogo, Agnes; Langone, Anthony

2017-09-01

Light chain (AL) amyloidosis frequently involves the kidney, causing significant morbidity and mortality. A pathologic scoring system with prognostic utility has not been developed. We hypothesized that the extent of amyloid deposition and degree of scarring injury on kidney biopsy, could provide prognostic value, and aimed to develop pathologic scoring tools based on these features. This is a case-control study of 39 patients treated for AL amyloidosis with biopsy-proven kidney involvement at a large academic medical center. Our novel scoring tools, composite scarring injury score (CSIS) and amyloid score (AS) were applied to each kidney biopsy. The primary outcome was progression to dialysis-dependent end-stage kidney disease (ESKD) using a 12-month landmark analysis. At 12 months, nine patients had progressed to ESKD. Patients with an AS ≥7.5 had a significantly higher cumulative incidence of ESKD than those with AS <7.5 (p = .04, 95% CI 0.13-0.64). Using a 12-month landmark analysis, AS correlated with progression to ESKD. These data suggest that a kidney biopsy, in addition to providing diagnostic information, can be the basis for a pathologic scoring system with prognostic significance.

Systemic and kidney toxicity of intraocular administration of vascular endothelial growth factor inhibitors.

PubMed

Pellé, Gaëlle; Shweke, Nasim; Duong Van Huyen, Jean-Paul; Tricot, Leïla; Hessaïne, Sadika; Frémeaux-Bacchi, Véronique; Hiesse, Christian; Delahousse, Michel

2011-05-01

Intravenous injection of angiogenesis-inhibitor drugs is used widely to treat cancers. Associated renal complications primarily involve proteinuria and hypertension, and thrombotic microangiopathies also have been described. Intravitreal anti-vascular endothelial growth factor (VEGF) therapy currently is used by ophthalmologists to treat neovascularization in age-related macular degeneration. However, there is some evidence that intravitreal anti-VEGF injections may result in systemic absorption, with the potential for injury in organs that are reliant on VEGF, such as the kidney. We report the first case to our knowledge of a patient who developed an acute decrease in kidney function, nonimmune microangiopathic hemolytic anemia with schistocytes, and thrombocytopenia after 4 intravitreal injections of ranibizumab. Light microscopy of a kidney biopsy specimen showed segmental duplications of glomerular basement membranes with endothelial swelling and several recanalized arteriolar thrombi. Because of the increasing use of intravitreal anti-VEGF agents, ophthalmologists and nephrologists should be aware of the associated risk of kidney disease. Early detection is crucial so that intravitreal injections can be stopped before severe kidney disease occurs. Copyright © 2011 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.

Redox system and phospholipid metabolism in the kidney of hypertensive rats after FAAH inhibitor URB597 administration.

PubMed

Biernacki, Michał; Ambrożewicz, Ewa; Gęgotek, Agnieszka; Toczek, Marek; Bielawska, Katarzyna; Skrzydlewska, Elżbieta

2018-05-01

Primary and secondary hypertension is associated with kidney redox imbalance resulting in enhanced reactive oxygen species (ROS) and enzymes dependent phospholipid metabolism. The fatty acid amide hydrolase inhibitor, URB597, modulates the levels of endocannabinoids, particularly of anandamide, which is responsible for controlling blood pressure and regulating redox balance. Therefore, this study aimed to compare the effects of chronic URB597 administration to spontaneously hypertensive rats (SHR) and rats with secondary hypertension (DOCA-salt rats) on the kidney metabolism associated with the redox and endocannabinoid systems. It was shown fatty acid amide hydrolase (FAAH) inhibitor decreased the activity of ROS-generated enzymes what resulted in a reduction of ROS level. Moreover varied changes in antioxidant parameters were observed with tendency to improve antioxidant defense in SHR kidney. Moreover, URB597 administration to hypertensive rats decreased pro-inflammatory response, particularly in the kidneys of DOCA-salt hypertensive rats. URB597 had tendency to enhance ROS-dependent phospholipid oxidation, estimated by changes in neuroprostanes in the kidney of SHR and reactive aldehydes (4-hydroxynonenal and malondialdehyde) in DOCA-salt rats, in particular. The administration of FAAH inhibitor resulted in increased level of endocannabinoids in kidney of both groups of hypertensive rats led to enhanced expression of the cannabinoid receptors type 1 and 2 in SHR as well as vanilloid receptor 1 receptors in DOCA-salt rats. URB597 given to normotensive rats also affected kidney oxidative metabolism, resulting in enhanced level of neuroprostanes in Wistar Kyoto rats and reactive aldehydes in Wistar rats. Moreover, the level of endocannabinoids and cannabinoid receptors were significantly higher in both control groups of rats after URB597 administration. In conclusion, because URB597 disturbed the kidney redox system and phospholipid ROS-dependent and enzymatic-dependent metabolism, the administration of this inhibitor may enhance kidney disorders depending on model of hypertension, but may also cause kidney disturbances in control rats. Therefore, further studies are warranted. Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.

A Bioinformatics Approach Identifies Signal Transducer and Activator of Transcription-3 and Checkpoint Kinase 1 as Upstream Regulators of Kidney Injury Molecule-1 after Kidney Injury

PubMed Central

Ajay, Amrendra Kumar; Kim, Tae-Min; Ramirez-Gonzalez, Victoria; Park, Peter J.; Frank, David A.

2014-01-01

Kidney injury molecule-1 (KIM-1)/T cell Ig and mucin domain-containing protein-1 (TIM-1) is upregulated more than other proteins after AKI, and it is highly expressed in renal damage of various etiologies. In this capacity, KIM-1/TIM-1 acts as a phosphatidylserine receptor on the surface of injured proximal tubular epithelial cells, mediating phagocytosis of apoptotic cells, and it may also act as a costimulatory molecule for immune cells. Despite recognition of KIM-1 as an important therapeutic target for kidney disease, the regulators of KIM-1 transcription in the kidney remain unknown. Using a bioinformatics approach, we identified upstream regulators of KIM-1 after AKI. In response to tubular injury in rat and human kidneys or oxidant stress in human proximal tubular epithelial cells (HPTECs), KIM-1 expression increased significantly in a manner that corresponded temporally and regionally with increased phosphorylation of checkpoint kinase 1 (Chk1) and STAT3. Both ischemic and oxidant stress resulted in a dramatic increase in reactive oxygen species that phosphorylated and activated Chk1, which subsequently bound to STAT3, phosphorylating it at S727. Furthermore, STAT3 bound to the KIM-1 promoter after ischemic and oxidant stress, and pharmacological or genetic induction of STAT3 in HPTECs increased KIM-1 mRNA and protein levels. Conversely, inhibition of STAT3 using siRNAs or dominant negative mutants reduced KIM-1 expression in a kidney cancer cell line (769-P) that expresses high basal levels of KIM-1. These observations highlight Chk1 and STAT3 as critical upstream regulators of KIM-1 expression after AKI and may suggest novel approaches for therapeutic intervention. PMID:24158981

Immune cells and type 1 IFN in urine of SLE patients correlate with immunopathology in the kidney.

PubMed

Scott, Eric; Dooley, Mary Anne; Vilen, Barbara J; Clarke, Stephen H

2016-07-01

The immunopathological events in the kidneys of lupus nephritis (LN) patients are poorly understood due in part to the difficulty in acquiring serial biopsies and the inherent limitations in their analysis. To identify a means to circumvent these limitations, we investigated whether immune cells of kidney origin are present in patient urine and whether they correlate with kidney pathology. Flow cytometry analysis was performed on peripheral blood and urine cells of 69 SLE patients, of whom 41 were LN patients. In addition, type I IFN (IFNα/β) levels were determined in plasma and urine by bioassay. Approximately 60% of non-LN patients had urine lymphocytes. In these patients, T cells were always present and predominantly CD8(+), while B cells were either absent or a mixture of naïve and memory B cells. In contrast, >90% of LN patients had urine lymphocytes. In half, the B and T cells resembled those in non-LN patient urine; however, in the remaining patients, the B cells were exclusively Ig-secreting plasmablasts or plasma cells (PB/PCs) and the T cells were predominantly CD4(+). In addition, pDCs and IFNα/β frequently accompanied PB/PCs. The majority of patients with urine PB/PCs presented with proliferative nephritis and a significant loss of kidney function, which in some cases had progressed to end stage renal disease (ESRD). In conclusion, urine can provide access to cells of kidney resident populations for phenotypic and functional characterization. Analysis of these cells provides insight into the kidney immunopathology and may serve as biomarkers to identify patients at risk for developing LN and progressing to ESRD. Copyright © 2016 Elsevier Inc. All rights reserved.

Contemporary, age-based trends in the incidence and management of patients with early-stage kidney cancer.

PubMed

Tan, Hung-Jui; Filson, Christopher P; Litwin, Mark S

2015-01-01

Although kidney cancer incidence and nephrectomy rates have risen in tandem, clinical advances have generated new uncertainty regarding the optimal management of patients with small renal tumors, especially the elderly. To clarify existing practice patterns, we assessed contemporary trends in the incidence and management of patients with early-stage kidney cancer. Using Surveillance, Epidemiology, and End Results data, we identified adult patients diagnosed with T1aN0M0 kidney cancer from 2000 to 2010. We determined age-adjusted and age-specific incidence and management rates (i.e., nonoperative, ablation, partial nephrectomy [PN], and radical nephrectomy) per 100,000 adults and determined the average annual percent change (AAPC). Finally, we compared management groups using multinomial logistic regression accounting for patient characteristics, cancer information, and county-level measures for health. From 2000 to 2010, we identified 41,645 adults diagnosed with T1aN0M0 kidney cancer. Overall incidence increased from 3.7 to 7.0 per 100,000 adults (AAPC = 7.0%, P<0.001). Over the study interval, rates of PN (AAPC = 13.1%, P<0.001) increased substantially, becoming the most used treatment by 2010. Among the elderly, rates of nonoperative management and ablation approached nephrectomy rates for those aged 75 to 84 years and became the predominant strategy for patients older than 84 years. Adjusting for clinical, oncological, and environmental factors, older patients less frequently underwent PN and more often received ablative or nonoperative management (P<0.001). As the incidence of early-stage kidney cancer rises, patients are increasingly treated with nonoperative and nephron-sparing strategies, especially among the most elderly. The broader array of treatment options suggests opportunities to better personalize kidney cancer care for seniors. Published by Elsevier Inc.

African American kidney transplant patients’ perspectives on challenges in the living donation process

PubMed Central

Sieverdes, John C.; Nemeth, Lynne S.; Magwood, Gayenell S.; Baliga, Prabhakar K.; Chavin, Kenneth D.; Ruggiero, Ken J.; Treiber, Frank A.

2015-01-01

Context The increasing shortage of deceased donor kidneys suitable for African Americans highlights the critical need to increase living donations among African Americans. Little research has addressed African American transplant recipients’ perspectives on challenges and barriers related to the living donation process. Objective To understand the perspectives of African American recipients of deceased and living donor kidney transplants on challenges, barriers, and educational needs related to pursuing such transplants. Participants and Design A mixed-method design involved 27 African American kidney recipients (13 male) in 4 focus groups (2 per recipient type: 16 African American deceased donor and 11 living donor recipients) and questionnaires. Focus group transcripts were evaluated with NVivo 10.0 (QSR, International) by using inductive and deductive qualitative methods along with crystallization to develop themes of underlying barriers to the living donor kidney transplant process and were compared with the questionnaires. Results Four main themes were identified from groups: concerns, knowledge and learning, expectations of support, and communication. Many concerns for the donor were identified (eg, process too difficult, financial burden, effect on relationships). A general lack of knowledge about the donor process and lack of behavioral skills on how to approach others was noted. The latter was especially evident among deceased donor recipients. Findings from the questionnaires on myths and perceptions supported the lack of knowledge in a variety of domains, including donors’ surgical outcomes risks, costs of surgery, and impact on future health. Participants thought that an educational program led by an African American recipient of a living donor kidney transplant, including practice in approaching others, would increase the likelihood of transplant-eligible patients pursuing living donor kidney transplant. PMID:26107278

Evaluation of Kidney Stones with Reduced-Radiation Dose CT: Progress from 2011-2012 to 2015-2016-Not There Yet.

PubMed

Weisenthal, Karrin; Karthik, Priyadarshini; Shaw, Melissa; Sengupta, Debapriya; Bhargavan-Chatfield, Mythreyi; Burleson, Judy; Mustafa, Adel; Kalra, Mannudeep; Moore, Christopher

2018-02-01

Purpose To determine if the use of reduced-dose computed tomography (CT) for evaluation of kidney stones increased in 2015-2016 compared with that in 2011-2012, to determine variability in radiation exposure according to facility for this indication, and to establish a current average radiation dose for CT evaluation for kidney stones by querying a national dose registry. Materials and Methods This cross-sectional study was exempt from institutional review board approval. Data were obtained from the American College of Radiology dose registry for CT examinations submitted from July 2015 to June 2016. Study descriptors consistent with single-phase unenhanced CT for evaluation of kidney stones and associated RadLex® Playbook identifiers (RPIDs) were retrospectively identified. Facilities actively submitting data on kidney stone-specific CT examinations were included. Dose metrics including volumetric CT dose index, dose-length product, and size-specific dose estimate, when available, were reported, and a random effects model was run to account for clustering of CT examinations at facilities. A z-ratio was calculated to test for a significant difference between the proportion of reduced-radiation dose CT examinations (defined as those with a dose-length product of 200 mGy · cm or less) performed in 2015-2016 and the proportion performed in 2011-2012. Results Three hundred four study descriptors for kidney stone CT corresponding to data from 328 facilities that submitted 105 334 kidney stone CT examinations were identified. Reduced-dose CT examinations accounted for 8040 of 105 334 (7.6%) CT examinations, a 5.6% increase from the 1010 of 49 903 (2%) examinations in 2011-2012 (P < .001). Mean overall dose-length product was 689 mGy · cm (95% confidence interval: 667, 712), decreased from the mean of 746 mGy · cm observed in 2011-2012. Median facility dose-length product varied up to sevenfold, from less than 200 mGy · cm to greater than 1600 mGy · cm. Conclusion Use of reduced-radiation dose CT for evaluation of kidney stones has increased since 2011-2012, but remains low; variability of radiation dose according to facility continues to be wide. National mean CT radiation exposure for evaluation of renal colic during 2015-2016 decreased relative to 2011-2012 values, but remained well above what is reasonably achievable. © RSNA, 2017.

The renaissance of complement therapeutics

PubMed Central

Ricklin, Daniel; Mastellos, Dimitrios C.; Reis, Edimara S.; Lambris, John D.

2018-01-01

The increasing number of clinical conditions that involve a pathological contribution from the complement system — many of which affect the kidneys — has spurred a regained interest in therapeutic options to modulate this host defence pathway. Molecular insight, technological advances, and the first decade of clinical experience with the complement-specific drug eculizumab, have contributed to a growing confidence in therapeutic complement inhibition. More than 20 candidate drugs that target various stages of the complement cascade are currently being evaluated in clinical trials, and additional agents are in preclinical development. Such diversity is clearly needed in view of the complex and distinct involvement of complement in a wide range of clinical conditions, including rare kidney disorders, transplant rejection and haemodialysis-induced inflammation. The existing drugs cannot be applied to all complement-driven diseases, and each indication has to be assessed individually. Alongside considerations concerning optimal points of intervention and economic factors, patient stratification will become essential to identify the best complement-specific therapy for each individual patient. This Review provides an overview of the therapeutic concepts, targets and candidate drugs, summarizes insights from clinical trials, and reflects on existing challenges for the development of complement therapeutics for kidney diseases and beyond. PMID:29199277

Emergency department revisits for patients with kidney stones in California.

PubMed

Scales, Charles D; Lin, Li; Saigal, Christopher S; Bennett, Carol J; Ponce, Ninez A; Mangione, Carol M; Litwin, Mark S

2015-04-01

Kidney stones affect nearly one in 11 persons in the United States, and among those experiencing symptoms, emergency care is common. In this population, little is known about the incidence of and factors associated with repeat emergency department (ED) visits. The objective was to identify associations between potentially mutable factors and the risk of an ED revisit for patients with kidney stones in a large, all-payer cohort. This was a retrospective cohort study of all patients in California initially treated and released from EDs for kidney stones between February 2008 and November 2009. A multivariable regression model was created to identify associations between patient-level characteristics, area health care resources, processes of care, and the risk of repeat ED visits. The primary outcome was a second ED visit within 30 days of the initial discharge from emergent care. Among 128,564 patients discharged from emergent care, 13,684 (11%) had at least one additional emergent visit for treatment of their kidney stone. In these patients, nearly one in three required hospitalization or an urgent temporizing procedure at the second visit. On multivariable analysis, the risk of an ED revisit was associated with insurance status (e.g., Medicaid vs. private insurance; odds ratio [OR] = 1.52, 95% confidence interval [CI] = 1.43 to 1.61; p < 0.001). Greater access to urologic care was associated with lower odds of an ED revisit (highest quartile OR = 0.88, 95% CI = 0.80 to 0.97; p < 0.01 vs. lowest quartile). In exploratory models, performance of a complete blood count was associated with a decreased odds of revisit (OR = 0.86, 95% CI = 0.75 to 0.97; p = 0.02). Repeat high-acuity care affects one in nine patients discharged from initial emergent evaluations for kidney stones. Access to urologic care and processes of care are associated with lower risk of repeat emergent encounters. Efforts are indicated to identify preventable causes of ED revisits for kidney stone patients and design interventions to reduce the risk of high-cost, high-acuity, repeat care. © 2015 by the Society for Academic Emergency Medicine.

Crossing Anatomic Barriers-Transplantation of a Kidney with 5 Arteries, Duplication of the Pyelocalyceal System, and Double Ureter.

PubMed

Bachul, Piotr J; Osuch, Czesław; Chang, Ea-Sle; Bętkowska-Prokop, Alina; Pasternak, Artur; Szura, Mirosław; Matyja, Andrzej; Walocha, Jerzy A

2017-10-01

During the time of organ harvest, it is crucial for the kidney procurement team to consider significant vascular anatomical variations. Multiple renal arteries are not uncommon, and unintentional injury can result in an irreversibly damaged kidney graft that needs to be discarded. We present a kidney graft with 5 renal arteries and a single vein that was successfully procured and implanted with good graft function at discharge and at 4-yr follow-up. According to the literature, additional renal arteries can be found in about 33% of kidneys. This is the first study on a kidney with 5 arteries in the published literature, especially in the context of transplantation.

A kidney-specific genetic control module in mice governs endocrine regulation of the cytochrome P450 gene Cyp27b1 essential for vitamin D3 activation

PubMed Central

Meyer, Mark B.; Benkusky, Nancy A.; Kaufmann, Martin; Lee, Seong Min; Onal, Melda; Jones, Glenville; Pike, J. Wesley

2017-01-01

The vitamin D endocrine system regulates mineral homeostasis through its activities in the intestine, kidney, and bone. Terminal activation of vitamin D3 to its hormonal form, 1α,25-dihydroxyvitamin D3 (1,25(OH)2D3), occurs in the kidney via the cytochrome P450 enzyme CYP27B1. Despite its importance in vitamin D metabolism, the molecular mechanisms underlying the regulation of the gene for this enzyme, Cyp27b1, are unknown. Here, we identified a kidney-specific control module governed by a renal cell-specific chromatin structure located distal to Cyp27b1 that mediates unique basal and parathyroid hormone (PTH)-, fibroblast growth factor 23 (FGF23)-, and 1,25(OH)2D3-mediated regulation of Cyp27b1 expression. Selective genomic deletion of key components within this module in mice resulted in loss of either PTH induction or FGF23 and 1,25(OH)2D3 suppression of Cyp27b1 gene expression; the former loss caused a debilitating skeletal phenotype, whereas the latter conferred a quasi-normal bone mineral phenotype through compensatory homeostatic mechanisms involving Cyp24a1. We found that Cyp27b1 is also expressed at low levels in non-renal cells, in which transcription was modulated exclusively by inflammatory factors via a process that was unaffected by deletion of the kidney-specific module. These results reveal that differential regulation of Cyp27b1 expression represents a mechanism whereby 1,25(OH)2D3 can fulfill separate functional roles, first in the kidney to control mineral homeostasis and second in extra-renal cells to regulate target genes linked to specific biological responses. Furthermore, we conclude that these mouse models open new avenues for the study of vitamin D metabolism and its involvement in therapeutic strategies for human health and disease. PMID:28808057

Boldine Improves Kidney Damage in the Goldblatt 2K1C Model Avoiding the Increase in TGF-β.

PubMed

Gómez, Gonzalo I; Velarde, Victoria

2018-06-25

Boldine, a major aporphine alkaloid found in the Chilean boldo tree, is a potent antioxidant. Oxidative stress plays a detrimental role in the pathogenesis of kidney damage in renovascular hypertension (RVH). The activation of the renin-angiotensin system (RAS) is crucial to the development and progression of hypertensive renal damage and TGF-β is closely associated with the activation of RAS. In the present study, we assessed the effect of boldine on the progression of kidney disease using the 2K1C hypertension model and identifying mediators in the RAS, such as TGF-β, that could be modulated by this alkaloid. Toward this hypothesis, rats ( n = 5/group) were treated with boldine (50 mg/kg/day, gavage) for six weeks after 2K1C surgery (pressure ≥ 180 mmHg). Kidney function was evaluated by measuring of proteinuria/creatininuria ratio (U prot/U Crea), oxidative stress (OS) by measuring thiobarbituric acid reactive substances (TBARS). The evolution of systolic blood pressure (SBP) was followed weekly. Alpha-smooth muscle actin (α-SMA) and Col III were used as markers of kidney damage; ED-1 and osteopontin (OPN) were used as markers of inflammation. We also explored the effect in RAS mediators, such as ACE-1 and TGF-β. Boldine treatment reduced the UProt/UCrea ratio, plasma TBARS, and slightly reduced SBP in 2K1C hypertensive rats, producing no effect in control animals. In 2K1C rats treated with boldine the levels of α-SMA, Col III, ED-1, and OPN were lower when compared to 2K1C rats. Boldine prevented the increase in ACE-1 and TGF-β in 2K1C rats, suggesting that boldine reduces kidney damage. These results suggest that boldine could potentially be used as a nutraceutic.

Organ quality metrics are a poor predictor of costs and resource utilization in deceased donor kidney transplantation.

PubMed

Stahl, Christopher C; Wima, Koffi; Hanseman, Dennis J; Hoehn, Richard S; Ertel, Audrey; Midura, Emily F; Hohmann, Samuel F; Paquette, Ian M; Shah, Shimul A; Abbott, Daniel E

2015-12-01

The desire to provide cost-effective care has lead to an investigation of the costs of therapy for end-stage renal disease. Organ quality metrics are one way to attempt to stratify kidney transplants, although the ability of these metrics to predict costs and resource use is undetermined. The Scientific Registry of Transplant Recipients database was linked to the University HealthSystem Consortium Database to identify adult deceased donor kidney transplant recipients from 2009 to 2012. Patients were divided into cohorts by kidney criteria (standard vs expanded) or kidney donor profile index (KDPI) score (<85 vs 85+). Length of stay, 30-day readmission, discharge disposition, and delayed graft function were used as indicators of resource use. Cost was defined as reimbursement based on Medicare cost/charge ratios and included the costs of readmission when applicable. More than 19,500 patients populated the final dataset. Lower-quality kidneys (expanded criteria donor or KDPI 85+) were more likely to be transplanted in older (both P < .001) and diabetic recipients (both P < .001). After multivariable analysis controlling for recipient characteristics, we found that expanded criteria donor transplants were not associated with increased costs compared with standard criteria donor transplants (risk ratio [RR] 0.97, 95% confidence interval [CI] 0.93-1.00, P = .07). KDPI 85+ was associated with slightly lower costs than KDPI <85 transplants (RR 0.95, 95% CI 0.91-0.99, P = .02). When KDPI was considered as a continuous variable, the association was maintained (RR 0.9993, 95% CI 0.999-0.9998, P = .01). Organ quality metrics are less influential predictors of short-term costs than recipient factors. Future studies should focus on recipient characteristics as a way to discern high versus low cost transplantation procedures. Copyright © 2015 Elsevier Inc. All rights reserved.

Differences in Access to Kidney Transplantation between Hispanic and Non-Hispanic Whites by Geographic Location in the United States

PubMed Central

Goldstein, Benjamin A.; Mitani, Aya A.; Lenihan, Colin R.; Winkelmayer, Wolfgang C.

2013-01-01

Summary Background and objectives Hispanic patients undergoing chronic dialysis are less likely to receive a kidney transplant compared with non-Hispanic whites. This study sought to elucidate disparities in the path to receipt of a deceased donor transplant between Hispanic and non-Hispanic whites. Design, setting, participants, & measurements Using the US Renal Data System, 417,801 Caucasians who initiated dialysis between January 1, 1995 and December 31, 2007 with follow-up through 2008 were identified. This study investigated time from first dialysis to first kidney transplantation, time from first dialysis to waitlisting, and time from waitlisting to kidney transplantation. Multivariable Cox regression estimated cause-specific hazard ratios (HRCS) and subdistribution (competing risk) hazard ratios (HRSD) for Hispanics versus non-Hispanic whites. Results Hispanics experienced lower adjusted rates of deceased donor kidney transplantation than non-Hispanic whites (HRCS, 0.77; 95% confidence interval [95% CI], 0.75 to 0.80) measured from dialysis initiation. No meaningful differences were found in time from dialysis initiation to placement on the transplant waitlist. Once waitlisted, Hispanics had lower adjusted rates of deceased donor kidney transplantation (HRCS, 0.66; 95% CI, 0.64 to 0.68), and the association attenuated once accounting for competing risks (HRSD, 0.79; 95% CI, 0.77 to 0.81). Additionally controlling for blood type and organ procurement organization further reduced the disparity (HRSD, 0.99; 95% CI, 0.96 to 1.02). Conclusions After accounting for geographic location and controlling for competing risks (e.g., Hispanic survival advantage), the disparity in access to deceased donor transplantation was markedly attenuated among Hispanics compared with non-Hispanic whites. To overcome the geographic disparities that Hispanics encounter in the path to transplantation, organ allocation policy revisions are needed to improve donor organ equity. PMID:24115195

Identification and transcriptional profile of multiple genes in the posterior kidney of Nile tilapia at 6h post bacterial infections

USDA-ARS?s Scientific Manuscript database

To understand the molecular mechanisms involved in response of Nile tilapia (Oreochromis niloticus) to bacterial infection, suppression subtractive cDNA hybridization technique was used to identify upregulated genes in the posterior kidney of Nile tilapia at 6h post infection with Aeromonas hydrophi...

Decision aids to increase living donor kidney transplantation

PubMed Central

Gander, Jennifer C.; Gordon, Elisa J.; Patzer, Rachel E.

2017-01-01

Purpose of review For the more than 636,000 adults with end-stage renal disease (ESRD) in the U.S., kidney transplantation is the preferred treatment compared to dialysis. Living donor kidney transplantation (LDKT) comprised 31% of kidney transplantations in 2015, an 8% decrease since 2004. We aimed to summarize the current literature on decision aids that could be used to improve LDKT rates. Recent findings Decision aids are evidence-based tools designed to help patients and their families make difficult treatment decisions. LDKT decision aids can help ESRD patients, patients’ family and friends, and healthcare providers engage in treatment decisions and thereby overcome multifactorial LDKT barriers. Summary We identified 12 LDKT decision aids designed to provide information about LDKT, and/or to help ESRD patients identify potential living donors, and/or to help healthcare providers make decisions about treatment for ESRD or living donation. Of these, 4 were shown to be effective in increasing LDKT, donor inquiries, LDKT knowledge, and willingness to discuss LDKT. Although each LDKT decision aid has limitations, adherence to decision aid development guidelines may improve decision aid utilization and access to LDKT. PMID:29034143

The effect of triploidy and vaccination on neutrophils and B-cells in the peripheral blood and head kidney of 0+ and 1+ Atlantic salmon (Salmo salar L.) post-smolts.

PubMed

Fraser, Thomas W K; Rønneseth, Anita; Haugland, Gyri T; Fjelldal, Per Gunnar; Mayer, Ian; Wergeland, Heidrun I

2012-07-01

Sterile triploid fish are being used in aquaculture to prevent early unwanted sexual maturation and the genetic interaction between wild and cultured fish; however, triploid fish are typically considered to be more susceptible to disease than diploid counterparts. Proportions of leucocytes from the head kidney and peripheral blood were identified using monoclonal antibodies and flow cytometry in triploid and diploid, vaccinated and unvaccinated, out-of-season (0+) and 1+ Atlantic salmon (Salmo salar L.) three weeks post seawater transfer. Triploid 1+ fish were significantly (P<0.05) heavier than diploid fish at the time of sampling, whereas triploid 0+ had a significantly lower condition factor than diploids. Ploidy had a significant effect on the proportion of B-cells in the blood of both 0+ and 1+ fish, and the head kidney of 1+ fish, with triploids having lower proportions of B-cells to diploids in both smolt groups. In addition, a significant ploidy×vaccination interaction effect was observed in the response of neutrophils in the blood (vaccinated diploids had a higher mean proportion than diploid unvaccinated) and B-cells in the head kidney (in vaccinated fish, triploids had a lower mean proportion than diploids) in 0+ smolts. Vaccination was found to significantly increase the proportion of B-cells in the head kidney of 1+ smolts in both ploidy. Size (fish weight) was positively correlated with neutrophil proportions in 1+ fish. Our findings are discussed in relation to the physiological differences related to ploidy. The results suggest that ploidy as well as smelting regime influences the immune system of Atlantic salmon post-smolts. Copyright © 2012 Elsevier Ltd. All rights reserved.

Intra-Abdominal Cooling System Limits Ischemia-Reperfusion Injury During Robot-Assisted Renal Transplantation.

PubMed

Meier, R P H; Piller, V; Hagen, M E; Joliat, C; Buchs, J-B; Nastasi, A; Ruttimann, R; Buchs, N C; Moll, S; Vallée, J-P; Lazeyras, F; Morel, P; Bühler, L

2018-01-01

Robot-assisted kidney transplantation is feasible; however, concerns have been raised about possible increases in warm ischemia times. We describe a novel intra-abdominal cooling system to continuously cool the kidney during the procedure. Porcine kidneys were procured by standard open technique. Groups were as follows: Robotic renal transplantation with (n = 11) and without (n = 6) continuous intra-abdominal cooling and conventional open technique with intermittent 4°C saline cooling (n = 6). Renal cortex temperature, magnetic resonance imaging, and histology were analyzed. Robotic renal transplantation required a longer anastomosis time, either with or without the cooling system, compared to the open approach (70.4 ± 17.7 min and 74.0 ± 21.5 min vs. 48.7 ± 11.2 min, p-values < 0.05). The temperature was lower in the robotic group with cooling system compared to the open approach group (6.5 ± 3.1°C vs. 22.5 ± 6.5°C; p = 0.001) or compared to the robotic group without the cooling system (28.7 ± 3.3°C; p < 0.001). Magnetic resonance imaging parenchymal heterogeneities and histologic ischemia-reperfusion lesions were more severe in the robotic group without cooling than in the cooled (open and robotic) groups. Robot-assisted kidney transplantation prolongs the warm ischemia time of the donor kidney. We developed a novel intra-abdominal cooling system that suppresses the noncontrolled rewarming of donor kidneys during the transplant procedure and prevents ischemia-reperfusion injuries. © 2017 The Authors. American Journal of Transplantation published by Wiley Periodicals, Inc. on behalf of American Society of Transplant Surgeons.

Preliminary feasibility study of a new method of hypothermia in an experimental canine model

PubMed Central

Sert, İbrahim Ünal; Akand, Murat; Kılıç, Özcan; Yavru, Nuri; Bulut, Ersan

2017-01-01

Objective To build up a new microcontroller thermoelectric system to achieve renal hypothermia. Material and methods Renal hypothermia system was tested under in vivo conditions in the kidneys of ten Mongrel dogs. Ambient temperature was evaluated using two different microcontrollers. In order to ensure hypothermia in the renal parenchyma, selection can be made among 4 modules and sensors which detect the temperature of the area. The temperature range of the system was adjusted between −50°C and +50°C. Results When single and double poles of the kidney were cooled, initial mean intraperitoneal temperature values were found 37.7°C for rectum and 36.5°C for renal cortex and medulla. After the temperature of the cooling module was set to 12°C, the module was placed on the poles of the kidney. After fifteen minutes, temperature was 15.4°C in the lower pole of the kidney, 28.1°C in the cortex of the other side and 29.2°C in the intramedullary region. The temperature was found to be 15°C in the vicinity and 26.1°C in the cortex across the module. After the system was stabilized, a very slight change was observed in the temperature. Conclusion Hypothermia system developed ensured desired cooling of the targeted part of the kidney; however, it did not cause a change in the temperature of other parts of the kidney or general body temperature. Thus, it was possible to create a long-term study area for renal parenchymal surgery. PMID:28861307

Preliminary feasibility study of a new method of hypothermia in an experimental canine model.

PubMed

Sert, İbrahim Ünal; Akand, Murat; Kılıç, Özcan; Yavru, Nuri; Bulut, Ersan

2017-09-01

To build up a new microcontroller thermoelectric system to achieve renal hypothermia. Renal hypothermia system was tested under in vivo conditions in the kidneys of ten Mongrel dogs. Ambient temperature was evaluated using two different microcontrollers. In order to ensure hypothermia in the renal parenchyma, selection can be made among 4 modules and sensors which detect the temperature of the area. The temperature range of the system was adjusted between -50°C and +50°C. When single and double poles of the kidney were cooled, initial mean intraperitoneal temperature values were found 37.7°C for rectum and 36.5°C for renal cortex and medulla. After the temperature of the cooling module was set to 12°C, the module was placed on the poles of the kidney. After fifteen minutes, temperature was 15.4°C in the lower pole of the kidney, 28.1°C in the cortex of the other side and 29.2°C in the intramedullary region. The temperature was found to be 15°C in the vicinity and 26.1°C in the cortex across the module. After the system was stabilized, a very slight change was observed in the temperature. Hypothermia system developed ensured desired cooling of the targeted part of the kidney; however, it did not cause a change in the temperature of other parts of the kidney or general body temperature. Thus, it was possible to create a long-term study area for renal parenchymal surgery.

Evidence for a distinct gut microbiome in kidney stone formers compared to non-stone formers.

PubMed

Stern, Joshua M; Moazami, Saman; Qiu, Yunping; Kurland, Irwin; Chen, Zigui; Agalliu, Ilir; Burk, Robert; Davies, Kelvin P

2016-10-01

The trillions of microbes that colonize our adult intestine are referred to as the gut microbiome (GMB). Functionally it behaves as a metabolic organ that communicates with, and complements, our own human metabolic apparatus. While the relationship between the GMB and kidney stone disease (KSD) has not been investigated, dysbiosis of the GMB has been associated with diabetes, obesity and cardiovascular disease. In this pilot study we sought to identify unique changes in the GMB of kidney stone patients compared to patients without KSD. With an IRB-approved protocol we enrolled 29 patients into our pilot study. 23 patients were kidney stone formers and six were non-stone forming controls. Specimens were collected after a 6h fast and were flash frozen in dry ice and then stored at -80 °C. Microbiome: determination of bacterial abundance was by analysis of 16 s rRNA marker gene sequences using next generation sequencing. Sequencing of the GMB identified 178 bacterial genera. The five most abundant enterotypes within each group made up to greater than 50 % of the bacterial abundance identified. Bacteroides was 3.4 times more abundant in the KSD group as compared to control (34.9 vs 10.2 %; p = 0.001). Prevotella was 2.8 times more abundant in the control group as compared to the KSD group (34.7 vs 12.3 %; p = 0.005). In a multivariate analysis including age, gender, BMI, and DM, kidney stone disease remained an increased risk for high prevalence for Bacteroides (OR = 3.26, p = 0.033), whereas there was an inverse association with Prevotella (OR = 0.37, p = 0.043). There were no statistically significant differences in bacterial abundance levels for Bacteroides or Prevotella when comparing patients with and without DM, obesity (BMI >30), HTN or HLD. 11 kidney stone patients completed 24 h urine analysis at the time of this writing. Looking at the bacterial genuses with at least 4 % abundance in the kidney stone group, Eubacterium was inversely correlated with oxalate levels (r = -0.60, p < 0.06) and Escherichia trended to an inverse correlation with citrate (r = -0.56, p < 0.08). We also compared bacterial abundance between uric acid (UA) stone formers (n = 5) and non UA stone formers (n = 18) and found no significant difference between them. We identified two genus of bacteria in the GMB that had significant association with KSD. Interestingly, components of the 24-h urine appear to be correlated to bacterial abundance. These preliminary studies for the first time associate differences in the GMB with kidney stone formation. Further studies are warranted to evaluate the potential causative role of preexisting dysbiosis in kidney stone disease.

Renal Insufficiency After Contrast Media Administration Trial II (REMEDIAL II): RenalGuard System in high-risk patients for contrast-induced acute kidney injury.

PubMed

Briguori, Carlo; Visconti, Gabriella; Focaccio, Amelia; Airoldi, Flavio; Valgimigli, Marco; Sangiorgi, Giuseppe Massimo; Golia, Bruno; Ricciardelli, Bruno; Condorelli, Gerolama

2011-09-13

The RenalGuard System, which creates high urine output and fluid balancing, may be beneficial in preventing contrast-induced acute kidney injury. The Renal Insufficiency After Contrast Media Administration Trial II (REMEDIAL II) trial is a randomized, multicenter, investigator-driven trial addressing the prevention of contrast-induced acute kidney injury in high-risk patients. Patients with an estimated glomerular filtration rate ≤30 mL · min(-1) · 1.73 m(-2) and/or a risk score ≥11 were randomly assigned to sodium bicarbonate solution and N-acetylcysteine (control group) or hydration with saline and N-acetylcysteine controlled by the RenalGuard System and furosemide (RenalGuard group). The primary end point was an increase of ≥0.3 mg/dL in the serum creatinine concentration at 48 hours after the procedure. The secondary end points included serum cystatin C kinetics and rate of in-hospital dialysis. Contrast-induced acute kidney injury occurred in 16 of 146 patients in the RenalGuard group (11%) and in 30 of 146 patients in the control group (20.5%; odds ratio, 0.47; 95% confidence interval, 0.24 to 0.92). There were 142 patients (48.5%) with an estimated glomerular filtration rate ≤30 mL · min(-1) · 1.73 and 149 patients (51.5%) with only a risk score ≥11. Subgroup analysis according to inclusion criteria showed a similarly lower risk of adverse events (estimated glomerular filtration rate ≤30 mL · min(-1) · 1.73 m(-2): odds ratio, 0.44; risk score ≥11: odds ratio, 0.45; P for interaction=0.97). Changes in cystatin C at 24 hours (0.02±0.32 versus -0.08±0.26; P=0.002) and 48 hours (0.12±0.42 versus 0.03±0.31; P=0.001) and the rate of in-hospital dialysis (4.1% versus 0.7%; P=0.056) were higher in the control group. RenalGuard therapy is superior to sodium bicarbonate and N-acetylcysteine in preventing contrast-induced acute kidney injury in high-risk patients. URL: http://www.clinicaltrial.gov. Unique identifier: NCT01098032.

Periodontitis associated with chronic kidney disease among Mexican Americans.

PubMed

Ioannidou, Effie; Hall, Yoshio; Swede, Helen; Himmelfarb, Jonathan

2013-01-01

In comparison to non-Hispanic whites, a number of health-care disparities, including poor oral health, have been identified among Hispanics in general and Mexican Americans in particular. We hypothesized that Mexican Americans with chronic kidney disease (CKD) would have higher prevalence of chronic periodontitis compared with Mexican Americans with normal kidney function, and that the level of kidney function would be inversely related to the prevalence of periodontal disease. We examined this hypothesis using the National Health and Nutrition Examination Survey 1988-1994 (NHANES III) data set. We followed the American Academy of Periodontology/Center for Disease Control and Prevention case definition for periodontitis. Glomerular filtration rate was estimated using the CKD-Epidemiology equation for Hispanic populations. The classification to CKD stages was based on the National Kidney Foundation Kidney Disease Outcomes Quality Initiative. Periodontitis prevalence increased across the kidney function groups showing a statistically significant dose-response association (P<0.001). Mexican Americans with reduced kidney function were twofold more likely to have periodontitis compared with Mexican Americans with normal kidney function after adjusting for potential confounders such as smoking, diabetes, and socioeconomic status. Multivariate adjusted odds ratio for periodontitis significantly increased with 1, 5, and 10 mL/minute estimated glomerular filtration rate reduction from the mean. This is the first report, to the best our knowledge, that showed an increase of periodontitis prevalence with decreased kidney function in this population. © 2012 American Association of Public Health Dentistry.

Periodontitis associated with Chronic Kidney Disease among Mexican Americans

PubMed Central

Ioannidou, Effie; Hall, Yoshio; Swede, Helen; Himmelfarb, Jonathan

2012-01-01

Objective In comparison to non-Hispanic whites, a number of healthcare disparities, including poor oral health, have been identified among Hispanics in general and Mexican-Americans in particular. We hypothesized that Mexican-Americans with Chronic Kidney disease (CKD) would have higher prevalence of chronic periodontitis compared to Mexican Americans with normal kidney function, and that the level of kidney function would be inversely related to the prevalence of periodontal disease. Method We examined this hypothesis using the National Health and Nutrition Examination Survey 1988–1994 (NHANES III) dataset. We followed the American Academy of Periodontology (AAP)/Center for Disease Control and Prevention (CDC) case definition for periodontitis. Glomerular filtration rate was estimated using the CKD-Epidemiology (EPI) equation for Hispanic populations. The classification to CKD stages was based on the National Kidney Foundation Kidney Disease Outcomes Quality Initiative. Results Periodontitis prevalence increased across the kidney function groups showing a statistically significant dose-response association (p<0.001). Mexican Americans with reduced kidney function were 2-fold more likely to have periodontitis compared to Mexican Americans with normal kidney function after adjusting for potential confounders such as smoking, diabetes and socioeconomic status. Multivariate adjusted Odds Ratio for periodontitis significantly increased with 1, 5 and 10 mL/minute eGFR reduction from the mean. Conclusion This is the first report, to the best our knowledge, that showed an increase of periodontitis prevalence with decreased kidney function in this population. PMID:22775287

Determination of minor and trace elements in kidney stones by x-ray fluorescence analysis

NASA Astrophysics Data System (ADS)

Srivastava, Anjali; Heisinger, Brianne J.; Sinha, Vaibhav; Lee, Hyong-Koo; Liu, Xin; Qu, Mingliang; Duan, Xinhui; Leng, Shuai; McCollough, Cynthia H.

2014-03-01

The determination of accurate material composition of a kidney stone is crucial for understanding the formation of the kidney stone as well as for preventive therapeutic strategies. Radiations probing instrumental activation analysis techniques are excellent tools for identification of involved materials present in the kidney stone. In particular, x-ray fluorescence (XRF) can be very useful for the determination of minor and trace materials in the kidney stone. The X-ray fluorescence measurements were performed at the Radiation Measurements and Spectroscopy Laboratory (RMSL) of department of nuclear engineering of Missouri University of Science and Technology and different kidney stones were acquired from the Mayo Clinic, Rochester, Minnesota. Presently, experimental studies in conjunction with analytical techniques were used to determine the exact composition of the kidney stone. A new type of experimental set-up was developed and utilized for XRF analysis of the kidney stone. The correlation of applied radiation source intensity, emission of X-ray spectrum from involving elements and absorption coefficient characteristics were analyzed. To verify the experimental results with analytical calculation, several sets of kidney stones were analyzed using XRF technique. The elements which were identified from this techniques are Silver (Ag), Arsenic (As), Bromine (Br), Chromium (Cr), Copper (Cu), Gallium (Ga), Germanium (Ge), Molybdenum (Mo), Niobium (Nb), Rubidium (Rb), Selenium (Se), Strontium (Sr), Yttrium (Y), Zirconium (Zr). This paper presents a new approach for exact detection of accurate material composition of kidney stone materials using XRF instrumental activation analysis technique.

The DESCARTES-Nantes survey of kidney transplant recipients displaying clinical operational tolerance identifies 35 new tolerant patients and 34 almost tolerant patients.

PubMed

Massart, Annick; Pallier, Annaïck; Pascual, Julio; Viklicky, Ondrej; Budde, Klemens; Spasovski, Goce; Klinger, Marian; Sever, Mehmet Sukru; Sørensen, Søren Schwartz; Hadaya, Karine; Oberbauer, Rainer; Dudley, Christopher; De Fijter, Johan W; Yussim, Alexander; Hazzan, Marc; Wekerle, Thomas; Berglund, David; De Biase, Consuelo; Pérez-Sáez, María José; Mühlfeld, Anja; Orlando, Giuseppe; Clemente, Katia; Lai, Quirino; Pisani, Francesco; Kandus, Aljosa; Baas, Marije; Bemelman, Frederike; Ponikvar, Jadranka Buturovic; Mazouz, Hakim; Stratta, Piero; Subra, Jean-François; Villemain, Florence; Hoitsma, Andries; Braun, Laura; Cantarell, Maria Carmen; Colak, Hulya; Courtney, Aisling; Frasca, Giovanni Maria; Howse, Matthew; Naesens, Maarten; Reischig, Tomas; Serón, Daniel; Seyahi, Nurhan; Tugmen, Cem; Alonso Hernandez, Angel; Beňa, Luboslav; Biancone, Luigi; Cuna, Vania; Díaz-Corte, Carmen; Dufay, Alexandre; Gaasbeek, André; Garnier, Arnaud; Gatault, Philippe; Gentil Govantes, Miguel Angel; Glowacki, François; Gross, Oliver; Hurault de Ligny, Bruno; Huynh-Do, Uyen; Janbon, Bénédicte; Jiménez Del Cerro, Luis Antonio; Keller, Frieder; La Manna, Gaetano; Lauzurica, Ricardo; Le Monies De Sagazan, Hervé; Thaiss, Friedrich; Legendre, Christophe; Martin, Séverine; Moal, Marie-Christine; Noël, Christian; Pillebout, Evangeline; Piredda, Gian Benedetto; Puga, Ana Ramírez; Sulowicz, Wladyslaw; Tuglular, Serhan; Prokopova, Michaela; Chesneau, Mélanie; Le Moine, Alain; Guérif, Pierrick; Soulillou, Jean-Paul; Abramowicz, Marc; Giral, Magali; Racapé, Judith; Maggiore, Umberto; Brouard, Sophie; Abramowicz, Daniel

2016-06-01

Kidney recipients maintaining a prolonged allograft survival in the absence of immunosuppressive drugs and without evidence of rejection are supposed to be exceptional. The ERA-EDTA-DESCARTES working group together with Nantes University launched a European-wide survey to identify new patients, describe them and estimate their frequency for the first time. Seventeen coordinators distributed a questionnaire in 256 transplant centres and 28 countries in order to report as many 'operationally tolerant' patients (TOL; defined as having a serum creatinine <1.7 mg/dL and proteinuria <1 g/day or g/g creatinine despite at least 1 year without any immunosuppressive drug) and 'almost tolerant' patients (minimally immunosuppressed patients (MIS) receiving low-dose steroids) as possible. We reported their number and the total number of kidney transplants performed at each centre to calculate their frequency. One hundred and forty-seven questionnaires were returned and we identified 66 TOL (61 with complete data) and 34 MIS patients. Of the 61 TOL patients, 26 were previously described by the Nantes group and 35 new patients are presented here. Most of them were noncompliant patients. At data collection, 31/35 patients were alive and 22/31 still operationally tolerant. For the remaining 9/31, 2 were restarted on immunosuppressive drugs and 7 had rising creatinine of whom 3 resumed dialysis. Considering all patients, 10-year death-censored graft survival post-immunosuppression weaning reached 85% in TOL patients and 100% in MIS patients. With 218 913 kidney recipients surveyed, cumulative incidences of operational tolerance and almost tolerance were estimated at 3 and 1.5 per 10 000 kidney recipients, respectively. In kidney transplantation, operational tolerance and almost tolerance are infrequent findings associated with excellent long-term death-censored graft survival. © The Author 2016. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved.

Advances in the diagnosis of hereditary kidney cancer: Initial results of a multigene panel test.

PubMed

Nguyen, Kevin A; Syed, Jamil S; Espenschied, Carin R; LaDuca, Holly; Bhagat, Ansh M; Suarez-Sarmiento, Alfredo; O'Rourke, Timothy K; Brierley, Karina L; Hofstatter, Erin W; Shuch, Brian

2017-11-15

Panel testing has been recently introduced to evaluate hereditary cancer; however, limited information is available regarding its use in kidney cancer. The authors retrospectively reviewed test results and clinical data from patients who underwent targeted multigene panel testing of up to 19 genes associated with hereditary kidney cancer from 2013 to 2016. The frequency of positive (mutation/variant likely pathogenic), inconclusive (variant of unknown significance), and negative results was evaluated. A logistic regression analysis evaluated predictive factors for a positive test. Patients (n = 1235) had a median age at diagnosis of 46 years, which was significantly younger than the US population of individuals with kidney cancer (P < .0001). Overall, 6.1%, 75.5%, and 18.4% of individuals had positive, negative, and inconclusive results, respectively. The most commonly altered genes included folliculin (FLCN) and fumarate hydratase (FH), which were altered in 1.8% and 1.3% of patients, respectively. Tuberous Sclerosis Complex 2 (TSC2), mesenchymal epithelial transition factor proto-oncogene (MET), and PMS1 homolog 2 (PMS2) had the highest rates of variants of unknown significance, which were identified in 2.7%, 2.2%, and 1.7% of patients, respectively. Early age of onset was the only factor that was identified as predictive of a positive test on multivariate analysis (odds ratio, 0.975; P = .0052) and may be the only identifying characteristic of low-penetrant syndromes, such as those associated with MITF (melanogenesis-associated transcription factor) mutations, which do not have singular histology or a family history of kidney cancer. Panel tests may be particularly useful for patients who lack distinguishing clinical characteristics of known hereditary kidney cancer syndromes. The current results support the use of early age of onset for genetic counseling and/or testing. Cancer 2017;123:4363-71. © 2017 American Cancer Society. © 2017 American Cancer Society.

Towards nonionizing photoacoustic cystography

NASA Astrophysics Data System (ADS)

Kim, Chulhong; Jeon, Mansik; Wang, Lihong V.

2012-02-01

Normally, urine flows down from kidneys to bladders. Vesicoureteral reflux (VUR) is the abnormal flow of urine from bladders back to kidneys. VUR commonly follows urinary tract infection and leads to renal infection. Fluoroscopic voiding cystourethrography and direct radionuclide voiding cystography have been clinical gold standards for VUR imaging, but these methods are ionizing. Here, we demonstrate the feasibility of a novel and nonionizing process for VUR mapping in vivo, called photoacoustic cystography (PAC). Using a photoacoustic (PA) imaging system, we have successfully imaged a rat bladder filled with clinically being used methylene blue dye. An image contrast of ~8 was achieved. Further, spectroscopic PAC confirmed the accumulation of methylene blue in the bladder. Using a laser pulse energy of less than 1 mJ/cm2, bladder was clearly visible in the PA image. Our results suggest that this technology would be a useful clinical tool, allowing clinicians to identify bladder noninvasively in vivo.

Non-Alcoholic Fatty Liver Disease: The Emerging Burden in Cardiometabolic and Renal Diseases.

PubMed

Han, Eugene; Lee, Yong Ho

2017-12-01

As the number of individuals with non-alcoholic fatty liver disease (NAFLD) has increased, the influence of NAFLD on other metabolic diseases has been highlighted. Accumulating epidemiologic evidence indicates that NAFLD not only affects the liver but also increases the risk of extra-hepatic diseases such as type 2 diabetes mellitus, metabolic syndrome, dyslipidemia, hypertension, cardiovascular or cerebrovascular diseases, and chronic kidney disease. Non-alcoholic steatohepatitis, an advanced type of NAFLD, can aggravate these inter-organ relationships and lead to poorer outcomes. NAFLD induces insulin resistance and exacerbates systemic chronic inflammation and oxidative stress, which leads to organ dysfunction in extra-hepatic tissues. Although more research is needed to identify the pathophysiological mechanisms and causal relationship between NAFLD and cardiometabolic and renal diseases, screening for heart, brain, and kidney diseases, risk assessment for diabetes, and a multidisciplinary approach for managing these patients should be highly encouraged. Copyright © 2017 Korean Diabetes Association.

TRPP2-dependent Ca2+ signaling in dorso-lateral mesoderm is required for kidney field establishment in Xenopus.

PubMed

Futel, Mélinée; Leclerc, Catherine; Le Bouffant, Ronan; Buisson, Isabelle; Néant, Isabelle; Umbhauer, Muriel; Moreau, Marc; Riou, Jean-François

2015-03-01

In Xenopus laevis embryos, kidney field specification is dependent on retinoic acid (RA) and coincides with a dramatic increase of Ca(2+) transients, but the role of Ca(2+) signaling in the kidney field is unknown. Here, we identify TRPP2, a member of the transient receptor potential (TRP) superfamily of channel proteins encoded by the pkd2 gene, as a central component of Ca(2+) signaling in the kidney field. TRPP2 is strongly expressed at the plasma membrane where it might regulate extracellular Ca(2+) entry. Knockdown of pkd2 in the kidney field results in the downregulation of pax8, but not of other kidney field genes (lhx1, osr1 and osr2). We further show that inhibition of Ca(2+) signaling with an inducible Ca(2+) chelator also causes downregulation of pax8, and that pkd2 knockdown results in a severe inhibition of Ca(2+) transients in kidney field explants. Finally, we show that disruption of RA results both in an inhibition of intracellular Ca(2+) signaling and of TRPP2 incorporation into the plasma membrane of kidney field cells. We propose that TRPP2-dependent Ca(2+) signaling is a key component of pax8 regulation in the kidney field downstream of RA-mediated non-transcriptional control of TRPP2. © 2015. Published by The Company of Biologists Ltd.

Kidney disease among children in sub-Saharan Africa: a systematic review

PubMed Central

Tallman, Jacob E.; Chu, Emily Y.; Fitzgerald, Daniel W.; Pain, Kevin J.; Peck, Robert N.

2015-01-01

The global burden of kidney disease is increasing, and several etiologies first begin in childhood. Risk factors for pediatric kidney disease are common in Africa, but data regarding its prevalence are lacking. We completed a systematic review of community-based studies describing the prevalence of proteinuria, hematuria, abnormal imaging, or kidney dysfunction among children in sub-Saharan Africa. Medline and Embase were searched. Five hundred twenty-three references were reviewed. Thirty-two references from 9 countries in sub-Saharan Africa were included in the qualitative synthesis. The degree of kidney damage and abnormal imaging varied widely: proteinuria 32.5% (2.2%-56.0%); hematuria 31.1% (0.6%-67.0%); hydronephrosis 11.3% (0.0%-38.0%), hydroureter 7.5% (0.0%-26.4%), major kidney abnormalities 0.1% (0.0%-0.8%). Serum creatinine was reported in four studies with insufficient detail to identify the prevalence renal dysfunction. A majority of the studies were performed in Schistosoma haematobium endemic areas. A lower prevalence of kidney disease was observed in the few studies from non-endemic areas. Published data on pediatric kidney disease in sub-Saharan Africa is highly variable and dependent on S. haematobium prevalence. More community-based studies are needed to describe the burden of pediatric kidney disease, particularly in regions where S. haematobium infection is non-endemic. PMID:25420180

Low birth weight is associated with impaired murine kidney development and function.

PubMed

Barnett, Christina; Nnoli, Oluwadara; Abdulmahdi, Wasan; Nesi, Lauren; Shen, Michael; Zullo, Joseph A; Payne, David L; Azar, Tala; Dwivedi, Parth; Syed, Kunzah; Gromis, Jonathan; Lipphardt, Mark; Jules, Edson; Maranda, Eric L; Patel, Amy; Rabadi, May M; Ratliff, Brian B

2017-08-01

BackgroundLow birth weight (LBW) neonates have impaired kidney development that leaves them susceptible to kidney disease and hypertension during adulthood. The study here identifies events that blunt nephrogenesis and kidney development in the murine LBW neonate.MethodsWe examined survival, kidney development, GFR, gene expression, and cyto-/chemokines in the LBW offspring of malnourished (caloric and protein-restricted) pregnant mice.ResultsMalnourished pregnant mothers gave birth to LBW neonates that had 40% reduced body weight and 54% decreased survival. Renal blood perfusion was reduced by 37%, whereas kidney volume and GFR were diminished in the LBW neonate. During gestation, the LBW neonatal kidney had 2.2-fold increased apoptosis, 76% decreased SIX2+ progenitor cells, downregulation of mesenchymal-to-epithelial signaling factors Wnt9b and Fgf8, 64% less renal vesicle formation, and 32% fewer nephrons than controls. At birth, increased plasma levels of IL-1β, IL-6, IL-12(p70), and granulocyte-macrophage colony-stimulating factor in the LBW neonate reduced SIX2+ progenitor cells.ConclusionIncreased pro-inflammatory cytokines in the LBW neonate decrease SIX2+ stem cells in the developing kidney. Reduced renal stem cells (along with the decreased mesenchymal-to-epithelial signaling) blunt renal vesicle generation, nephron formation, and kidney development. Subsequently, the mouse LBW neonate has reduced glomeruli volume, renal perfusion, and GFR.

Progression of hypertension and kidney disease in aging fawn-hooded rats is mediated by enhanced influence of renin-angiotensin system and suppression of nitric oxide system and epoxyeicosanoids.

PubMed

Doleželová, Šárka; Jíchová, Šárka; Husková, Zuzana; Vojtíšková, Alžběta; Kujal, Petr; Hošková, Lenka; Kautzner, Josef; Sadowski, Janusz; Červenka, Luděk; Kopkan, Libor

The fawn-hooded hypertensive (FHH) rat serves as a genetic model of spontaneous hypertension associated with glomerular hyperfiltration and proteinuria. However, the knowledge of the natural course of hypertension and kidney disease in FHH rats remains fragmentary and the underlying pathophysiological mechanisms are unclear. In this study, over the animals' lifetime, we followed the survival rate, blood pressure (telemetry), indices of kidney damage, the activity of renin-angiotensin (RAS) and nitric oxide (NO) systems, and CYP450-epoxygenase products (EETs). Compared to normotensive controls, no elevation of plasma and renal RAS was observed in prehypertensive and hypertensive FHH rats; however, RAS inhibition significantly reduced systolic blood pressure (137 ± 9 to 116 ± 8, and 159 ± 8 to 126 ± 4 mmHg, respectively) and proteinuria (62 ± 2 to 37 ± 3, and 132 ± 8 to 87 ± 5 mg/day, respectively). Moreover, pharmacological RAS inhibition reduced angiotensin (ANG) II and increased ANG 1-7 in the kidney and thereby may have delayed the progression of kidney disease. Furthermore, renal NO and EETs declined in the aging FHH rats but not in the control strain. The present results, especially the demonstration of exaggerated vascular responsiveness to ANG II, indicate that RAS may contribute to the development of hypertension and kidney disease in FHH rats. The activity of factors opposing the development of hypertension and protecting the kidney declined with age in this model. Therefore, therapeutic enhancement of this activity besides RAS inhibition could be attempted in the therapy of human hypertension associated with kidney disease.

Inhibition of plasma kallikrein-kinin system to alleviate renal injury and arthritis symptoms in rats with adjuvant-induced arthritis.

PubMed

Zhu, Jie; Wang, Hui; Chen, Jingyu; Wei, Wei

2018-04-01

Rheumatoid arthritis (RA) is a chronic systemic autoimmune disease. Impairment of kidney functions in RA was observed. However, the mechanism of kidney injury of RA has not been clear. Plasma kallikrein-kinin system (KKS) was involved in inflammatory processes in kidney disease. This study aimed to explore the role of plasma KKS in immune reactions and kidney injury of RA. The paw of AA rats appeared to be swelling and redness, the arthritis index was significantly increased on the 18, 21 and 24 d after injection and secondary inflammation in multi-sites was observed. Kidney dysfunction accompanied with inflammatory cell infiltration, tubular epithelial cell mitochondrial swelling and vacuolar degeneration, renal glomerular foot process fusions and glomerular basement membrane thickening were observed in AA rats. The expressions of neutrophil gelatinase-associated lipocalin (NGAL) and kidney injury molecule-1 (Kim-1) in kidney of AA rats were increased. In addition, expressions of BK, PK, B1R and B2R in the renal tissue of AA rats were up-regulated. Pro-inflammatory cytokines IL-2, IFN-γ and TNF-α were increased and anti-inflammatory cytokines IL-4 and IL-10 were low in kidney. Plasma kallikrein (PK) inhibitor PKSI-527 attenuated arthritis signs and renal damage, and inhibited BK, PK, B1R and B2R expressions. The protein expressions of P38, p-P38 and p-JNK and IFN-γ and TNF-α were inhibited by PKSI-527. These findings demonstrate that plasma KKS activation contributed to the renal injury of AA rats through MAPK signaling pathway. Plasma KKS might be a potential target for RA therapy.

The weekend effect alters the procurement and discard rates of deceased donor kidneys in the United States

PubMed Central

Mohan, Sumit; Foley, Karl; Chiles, Mariana C; Dube, Geoffrey K; Patzer, Rachel E; Pastan, Stephen; Crew, R John; Cohen, David; Ratner, Lloyd

2016-01-01

Factors contributing to the high rate of discard among deceased donor kidneys remain poorly understood and the influence of resource limitations of weekends on kidney transplantation is unknown. To quantify this we used data from the Scientific Registry of Transplant Recipients and assembled a retrospective cohort of 181,799 deceased donor kidneys recovered for transplantation from 2000-2013. We identified the impact of the day of the week on the procurement and subsequent utilization or discard of deceased donor kidneys in the United States, as well as report the geographic variation on the impact of weekends on transplantation. Compared to weekday kidneys, organs procured on weekends were significantly more likely to be discarded than transplanted (odds ratio: 1.16; 95% confidence interval 1.13 – 1.19), even after adjusting for organ quality (adjusted odds ratio: 1.13; 95% confidence interval 1.10 – 1.17). Weekend discards were of a significantly higher quality than weekday discards (kidney donor profile index: 76.5 vs 77.3%). Considerable geographic variation was noted in the proportion of transplants that occurred over the weekend. Kidneys available for transplant over the weekend were significantly more likely to be used at larger transplant centers, be shared without payback, and experienced shorter cold ischemia times. Thus, factors other than kidney quality are contributing to the discard of deceased donor kidneys, particularly during weekends. Policy prescriptions, administrative or organizational solutions within transplant programs may potentially mitigate against the recent increase in kidney discards. PMID:27182001

Coronary heart disease is not significantly linked to acute kidney injury identified using Acute Kidney Injury Group criteria.

PubMed

Yayan, Josef

2012-01-01

Patients with unstable angina or myocardial infarction are at risk of acute kidney injury, which may be aggravated by the iodine-containing contrast agent used during coronary angiography; however, the relationship between these two conditions remains unclear. The current study investigated the relationship between acute kidney injury and coronary heart disease prior to coronary angiography. All patients were evaluated after undergoing coronary angiography in the cardiac catheterization laboratory of the Vinzentius Hospital in Landau, Germany, in 2011. The study group included patients with both acute coronary heart disease and acute kidney injury (as defined according to the classification of the Acute Kidney Injury Group); the control group included patients without acute coronary heart disease. Serum creatinine profiles were evaluated in all patients, as were a variety of demographic and health characteristics. Of the 303 patients examined, 201 (66.34%) had coronary artery disease. Of these, 38 (18.91%) also had both acute kidney injury and acute coronary heart disease prior to and after coronary angiography, and of which in turn 34 (16.91%) had both acute kidney injury and acute coronary heart disease only prior to the coronary angiography. However, the occurrence of acute kidney injury was not significantly related to the presence of coronary heart disease (P = 0.95, Chi-square test). The results of this study indicate that acute kidney injury is not linked to acute coronary heart disease. However, physicians should be aware that many coronary heart patients may develop kidney injury while hospitalized for angiography.

Enzyme activities in plasma, kidney, liver, and muscle of five avian species

USGS Publications Warehouse

Franson, J.C.; Murray, H.C.; Bunck, C.

1985-01-01

Activities of alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), creatine phosphokinase (CPK), and lactate dehydrogenase (LDH) were determined in plasma, kidney, liver, and muscle from five species of captive birds. Few differences occurred in plasma activities between sexes but considerable differences occurred between species. All five enzymes were detected in each of the tissues sampled. Relative enzyme activities in liver, kidney, and muscle were similar for each species. CPK activity was much higher in muscle than in liver or kidney and, of the five enzymes studied, may be the best indicator of muscle damage. Most of the other enzymes were more evenly distributed among the three tissues, and no organ-specific enzyme could be identified for liver or kidney. Because of interspecific variations in plasma enzyme activities, it is important to establish baseline values for each species to ensure accurate interpretation of results.

Opportunities for improving management of advanced chronic kidney disease.

PubMed

Patwardhan, Meenal B; Matchar, David B; Samsa, Gregory P; Haley, William E

2008-01-01

Evidence suggests that management of advanced chronic kidney disease affects patient outcomes. To identify clinical areas that demand attention from a quality improvement perspective, we sought to examine the extent of conformance to an advanced chronic kidney disease guideline in a range of practices. A total of 237 patient medical records were abstracted from 4 primary care providers and 4 nephrology private practices across the country. In the practices studied, management of advanced chronic kidney disease patients was suboptimal for patients managed by primary care providers as well as those managed by nephrologists (overall conformance 27% and 42%, respectively), specifically for anemia, bone disease, and timing for renal replacement therapy. The current exercise (in conjunction with a literature search and focused and individual interviews with providers and patients) offered valuable information that was used to develop a toolkit for optimizing management of advanced chronic kidney disease.

Renal Gene Expression Database (RGED): a relational database of gene expression profiles in kidney disease

PubMed Central

Zhang, Qingzhou; Yang, Bo; Chen, Xujiao; Xu, Jing; Mei, Changlin; Mao, Zhiguo

2014-01-01

We present a bioinformatics database named Renal Gene Expression Database (RGED), which contains comprehensive gene expression data sets from renal disease research. The web-based interface of RGED allows users to query the gene expression profiles in various kidney-related samples, including renal cell lines, human kidney tissues and murine model kidneys. Researchers can explore certain gene profiles, the relationships between genes of interests and identify biomarkers or even drug targets in kidney diseases. The aim of this work is to provide a user-friendly utility for the renal disease research community to query expression profiles of genes of their own interest without the requirement of advanced computational skills. Availability and implementation: Website is implemented in PHP, R, MySQL and Nginx and freely available from http://rged.wall-eva.net. Database URL: http://rged.wall-eva.net PMID:25252782

Renal Gene Expression Database (RGED): a relational database of gene expression profiles in kidney disease.

PubMed

Zhang, Qingzhou; Yang, Bo; Chen, Xujiao; Xu, Jing; Mei, Changlin; Mao, Zhiguo

2014-01-01

We present a bioinformatics database named Renal Gene Expression Database (RGED), which contains comprehensive gene expression data sets from renal disease research. The web-based interface of RGED allows users to query the gene expression profiles in various kidney-related samples, including renal cell lines, human kidney tissues and murine model kidneys. Researchers can explore certain gene profiles, the relationships between genes of interests and identify biomarkers or even drug targets in kidney diseases. The aim of this work is to provide a user-friendly utility for the renal disease research community to query expression profiles of genes of their own interest without the requirement of advanced computational skills. Website is implemented in PHP, R, MySQL and Nginx and freely available from http://rged.wall-eva.net. http://rged.wall-eva.net. © The Author(s) 2014. Published by Oxford University Press.

Stem cells for kidney repair: useful tool for acute renal failure?

PubMed

Yokoo, Takashi; Kawamura, Tetsuya; Kobayashi, Eiji

2008-10-01

Several cell types isolated from adult tissues have been reported to differentiate into mature kidney cells that may participate in renal repair after systemic administration. Chen et al. report that local mesenchymal stem cells derived from adult mouse kidneys are another source of cells with similar properties. Although these cells have the potential to differentiate into endothelial-lineage cell types, their therapeutic benefit to the ischemic kidney is mainly via the production of renoprotective factors.

Assessment of Fetal Kidney Growth and Birth Weight in an Indigenous Australian Cohort.

PubMed

Diehm, Christopher J; Lumbers, Eugenie R; Weatherall, Loretta; Keogh, Lyniece; Eades, Sandra; Brown, Alex; Smith, Roger; Johnson, Vanessa; Pringle, Kirsty G; Rae, Kym M

2017-01-01

Introduction: Indigenous Australians experience higher rates of renal disease and hypertension than non-Indigenous Australians. Low birth weight is recognized as a contributing factor in chronic disease and has been shown to increase the risk of renal failure in adulthood. A smaller kidney volume with fewer nephrons places an individual at risk of hypertension and renal failure. Indigenous Australians have fewer nephrons than non-Indigenous Australians. In this study, intrauterine fetal and kidney growth were evaluated in 174 Indigenous Australian babies throughout gestation in order to record and evaluate fetal growth and kidney size, within a population that is at high risk for chronic illness. Methods: Pregnant women that identified as Indigenous, or non-Indigenous women that were pregnant with a partner who identified as an Indigenous Australian were eligible to participate. Maternal history, smoking status, blood and urine samples and fetal ultrasounds were collected throughout pregnancy. Fetal kidney measurements were collected using ultrasound. Statistical analysis was performed using the Stata 14.1 software package. Results: 15.2% of babies were born prematurely. 44% of the mothers reported smoking in pregnancy. The median birth weight of this cohort was 3,240 g. Male fetuses had higher kidney to body weight ratios than female fetuses ( P = 0.02). The birth weights of term neonates whose mothers smoked during pregnancy were lower (327 g, P < 0.001) than the birth weights of term babies from non-smoking mothers. The kidney volumes of babies whose mothers smoked were also smaller ( P = 0.02), but were in proportion to body weight. Conclusion: In this cohort of Indigenous women smoking was associated with both increased number of preterm births and with a reduction in birth weights, even of term infants. Since kidney volume is a surrogate measure of nephron number and nephrogenesis is complete at birth, babies whose mothers smoked during pregnancy must have fewer nephrons than those from non-smoking mothers. Previous studies have shown that glomerular filtration rate is not related to birth weight, thus infants with smaller kidney volumes are hyperfiltering from birth and therefore are likely to be more susceptible to early onset renal disease in later life.

From 20th century metabolic wall charts to 21st century systems biology: database of mammalian metabolic enzymes

PubMed Central

Corcoran, Callan C.; Grady, Cameron R.; Pisitkun, Trairak; Parulekar, Jaya

2017-01-01

The organization of the mammalian genome into gene subsets corresponding to specific functional classes has provided key tools for systems biology research. Here, we have created a web-accessible resource called the Mammalian Metabolic Enzyme Database (https://hpcwebapps.cit.nih.gov/ESBL/Database/MetabolicEnzymes/MetabolicEnzymeDatabase.html) keyed to the biochemical reactions represented on iconic metabolic pathway wall charts created in the previous century. Overall, we have mapped 1,647 genes to these pathways, representing ~7 percent of the protein-coding genome. To illustrate the use of the database, we apply it to the area of kidney physiology. In so doing, we have created an additional database (Database of Metabolic Enzymes in Kidney Tubule Segments: https://hpcwebapps.cit.nih.gov/ESBL/Database/MetabolicEnzymes/), mapping mRNA abundance measurements (mined from RNA-Seq studies) for all metabolic enzymes to each of 14 renal tubule segments. We carry out bioinformatics analysis of the enzyme expression pattern among renal tubule segments and mine various data sources to identify vasopressin-regulated metabolic enzymes in the renal collecting duct. PMID:27974320

An Observational Cohort Feasibility Study to Identify Microvesicle and Micro-RNA Biomarkers of Acute Kidney Injury Following Pediatric Cardiac Surgery.

PubMed

Sullo, Nikol; Mariani, Silvia; JnTala, Maria; Kumar, Tracy; Woźniak, Marcin J; Smallwood, Dawn; Pais, Paolo; Westrope, Claire; Lotto, Attilio; Murphy, Gavin J

2018-06-15

Micro-RNA, small noncoding RNA fragments involved in gene regulation, and microvesicles, membrane-bound particles less than 1 μm known to regulate cellular processes including responses to injury, may serve as disease-specific biomarkers of acute kidney injury. We evaluated the feasibility of measuring these signals as well as other known acute kidney injury biomarkers in a mixed pediatric cardiac surgery population. Single center prospective cohort feasibility study. PICU. Twenty-four children (≤ 17 yr) undergoing cardiac surgery with cardiopulmonary bypass without preexisting inflammatory state, acute kidney injury, or extracorporeal life support. None. Acute kidney injury was defined according to modified Kidney Diseases Improving Global Outcomes criteria. Blood and urine samples were collected preoperatively and at 6-12 and 24 hours. Microvesicles derivation was assessed using flow cytometry and NanoSight analysis. Micro-RNAs were isolated from plasma and analyzed by microarray and quantitative real-time polymerase chain reaction. Data completeness for the primary outcomes was 100%. Patients with acute kidney injury (n = 14/24) were younger, underwent longer cardiopulmonary bypass, and required greater inotrope support. Acute kidney injury subjects had different fractional content of platelets and endothelial-derived microvesicles before surgery. Platelets and endothelial microvesicles levels were higher in acute kidney injury patients. A number of micro-RNA species were differentially expressed in acute kidney injury patients. Pathway analysis of candidate target genes in the kidney suggested that the most often affected pathways were phosphatase and tensin homolog and signal transducer and activator of transcription 3 signaling. Microvesicles and micro-RNAs expression patterns in pediatric cardiac surgery patients can be measured in children and potentially serve as tools for stratification of patients at risk of acute kidney injury.

Kidney Disease Among Registered Métis Citizens of Ontario: A Population-Based Cohort Study

PubMed Central

Hayward, Jade S.; McArthur, Eric; Nash, Danielle M.; Sontrop, Jessica M.; Russell, Storm J.; Khan, Saba; Walker, Jennifer D.; Nesrallah, Gihad E.; Sood, Manish M.; Garg, Amit X.

2017-01-01

Background: Indigenous peoples in Canada have higher rates of kidney disease than non-Indigenous Canadians. However, little is known about the risk of kidney disease specifically in the Métis population in Canada. Objective: To compare the prevalence of chronic kidney disease and incidence of acute kidney injury and end-stage kidney disease among registered Métis citizens in Ontario and a matched sample from the general Ontario population. Design: Population-based, retrospective cohort study using data from the Métis Nation of Ontario’s Citizenship Registry and administrative databases. Setting: Ontario, Canada; 2003-2013. Patients: Ontario residents ≥18 years. Measurements: Prevalence of chronic kidney disease and incidence of acute kidney injury and end-stage kidney disease. Secondary outcomes among patients hospitalized with acute kidney injury included non-recovery of kidney function and mortality within 1 year of discharge. Methods: Database codes and laboratory values were used to determine study outcomes. Métis citizens were matched (1:4) to Ontario residents on age, sex, and area of residence. The analysis included 12 229 registered Métis citizens and 48 916 adults from the general population. Results: We found the prevalence of chronic kidney disease was slightly higher among Métis citizens compared with the general population (3.1% vs 2.6%, P = 0.002). The incidence of acute kidney injury was 1.2 per 1000 person-years in both Métis citizens and the general population (P = 0.54). Of those hospitalized with acute kidney injury, outcomes were similar among Métis citizens and the general population except 1-year mortality, which was higher for Métis citizens (24.5% vs 15.3%, P = 0.03). The incidence of end-stage kidney disease did not differ between groups (<3.0 per 10 000 person-years, P = 0.73). Limitations: The Métis Nation of Ontario Citizenship Registry only captures about 20% of Métis people in Ontario. Administrative health care codes used to identify kidney disease are highly specific but have low sensitivity. Conclusions: Rates of kidney disease were similar or slightly higher for Métis citizens in Ontario compared with the matched general population. PMID:28491337

Ureteroscopy-assisted Percutaneous Kidney Access Made Easy: First Clinical Experience with a Novel Navigation System Using Electromagnetic Guidance (IDEAL Stage 1).

PubMed

Lima, Estevao; Rodrigues, Pedro L; Mota, Paulo; Carvalho, Nuno; Dias, Emanuel; Correia-Pinto, Jorge; Autorino, Riccardo; Vilaça, João L

2017-10-01

Puncture of the renal collecting system represents a challenging step in percutaneous nephrolithotomy (PCNL). Limitations related to the use of standard fluoroscopic-based and ultrasound-based maneuvers have been recognized. To describe the technique and early clinical outcomes of a novel navigation system for percutaneous kidney access. This was a proof-of-concept study (IDEAL phase 1) conducted at a single academic center. Ten PCNL procedures were performed for patients with kidney stones. Flexible ureterorenoscopy was performed to determine the optimal renal calyx for access. An electromagnetic sensor was inserted through the working channel. Then the selected calyx was punctured with a needle with a sensor on the tip guided by real-time three-dimensional images observed on the monitor. The primary endpoints were the accuracy and clinical applicability of the system in clinical use. Secondary endpoints were the time to successful puncture, the number of attempts for successful puncture, and complications. Ten patients were enrolled in the study. The median age was 47.1 yr (30-63), median body mass index was 22.85kg/m 2 (19-28.3), and median stone size was 2.13cm (1.5-2.5cm). All stones were in the renal pelvis. The Guy's stone score was 1 in nine cases and 2 in one case. All 10 punctures of the collecting system were successfully completed at the first attempt without X-ray exposure. The median time to successful puncture starting from insertion of the needle was 20 s (range 15-35). No complications occurred. We describe the first clinical application of a novel navigation system using real-time electromagnetic sensors for percutaneous kidney access. This new technology overcomes the intrinsic limitations of traditional methods of kidney access, allowing safe, precise, fast, and effective puncture of the renal collecting system. We describe a new technology allowing safe and easy puncture of the kidney without radiation exposure. This could significantly facilitate one of the most challenging steps in percutaneous removal of kidney stones. Copyright © 2017 European Association of Urology. Published by Elsevier B.V. All rights reserved.

Cytotoxic effect of fenitrothion and lambda-cyhalothrin mixture on lipid peroxidation and antioxidant defense system in rat kidney.

PubMed

El-Demerdash, Fatma M

2012-01-01

A mixture of pyrethroids plus organophosphates was assessed for their potential effects on lipid peroxidation, the antioxidant defense system and lactate dehydrogenase (LDH) in rat kidney in vitro. Various insecticide concentrations were incubated with kidney homogenate at 37°C for different incubation times. Treatment with fenitothion (FNT) plus lambda-cyhalothrin (LC) caused a significant induction (P < 0.05) in thiobarbituric acid reactive substances (TBARS), which might be associated to decreased levels of reduced glutathione (GSH), superoxide dismutase (SOD), catalase (CAT), glutathione S-transferase (GST) activities and protein content in rat kidney. However, a significant induction of lactate dehydrogenase (LDH) activity was observed. The effect was concentration and time dependent. It can be concluded that depletion of GSH might indicate that reactive oxygen species (ROS) could be involved in the toxic effects of FNT plus LC which lead to marked perturbations in antioxidant defense system.

Drying Characteristics and Water-soluble Polysaccharides Evaluation of Kidney Shape Ganoderma lucidum Drying in Air Circulation System

NASA Astrophysics Data System (ADS)

Prasetyo, D. J.; Jatmiko, T. H.; Poeloengasih, C. D.; Kismurtono, M.

2017-12-01

In this project, drying kinetic of kidney shape Ganoderma lucidum fruiting body in air circulation system was studied. The drying experiments were conducted at 40, 50 and 60°C with air flow rate of 1.3 ms-1. Samples were weighted periodically until no change in sample weight was recorded, and then the samples were analyzed for its moisture content. Four different thin-layer mathematical models (Newton, Page, Two-term, Midilli) were used and compare to evaluate the drying curves of kidney shape G. lucidum. The water-soluble polysaccharides were evaluated in order to find the best drying temperature condition. The results indicates that Midilli model was the fittest model to describe the characteristic of kidney shape G. lucidum in the air circulation drying system and temperature of 50°C was the best drying condition to get highest value of water-soluble polysaccharides.

The potential role of perivascular lymphatic vessels in preservation of kidney allograft function.

PubMed

Tsuchimoto, Akihiro; Nakano, Toshiaki; Hasegawa, Shoko; Masutani, Kosuke; Matsukuma, Yuta; Eriguchi, Masahiro; Nagata, Masaharu; Nishiki, Takehiro; Kitada, Hidehisa; Tanaka, Masao; Kitazono, Takanari; Tsuruya, Kazuhiko

2017-08-01

Lymphangiogenesis occurs in diseased native kidneys and kidney allografts, and correlates with histological injury; however, the clinical significance of lymphatic vessels in kidney allografts is unclear. This study retrospectively reviewed 63 kidney transplant patients who underwent protocol biopsies. Lymphatic vessels were identified by immunohistochemical staining for podoplanin, and were classified according to their location as perivascular or interstitial lymphatic vessels. The associations between perivascular lymphatic density and kidney allograft function and pathological findings were analyzed. There were no significant differences in perivascular lymphatic densities in kidney allograft biopsy specimens obtained at 0 h, 3 months and 12 months. The groups with higher perivascular lymphatic density showed a lower proportion of progression of interstitial fibrosis/tubular atrophy grade from 3 to 12 months (P for trend = 0.039). Perivascular lymphatic density was significantly associated with annual decline of estimated glomerular filtration rate after 12 months (r = -0.31, P = 0.017), even after adjusting for multiple confounders (standardized β = -0.30, P = 0.019). High perivascular lymphatic density is associated with favourable kidney allograft function. The perivascular lymphatic network may be involved in inhibition of allograft fibrosis and stabilization of graft function.

Value of laboratory tests in employer-sponsored health risk assessments for newly identifying health conditions: analysis of 52,270 participants.

PubMed

Kaufman, Harvey W; Williams, Fred R; Odeh, Mouneer A

2011-01-01

Employer-sponsored health risk assessments (HRA) may include laboratory tests to provide evidence of disease and disease risks for common medical conditions. We evaluated the ability of HRA-laboratory testing to provide new disease-risk information to participants. We performed a cross-sectional analysis of HRA-laboratory results for participating adult employees and their eligible spouses or their domestic partners, focusing on three common health conditions: hyperlipidemia, diabetes mellitus, and chronic kidney disease. HRA with laboratory results of 52,270 first-time participants were analyzed. Nearly all participants had access to health insurance coverage. Twenty-four percent (12,392) self-reported one or more of these medical conditions: 21.1% (11,017) self-identified as having hyperlipidemia, 4.7% (2,479) self-identified as having diabetes, and 0.7% (352) self-identified as having chronic kidney disease. Overall, 36% (n = 18,540) of participants had laboratory evidence of at least one medical condition newly identified: 30.7% (16,032) had laboratory evidence of hyperlipidemia identified, 1.9% (984) had laboratory evidence of diabetes identified, and 5.5% (2,866) had laboratory evidence of chronic kidney disease identified. Of all participants with evidence of hyperlipidemia 59% (16,030 of 27,047), were newly identified through the HRA. Among those with evidence of diabetes 28% (984 of 3,463) were newly identified. The highest rate of newly identified disease risk was for chronic kidney disease: 89% (2,866 of 3,218) of participants with evidence of this condition had not self-reported it. Men (39%) were more likely than women (33%) to have at least one newly identified condition (p<0.0001). Among men, lower levels of educational achievement were associated with modestly higher rates of newly identified disease risk (p<0.0001); the association with educational achievement among women was unclear. Even among the youngest age range (20 to 29 year olds), nearly 1 in 4 participants (24%) had a newly identified risk for disease. These results support the important role of employer-sponsored laboratory testing as an integral element of HRA for identifying evidence of previously undiagnosed common medical conditions in individuals of all working age ranges, regardless of educational level and gender.

Provision of care for chronic kidney disease by non-nephrologists in a developing nation: a national survey

PubMed Central

Al Shamsi, S; Al Dhanhani, A; Sheek-Hussein, M M

2016-01-01

Objectives The prevalence of chronic kidney disease (CKD) in developing countries has increased dramatically. This study aimed to explore the practice patterns of non-dialysis-dependent CKD care in an affluent developing country. Settings Primary and specialised healthcare facilities of public and private sectors in the United Arab Emirates. Participants 159 non-nephrologist physicians practising in the United Arab Emirates. Interventions A 28-item online self-administered questionnaire based on CKD clinical practice guidelines. Primary and secondary outcome measures The physicians' approach to identifying and managing patients with CKD. Results The survey was completed by 159 non-nephrologists, of whom 135 reported having treated patients with CKD. Almost all the respondents screen patients with hypertension and diabetes for CKD, but one-third of them do not screen patients with cardiovascular disease and elderly patients for CKD. The use of accurate CKD screening tests (estimated glomerular filtration rate and albumin/creatinine ratio) was suboptimal (77% and 59% of physicians used the procedures, respectively). One-third of the physicians do not offer treatment with inhibitors of the renin–angiotensin system to patients with CKD, and only 66% offer antilipid treatment. In general, the primary healthcare physicians are more familiar than secondary healthcare physicians with the diagnosis and management of patients with CKD. Conclusions We identified substantial physician-declared deficiencies in the practice of identifying and managing early CKD. Integration of quality CKD care within the healthcare system is required to face the increasing burden of CKD in the United Arab Emirates and possibly in other developing nations. PMID:27481619

Aldosterone is associated with left ventricular hypertrophy in hemodialysis patients.

PubMed

Feniman De Stefano, Greicy Mara Mengue; Zanati-Basan, Silméia Garcia; De Stefano, Laercio Martins; Silva, Viviana Rugolo Oliveira E; Xavier, Patrícia Santi; Barretti, Pasqual; da Silva Franco, Roberto Jorge; Caramori, Jacqueline Costa Teixeira; Martin, Luis Cuadrado

2016-10-01

Patients with chronic kidney disease present a higher degree of left ventricular hypertrophy than expected for hypertension levels. In chronic kidney disease the plot between the quotient extracellular water/total body water and aldosterone is shifted up and to the right. There are few studies that verified the role of aldosterone in cardiac remodeling in this set of patients. The aim of this study was to evaluate the relationship between serum aldosterone and left ventricular mass index in patients with chronic kidney disease on hemodialysis. The patients were submitted to clinical and laboratory evaluation, bioelectrical impedance, echocardiography and ambulatory blood pressure monitoring. The 27 patients included were divided into two groups according to aldosterone level and compared with each other. The group of patients with higher aldosterone levels had higher left ventricular mass index. These groups were heterogeneous with regard to ambulatory systolic blood pressure, body mass index, and aldosterone levels and homogeneous with regard to the quotient extracellular water/total body water, renin-angiotensin-aldosterone system blockers, beta blocker use and other clinical characteristics. The association between aldosterone levels and left ventricular mass index was adjusted to confounding variables by a multiple linear regression analysis in which aldosterone was independently associated with left ventricular mass index. The data presented are consistent with a pathogenic role of aldosterone in left ventricular hypertrophy in patients with chronic kidney dialysis in dialysis patients. ClinicalTrials.gov identifier: NCT01128101. © The Author(s), 2016.

Preventing Acute Kidney Injury: a qualitative study exploring 'sick day rules' implementation in primary care.

PubMed

Morris, Rebecca L; Ashcroft, Darren; Phipps, Denham; Bower, Peter; O'Donoghue, Donal; Roderick, Paul; Harding, Sarah; Lewington, Andrew; Blakeman, Thomas

2016-07-22

In response to growing demand for urgent care services there is a need to implement more effective strategies in primary care to support patients with complex care needs. Improving primary care management of kidney health through the implementation of 'sick day rules' (i.e. temporary cessation of medicines) to prevent Acute Kidney Injury (AKI) has the potential to address a major patient safety issue and reduce unplanned hospital admissions. The aim of this study is to examine processes that may enable or constrain the implementation of 'sick day rules' for AKI prevention into routine care delivery in primary care. Forty semi-structured interviews were conducted with patients with stage 3 chronic kidney disease and purposefully sampled, general practitioners, practice nurses and community pharmacists who either had, or had not, implemented a 'sick day rule'. Normalisation Process Theory was used as a framework for data collection and analysis. Participants tended to express initial enthusiasm for sick day rules to prevent AKI, which fitted with the delivery of comprehensive care. However, interest tended to diminish with consideration of factors influencing their implementation. These included engagement within and across services; consistency of clinical message; and resources available for implementation. Participants identified that supporting patients with multiple conditions, particularly with chronic heart failure, made tailoring initiatives complex. Implementation of AKI initiatives into routine practice requires appropriate resourcing as well as training support for both patients and clinicians tailored at a local level to support system redesign.

Patient and Other Stakeholder Engagement in Patient-Centered Outcomes Research Institute Funded Studies of Patients with Kidney Diseases.

PubMed

Cukor, Daniel; Cohen, Lewis M; Cope, Elizabeth L; Ghahramani, Nasrollah; Hedayati, S Susan; Hynes, Denise M; Shah, Vallabh O; Tentori, Francesca; Unruh, Mark; Bobelu, Jeanette; Cohen, Scott; Dember, Laura M; Faber, Thomas; Fischer, Michael J; Gallardo, Rani; Germain, Michael J; Ghahate, Donica; Grote, Nancy; Hartwell, Lori; Heagerty, Patrick; Kimmel, Paul L; Kutner, Nancy; Lawson, Susan; Marr, Lisa; Nelson, Robert G; Porter, Anna C; Sandy, Phillip; Struminger, Bruce B; Subramanian, Lalita; Weisbord, Steve; Young, Bessie; Mehrotra, Rajnish

2016-09-07

Including target populations in the design and implementation of research trials has been one response to the growing health disparities endemic to our health care system, as well as an aid to study generalizability. One type of community-based participatory research is "Patient Centered-Research", in which patient perspectives on the germane research questions and methodologies are incorporated into the study. The Patient-Centered Outcomes Research Institute (PCORI) has mandated that meaningful patient and stakeholder engagement be incorporated into all applications. As of March 2015, PCORI funded seven clinically-focused studies of patients with kidney disease. The goal of this paper is to synthesize the experiences of these studies to gain an understanding of how meaningful patient and stakeholder engagement can occur in clinical research of kidney diseases, and what the key barriers are to its implementation. Our collective experience suggests that successful implementation of a patient- and stakeholder-engaged research paradigm involves: (1) defining the roles and process for the incorporation of input; (2) identifying the particular patients and other stakeholders; (3) engaging patients and other stakeholders so they appreciate the value of their own participation and have personal investment in the research process; and (4) overcoming barriers and challenges that arise and threaten the productivity of the collaboration. It is our hope that the experiences of these studies will further interest and capacity for incorporating patient and stakeholder perspectives in research of kidney diseases. Copyright © 2016 by the American Society of Nephrology.

Patient and Other Stakeholder Engagement in Patient-Centered Outcomes Research Institute Funded Studies of Patients with Kidney Diseases

PubMed Central

Cukor, Daniel; Cohen, Lewis M.; Cope, Elizabeth L.; Ghahramani, Nasrollah; Hedayati, S. Susan; Hynes, Denise M.; Shah, Vallabh O.; Tentori, Francesca; Unruh, Mark; Bobelu, Jeanette; Cohen, Scott; Dember, Laura M.; Faber, Thomas; Fischer, Michael J.; Gallardo, Rani; Germain, Michael J.; Ghahate, Donica; Grote, Nancy; Hartwell, Lori; Heagerty, Patrick; Kimmel, Paul L.; Kutner, Nancy; Lawson, Susan; Marr, Lisa; Nelson, Robert G.; Porter, Anna C.; Sandy, Phillip; Struminger, Bruce B.; Subramanian, Lalita; Weisbord, Steve; Young, Bessie

2016-01-01

Including target populations in the design and implementation of research trials has been one response to the growing health disparities endemic to our health care system, as well as an aid to study generalizability. One type of community-based participatory research is “Patient Centered-Research”, in which patient perspectives on the germane research questions and methodologies are incorporated into the study. The Patient-Centered Outcomes Research Institute (PCORI) has mandated that meaningful patient and stakeholder engagement be incorporated into all applications. As of March 2015, PCORI funded seven clinically-focused studies of patients with kidney disease. The goal of this paper is to synthesize the experiences of these studies to gain an understanding of how meaningful patient and stakeholder engagement can occur in clinical research of kidney diseases, and what the key barriers are to its implementation. Our collective experience suggests that successful implementation of a patient- and stakeholder-engaged research paradigm involves: (1) defining the roles and process for the incorporation of input; (2) identifying the particular patients and other stakeholders; (3) engaging patients and other stakeholders so they appreciate the value of their own participation and have personal investment in the research process; and (4) overcoming barriers and challenges that arise and threaten the productivity of the collaboration. It is our hope that the experiences of these studies will further interest and capacity for incorporating patient and stakeholder perspectives in research of kidney diseases. PMID:27197911

Impact of S100A8 expression on kidney cancer progression and molecular docking studies for kidney cancer therapeutics.

PubMed

Mirza, Zeenat; Schulten, Hans-Juergen; Farsi, Hasan Ma; Al-Maghrabi, Jaudah A; Gari, Mamdooh A; Chaudhary, Adeel Ga; Abuzenadah, Adel M; Al-Qahtani, Mohammed H; Karim, Sajjad

2014-04-01

The proinflammatory protein S100A8, which is expressed in myeloid cells under physiological conditions, is strongly expressed in human cancer tissues. Its role in tumor cell differentiation and tumor progression is largely unclear and virtually unstudied in kidney cancer. In the present study, we investigated whether S100A8 could be a potential anticancer drug target and therapeutic biomarker for kidney cancer, and the underlying molecular mechanisms by exploiting its interaction profile with drugs. Microarray-based transcriptomics experiments using Affymetrix HuGene 1.0 ST arrays were applied to renal cell carcinoma specimens from Saudi patients for identification of significant genes associated with kidney cancer. In addition, we retrieved selected expression data from the National Center for Biotechnology Information Gene Expression Omnibus database for comparative analysis and confirmation of S100A8 expression. Ingenuity Pathway Analysis (IPA) was used to elucidate significant molecular networks and pathways associated with kidney cancer. The probable polar and non-polar interactions of possible S100A8 inhibitors (aspirin, celecoxib, dexamethasone and diclofenac) were examined by performing molecular docking and binding free energy calculations. Detailed analysis of bound structures and their binding free energies was carried out for S100A8, its known partner (S100A9), and S100A8-S100A9 complex (calprotectin). In our microarray experiments, we identified 1,335 significantly differentially expressed genes, including S100A8, in kidney cancer using a cut-off of p<0.05 and fold-change of 2. Functional analysis of kidney cancer-associated genes showed overexpression of genes involved in cell-cycle progression, DNA repair, cell death, tumor morphology and tissue development. Pathway analysis showed significant disruption of pathways of atherosclerosis signaling, liver X receptor/retinoid X receptor (LXR/RXR) activation, notch signaling, and interleukin-12 (IL-12) signaling. We identified S100A8 as a prospective biomarker for kidney cancer and in silico analysis showed that aspirin, celecoxib, dexamethasone and diclofenac binds to S100A8 and may inhibit downstream signaling in kidney cancer. The present study provides an initial overview of differentially expressed genes in kidney cancer of Saudi Arabian patients using whole-transcript, high-density expression arrays. Our analysis suggests distinct transcriptomic signatures, with significantly high levels of S100A8, and underlying molecular mechanisms contributing to kidney cancer progression. Our docking-based findings shed insight into S100A8 protein as an attractive anticancer target for therapeutic intervention in kidney cancer. To our knowledge, this is the first structure-based docking study for the selected protein targets using the chosen ligands.

Effects of RAAS Inhibitors in Patients with Kidney Disease.

PubMed

Zhang, Fan; Liu, Hong; Liu, Di; Liu, Yexin; Li, Huiqiong; Tan, Xia; Liu, Fuyou; Peng, Youming; Zhang, Hongqing

2017-08-08

Proteinuria and decline of renal function are associated with progression of kidney disease. The Renin Angiotensin Aldosterone System (RAAS) plays an important role in blood pressure regulation, fluid volume, and sodium balance. Overactivity of RAAS contributes to the pathogenesis of a variety of clinical conditions including progress of chronic kidney disease (CKD). This review summarizes the use of RAAS inhibitors as dual therapy or monotherapy in different stages of kidney disease. Experimental and clinical studies have demonstrated RAAS inhibitors prevent proteinuria, kidney fibrosis and slow decline of renal function and thus play a protective role in both early and end stages of kidney disease. While combination use of RAAS inhibitors showed higher efficiency compared with monotherapy, it is also associated with higher incidence of adverse events. Besides ACEI/ARBs, more mechanism research of mineralocorticoid receptor antagonists in kidney disease should be performed.

Potential Use of Autologous Renal Cells from Diseased Kidneys for the Treatment of Renal Failure.

PubMed

George, Sunil K; Abolbashari, Mehran; Jackson, John D; Aboushwareb, Tamer; Atala, Anthony; Yoo, James J

2016-01-01

Chronic kidney disease (CKD) occurs when certain conditions cause the kidneys to gradually lose function. For patients with CKD, renal transplantation is the only treatment option that restores kidney function. In this study, we evaluated primary renal cells obtained from diseased kidneys to determine whether their normal phenotypic and functional characteristics are retained, and could be used for cell therapy. Primary renal cells isolated from both normal kidneys (NK) and diseased kidneys (CKD) showed similar phenotypic characteristics and growth kinetics. The expression levels of renal tubular cell markers, Aquaporin-1 and E-Cadherin, and podocyte-specific markers, WT-1 and Nephrin, were similar in both NK and CKD kidney derived cells. Using fluorescence- activated cell sorting (FACS), specific renal cell populations were identified and included proximal tubular cells (83.1% from NK and 80.3% from CKD kidneys); distal tubular cells (11.03% from NK and 10.9% from CKD kidneys); and podocytes (1.91% from NK and 1.78% from CKD kidneys). Ultra-structural analysis using scanning electron microscopy (SEM) revealed microvilli on the apical surface of cultured cells from NK and CKD samples. Moreover, transmission electron microscopy (TEM) analysis showed a similar organization of tight junctions, desmosomes, and other intracellular structures. The Na+ uptake characteristics of NK and CKD derived renal cells were also similar (24.4 mmol/L and 25 mmol/L, respectively) and no significant differences were observed in the protein uptake and transport characteristics of these two cell isolates. These results show that primary renal cells derived from diseased kidneys such as CKD have similar structural and functional characteristics to their counterparts from a normal healthy kidney (NK) when grown in vitro. This study suggests that cells derived from diseased kidney may be used as an autologous cell source for renal cell therapy, particularly in patients with CKD or end-stage renal disease (ESRD).

Kidney black markets and legal transplants: are they opposite sides of the same coin?

PubMed

Mendoza, Roger Lee

2010-03-01

This study investigates why the illegal traffic of kidneys exists and remains resilient in the Philippines. It also evaluates the efficacy of the legal and regulatory framework for kidney (and organ) transplantation, and the corresponding implications for health policy. The experiences of comparable countries are noted. Three surveys were employed in this study: 1) a review of related literature on kidney black markets; 2) questionnaire-based interviews of a multi-stage probability sample of 131 kidney vendors from the two largest supplier regions in the Philippines; and 3) a comparative content analysis of pertinent legal and regulatory measures to address the underground kidney trade. Survey results, based on a 4.0 percent statistical margin of error, indicate that kidney vendors are typically males (98.4 percent) who belong to the lower income classes/groups D and E (88.5 percent). The vast majority of vendors (89.2 percent) were unrelated to kidney recipients, many of whom were of foreign descent (60.3 percent). The study finds that certain key elements underpin the kidney black market in the Philippines: an open, brokered and compensation-based contractual system between unrelated donors and sellers. These elements are sustained and reinforced by a robust supply-and-demand interface anchored on brokerage pricing, government incapacity, policy contradictions and public tolerance or indifference. The study suggests that the relative ambiguity of, and continuity between, the legal and underground kidney transplant systems be carefully addressed prior to enacting more specific reforms. The study also calls attention to the unintended consequences of various reform efforts, which are often neglected in formulating health policy and evaluating its costs and benefits.

Vitamin D, Hypercalciuria and Kidney Stones

PubMed Central

Letavernier, Emmanuel; Daudon, Michel

2018-01-01

The estimated lifetime risk of nephrolithiasis is growing nowadays, and the formation of kidney stones is frequently promoted by hypercalciuria. Vitamin D, and especially its active metabolite calcitriol, increase digestive calcium absorption—as urinary calcium excretion is directly correlated with digestive calcium absorption, vitamin D metabolites could theoretically increase calciuria and promote urinary stone formation. Nevertheless, there was, until recently, low evidence that 25-hydroxyvitamin D serum levels would be correlated with kidney stone formation, even if high calcitriol concentrations are frequently observed in hypercalciuric stone formers. Low 25-hydroxyvitamin D serum levels have been associated with a broad spectrum of diseases, leading to a huge increase in vitamin D prescription in the general population. In parallel, an increased frequency of kidney stone episodes has been observed in prospective studies evaluating vitamin D alone or in association with calcium supplements, and epidemiological studies have identified an association between high 25-hydroxyvitamin D serum levels and kidney stone formation in some groups of patients. Moreover, urinary calcium excretion has been shown to increase in response to vitamin D supplements, at least in some groups of kidney stone formers. It seems likely that predisposed individuals may develop hypercalciuria and kidney stones in response to vitamin D supplements. PMID:29562593

Practice-Based Recommendations from the American Society of Transplantation Liver and Intestine Community of Practice

PubMed Central

Levitsky, J.; O’Leary, J.G.; Asrani, S.; Sharma, P.; Fung, J.; Wiseman, A.; Niemann, C.U.

2016-01-01

Acute and chronic kidney disease after liver transplantation is common and results in significant morbidity and mortality. The introduction of MELD has directly correlated with an increased prevalence of perioperative renal dysfunction and the number of simultaneous liver-kidney transplants performed. Thus, kidney dysfunction in this population is typically multifactorial and related to pre-existing conditions, pre-transplant renal injury, peri-operative events, and post-transplant nephrotoxic immunosuppressive therapies. The management of kidney disease following liver transplantation is challenging, as by the time the serum creatinine is significantly elevated, few interventions impact the course of progression. Also, immunological factors such as antibody-mediated rejection have become of greater interest given the rising liver-kidney transplant population. Therefore this review, assembled by experts in the field and endorsed by the American Society of Transplantation Liver and Intestinal Community of Practice, provides a critical assessment of measures of renal function and interventions aimed at preserving renal function early and late after liver and simultaneous liver-kidney transplantation. Key points and practice-based recommendations for the prevention and management of kidney injury in this population are provided to offer guidance for clinicians and identify gaps in knowledge for future investigations. PMID:26932352

Glutamine Addiction in Kidney Cancer Suppresses Oxidative Stress and Can Be Exploited for Real-Time Imaging

DOE PAGES

Abu Aboud, Omran; Habib, Samy L.; Trott, Josephine; ...

2017-10-11

Many cancers appear to activate intrinsic antioxidant systems as a means to counteract oxidative stress. Some cancers, such as clear cell renal cell carcinoma (ccRCC), require exogenous glutamine for growth and exhibit reprogrammed glutamine metabolism, at least in part due to the glutathione pathway, an efficient cellular buffering system that counteracts reactive oxygen species (ROS) and other oxidants. We show here that ccRCC xenograft tumors under the renal capsule exhibit enhanced oxidative stress compared to adjacent normal tissue and the contralateral kidney. Upon glutaminase inhibition with CB-839 or BPTES, the RCC cell lines SN12PM-6-1 (SN12) and 786-O exhibited decreased survivalmore » and pronounced apoptosis associated with a decreased GSH/GSSG ratio, augmented nuclear factor erythroid related factor 2 (NRF2), and increased 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodG), a marker of DNA damage. SN12 tumor xenografts showed decreased growth when treated with CB-839. Furthermore, PET imaging confirmed that ccRCC tumors exhibited increased tumoral uptake of 18F-(2S,4R)4- fluoroglutamine (18F-FGln) compared to the kidney in the orthotopic mouse model. This technique can be utilized to follow changes in ccRCC metabolism in vivo. Further development of these paradigms will lead to new treatment options with glutaminase inhibitors and the utility of PET to identify and manage ccRCC patients who are likely to respond to glutaminase inhibitors in the clinic.« less

Glutamine Addiction in Kidney Cancer Suppresses Oxidative Stress and Can Be Exploited for Real-Time Imaging

DOE Office of Scientific and Technical Information (OSTI.GOV)

Abu Aboud, Omran; Habib, Samy L.; Trott, Josephine

Many cancers appear to activate intrinsic antioxidant systems as a means to counteract oxidative stress. Some cancers, such as clear cell renal cell carcinoma (ccRCC), require exogenous glutamine for growth and exhibit reprogrammed glutamine metabolism, at least in part due to the glutathione pathway, an efficient cellular buffering system that counteracts reactive oxygen species (ROS) and other oxidants. We show here that ccRCC xenograft tumors under the renal capsule exhibit enhanced oxidative stress compared to adjacent normal tissue and the contralateral kidney. Upon glutaminase inhibition with CB-839 or BPTES, the RCC cell lines SN12PM-6-1 (SN12) and 786-O exhibited decreased survivalmore » and pronounced apoptosis associated with a decreased GSH/GSSG ratio, augmented nuclear factor erythroid related factor 2 (NRF2), and increased 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodG), a marker of DNA damage. SN12 tumor xenografts showed decreased growth when treated with CB-839. Furthermore, PET imaging confirmed that ccRCC tumors exhibited increased tumoral uptake of 18F-(2S,4R)4- fluoroglutamine (18F-FGln) compared to the kidney in the orthotopic mouse model. This technique can be utilized to follow changes in ccRCC metabolism in vivo. Further development of these paradigms will lead to new treatment options with glutaminase inhibitors and the utility of PET to identify and manage ccRCC patients who are likely to respond to glutaminase inhibitors in the clinic.« less

Optimization and critical evaluation of decellularization strategies to develop renal extracellular matrix scaffolds as biological templates for organ engineering and transplantation.

PubMed

Caralt, M; Uzarski, J S; Iacob, S; Obergfell, K P; Berg, N; Bijonowski, B M; Kiefer, K M; Ward, H H; Wandinger-Ness, A; Miller, W M; Zhang, Z J; Abecassis, M M; Wertheim, J A

2015-01-01

The ability to generate patient-specific cells through induced pluripotent stem cell (iPSC) technology has encouraged development of three-dimensional extracellular matrix (ECM) scaffolds as bioactive substrates for cell differentiation with the long-range goal of bioengineering organs for transplantation. Perfusion decellularization uses the vasculature to remove resident cells, leaving an intact ECM template wherein new cells grow; however, a rigorous evaluative framework assessing ECM structural and biochemical quality is lacking. To address this, we developed histologic scoring systems to quantify fundamental characteristics of decellularized rodent kidneys: ECM structure (tubules, vessels, glomeruli) and cell removal. We also assessed growth factor retention--indicating matrix biofunctionality. These scoring systems evaluated three strategies developed to decellularize kidneys (1% Triton X-100, 1% Triton X-100/0.1% sodium dodecyl sulfate (SDS) and 0.02% Trypsin-0.05% EGTA/1% Triton X-100). Triton and Triton/SDS preserved renal microarchitecture and retained matrix-bound basic fibroblast growth factor and vascular endothelial growth factor. Trypsin caused structural deterioration and growth factor loss. Triton/SDS-decellularized scaffolds maintained 3 h of leak-free blood flow in a rodent transplantation model and supported repopulation with human iPSC-derived endothelial cells and tubular epithelial cells ex vivo. Taken together, we identify an optimal Triton/SDS-based decellularization strategy that produces a biomatrix that may ultimately serve as a rodent model for kidney bioengineering. © Copyright 2014 The American Society of Transplantation and the American Society of Transplant Surgeons.

Oxidative Stress in Hypertension: Role of the Kidney

PubMed Central

Araujo, Magali

2014-01-01

Abstract Significance: Renal oxidative stress can be a cause, a consequence, or more often a potentiating factor for hypertension. Increased reactive oxygen species (ROS) in the kidney have been reported in multiple models of hypertension and related to renal vasoconstriction and alterations of renal function. Nicotinamide adenine dinucleotide phosphate oxidase is the central source of ROS in the hypertensive kidney, but a defective antioxidant system also can contribute. Recent Advances: Superoxide has been identified as the principal ROS implicated for vascular and tubular dysfunction, but hydrogen peroxide (H2O2) has been implicated in diminishing preglomerular vascular reactivity, and promoting medullary blood flow and pressure natriuresis in hypertensive animals. Critical Issues and Future Directions: Increased renal ROS have been implicated in renal vasoconstriction, renin release, activation of renal afferent nerves, augmented contraction, and myogenic responses of afferent arterioles, enhanced tubuloglomerular feedback, dysfunction of glomerular cells, and proteinuria. Inhibition of ROS with antioxidants, superoxide dismutase mimetics, or blockers of the renin-angiotensin-aldosterone system or genetic deletion of one of the components of the signaling cascade often attenuates or delays the onset of hypertension and preserves the renal structure and function. Novel approaches are required to dampen the renal oxidative stress pathways to reduced O2−• rather than H2O2 selectivity and/or to enhance the endogenous antioxidant pathways to susceptible subjects to prevent the development and renal-damaging effects of hypertension. Antioxid. Redox Signal. 20, 74–101. PMID:23472618

Systemic effect of mineral aggregate-based cements: histopathological analysis in rats.

PubMed

Garcia, Lucas da Fonseca Roberti; Huck, Claudia; Magalhães, Fernando Augusto Cintra; Souza, Pedro Paulo Chaves de; Souza Costa, Carlos Alberto de

2017-01-01

Several studies reported the local tissue reaction caused by mineral aggregate-based cements. However, few studies have investigated the systemic effects promoted by these cements on liver and kidney when directly applied to connective tissue. The purpose of this in vivo study was to investigate the systemic effect of mineral aggregate-based cements on the livers and kidneys of rats. Samples of Mineral Trioxide Aggregate (MTA) and a calcium aluminate-based cement (EndoBinder) containing different radiopacifiers were implanted into the dorsum of 40 rats. After 7 and 30 d, samples of subcutaneous, liver and kidney tissues were submitted to histopathological analysis. A score (0-3) was used to grade the inflammatory reaction. Blood samples were collected to evaluate changes in hepatic and renal functions of animals. The moderate inflammatory reaction (2) observed for 7 d in the subcutaneous tissue decreased with time for all cements. The thickness of inflammatory capsules also presented a significant decrease with time (P<.05). Systemically, all cements caused adverse inflammatory reactions in the liver and kidney, being more evident for MTA, persisting until the end of the analysis. Liver functions increased significantly for MTA during 30 d (P<.05). The different cements induced to a locally limited inflammatory reaction. However, from the systemic point of view, the cements promoted significant inflammatory reactions in the liver and kidney. For MTA, the reactions were more accentuated.

Quality indicators for the detection and management of chronic kidney disease in primary care in Canada derived from a modified Delphi panel approach.

PubMed

Tu, Karen; Bevan, Lindsay; Hunter, Katie; Rogers, Jess; Young, Jacqueline; Nesrallah, Gihad

2017-01-01

The detection and management of chronic kidney disease lies within primary care; however, performance measures applicable in the Canadian context are lacking. We sought to develop a set of primary care quality indicators for chronic kidney disease in the Canadian setting and to assess the current state of the disease's detection and management in primary care. We used a modified Delphi panel approach, involving 20 panel members from across Canada (10 family physicians, 7 nephrologists, 1 patient, 1 primary care nurse and 1 pharmacist). Indicators identified from peer-reviewed and grey literature sources were subjected to 3 rounds of voting to develop a set of quality indicators for the detection and management of chronic kidney disease in the primary care setting. The final indicators were applied to primary care electronic medical records in the Electronic Medical Record Administrative data Linked Database (EMRALD) to assess the current state of primary care detection and management of chronic kidney disease in Ontario. Seventeen indicators made up the final list, with 1 under the category Prevalence, Incidence and Mortality; 4 under Screening, Diagnosis and Risk Factors; 11 under Management; and 1 under Referral to a Specialist. In a sample of 139 993 adult patients not on dialysis, 6848 (4.9%) had stage 3 or higher chronic kidney disease, with the average age of patients being 76.1 years (standard deviation [SD] 11.0); 62.9% of patients were female. Diagnosis and screening for chronic kidney disease were poorly performed. Only 27.1% of patients with stage 3 or higher disease had their diagnosis documented in their cumulative patient profile. Albumin-creatinine ratio testing was only performed for 16.3% of patients with a low estimated glomerular filtration rate (eGFR) and for 28.5% of patients with risk factors for chronic kidney disease. Family physicians performed relatively better with the management of chronic kidney disease, with 90.4% of patients with stage 3 or higher disease having an eGFR performed in the previous 18 months and 83.1% having a blood pressure recorded in the previous 9 months. We propose a set of measurable indicators to evaluate the quality of the management of chronic kidney disease in primary care. These indicators may be used to identify opportunities to improve current practice in Canada.

The effectiveness and cost-effectiveness of methods of storing donated kidneys from deceased donors: a systematic review and economic model.

PubMed

Bond, M; Pitt, M; Akoh, J; Moxham, T; Hoyle, M; Anderson, R

2009-08-01

To review the evidence for the effectiveness and cost-effectiveness of storing kidneys from deceased donors prior to transplantation, using cold static storage solutions or pulsatile hypothermic machine perfusion. Electronic databases were searched in January 2008 and updated in May 2008 for systematic reviews and/or meta-analyses, randomised controlled trials (RCTs), other study designs and ongoing research. Sources included: Cochrane Library, MEDLINE, EMBASE, CINAHL, ISI Web of Knowledge, DARE, NRR, ReFeR, Current Controlled Trials, and (NHS) HTA. Bibliographies of articles were searched for further relevant studies, and the Food and Drugs Administration (FDA) and European Regulatory Agency Medical Device Safety Service websites were searched. Only English language papers were sought. The perfusion machines identified were the LifePort Kidney Transporter (Organ Recovery Systems) and the RM3 Renal Preservation System (Waters Medical Systems). The cold storage solutions reviewed were: University of Wisconsin, ViaSpan; Marshall's hypertonic citrate, Soltran; and Genzyme, Celsior. Each intervention was compared with the others as data permitted. The population was recipients of kidneys from deceased donors. The main outcomes were measures of graft survival, patient survival, delayed graft function (DGF), primary non-function (PNF), discard rates of non-viable kidneys, health-related quality of life and cost-effectiveness. Where data permitted the results of studies were pooled using meta-analysis. A Markov (state transition) model was developed to simulate the main post-transplantation outcomes of kidney graft recipients. Eleven studies were included: three full journal published RCTs, two ongoing RCTs [European Machine Preservation Trial (MPT) and UK Pulsatile Perfusion in Asystolic donor Renal Transplantation (PPART) study], one cohort study, three full journal published retrospective record reviews and two retrospective record reviews published as posters or abstracts only. For LifePort versus ViaSpan, no significant differences were found for DGF, PNF, acute rejection, duration of DGF, creatinine clearance or toxicity, patient survival or graft survival at 6 months, but graft survival was better at 12 months post transplant with machine perfusion (LifePort = 98%, ViaSpan = 94%, p < 0.03). For LifePort versus RM3, all outcomes favoured RM3, although the results may be unreliable. For ViaSpan versus Soltran, there were no significant differences in graft survival for cold ischaemic times up to 36 hours. For ViaSpan versus Celsior, no significant differences were found on any outcome measure. In terms of cost-effectiveness, data from the MPT suggested that machine preservation was cheaper and generated more quality-adjusted life-years (QALYs), while the PPART study data suggested that cold storage was preferable on both counts. The less reliable deterministic outputs of the cohort study suggested that LifePort would be cheaper and would generate more QALYs than Soltran. Sensitivity analyses found that changes to the differential kidney storage costs between comparators have a very low impact on overall net benefit estimates; where differences in effectiveness exist, dialysis costs are important in determining overall net benefit; DGF levels become important only when differences in graft survival are apparent between patients experiencing immediate graft function (IGF) versus DGF; relative impact of differential changes to graft survival for patients experiencing IGF as opposed to DGF depends on the relative proportion of patients experiencing each of these two outcomes. The conclusions drawn for the comparison of machine perfusion with cold storage depend on which trial data are used in the model. Owing to the lack of good research evidence that either ViaSpan or Soltran is better than the other, the cheaper, Soltran, may be preferable. In the absence of a cost-utility analysis, the results of our meta-analysis of the RCTs comparing ViaSpan with Celsior indicate that these cold storage solutions are equivalent. Further RCTs of comparators of interest to allow for appropriate analysis of subgroups and to determine whether either of the two machines under consideration produces better outcomes may be useful. In addition, research is required to: establish the strength and reliability of the presumed causal association between DGF and graft, and patient survival; investigate the utility impacts of renal replacement therapy; determine what the additional cost, survival and QALY impacts are of decreased or increased non-viable kidneys when discarded pre transplantation; and identify a reliable measure for predicting kidney viability from machine perfusion.

Prediction of acute kidney injury within 30 days of cardiac surgery.

PubMed

Ng, Shu Yi; Sanagou, Masoumeh; Wolfe, Rory; Cochrane, Andrew; Smith, Julian A; Reid, Christopher Michael

2014-06-01

To predict acute kidney injury after cardiac surgery. The study included 28,422 cardiac surgery patients who had had no preoperative renal dialysis from June 2001 to June 2009 in 18 hospitals. Logistic regression analyses were undertaken to identify the best combination of risk factors for predicting acute kidney injury. Two models were developed, one including the preoperative risk factors and another including the pre-, peri-, and early postoperative risk factors. The area under the receiver operating characteristic curve was calculated, using split-sample internal validation, to assess model discrimination. The incidence of acute kidney injury was 5.8% (1642 patients). The mortality for patients who experienced acute kidney injury was 17.4% versus 1.6% for patients who did not. On validation, the area under the curve for the preoperative model was 0.77, and the Hosmer-Lemeshow goodness-of-fit P value was .06. For the postoperative model area under the curve was 0.81 and the Hosmer-Lemeshow P value was .6. Both models had good discrimination and acceptable calibration. Acute kidney injury after cardiac surgery can be predicted using preoperative risk factors alone or, with greater accuracy, using pre-, peri-, and early postoperative risk factors. The ability to identify high-risk individuals can be useful in preoperative patient management and for recruitment of appropriate patients to clinical trials. Prediction in the early stages of postoperative care can guide subsequent intensive care of patients and could also be the basis of a retrospective performance audit tool. Copyright © 2014 The American Association for Thoracic Surgery. Published by Mosby, Inc. All rights reserved.

Diffusion of surgical innovation among patients with kidney cancer

PubMed Central

Miller, David C.; Saigal, Christopher S.; Banerjee, Mousumi; Hanley, Jan; Litwin, Mark S.

2009-01-01

Background Despite their potential benefits to patients with kidney cancer, the adoption of partial nephrectomy and laparoscopy has been gradual and asymmetric. To clarify whether this trend reflects differences in kidney cancer patients or differences in surgeon practice styles, we compared the magnitude of surgeon-attributable variance in the use of partial nephrectomy and laparoscopic radical nephrectomy with that attributable to patient and tumor characteristics. Methods Using linked Surveillance, Epidemiology, and End Results-Medicare data, we identified a cohort of 5,483 Medicare beneficiaries treated surgically for kidney cancer between 1997 and 2002. We defined two primary outcomes: (1) use of partial nephrectomy, and (2) use of laparoscopy among patients undergoing radical nephrectomy. Using multilevel models, we estimated surgeon- and patient-level contributions to observed variations in the use of partial nephrectomy and laparoscopic radical nephrectomy. Results Of the 5,483 cases identified, 611(11.1%) underwent partial nephrectomy (43 performed laparoscopically), and 4,872 (88.9%) underwent radical nephrectomy (515 performed laparoscopically). After adjusting for patient demographics, comorbidity, tumor size and surgeon volume, the surgeon-attributable variance was 18.1% for partial nephrectomy and 37.4% for laparoscopy. For both outcomes, the percentage of total variance attributable to surgeon factors was consistently higher than that attributable to patient characteristics. Conclusions For many patients with kidney cancer, the surgery provided depends more on their surgeon’s practice style than on the characteristics of the patient and his or her disease. Consequently, dismantling barriers to surgeon adoption of partial nephrectomy and laparoscopy is an important step toward improving the quality of care for patients with early-stage kidney cancer. PMID:18330868

Temporal and geographical external validation study and extension of the Mayo Clinic prediction model to predict eGFR in the younger population of Swiss ADPKD patients.

PubMed

Girardat-Rotar, Laura; Braun, Julia; Puhan, Milo A; Abraham, Alison G; Serra, Andreas L

2017-07-17

Prediction models in autosomal dominant polycystic kidney disease (ADPKD) are useful in clinical settings to identify patients with greater risk of a rapid disease progression in whom a treatment may have more benefits than harms. Mayo Clinic investigators developed a risk prediction tool for ADPKD patients using a single kidney value. Our aim was to perform an independent geographical and temporal external validation as well as evaluate the potential for improving the predictive performance by including additional information on total kidney volume. We used data from the on-going Swiss ADPKD study from 2006 to 2016. The main analysis included a sample size of 214 patients with Typical ADPKD (Class 1). We evaluated the Mayo Clinic model performance calibration and discrimination in our external sample and assessed whether predictive performance could be improved through the addition of subsequent kidney volume measurements beyond the baseline assessment. The calibration of both versions of the Mayo Clinic prediction model using continuous Height adjusted total kidney volume (HtTKV) and using risk subclasses was good, with R 2 of 78% and 70%, respectively. Accuracy was also good with 91.5% and 88.7% of the predicted within 30% of the observed, respectively. Additional information regarding kidney volume did not substantially improve the model performance. The Mayo Clinic prediction models are generalizable to other clinical settings and provide an accurate tool based on available predictors to identify patients at high risk for rapid disease progression.

Anatomy of the collecting system of lower pole of the kidney in patients with a single renal stone: a comparative study with individuals with normal kidneys.

PubMed

Zomorrodi, Afshar; Buhluli, Abulfazel; Fathi, Samad

2010-07-01

At least 5% of women and 12% of men during their lives will experience renal colic, at least once. Many theories have been suggested for the etiology of renal stones and variations in the anatomy of the collecting system have been suggested to have a role in stone formation. This study was conducted to examine the role of variation of lower pole collecting system in patients with lower pole kidney stone and compared the same in normal persons (kidney donors). Investigation for the anatomy of the lower pole of the kidney (angle between lower infundibulum and pelvis, length and diameter of the infundibulum and number and pattern distribution of calyces) was carried out using intravenous pyelogram (IVP) in 100 cases with urinary stone (study cases) and 400 persons with normal kidneys (control subjects). The study was a retrospective cross-sectional case control study. Results were analyzed by Mann-Whitney and independent sample chi square tests. The mean infundibulum-pelvic angle (IPA) in control subjects and in patients was 112.5 +/- 10.7 and 96.6 +/- 28.8, respectively. There was significant correlation between reduced angle and stone formation (P= < 0.001). The mean infundibulum-uretero-pelvic angle (IUPA) in control subjects and study cases was 53.5 +/- 12.7 and 42.6 +/- 13.4, respectively. There was significant correlation between decreased angle and stone formation (P = or < 0.001). The mean length of infundibulum of lower pole of kidney (IPIL) in controls and study patients was 22.5 +/- 4.1 and 27.5 +/- 7.7, respectively, which was statistically significant (P< 0.001). The mean number of calyces in lower pole of the kidney (LPCN) in controls and study patients was 2.6 +/- 0.6 and 3 +/- 0.9, respectively, which was statistically significant (P = or < 0.002). There was no significant correlation between distribution of calyces and stone formation (P= 0.366). Our study suggests that abnormal renal anatomy was more common in patients with lower pole kidney stone and should be considered a risk factor for forming lower pole kidney stone.

Incidence and risk factors for development of new-onset diabetes after kidney transplantation.

PubMed

Bee, Yong Mong; Tan, Hong Chang; Tay, Tunn Lin; Kee, Terence Ys; Goh, Su Yen; Kek, Peng Chin

2011-04-01

New-onset diabetes after transplantation (NODAT) is an increasingly recognised metabolic complication of kidney transplantation that is associated with increased morbidity and mortality. This study aimed to determine the incidence of NODAT and identify risk factors for development of NODAT among kidney allograft recipients in a single centre. We retrospectively reviewed all kidney allograft recipients in our centre between 1998 and 2007. NODAT were determined using criteria as per American Diabetes Association guidelines. Logistic regression analyses were performed to identify predictors of NODAT. Among 388 patients included in the analysis, NODAT was reported in 94 patients (24.2%) after a median follow-up time of 52.1 months. The cumulative incidence of NODAT was 15.8%, 22.8% and 24.5% at 1, 3, and 5 years following transplantation. Seven clinical factors were independent predictors of NODAT: older age, HLA B13 and B15 phenotypes, use of sirolimus, acute rejections, higher pre-transplant and post-transplant (day 1) plasma glucose levels. Patients with NODAT had poorer outcomes in both graft and patient survival. Our study demonstrates a significant risk and burden of NODAT in an Asian transplant population. Risk stratification and aggressive monitoring of blood glucose early post-transplantation is necessary to identify high-risk patients so that appropriate tailoring of immunosuppression and early institution of lifestyle modifications can be implemented.

Novel risk score of contrast-induced nephropathy after percutaneous coronary intervention.

PubMed

Ji, Ling; Su, XiaoFeng; Qin, Wei; Mi, XuHua; Liu, Fei; Tang, XiaoHong; Li, Zi; Yang, LiChuan

2015-08-01

Contrast-induced nephropathy (CIN) post-percutaneous coronary intervention (PCI) is a major cause of acute kidney injury. In this study, we established a comprehensive risk score model to assess risk of CIN after PCI procedure, which could be easily used in a clinical environment. A total of 805 PCI patients, divided into analysis cohort (70%) and validation cohort (30%), were enrolled retrospectively in this study. Risk factors for CIN were identified using univariate analysis and multivariate logistic regression in the analysis cohort. Risk score model was developed based on multiple regression coefficients. Sensitivity and specificity of the new risk score system was validated in the validation cohort. Comparisons between the new risk score model and previous reported models were applied. The incidence of post-PCI CIN in the analysis cohort (n = 565) was 12%. Considerably high CIN incidence (50%) was observed in patients with chronic kidney disease (CKD). Age >75, body mass index (BMI) >25, myoglobin level, cardiac function level, hypoalbuminaemia, history of chronic kidney disease (CKD), Intra-aortic balloon pump (IABP) and peripheral vascular disease (PVD) were identified as independent risk factors of post-PCI CIN. A novel risk score model was established using multivariate regression coefficients, which showed highest sensitivity and specificity (0.917, 95%CI 0.877-0.957) compared with previous models. A new post-PCI CIN risk score model was developed based on a retrospective study of 805 patients. Application of this model might be helpful to predict CIN in patients undergoing PCI procedure. © 2015 Asian Pacific Society of Nephrology.

Distinctive gene expression profiles characterize donor biopsies from HCV-positive kidney donors.

PubMed

Mas, Valeria R; Archer, Kellie J; Suh, Lacey; Scian, Mariano; Posner, Marc P; Maluf, Daniel G

2010-12-15

Because of the shortage of organs for transplantation, procurement of kidneys from extended criteria donors is inevitable. Frequently, donors infected with hepatitis C virus (HCV) are used. To elucidate an initial compromise of molecular pathways in HCV graft, gene expression profiles were evaluated. Twenty-four donor allograft biopsies (n=12 HCV positive (+) and n=12 HCV negative (-)) were collected at preimplantation time and profiled using microarrays. Donors were age, race, gender, and cold and warm ischemia time matched between groups. Probe level data were read into the R programming environment using the affy Bioconductor package, and the robust multiarray average method was used to obtain probe set expression summaries. To identify probe sets exhibiting differential expression, a two sample t test was performed. Molecular and biologic functions were analyzed using Interaction Networks and Functional Analysis. Fifty-eight probe sets were differentially expressed between HCV (+) versus HCV (-) donors (P<0.001). The molecular functions associated with the two top scored networks from the analysis of the differentially expressed genes were connective tissue development and function and tissue morphology (score 34), cell death, cell signaling, cellular assembly, and organization (score 32). Among the differentially affected top canonical pathways, we found the role of RIG1-like receptors in antiviral innate immunity (P<0.001), natural killer cell signaling (P=0.007), interleukin-8 signaling (P=0.048), interferon signaling (P=0.0 11; INFA21, INFGR1, and MED14), ILK signaling (P=0.001), and apoptosis signaling. A unique gene expression pattern was identified in HCV (+) kidney grafts. Innate immune system and inflammatory pathways were the most affected.

Safety of cerebral angiography and neuroendovascular therapy in patients with chronic kidney disease.

PubMed

Kim, Jae; Male, Shailesh; Jagadeesan, Bharathi D; Streib, Christopher; Tummala, Ramachandra P

2018-05-01

Contrast-induced nephropathy is a common clinical concern in patients undergoing neuroendovascular procedures, especially in those with pre-existent kidney disease. We aimed to define the incidence of contrast-induced nephropathy in these high-risk patients in our practice. We analyzed data retrospectively from patients undergoing neuroendovascular procedures at two academic medical centers over a 4-year period. Contrast-induced nephropathy was determined by an absolute increase in serum creatinine of 0.5 mg/dL or a rise from its baseline value by ≥ 25%, at 48-72 h after exposure to contrast agent after excluding other causes of renal impairment. High-risk patients were identified as those with pre-procedural estimated glomerular filtration rate < 60 mL/min irrespective of creatinine level, corresponding to stages 3-5 of chronic kidney disease. One hundred eighty-five high-risk patients undergoing conventional cerebral angiography and neuroendovascular interventions were identified. Only 1 out of 184 (0.54%) high-risk patients developed contrast-induced nephropathy. That one patient had stage 5 chronic kidney disease and multiple other risk factors. We have observed a very low rate of renal injury in patients with chronic kidney disease, traditionally considered high risk for neuroendovascular procedures. Multiple factors may be responsible in the risk reduction of contrast-induced nephropathy in this patient population.

A novel podocyte gene, semaphorin 3G, protects glomerular podocyte from lipopolysaccharide-induced inflammation.

PubMed

Ishibashi, Ryoichi; Takemoto, Minoru; Akimoto, Yoshihiro; Ishikawa, Takahiro; He, Peng; Maezawa, Yoshiro; Sakamoto, Kenichi; Tsurutani, Yuya; Ide, Shintaro; Ide, Kana; Kawamura, Harukiyo; Kobayashi, Kazuki; Tokuyama, Hirotake; Tryggvason, Karl; Betsholtz, Christer; Yokote, Koutaro

2016-05-16

Kidney diseases including diabetic nephropathy have become huge medical problems, although its precise mechanisms are still far from understood. In order to increase our knowledge about the patho-physiology of kidney, we have previously identified >300 kidney glomerulus-enriched transcripts through large-scale sequencing and microarray profiling of the mouse glomerular transcriptome. One of the glomerulus-specific transcripts identified was semaphorin 3G (Sema3G) which belongs to the semaphorin family. The aim of this study was to analyze both the in vivo and in vitro functions of Sema3G in the kidney. Sema3G was expressed in glomerular podocytes. Although Sema3G knockout mice did not show obvious glomerular defects, ultrastructural analyses revealed partially aberrant podocyte foot processes structures. When these mice were injected with lipopolysaccharide to induce acute inflammation or streptozotocin to induce diabetes, the lack of Sema3G resulted in increased albuminuria. The lack of Sema3G in podocytes also enhanced the expression of inflammatory cytokines including chemokine ligand 2 and interleukin 6. On the other hand, the presence of Sema3G attenuated their expression through the inhibition of lipopolysaccharide-induced Toll like receptor 4 signaling. Taken together, our results surmise that the Sema3G protein is secreted by podocytes and protects podocytes from inflammatory kidney diseases and diabetic nephropathy.

A novel podocyte gene, semaphorin 3G, protects glomerular podocyte from lipopolysaccharide-induced inflammation

PubMed Central

Ishibashi, Ryoichi; Takemoto, Minoru; Akimoto, Yoshihiro; Ishikawa, Takahiro; He, Peng; Maezawa, Yoshiro; Sakamoto, Kenichi; Tsurutani, Yuya; Ide, Shintaro; Ide, Kana; Kawamura, Harukiyo; Kobayashi, Kazuki; Tokuyama, Hirotake; Tryggvason, Karl; Betsholtz, Christer; Yokote, Koutaro

2016-01-01

Kidney diseases including diabetic nephropathy have become huge medical problems, although its precise mechanisms are still far from understood. In order to increase our knowledge about the patho-physiology of kidney, we have previously identified >300 kidney glomerulus-enriched transcripts through large-scale sequencing and microarray profiling of the mouse glomerular transcriptome. One of the glomerulus-specific transcripts identified was semaphorin 3G (Sema3G) which belongs to the semaphorin family. The aim of this study was to analyze both the in vivo and in vitro functions of Sema3G in the kidney. Sema3G was expressed in glomerular podocytes. Although Sema3G knockout mice did not show obvious glomerular defects, ultrastructural analyses revealed partially aberrant podocyte foot processes structures. When these mice were injected with lipopolysaccharide to induce acute inflammation or streptozotocin to induce diabetes, the lack of Sema3G resulted in increased albuminuria. The lack of Sema3G in podocytes also enhanced the expression of inflammatory cytokines including chemokine ligand 2 and interleukin 6. On the other hand, the presence of Sema3G attenuated their expression through the inhibition of lipopolysaccharide-induced Toll like receptor 4 signaling. Taken together, our results surmise that the Sema3G protein is secreted by podocytes and protects podocytes from inflammatory kidney diseases and diabetic nephropathy. PMID:27180624

A mouse model of alcoholic liver fibrosis-associated acute kidney injury identifies key molecular pathways

DOE Office of Scientific and Technical Information (OSTI.GOV)

Furuya, Shinji; Chappell, Grace A.; Iwata, Yasuhir

Clinical data strongly indicate that acute kidney injury (AKI) is a critical complication in alcoholic hepatitis, an acute-on-chronic form of liver failure in patients with advanced alcoholic fibrosis. Development of targeted therapies for AKI in this setting is hampered by the lack of an animal model. To enable research into molecular drivers and novel therapies for fibrosis- and alcohol-associated AKI, we aimed to combine carbon tetrachloride (CCl{sub 4})-induced fibrosis with chronic intra-gastric alcohol feeding. Male C57BL/6J mice were administered a low dose of CCl{sub 4} (0.2 ml/kg 2 × week/6 weeks) followed by alcohol intragastrically (up to 25 g/kg/day formore » 3 weeks) and with continued CCl{sub 4}. We observed that combined treatment with CCl{sub 4} and alcohol resulted in severe liver injury, more pronounced than using each treatment alone. Importantly, severe kidney injury was evident only in the combined treatment group. This mouse model reproduced distinct pathological features consistent with AKI in human alcoholic hepatitis. Transcriptomic analysis of kidneys revealed profound effects in the combined treatment group, with enrichment for damage-associated pathways, such as apoptosis, inflammation, immune-response and hypoxia. Interestingly, Havcr1 and Lcn2, biomarkers of AKI, were markedly up-regulated. Overall, this study established a novel mouse model of fibrosis- and alcohol-associated AKI and identified key mechanistic pathways. - Highlights: • Acute kidney injury (AKI) is a critical complication in alcoholic hepatitis • We developed a novel mouse model of fibrosis- and alcohol-associated AKI • This model reproduces key molecular and pathological features of human AKI • This animal model can help identify new targeted therapies for alcoholic hepatitis.« less

[Identifying the specific causes of kidney allograft loss: A population-based study].

PubMed

Lohéac, Charlotte; Aubert, Olivier; Loupy, Alexandre; Legendre, Christophe

2018-04-01

Results of kidney transplantation have been improving but long-term allograft survival remains disappointing. The objective of the present study was to identify the specific causes of renal allograft loss, to assess their incidence and long-term outcomes. A total of 4783 patients from four French centres, transplanted between January 2004 and January 2014 were prospectively included. A total of 9959 kidney biopsies (protocol and for cause) performed between January 2004 and March 2015 were included. Donor and recipient clinical and biological parameters as well as anti-HLA antibody directed against the donor were included. The main outcome was the long-term kidney allograft survival, including the study of the associated causes of graft loss, the delay of graft loss according to their causes and the determinants of graft loss. There were 732 graft losses during the follow-up period (median time: 4.51 years) with an identified cause in 95.08 %. Kidney allograft survival at 9 years post-transplant was 78 %. The causes of allograft loss were: antibody-mediated rejection (31.69 %), thrombosis (25.55 %), medical intercurrent disease (14.62 %), recurrence of primary renal disease (7.1 %), BK- or CMV-associated nephropathy (n=35, 4.78 %), T cell-mediated rejection (4.78 %), urological disease (2.46 %) and calcineurin inhibitor nephrotoxicity (1.09 %). The main causes of allograft loss were antibody-mediated rejection and thrombosis. These results encourage efforts to prevent and detect these complications earlier in order to improve allograft survival. Copyright © 2018 Association Société de néphrologie. Published by Elsevier Masson SAS. All rights reserved.

Identification and characterization of kidney transplants with good glomerular filtration rate at 1 year but subsequent progressive loss of renal function.

PubMed

Park, Walter D; Larson, Timothy S; Griffin, Matthew D; Stegall, Mark D

2012-11-15

After the first year after kidney transplantation, 3% to 5% of grafts fail each year but detailed studies of how grafts progress to failure are lacking. This study aimed to analyze the functional stability of kidney transplants between 1 and 5 years after transplantation and to identify initially well-functioning grafts with progressive decline in allograft function. The study included 788 adult conventional kidney transplants performed at the Mayo Clinic Rochester between January 2000 and December 2005 with a minimum graft survival and follow-up of 2.6 years. The modification of diet in renal disease equation for estimating glomerular filtration rate (eGFR(MDRD)) was used to calculate the slope of renal function over time using all available serum creatinine values between 1 and 5 years after transplantation. Most transplants demonstrated good function (eGFR(MDRD) ≥40 mL/min) at 1 year with positive eGFR(MDRD) slope between 1 and 5 years after transplantation. However, a subset of grafts with 1-year eGFR(MDRD) ≥40 mL/min exhibited strongly negative eGFR(MDRD) slope between 1 and 5 years suggestive of progressive loss of graft function. Forty-one percent of this subset reached graft failure during follow-up, accounting for 69% of allograft failures occurring after 2.5 years after transplantation. This pattern of progressive decline in estimated glomerular filtration rate despite good early function was associated with but not fully attributable to factors suggestive of enhanced antidonor immunity. Longitudinal analysis of serial estimated glomerular filtration ratemeasurements identifies initially well-functioning kidney transplants at high risk for subsequent graft loss. For this subset, further studies are needed to identify modifiable causes of functional decline.

A mouse diversity panel approach reveals the potential for clinical kidney injury due to DB289 not predicted by classical rodent models.

PubMed

Harrill, Alison H; Desmet, Kristina D; Wolf, Kristina K; Bridges, Arlene S; Eaddy, J Scott; Kurtz, C Lisa; Hall, J Ed; Paine, Mary F; Tidwell, Richard R; Watkins, Paul B

2012-12-01

DB289 is the first oral drug shown in clinical trials to have efficacy in treating African trypanosomiasis (African sleeping sickness). Mild liver toxicity was noted but was not treatment limiting. However, development of DB289 was terminated when several treated subjects developed severe kidney injury, a liability not predicted from preclinical testing. We tested the hypothesis that the kidney safety liability of DB289 would be detected in a mouse diversity panel (MDP) comprised of 34 genetically diverse inbred mouse strains. MDP mice received 10 days of oral treatment with DB289 or vehicle and classical renal biomarkers blood urea nitrogen (BUN) and serum creatinine (sCr), as well as urine biomarkers of kidney injury were measured. While BUN and sCr remained within reference ranges, marked elevations were observed for kidney injury molecule-1 (KIM-1) in the urine of sensitive mouse strains. KIM-1 elevations were not always coincident with elevations in alanine aminotransferase (ALT), suggesting that renal injury was not linked to hepatic injury. Genome-wide association analyses of KIM-1 elevations indicated that genes participating in cholesterol and lipid biosynthesis and transport, oxidative stress, and cytokine release may play a role in DB289 renal injury. Taken together, the data resulting from this study highlight the utility of using an MDP to predict clinically relevant toxicities, to identify relevant toxicity biomarkers that may translate into the clinic, and to identify potential mechanisms underlying toxicities. In addition, the sensitive mouse strains identified in this study may be useful in screening next-in-class compounds for renal injury.

Independent Pre-Transplant Recipient Cancer Risk Factors after Kidney Transplantation and the Utility of G-Chart Analysis for Clinical Process Control.

PubMed

Schrem, Harald; Schneider, Valentin; Kurok, Marlene; Goldis, Alon; Dreier, Maren; Kaltenborn, Alexander; Gwinner, Wilfried; Barthold, Marc; Liebeneiner, Jan; Winny, Markus; Klempnauer, Jürgen; Kleine, Moritz

2016-01-01

The aim of this study is to identify independent pre-transplant cancer risk factors after kidney transplantation and to assess the utility of G-chart analysis for clinical process control. This may contribute to the improvement of cancer surveillance processes in individual transplant centers. 1655 patients after kidney transplantation at our institution with a total of 9,425 person-years of follow-up were compared retrospectively to the general German population using site-specific standardized-incidence-ratios (SIRs) of observed malignancies. Risk-adjusted multivariable Cox regression was used to identify independent pre-transplant cancer risk factors. G-chart analysis was applied to determine relevant differences in the frequency of cancer occurrences. Cancer incidence rates were almost three times higher as compared to the matched general population (SIR = 2.75; 95%-CI: 2.33-3.21). Significantly increased SIRs were observed for renal cell carcinoma (SIR = 22.46), post-transplant lymphoproliferative disorder (SIR = 8.36), prostate cancer (SIR = 2.22), bladder cancer (SIR = 3.24), thyroid cancer (SIR = 10.13) and melanoma (SIR = 3.08). Independent pre-transplant risk factors for cancer-free survival were age <52.3 years (p = 0.007, Hazard ratio (HR): 0.82), age >62.6 years (p = 0.001, HR: 1.29), polycystic kidney disease other than autosomal dominant polycystic kidney disease (ADPKD) (p = 0.001, HR: 0.68), high body mass index in kg/m2 (p<0.001, HR: 1.04), ADPKD (p = 0.008, HR: 1.26) and diabetic nephropathy (p = 0.004, HR = 1.51). G-chart analysis identified relevant changes in the detection rates of cancer during aftercare with no significant relation to identified risk factors for cancer-free survival (p<0.05). Risk-adapted cancer surveillance combined with prospective G-chart analysis likely improves cancer surveillance schemes by adapting processes to identified risk factors and by using G-chart alarm signals to trigger Kaizen events and audits for root-cause analysis of relevant detection rate changes. Further, comparative G-chart analysis would enable benchmarking of cancer surveillance processes between centers.

Independent Pre-Transplant Recipient Cancer Risk Factors after Kidney Transplantation and the Utility of G-Chart Analysis for Clinical Process Control

PubMed Central

Kurok, Marlene; Goldis, Alon; Dreier, Maren; Kaltenborn, Alexander; Gwinner, Wilfried; Barthold, Marc; Liebeneiner, Jan; Winny, Markus; Klempnauer, Jürgen; Kleine, Moritz

2016-01-01

Background The aim of this study is to identify independent pre-transplant cancer risk factors after kidney transplantation and to assess the utility of G-chart analysis for clinical process control. This may contribute to the improvement of cancer surveillance processes in individual transplant centers. Patients and Methods 1655 patients after kidney transplantation at our institution with a total of 9,425 person-years of follow-up were compared retrospectively to the general German population using site-specific standardized-incidence-ratios (SIRs) of observed malignancies. Risk-adjusted multivariable Cox regression was used to identify independent pre-transplant cancer risk factors. G-chart analysis was applied to determine relevant differences in the frequency of cancer occurrences. Results Cancer incidence rates were almost three times higher as compared to the matched general population (SIR = 2.75; 95%-CI: 2.33–3.21). Significantly increased SIRs were observed for renal cell carcinoma (SIR = 22.46), post-transplant lymphoproliferative disorder (SIR = 8.36), prostate cancer (SIR = 2.22), bladder cancer (SIR = 3.24), thyroid cancer (SIR = 10.13) and melanoma (SIR = 3.08). Independent pre-transplant risk factors for cancer-free survival were age <52.3 years (p = 0.007, Hazard ratio (HR): 0.82), age >62.6 years (p = 0.001, HR: 1.29), polycystic kidney disease other than autosomal dominant polycystic kidney disease (ADPKD) (p = 0.001, HR: 0.68), high body mass index in kg/m2 (p<0.001, HR: 1.04), ADPKD (p = 0.008, HR: 1.26) and diabetic nephropathy (p = 0.004, HR = 1.51). G-chart analysis identified relevant changes in the detection rates of cancer during aftercare with no significant relation to identified risk factors for cancer-free survival (p<0.05). Conclusions Risk-adapted cancer surveillance combined with prospective G-chart analysis likely improves cancer surveillance schemes by adapting processes to identified risk factors and by using G-chart alarm signals to trigger Kaizen events and audits for root-cause analysis of relevant detection rate changes. Further, comparative G-chart analysis would enable benchmarking of cancer surveillance processes between centers. PMID:27398803

Posterior approach to kidney dissection: An old surgical approach for integrated medical curricula.

PubMed

Daly, Frank J; Bolender, David L; Jain, Deepali; Uyeda, Sheryl; Hoagland, Todd M

2015-01-01

Integrated medical curricular changes are altering the historical regional anatomy approach to abdominal dissection. The renal system is linked physiologically and biochemically to the cardiovascular and respiratory systems; yet, anatomists often approach the urinary system as part of the abdomen and pelvic regions. As part of an integrated curriculum, the renal system must be covered relatively quickly after the thorax in the cadaver laboratory, often without the opportunity to fully appreciate the rest of the abdominal contents. This article provides dissection instructions that follow one of the historical surgical approaches for nephrectomy, including preservation of the posterior abdominal wall neurovasclature. Dissection procedures were developed for first-year medical students, intending this posterior approach to the kidneys to be their first introduction to the renal system. It has been successfully implemented with the first-year medical students at the University of New England, College of Osteopathic Medicine. Utilizing this posterior approach to the kidney enabled the study of the anatomy of the kidneys, suprarenal glands, and renal vessels, as well as the muscles of the lumbar spine, while maintaining the integrity of the anterior abdominal wall and peritoneal cavity for future gastrointestinal and reproductive system-based dissections. © 2015 American Association of Anatomists.

The ASCENT (Allocation System Changes for Equity in Kidney Transplantation) Study: a Randomized Effectiveness-Implementation Study to Improve Kidney Transplant Waitlisting and Reduce Racial Disparity.

PubMed

Patzer, Rachel E; Smith, Kayla; Basu, Mohua; Gander, Jennifer; Mohan, Sumit; Escoffery, Cam; Plantinga, Laura; Melanson, Taylor; Kalloo, Sean; Green, Gary; Berlin, Alex; Renville, Gary; Browne, Teri; Turgeon, Nicole; Caponi, Susan; Zhang, Rebecca; Pastan, Stephen

2017-05-01

The United Network for Organ Sharing (UNOS) implemented a new Kidney Allocation System (KAS) in December 2014 that is expected to substantially reduce racial disparities in kidney transplantation among waitlisted patients. However, not all dialysis facility clinical providers and end stage renal disease (ESRD) patients are aware of how the policy change could improve access to transplant. We describe the ASCENT (Allocation System Changes for Equity in KidNey Transplantation) study, a randomized controlled effectiveness-implementation study designed to test the effectiveness of a multicomponent intervention to improve access to the early steps of kidney transplantation among dialysis facilities across the United States. The multicomponent intervention consists of an educational webinar for dialysis medical directors, an educational video for patients and an educational video for dialysis staff, and a dialysis-facility specific transplant performance feedback report. Materials will be developed by a multidisciplinary dissemination advisory board and will undergo formative testing in dialysis facilities across the United States. This study is estimated to enroll ~600 U.S. dialysis facilities with low waitlisting in all 18 ESRD Networks. The co-primary outcomes include change in waitlisting, and waitlist disparity at 1 year; secondary outcomes include changes in facility medical director knowledge about KAS, staff training regarding KAS, patient education regarding transplant, and a medical director's intent to refer patients for transplant evaluation. The results from the ASCENT study will demonstrate the feasibility and effectiveness of a multicomponent intervention designed to increase access to the deceased-donor kidney waitlist and reduce racial disparities in waitlisting.

Renal hemodynamics and renin-angiotensin system activity in humans with multifocal renal artery fibromuscular dysplasia.

PubMed

van Twist, Daan J L; Houben, Alphons J H M; de Haan, Michiel W; de Leeuw, Peter W; Kroon, Abraham A

2016-06-01

Fibromuscular dysplasia (FMD) is the second most common cause of renovascular hypertension. Nonetheless, knowledge on the renal microvasculature and renin-angiotensin system (RAS) activity in kidneys with FMD is scarce. Given the fairly good results of revascularization, we hypothesized that the renal microvasculature and RAS are relatively spared in kidneys with FMD. In 58 hypertensive patients with multifocal renal artery FMD (off medication) and 116 matched controls with essential hypertension, we measured renal blood flow (Xenon washout method) per kidney and drew blood samples from the aorta and both renal veins to determine renin secretion and glomerular filtration rate per kidney. We found that renal blood flow and glomerular filtration rate in FMD were comparable to those in controls. Although systemic renin levels were somewhat higher in FMD, renal renin secretion was not elevated. Moreover, in patients with unilateral FMD, no differences between the affected and unaffected kidney were observed with regard to renal blood flow, glomerular filtration rate, or renin secretion. In men, renin levels and renin secretion were higher as compared with women. The renal blood flow response to RAS modulation (by intrarenal infusion of angiotensin II, angiotensin-(1-7), an angiotensin II type 1 receptor blocker, or a nitric oxide synthase blocker) was also comparable between FMD and controls. Renal blood flow, glomerular filtration, and the response to vasoactive substances in kidneys with multifocal FMD are comparable to patients with essential hypertension, suggesting that microvascular function is relatively spared. Renin secretion was not increased and the response to RAS modulation was not affected in kidneys with FMD.

The Kinase STK3 Interacts with the Viral Structural Protein VP1 and Inhibits Foot-and-Mouth Disease Virus Replication

PubMed Central

Xue, Qiao

2017-01-01

Foot-and-mouth disease virus (FMDV) is the etiological agent of FMD, which affects domestic and wild cloven-hoofed animals. The structural protein VP1 plays an important role in FMDV pathogenesis. However, the interacting partners of VP1 in host cells and the effects of these interactions in FMDV replication remain incompletely elucidated. Here, we identified a porcine cell protein, serine/threonine kinase 3 (STK3), which interacts with FMDV VP1 using the yeast two-hybrid system. The VP1-STK3 interaction was further confirmed by coimmunoprecipitation experiments in human embryonic kidney 293T and porcine kidney 15 (PK-15) cells. The carboxyl-terminal region (amino acids 180–214) of VP1 was essential for its interaction with STK3. The effects of overexpression and underexpressing of STK3 in PK-15 cells were assessed, and the results indicated that STK3 significantly inhibited FMDV replication. Our data expand the role of STK3 during viral infection, provide new information regarding the host cell kinases that are involved in viral replication, and identify potential targets for future antiviral strategies. PMID:29226127

Biochemical basis for pharmacological intervention as a reprogramming strategy against hypertension and kidney disease of developmental origin.

PubMed

Tain, You-Lin; Chan, Samuel H H; Chan, Julie Y H

2018-07-01

The concept of "developmental origins of health and disease" (DOHaD) stipulates that both hypertension and kidney disease may take origin from early-life insults. The DOHaD concept also offers reprogramming strategies aiming at shifting therapeutic interventions from adulthood to early life, even before clinical symptoms are evident. Based on those two concepts, this review will present the evidence for the existence of, and the programming mechanisms in, kidney developmental programming that may lead to hypertension and kidney disease. This will be followed by potential pharmacological interventions that may serve as a reprogramming strategy to counter the rising epidemic of hypertension and kidney disease. We point out that before patients could benefit from this strategy, the most pressing issue is for the growing body of evidence from animal studies in support of pharmacological intervention as a reprogramming strategy to long-term protect against hypertension and kidney disease of developmental origins to be validated clinically and the critical window, drug dose, dosing regimen, and therapeutic duration identified. Copyright © 2018 Elsevier Inc. All rights reserved.

Transcript profiling of Wilms tumors reveals connections to kidney morphogenesis and expression patterns associated with anaplasia.

PubMed

Li, Wenliang; Kessler, Patricia; Williams, Bryan R G

2005-01-13

Anaplasia (unfavorable histology) is associated with therapy resistance and poor prognosis of Wilms tumor, but the molecular basis for this phenotype is unclear. Here, we used a cDNA array with 9240 clones relevant to cancer biology and/or kidney development to examine the expression profiles of 54 Wilms tumors, five normal kidneys and fetal kidney. By linking genes differentially expressed between fetal kidney and Wilms tumors to kidney morphogenesis, we found that genes expressed at a higher level in Wilms tumors tend to be expressed more in uninduced metanephrogenic mesenchyme or blastema than in their differentiated structures. Conversely, genes expressed at a lower level in Wilms tumors tend to be expressed less in uninduced metanephrogenic mesenchyme or blastema. We also identified 97 clones representing 76 Unigenes or unclustered ESTs that clearly separate anaplastic Wilms tumors from tumors with favorable histology. Genes in this set provide insight into the nature of the abnormal nuclear morphology of anaplastic tumors and may facilitate identification of molecular targets to improve their responsiveness to treatment.

Educating Prospective Kidney Transplant Recipients and Living Donors about Living Donation: Practical and Theoretical Recommendations for Increasing Living Donation Rates

PubMed Central

Waterman, Amy D.; Robbins, Mark L.; Peipert, John D.

2016-01-01

A promising strategy for increasing living donor kidney transplant (LDKT) rates is improving education about living donation for both prospective kidney transplant recipients and living donors to help overcome the proven knowledge, psychological, and socioeconomic barriers to LDKT. A recent Consensus Conference on Best Practices in Live Kidney Donation recommended that comprehensive LDKT education be made available to patients at all stages of chronic kidney disease (CKD). However, in considering how to implement this recommendation across different healthcare learning environments, the current lack of available guidance regarding how to design, deliver, and measure the efficacy of LDKT education programs is notable. In the current article, we provide an overview of how one behavior change theory, the Transtheoretical Model of Behavior Change, can guide the delivery of LDKT education for patients at various stages of CKD and readiness for LDKT. We also discuss the importance of creating educational programs for both potential kidney transplant recipients and living donors, and identify key priorities for educational research to reduce racial disparities in LDKT and increase LDKT rates. PMID:27347475

Does Altered Uric Acid Metabolism Contribute to Diabetic Kidney Disease Pathophysiology?

PubMed

Gul, Ambreen; Zager, Philip

2018-03-01

Multiple experimental and clinical studies have identified pathways by which uric acid may facilitate the development and progression of chronic kidney disease (CKD) in people with diabetes. However, it remains uncertain if the association of uric acid with CKD represents a pathogenic effect or merely reflects renal impairment. In contrast to many published reports, a recent Mendelian randomization study did not identify a causal link between uric acid and CKD in people with type 1 diabetes. Two recent multicenter randomized control trials, Preventing Early Renal Function Loss in Diabetes (PERL) and FEbuxostat versus placebo rAndomized controlled Trial regarding reduced renal function in patients with Hyperuricemia complicated by chRonic kidney disease stage 3 (FEATHER), were recently designed to assess if uric acid lowering slows progression of CKD. We review the evidence supporting a role for uric acid in the pathogenesis of CKD in people with diabetes and the putative benefits of uric acid lowering.

Ochratoxin A induces rat renal carcinogenicity with limited induction of oxidative stress responses

DOE Office of Scientific and Technical Information (OSTI.GOV)

Qi, Xiaozhe; Yu, Tao; Zhu, Liye

Ochratoxin A (OTA) has displayed nephrotoxicity and renal carcinogenicity in mammals, however, no clear mechanisms have been identified detailing the relationship between oxidative stress and these toxicities. This study was performed to clarify the relationship between oxidative stress and the renal carcinogenicity induced by OTA. Rats were treated with 70 or 210 μg/kg b.w. OTA for 4 or 13 weeks. In the rats administrated with OTA for 13 weeks, the kidney was damaged seriously. Cytoplasmic vacuolization was observed in the outer stripe of the outer medulla. Karyomegaly was prominent in the tubular epithelium. Kidney injury molecule-1 (Kim-1) was detected inmore » the outer stripe of the outer medulla in both low- and high-dose groups. OTA increased the mRNA levels of clusterin in rat kidneys. Interestingly, OTA did not significantly alter the oxidative stress level in rat liver and kidney. Yet, some indications related to proliferation and carcinogenicity were observed. A dose-related increase in proliferating cell nuclear antigen (PCNA) was observed at 4 weeks in both liver and kidney, but at 13 weeks, only in the kidney. OTA down-regulated reactive oxygen species (ROS) and up-regulated vimentin and lipocalin 2 in rat kidney at 13 weeks. The p53 gene was decreased in both liver and kidney at 13 weeks. These results suggest that OTA caused apparent kidney damage within 13 weeks but exerted limited effect on oxidative stress parameters. It implies that cell proliferation is the proposed mode of action for OTA-induced renal carcinogenicity. - Highlights: • We studied OTA toxicities in both the rat liver and kidney for 13 weeks. • OTA exerts limited effects on oxidative stress in the rat liver and kidney. • OTA induced renal carcinogenicity resulting from cell proliferation.« less

Nitric Oxide Decreases Acute Kidney Injury and Stage 3 Chronic Kidney Disease after Cardiac Surgery.

PubMed

Lei, Chong; Berra, Lorenzo; Rezoagli, Emanuele; Yu, Binglan; Dong, Hailong; Yu, Shiqiang; Hou, Lihong; Chen, Min; Chen, Wensheng; Wang, Hongbing; Zheng, Qijun; Shen, Jie; Jin, Zhenxiao; Chen, Tao; Zhao, Rong; Christie, Emily; Sabbisetti, Venkata S; Nordio, Francesco; Bonventre, Joseph V; Xiong, Lize; Zapol, Warren M

2018-06-22

No medical intervention has been identified that decreases acute kidney injury and improves renal outcome at 1-year after cardiac surgery. To determine whether administration of nitric oxide reduces the incidence of post-operative acute kidney injury and improves long-term kidney outcomes after multiple cardiac valve replacement requiring prolonged cardiopulmonary bypass. 244 Patients undergoing elective, multiple valve replacement surgery mostly due to rheumatic fever were randomized to receive either nitric oxide (treatment) or nitrogen (control). Nitric oxide and nitrogen were administered via the gas exchanger during cardiopulmonary bypass and by inhalation for 24h post-operatively. Primary outcome: Oxidation of ferrous plasma oxyhemoglobin to ferric methemoglobin was associated to a reduced post-operative acute kidney injury from 64% (control group) to 50% (nitric oxide) (RR, 95% CI; 0.78, 0.62-0.97;P=0.014). At 90-days, transition to stage 3 chronic kidney disease was reduced from 33% in the controls to 21% in the treatment group (RR, 95%CI; 0.64, 0.41 - 0.99;P=0.024); and at 1-year, from 31% to 18% (RR, 95% CI; 0.59, 0.36 - 0.96;P=0.017). Nitric oxide treatment reduced the overall major adverse kidney events at 30-days (RR, 95% CI; 0.40, 0.18 - 0.92;P=0.016, 90-days (RR, 95% CI; 0.40, 0.17 - 0.92;P=0.015 and 1-year (RR, 95% CI; 0.47, 0.20-1.10;P=0.041). In patients undergoing multiple valve replacement and prolonged cardiopulmonary bypass, administration of nitric oxide decreased the incidence of acute kidney injury, transition to stage 3 chronic kidney disease and major adverse kidney events at 30-days, 90-days, and 1-year. Clinical trial registered with ClinicalTrials.gov (NCT01802619).

MYH9 genetic variants associated with glomerular disease: what is the role for genetic testing?

PubMed

Kopp, Jeffrey B; Winkler, Cheryl A; Nelson, George W

2010-07-01

Genetic variation in MYH9, encoding nonmuscle myosin IIA heavy chain, has been associated recently with increased risk for kidney disease. Previously, MYH9 missense mutations have been shown to cause the autosomal-dominant MYH9 (ADM9) spectrum, characterized by large platelets, leukocyte Döhle bodies, and, variably, sensorineural deafness, cataracts, and glomerulopathy. Genetic testing is indicated for familial and sporadic cases that fit this spectrum. By contrast, the MYH9 kidney risk variant is characterized by multiple intronic single nucleotide polymorphisms, but the causative variant has not been identified. Disease associations include human immunodeficiency virus-associated collapsing glomerulopathy, focal segmental glomerulosclerosis, hypertension-attributed end-stage kidney disease, and diabetes-attributed end-stage kidney disease. One plausible hypothesis is that the MYH9 kidney risk variant confers a fragile podocyte phenotype. In the case of hypertension-attributed kidney disease, it remains unclear if the hypertension is a contributing cause or a consequence of glomerular injury. The MYH9 kidney risk variant is strikingly more common among individuals of African descent, but only some will develop clinical kidney disease in their lifetime. Thus, it is likely that additional genes and/or environmental factors interact with the MYH9 kidney risk variant to trigger glomerular injury. A preliminary genetic risk stratification scheme, using two single nucleotide polymorphisms, may estimate lifetime risk for kidney disease. Nevertheless, at present, no role has been established for genetic testing as part of personalized medicine, but testing should be considered in clinical studies of glomerular diseases among populations of African descent. Such studies will address critical questions pertaining to MYH9-associated kidney disease, including mechanism, course, and response to therapy. Published by Elsevier Inc.

Dual Kidney Allocation Score: A Novel Algorithm Utilizing Expanded Donor Criteria for the Allocation of Dual Kidneys in Adults.

PubMed

Johnson, Adam P; Price, Thea P; Lieby, Benjamin; Doria, Cataldo

2016-09-08

BACKGROUND Dual kidney transplantation (DKT) of expanded-criteria donors is a cost-intensive procedure that aims to increase the pool of available deceased organ donors and has demonstrated equivalent outcomes to expanded-criteria single kidney transplantation (eSKT). The objective of this study was to develop an allocation score based on predicted graft survival from historical dual and single kidney donors. MATERIAL AND METHODS We analyzed United Network for Organ Sharing (UNOS) data for 1547 DKT and 26 381 eSKT performed between January 1994 and September 2013. We utilized multivariable Cox regression to identify variables independently associated with graft survival in dual and single kidney transplantations. We then derived a weighted multivariable product score from calculated hazard ratios to model the benefit of transplantation as dual kidneys. RESULTS Of 36 donor variables known at the time of listing, 13 were significantly associated with graft survival. The derived dual allocation score demonstrated good internal validity with strong correlation to improved survival in dual kidney transplants. Donors with scores less than 2.1 transplanted as dual kidneys had a worsened median survival of 594 days (24%, p-value 0.031) and donors with scores greater than 3.9 had improved median survival of 1107 days (71%, p-value 0.002). There were 17 733 eSKT (67%) and 1051 DKT (67%) with scores in between these values and no differences in survival (p-values 0.676 and 0.185). CONCLUSIONS We have derived a dual kidney allocation score (DKAS) with good internal validity. Future prospective studies will be required to demonstrate external validity, but this score may help to standardize organ allocation for dual kidney transplantation.

Acoustic radiation force impulse elastography of the kidneys: is shear wave velocity affected by tissue fibrosis or renal blood flow?

PubMed

Asano, Kenichiro; Ogata, Ai; Tanaka, Keiko; Ide, Yoko; Sankoda, Akiko; Kawakita, Chieko; Nishikawa, Mana; Ohmori, Kazuyoshi; Kinomura, Masaru; Shimada, Noriaki; Fukushima, Masaki

2014-05-01

The aim of this study was to identify the main influencing factor of the shear wave velocity (SWV) of the kidneys measured by acoustic radiation force impulse elastography. The SWV was measured in the kidneys of 14 healthy volunteers and 319 patients with chronic kidney disease. The estimated glomerular filtration rate was calculated by the serum creatinine concentration and age. As an indicator of arteriosclerosis of large vessels, the brachial-ankle pulse wave velocity was measured in 183 patients. Compared to the degree of interobserver and intraobserver deviation, a large variance of SWV values was observed in the kidneys of the patients with chronic kidney disease. Shear wave velocity values in the right and left kidneys of each patient correlated well, with high correlation coefficients (r = 0.580-0.732). The SWV decreased concurrently with a decline in the estimated glomerular filtration rate. A low SWV was obtained in patients with a high brachial-ankle pulse wave velocity. Despite progression of renal fibrosis in the advanced stages of chronic kidney disease, these results were in contrast to findings for chronic liver disease, in which progression of hepatic fibrosis results in an increase in the SWV. Considering that a high brachial-ankle pulse wave velocity represents the progression of arteriosclerosis in the large vessels, the reduction of elasticity succeeding diminution of blood flow was suspected to be the main influencing factor of the SWV in the kidneys. This study indicates that diminution of blood flow may affect SWV values in the kidneys more than the progression of tissue fibrosis. Future studies for reducing data variance are needed for effective use of acoustic radiation force impulse elastography in patients with chronic kidney disease.

Hypertension in pediatric patients with chronic kidney disease: management challenges.

PubMed

Gallibois, Claire M; Jawa, Natasha A; Noone, Damien G

2017-01-01

In contrast to adults where hypertension is a leading cause of chronic kidney disease, in pediatrics, hypertension is predominantly a sequela, however, an important one that, like in adults, is likely associated with a more rapid decline in kidney function or progression of chronic kidney disease to end stage. There is a significant issue with unrecognized, or masked, hypertension in childhood chronic kidney disease. Recent evidence and, therefore, guidelines now suggest targeting a blood pressure of <50th percentile for age, sex, and height in children with proteinuria and chronic kidney disease. This often cannot be achieved by monotherapy and additional agents need to be added. Blockade of the renin angiotensin aldosterone system represents the mainstay of therapy, although often limited by the side effect of hyperkalemia. The addition of a diuretic, at least in the earlier stages of chronic kidney disease, might help mitigate this problem.

Cardio-renal syndromes: a systematic approach for consensus definition and classification.

PubMed

Ronco, Claudio; Ronco, Federico

2012-03-01

The "Cardio-Renal Syndrome" (CRS) is a disorder of the heart and kidneys whereby acute or chronic dysfunction in one organ may induce acute or chronic dysfunction of the other. The general definition has been expanded to five subtypes reflecting the primacy of organ dysfunction and the time-frame of the syndrome: CRS type I: acute worsening of heart function (AHF-ACS) leading to kidney injury and/or dysfunction. CRS type II: chronic abnormalities in heart function (CHF-CHD) leading to kidney injury or dysfunction. CRS type III: acute worsening of kidney function (AKI) leading to heart injury and/or dysfunction. CRS type IV: chronic kidney disease (CKD) leading to heart injury, disease and/or dysfunction. CRS type V: systemic conditions leading to simultaneous injury and/or dysfunction of heart and kidney. Different pathophysiological mechanisms are involved in the combined dysfunction of heart and kidney in these five types of the syndrome.

Continuous Real-time Viability Assessment of Kidneys Based on Oxygen Consumption

PubMed Central

Weegman, B.P.; Kirchner, V.A.; Scott, W.E.; Avgoustiniatos, E.S.; Suszynski, T.M.; Ferrer-Fabrega, J.; Rizzari, M.D.; Kidder, L.S.; Kandaswamy, R.; Sutherland, D.E.R.; Papas, K.K.

2010-01-01

Background Current ex vivo quality assessment of donor kidneys is limited to vascular resistance measurements and histological analysis. New techniques for the assessment of organ quality before transplantation may further improve clinical outcomes while expanding the depleted deceased-donor pool. We propose the measurement of whole organ oxygen consumption rate (WOOCR) as a method to assess the quality of kidneys in real time before transplantation. Methods Five porcine kidneys were procured using a donation after cardiac death (DCD) model. The renal artery and renal vein were cannulated and the kidney connected to a custom-made hypothermic machine perfusion (HMP) system equipped with an inline oxygenator and fiber-optic oxygen sensors. Kidneys were perfused at 8°C, and the perfusion parameters and partial oxygen pressures (pO2) were measured to calculate WOOCR. Results Without an inline oxygenator, the pO2 of the perfusion solution at the arterial inlet and venous outlet diminished to near 0 within minutes. However, once adequate oxygenation was provided, a significant pO2 difference was observed and used to calculate the WOOCR. The WOOCR was consistently measured from presumably healthy kidneys, and results suggest that it can be used to differentiate between healthy and purposely damaged organs. Conclusions Custom-made HMP systems equipped with an oxygenator and inline oxygen sensors can be applied for WOOCR measurements. We suggest that WOOCR is a promising approach for the real-time quality assessment of kidneys and other organs during preservation before transplantation. PMID:20692397

Exome-first approach identified a novel gloss deletion associated with Lowe syndrome.

PubMed

Watanabe, Miki; Nakagawa, Ryuji; Kohmoto, Tomohiro; Naruto, Takuya; Suga, Ken-Ichi; Goji, Aya; Horikawa, Hideaki; Masuda, Kiyoshi; Kagami, Shoji; Imoto, Issei

2016-01-01

Lowe syndrome (LS) is an X-linked disorder affecting the eyes, nervous system and kidneys, typically caused by missense or nonsense/frameshift OCRL mutations. We report a 6-month-old male clinically suspected to have LS, but without the Fanconi-type renal dysfunction. Using a targeted-exome sequencing-first approach, LS was diagnosed by the identification of a deletion involving 1.7 Mb at Xq25-q26.1, encompassing the entire OCRL gene and neighboring loci.

Exome-first approach identified a novel gloss deletion associated with Lowe syndrome

PubMed Central

Watanabe, Miki; Nakagawa, Ryuji; Kohmoto, Tomohiro; Naruto, Takuya; Suga, Ken-ichi; Goji, Aya; Horikawa, Hideaki; Masuda, Kiyoshi; Kagami, Shoji; Imoto, Issei

2016-01-01

Lowe syndrome (LS) is an X-linked disorder affecting the eyes, nervous system and kidneys, typically caused by missense or nonsense/frameshift OCRL mutations. We report a 6-month-old male clinically suspected to have LS, but without the Fanconi-type renal dysfunction. Using a targeted-exome sequencing-first approach, LS was diagnosed by the identification of a deletion involving 1.7 Mb at Xq25-q26.1, encompassing the entire OCRL gene and neighboring loci. PMID:27867521

Microbubbles induce renal hemorrhage when exposed to diagnostic ultrasound in anesthetized rats.

PubMed

Wible, James H; Galen, Karen P; Wojdyla, Jolette K; Hughes, Michael S; Klibanov, Alexander L; Brandenburger, Gary H

2002-01-01

The generation of ultrasound (US) bioeffects using a clinical imaging system is controversial. We tested the hypothesis that the presence of microbubbles in the US field of a medical imager induces biologic effects. Both kidneys of anesthetized rats were insonified for 5 min using a medical imaging system after the administration of microbubbles. One kidney was insonified using a continuous mode (30 Hz) and the opposite kidney was insonified using an intermittent (1 Hz) technique. The microbubbles were exposed to three different transducer frequencies and four transducer output powers. After insonification, the animals were euthanized, the kidneys were removed and their gross appearance scored under "blinded" conditions using a defined scale. After the administration of microbubbles, US imaging of the kidney caused hemorrhage in the renal tissue. The severity and area of hemorrhage increased with an increase in the transducer power and a decrease in the transducer frequency. Intermittent insonification in the presence of microbubbles produced a greater degree of renal hemorrhage than continuous imaging techniques.

Present and Future in the Treatment of Diabetic Kidney Disease

PubMed Central

de Arriba, Gabriel

2015-01-01

Diabetic kidney disease is the leading cause of end-stage renal disease. Albuminuria is recognized as the most important prognostic factor for chronic kidney disease progression. For this reason, blockade of renin-angiotensin system remains the main recommended strategy, with either angiotensin converting enzyme inhibitors or angiotensin II receptor blockers. However, other antiproteinuric treatments have begun to be studied, such as direct renin inhibitors or aldosterone blockers. Beyond antiproteinuric treatments, other drugs such as pentoxifylline or bardoxolone have yielded conflicting results. Finally, alternative pathogenic pathways are being explored, and emerging therapies including antifibrotic agents, endothelin receptor antagonists, or transcription factors show promising results. The aim of this review is to explain the advances in newer agents to treat diabetic kidney disease, along with the background of the renin-angiotensin system blockade. PMID:25945357

Dual renin-angiotensin-aldosterone system blockade for diabetic kidney disease.

PubMed

Pichler, Raimund H; de Boer, Ian H

2010-08-01

Blockade of the renin-angiotensin-aldosterone system (RAAS) prevents the development and progression of diabetic kidney disease (DKD). It is controversial whether the simultaneous use of two RAAS inhibitors (ie, dual RAAS blockade) further improves renal outcomes. This review examines the scientific rationale and current clinical evidence addressing the use of dual RAAS blockade to prevent and treat DKD. It is concluded that dual RAAS blockade should not be routinely applied to patients with low or moderate risk of progressive kidney disease (normoalbuminuria or microalbuminuria with preserved glomerular filtration rate). For patients with high risk of progressive kidney disease (substantial albuminuria or impaired glomerular filtration rate), clinicians should carefully weigh the potential risks and benefits of dual RAAS blockade on an individual basis until ongoing clinical trials provide further insight.

[Analysis of contractual incentives for kidney transplants in Brazil using the principal-agent model].

PubMed

Costa, Cassia Kely Favoretto; Balbinotto, Giácomo; Sampaio, Luciano Menezes Bezerra

2016-09-12

The aim of this article was to analyze contractual incentives for kidney transplants in Brazil based on the principal-agent model. The approach assumes that the Brazilian Ministry of Health is the principal and the public hospitals accredited by the National Transplant System are the agent. The Ministry of Health's welfare depends on measures taken by hospitals in kidney uptake. Hospitals allocate administrative, financial, and management efforts to conduct measures in kidney donation, removal, uptake, and transplantation. Hospitals may choose the levels of effort that are consistent with the payments and incentives received in relation to transplantation costs. The solution to this type of problem lies in structuring an optimal incentives contract, which requires aligning the interests of both parties involved in the transplantation system.

Heroin crystal nephropathy

PubMed Central

Bautista, Josef Edrik Keith; Merhi, Basma; Gregory, Oliver; Hu, Susie; Henriksen, Kammi; Gohh, Reginald

2015-01-01

In this paper we present an interesting case of acute kidney injury and severe metabolic alkalosis in a patient with a history of heavy heroin abuse. Urine microscopy showed numerous broomstick-like crystals. These crystals are also identified in light and electron microscopy. We hypothesize that heroin crystalizes in an alkaline pH, resulting in tubular obstruction and acute kidney injury. Management is mainly supportive as there is no known specific therapy for this condition. This paper highlights the utility of urine microscopy in diagnosing the etiology of acute kidney injury and proposes a novel disease called heroin crystal nephropathy. PMID:26034599

Severe hyperkalemia presenting with wide-complex tachycardia in a puppy with acute kidney injury secondary to leptospirosis.

PubMed

Rubanick, Jean V; Fries, Ryan C; Waugh, Carly E; Pashmakova, Medora B

2016-11-01

To describe a case of hyperkalemia coinciding with wide-complex tachycardia (WCT) in a dog with acute kidney injury secondary to leptospirosis infection. An 11-week-old Golden Retriever-Standard Poodle cross puppy was referred for acute kidney injury and hepatopathy. WCT coinciding with marked hyperkalemia was identified on presentation. Tachycardia persisted until resolution of hyperkalemia. To our knowledge, this is the first report of severe hyperkalemia presenting with WCT in a dog. Hyperkalemia should be considered a differential for WCT in dogs. © Veterinary Emergency and Critical Care Society 2016.

Integrated transcriptomic and proteomic analyses uncover regulatory roles of Nrf2 in the kidney

PubMed Central

Walsh, Joanne; Jenkins, Rosalind E.; Wong, Michael H. L.; Rowe, Cliff; Ricci, Emanuele; Ressel, Lorenzo; Fang, Yongxiang; Demougin, Philippe; Vukojevic, Vanja; O’Neill, Paul M.; Goldring, Christopher E.; Kitteringham, Neil R.; Park, B. Kevin; Odermatt, Alex; Copple, Ian M.

2015-01-01

The transcription factor Nrf2 exerts protective effects in numerous experimental models of acute kidney injury, and is a promising therapeutic target in chronic kidney disease. To provide a detailed insight into the regulatory roles of Nrf2 in the kidney, we performed integrated transcriptomic and proteomic analyses of kidney tissue from wild-type and Nrf2 knockout mice treated with the Nrf2 inducer methyl-2-cyano-3,12-dioxooleano-1,9-dien-28-oate (CDDO-Me, also known as bardoxolone methyl). After 24 hours, analyses identified 2561 transcripts and 240 proteins that were differentially expressed in the kidneys of Nrf2 knockout mice, compared to wild-type counterparts, and 3122 transcripts and 68 proteins that were differentially expressed in wild-type mice treated with CDDO-Me, compared to vehicle control. In light of their sensitivity to genetic and pharmacological modulation of renal Nrf2 activity, genes/proteins that regulate xenobiotic disposition, redox balance, the intra/extracellular transport of small molecules, and the supply of NADPH and other cellular fuels were found to be positively regulated by Nrf2 in the kidney. This was verified by qPCR, immunoblotting, pathway analysis and immunohistochemistry. In addition, the levels of NADPH and glutathione were found to be significantly decreased in the kidneys of Nrf2 knockout mice. Thus, Nrf2 regulates genes that coordinate homeostatic processes in the kidney, highlighting its potential as a novel therapeutic target. PMID:26422507

Kidney Cancer Incidence and Mortality Among American Indians and Alaska Natives in the United States, 1990–2009

PubMed Central

Weir, Hannah K.; Jim, Melissa A.; King, Sallyann M.; Wilson, Reda; Master, Viraj A.

2014-01-01

Objectives. We describe rates and trends in kidney cancer incidence and mortality and identify disparities between American Indian/Alaska Native (AI/AN) and White populations. Methods. To improve identification of AI/AN race, incidence and mortality data were linked with Indian Health Service (IHS) patient records. Analysis focused on residents of IHS Contract Health Service Delivery Area counties; Hispanics were excluded. We calculated age-adjusted kidney cancer incidence (2001–2009) and death rates (1990–2009) by sex, age, and IHS region. Results. AI/AN persons have a 1.6 times higher kidney cancer incidence and a 1.9 times higher kidney cancer death rate than Whites. Despite a significant decline in kidney cancer death rates for Whites (annual percentage change [APC] = −0.3; 95% confidence interval [CI] = −0.5, 0.0), death rates for AI/AN persons remained stable (APC = 0.4; 95% CI = −0.7, 1.5). Kidney cancer incidence rates rose more rapidly for AI/AN persons (APC = 3.5; 95% CI = 1.2, 5.8) than for Whites (APC = 2.1; 95% CI = 1.4, 2.8). Conclusions. AI/AN individuals have greater risk of developing and dying of kidney cancers. Incidence rates have increased faster in AI/AN populations than in Whites. Death rates have decreased slightly in Whites but remained stable in AI/AN populations. Racial disparities in kidney cancer are widening. PMID:24754655

Hypovitaminosis D in patients undergoing kidney transplant: the importance of sunlight exposure

PubMed Central

Vilarta, Cristiane F.; Unger, Marianna D.; dos Reis, Luciene M.; Dominguez, Wagner V.; David-Neto, Elias; Moysés, Rosa M.; Titan, Silvia; Custodio, Melani R.; Hernandez, Mariel J.; Jorgetti, Vanda

2017-01-01

OBJECTIVES: Recent studies have shown a high prevalence of hypovitaminosis D, defined as a serum 25-hydroxyvitamin D level less than 30 ng/ml, in both healthy populations and patients with chronic kidney disease. Patients undergoing kidney transplant are at an increased risk of skin cancer and are advised to avoid sunlight exposure. Therefore, these patients might share two major risk factors for hypovitaminosis D: chronic kidney disease and low sunlight exposure. This paper describes the prevalence and clinical characteristics of hypovitaminosis D among patients undergoing kidney transplant. METHODS: We evaluated 25-hydroxyvitamin D serum levels in a representative sample of patients undergoing kidney transplant. We sought to determine the prevalence of hypovitaminosis D, compare these patients with a control group, and identify factors associated with hypovitaminosis D (e.g., sunlight exposure and dietary habits). RESULTS: Hypovitaminosis D was found in 79% of patients undergoing kidney transplant, and the major associated factor was low sunlight exposure. These patients had higher creatinine and intact parathyroid hormone serum levels, with 25-hydroxyvitamin D being inversely correlated with intact parathyroid hormone serum levels. Compared with the control group, patients undergoing kidney transplant presented a higher prevalence of 25-hydroxyvitamin D deficiency and lower serum calcium, phosphate and albumin but higher creatinine and intact parathyroid hormone levels. CONCLUSIONS: Our results confirmed the high prevalence of hypovitaminosis D in patients undergoing kidney transplant. Therapeutic strategies such as moderate sunlight exposure and vitamin D supplementation should be seriously considered for this population. PMID:28793001

The role of aldosterone antagonism agents in diabetic kidney disease.

PubMed

Wombwell, Eric; Naglich, Andrew

2015-03-01

Diabetic kidney disease is a common consequence of the development of diabetes. In the United Kingdom 18-30% of chronic kidney disease cases and 44% of end-stage renal disease cases in the United States have been attributed to complications of diabetic kidney disease. Angiotensin blockade using angiotensin converting enzyme inhibitors or angiotensin receptor blockers is the standard for slowing the progression of diabetic kidney disease. Evidence suggests that aldosterone antagonism added to standard therapy may be beneficial. This paper aims to explore the pathophysiological contribution of aldosterone in diabetic kidney disease and review available literature for aldosterone antagonism through mineralocorticoid receptor blockade. A comprehensive literature search was conducted. Results were analysed and summarised. Nine trials evaluating a total of 535 patients with diabetic kidney disease were identified that evaluated the use of aldosterone antagonists for reducing the signs of diabetic kidney disease. All trials demonstrated a marked decrease in urinary protein excretion when compared to, or added to angiotensin converting enzyme inhibition or angiotensin receptor blockade. The most commonly reported side effect in all of the trials was hyperkalaemia, which occurred in 6.1% of all patients evaluated. Aldosterone antagonists were generally well tolerated in the evaluated patient populations. Aldosterone antagonism may represent a safe and effective complimentary therapy to the use of angiotensin converting enzyme inhibition, or angiotensin receptor blockade, for slowing the progression of diabetic kidney disease. © 2014 European Dialysis and Transplant Nurses Association/European Renal Care Association.

Hypovitaminosis D in patients undergoing kidney transplant: the importance of sunlight exposure.

PubMed

Vilarta, Cristiane F; Unger, Marianna D; Dos Reis, Luciene M; Dominguez, Wagner V; David-Neto, Elias; Moysés, Rosa M; Titan, Silvia; Custodio, Melani R; Hernandez, Mariel J; Jorgetti, Vanda

2017-07-01

Recent studies have shown a high prevalence of hypovitaminosis D, defined as a serum 25-hydroxyvitamin D level less than 30 ng/ml, in both healthy populations and patients with chronic kidney disease. Patients undergoing kidney transplant are at an increased risk of skin cancer and are advised to avoid sunlight exposure. Therefore, these patients might share two major risk factors for hypovitaminosis D: chronic kidney disease and low sunlight exposure. This paper describes the prevalence and clinical characteristics of hypovitaminosis D among patients undergoing kidney transplant. We evaluated 25-hydroxyvitamin D serum levels in a representative sample of patients undergoing kidney transplant. We sought to determine the prevalence of hypovitaminosis D, compare these patients with a control group, and identify factors associated with hypovitaminosis D (e.g., sunlight exposure and dietary habits). Hypovitaminosis D was found in 79% of patients undergoing kidney transplant, and the major associated factor was low sunlight exposure. These patients had higher creatinine and intact parathyroid hormone serum levels, with 25-hydroxyvitamin D being inversely correlated with intact parathyroid hormone serum levels. Compared with the control group, patients undergoing kidney transplant presented a higher prevalence of 25-hydroxyvitamin D deficiency and lower serum calcium, phosphate and albumin but higher creatinine and intact parathyroid hormone levels. Our results confirmed the high prevalence of hypovitaminosis D in patients undergoing kidney transplant. Therapeutic strategies such as moderate sunlight exposure and vitamin D supplementation should be seriously considered for this population.

Medical student attitudes toward kidney physiology and nephrology: a qualitative study.

PubMed

Roberts, John K; Sparks, Matthew A; Lehrich, Ruediger W

2016-11-01

Interest in nephrology among trainees is waning in the USA. Early perceptions and attitudes to subject matter can be linked to the quality of pre-clinical curricula. We wanted to explore these attitudes in the setting of modern curriculum redesign. We utilized Q methodology to understand first-year medical student attitudes after an innovative kidney physiology curriculum redesign that focuses on blending multiple learning methods. First-year medical students were invited to take a Q sort survey at the conclusion of a kidney physiology course. Students prioritized statements related to their understanding of kidney physiology, learning preferences, preferred course characteristics, perceived clinical relevance of kidney physiology, and interest in nephrology as a career. Factor analysis was performed to identify different student viewpoints. At the conclusion of our modified course, all students (n = 108) were invited to take the survey and 44 (41%) Q sorts were returned. Two dominant viewpoints were defined according to interest in nephrology. The Potentials are students who understand kidney physiology, perceive kidney physiology as clinically relevant, attend class sessions, utilize videos, and are willing to shadow a nephrologist. The Uninterested are students who are less satisfied with their kidney physiology knowledge, prefer to study alone with a textbook, avoid lectures, and are not interested in learning about nephrology. In an updated renal physiology course, students that use multiple learning methods also have favorable attitudes toward learning kidney physiology. Thus, modern curriculum changes that accommodate a variety of learning styles may promote positive attitudes toward nephrology.

Proposal for a functional classification system of heart failure in patients with end-stage renal disease: proceedings of the acute dialysis quality initiative (ADQI) XI workgroup.

PubMed

Chawla, Lakhmir S; Herzog, Charles A; Costanzo, Maria Rosa; Tumlin, James; Kellum, John A; McCullough, Peter A; Ronco, Claudio

2014-04-08

Structural heart disease is highly prevalent in patients with chronic kidney disease requiring dialysis. More than 80% of patients with end-stage renal disease (ESRD) are reported to have cardiovascular disease. This observation has enormous clinical relevance because the leading causes of death for patients with ESRD are of cardiovascular disease etiology, including heart failure, myocardial infarction, and sudden cardiac death. The 2 systems most commonly used to classify the severity of heart failure are the New York Heart Association (NYHA) functional classification and the American Heart Association (AHA)/American College of Cardiology (ACC) staging system. With rare exceptions, patients with ESRD who do not receive renal replacement therapy (RRT) develop signs and symptoms of heart failure, including dyspnea and edema due to inability of the severely diseased kidneys to excrete sodium and water. Thus, by definition, nearly all patients with ESRD develop a symptomatology consistent with heart failure if fluid removal by RRT is delayed. Neither the AHA/ACC heart failure staging nor the NYHA functional classification system identifies the variable symptomatology that patients with ESRD experience depending upon whether evaluation occurs before or after fluid removal by RRT. Consequently, the incidence, severity, and outcomes of heart failure in patients with ESRD are poorly characterized. The 11th Acute Dialysis Quality Initiative has identified this issue as a critical unmet need for the proper evaluation and treatment of heart failure in patients with ESRD. We propose a classification schema based on patient-reported dyspnea assessed both pre- and post-ultrafiltration, in conjunction with echocardiography. Copyright © 2014 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

The Organic Anion Transporter (OAT) Family: A Systems Biology Perspective

PubMed Central

Nigam, Sanjay K.; Bush, Kevin T.; Martovetsky, Gleb; Ahn, Sun-Young; Liu, Henry C.; Richard, Erin; Bhatnagar, Vibha; Wu, Wei

2015-01-01

The organic anion transporter (OAT) subfamily, which constitutes roughly half of the SLC22 (solute carrier 22) transporter family, has received a great deal of attention because of its role in handling of common drugs (antibiotics, antivirals, diuretics, nonsteroidal anti-inflammatory drugs), toxins (mercury, aristolochic acid), and nutrients (vitamins, flavonoids). Oats are expressed in many tissues, including kidney, liver, choroid plexus, olfactory mucosa, brain, retina, and placenta. Recent metabolomics and microarray data from Oat1 [Slc22a6, originally identified as NKT (novel kidney transporter)] and Oat3 (Slc22a8) knockouts, as well as systems biology studies, indicate that this pathway plays a central role in the metabolism and handling of gut microbiome metabolites as well as putative uremic toxins of kidney disease. Nuclear receptors and other transcription factors, such as Hnf4α and Hnf1α, appear to regulate the expression of certain Oats in conjunction with phase I and phase II drug metabolizing enzymes. Some Oats have a strong selectivity for particular signaling molecules, including cyclic nucleotides, conjugated sex steroids, odorants, uric acid, and prostaglandins and/or their metabolites. According to the “Remote Sensing and Signaling Hypothesis,” which is elaborated in detail here, Oats may function in remote interorgan communication by regulating levels of signaling molecules and key metabolites in tissues and body fluids. Oats may also play a major role in interorganismal communication (via movement of small molecules across the intestine, placental barrier, into breast milk, and volatile odorants into the urine). The role of various Oat isoforms in systems physiology appears quite complex, and their ramifications are discussed in the context of remote sensing and signaling. PMID:25540139

Long interspersed nuclear element-1 retroelements are expressed in patients with systemic autoimmune disease and induce type I interferon

PubMed Central

Mavragani, Clio P.; Sagalovskiy, Irina; Guo, Qiu; Nezos, Adrianos; Kapsogeorgou, Efstathia K.; Lu, Pin; Zhou, Jun Liang; Kirou, Kyriakos A.; Seshan, Surya V.; Moutsopoulos, Haralampos M.; Crow, Mary K.

2016-01-01

Objective Increased type I interferon (IFN-I) and a broad signature of IFN-I-induced gene transcripts are observed in patients with SLE and other systemic autoimmune diseases. To identify disease-relevant triggers of the IFN-I pathway we investigated whether endogenous virus-like genomic repeat elements, normally silent, might be expressed in patients with systemic autoimmune disease, activate an innate immune response and induce IFN-I. Methods Expression of IFN-I and long interspersed nuclear element-1 (LINE-1; L1) was studied in kidney tissue from lupus patients and minor salivary gland (MSG) tissue from patients with primary Sjogren’s syndrome (SS) by PCR, western blot and immunohistochemistry. Induction of IFN-I by L1 was investigated by transfection of plasmacytoid dendritic cells (pDCs) or monocytes with an L1-encoding plasmid or L1 RNA. Involvement of innate immune pathways and altered L1 methylation were assessed. Results L1 mRNA transcripts were increased in lupus nephritis kidneys and in MSG from SS patients and correlated with IFN-I expression and L1 DNA demethylation. L1 open reading frame 1/p40 protein and IFNβ were expressed in MSG ductal epithelial cells and in lupus kidneys, and IFNα was detected in infiltrating pDCs. Transfection of pDCs or monocytes with L1-encoding DNA or RNA induced IFN-I. Inhibition of TLR7/8 reduced L1 induction of IFNα in pDCs and an inhibitor of IKKε/TBK1 abrogated induction of IFN-I by L1 RNA in monocytes. Conclusion L1 genomic repeat elements represent endogenous nucleic acid triggers of the IFN-I pathway in SLE and SS and may contribute to initiation or amplification of autoimmune disease. PMID:27338297

Personalized Comments on Challenges and Opportunities in Kidney Disease Therapeutics: The Glom-NExT Symposium.

PubMed

Greka, Anna; Gibson, Deb; Mundel, Peter; Demetri, George; Hildebrandt, Friedhelm; Pollak, Martin; Florez, Jose

2016-11-01

In the face of ever-increasing incidence and prevalence of kidney disease worldwide, the unmet need for new treatments is unprecedented. Precision medicine is defined as the use of modern technologies to identify mechanisms of diseases in individual patients, and thus deploy treatment using tailored, targeted approaches, in the hopes of avoiding unnecessary toxicities and complications. Is there a place for kidney disease therapeutics in this space? If so, what is required to make significant progress toward precision nephrology? To answer these critical questions, we present a series of personalized comments corresponding to the responses offered to these very questions during the Inaugural Glom-NExT Symposium held at Harvard Medical School on October 23, 2014, a national meeting focused exclusively on kidney disease therapeutics. Copyright © 2016.

Close pathological correlations between chronic kidney disease and reproductive organ-associated abnormalities in female cotton rats.

PubMed

Ichii, Osamu; Nakamura, Teppei; Irie, Takao; Kouguchi, Hirokazu; Sotozaki, Kozue; Horino, Taro; Sunden, Yuji; Elewa, Yaser Hosny Ali; Kon, Yasuhiro

2018-03-01

Cotton rat ( Sigmodon hispidus) is a useful experimental rodent for the study of human infectious diseases. We previously clarified that cotton rats, particularly females, developed chronic kidney disease characterized by cystic lesions, inflammation, and fibrosis. The present study investigated female-associated factors for chronic kidney disease development in cotton rats. Notably, female cotton rats developed separation of the pelvic symphysis and hypertrophy in the vaginal parts of the cervix with age, which strongly associated with pyometra. The development of pyometra closely associated with the deterioration of renal dysfunction or immunological abnormalities was indicated by blood urea nitrogen and serum creatinine or spleen weight and serum albumin/globulin ratio, respectively. These parameters for renal dysfunction and immunological abnormalities were statistically correlated. These phenotypes found in the female reproductive organs were completely inhibited by ovariectomy. Further, the female cotton rats with pyometra tended to show more severe chronic kidney disease phenotypes and immunological abnormalities than those without pyometra; these changes were inhibited in ovariectomized cotton rats. With regard to renal histopathology, cystic lesions, inflammation, and fibrosis were ameliorated by ovariectomy. Notably, the immunostaining intensity of estrogen receptor α and estrogen receptor β were weak in the healthy kidneys, but both estrogen receptors were strongly induced in the renal tubules showing cystic changes. In conclusion, the close correlations among female reproductive organ-associated abnormalities, immunological abnormalities, and renal dysfunction characterize the chronic kidney disease features of female cotton rats. Thus, the cotton rat is a unique rodent model to elucidate the pathological crosstalk between chronic kidney disease and sex-related factors. Impact statement The increasing number of elderly individuals in the overall population has led to a concomitant age-related increase in chronic kidney disease. Moreover, the global prevalence of patients with chronic kidney disease is gradually increasing, which poses a serious public health problem. The limited number of spontaneous chronic kidney disease animal models, which resemble chronic kidney disease pathogenesis in elderly individuals, is a major limitation in the development of experimental and curative medicines for chronic kidney disease. This pathological study clarified that sex-related factors, including hormones, and abnormalities of the female reproductive system, such as pyometra, are closely associated with chronic kidney disease development by using cotton rats ( Sigmodon hispidus). Further, ovariectomy inhibited the phenotypes of the female reproductive system, immunological abnormalities, and chronic kidney disease. Thus, this laboratory rodent serves as a novel and useful spontaneous chronic kidney disease model to elucidate the candidate disease factors and the pathogenesis of chronic kidney disease both in human and experimental medicine.

Kidney function after off-pump or on-pump coronary artery bypass graft surgery: a randomized clinical trial.

PubMed

Garg, Amit X; Devereaux, P J; Yusuf, Salim; Cuerden, Meaghan S; Parikh, Chirag R; Coca, Steven G; Walsh, Michael; Novick, Richard; Cook, Richard J; Jain, Anil R; Pan, Xiangbin; Noiseux, Nicolas; Vik, Karel; Stolf, Noedir A; Ritchie, Andrew; Favaloro, Roberto R; Parvathaneni, Sirish; Whitlock, Richard P; Ou, Yongning; Lawrence, Mitzi; Lamy, Andre

2014-06-04

Most acute kidney injury observed in the hospital is defined by sudden mild or moderate increases in the serum creatinine concentration, which may persist for several days. Such acute kidney injury is associated with lower long-term kidney function. However, it has not been demonstrated that an intervention that reduces the risk of such acute kidney injury better preserves long-term kidney function. To characterize the risk of acute kidney injury with an intervention in a randomized clinical trial and to determine if there is a difference between the 2 treatment groups in kidney function 1 year later. The Coronary Artery Bypass Grafting Surgery Off- or On-pump Revascularisation Study (CORONARY) enrolled 4752 patients undergoing first isolated coronary artery bypass graft (CABG) surgery at 79 sites in 19 countries. Patients were randomized to receive CABG surgery either with a beating-heart technique (off-pump) or with cardiopulmonary bypass (on-pump). From January 2010 to November 2011, 2932 patients (from 63 sites in 16 countries) from CORONARY were enrolled into a kidney function substudy to record serum creatinine concentrations during the postoperative period and at 1 year. The last 1-year serum creatinine concentration was recorded on January 18, 2013. Acute kidney injury within 30 days of surgery (≥50% increase in serum creatinine concentration from prerandomization concentration) and loss of kidney function at 1 year (≥20% loss in estimated glomerular filtration rate from prerandomization level). Off-pump (n = 1472) vs on-pump (n = 1460) CABG surgery reduced the risk of acute kidney injury (17.5% vs 20.8%, respectively; relative risk, 0.83 [95% CI, 0.72-0.97], P = .01); however, there was no significant difference between the 2 groups in the loss of kidney function at 1 year (17.1% vs 15.3%, respectively; relative risk, 1.10 [95% CI, 0.95-1.29], P = .23). Results were consistent with multiple alternate continuous and categorical definitions of acute kidney injury or kidney function loss, and in the subgroup with baseline chronic kidney disease. Use of off-pump compared with on-pump CABG surgery reduced the risk of postoperative acute kidney injury, without evidence of better preserved kidney function with off-pump CABG surgery at 1 year. In this setting, an intervention that reduced the risk of mild to moderate acute kidney injury did not alter longer-term kidney function. clinicaltrials.gov Identifier: NCT00463294.

Decellularized Human Kidney Cortex Hydrogels Enhance Kidney Microvascular Endothelial Cell Maturation and Quiescence.

PubMed

Nagao, Ryan J; Xu, Jin; Luo, Ping; Xue, Jun; Wang, Yi; Kotha, Surya; Zeng, Wen; Fu, Xiaoyun; Himmelfarb, Jonathan; Zheng, Ying

2016-10-01

The kidney peritubular microvasculature is highly susceptible to injury from drugs and toxins, often resulting in acute kidney injury and progressive chronic kidney disease. Little is known about the process of injury and regeneration of human kidney microvasculature, resulting from the lack of appropriate kidney microvascular models that can incorporate the proper cells, extracellular matrices (ECMs), and architectures needed to understand the response and contribution of individual vascular components in these processes. In this study, we present methods to recreate the human kidney ECM (kECM) microenvironment by fabricating kECM hydrogels derived from decellularized human kidney cortex. The majority of native matrix proteins, such as collagen-IV, laminin, and heparan sulfate proteoglycan, and their isoforms were preserved in similar proportions as found in normal kidneys. Human kidney peritubular microvascular endothelial cells (HKMECs) became more quiescent when cultured on this kECM gel compared with culture on collagen-I-assessed using phenotypic, genotypic, and functional assays; whereas human umbilical vein endothelial cells became stimulated on kECM gels. We demonstrate for the first time that human kidney cortex can form a hydrogel suitable for use in flow-directed microphysiological systems. Our findings strongly suggest that selecting the proper ECM is a critical consideration in the development of vascularized organs on a chip and carries important implications for tissue engineering of all vascularized organs.

The role of the uncertainty of measurement of serum creatinine concentrations in the diagnosis of acute kidney injury.

PubMed

Kin Tekce, Buket; Tekce, Hikmet; Aktas, Gulali; Uyeturk, Ugur

2016-01-01

Uncertainty of measurement is the numeric expression of the errors associated with all measurements taken in clinical laboratories. Serum creatinine concentration is the most common diagnostic marker for acute kidney injury. The goal of this study was to determine the effect of the uncertainty of measurement of serum creatinine concentrations on the diagnosis of acute kidney injury. We calculated the uncertainty of measurement of serum creatinine according to the Nordtest Guide. Retrospectively, we identified 289 patients who were evaluated for acute kidney injury. Of the total patient pool, 233 were diagnosed with acute kidney injury using the AKIN classification scheme and then were compared using statistical analysis. We determined nine probabilities of the uncertainty of measurement of serum creatinine concentrations. There was a statistically significant difference in the number of patients diagnosed with acute kidney injury when uncertainty of measurement was taken into consideration (first probability compared to the fifth p = 0.023 and first probability compared to the ninth p = 0.012). We found that the uncertainty of measurement for serum creatinine concentrations was an important factor for correctly diagnosing acute kidney injury. In addition, based on the AKIN classification scheme, minimizing the total allowable error levels for serum creatinine concentrations is necessary for the accurate diagnosis of acute kidney injury by clinicians.

History of kidney stones and risk of chronic kidney disease: a meta-analysis.

PubMed

Shang, Weifeng; Li, Lixi; Ren, Yali; Ge, Qiangqiang; Ku, Ming; Ge, Shuwang; Xu, Gang

2017-01-01

Although the relationship between a history of kidney stones and chronic kidney disease (CKD) has been explored in many studies, it is still far from being well understood. Thus, we conducted a meta-analysis of studies comparing rates of CKD in patients with a history of kidney stones. PubMed, EMBASE, and the reference lists of relevant articles were searched to identify observational studies related to the topic. A random-effects model was used to combine the study-specific risk estimates. We explored the potential heterogeneity by subgroup analyses and meta-regression analyses. Seven studies were included in this meta-analysis. Pooled results suggested that a history of kidney stones was associated with an increased adjusted risk estimate for CKD [risk ratio (RR), 1.47 95% confidence interval (CI) [1.23-1.76])], with significant heterogeneity among these studies ( I 2  = 93.6%, P  < 0.001). The observed positive association was observed in most of the subgroup analyses, whereas the association was not significant among studies from Asian countries, the mean age ≥50 years and male patients. A history of kidney stones is associated with increased risk of CKD. Future investigations are encouraged to reveal the underlying mechanisms in the connection between kidney stones and CKD, which may point the way to more effective preventive and therapeutic measures.

Compensatory Growth of Congenital Solitary Kidneys in Pigs Reflects Increased Nephron Numbers Rather Than Hypertrophy

PubMed Central

van Vuuren, Stefan H.; Sol, Chalana M.; Broekhuizen, Roel; Lilien, Marc R.; Oosterveld, Michiel J. S.; Nguyen, Tri Q.

2012-01-01

Background Patients with unilateral MultiCystic Kidney Dysplasia (MCKD) or unilateral renal agenesis (URA) have a congenital solitary functioning kidney (CSFK) that is compensatory enlarged. The question whether this enlargement is due to increased nephron numbers and/or to nephron hypertrophy is unresolved. This question is of utmost clinical importance, since hypertrophy is associated with a risk of developing hypertension and proteinuria later in life with consequent development of CKD and cardiovascular disease. Methodology/Principal Findings In a cohort of 32,000 slaughter pigs, 7 congenital solitary functioning kidneys and 7 control kidneys were identified and harvested. Cortex volume was measured and with a 3-dimensional stereologic technique the number and volume of glomeruli was determined and compared. The mean total cortex volume was increased by more than 80% and the mean number of glomeruli per kidney was 50% higher in CSFKs than in a single control kidney, equaling 75% of the total nephron number in both kidneys of control subjects. The mean total glomerular volume in the CSFKs was not increased relative to the controls. Conclusions/Significance Thus, in pigs, compensatory enlargement of a CSFK is based on increased nephron numbers. Extrapolation of these findings to the human situation suggests that patients with a CSFK might not be at increased risk for developing hyperfiltration-associated renal and cardiovascular disease in later life due to a lower nephron number. PMID:23185419

High mortality in diabetic recipients of high KDPI deceased donor kidneys.

PubMed

Pelletier, Ronald P; Pesavento, Todd E; Rajab, Amer; Henry, Mitchell L

2016-08-01

Deceased donor (DD) kidney quality is determined by calculating the Kidney Donor Profile Index (KDPI). Optimizing high KDPI (≥85%) DD transplant outcome is challenging. This retrospective study was performed to review our high KDPI DD transplant results to identify clinical practices that can improve future outcomes. We retrospectively calculated the KDPI for 895 DD kidney recipients transplanted between 1/2002 and 11/2013. Age, race, body mass index (BMI), retransplantation, gender, diabetes (DM), dialysis time, and preexisting coronary artery disease (CAD) (previous myocardial infarction (MI), coronary artery bypass (CABG), or stenting) were determined for all recipients. About 29.7% (266/895) of transplants were from donors with a KDPI ≥85%. By Cox regression older age, diabetes, female gender, and dialysis time >4 years correlated with shorter patient survival time. Diabetics with CAD who received a high KDPI donor kidney had a significantly increased risk of death (HR 4.33 (CI 1.82-10.30), P=.001) compared to low KDPI kidney recipients. The Kaplan-Meier survival curve for diabetic recipients of high KDPI kidneys was significantly worse if they had preexisting CAD (P<.001 by log-rank test). Patient survival using high KDPI donor kidneys may be improved by avoiding diabetic candidates with preexisting CAD. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Large Renal Corpuscle: Clinical Significance of Evaluation of the Largest Renal Corpuscle in Kidney Biopsy Specimens.

PubMed

Kataoka, Hiroshi; Mochizuki, Toshio; Nitta, Kosaku

2018-01-01

Renal prognostic factors of chronic kidney disease are important concerns for patients. Kidney biopsy can be used to evaluate not only the activity of the original disease but also various risk factors related to the lifestyle of patients. Considering that lifestyle-related factors, including obesity and metabolic syndrome, are crucial prognostic risk factors of kidney disease progression and all-cause mortality, evaluation of lifestyle-related prognostic factors in kidney biopsy of all kidney diseases is important. Renal corpuscle size (glomerular size) is an easily measured parameter and potentially acts as a predictor of long-term renal function. Large renal corpuscle found on kidney biopsy is a classic and simple indicator, and has merit owing to its quantitative nature, but it has yet to be used to its full potential in clinical settings. Large renal corpuscle is an index that includes not only the activity of the original disease but also the damage of various metabolic risk states as represented by obesity, diabetes, and metabolic syndrome. Large renal corpuscles could be used to guide therapy. In this review, after identifying the pitfalls regarding the assessment of mean values in medical research, we propose that measurement of the maximum renal corpuscle profile (glomerular profile) in renal biopsies would provide valuable insights into the diagnosis, prognosis, and management of kidney diseases. © 2018 S. Karger AG, Basel.

Hydrogen Sulfide in Hypertension and Kidney Disease of Developmental Origins.

PubMed

Hsu, Chien-Ning; Tain, You-Lin

2018-05-11

Adverse environments occurring during kidney development may produce long-term programming effects, namely renal programming, to create increased vulnerability to the development of later-life hypertension and kidney disease. Conversely, reprogramming is a strategy aimed at reversing the programming processes in early life, even before the onset of clinical symptoms, which may counter the rising epidemic of hypertension and kidney disease. Hydrogen sulfide (H₂S), the third gasotransmitter, plays a key role in blood pressure regulation and renal physiology. This review will first present the role of H₂S in the renal system and provide evidence for the links between H₂S signaling and the underlying mechanisms of renal programming, including the renin⁻angiotensin system, oxidative stress, nutrient-sensing signals, sodium transporters, and epigenetic regulation. This will be followed by potential H₂S treatment modalities that may serve as reprogramming strategies to prevent hypertension and kidney disease of developmental origins. These H₂S treatment modalities include precursors for H₂S synthesis, H₂S donors, and natural plant-derived compounds. Despite emerging evidence from experimental studies in support of reprogramming strategies targeting the H₂S signaling pathway to protect against hypertension and kidney disease of developmental origins, these results need further clinical translation.

Klotho and activin A in kidney injury: plasma Klotho is maintained in unilateral obstruction despite no upregulation of Klotho biosynthesis in the contralateral kidney.

PubMed

Nordholm, Anders; Mace, Maria L; Gravesen, Eva; Hofman-Bang, Jacob; Morevati, Marya; Olgaard, Klaus; Lewin, Ewa

2018-05-01

In a new paradigm of etiology related to chronic kidney disease-mineral and bone disorder (CKD-MBD), kidney injury may cause induction of factors in the injured kidney that are released into the circulation and thereby initiate and maintain renal fibrosis and CKD-MBD. Klotho is believed to ameliorate renal fibrosis and CKD-MBD, while activin A might have detrimental effects. The unilateral ureter obstruction (UUO) model is used here to examine this concept by investigating early changes related to renal fibrosis in the obstructed kidney, untouched contralateral kidney, and vasculature which might be affected by secreted factors from the obstructed kidney, and comparing with unilateral nephrectomized controls (UNX). Obstructed kidneys showed early Klotho gene and protein depletion, whereas plasma Klotho increased in both UUO and UNX rats, indicating an altered metabolism of Klotho. Contralateral kidneys had no compensatory upregulation of Klotho and maintained normal expression of the examined fibrosis-related genes, as did remnant UNX kidneys. UUO caused upregulation of transforming growth factor-β and induction of periostin and activin A in obstructed kidneys without changes in the contralateral kidneys. Plasma activin A doubled in UUO rats after 10 days while no changes were seen in UNX rats, suggesting secretion of activin A from the obstructed kidney with potentially systemic effects on CKD-MBD. As such, increased aortic sclerostin was observed in UUO rats compared with UNX and normal controls. The present results are in line with the new paradigm and show very early vascular effects of unilateral kidney fibrosis, supporting the existence of a new kidney-vasculature axis.

A Five-Tier System for Improving the Categorization of Transplant Program Performance.

PubMed

Wey, Andrew; Salkowski, Nicholas; Kasiske, Bertram L; Israni, Ajay K; Snyder, Jon J

2018-06-01

To better inform health care consumers by better identifying differences in transplant program performance. Adult kidney transplants performed in the United States, January 1, 2012-June 30, 2014. In December 2016, the Scientific Registry of Transplant Recipients instituted a five-tier system for reporting transplant program performance. We compare the differentiation of program performance and the simulated misclassification rate of the five-tier system with the previous three-tier system based on the 95 percent credible interval. Scientific Registry of Transplant Recipients database. The five-tier system improved differentiation and maintained a low misclassification rate of less than 22 percent for programs differing by two tiers. The five-tier system will better inform health care consumers of transplant program performance. © Health Research and Educational Trust.

Contrast-induced acute kidney injury and mortality in ST elevation myocardial infarction treated with primary percutaneous coronary intervention.

PubMed

Silvain, Johanne; Nguyen, Lee S; Spagnoli, Vincent; Kerneis, Mathieu; Guedeney, Paul; Vignolles, Nicolas; Cosker, Kristel; Barthelemy, Olivier; Le Feuvre, Claude; Helft, Gérard; Collet, Jean-Philippe; Montalescot, Gilles

2018-05-01

Contrast-induced acute kidney injury (CI-AKI) is a common and potentially severe complication in patients with ST elevation myocardial infarction (STEMI) treated with primary percutaneous coronary intervention (pPCI). There is no consensus on the best definition of CI-AKI to identify patients at risk of haemodialysis or death. The objective of this study was to assess the association of CI-AKI, using four definitions, on inhospital mortality, mortality or haemodialysis requirement over 1-year follow-up, in patients with STEMI treated with pPCI. In this prospective, observational study, all patients with STEMI referred for pPCI were included. We identified independent variables associated with CI-AKI and mortality. We included 1114 consecutive patients with STEMI treated by pPCI. CI-AKI occurred in 18.3%, 12.2%, 15.6% and 10.5% of patients according to the CIN, Acute Kidney Injury Network (AKIN), Risk, Injury, Failure, Loss of kidney function, and End-stage kidney disease (RIFLE) Modification of Diet in Renal Disease (MDRD) and RIFLE Chronic Kidney Disease - Epidemiology Collaboration (CKD-EPI) definitions, respectively. The RIFLE (CKD-EPI) definition was the most discriminant definition to identify patients at higher risk of inhospital mortality (27.1% vs 4.0%; adjusted OR 2.7 (95% CI 1.4 to 5.1), p=0.003), 1-year mortality (27.4% vs 6.6%; adjusted OR 2.8 (95% CI 1.5 to 5.3), p=0.002) and haemodialysis requirement at 1-year follow-up (15.6% vs 2.7%; adjusted OR 6.7 (95% CI 3.3 to 13.6), p=0.001). Haemodynamic instability, cardiac arrest, preexisting renal failure, elderly age and a high contrast media volume were independently associated with 1-year mortality. Of interest, contrast-media volume was not correlated to increase of creatininaemia (r=0.06) or decrease in estimated glomerular filtration rate (r=0.05) after percutaneous coronary intervention in our population. CI-AKI is a frequent and serious complication of STEMI treated by pPCI. The RIFLE definition is the most accurate definition to identify patients with CI-AKI at high risk of mortality or haemodialysis. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Systemic effect of mineral aggregate-based cements: histopathological analysis in rats

PubMed Central

Garcia, Lucas da Fonseca Roberti; Huck, Claudia; Magalhães, Fernando Augusto Cintra; de Souza, Pedro Paulo Chaves; de Souza Costa, Carlos Alberto

2017-01-01

Abstract Objective: Several studies reported the local tissue reaction caused by mineral aggregate-based cements. However, few studies have investigated the systemic effects promoted by these cements on liver and kidney when directly applied to connective tissue. The purpose of this in vivo study was to investigate the systemic effect of mineral aggregate-based cements on the livers and kidneys of rats. Material and Methods: Samples of Mineral Trioxide Aggregate (MTA) and a calcium aluminate-based cement (EndoBinder) containing different radiopacifiers were implanted into the dorsum of 40 rats. After 7 and 30 d, samples of subcutaneous, liver and kidney tissues were submitted to histopathological analysis. A score (0-3) was used to grade the inflammatory reaction. Blood samples were collected to evaluate changes in hepatic and renal functions of animals. Results: The moderate inflammatory reaction (2) observed for 7 d in the subcutaneous tissue decreased with time for all cements. The thickness of inflammatory capsules also presented a significant decrease with time (P<.05). Systemically, all cements caused adverse inflammatory reactions in the liver and kidney, being more evident for MTA, persisting until the end of the analysis. Liver functions increased significantly for MTA during 30 d (P<.05). Conclusion: The different cements induced to a locally limited inflammatory reaction. However, from the systemic point of view, the cements promoted significant inflammatory reactions in the liver and kidney. For MTA, the reactions were more accentuated. PMID:29211283

Anatomical Relationship Between the Kidney Collecting System and the Intrarenal Arteries in the Sheep: Contribution for a New Urological Model.

PubMed

Buys-Gonçalves, Gabriela Faria; De Souza, Diogo Benchimol; Sampaio, Francisco José Barcellos; Pereira-Sampaio, Marco Aurélio

2016-04-01

Previous studies have demonstrated that the pig collecting system heals after partial nephrectomy without closure. Recently, a study in sheep showed that partial nephrectomy without closure of the collecting system resulted in urinary leakage and urinoma. The aim of this study was to present detailed anatomical findings on the intrarenal anatomy of the sheep. Forty two kidneys were used to produce tridimensional endocasts of the collecting system together with the intrarenal arteries. A renal pelvis which displayed 11-19 (mean of 16) renal recesses was present. There were no calices present. The renal artery was singular in each kidney and gave two primary branches one to the dorsal surface and one to ventral surface. Dorsal and ventral branches of the renal artery were classified based on the relationship between their branching pattern and the collecting system as: type I (cranial and caudal segmental arteries), type II (cranial, middle and caudal segmental arteries) or type III (cranial, cranial middle, caudal middle, and caudal segmental arteries). Type I was the most common branching pattern for the dorsal and ventral branches of the renal artery. The arterial supply of the caudal pole of the sheep kidney supports its use as an experimental model due to the similarity to the human kidney. However, the lack of a retropelvic artery discourages the use of the cranial pole in experiments in which the arteries are an important aspect to be considered. © 2016 Wiley Periodicals, Inc.

Histology of the Urogenital System in the American Bullfrog (Rana catesbeiana), with Emphasis on Male Reproductive Morphology.

PubMed

Rheubert, Justin L; Cook, Hanna E; Siegel, Dustin S; Trauth, Stanley E

2017-10-01

Previous studies have revealed variations in the urogenital system morphology of amphibians. Recently, the urogenital system of salamanders was reviewed and terminology was synonymized across taxa. Discrepancies exist in the terminology describing the urogenital system of anurans, which prompted our group to develop a complete, detailed description of the urogenital system in an anuran species and provide nomenclature that is synonymous with those of other amphibian taxa. In Rana catesbeiana, sperm mature within spermatocysts of the seminiferous tubule epithelia and are transported to a series of intratesticular ducts that exit the testes and merge to form vasa efferentia. Vasa efferentia converge into single longitudinal ducts (Bidder's ducts) on the lateral aspects of the kidneys. Branches from the longitudinal ducts merge with genital kidney renal tubules through renal corpuscles. The nephrons travel caudally and empty into the Wöffian ducts. Similar to salamanders, the caudal portion of the kidneys (termed the pelvic kidneys in salamanders) only possesses nephrons involved in urine formation, not sperm transport. Data from the present study provide a detailed description and synonymous nomenclature that can be used to make future comparative analyses between taxa more efficient.

Microsphere-Based Rapamycin Delivery, Systemic Versus Local Administration in a Rat Model of Renal Ischemia/Reperfusion Injury.

PubMed

Zandstra, Jurjen; van Beuge, Marike M; Zuidema, Johan; Petersen, Arjen H; Staal, Mark; Duque, Luisa F; Rodriguez, Sergio; Lathuile, Audrey A R; Veldhuis, Gert J; Steendam, Rob; Bank, Ruud A; Popa, Eliane R

2015-10-01

The increasing prevalence and treatment costs of kidney diseases call for innovative therapeutic strategies that prevent disease progression at an early stage. We studied a novel method of subcapsular injection of monodisperse microspheres, to use as a local delivery system of drugs to the kidney. We generated placebo- and rapamycin monodisperse microspheres to investigate subcapsular delivery of drugs. Using a rat model of acute kidney injury, subcapsular injection of placebo and rapamycin monodisperse microspheres (monospheres) was compared to subcutaneous injection, mimicking systemic administration. We did not find any adverse effects related to the delivery method. Irrespective of the injection site, a similar low dose of rapamycin was present in the circulation. However, only local intrarenal delivery of rapamycin from monospheres led to decreased macrophage infiltration and a significantly lower amount of myofibroblasts in the kidney, where systemic administration did not. Local delivery of rapamycin did cause a transient increase in the deposition of collagen I, but not of collagen III. We conclude that therapeutic effects can be increased when rapamycin is delivered subcapsularly by monospheres, which, combined with low systemic concentrations, may lead to an effective intrarenal delivery method.

Expression Profile of Cytokines and Enzymes mRNA in Blood Leukocytes of Dogs with Leptospirosis and Its Associated Pulmonary Hemorrhage Syndrome.

PubMed

Maissen-Villiger, Carla A; Schweighauser, Ariane; van Dorland, H Anette; Morel, Claudine; Bruckmaier, Rupert M; Zurbriggen, Andreas; Francey, Thierry

2016-01-01

Dogs with leptospirosis show similar organ manifestations and disease course as human patients, including acute kidney injury and pulmonary hemorrhage, making this naturally-occurring infection a good animal model for human leptospirosis. Expression patterns of cytokines and enzymes have been correlated with disease manifestations and clinical outcome in humans and animals. The aim of this study was to describe mRNA expression of pro- and anti-inflammatory mediators in canine leptospirosis and to compare it with other renal diseases to identify patterns characterizing the disease and especially its pulmonary form. The mRNA abundance of cytokines (IL-1α, IL-1β, IL-8, IL-10, TNF-α, TGF-β) and enzymes (5-LO, iNOS) was measured prospectively in blood leukocytes from 34 dogs with severe leptospirosis and acute kidney injury, including 22 dogs with leptospirosis-associated pulmonary hemorrhages. Dogs with leptospirosis were compared to 14 dogs with acute kidney injury of other origin than leptospirosis, 8 dogs with chronic kidney disease, and 10 healthy control dogs. Canine leptospirosis was characterized by high 5-LO and low TNF-α expression compared to other causes of acute kidney injury, although the decreased TNF-α expression was also seen in chronic kidney disease. Leptospirosis-associated pulmonary hemorrhage was not characterized by a specific pattern, with only mild changes noted, including increased IL-10 and decreased 5-LO expression on some days in affected dogs. Fatal outcome from pulmonary hemorrhages was associated with low TNF-α, high IL-1β, and high iNOS expression, a pattern possibly expressed also in dogs with other forms of acute kidney injury. The patterns of cytokine and enzyme expression observed in the present study indicate a complex pro- and anti-inflammatory response to the infection with leptospires. The recognition of these signatures may be of diagnostic and prognostic relevance for affected individuals and they may indicate options for newer therapies targeting the identified pathways.

Urine Fibrosis Markers and Risk of Allograft Failure in Kidney Transplant Recipients: A Case-Cohort Ancillary Study of the FAVORIT Trial.

PubMed

Ix, Joachim H; Katz, Ronit; Bansal, Nisha; Foster, Meredith; Weiner, Daniel E; Tracy, Russell; Jotwani, Vasantha; Hughes-Austin, Jan; McKay, Dianne; Gabbai, Francis; Hsu, Chi-Yuan; Bostom, Andrew; Levey, Andrew S; Shlipak, Michael G

2017-03-01

Kidney tubulointerstitial fibrosis marks risk for allograft failure in kidney transplant recipients, but is poorly captured by estimated glomerular filtration rate (eGFR) or urine albumin-creatinine ratio (ACR). Whether urinary markers of tubulointerstitial fibrosis can noninvasively identify risk for allograft failure above and beyond eGFR and ACR is unknown. Case-cohort study. The FAVORIT (Folic Acid for Vascular Outcome Reduction in Transplantation) Trial was a randomized double-blind trial testing vitamin therapy to lower homocysteine levels in stable kidney transplant recipients. We selected a subset of participants at random (n=491) and all individuals with allograft failure during follow-up (cases; n=257). Using spot urine specimens from the baseline visit, we measured 4 urinary proteins known to correlate with tubulointerstitial fibrosis on biopsy (urine α 1 -microglobulin [A1M], monocyte chemoattractant protein 1 [MCP-1], and procollagen type III and type I amino-terminal amino pro-peptide). Death-censored allograft failure. In models adjusted for demographics, chronic kidney disease risk factors, eGFR, and ACR, higher concentrations of urine A1M (HR per doubling, 1.73; 95% CI, 1.43-2.08) and MCP-1 (HR per doubling, 1.60; 95% CI, 1.32-1.93) were strongly associated with allograft failure. When additionally adjusted for concentrations of other urine fibrosis and several urine injury markers, urine A1M (HR per doubling, 1.76; 95% CI, 1.27-2.44]) and MCP-1 levels (HR per doubling, 1.49; 95% CI, 1.17-1.89) remained associated with allograft failure. Urine procollagen type III and type I levels were not associated with allograft failure. We lack kidney biopsy data, BK titers, and HLA antibody status. Urine measurement of tubulointerstitial fibrosis may provide a noninvasive method to identify kidney transplant recipients at higher risk for future allograft failure, above and beyond eGFR and urine ACR. Published by Elsevier Inc.

The Consistency and Reporting of Quality-of-Life Outcomes in Trials of Immunosuppressive Agents in Kidney Transplantation: A Systematic Review and Meta-analysis.

PubMed

Howell, Martin; Wong, Germaine; Turner, Robin M; Tan, Ho Teck; Tong, Allison; Craig, Jonathan C; Howard, Kirsten

2016-05-01

Shared decision making regarding immunosuppression in kidney transplantation requires an understanding of effects on quality of life (QoL). Our aim was to review the frequency and reliability of QoL measures reported in randomized controlled trials of maintenance immunosuppression following kidney transplantation. Systematic literature review. Kidney transplant recipients enrolled in randomized trials of maintenance immunosuppression. Systematic search of the Cochrane Kidney and Transplant register, CENTRAL, MEDLINE, EMBASE, PsycINFO, and CINAHL databases to January 2014 identifying maintenance immunosuppression trials. An EQUATOR Network-endorsed checklist was used to assess QoL reporting and effect sizes estimated. Maintenance immunosuppression (comparative studies, dose adjustment, and agent withdrawal). Any quantitative patient-reported measure of physical, emotional, or social well-being. Of 2,272 reports, 41 (2%; involving 4,549 participants from 23 trials) included QoL outcomes using 22 instruments (8 generic, 2 disease specific, and 12 symptom specific). Reporting was incomplete for the majority with 1 (4%) addressing all 11 items of the checklist, 4 (17%) addressing clinical significance, and 15 (65%) reporting outcomes selectively. Almost all (n = 96 [95%]) effect size estimates for 101 QoL outcomes (18 trials; 3,919 participants) favored the interventions, with 37 (37%) statistically significant. In comparison, 30 (73%) clinical outcomes favored the intervention and 13 (31%) were significant. QoL outcomes are commonly secondary outcomes and may not be indexed or found using text word searches. Effect sizes were estimated from different QoL measures, populations, and interventions. The small number of trials limits the ability to identify statistically significant associations between effect size and study-/patient-related factors. QoL is infrequently reported in immunosuppression trials in kidney transplantation, appears subject to major biases, and thus may be unreliable for decision making. Copyright © 2016 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.

3D element imaging using NSECT for the detection of renal cancer: a simulation study in MCNP.

PubMed

Viana, R S; Agasthya, G A; Yoriyaz, H; Kapadia, A J

2013-09-07

This work describes a simulation study investigating the application of neutron stimulated emission computed tomography (NSECT) for noninvasive 3D imaging of renal cancer in vivo. Using MCNP5 simulations, we describe a method of diagnosing renal cancer in the body by mapping the 3D distribution of elements present in tumors using the NSECT technique. A human phantom containing the kidneys and other major organs was modeled in MCNP5. The element composition of each organ was based on values reported in literature. The two kidneys were modeled to contain elements reported in renal cell carcinoma (RCC) and healthy kidney tissue. Simulated NSECT scans were executed to determine the 3D element distribution of the phantom body. Elements specific to RCC and healthy kidney tissue were then analyzed to identify the locations of the diseased and healthy kidneys and generate tomographic images of the tumor. The extent of the RCC lesion inside the kidney was determined using 3D volume rendering. A similar procedure was used to generate images of each individual organ in the body. Six isotopes were studied in this work - (32)S, (12)C, (23)Na, (14)N, (31)P and (39)K. The results demonstrated that through a single NSECT scan performed in vivo, it is possible to identify the location of the kidneys and other organs within the body, determine the extent of the tumor within the organ, and to quantify the differences between cancer and healthy tissue-related isotopes with p ≤ 0.05. All of the images demonstrated appropriate concentration changes between the organs, with some discrepancy observed in (31)P, (39)K and (23)Na. The discrepancies were likely due to the low concentration of the elements in the tissue that were below the current detection sensitivity of the NSECT technique.

β-Arrestin-1 deficiency ameliorates renal interstitial fibrosis by blocking Wnt1/β-catenin signaling in mice.

PubMed

Xu, Huiyan; Li, Quanxin; Liu, Jiang; Zhu, Jiaqing; Li, Liang; Wang, Ziying; Zhang, Yan; Sun, Yu; Sun, Jinpeng; Wang, Rong; Yi, Fan

2018-01-01

Despite substantial progress being made in understanding the mechanisms contributing to the pathogenesis of renal fibrosis, there are only a few therapies available to treat or prevent renal fibrosis in clinical use today. Therefore, identifying the key cellular and molecular mediators involved in the pathogenesis of renal fibrosis will provide new therapeutic strategy for treating patients with chronic kidney disease (CKD). β-Arrestin-1, a member of β-arrestin family, not only is a negative adaptor of G protein-coupled receptors (GPCRs), but also acts as a scaffold protein and regulates a diverse array of cellular functions independent of GPCR activation. In this study, we identified for the first time that β-arrestin-1 was upregulated in the kidney from mice with unilateral ureteral obstruction nephropathy as well as in the paraffin-embedded sections of human kidneys from the patients with diabetic nephropathy, polycystic kidney, or uronephrosis, which normally causes renal fibrosis. Deficiency of β-arrestin-1 in mice significantly alleviated renal fibrosis by the regulation of inflammatory responses, kidney fibroblast activation, and epithelial-mesenchymal transition (EMT) in both in vivo and in vitro studies. Furthermore, we found that among the major isoforms of Wnts, Wnt1 was regulated by β-arrestin-1 and gene silencing of Wnt1 inhibited the activation of β-catenin and suppressed β-arrestin-1-mediated renal fibrosis. Collectively, our results indicate that β-arrestin-1 is one of the critical components of signal transduction pathways in the development of renal fibrosis. Modulation of these pathways may be an innovative therapeutic strategy for treating patients with renal fibrosis. β-Arrestin-1 was upregulated in the kidney from mice with UUO nephropathy. β-Arrestin-1 regulated kidney fibroblast activation and epithelial-mesenchymal transition. β-Arrestin-1 exacerbated renal fibrosis via mediating Wnt1/β-catenin signaling.

An interactive, bilingual, culturally targeted website about living kidney donation and transplantation for hispanics: development and formative evaluation.

PubMed

Gordon, Elisa J; Feinglass, Joe; Carney, Paula; Ramirez, Daney; Olivero, Maria; O'Connor, Kate; MacLean, Jessica; Brucker, James; Caicedo, Juan Carlos

2015-04-20

As the kidney shortage continues to grow, patients on the waitlist are increasingly turning to live kidney donors for transplantation. Despite having a disproportionately higher prevalence of end-stage kidney disease (ESKD), fewer waitlisted Hispanic patients received living donor kidney transplants (LDKTs) than non-Hispanic whites in 2014. Although lack of knowledge has been identified as a barrier to living kidney donation (LKD) among Hispanics, little is known about information needs, and few bilingual educational resources provide transplant-related information addressing Hispanics' specific concerns. This paper describes the process of developing a bilingual website targeted to the Hispanic community. The website was designed to increase knowledge about LKD among Hispanic patients with ESKD, their families, and the public, and was inspired by educational sessions targeted to Hispanic transplant patients provided by Northwestern University's Hispanic Kidney Transplant Program. Northwestern faculty partnered with the National Kidney Foundation of Illinois for expertise in ESKD and Hispanic community partners across the Chicago area. We established a Community Advisory Board (CAB) of 10 Chicago-area Hispanic community leaders to provide insight into cultural concerns and community and patients' needs. Website content development was informed by 9 focus groups with 76 adult Hispanic kidney transplant recipients, living kidney donors, dialysis patients, and the general Hispanic public. The website development effort was guided by community input on images, telenovela scripts, and messages. After initial development, formal usability testing was conducted with 18 adult Hispanic kidney transplant recipients, dialysis patients, and living kidney donors to identify ways to improve navigability, design, content, comprehension, and cultural sensitivity. Usability testing revealed consistently high ratings as "easy to navigate", "informative", and "culturally appropriate". Bandura's Social Cognitive Theory and Gagne's Conditions of Learning Theory guided website design to facilitate adult learning. The website, "Infórmate: Living Kidney Donation for Hispanics/Latinos" (Infórmate Acerca de la Donación de Riñón en Vida), includes six sections: Treatment Options, Donation: Step-by-Step, Benefits and Risks, Financial Issues, Immigrant Issues, and Cultural Beliefs and Myths. Sections host 5-10 interactive messages that summarize important points and link to detailed explanations for users interested in learning more about specific issues. The website hosts interactive videos, multimedia testimonials, telenovelas, games, and quizzes. Photographs and videos of Hispanic living donors are shown to promote pride and ownership. Our success in developing a website was driven by a development team with expertise in transplantation, social science, evaluation, instructional design, and Hispanic perspectives, and by a patient-centered approach toward content and design. Based on feedback from usability testing and our CAB, the website is sensitive to Hispanic cultural sensibilities. We have nearly completed a formal evaluation of the website's impact on increasing Hispanics' knowledge about LKD and will disseminate the website thereafter.

An Interactive, Bilingual, Culturally Targeted Website About Living Kidney Donation and Transplantation for Hispanics: Development and Formative Evaluation

PubMed Central

Feinglass, Joe; Carney, Paula; Ramirez, Daney; Olivero, Maria; O'Connor, Kate; MacLean, Jessica; Brucker, James; Caicedo, Juan Carlos

2015-01-01

Background As the kidney shortage continues to grow, patients on the waitlist are increasingly turning to live kidney donors for transplantation. Despite having a disproportionately higher prevalence of end-stage kidney disease (ESKD), fewer waitlisted Hispanic patients received living donor kidney transplants (LDKTs) than non-Hispanic whites in 2014. Although lack of knowledge has been identified as a barrier to living kidney donation (LKD) among Hispanics, little is known about information needs, and few bilingual educational resources provide transplant-related information addressing Hispanics’ specific concerns. Objective This paper describes the process of developing a bilingual website targeted to the Hispanic community. The website was designed to increase knowledge about LKD among Hispanic patients with ESKD, their families, and the public, and was inspired by educational sessions targeted to Hispanic transplant patients provided by Northwestern University’s Hispanic Kidney Transplant Program. Methods Northwestern faculty partnered with the National Kidney Foundation of Illinois for expertise in ESKD and Hispanic community partners across the Chicago area. We established a Community Advisory Board (CAB) of 10 Chicago-area Hispanic community leaders to provide insight into cultural concerns and community and patients’ needs. Website content development was informed by 9 focus groups with 76 adult Hispanic kidney transplant recipients, living kidney donors, dialysis patients, and the general Hispanic public. The website development effort was guided by community input on images, telenovela scripts, and messages. After initial development, formal usability testing was conducted with 18 adult Hispanic kidney transplant recipients, dialysis patients, and living kidney donors to identify ways to improve navigability, design, content, comprehension, and cultural sensitivity. Usability testing revealed consistently high ratings as “easy to navigate”, “informative”, and “culturally appropriate”. Bandura’s Social Cognitive Theory and Gagne’s Conditions of Learning Theory guided website design to facilitate adult learning. Results The website, “Infórmate: Living Kidney Donation for Hispanics/Latinos” (Infórmate Acerca de la Donación de Riñón en Vida), includes six sections: Treatment Options, Donation: Step-by-Step, Benefits and Risks, Financial Issues, Immigrant Issues, and Cultural Beliefs and Myths. Sections host 5-10 interactive messages that summarize important points and link to detailed explanations for users interested in learning more about specific issues. The website hosts interactive videos, multimedia testimonials, telenovelas, games, and quizzes. Photographs and videos of Hispanic living donors are shown to promote pride and ownership. Conclusions Our success in developing a website was driven by a development team with expertise in transplantation, social science, evaluation, instructional design, and Hispanic perspectives, and by a patient-centered approach toward content and design. Based on feedback from usability testing and our CAB, the website is sensitive to Hispanic cultural sensibilities. We have nearly completed a formal evaluation of the website’s impact on increasing Hispanics’ knowledge about LKD and will disseminate the website thereafter. PMID:25896143

Peptide and low molecular weight proteins based kidney targeted drug delivery systems.

PubMed

Xu, Pengfei; Zhang, Hailiang; Dang, Ruili; Jiang, Pei

2018-05-30

Renal disease is a worldwide public health problem, and unfortunately, the therapeutic index of regular drugs is limited. Thus, it is a great need to develop effective treatment strategies. Among the reported strategies, kidney-targeted drug delivery system is a promising method to increase renal efficacy and reduce extra-renal toxicity. In recent years, working as vehicles for targeted drug delivery, low molecular weight proteins (LMWP) and peptide have received immense attention due to their many advantages, such as selective accumulation in kidney, high drug loading capability, control over routes of biodegradation, convenience in modification at the amino terminus, and good biocompatibility. In this review, we describe the current LMWP and peptide carriers for kidney targeted drug delivery systems. In addition, we discuss different linking strategies between carriers and drugs. Furthermore, we briefly outline the current status and attempt to give an outlook on the further study. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Anatomic variations in vascular and collecting systems of kidneys from deceased donors.

PubMed

Costa, H C; Moreira, R J; Fukunaga, P; Fernandes, R C; Boni, R C; Matos, A C

2011-01-01

Nephroureterectomy for transplantation has increased owing to the greater number of deceased donors. Anatomic variations may complicate the procedure or, if unrecognized, compromise the viability of kidneys for transplantation. We reviewed 254 surgical descriptions of nephroureterectomy specimens from January 2008 to December 2009. All organs collected according by standard techniques were evaluated for age, cause of death, renal function, frequency of injury during the procedure, as well as variations in the vascular and collecting systems. The mean donor age was 42 years (range, 2-74). The mean serum creatinine was 1.2 mg/dL (range, 1.0-7.0). The causes of death were cerebrovascular cause (stroke; n = 130), traumatic brain injury (n = 81) or other cause (n = 43). Among the anatomic variations: 8.6% (n = 22) were right arterial anatomical variations: 19 cases with 2 arteries and 3 cases with 3 arteries. In 25 cases (9.8%) the identified variation was the left artery: 2 arteries (n = 23), 3 arteries (n = 1) and 4 arteries (n = 1). We observed 9.8% on right side and 1.5% on left side venous anatomic variations, including 24 cases with 2 veins on the right side and 4 cases with 2 veins on the left side. Three cases of a retroaortic left renal vein and 1 case of a retro necklace vein (anterior and posterior to the aorta). Two cases of ureteral duplication were noted on the left and 1 on the right kidney. There were 3 horseshoe and 1 pelvic kidney. In 7.5% of cases, an injury to the graft included ureteral (n = 3), arterial (n = 10), or venous (n = 6). The most common anatomic variation was arterial (17.8%). Duplication of the renal vein was more frequent on the right. The high incidences of anatomic variations require more attention in the dissection of the renal hilum to avoid an injury that may compromise the graft. Copyright © 2011 Elsevier Inc. All rights reserved.

Trends in Relative Mortality Between Hispanic and Non-Hispanic Whites Initiating Dialysis: A Retrospective Study of the US Renal Data System

PubMed Central

Arce, Cristina M.; Goldstein, Benjamin A.; Mitani, Aya A.; Winkelmayer, Wolfgang C.

2014-01-01

Background Hispanic patients undergoing long-term dialysis experience better survival compared with non-Hispanic whites. It is unknown whether this association differs by age, has changed over time, or is due to differential access to kidney transplantation. Study Design National retrospective cohort study. Setting & Participants Using the US Renal Data System, we identified 615,618 white patients 18 years or older who initiated dialysis therapy between January 1, 1995, and December 31, 2007. Predictors Hispanic ethnicity (vs non-Hispanic whites), year of end-stage renal disease incidence, age (as potential effect modifier). Outcomes All-cause and cause-specific mortality. Results We found that Hispanics initiating dialysis therapy experienced lower mortality, but age modified this association (P < 0.001). Compared with non-Hispanic whites, mortality in Hispanics was 33% lower at ages 18–39 years (adjusted cause-specific HR [HRcs], 0.67; 95% CI, 0.64–0.71) and 40–59 years (HRcs, 0.67; 95% CI, 0.66–0.68), 19% lower at ages 60–79 years (HRcs, 0.81; 95% CI, 0.80–0.82), and 6% lower at 80 years or older (HRcs, 0.94; 95% CI, 0.91–0.97). Accounting for the differential rates of kidney transplantation, the associations were attenuated markedly in the younger age strata; the survival benefit for Hispanics was reduced from 33% to 10% at ages 18–39 years (adjusted subdistribution-specific HR [HRsd], 0.90; 95% CI, 0.85–0.94) and from 33% to 19% among those aged 40–59 years (HRsd, 0.81; 95% CI, 0.80–0.83). Limitations Inability to analyze Hispanic subgroups that may experience heterogeneous mortality outcomes. Conclusions Overall, Hispanics experienced lower mortality, but differential access to kidney transplantation was responsible for much of the apparent survival benefit noted in younger Hispanics. Am J Kidney Dis. 62(2):312–321. PMID:23647836

What we need to know about the effect of lithium on the kidney.

PubMed

Gong, Rujun; Wang, Pei; Dworkin, Lance

2016-12-01

Lithium has been a valuable treatment for bipolar affective disorders for decades. Clinical use of lithium, however, has been problematic due to its narrow therapeutic index and concerns for its toxicity in various organ systems. Renal side effects associated with lithium include polyuria, nephrogenic diabetes insipidus, proteinuria, distal renal tubular acidosis, and reduction in glomerular filtration rate. Histologically, chronic lithium nephrotoxicity is characterized by interstitial nephritis with microcyst formation and occasional focal segmental glomerulosclerosis. Nevertheless, this type of toxicity is uncommon, with the strongest risk factors being high serum levels of lithium and longer time on lithium therapy. In contrast, in experimental models of acute kidney injury and glomerular disease, lithium has antiproteinuric, kidney protective, and reparative effects. This paradox may be partially explained by lower lithium doses and short duration of therapy. While long-term exposure to higher psychiatric doses of lithium may be nephrotoxic, short-term low dose of lithium may be beneficial and ameliorate kidney and podocyte injury. Mechanistically, lithium targets glycogen synthase kinase-3β, a ubiquitously expressed serine/threonine protein kinase implicated in the processes of tissue injury, repair, and regeneration in multiple organ systems, including the kidney. Future studies are warranted to discover the exact "kidney-protective dose" of lithium and test the effects of low-dose lithium on acute and chronic kidney disease in humans. Copyright © 2016 the American Physiological Society.

What we need to know about the effect of lithium on the kidney

PubMed Central

Gong, Rujun; Wang, Pei

2016-01-01

Lithium has been a valuable treatment for bipolar affective disorders for decades. Clinical use of lithium, however, has been problematic due to its narrow therapeutic index and concerns for its toxicity in various organ systems. Renal side effects associated with lithium include polyuria, nephrogenic diabetes insipidus, proteinuria, distal renal tubular acidosis, and reduction in glomerular filtration rate. Histologically, chronic lithium nephrotoxicity is characterized by interstitial nephritis with microcyst formation and occasional focal segmental glomerulosclerosis. Nevertheless, this type of toxicity is uncommon, with the strongest risk factors being high serum levels of lithium and longer time on lithium therapy. In contrast, in experimental models of acute kidney injury and glomerular disease, lithium has antiproteinuric, kidney protective, and reparative effects. This paradox may be partially explained by lower lithium doses and short duration of therapy. While long-term exposure to higher psychiatric doses of lithium may be nephrotoxic, short-term low dose of lithium may be beneficial and ameliorate kidney and podocyte injury. Mechanistically, lithium targets glycogen synthase kinase-3β, a ubiquitously expressed serine/threonine protein kinase implicated in the processes of tissue injury, repair, and regeneration in multiple organ systems, including the kidney. Future studies are warranted to discover the exact “kidney-protective dose” of lithium and test the effects of low-dose lithium on acute and chronic kidney disease in humans. PMID:27122541

Sox11 gene disruption causes congenital anomalies of the kidney and urinary tract (CAKUT).

PubMed

Neirijnck, Yasmine; Reginensi, Antoine; Renkema, Kirsten Y; Massa, Filippo; Kozlov, Vladimir M; Dhib, Haroun; Bongers, Ernie M H F; Feitz, Wout F; van Eerde, Albertien M; Lefebvre, Veronique; Knoers, Nine V A M; Tabatabaei, Mansoureh; Schulz, Herbert; McNeill, Helen; Schaefer, Franz; Wegner, Michael; Sock, Elisabeth; Schedl, Andreas

2018-05-01

Congenital abnormalities of the kidney and the urinary tract (CAKUT) belong to the most common birth defects in human, but the molecular basis for the majority of CAKUT patients remains unknown. Here we show that the transcription factor SOX11 is a crucial regulator of kidney development. SOX11 is expressed in both mesenchymal and epithelial components of the early kidney anlagen. Deletion of Sox11 in mice causes an extension of the domain expressing Gdnf within rostral regions of the nephrogenic cord and results in duplex kidney formation. On the molecular level SOX11 directly binds and regulates a locus control region of the protocadherin B cluster. At later stages of kidney development, SOX11 becomes restricted to the intermediate segment of the developing nephron where it is required for the elongation of Henle's loop. Finally, mutation analysis in a cohort of patients suffering from CAKUT identified a series of rare SOX11 variants, one of which interferes with the transactivation capacity of the SOX11 protein. Taken together these data demonstrate a key role for SOX11 in normal kidney development and may suggest that variants in this gene predispose to CAKUT in humans. Copyright © 2017 International Society of Nephrology. Published by Elsevier Inc. All rights reserved.

Tenascin-C Is a Major Component of the Fibrogenic Niche in Kidney Fibrosis

PubMed Central

Fu, Haiyan; Tian, Yuan; Zhou, Lili; Zhou, Dong; Tan, Roderick J.; Stolz, Donna B.

2017-01-01

Kidney fibrosis initiates at certain focal sites in which the fibrogenic niche provides a specialized microenvironment that facilitates fibroblast activation and proliferation. However, the molecular identity of these fibrogenic niches is poorly characterized. Here, we determined whether tenascin-C (TNC), an extracellular matrix glycoprotein, is a component of the fibrogenic niche in kidney fibrosis. In vivo, TNC expression increased rapidly in kidneys subjected to unilateral ureteral obstruction or ischemia/reperfusion injury and predominantly localized at the foci rich in fibroblasts in renal interstitium. In vitro, TNC selectively promoted renal interstitial fibroblast proliferation, bromodeoxyuridine incorporation, and the expression of proliferation-related genes. The mitogenic activity of TNC required the integrin/focal adhesion kinase/mitogen-activated protein kinase signaling cascade. Using decellularized extracellular matrix scaffolds, we found that TNC-enriched scaffolds facilitated fibroblast proliferation, whereas TNC-deprived scaffolds inhibited proliferation. Matrix scaffold prepared from fibrotic kidney also promoted greater ex vivo fibroblast proliferation than did scaffolds prepared from healthy kidney. Conversely, small interfering RNA-mediated knockdown of TNC in vivo repressed injury-induced fibroblast expansion and renal fibrosis. These studies identify TNC as a major constituent of the fibrogenic niche that promotes fibroblast proliferation, and illustrate a pivotal role for the TNC-enriched microenvironment in kidney fibrogenesis. PMID:27612995

Risk factors for gallstones and kidney stones in a cohort of patients with inflammatory bowel diseases

PubMed Central

Rossel, Jean-Benoît; Biedermann, Luc; Frei, Pascal; Zeitz, Jonas; Spalinger, Marianne; Battegay, Edouard; Zimmerli, Lukas; Vavricka, Stephan R.; Rogler, Gerhard

2017-01-01

Background Gallstones and kidney stones are known complications of inflammatory bowel diseases (IBD). Risk factors have been insufficiently studied and explanatory studies date back up to 30 years. It remains unclear, whether improved treatment options also influenced risk factors for these complications. Objectives Identifying risk factors for gallstones and kidney stones in IBD patients. Methods Using data from the Swiss Inflammatory Bowel Disease Cohort Study we assessed associations of diseases characteristics with gallstones and kidney stones in univariate and multivariate logistic regression analyses. Results Out of 2323 IBD patients, 104 (7.8%) Crohn’s disease (CD) and 38 (3.8%) ulcerative colitis (UC) patients were diagnosed with gallstones. Significant risk factors for gallstones were diagnosis of CD, age at diagnosis, disease activity and duration, NSAID intake, extra-intestinal manifestations and intestinal surgery. Kidney stones were described in 61 (4.6%) CD and 30 (3.0%) UC patients. Male gender, disease activity, intestinal surgery, NSAID usage and reduced physical activity were significant risk factors. Hospitalization was associated with gallstones and kidney stones. The presence of gallstones increased the risk for kidney stones (OR 4.87, p<0.001). Conclusion The diagnosis of CD, intestinal surgery, prolonged NSAID use, disease activity and duration and bowel stenosis were significantly associated with cholecystonephrolithiasis in IBD. PMID:29023532

Risk factors for gallstones and kidney stones in a cohort of patients with inflammatory bowel diseases.

PubMed

Fagagnini, Stefania; Heinrich, Henriette; Rossel, Jean-Benoît; Biedermann, Luc; Frei, Pascal; Zeitz, Jonas; Spalinger, Marianne; Battegay, Edouard; Zimmerli, Lukas; Vavricka, Stephan R; Rogler, Gerhard; Scharl, Michael; Misselwitz, Benjamin

2017-01-01

Gallstones and kidney stones are known complications of inflammatory bowel diseases (IBD). Risk factors have been insufficiently studied and explanatory studies date back up to 30 years. It remains unclear, whether improved treatment options also influenced risk factors for these complications. Identifying risk factors for gallstones and kidney stones in IBD patients. Using data from the Swiss Inflammatory Bowel Disease Cohort Study we assessed associations of diseases characteristics with gallstones and kidney stones in univariate and multivariate logistic regression analyses. Out of 2323 IBD patients, 104 (7.8%) Crohn's disease (CD) and 38 (3.8%) ulcerative colitis (UC) patients were diagnosed with gallstones. Significant risk factors for gallstones were diagnosis of CD, age at diagnosis, disease activity and duration, NSAID intake, extra-intestinal manifestations and intestinal surgery. Kidney stones were described in 61 (4.6%) CD and 30 (3.0%) UC patients. Male gender, disease activity, intestinal surgery, NSAID usage and reduced physical activity were significant risk factors. Hospitalization was associated with gallstones and kidney stones. The presence of gallstones increased the risk for kidney stones (OR 4.87, p<0.001). The diagnosis of CD, intestinal surgery, prolonged NSAID use, disease activity and duration and bowel stenosis were significantly associated with cholecystonephrolithiasis in IBD.

Detection of medical errors in kidney transplantation: a pilot study comparing proactive clinician debriefings to a hospital-wide incident reporting system.

PubMed

McElroy, Lisa M; Daud, Amna; Lapin, Brittany; Ross, Olivia; Woods, Donna M; Skaro, Anton I; Holl, Jane L; Ladner, Daniela P

2014-11-01

Rates of medical errors and adverse events remain high for patients who undergo kidney transplantation; they are particularly vulnerable because of the complexity of their disease and the kidney transplantation procedure. Although institutional incident-reporting systems are used in hospitals around the country, they often fail to capture a substantial proportion of medical errors. The goal of this study was to assess the ability of a proactive, web-based clinician safety debriefing to augment the information about medical errors and adverse events obtained via traditional incident reporting systems. Debriefings were sent to all individuals listed on operating room personnel reports for kidney transplantation surgeries between April 2010 and April 2011, and incident reports were collected for the same time period. The World Health Organization International Classification for Patient Safety was used to classify all issues reported. A total of 270 debriefings reported 334 patient safety issues (179 safety incidents, 155 contributing factors), and 57 incident reports reported 92 patient safety issues (56 safety incidents, 36 contributing factors). Compared with incident reports, more attending physicians completed the debriefings (32.0 vs 3.5%). The use of a proactive, web-based debriefing to augment an incident reporting system in assessing safety risks in kidney transplantation demonstrated increased information, more perspectives of a single safety issue, and increased breadth of participants. Copyright © 2014 Elsevier Inc. All rights reserved.

How to reduce the incidence of contrast induced acute kidney injury after cardiac invasive procedures, a review and practical recommendations.

PubMed

de Bie, Mihály K; van Rees, Johannes B; Herzog, Charles A; Rabelink, Ton J; Schalij, Martin J; Jukema, J Wouter

2011-07-01

Contrast induced acute kidney injury is an important complication after cardiac (invasive) procedures and is associated with substantial morbidity and mortality. The aim of the current article is to provide a comprehensive overview of the current knowledge regarding contrast induced acute kidney injury. Current literature was reviewed and relevant articles were selected. Articles were identified through MEDLINE and Pubmed selecting articles, limited between 1980 and 2010. The pathophysiological process resulting in contrast induced acute kidney injury is not completely understood, nevertheless several mechanisms involved have been proposed. However, the risk factors for contrast induced acute kidney injury and its timing are well known, making it amenable for preventive strategies. In the past decade various preventive strategies have been investigated with different results. Currently, only adequate hydration, with saline, is uniformly accepted as a beneficial prophylactic strategy. Furthermore promising results have also been reported for several other prophylactic strategies. These results, however, need to be confirmed in future trials.

Attitudes toward live and postmortem kidney donation: a survey of Chinese medical students.

PubMed

Ge, Fangmin; Kaczmarczyk, Gabriele; Biller-Andorno, Nikola

2014-12-01

As the gap between supply and demand for donor organs is increasing, we sought to clarify the knowledge and attitudes regarding living-organ donation among Chinese medical students and analyze their incentives and influencing factors. Data were collected from Chinese medical students using a standardized questionnaire. Of 320 surveyed participants, 261 participants (81.6%) said they would consider donating their live kidney organ, and 262 participants (81.9%) were willing to donate posthumously. Although 177 participants (55.7%) confirmed current regulations on posthumous organ donation, only 85 participants (26.7%) could correctly identify the regulations on live organ donation in China. Gender differences were not significantly associated with willingness to donate a kidney, whereas religion and socioeconomic status of the respondents were significantly associated with willingness to donate a live or posthumous kidney. Among well-informed, young, healthy, and economically well-off Chinese male and female medical students, most were willing to be live kidney donors. Religion and socioeconomic status may affect the decision-making process for organ disposition.

Developing better mouse models to study cisplatin-induced kidney injury.

PubMed

Sharp, Cierra N; Siskind, Leah J

2017-10-01

Cisplatin is a potent chemotherapeutic used for the treatment of many types of cancer. However, its dose-limiting side effect is nephrotoxicity leading to acute kidney injury (AKI). Patients who develop AKI have an increased risk of mortality and are more likely to develop chronic kidney disease (CKD). Unfortunately, there are no therapeutic interventions for the treatment of AKI. It has been suggested that the lack of therapies is due in part to the fact that the established mouse model used to study cisplatin-induced AKI does not recapitulate the cisplatin dosing regimen patients receive. In recent years, work has been done to develop more clinically relevant models of cisplatin-induced kidney injury, with much work focusing on incorporation of multiple low doses of cisplatin administered over a period of weeks. These models can be used to recapitulate the development of CKD after AKI and, by doing so, increase the likelihood of identifying novel therapeutic targets for the treatment of cisplatin-induced kidney injury. Copyright © 2017 the American Physiological Society.

[Hispanic American kidney patients in the age of online social networks: content analysis of postings, 2010 - 2012].

PubMed

Mercado-Martínez, Francisco J; Urias-Vázquez, Jorge E

2014-01-01

Describe the use of online social networks by people with chronic kidney disease, their caregivers, and family members, living in Hispanic American countries, and identify the most frequent topics and subtopics in their postings. A qualitative study was conducted of postings by chronic kidney patients, their caregivers, and family members, living in Hispanic America, on five social networks: Blogger, Facebook, Twitter, WordPress, and YouTube, from 2010 to 2012. The internal search engines of each network were used with medical and lay terms in Spanish: chronic kidney disease, renal failure, peritoneal dialysis, hemodialysis, renal transplant, renal patient, nephropathy, and kidney patients association. An analysis was carried out of the thematic content of 1 846 postings on Facebook, Blogger, and WordPress. A total of 162 social network accounts were identified (97 individuals and 65 groups); the majority was in Mexico (46), with others in Argentina, Chile, Colombia, and Peru (44 accounts). The most frequent topics were exchange of information (46.0%), descriptions of experiences as patients (17.9%), support (15.6%), descriptions of experiences with health services (8.5%), interaction with peers (3.5%), and promotion of behavior change (3.4%). Chronic kidney patients living in Hispanic America use online social networks to inform and to be informed, describe their experiences with the disease and health services, and as a support mechanism. This produces knowledge that is different from and complementary to knowledge conveyed by health professionals. There is a pressing need to promote studies of the opportunities that these technologies offer in the Americas, a region characterized by enormous social inequality.

Resistant starch alters gut microbiome and metabolomic profiles concurrent with amelioration of chronic kidney disease in rats

PubMed Central

Kieffer, Dorothy A.; Piccolo, Brian D.; Vaziri, Nosratola D.; Liu, Shuman; Lau, Wei L.; Khazaeli, Mahyar; Nazertehrani, Sohrab; Moore, Mary E.; Marco, Maria L.; Martin, Roy J.

2016-01-01

Patients and animals with chronic kidney disease (CKD) exhibit profound alterations in the gut environment including shifts in microbial composition, increased fecal pH, and increased blood levels of gut microbe-derived metabolites (xenometabolites). The fermentable dietary fiber high amylose maize-resistant starch type 2 (HAMRS2) has been shown to alter the gut milieu and in CKD rat models leads to markedly improved kidney function. The aim of the present study was to identify specific cecal bacteria and cecal, blood, and urinary metabolites that associate with changes in kidney function to identify potential mechanisms involved with CKD amelioration in response to dietary resistant starch. Male Sprague-Dawley rats with adenine-induced CKD were fed a semipurified low-fiber diet or a high-fiber diet [59% (wt/wt) HAMRS2] for 3 wk (n = 9 rats/group). The cecal microbiome was characterized, and cecal contents, serum, and urine metabolites were analyzed. HAMRS2-fed rats displayed decreased cecal pH, decreased microbial diversity, and an increased Bacteroidetes-to-Firmicutes ratio. Several uremic retention solutes were altered in the cecal contents, serum, and urine, many of which had strong correlations with specific gut bacteria abundances, i.e., serum and urine indoxyl sulfate were reduced by 36% and 66%, respectively, in HAMRS2-fed rats and urine p-cresol was reduced by 47% in HAMRS2-fed rats. Outcomes from this study were coincident with improvements in kidney function indexes and amelioration of CKD outcomes previously reported for these rats, suggesting an important role for microbial-derived factors and gut microbe metabolism in regulating host kidney function. PMID:26841824

Gout after living kidney donation: Correlations with demographic traits and renal complications

PubMed Central

Lam, Ngan N.; Garg, Amit X.; Segev, Dorry L.; Schnitzler, Mark A.; Xiao, Huiling; Axelrod, David; Brennan, Daniel C.; Kasiske, Bertram L.; Tuttle-Newhall, Janet E.; Lentine, Krista L.

2015-01-01

Background The demographic and clinical correlates of gout after living kidney donation are not well described. Methods Using a unique database that integrates national registry identifiers of U.S. living kidney donors (1987-2007) with billing claims from a private health insurer (2000-2007), we identified post-donation gout based on medical diagnosis codes or pharmacy fills for gout therapies. The frequencies and demographic correlates of gout after donation were estimated by Cox regression with left- and right-censoring. We also compared rates of renal diagnoses among donors with and without gout, matched 1:3 by age, sex, and race. Results The study sample of 4,650 donors included 13.1% African-Americans. By seven years, African-Americans were almost twice as likely to develop gout as Caucasian donors (4.4% vs. 2.4%; adjusted hazard ratio, aHR, 1.8; 95% confidence interval, CI, 1.0–3.2). Post-donation gout risk also increased with older age at donation (aHR per year 1.05) and was higher in men (aHR 2.80). Gout rates were similar in donors and age- and sex-matched general non-donors (rate ratio 0.86, 95% CI 0.66–1.13). Compared to matched donors without gout, donors with gout had more frequent renal diagnoses, reaching significance for acute kidney failure (rate ratio 12.5; 95% CI 1.5–107.0), chronic kidney disease (rate ratio 5.0; 95% CI 2.1–11.7), and other disorders of the kidney (rate ratio 2.2; 95% CI 1.2–4.2). Conclusion Donor subgroups at increased risk of gout include African-Americans, older donors, and men. Donors with gout have a higher burden of renal complications after demographic adjustment. PMID:25896309

Validation of Living Donor Nephrectomy Codes

PubMed Central

Lam, Ngan N.; Lentine, Krista L.; Klarenbach, Scott; Sood, Manish M.; Kuwornu, Paul J.; Naylor, Kyla L.; Knoll, Gregory A.; Kim, S. Joseph; Young, Ann; Garg, Amit X.

2018-01-01

Background: Use of administrative data for outcomes assessment in living kidney donors is increasing given the rarity of complications and challenges with loss to follow-up. Objective: To assess the validity of living donor nephrectomy in health care administrative databases compared with the reference standard of manual chart review. Design: Retrospective cohort study. Setting: 5 major transplant centers in Ontario, Canada. Patients: Living kidney donors between 2003 and 2010. Measurements: Sensitivity and positive predictive value (PPV). Methods: Using administrative databases, we conducted a retrospective study to determine the validity of diagnostic and procedural codes for living donor nephrectomies. The reference standard was living donor nephrectomies identified through the province’s tissue and organ procurement agency, with verification by manual chart review. Operating characteristics (sensitivity and PPV) of various algorithms using diagnostic, procedural, and physician billing codes were calculated. Results: During the study period, there were a total of 1199 living donor nephrectomies. Overall, the best algorithm for identifying living kidney donors was the presence of 1 diagnostic code for kidney donor (ICD-10 Z52.4) and 1 procedural code for kidney procurement/excision (1PC58, 1PC89, 1PC91). Compared with the reference standard, this algorithm had a sensitivity of 97% and a PPV of 90%. The diagnostic and procedural codes performed better than the physician billing codes (sensitivity 60%, PPV 78%). Limitations: The donor chart review and validation study was performed in Ontario and may not be generalizable to other regions. Conclusions: An algorithm consisting of 1 diagnostic and 1 procedural code can be reliably used to conduct health services research that requires the accurate determination of living kidney donors at the population level. PMID:29662679

Resistant starch alters gut microbiome and metabolomic profiles concurrent with amelioration of chronic kidney disease in rats.

PubMed

Kieffer, Dorothy A; Piccolo, Brian D; Vaziri, Nosratola D; Liu, Shuman; Lau, Wei L; Khazaeli, Mahyar; Nazertehrani, Sohrab; Moore, Mary E; Marco, Maria L; Martin, Roy J; Adams, Sean H

2016-05-01

Patients and animals with chronic kidney disease (CKD) exhibit profound alterations in the gut environment including shifts in microbial composition, increased fecal pH, and increased blood levels of gut microbe-derived metabolites (xenometabolites). The fermentable dietary fiber high amylose maize-resistant starch type 2 (HAMRS2) has been shown to alter the gut milieu and in CKD rat models leads to markedly improved kidney function. The aim of the present study was to identify specific cecal bacteria and cecal, blood, and urinary metabolites that associate with changes in kidney function to identify potential mechanisms involved with CKD amelioration in response to dietary resistant starch. Male Sprague-Dawley rats with adenine-induced CKD were fed a semipurified low-fiber diet or a high-fiber diet [59% (wt/wt) HAMRS2] for 3 wk (n = 9 rats/group). The cecal microbiome was characterized, and cecal contents, serum, and urine metabolites were analyzed. HAMRS2-fed rats displayed decreased cecal pH, decreased microbial diversity, and an increased Bacteroidetes-to-Firmicutes ratio. Several uremic retention solutes were altered in the cecal contents, serum, and urine, many of which had strong correlations with specific gut bacteria abundances, i.e., serum and urine indoxyl sulfate were reduced by 36% and 66%, respectively, in HAMRS2-fed rats and urine p-cresol was reduced by 47% in HAMRS2-fed rats. Outcomes from this study were coincident with improvements in kidney function indexes and amelioration of CKD outcomes previously reported for these rats, suggesting an important role for microbial-derived factors and gut microbe metabolism in regulating host kidney function. Copyright © 2016 the American Physiological Society.