An improved method of renal tissue engineering, by combining renal dissociation and reaggregation with a low-volume culture technique, results in development of engineered kidneys complete with loops of Henle.

PubMed

Chang, C-Hong; Davies, Jamie A

2012-01-01

Tissue engineering of functional kidney tissue is an important goal for clinical restoration of renal function in patients damaged by infectious, toxicological, or genetic disease. One promising approach is the use of the self-organizing abilities of embryonic kidney cells to arrange themselves, from a simply reaggregated cell suspension, into engineered organs similar to fetal kidneys. The previous state-of-the-art method for this results in the formation of a branched collecting duct tree, immature nephrons (S-shaped bodies) beside and connected to it, and supportive stroma. It does not, though, result in the significant formation of morphologically detectable loops of Henle - anatomical features of the nephron that are critical to physiological function. We have combined the best existing technique for renal tissue engineering from cell suspensions with a low-volume culture technique that allows intact kidney rudiments to make loops of Henle to test whether engineered kidneys can produce these loops. The result is the formation of loops of Henle in engineered cultured 'fetal kidneys', very similar in both morphology and in number to those formed by intact organ rudiments. This brings the engineering technique one important step closer to production of a fully realistic organ. Copyright © 2012 S. Karger AG, Basel.

Liver fatty-acid-binding protein in heart and kidney allograft recipients in relation to kidney function.

PubMed

Przybylowski, P; Koc-Zorawska, E; Malyszko, J S; Kozlowska, S; Mysliwiec, M; Malyszko, J

2011-10-01

Mammalian intracellular fatty-acid-binding proteins (FABPs), a large multigene family, encode 14-kD proteins that are members of a superfamily of lipid-binding proteins. FABPs are tissue specific. Liver-type FABP (L-FABP) can be filtered through the glomerulus owing to its small molecular size, similar to cystatin C, but it is reabsorbed by proximal tubule epithelial cells like other small proteins. In the human kidney, L-FABP is expressed predominantly in proximal tubules. It had been suggested that the presence of L-FABP in urine reflects hypoxic conditions resulting from decreased peritubular capillary flow, serving as a marker of acute kidney injury. The aim of this study was to assess urinary L-FABP in 111 heart and 76 kidney transplant recipients in relation to kidney function. Complete blood count, urea, fasting glucose, creatinine, and the N-terminal fragment of brain natriuretic protein were studied by standard laboratory methods; L-FABP and cystatin C, by ELISA using commercially available kits. Kidney transplant recipients displayed significantly higher L-FABP than heart recipients. Upon univariate analysis, urinary L-FABP correlated, with serum creatinine, cystatin C and estimated glomerular filtration ratio (eGFR) in kidney allograft recipients. However, in heart transplant recipients it was not related to kidney function, as reflected by creatinine or eGFR; was strongly related to cystatin C (r=0.34; P<.001) and urinary creatinine (r=-0.29; P<.01), and NGAL (r=0.29; P<.01). Upon multiple regression analysis, the best predictor of urinary L-FABP in kidney allograft recipients, was eGFR whereas in heart recipients, no parameter independently predicted L-FABP. Successful heart transplantation is associated with kidney injury as reflected by a reduced eGFR; however, in this population, L-FABP did not serve as a marker of kidney function. In contrast, in kidney allograft recipients, L-FABP may be a potential early marker for impaired kidney function/injury. Copyright © 2011 Elsevier Inc. All rights reserved.

Supplementary Administration of Everolimus Reduces Cardiac Systolic Function in Kidney Transplant Recipients.

PubMed

Tsujimura, Kazuma; Ota, Morihito; Chinen, Kiyoshi; Nagayama, Kiyomitsu; Oroku, Masato; Nishihira, Morikuni; Shiohira, Yoshiki; Abe, Masami; Iseki, Kunitoshi; Ishida, Hideki; Tanabe, Kazunari

2017-05-26

BACKGROUND The effect of everolimus, one of the mammalian targets of rapamycin inhibitors, on cardiac function was evaluated in kidney transplant recipients. MATERIAL AND METHODS Seventy-six participants who underwent kidney transplant between March 2009 and May 2016 were retrospectively reviewed. To standardize everolimus administration, the following criteria were used: (1) the recipient did not have a donor-specific antigen before kidney transplantation; (2) the recipient did not have proteinuria and uncontrollable hyperlipidemia after kidney transplantation; and (3) acute rejection was not observed on protocol biopsy 3 months after kidney transplantation. According to these criteria, everolimus administration for maintenance immunosuppression after kidney transplantation was included. Cardiac function was compared between the treatment group (n=30) and non-treatment group (n=46). RESULTS The mean observation periods of the treatment and non-treatment groups were 41.3±12.6 and 43.9±19.8 months, respectively (p=0.573). The mean ejection fraction and fractional shortening of the treatment and non-treatment groups after kidney transplant were 66.5±7.9% vs. 69.6±5.5% (p=0.024) and 37.1±6.2% vs. 39.3±4.7% (p=0.045), respectively. In the treatment group, the mean ejection fraction and fractional shortening before and after kidney transplantation did not differ significantly (p=0.604 and 0.606, respectively). In the non-treatment group, the mean ejection fraction and fractional shortening before and after kidney transplantation differed significantly (p=0.004 and 0.006, respectively). CONCLUSIONS Supplementary administration of everolimus after kidney transplantation can reduce cardiac systolic function.

Does size matter? Kidney transplant donor size determines kidney function among living donors

PubMed Central

Narasimhamurthy, Meenakshi; Smith, Lachlan M.; Machan, Jason T.; Reinert, Steven E.; Gohh, Reginald Y.; Dworkin, Lance D.; Merhi, Basma; Patel, Nikunjkumar; Beland, Michael D.

2017-01-01

Background Kidney donor outcomes are gaining attention, particularly as donor eligibility criteria continue to expand. Kidney size, a useful predictor of recipient kidney function, also likely correlates with donor outcomes. Although donor evaluation includes donor kidney size measurements, the association between kidney size and outcomes are poorly defined. Methods We examined the relationship between kidney size (body surface area-adjusted total volume, cortical volume and length) and renal outcomes (post-operative recovery and longer-term kidney function) among 85 kidney donors using general linear models and time-to-chronic kidney disease data. Results Donors with the largest adjusted cortical volume were more likely to achieve an estimated glomerular filtration rate (eGFR) ≥60 mL/min/1.73 m2 over a median 24-month follow-up than those with smaller cortical volumes (P <0.001), had a shorter duration of renal recovery (1.3–2.2 versus 32.5 days) and started with a higher eGFR at pre-donation (107–110 versus 91 mL/min/1.73 m2) and immediately post-nephrectomy (∼63 versus 50–51 mL/min/1.73 m2). Similar findings were seen with adjusted total volume and length. Conclusions Larger kidney donors were more likely to achieve an eGFR ≥60 mL/min/1.73 m2 with renal recovery over a shorter duration due to higher pre-donation and initial post-nephrectomy eGFRs. PMID:28638611

Nephron Deficiency and Predisposition to Renal Injury in a Novel One-Kidney Genetic Model

PubMed Central

Wang, Xuexiang; Johnson, Ashley C.; Williams, Jan M.; White, Tiffani; Chade, Alejandro R.; Zhang, Jie; Liu, Ruisheng; Roman, Richard J.; Lee, Jonathan W.; Kyle, Patrick B.; Solberg-Woods, Leah

2015-01-01

Some studies have reported up to 40% of patients born with a single kidney develop hypertension, proteinuria, and in some cases renal failure. The increased susceptibility to renal injury may be due, in part, to reduced nephron numbers. Notably, children who undergo nephrectomy or adults who serve as kidney donors exhibit little difference in renal function compared with persons who have two kidneys. However, the difference in risk between being born with a single kidney versus being born with two kidneys and then undergoing nephrectomy are unclear. Animal models used previously to investigate this question are not ideal because they require invasive methods to model congenital solitary kidney. In this study, we describe a new genetic animal model, the heterogeneous stock-derived model of unilateral renal agenesis (HSRA) rat, which demonstrates 50%–75% spontaneous incidence of a single kidney. The HSRA model is characterized by reduced nephron number (more than would be expected by loss of one kidney), early kidney/glomerular hypertrophy, and progressive renal injury, which culminates in reduced renal function. Long-term studies of temporal relationships among BP, renal hemodynamics, and renal function demonstrate that spontaneous single-kidney HSRA rats are more likely than uninephrectomized normal littermates to exhibit renal impairment because of the combination of reduced nephron numbers and prolonged exposure to renal compensatory mechanisms (i.e., hyperfiltration). Future studies with this novel animal model may provide additional insight into the genetic contributions to kidney development and agenesis and the factors influencing susceptibility to renal injury in individuals with congenital solitary kidney. PMID:25349207

Nephron Deficiency and Predisposition to Renal Injury in a Novel One-Kidney Genetic Model.

PubMed

Wang, Xuexiang; Johnson, Ashley C; Williams, Jan M; White, Tiffani; Chade, Alejandro R; Zhang, Jie; Liu, Ruisheng; Roman, Richard J; Lee, Jonathan W; Kyle, Patrick B; Solberg-Woods, Leah; Garrett, Michael R

2015-07-01

Some studies have reported up to 40% of patients born with a single kidney develop hypertension, proteinuria, and in some cases renal failure. The increased susceptibility to renal injury may be due, in part, to reduced nephron numbers. Notably, children who undergo nephrectomy or adults who serve as kidney donors exhibit little difference in renal function compared with persons who have two kidneys. However, the difference in risk between being born with a single kidney versus being born with two kidneys and then undergoing nephrectomy are unclear. Animal models used previously to investigate this question are not ideal because they require invasive methods to model congenital solitary kidney. In this study, we describe a new genetic animal model, the heterogeneous stock-derived model of unilateral renal agenesis (HSRA) rat, which demonstrates 50%-75% spontaneous incidence of a single kidney. The HSRA model is characterized by reduced nephron number (more than would be expected by loss of one kidney), early kidney/glomerular hypertrophy, and progressive renal injury, which culminates in reduced renal function. Long-term studies of temporal relationships among BP, renal hemodynamics, and renal function demonstrate that spontaneous single-kidney HSRA rats are more likely than uninephrectomized normal littermates to exhibit renal impairment because of the combination of reduced nephron numbers and prolonged exposure to renal compensatory mechanisms (i.e., hyperfiltration). Future studies with this novel animal model may provide additional insight into the genetic contributions to kidney development and agenesis and the factors influencing susceptibility to renal injury in individuals with congenital solitary kidney. Copyright © 2015 by the American Society of Nephrology.

Assessing Intrarenal Non-perfusion and Vascular Leakage in Acute Kidney Injury withzz 19F MRI and Perfluorocarbon Nanoparticles

PubMed Central

Hu, Lingzhi; Chen, Junjie; Yang, Xiaoxia; Senpan, Angana; Allen, John S.; Yanaba, Noriko; Caruthers, Shelton D.; Lanza, Gregory M.; Hammerman, Marc R.; Wickline, Samuel A.

2014-01-01

Purpose We sought to develop a unique sensor-reporter approach for functional kidney imaging that employs circulating perfluorocarbon nanoparticles (PFC NPs) and 19F MRI. Methods Because the detected 19F signal intensity directly reflects local blood volume, and the 19F R1 is linearly proportional to local blood oxygen content (pO2), 19F spin density weighted and T1 weighted images were utilized to generate quantitative functional mapping in both healthy and ischemia-reperfusion (acute kidney injury, AKI) injured mouse kidneys. 1H Blood-Oxygenation-Level-Dependant (BOLD) MRI was also employed as a supplementary approach to facilitate the compressive analysis of renal circulation and its pathological changes in AKI. Results Heterogeneous blood volume distribution and intrarenal oxygenation gradient were confirmed in healthy kidneys by 19F MRI. In a mouse model of AKI, 19F MRI, in conjunction with BOLR MRI, sensitively delineated renal vascular damage and recovery. In the cortico-medullary (CM) junction region, we observed 25% lower 19F signal (p<0.05) and 70% longer 1H T2* (p<0.01) in injured kidneys compared to contralateral kidneys at 24 hours after initial ischemia-reperfusion injury. We also detected 71% higher 19F signal (p<0.01) and 40% lower 1H T2* (p<0.05) in the renal medulla region of injured kidneys compared to contralateral kidneys. Conclusion With demonstrated superior diagnostic capability, functional kidney 19F MRI using PFC NPs could serve as a new diagnostic measures for comprehensive evaluation of renal function and pathology. PMID:23929727

Assessment of the Renal Function in Potential Donors of Living Kidney Transplants: Expanded Study.

PubMed

Macías, L B; Poblet, M S; Pérez, N N; Jerez, R I; Gonzalez Roncero, F M; Blanco, G B; Valdivia, M A P; Benjumea, A S; Gentil Govantes, M A

2015-11-01

It is very important to determine as accurately as possible the renal function in potential living renal transplant donors, especially those with limited renal function (CrCl <90 mL/m/1.73 m(2)), age older than 50 years, and cardiovascular risk factors that might favor the development of long-term kidney diseases. The objective of this study was to compare the direct measurement of glomerular filtration rate (GFR) using EDTA-Cr51 and the estimations based on creatinine (eGFR): Cr clearance (CCr) with 24-hour urine and estimated using Cockroft-Gault (adjusted by using body surface area-Mosteller formula-SC), MDRD-4, MDRD-6, and CKD-EPI to determine the usefulness of different methods from EDTA-Cr51to evaluate the kidney function. The kidney function evaluation has been made to 105 potential kidney donors using the EDTA-Cr51 method. The GFR obtained through the EDTA-Cr51 is compared with the CCr values in 24-hour urine and eGFR based on creatinine (Cockcroft-Gault, MDRD4, MDRD6, and CKD-EPI). Using the Bland Altman graphic we have observed that the most dispersed results are obtained with the eGFR using CCr in 24-hour urine and CKD-EPI. By means of Pasing & Bablock, we realized that MDRD-4 and MDRD-6 show the highest approximation to the reference method proposed to be substituted, whereas CCr shows a high dispersion. eGFR using MDRD-4 and MDRD-6 formulas reveal the best adjustment to the measure by EDTA-Cr51. This might represent the best option if a direct eGFR measure is not available. Copyright © 2015 Elsevier Inc. All rights reserved.

Whole kidney engineering for clinical translation.

PubMed

Kim, Ick-Hee; Ko, In Kap; Atala, Anthony; Yoo, James J

2015-04-01

Renal transplantation is currently the only definitive treatment for end-stage renal disease; however, this treatment is severely limited by the shortage of implantable kidneys. To address this shortcoming, development of an engineered, transplantable kidney has been proposed. Although current advances in engineering kidneys based on decellularization and recellularization techniques have offered great promises for the generation of functional kidney constructs, most studies have been conducted using rodent kidney constructs and short-term in-vivo evaluation. Toward clinical translations of this technique, several limitations need to be addressed. Human-sized renal scaffolds are desirable for clinical application, and the fabrication is currently feasible using native porcine and discarded human kidneys. Current progress in stem cell biology and cell culture methods have demonstrated feasibility of the use of embryonic stem cells, induced pluripotent stem cells, and primary renal cells as clinically relevant cell sources for the recellularization of renal scaffolds. Finally, approaches to long-term implantation of engineered kidneys are under investigation using antithrombogenic strategies such as functional reendothelialization of acellular kidney matrices. In the field of bioengineering, whole kidneys have taken a number of important initial steps toward clinical translations, but many challenges must be addressed to achieve a successful treatment for the patient with end-stage renal disease.

Long-term Effects of Off-Pump Coronary Bypass Versus Conventional Coronary Bypass Grafting on Renal Function.

PubMed

Hynes, Conor F; Colo, Sanchez; Amdur, Richard L; Chawla, Lakhmir S; Greenberg, Michael D; Trachiotis, Gregory D

2016-01-01

This study aimed to evaluate the short- and long-term effects of conventional on-pump coronary bypass grafting (cCABG) compared with off-pump coronary artery bypass (OPCAB) on renal function. A retrospective review of patients undergoing coronary bypass grafting from 2004 through 2013 at a single center was conducted. Preoperative renal function, perioperative acute kidney injury, and long-term glomerular filtration were evaluated. Multivariable analyses were used to determine factors contributing to short- and long-term renal impairment. A total of 234 patients underwent cCABG, and 582 underwent OPCAB. Patients undergoing OPCAB were significantly older, had greater preoperative renal dysfunction, had greater functional dependence, and took more hypertension medications. Multivariable analyses found that 30-day acute kidney injury was an independent risk factor for a 10% decline in glomerular filtration rate at 1 and 5 years (P < 0.0001 and 0.002, respectively). However, the use of cardiopulmonary bypass was not found to influence long-term renal function (P = 0.78 at 1 year, P = 0.76 at 5 years). The percentage of patients experiencing a 10% drop in renal function from baseline at 1 year (33% OPCAB, 35% cCABG; P = 0.73) and 5 years (16% OPCAB, 16% cCABG; P = 0.93) were not significantly different. Independent predictors of acute kidney injury included baseline kidney function (P = 0.04) and age (P < 0.0001), whereas cardiopulmonary bypass did not affect the incidence (P = 0.17). A propensity-matched analysis confirmed these findings. Acute kidney injury is a risk factor for long-term renal dysfunction after either bypass method and was not greater after cCABG compared with OPCAB. Patients undergoing OPCAB did not experience greater decrease in long-term kidney function despite having worse baseline kidney function.

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.

Renal uptake of radioactive mercury (/sup 197/HgCl/sub 2/): method for testing the functional value of each kidney. Technique--results--and clinical application in urology and nephrology

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

Raynaud, C.

The first three chapters consider measurement of mercury renal uptake by external counting, by quantitative scintigraphy, and by the gamma camera. Some topics discussed in the remaining 14 chapters are as follows: renal depth; phantoms; precautions regarding the liver, spleen, and intestine; stability of /sup 197/HgCl/sub 2/ solutions; use of mercury renal uptake in pediatric and adult urology; indications for mercury renal uptake in renal transplants; and appraisal of the radiological and chemical toxicity of /sup 197/HgCl/sub 2/. It was concluded that mercury renal uptake is an accurate and nontraumatizing method of measuring the functional value of each kidney. Itmore » makes it possible to determine whether a kidney is normal or pathological and to what extent its function is diminished or increased. (HLW)« less

Real-time point-of-care measurement of impaired renal function in a rat acute injury model employing exogenous fluorescent tracer agents

NASA Astrophysics Data System (ADS)

Dorshow, Richard B.; Fitch, Richard M.; Galen, Karen P.; Wojdyla, Jolette K.; Poreddy, Amruta R.; Freskos, John N.; Rajagopalan, Raghavan; Shieh, Jeng-Jong; Demirjian, Sevag G.

2013-02-01

Renal function assessment is needed for the detection of acute kidney injury and chronic kidney disease. Glomerular filtration rate (GFR) is now widely accepted as the best indicator of renal function, and current clinical guidelines advocate its use in the staging of kidney disease. The optimum measure of GFR is by the use of exogenous tracer agents. However current clinically employed agents lack sensitivity or are cumbersome to use. An exogenous GFR fluorescent tracer agent, whose elimination rate could be monitored noninvasively through skin would provide a substantial improvement over currently available methods. We developed a series of novel aminopyrazine analogs for use as exogenous fluorescent GFR tracer agents that emit light in the visible region for monitoring GFR noninvasively over skin. In rats, these compounds are eliminated by the kidney with urine recovery greater than 90% of injected dose, are not broken down or metabolized in vivo, are not secreted by the renal tubules, and have clearance values similar to a GFR reference compound, iothalamate. In addition, biological half-life of these compounds measured in rats by noninvasive optical methods correlated with plasma derived methods. In this study, we show that this noninvasive methodology with our novel fluorescent tracer agents can detect impaired renal function. A 5/6th nephrectomy rat model is employed.

A best-practice position statement on pregnancy after kidney transplantation: focusing on the unsolved questions. The Kidney and Pregnancy Study Group of the Italian Society of Nephrology.

PubMed

Gianfranca, Cabiddu; Donatella, Spotti; Giuseppe, Gernone; Domenico, Santoro; Gabriella, Moroni; Gina, Gregorini; Franca, Giacchino; Rossella, Attini; Monica, Limardo; Linda, Gammaro; Tullia, Todros; Piccoli, Giorgina Barbara

2018-06-14

Kidney transplantation (KT) is often considered to be the method best able to restore fertility in a woman with chronic kidney disease (CKD). However, pregnancies in KT are not devoid of risks (in particular prematurity, small for gestational age babies, and the hypertensive disorders of pregnancy). An ideal profile of the potential KT mother includes "normal" or "good" kidney function (usually defined as glomerular filtration rate, GFR ≥ 60 ml/min), scant or no proteinuria (usually defined as below 500 mg/dl), normal or well controlled blood pressure (one drug only and no sign of end-organ damage), no recent acute rejection, good compliance and low-dose immunosuppression, without the use of potentially teratogen drugs (mycophenolic acid and m-Tor inhibitors) and an interval of at least 1-2 years after transplantation. In this setting, there is little if any risk of worsening of the kidney function. Less is known about how to manage "non-ideal" situations, such as a pregnancy a short time after KT, or one in the context of hypertension or a failing kidney. The aim of this position statement by the Kidney and Pregnancy Group of the Italian Society of Nephrology is to review the literature and discuss what is known about the clinical management of CKD after KT, with particular attention to women who start a pregnancy in non-ideal conditions. While the experience in such cases is limited, the risks of worsening the renal function are probably higher in cases with markedly reduced kidney function, and in the presence of proteinuria. Well-controlled hypertension alone seems less relevant for outcomes, even if its effect is probably multiplicative if combined with low GFR and proteinuria. As in other settings of kidney disease, superimposed preeclampsia (PE) is differently defined and this impairs calculating its real incidence. No specific difference between non-teratogen immunosuppressive drugs has been shown, but calcineurin inhibitors have been associated with foetal growth restriction and low birth weight. The clinical choices in cases at high risk for malformations or kidney function impairment (pregnancies under mycophenolic acid or with severe kidney-function impairment) require merging clinical and ethical approaches in which, beside the mother and child dyad, the grafted kidney is a crucial "third element".

Comparison of computer tomographic volumetry versus nuclear split renal function to determine residual renal function after living kidney donation.

PubMed

Patankar, Khalil; Low, Ronny Su-Tong; Blakeway, Darryn; Ferrari, Paolo

2014-07-01

Living-donor kidney transplantation is an established practice. Traditionally a combination of renal scintigram and computed tomography (CT) is used to select the kidney that is to be harvested in each donor. To evaluate the ability of split renal volume (SRV) calculated from volumetric examination of CT images compared to nuclear split renal function (nSRF) derived from gamma camera scintigram to predict donor residual single kidney function after donor nephrectomy. This pilot study comprised a retrospective analysis of CT images and renal scintigrams from 12 subsequent live kidney donors who had at least 12 months post-donation renal function follow-up. nSRF derived from the renal scintigram, expressed as the right kidney's function in percent of the total, was 50.2 ± 3.3 (range, 44.1-54.0%) and SRV estimated following analysis of CT imaging was 49.0 ± 2.9 (range, 46.4-52.3%). Although the correlation between nSRF and SRV was moderate (R = 0.46), there was 92% agreement on the dominant kidney if a difference of <2% in nSRF versus SRV was considered. Post-donation glomerular filtration rate (GFR) by CKD-EPI formula was 92 ± 10 mL/min/1.73m2 at 1 year and the correlation between estimated GFR (eGFR) at 1 year and extrapolated single kidney eGFR adjusted by nSRF (R(2 )= 0.69, P = 0.0007) or SRV (R(2 )= 0.74, P = 0.0003) was similar. Calculation of SRV from pre-donation CT examination is a valid method to estimate nSRF with good concordance with nSRF determined by renal scintigram and could replace the latter in the assessment of potential kidney donors. © The Foundation Acta Radiologica 2013 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav.

Two-as-one monolateral dual kidney transplantation.

PubMed

Veroux, Pierfrancesco; Giuffrida, Giuseppe; Cappellani, Alessandro; Caglià, Pietro; Palmucci, Stefano; Sorbello, Massimiliano; Puzzo, Lidia; Veroux, Massimiliano

2011-01-01

Dual kidney transplantation (DKT) of marginal kidneys could offer transplant candidates a very satisfactory kidney transplantation in terms of renal function. However, DKT might be considered a major surgical procedure and, in older recipients, has a potentially greater risk of surgical complications compared with single kidney transplantation. Because of these findings, some transplant centers have replaced the classic bilateral placement of 2 kidneys with the monolateral placement of both kidneys. In a group of 35 DKTs performed during a 5-year period, we applied a new technique of monolateral placement of DKT in 10 recipients. In these 10 patients, the arteries and veins of the 2 kidneys were joined through a running suture, and the joined kidneys were anastomosed into the external iliac vessels in the recipient. The delayed graft function rate was 20%. No surgical complications developed in the entire series. One patient experienced late rejection with ureteral stricture. The graft and patient survival rate at a median follow-up of 30 months was 90%. To reduce the surgical risk and morbidity rate, the monolateral placement of both kidneys seems the safest method to perform DKT. The joined monolateral DKT, by reducing the cold ischemia time and the surgical trauma, could represent a step forward in the delicate treatment of these patients. Copyright © 2011 Elsevier Inc. All rights reserved.

Fully automatic region of interest selection in glomerular filtration rate estimation from 99mTc-DTPA renogram.

PubMed

Lin, Kun-Ju; Huang, Jia-Yann; Chen, Yung-Sheng

2011-12-01

Glomerular filtration rate (GFR) is a common accepted standard estimation of renal function. Gamma camera-based methods for estimating renal uptake of (99m)Tc-diethylenetriaminepentaacetic acid (DTPA) without blood or urine sampling have been widely used. Of these, the method introduced by Gates has been the most common method. Currently, most of gamma cameras are equipped with a commercial program for GFR determination, a semi-quantitative analysis by manually drawing region of interest (ROI) over each kidney. Then, the GFR value can be computed from the scintigraphic determination of (99m)Tc-DTPA uptake within the kidney automatically. Delineating the kidney area is difficult when applying a fixed threshold value. Moreover, hand-drawn ROIs are tedious, time consuming, and dependent highly on operator skill. Thus, we developed a fully automatic renal ROI estimation system based on the temporal changes in intensity counts, intensity-pair distribution image contrast enhancement method, adaptive thresholding, and morphological operations that can locate the kidney area and obtain the GFR value from a (99m)Tc-DTPA renogram. To evaluate the performance of the proposed approach, 30 clinical dynamic renograms were introduced. The fully automatic approach failed in one patient with very poor renal function. Four patients had a unilateral kidney, and the others had bilateral kidneys. The automatic contours from the remaining 54 kidneys were compared with the contours of manual drawing. The 54 kidneys were included for area error and boundary error analyses. There was high correlation between two physicians' manual contours and the contours obtained by our approach. For area error analysis, the mean true positive area overlap is 91%, the mean false negative is 13.4%, and the mean false positive is 9.3%. The boundary error is 1.6 pixels. The GFR calculated using this automatic computer-aided approach is reproducible and may be applied to help nuclear medicine physicians in clinical practice.

Assessing the kidney function parameters glomerular filtration rate and effective renal plasma flow with dynamic FDG-PET/MRI in healthy subjects.

PubMed

Geist, Barbara K; Baltzer, Pascal; Fueger, Barbara; Hamboeck, Martina; Nakuz, Thomas; Papp, Laszlo; Rasul, Sazan; Sundar, Lalith Kumar Shiyam; Hacker, Marcus; Staudenherz, Anton

2018-05-09

A method was developed to assess the kidney parameters glomerular filtration rate (GFR) and effective renal plasma flow (ERPF) from 2-deoxy-2-[ 18 F]fluoro-D-glucose (FDG) concentration behavior in kidneys, measured with positron emission tomography (PET) scans. Twenty-four healthy adult subjects prospectively underwent dynamic simultaneous PET/magnetic resonance imaging (MRI) examination. Time activity curves (TACs) were obtained from the dynamic PET series, with the guidance of MR information. Patlak analysis was performed to determine the GFR, and based on integrals, ERPF was calculated. Results were compared to intra-individually obtained reference values determined from venous blood samples. Total kidney GFR and ERPF as estimated by dynamic PET/MRI were highly correlated to their reference values (r = 0.88/p < 0.0001 and r = 0.82/p < 0.0001, respectively) with no significant difference between their means. The study is a proof of concept that GFR and ERPF can be assessed with dynamic FDG PET/MRI scans in healthy kidneys. This has advantages for patients getting a routine scan, where additional examinations for kidney function estimation could be avoided. Further studies are required for transferring this PET/MRI method to PET/CT applications.

First successful combined heart and kidney transplant in Iran: a case report.

PubMed

Ahmadi, Zargham-Hossein; Mirhosseini, Seyed Mohsen; Fakhri, Mohammad; Mozaffary, Amirhossein; Lotfaliany, Mojtaba; Nejatollahi, Seyed Mohammad Reza; Marashi, Seyed-Ali; Behzadnia, Neda; Sharif-Kashani, Babak

2013-08-01

Combined heart and kidney transplant has become an accepted therapy for patients with coexisting heart and kidney failure. This method, compared with single-organ transplant, has a better outcome. Here, we report the first successful combined heart and kidney transplant in Iran. The patient was a 36-year-old man with end-stage renal disease owing to IgA nephropathy, admitted to Masih Daneshvari Hospital in Tehran, Iran for progressive dyspnea and chest pain. In-patient evaluations revealed cardiomyopathy leading to end-stage heart failure. Owing to concurrent heart and kidney end-stage diseases, combined cardiorenal transplant was done. Eight months after his transplant, routine follow-ups have not shown any signs of acute rejection. He is now New York Heart Association functional class I. Both cardiac and renal functions are within normal ranges. Good outcome during follow-up for this case justifies simultaneous heart plus kidney transplants as an alternate treatment for patients with advanced disease of both organs.

Sildenafil improves renal function in patients with pulmonary arterial hypertension

PubMed Central

Webb, David J; Vachiery, Jean-Luc; Hwang, Lie-Ju; Maurey, Julie O

2015-01-01

Aim Elevated serum creatinine (sCr) and low estimated glomerular filtration rate (eGFR) are associated with poor outcomes in patients with pulmonary arterial hypertension (PAH) whereas sildenafil treatment improves PAH outcomes. This post hoc analysis assessed the effect of sildenafil on kidney function and links with clinical outcomes including 6-min walk distance, functional class, time to clinical worsening and survival. Methods Patients with PAH received placebo or sildenafil 20, 40 or 80 mg three times daily in the SUPER-1 study and open-label sildenafil titrated to 80 mg three times daily (as tolerated) in the extension study. Results Baseline characteristics were similar among groups (n = 277). PAH was mostly idiopathic (63%) and functional class II (39%) or III (58%). From baseline to week 12, kidney function improved (increased eGFR, decreased sCr) with sildenafil and worsened with placebo. In univariate logistic regression, improved kidney function was associated with significantly improved exercise and functional class (odds ratios 1.17 [95% CI 1.01, 1.36] and 1.21 [95% CI 1.03, 1.41], respectively, for sCr and 0.97 [95% CI 0.94, 0.99] and 0.97 [95% CI 0.94, 0.99] for eGFR, all P < 0.05). In patients who maintained or improved kidney function, time to worsening was significantly delayed (P < 0.02 for both kidney parameters). Observed trends towards improved survival were not significant. Patients with eGFR <60 (vs. ≥60) ml min–1 1.73 m–2 appeared to have worse survival. Conclusions Sildenafil treatment was associated with improved kidney function in patients with PAH, which was in turn associated with improved exercise capacity and functional class, a reduced risk of clinical worsening, and a trend towards reduced mortality. PMID:25727860

Cystatin C– and Creatinine-Based Estimated Glomerular Filtration Rate, Vascular Disease, and Mortality in Persons With Diabetes in the U.S.

PubMed Central

Tsai, Ching-Wei; Grams, Morgan E.; Inker, Lesley A.; Coresh, Josef; Selvin, Elizabeth

2014-01-01

OBJECTIVE Serum cystatin C is an alternative to serum creatinine for estimating glomerular filtration rate (GFR), since cystatin C is less influenced by age and muscle mass. Among persons with diabetes, we compared the performance of GFR estimated using cystatin C (eGFRcys) with that using creatinine (eGFRcr) for the identification of reduced kidney function and its association with diabetes complications. RESEARCH DESIGN AND METHODS We analyzed data from adult participants from the 1999–2002 National Health and Nutrition Examination Survey with available cystatin C (N = 4,457). Kidney function was dichotomized as preserved (eGFR ≥60 mL/min/1.73 m2) or reduced (eGFR <60 mL/min/1.73 m2) using the 2012 Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) cystatin C and the 2009 CKD-EPI creatinine equations. RESULTS Among 778 persons with diabetes, the prevalence of reduced kidney function was 16.5% using eGFRcr and 22.0% using eGFRcys. More persons with diabetes were reclassified from preserved kidney function by eGFRcr to reduced kidney function by eGFRcys than persons without diabetes (odds ratio 3.1 [95% CI 1.9–4.9], P < 0.001). The associations between lower eGFR and higher prevalence of albuminuria, retinopathy, peripheral arterial disease, and coronary artery disease were robust regardless of filtration marker. Similarly, the risk of all-cause mortality increased with lower eGFRcr and eGFRcys. Only lower eGFRcys was significantly associated with cardiovascular mortality. CONCLUSIONS More persons with diabetes had reduced kidney function by eGFRcys than by eGFRcr, and lower eGFRcys was strongly associated with diabetes complications. Whether eGFRcys is superior to eGFRcr in approximating true kidney function in a diabetic population requires additional study. PMID:24271191

Assessment of kidney function in children by enzymatic determination of 2- or 24-h creatinine clearance: comparison with inulin clearance.

PubMed

Uemura, Osamu; Nagai, Takuhito; Yamakawa, Satoshi; Kaneko, Tetsuji; Hibi, Yoshiko; Yamasaki, Yasuhito; Yamamoto, Masaki; Nakano, Masaru; Iwata, Naoyuki; Hibino, Satoshi

2016-06-01

Although renal inulin clearance (Cin) is the gold standard for evaluation of kidney function, it cannot be measured easily. Therefore, creatinine clearance (Ccr) is often used clinically to evaluate kidney function. Enzymatically measured Ccr was recently found to be much higher than Cin because of the tubular secretion of creatinine (Cr). This study compared three measures of renal clearance, inulin, 2-h Ccr, and 24-h Ccr, in children. Kidney function was evaluated in 76 children (51 males and 25 females) aged 1 month to 18 years with chronic kidney disease (CKD) by three renal clearance methods at almost the same time. Correlations between each pair of three renal clearance measurements were determined. Approximate glomerular filtration rate (GFR) was equal to 62 % of 2-h Ccr or 76 % of 24-h Ccr. Cr secretion by renal tubules was approximately 50 % of the GFR. In this study, we indicate that the measurements of 2-h Ccr or 24-h Ccr do not show true GFR but we could infer approximate GFR from the values. The use of 2- or 24-h Ccr might contribute to the treatment of pediatric CKD patients.

Definition of chronic kidney disease and measurement of kidney function in original research papers: a review of the literature.

PubMed

Anderson, Jocelyn; Glynn, Liam G

2011-09-01

Over the past decade, chronic kidney disease (CKD) has become an area of intensive clinical and epidemiological research. Despite the clarity provided by the Kidney Disease Outcomes Quality Initiative (KDOQI) guidelines, there appears to be within the CKD research literature significant disagreement on how to define CKD and measure kidney function. The objectives of this study were to investigate the variety of methods used to define CKD and to measure kidney function in original research papers as well as to investigate whether the quality of the journal had any effect on the quality of the methodology used. This was a descriptive review and not a meta-analysis. Information was extracted from each article including publication details (including the journal's impact factor), definition of CKD, method used to estimate kidney function and quantity of serum creatinine readings used to define CKD. An electronic search of MEDLINE through OVID was completed using the search term CKD. The search was limited to articles in English published in 2009. Studies were included in the review only if they were original research articles including patients with CKD. Articles were excluded if they reported data from a paediatric population, a population solely on dialysis or if there was no full-text access through OVID. Each article was assessed for quality with respect to using KDOQI CKD definition criteria. A description of the pooled data was completed and chi-square tests were used to investigate the relation between article quality and journal quality. Analysis was carried out using SPSS (15.0) and a P-value of <0.05 was considered to indicate statistical significance. The final review included 301 articles. There were a variety of methods used to define CKD in original research articles. Less than 20% (n = 59) of the articles adhered to the established international criteria for defining CKD. The majority of articles (52.1%) did not indicate the quantity of serum creatinine measurements used to define CKD. The impact factor or specialist nature of the scientific journal appears to have no bearing on whether or not published articles use the gold standard KDOQI guidelines for labelling a patient with a diagnosis of CKD. This review of literature found that a variety of definitions are being used in original research articles to define CKD and measure kidney function which calls into question the validity and reliability of such research findings and associated clinical guidelines. International consensus is urgently required to improve validity and generalizability of CKD research findings.

Electrophoretic separation and analysis of living cells from solid tissues by several methods - Human embryonic kidney cell cultures as a model

NASA Technical Reports Server (NTRS)

Todd, Paul; Plank, Lindsay D.; Kunze, M. Elaine; Lewis, Marian L.; Morrison, Dennis R.

1986-01-01

The use of free-fluid electrophoresis methods to separate tissue cells having a specific function is discussed. It is shown that cells suspended by trypsinization from cultures of human embryonic kidney are electrophoretically heterogeneous and tolerate a wide range of electrophoresis buffers and conditions without significant attenuation of function. Moreover, these cells do not separate electrophoretically on the basis of size or cell position alone and can be separated according to their ability to give rise to progeny that produce specific plasminogen activators.

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.

Nephrectomy (Kidney Removal)

MedlinePlus

... nephrectomy is needed because of other kidney diseases. Kidney function Most people have two kidneys — fist-sized ... and the disease that prompted the surgery? Monitoring kidney function Most people can function well with only ...

Improved split renal function after percutaneous nephrostomy in young adults with severe hydronephrosis due to ureteropelvic junction obstruction.

PubMed

Zhang, Shiwei; Zhang, Qing; Ji, Changwei; Zhao, Xiaozhi; Liu, Guangxiang; Zhang, Shun; Li, Xiaogong; Lian, Huibo; Zhang, Gutian; Guo, Hongqian

2015-01-01

We evaluated percutaneous nephrostomy for adult kidneys with severe hydronephrosis due to ureteropelvic junction obstruction and less than 10% split renal function. In this retrospective analysis we included patients who underwent percutaneous nephrostomy for unilateral ureteropelvic junction obstruction of the kidneys with hydronephrosis and less than 10% split renal function at our hospital between May 2009 and January 2012. Adults (age 18 years or greater) were divided into those 35 years or younger (young adults) and older than 35 years (older adults). The percutaneous nephrostomy remained in situ a mean ± SD of 6.62 ± 2.55 weeks and patients underwent repeat renography before pyeloplasty. When there was no significant improvement in split renal function (10% or greater) and drainage (greater than 400 ml per day), nephrectomy was performed. Otherwise pyeloplasty was performed. Patients were followed by renography, ultrasound and contrast computerized tomography at 3 and 6 months, at 1 year and annually thereafter. Of 53 patients 30 (56.6%) showed improvement after percutaneous nephrostomy drainage and urine output greater than 400 ml per day with percutaneous nephrostomy. Pyeloplasty was then performed. Of 29 young adults 24 (82.8%) showed improved split renal function vs 6 of 24 older adults (25%). Nephrectomy of the other 23 kidneys was performed. At a mean followup of 19.27 ± 7.82 months (range 12 to 36), no patient showed hypertension or urinary tract infection. Split renal function detected by renography may not accurately predict recovered, poorly functioning kidneys, especially in young adults. First observing the recoverability of hydronephrotic kidneys by percutaneous nephrostomy drainage and then preserving select kidneys may be an effective method to manage poorly functioning kidneys due to ureteropelvic junction obstruction. Copyright © 2015 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

MRI to assess renal structure and function.

PubMed

Artunc, Ferruh; Rossi, Cristina; Boss, Andreas

2011-11-01

In addition to excellent anatomical depiction, MRI techniques have expanded to study functional aspects of renal physiology, such as renal perfusion, glomerular filtration rate (GFR) or tissue oxygenation. This review will focus on current developments with an emphasis on clinical applicability. The method of GFR determination is largely heterogeneous and still has weaknesses. However, the technique of employing liver disappearance curves has been shown to be accurate in healthy persons and patients with chronic kidney disease. In potential kidney donors, complete evaluation of kidney anatomy and function can be accomplished in a single-stop investigation. Techniques without contrast media can be utilized to measure renal tissue oxygenation (blood oxygen level-dependent MRI) or perfusion (arterial spin labeling) and could aid in the diagnosis and treatment of ischemic renal diseases, such as renal artery stenosis. Diffusion imaging techniques may provide information on spatially restricted water diffusion and tumor cellularity. Functional MRI opens new horizons in studying renal physiology and pathophysiology in vivo. Although extensively utilized in research, labor-intensive postprocessing and lack of standardization currently limit the clinical applicability of functional MRI. Further studies are necessary to evaluate the clinical value of functional magnetic resonance techniques for early discovery and characterization of kidney disease.

High-resolution diffusion tensor imaging of the human kidneys using a free-breathing, multi-slice, targeted field of view approach

PubMed Central

Chan, Rachel W; Von Deuster, Constantin; Stoeck, Christian T; Harmer, Jack; Punwani, Shonit; Ramachandran, Navin; Kozerke, Sebastian; Atkinson, David

2014-01-01

Fractional anisotropy (FA) obtained by diffusion tensor imaging (DTI) can be used to image the kidneys without any contrast media. FA of the medulla has been shown to correlate with kidney function. It is expected that higher spatial resolution would improve the depiction of small structures within the kidney. However, the achievement of high spatial resolution in renal DTI remains challenging as a result of respiratory motion and susceptibility to diffusion imaging artefacts. In this study, a targeted field of view (TFOV) method was used to obtain high-resolution FA maps and colour-coded diffusion tensor orientations, together with measures of the medullary and cortical FA, in 12 healthy subjects. Subjects were scanned with two implementations (dual and single kidney) of a TFOV DTI method. DTI scans were performed during free breathing with a navigator-triggered sequence. Results showed high consistency in the greyscale FA, colour-coded FA and diffusion tensors across subjects and between dual- and single-kidney scans, which have in-plane voxel sizes of 2 × 2 mm2 and 1.2 × 1.2 mm2, respectively. The ability to acquire multiple contiguous slices allowed the medulla and cortical FA to be quantified over the entire kidney volume. The mean medulla and cortical FA values were 0.38 ± 0.017 and 0.21 ± 0.019, respectively, for the dual-kidney scan, and 0.35 ± 0.032 and 0.20 ± 0.014, respectively, for the single-kidney scan. The mean FA between the medulla and cortex was significantly different (p < 0.001) for both dual- and single-kidney implementations. High-spatial-resolution DTI shows promise for improving the characterization and non-invasive assessment of kidney function. © 2014 The Authors. NMR in Biomedicine published by John Wiley & Sons, Ltd. PMID:25219683

High-resolution diffusion tensor imaging of the human kidneys using a free-breathing, multi-slice, targeted field of view approach.

PubMed

Chan, Rachel W; Von Deuster, Constantin; Stoeck, Christian T; Harmer, Jack; Punwani, Shonit; Ramachandran, Navin; Kozerke, Sebastian; Atkinson, David

2014-11-01

Fractional anisotropy (FA) obtained by diffusion tensor imaging (DTI) can be used to image the kidneys without any contrast media. FA of the medulla has been shown to correlate with kidney function. It is expected that higher spatial resolution would improve the depiction of small structures within the kidney. However, the achievement of high spatial resolution in renal DTI remains challenging as a result of respiratory motion and susceptibility to diffusion imaging artefacts. In this study, a targeted field of view (TFOV) method was used to obtain high-resolution FA maps and colour-coded diffusion tensor orientations, together with measures of the medullary and cortical FA, in 12 healthy subjects. Subjects were scanned with two implementations (dual and single kidney) of a TFOV DTI method. DTI scans were performed during free breathing with a navigator-triggered sequence. Results showed high consistency in the greyscale FA, colour-coded FA and diffusion tensors across subjects and between dual- and single-kidney scans, which have in-plane voxel sizes of 2 × 2 mm(2) and 1.2 × 1.2 mm(2) , respectively. The ability to acquire multiple contiguous slices allowed the medulla and cortical FA to be quantified over the entire kidney volume. The mean medulla and cortical FA values were 0.38 ± 0.017 and 0.21 ± 0.019, respectively, for the dual-kidney scan, and 0.35 ± 0.032 and 0.20 ± 0.014, respectively, for the single-kidney scan. The mean FA between the medulla and cortex was significantly different (p < 0.001) for both dual- and single-kidney implementations. High-spatial-resolution DTI shows promise for improving the characterization and non-invasive assessment of kidney function. © 2014 The Authors. NMR in Biomedicine published by John Wiley & Sons, Ltd.

Aortic PWV in Chronic Kidney Disease: A CRIC Ancillary Study

PubMed Central

Townsend, Raymond R.; Wimmer, Neil J.; Chirinos, Julio A.; Parsa, Afshin; Weir, Matthew; Perumal, Kalyani; Lash, James P.; Chen, Jing; Steigerwalt, Susan P.; Flack, John; Go, Alan S.; Rafey, Mohammed; Rahman, Mahboob; Sheridan, Angela; Gadegbeku, Crystal A.; Robinson, Nancy A.; Joffe, Marshall

2009-01-01

Background Aortic PWV is a measure of arterial stiffness and has proved useful in predicting cardiovascular morbidity and mortality in several populations of patients, including the healthy elderly, hypertensives and those with end stage renal disease receiving hemodialysis. Little data exist characterizing aortic stiffness in patients with chronic kidney disease who are not receiving dialysis, and in particular the effect of reduced kidney function on aortic PWV. Methods We performed measurements of aortic PWV in a cross-sectional cohort of participants enrolled in the Chronic Renal Insufficiency Cohort (CRIC) study to determine factors which predict increased aortic PWV in chronic kidney disease. Results PWV measurements were obtained in 2564 participants. The tertiles of aortic PWV (adjusted for waist circumference) were < 7.7 m/sec, 7.7–10.2 m/sec and > 10.2 m/sec with an overall mean (± S.D.) value of 9.48 ± 3.03 m/sec [95% CI = 9.35–9.61 m/sec]. Multivariable regression identified significant independent positive associations of age, blood glucose concentrations, race, waist circumference, mean arterial blood pressure, gender, and presence of diabetes with aortic PWV and a significant negative association with the level of kidney function. Conclusions The large size of this unique cohort, and the targeted enrollment of chronic kidney disease participants provides an ideal situation to study the role of reduced kidney function as a determinant of arterial stiffness. Arterial stiffness may be a significant component of the enhanced cardiovascular risk associated with kidney failure. PMID:20019670

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

Stereological assessment of normal Persian squirrels (Sciurus anomalus) kidney.

PubMed

Akbari, Mohsen; Goodarzi, Nader; Tavafi, Majid

2017-03-01

The functions of the mammalian kidney are closely related to its structure. This suggests that renal function can be completely characterized by accurate knowledge of its quantitative morphological features. The aim of this study was to investigate the histomorphometric features of the kidney using design-based and unbiased stereological methods in the Persian squirrel (Sciurus anomalus), which is the only representative of the Sciuridae family in the Middle East. The left kidneys of five animals were examined. Total volume of the kidney, cortex, and medulla were determined to be 960.75 ± 87.4, 754.31 ± 77.09 and 206.1 ± 16.89 mm 3 , respectively. The glomerular number was 32844.03 ± 1069.19, and the total glomerular volume was estimated to be 36.7 ± 1.45 mm 3 . The volume and length of the proximal convoluted tubule were estimated at 585.67 ± 60.7 mm 3 and 328.8 ± 14.8 m, respectively, with both values being greater than those reported in the rat kidney. The volume and length of the distal convoluted tubule were calculated at 122.34 ± 7.38 mm 3 and 234.4 ± 17.45 m, respectively, which are also greater than those reported in the rat kidney. Despite the comparable body weight, the total number and mean individual volume of glomeruli in the Persian squirrel kidney were greater than those in the rat kidney. Overall, the stereological variables of the kidneys elucidated in this study are exclusive to the Persian squirrel. Our findings, together with future renal physiological data, will contribute to a better understanding of the renal structure-function relationship in the Persian squirrel.

Intermediate-Term Outcomes With Expanded Criteria Deceased Donors in Kidney Transplantation

PubMed Central

Stratta, Robert J.; Rohr, Michael S.; Sundberg, Aimee K.; Farney, Alan C.; Hartmann, Erica L.; Moore, Phillip S.; Rogers, Jeffrey; Iskandar, Samy S.; Gautreaux, Michael D.; Kiger, David F.; Doares, William; Anderson, Teresa K.; Hairston, Gloria; Adams, Patricia L.

2006-01-01

Objective: To compare intermediate-term outcomes in adult recipients of expanded criteria (ECD) versus concurrent standard criteria (SCD) deceased donor kidney transplants at a single center using a standardized approach. Summary Background Data: Expanded criteria donors (ECDs) are a source of kidneys that increase the donor organ pool, but the value of transplanting these kidneys has been questioned because of concerns regarding diminished survival and predicted poorer intermediate-term outcomes. Methods: Over a 47-month period, we performed 244 deceased donor kidney transplants into adult recipients, including 143 from SCDs and 101 from ECDs. Management algorithms were implemented to preserve nephron function, and recipient selection for an ECD kidney transplant was based on low immunologic risk. All patients received depleting antibody induction in combination with tacrolimus and mycophenolate mofetil. A total of 188 patients (77%) had at least a 1-year follow-up. Results: ECDs were older, had a higher BMI, had an increased incidence of cerebrovascular brain death and preexisting donor hypertension, and had a lower estimated creatinine clearance (CrCl, all P < 0.01) compared with SCDs. Cold ischemic times were similar between groups, but more ECD kidneys were preserved with pulsatile perfusion (P < 0.01). ECD kidney recipients were older, less sensitized, had a lower BMI, had fewer 0-antigen mismatches, and had a shorter waiting time (all P < 0.01) compared with SCD kidney recipients. Actual patient (93%) and kidney graft (83%) survival rates were similar between groups with a mean follow-up of 24 months. The rates of delayed graft function (DGF), acute rejection, readmissions, operative complications, major infections, and resource utilization were comparable between groups. Renal function followed longitudinally was consistently better in SCD patients (P < 0.05). Black recipients had higher rates of DGF, acute rejection, and graft loss (P < 0.05), but the effects were less pronounced in the ECD group. Conclusions: By appropriate donor and recipient profiling and the use of management algorithms to project and protect renal function, excellent intermediate-term outcomes can be achieved with ECD kidney transplants that are comparable to SCD kidney transplants. PMID:16632993

Practical application of stereological methods in experimental kidney animal models.

PubMed

Fernández García, María Teresa; Núñez Martínez, Paula; García de la Fuente, Vanessa; Sánchez Pitiot, Marta; Muñiz Salgueiro, María Del Carmen; Perillán Méndez, Carmen; Argüelles Luis, Juan; Astudillo González, Aurora

The kidneys are vital organs responsible for excretion, fluid and electrolyte balance and hormone production. The nephrons are the kidney's functional and structural units. The number, size and distribution of the nephron components contain relevant information on renal function. Stereology is a branch of morphometry that applies mathematical principles to obtain three-dimensional information from serial, parallel and equidistant two-dimensional microscopic sections. Because of the complexity of stereological studies and the lack of scientific literature on the subject, the aim of this paper is to clearly explain, through animal models, the basic concepts of stereology and how to calculate the main kidney stereological parameters that can be applied in future experimental studies. Copyright © 2016 Sociedad Española de Nefrología. Published by Elsevier España, S.L.U. All rights reserved.

BOLD magnetic resonance imaging in nephrology

PubMed Central

Hall, Michael E; Jordan, Jennifer H; Juncos, Luis A; Hundley, W Gregory; Hall, John E

2018-01-01

Magnetic resonance (MR) imaging, a non-invasive modality that provides anatomic and physiologic information, is increasingly used for diagnosis of pathophysiologic conditions and for understanding renal physiology in humans. Although functional MR imaging methods were pioneered to investigate the brain, they also offer powerful techniques for investigation of other organ systems such as the kidneys. However, imaging the kidneys provides unique challenges due to potential complications from contrast agents. Therefore, development of non-contrast techniques to study kidney anatomy and physiology is important. Blood oxygen level-dependent (BOLD) MR is a non-contrast imaging technique that provides functional information related to renal tissue oxygenation in various pathophysiologic conditions. Here we discuss technical considerations, clinical uses and future directions for use of BOLD MR as well as complementary MR techniques to better understand renal pathophysiology. Our intent is to summarize kidney BOLD MR applications for the clinician rather than focusing on the complex physical challenges that functional MR imaging encompasses; however, we briefly discuss some of those issues. PMID:29559807

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.

Thalidomide Ameliorates Inflammation and Vascular Injury but Aggravates Tubular Damage in the Irradiated Mouse Kidney

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

Scharpfenecker, Marion, E-mail: m.scharpfenecker@nki.nl; Floot, Ben; Russell, Nicola S.

Purpose: The late side effects of kidney irradiation include vascular damage and fibrosis, which are promoted by an irradiation-induced inflammatory response. We therefore treated kidney-irradiated mice with the anti-inflammatory and angiogenesis-modulating drug thalidomide in an attempt to prevent the development of late normal tissue damage and radiation nephropathy in the mouse kidney. Methods and Materials: Kidneys of C57Bl/6 mice were irradiated with a single dose of 14 Gy. Starting from week 16 after irradiation, the mice were fed with thalidomide-containing chow (100 mg/kg body weight/day). Gene expression and kidney histology were analyzed at 40 weeks and blood samples at 10, 20, 30, andmore » 40 weeks after irradiation. Results: Thalidomide improved the vascular structure and vessel perfusion after irradiation, associated with a normalization of pericyte coverage. The drug also reduced infiltration of inflammatory cells but could not suppress the development of fibrosis. Irradiation-induced changes in hematocrit and blood urea nitrogen levels were not rescued by thalidomide. Moreover, thalidomide worsened tubular damage after irradiation and also negatively affected basal tubular function. Conclusions: Thalidomide improved the inflammatory and vascular side effects of kidney irradiation but could not reverse tubular toxicity, which probably prevented preservation of kidney function.« less

Association between kidney function and telomere length: the Heart and Soul Study

PubMed Central

Bansal, Nisha; Whooley, Mary A.; Regan, Mathilda; McCulloch, Charles E.; Ix, Joachim H.; Epel, Elissa; Blackburn, Elizabeth; Lin, Jue; Hsu, Chi-yuan

2013-01-01

Background Telomere attrition is a novel risk factor for cardiovascular disease. Studies of telomere length in relation to kidney function are limited. We explored the association of kidney function with telomere length and telomere shortening. Methods The Heart and Soul study is a longitudinal study of patients with stable coronary heart disease (CHD). Measures of baseline kidney function included: serum creatinine, creatinine-derived estimated glomerular filtration rate (eGFRCKD-EPI), 24-hour urine measured creatinine clearance, cystatin C, cystatin C-derived estimated glomerular filtration rate (eGFRcys) and urine albumin to creatinine ratio. Telomere length was measured from peripheral blood leukocytes at baseline (N=954) and 5 years later (N=608). Linear regression models were used to test the association of kidney function with i) baseline telomere length and ii) change in telomere length over 5 years. Results At baseline, mean eGFRCKD-EPI was 72.6 (± 21.5) ml/min/1.73 m2, eGFRcys was 71.0 (± 23.1) ml/min/1.73 m2 and ACR was 8.6 (±12.3) mg/gm. Only lower baseline eGFRCKD-EPI was associated with shorter baseline telomere length (9.1 [95% CI 1.2–16.9] fewer base pairs for every 5 ml/min/1.73 m2 lower eGFRCKD-EPI). Lower baseline eGFRCKD-EPI (and all other measures of kidney function) predicted more rapid telomere shortening (10.8 [95% CI 4.3–17.3] decrease in base pairs over 5 years for every 5 ml/min/1.73 m2 lower eGFRCKD-EPI). After adjustment for age, these associations were no longer statistically significant. Conclusions In patients with CHD, reduced kidney function is associated with i) shorter baseline telomere length and ii) more rapid telomere shortening over 5 years, however these associations are entirely explained by older age. PMID:23108000

The Association Between Kidney Disease and Cardiovascular Risk in a Multiethnic Cohort

PubMed Central

Nickolas, Thomas L.; Khatri, Minesh; Boden-Albala, Bernadette; Kiryluk, Krzysztof; Luo, Xiaodong; Gervasi-Franklin, Palma; Paik, Myunghee; Sacco, Ralph L.

2011-01-01

Background and Purpose The objective of this study was to determine the relationship between chronic kidney disease (CKD), race–ethnicity, and vascular outcomes. Methods A prospective, multiracial cohort of 3298 stroke-free subjects with 6.5 years of mean follow-up time for vascular outcomes (stroke, myocardial infarction, vascular death) was used. Kidney function was estimated using serum creatinine and Cockcroft-Gault formula. Cox proportional hazards models were fitted to evaluate the relationship between kidney function and vascular outcomes. Results In multivariate analysis, Cockcroft-Gault formula between 15 and 59 mL/min was associated with a significant 43% increased stroke risk in the overall cohort. Blacks with Cockcroft-Gault formula between 15 and 59 mL/min had significantly increased risk of both stroke (hazard ratio, 2.65; 95% CI, 1.47 to 4.77) and combined vascular outcomes (hazard ratio, 1.59; 95% CI, 1.10–2.92). Conclusion Chronic kidney disease is a significant risk factor for stroke and combined vascular events, especially in blacks. PMID:18617655

Chronic Kidney Disease Screening Methods and Its Implication for Malaysia: An in Depth Review

PubMed Central

Almualm, Yasmin; Huri, Hasniza Zaman

2015-01-01

Chronic Kidney Disease has become a public health problem, imposing heath, social and human cost on societies worldwide. Chronic Kidney Disease remains asymptomatic till late stage when intervention cannot stop the progression of the disease. Therefore, there is an urgent need to detect the disease early. Despite the high prevalence of Chronic Kidney Disease in Malaysia, screening is still lacking behind. This review discusses the strengths and limitations of current screening methods for Chronic Kidney Disease from a Malaysian point of view. Diabetic Kidney Disease was chosen as focal point as Diabetes is the leading cause of Chronic Kidney Disease in Malaysia. Screening for Chronic Kidney Disease in Malaysia includes a urine test for albuminuria and a blood test for serum creatinine. Recent literature indicates that albuminuria is not always present in Diabetic Kidney Disease patients and serum creatinine is only raised after substantial kidney damage has occurred. Recently, cystatin C was proposed as a potential marker for kidney disease but this has not been studied thoroughly in Malaysia. Glomerular Filtration Rate is the best method for measuring kidney function and is widely estimated using the Modification of Diet for Renal Disease equation. Another equation, the Chronic Kidney Disease Epidemiology Collaboration Creatinine equation was introduced in 2009. The new equation retained the precision and accuracy of the Modification of Diet for Renal Disease equation at GFR < 60ml/min/1.73m2, showed less bias and improved precision at GFR>60ml/min/1.73m2. In Asian countries, adding an ethnic coefficient to the equation enhanced its performance. In Malaysia, a multi-ethnic Asian population, the Chronic Kidney Disease Epidemiology Collaboration equation should be validated and the Glomerular Filtration Rate should be reported whenever serum creatinine is ordered. Reporting estimated Glomerular Filtration Rate will help diagnose patients who would have been otherwise missed if only albuminuria and serum creatinine are measured. PMID:25946939

Chronic kidney disease screening methods and its implication for Malaysia: an in depth review.

PubMed

Almualm, Yasmin; Zaman Huri, Hasniza

2015-01-01

Chronic Kidney Disease has become a public health problem, imposing heath, social and human cost on societies worldwide. Chronic Kidney Disease remains asymptomatic till late stage when intervention cannot stop the progression of the disease. Therefore, there is an urgent need to detect the disease early. Despite the high prevalence of Chronic Kidney Disease in Malaysia, screening is still lacking behind. This review discusses the strengths and limitations of current screening methods for Chronic Kidney Disease from a Malaysian point of view. Diabetic Kidney Disease was chosen as focal point as Diabetes is the leading cause of Chronic Kidney Disease in Malaysia. Screening for Chronic Kidney Disease in Malaysia includes a urine test for albuminuria and a blood test for serum creatinine. Recent literature indicates that albuminuria is not always present in Diabetic Kidney Disease patients and serum creatinine is only raised after substantial kidney damage has occurred.  Recently, cystatin C was proposed as a potential marker for kidney disease but this has not been studied thoroughly in Malaysia.  Glomerular Filtration Rate is the best method for measuring kidney function and is widely estimated using the Modification of Diet for Renal Disease equation. Another equation, the Chronic Kidney Disease Epidemiology Collaboration Creatinine equation was introduced in 2009. The new equation retained the precision and accuracy of the Modification of Diet for Renal Disease equation at GFR < 60ml/min/1.73m2, showed less bias and improved precision at GFR>60ml/min/1.73m2. In Asian countries, adding an ethnic coefficient to the equation enhanced its performance. In Malaysia, a multi-ethnic Asian population, the Chronic Kidney Disease Epidemiology Collaboration equation should be validated and the Glomerular Filtration Rate should be reported whenever serum creatinine is ordered. Reporting estimated Glomerular Filtration Rate will help diagnose patients who would have been otherwise missed if only albuminuria and serum creatinine are measured.

Prophylactic Management of Contrast-Induced Acute Kidney Injury in High-Risk Patients.

PubMed

Nahar, Diya

2017-01-01

Contrast-induced acute kidney injury (CI-AKI) has been linked to morbidity and mortality, especially in high-risk patients whose kidney function is compromised. Recently, many studies have been conducted to search for more novel, preventative methods of decreasing CI-AKI. Through a detailed analysis of recent studies, this article discusses recommendations for hydration, N-acetylcysteine, and statin therapy in relation to the prophylactic management of CI-AKI in high-risk patients. Copyright© by the American Nephrology Nurses Association.

Determination of single-kidney glomerular filtration rate (GFR) with CT urography versus renal dynamic imaging Gates method.

PubMed

You, Shan; Ma, XianWu; Zhang, ChangZhu; Li, Qiang; Shi, WenWei; Zhang, Jing; Yuan, XiaoDong

2018-03-01

To present a single-kidney CT-GFR measurement and compare it with the renal dynamic imaging Gates-GFR. Thirty-six patients with hydronephrosis referred for CT urography and 99mTc-DTPA renal dynamic imaging were prospectively included. Informed consent was obtained from all patients. The CT urography protocol included non-contrast, nephrographic, and excretory phase imaging. The total CT-GFR was calculated by dividing the CT number increments of the total urinary system between the nephrographic and excretory phase by the products of iodine concentration in the aorta and the elapsed time, then multiplied by (1- Haematocrit). The total CT-GFR was then split into single-kidney CT-GFR by a left and right kidney proportionality factor. The results were compared with single-kidney Gates-GFR by using paired t-test, correlation analysis, and Bland-Altman plots. Paired difference between single-kidney CT-GFR (45.02 ± 13.91) and single-kidney Gates-GFR (51.21 ± 14.76) was 6.19 ± 5.63 ml/min, p<0.001, demonstrating 12.1% systematic underestimation with ±11.03 ml/min (±21.5%) measurement deviation. A good correlation was revealed between both measurements (r=0.87, p<0.001). The proposed single-kidney CT-GFR correlates and agrees well with the reference standard despite a systematic underestimation, therefore it could be a one-stop-shop for evaluating urinary tract morphology and split renal function. • A new CT method can assess split renal function • Only using images from CT urography and the value of haematocrit • A one-stop-shop CT technique without additional radiation dose.

New magnetic resonance imaging methods in nephrology

PubMed Central

Zhang, Jeff L.; Morrell, Glen; Rusinek, Henry; Sigmund, Eric; Chandarana, Hersh; Lerman, Lilach O.; Prasad, Pottumarthi Vara; Niles, David; Artz, Nathan; Fain, Sean; Vivier, Pierre H.; Cheung, Alfred K.; Lee, Vivian S.

2013-01-01

Established as a method to study anatomic changes, such as renal tumors or atherosclerotic vascular disease, magnetic resonance imaging (MRI) to interrogate renal function has only recently begun to come of age. In this review, we briefly introduce some of the most important MRI techniques for renal functional imaging, and then review current findings on their use for diagnosis and monitoring of major kidney diseases. Specific applications include renovascular disease, diabetic nephropathy, renal transplants, renal masses, acute kidney injury and pediatric anomalies. With this review, we hope to encourage more collaboration between nephrologists and radiologists to accelerate the development and application of modern MRI tools in nephrology clinics. PMID:24067433

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%.

Final Year Nursing Students in Nigeria; How Knowledgeable and Prepared are They to Offer Medical Care to Patients with Chronic Kidney Disease?

PubMed Central

Okwuonu, Chimezie Godswill; Kanu, Hannah Sylvanus; Odigie, Ojeh-Oziegbe

2017-01-01

Background: Nurses play an important role in the management of chronic kidney disease (CKD) patients at primary, secondary, and tertiary levels of care. In other to perform their functions, it is pertinent that they have a good understanding of kidney functions and CKD. We do not know if the current educational curriculum prepares them adequately for this role. Aim: To assess the knowledge level of kidney functions and diseases among final year nursing students in Abia State Nigeria. Materials and Methods: This was a cross sectional study involving final year diploma and Bachelor of nursing (B. Nursing) students who were randomly chosen. Structured, self-administered questionnaire containing 18 items was the tool for data collection. A score of one was given for each correctly answered question on functions of the kidney, symptoms, signs, causes, and complications of CKD. A score of 50% and above was regarded as good knowledge. Results: Two hundred questionnaires were distributed, but 186 were returned (response rate of 93%). Male:female ratio was 1:14.5. One hundred and seventeen (62.9%) knew the correct definition of CKD, but only 69 (37.1%) knew the normal range of glomerular filtration rate. Eighty-one percent had good knowledge of kidney functions while 39 (21%) had good knowledge of CKD. Overall, 42 (22.6%) had good knowledge of kidney functions and CKD. Students who rotated through the dialysis unit during their clinical posting had higher mean knowledge score than others (P = 0.03). There was no significant difference in the mean knowledge scores of the diploma and B. Nursing students (P = 0.76). Conclusion: The majority of the final year students had poor knowledge of CKD. There is need to expand the current teaching curriculum so as to increase the knowledge of these future nurses on the basic concepts of CKD to improve outcomes of patient management. PMID:28300046

En bloc transplantation of horseshoe kidney in Korea

PubMed Central

Bang, Jun Bae; Lee, Jae Myeong; Oh, Chang-Kwon; Lee, Kyo Won; Park, Jae Berm; Kim, Sung Joo

2017-01-01

Transplantation of the horseshoe kidney can be performed en bloc or split into 2 grafts according to the vascular anomaly and the existence of the urinary collecting system in isthmus. From 2011 to 2014, there were 3 horseshoe kidney transplantations in Korea and transplantations were performed at 2 different centers. The transplantations were carried out successfully for all recipients without complications. All recipients have shown good graft kidney function after transplantation. No severe complication was revealed during follow-up period. We described the surgical technique used in the en bloc method to overcome various vascular anomalies and difficulties in choosing cannulation site and postoperative complications. En bloc transplantation of a horseshoe kidney is a useful strategy for patients with end-stage renal disease, and can provide favorable outcomes compared to the transplantation of a normal kidney. PMID:28289672

Application of prescribing recommendations in older people with reduced kidney function: a cross-sectional study in general practice.

PubMed

Wood, Su; Petty, Duncan; Glidewell, Liz; Raynor, Dk Theo

2018-05-01

Kidney function reduces with age, increasing the risk of harm from increased blood levels of many medicines. Although estimated glomerular filtration rate (eGFR) is reported for prescribing decisions in those aged ≥65 years, creatinine clearance (Cockcroft-Gault) gives a more accurate estimate of kidney function. To explore the extent of prescribing outside recommendations for people aged ≥65 years with reduced kidney function in primary care and to assess the impact of using eGFR instead of creatinine clearance to calculate kidney function. A cross-sectional survey of anonymised prescribing data in people aged ≥65 years from all 80 general practices (70 900 patients) in a north of England former primary care trust. The prevalence of prescribing outside recommendations was analysed for eight exemplar drugs. Data were collected for age, sex, actual weight, serum creatinine, and eGFR. Kidney function as creatinine clearance (Cockcroft-Gault) was calculated using actual body weight and estimated ideal body weight. Kidney function was too low for recommended prescribing in 4-40% of people aged ≥65 years, and in 24-80% of people aged ≥85 years despite more than 90% of patients having recent recorded kidney function results. Using eGFR overestimated kidney function for 3-28% of those aged ≥65 years, and for 13-58% of those aged ≥85 years. Increased age predicted higher odds of having a kidney function estimate too low for recommended prescribing of the study drugs. Prescribing recommendations when kidney function is reduced are not applied for many people aged ≥65 years in primary care. Using eGFR considerably overestimates kidney function for prescribing and, therefore, creatinine clearance (Cockcroft-Gault) should be assessed when prescribing for these people. Interventions are needed to aid prescribers when kidney function is reduced. © British Journal of General Practice 2018.

CT volumetry is superior to nuclear renography for prediction of residual kidney function in living donors.

PubMed

Barbas, Andrew S; Li, Yanhong; Zair, Murtuza; Van, Julie A; Famure, Olusegun; Dib, Martin J; Laurence, Jerome M; Kim, S Joseph; Ghanekar, Anand

2016-09-01

Living kidney donor evaluation commonly includes nuclear renography to assess split kidney function and computed tomography (CT) scan to evaluate anatomy. To streamline donor workup and minimize exposure to radioisotopes, we sought to assess the feasibility of using proportional kidney volume from CT volumetry in lieu of nuclear renography. We examined the correlation between techniques and assessed their ability to predict residual postoperative kidney function following live donor nephrectomy. In a cohort of 224 live kidney donors, we compared proportional kidney volume derived by CT volumetry with split kidney function derived from nuclear renography and found only modest correlation (left kidney R(2) =26.2%, right kidney R(2) =26.7%). In a subset of 88 live kidney donors with serum creatinine measured 6 months postoperatively, we compared observed estimated glomerular filtration rate (eGFR) at 6 months with predicted eGFR from preoperative imaging. Compared to nuclear renography, CT volumetry more closely approximated actual observed postoperative eGFR for Chronic Kidney Disease Epidemiology Collaboration (J-test: P=.02, Cox-Pesaran test: P=.01) and Mayo formulas (J-test: P=.004, Cox-Pesaran test: P<.001). These observations support the use of CT volumetry for estimation of split kidney function in healthy individuals with normal kidney function and morphology. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

JBP485 improves gentamicin-induced acute renal failure by regulating the expression and function of Oat1 and Oat3 in rats

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

Guo, Xinjin; Meng, Qiang; Liu, Qi

2013-09-01

We investigated the effects of JBP485 (an anti-inflammatory dipeptide and a substrate of OAT) on regulation of the expression and function of renal Oat1 and Oat3, which can accelerate the excretion of accumulated uremic toxins (e.g. indoxyl sulfate) in the kidney to improve gentamicin-induced ARF in rats. JBP485 caused a significant decrease in the accumulation of endogenous substances (creatinine, blood urea nitrogen and indoxyl sulfate) in vivo, an increase in the excretion of exogenous compounds (lisinopril and inulin) into urine, and up-regulation of the expressions of renal Oat1 and Oat3 in the kidney tissues and slices via substrate induction. Tomore » determine the effect of JBP485 on the accelerated excretion of uremic toxins mediated by Oat1 and Oat3, the mRNA and protein expression levels of renal basolateral Oats were assessed by quantitative real-time PCR, western blot, immunohistochemical analysis and an immunofluorescence method. Gentamicin down-regulated the expression of Oats mRNA and protein in rat kidney, and these effects were reversed after administration of JBP485. In addition, JBP485 caused a significant decrease in MPO and MDA levels in the kidney, and improved the pathological condition of rat kidney. These results indicated that JBP485 improved acute renal failure by increasing the expression and function of Oat1 and Oat3, and by decreasing overoxidation of the kidney in gentamicin-induced ARF rats. - Highlights: • JBP485 could up-regulate function and expression of Oat1 and Oat3 in kidney. • Effects of JBP485 on ARF are mediated by stimulating excretion of uremic toxins. • JBP485 protected against gentamicin-induced ARF by decreasing MPO and MDA.« less

The science of Stewardship: due diligence for kidney donors and kidney function in living kidney donation--evaluation, determinants, and implications for outcomes.

PubMed

Poggio, Emilio D; Braun, William E; Davis, Connie

2009-10-01

Living kidney donor transplantation is now a common treatment for ESRD because it provides excellent outcomes to transplant recipients and is considered a safe procedure for prospective donors. The short- and long-term safety of prospective donors is paramount to the continued success of this procedure. Whereas the initial experiences with living kidney donors mostly included the healthiest, the increase in the need for organs and the changing demographic characteristics of the general population have subtly reshaped the suitability for donation. Kidney function assessment is a critical component of the evaluation of prospective donors; therefore, special emphasis is usually placed on this aspect of the evaluation. At the same time, consideration of kidney function after donation is important because it assists with the determination of renal health in donors. This review summarizes the process of predonation kidney function assessment, determinants of pre- and postdonation renal function, and, importantly, the potential implications of kidney function to the long-term outcomes of kidney donors.

Image-derived and arterial blood sampled input functions for quantitative PET imaging of the angiotensin II subtype 1 receptor in the kidney

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

Feng, Tao; Tsui, Benjamin M. W.; Li, Xin

Purpose: The radioligand {sup 11}C-KR31173 has been introduced for positron emission tomography (PET) imaging of the angiotensin II subtype 1 receptor in the kidney in vivo. To study the biokinetics of {sup 11}C-KR31173 with a compartmental model, the input function is needed. Collection and analysis of arterial blood samples are the established approach to obtain the input function but they are not feasible in patients with renal diseases. The goal of this study was to develop a quantitative technique that can provide an accurate image-derived input function (ID-IF) to replace the conventional invasive arterial sampling and test the method inmore » pigs with the goal of translation into human studies. Methods: The experimental animals were injected with [{sup 11}C]KR31173 and scanned up to 90 min with dynamic PET. Arterial blood samples were collected for the artery derived input function (AD-IF) and used as a gold standard for ID-IF. Before PET, magnetic resonance angiography of the kidneys was obtained to provide the anatomical information required for derivation of the recovery coefficients in the abdominal aorta, a requirement for partial volume correction of the ID-IF. Different image reconstruction methods, filtered back projection (FBP) and ordered subset expectation maximization (OS-EM), were investigated for the best trade-off between bias and variance of the ID-IF. The effects of kidney uptakes on the quantitative accuracy of ID-IF were also studied. Biological variables such as red blood cell binding and radioligand metabolism were also taken into consideration. A single blood sample was used for calibration in the later phase of the input function. Results: In the first 2 min after injection, the OS-EM based ID-IF was found to be biased, and the bias was found to be induced by the kidney uptake. No such bias was found with the FBP based image reconstruction method. However, the OS-EM based image reconstruction was found to reduce variance in the subsequent phase of the ID-IF. The combined use of FBP and OS-EM resulted in reduced bias and noise. After performing all the necessary corrections, the areas under the curves (AUCs) of the AD-IF were close to that of the AD-IF (average AUC ratio =1 ± 0.08) during the early phase. When applied in a two-tissue-compartmental kinetic model, the average difference between the estimated model parameters from ID-IF and AD-IF was 10% which was within the error of the estimation method. Conclusions: The bias of radioligand concentration in the aorta from the OS-EM image reconstruction is significantly affected by radioligand uptake in the adjacent kidney and cannot be neglected for quantitative evaluation. With careful calibrations and corrections, the ID-IF derived from quantitative dynamic PET images can be used as the input function of the compartmental model to quantify the renal kinetics of {sup 11}C-KR31173 in experimental animals and the authors intend to evaluate this method in future human studies.« less

Anti-Inflammatory Effect of Atorvastatin on the Kidney Graft of Living Donor Transplants.

PubMed

Fuentes-Orozco, Clotilde; Garcia-Salazar, Sara Jazmín; Gómez-Navarro, Benjamín; González-Espinoza, Eduardo; Zepeda-González, Alonso; Ramírez-Robles, Juan Narciso; Castañeda-Espinoza, Rafael; Yáñez-Sánchez, Irinea; Gálvez-Gastelum, Francisco Javier; Cervantes-Guevara, Gabino; Cervantes-Cardona, Guillermo Alonso; Contreras-Hernández, Guadalupe Ivette; Pérez-Landeros, Jacob Esau; García-Martinez, David; González-Ojeda, Alejandro

2018-06-29

BACKGROUND Recent studies have demonstrated that statins have anti-inflammatory and immunomodulatory properties, which could be considered beneficial in kidney transplantations. This study assesses the anti-inflammatory effect of atorvastatin on the kidney grafts of living donor transplants. MATERIAL AND METHODS In a randomized clinical trial, kidney donors were divided into 2 groups. The study group constituted 24 donors who received 40 mg atorvastatin, and 24 donors who received a placebo control, 4 weeks prior to transplantation. Serum C-reactive protein (CRP) levels were measured before and after atorvastatin administration. CRP and renal function of kidney recipients were measured at baseline and 1, 6, and 24 hours after transplantation. RESULTS After 4 weeks of treatment, the CRP level was 5.62±3.82 mg/dL in the control group and 3.27±0.62 mg/dL in the study group (P=0.007). Upon reperfusion, CRP levels in recipients at 1 hour were, 5.8±3.9 and 3.8±1.0 mg/dL, respectively (P=0.04). Twenty-four hours after the kidney transplantations, serum creatinine levels were 2.5±1.5 mg/dL in the study group and 3.7±2.4 mg/dL in the control group (P=0.04). CONCLUSIONS Our study suggests that the use of atorvastatin prior to allograft procurement of kidney transplant, reduces the acute kidney inflammatory burden profile, and promotes an improved kidney function recovery following transplantation.

[A case report of simultaneous liver, pancreas-duodenum, and kidney transplantation in a patient with post-hepatitic cirrhosis combined with uremia and insulin-dependent diabetes related to chronic pancreatitis].

PubMed

Wang, He; Dou, Ke-feng; Yang, Xiao-jian; Qin, Wei-jun; Zhang, Geng; Yu, Lei; Kang, Fu-xia; Chen, Shao-yang; Xiong, Li-ze; Song, Zhen-shun; Liu, Zheng-cai

2006-09-12

To study the effect of triple organ transplantation (liver, kidney, and pancreas) in patient of end-stage liver disease with renal failure and diabetes, and to explore the optimal surgical procedure. Simultaneous piggyback orthotopic heterotopic liver, pancreas-duodenum, and kidney transplantation was performed on a 43-year-old male patient with exocrine pancreatic insufficiency and insulin-dependent diabetes related to chronic pancreatitis (CP) who developed hepatic and renal failure. The pancreatic exocrine secretions were drained enterically to the jejunum. Prednisone, tacrolimus, mycophenolate mofetil, and ATG were used as immunosuppression therapy. Good liver and pancreas allograft function recovery was achieved within 7 days after the operation. And the recovery of renal allograft function was delayed. The renal allograft was removed because of break-down of renal blood flow 16 days after the transplantation. A new renal transplantation was performed at the same position. The second kidney graft recovered its normal function 3 days later. Up to the writing of this paper no acute rejection of organs and such complications as pancreatitis, thrombosis, and localized infection occurred. The patient became insulin independent with normal liver and renal function. Simultaneous piggyback orthotopic heterotopic liver, pancreas-duodenum, and kidney transplantation can be a good method for the patients with exocrine pancreatic insufficiency and insulin-dependent diabetes combined with hepatic and renal failure.

Assessing glomerular filtration rate (GFR) in critically ill patients with acute kidney injury - true GFR versus urinary creatinine clearance and estimating equations

PubMed Central

2013-01-01

Introduction Estimation of kidney function in critically ill patients with acute kidney injury (AKI), is important for appropriate dosing of drugs and adjustment of therapeutic strategies, but challenging due to fluctuations in kidney function, creatinine metabolism and fluid balance. Data on the agreement between estimating and gold standard methods to assess glomerular filtration rate (GFR) in early AKI are lacking. We evaluated the agreement of urinary creatinine clearance (CrCl) and three commonly used estimating equations, the Cockcroft Gault (CG), the Modification of Diet in Renal Disease (MDRD) and the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equations, in comparison to GFR measured by the infusion clearance of chromium-ethylenediaminetetraacetic acid (51Cr-EDTA), in critically ill patients with early AKI after complicated cardiac surgery. Methods Thirty patients with early AKI were studied in the intensive care unit, 2 to 12 days after complicated cardiac surgery. The infusion clearance for 51Cr-EDTA obtained as a measure of GFR (GFR51Cr-EDTA) was calculated from the formula: GFR (mL/min/1.73m2) = (51Cr-EDTA infusion rate × 1.73)/(arterial 51Cr-EDTA × body surface area) and compared with the urinary CrCl and the estimated GFR (eGFR) from the three estimating equations. Urine was collected in two 30-minute periods to measure urine flow and urine creatinine. Urinary CrCl was calculated from the formula: CrCl (mL/min/1.73m2) = (urine volume × urine creatinine × 1.73)/(serum creatinine × 30 min × body surface area). Results The within-group error was lower for GFR51Cr-EDTA than the urinary CrCl method, 7.2% versus 55.0%. The between-method bias was 2.6, 11.6, 11.1 and 7.39 ml/min for eGFRCrCl, eGFRMDRD, eGFRCKD-EPI and eGFRCG, respectively, when compared to GFR51Cr-EDTA. The error was 103%, 68.7%, 67.7% and 68.0% for eGFRCrCl, eGFRMDRD, eGFRCKD-EPI and eGFRCG, respectively, when compared to GFR51Cr-EDTA. Conclusions The study demonstrated poor precision of the commonly utilized urinary CrCl method for assessment of GFR in critically ill patients with early AKI, suggesting that this should not be used as a reference method when validating new methods for assessing kidney function in this patient population. The commonly used estimating equations perform poorly when estimating GFR, with high biases and unacceptably high errors. PMID:23767877

Advances in the Knowledge about Kidney Decellularization and Repopulation

PubMed Central

Destefani, Afrânio Côgo; Sirtoli, Gabriela Modenesi; Nogueira, Breno Valentim

2017-01-01

End-stage renal disease (ESRD) is characterized by the progressive deterioration of renal function that may compromise different tissues and organs. The major treatment indicated for patients with ESRD is kidney transplantation. However, the shortage of available organs, as well as the high rate of organ rejection, supports the need for new therapies. Thus, the implementation of tissue bioengineering to organ regeneration has emerged as an alternative to traditional organ transplantation. Decellularization of organs with chemical, physical, and/or biological agents generates natural scaffolds, which can serve as basis for tissue reconstruction. The recellularization of these scaffolds with different cell sources, such as stem cells or adult differentiated cells, can provide an organ with functionality and no immune response after in vivo transplantation on the host. Several studies have focused on improving these techniques, but until now, there is no optimal decellularization method for the kidney available yet. Herein, an overview of the current literature for kidney decellularization and whole-organ recellularization is presented, addressing the pros and cons of the actual techniques already developed, the methods adopted to evaluate the efficacy of the procedures, and the challenges to be overcome in order to achieve an optimal protocol. PMID:28620603

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.

The Relationship Between Pulmonary Emphysema and Kidney Function in Smokers

PubMed Central

Chandra, Divay; Stamm, Jason A.; Palevsky, Paul M.; Leader, Joseph K.; Fuhrman, Carl R.; Zhang, Yingze; Bon, Jessica; Duncan, Steven R.; Branch, Robert A.; Weissfeld, Joel; Gur, David; Gladwin, Mark T.

2012-01-01

Background: It has been reported that the prevalence of kidney dysfunction may be increased in patients exposed to tobacco with airflow obstruction. We hypothesized that kidney dysfunction would associate with emphysema rather than with airflow obstruction measured by the FEV1. Methods: Five hundred eight current and former smokers completed a chest CT scan, pulmonary function tests, medical questionnaires, and measurement of serum creatinine. Glomerular filtration rates (eGFRs) were estimated using the method of the Chronic Kidney Disease Epidemiology Collaboration. Quantitative determinants of emphysema and airway dimension were measured from multidetector chest CT scans. Results: The mean age was 66 ± 7 years, and mean eGFR was 101 ± 22 mL/min/1.73 m2. Univariate and multivariate analysis showed a significant association between radiographically measured emphysema and eGFR: Participants with 10% more emphysema had an eGFR that was lower by 4.4 mL/min/1.73 m2 (P = .01), independent of airflow obstruction (FEV1), age, sex, race, height, BMI, diabetes mellitus, hypertension, coronary artery disease, patient-reported dyspnea, pack-years of smoking, and current smoking. There was no association between eGFR and either FEV1 or quantitative CT scan measures of airway dimension. Conclusions: More severe emphysema, rather than airflow obstruction, is associated with kidney dysfunction in tobacco smokers, independent of common risk factors for kidney disease. This finding adds to recent observations of associations between emphysema and comorbidities of COPD, including osteoporosis and lung cancer, which are independent of the traditional measure of reduced FEV1. The mechanisms and clinical implications of kidney dysfunction in patients with emphysema need further investigation. PMID:22459775

Ex-vivo machine perfusion for kidney preservation.

PubMed

Hamar, Matyas; Selzner, Markus

2018-06-01

Machine perfusion is a novel strategy to decrease preservation injury, improve graft assessment, and increase organ acceptance for transplantation. This review summarizes the current advances in ex-vivo machine-based kidney preservation technologies over the last year. Ex-vivo perfusion technologies, such as hypothermic and normothermic machine perfusion and controlled oxygenated rewarming, have gained high interest in the field of organ preservation. Keeping kidney grafts functionally and metabolically active during the preservation period offers a unique chance for viability assessment, reconditioning, and organ repair. Normothermic ex-vivo kidney perfusion has been recently translated into clinical practice. Preclinical results suggest that prolonged warm perfusion appears superior than a brief end-ischemic reconditioning in terms of renal function and injury. An established standardized protocol for continuous warm perfusion is still not available for human grafts. Ex-vivo machine perfusion represents a superior organ preservation method over static cold storage. There is still an urgent need for the optimization of the perfusion fluid and machine technology and to identify the optimal indication in kidney transplantation. Recent research is focusing on graft assessment and therapeutic strategies.

Regional cyst concentration as a prognostic biomarker for polycystic kidney disease

NASA Astrophysics Data System (ADS)

Warner, Joshua D.; Irazabal, Maria V.; Torres, Vicente E.; King, Bernard F.; Erickson, Bradley J.

2014-03-01

Polycystic kidney disease (PKD) is a major cause of renal failure. Despite recent advances in understanding the biochemistry and genetics of PKD, the functional mechanisms underpinning the declines in renal function observed in the disorder are not well established. No studies investigating the distribution of cysts within polycystic kidneys exist. This work introduces regional cyst concentration as a new biomarker for evaluation of patients suffering from PKD. We derive a method to define central and peripheral regions of the kidney, approximating the anatomical division between cortex and medulla, and apply it to two cohorts of ten patients with early/mild or late/severe disease. Our results from the late/severe cohort show peripheral cyst concentration correlates with the current standard PKD biomarker, total kidney volume (TKV), signi cantly better than central cyst concentration (p < 0.05). We also find that cyst concentration was globally increased in the late/severe cohort (p << 0.01) compared to the early/mild cohort, for both central and peripheral regions. These findings show cysts in PKD are not distributed homogeneously throughout the renal tissues.

Measurements of renal shear wave velocities in chronic kidney disease patients.

PubMed

Sasaki, Yutaka; Hirooka, Yoshiki; Kawashima, Hiroki; Ishikawa, Takuya; Takeshita, Kyosuke; Goto, Hidemi

2018-07-01

Background Chronic kidney disease (CKD) patients have advanced glomerulosclerosis and renal interstitial fibrosis. Shear wave elastography (SWE) is useful to diagnose liver fibrosis. However, there are few data available regarding evaluation of kidney function on the use of SWE. Purpose To assess the utility of SWE by evaluating the correlation between renal function and renal elasticity using SWE. Material and Methods A total of 187 participants who had available serum creatinine levels and also underwent SWE of the kidney using a transabdominal ultrasonography were recruited at Nagoya University Hospital. We measured the depth of the shear wave (SW) in the right and left kidneys and calculated the measurement success rates. The glomerular filtration rate (GFR) classification and shear wave value (SWV) were compared. Results The success rates of the right and left kidneys were 93.6% and 71.6%, respectively. Based on these results, the correlation between GFR classification and SWV were analyzed in only the right kidneys because the success rates and the number of enrolled patients were low for the left kidney. There were significant differences found between G1 and G3a, G2 and G3a, G3a and G3b, G3a and G4, and G3a and G5. SWV significantly negatively and positively correlated with the G2-G3a and G3a-G3b classifications. Conclusion There is no correlation between renal function and SW. However, we can diagnose the progression to the CKD stages G3a and G3b by observing the changes over time using the SWV.

Estimation of single-kidney glomerular filtration rate without exogenous contrast agent.

PubMed

He, Xiang; Aghayev, Ayaz; Gumus, Serter; Ty Bae, K

2014-01-01

Measurement of single-kidney filtration fraction and glomerular filtration rate (GFR) without exogenous contrast is clinically important to assess renal function and pathophysiology, especially for patients with comprised renal function. The objective of this study is to develop a novel MR-based tool for noninvasive quantification of renal function using conventional MR arterial spin labeling water as endogenous tracer. The regional differentiation of the arterial spin labeling water between the glomerular capsular space and the renal parenchyma was characterized and measured according to their MR relaxation properties (T1ρ or T2 ), and applied to the estimation of filtration fraction and single-kidney GFR. The proposed approach was tested to quantify GFR in healthy volunteers at baseline and after a protein-loading challenge. Biexponential decay of the cortical arterial spin labeling water MR signal was observed. The major component decays the same as parenchyma water; the minor component decays much slower as expected from glomerular ultra-filtrates. The mean single-kidney GFR was estimated to be 49 ± 9 mL/min at baseline and increased by 28% after a protein-loading challenge. We developed an arterial spin labeling-based MR imaging method that allows us to estimate renal filtration fraction and singe-kidney GFR without use of exogenous contrast. Copyright © 2013 Wiley Periodicals, Inc.

Creatinine clearance test

MedlinePlus

Serum creatinine clearance; Kidney function - creatinine clearance; Renal function - creatinine clearance ... the body entirely by the kidneys. If kidney function is abnormal, creatinine level increases in the blood ...

Transport of organic anions and cations in murine embryonic kidney development and in serially-reaggregated engineered kidneys

PubMed Central

Lawrence, Melanie L.; Chang, C-Hong; Davies, Jamie A.

2015-01-01

Recent advances in renal tissue engineering have shown that dissociated, early renogenic tissue from the developing embryo can self-assemble into morphologically accurate kidney-like organs arranged around a central collecting duct tree. In order for such self-assembled kidneys to be useful therapeutically or as models for drug screening, it is necessary to demonstrate that they are functional. One of the main functional characteristics of mature kidneys is transport of organic anions and cations into and out of the proximal tubule. Here, we show that the transport function of embryonic kidneys allowed to develop in culture follows a developmental time-course that is comparable to embryonic kidney development in vivo. We also demonstrate that serially-reaggregated engineered kidneys can transport organic anions and cations through specific uptake and efflux channels. These results support the physiological relevance of kidneys grown in culture, a commonly used model for kidney development and research, and suggest that serially-reaggregated kidneys self-assembled from separated cells have some functional characteristics of intact kidneys. PMID:25766625

Kidney function monitoring and nonvitamin K oral anticoagulant dosage in atrial fibrillation.

PubMed

Andreu Cayuelas, Jose Manuel; Caro Martínez, Cesar; Flores Blanco, Pedro Jose; Elvira Ruiz, Gines; Albendin Iglesias, Helena; Cerezo Manchado, Juan Jose; Bailen Lorenzo, Jose Luis; Januzzi, James L; García Alberola, Arcadio; Manzano-Fernández, Sergio

2018-06-01

Clinical practice guidelines recommend regular kidney function monitoring in atrial fibrillation patients on nonvitamin K oral anticoagulants (NOAC); however, information regarding compliance with these recommendations in daily life conditions is scarce. We sought to determine the compliance with kidney function monitoring recommendations in nonvalvular atrial fibrillation (NVAF) patients starting NOAC and its implication on the appropriateness of NOAC dosage. This study involves the retrospective analysis of a multicentre registry including consecutive NVAF patients who started NOAC (n = 692). Drug dosage changes and serum creatinine determinations were recorded during 1-year follow-up. European Heart Rhythm Association criteria were used to define the appropriateness of kidney function monitoring as well as adequate NOAC dosage. During the follow-up (334 ± 89 days), the compliance with kidney function monitoring recommendations was 61% (n = 425). After multivariate adjustment, age (OR × year: 0.92 (CI 95%: 0.89-0.95) P < .001), creatinine clearance (OR × mL/min: 1.02 (CI 95%: 1.01-1.03) P < .001) and adequate NOAC dosage at baseline (OR: 1.54 (CI 95%: 1.06-2.23), P = .024) were independent predictors of appropriate kidney function monitoring. Compliance with kidney function monitoring recommendations was independently associated with change to appropriate NOAC dose after 1 year (OR: 2.80 (CI 95%: 1.01-7.80), P = .049). Noncompliance with kidney function monitoring recommendations is common in NVAF patients starting NOAC, especially in elderly patients with kidney dysfunction. Compliance with kidney function monitoring recommendations was associated with adequate NOAC dosage at 1-year follow-up. Further studies are warranted to evaluate the implication of kidney function monitoring on prognosis. © 2018 Stichting European Society for Clinical Investigation Journal Foundation.

Evaluating an alternative method for rapid urinary creatinine determination

EPA Science Inventory

Creatinine (CR) is an endogenously-produced chemical routinely assayed in urine specimens to assess kidney function, sample dilution. The industry-standard method for CR determination, known as the kinetic Jaffe (KJ) method, relies on an exponential rate of a colorimetric change,...

MR measures of renal perfusion, oxygen bioavailability and total renal blood flow in a porcine model: noninvasive regional assessment of renal function.

PubMed

Wentland, Andrew L; Artz, Nathan S; Fain, Sean B; Grist, Thomas M; Djamali, Arjang; Sadowski, Elizabeth A

2012-01-01

Magnetic resonance imaging (MRI) may be a useful adjunct to current methods of evaluating renal function. MRI is a noninvasive imaging modality that has the ability to evaluate the kidneys regionally, which is lacking in current clinical methods. Other investigators have evaluated renal function with MRI-based measurements, such as with techniques to measure cortical and medullary perfusion, oxygen bioavailability and total renal blood flow (TRBF). However, use of all three techniques simultaneously, and therefore the relationships between these MRI-derived functional parameters, have not been reported previously. To evaluate the ability of these MRI techniques to track changes in renal function, we scanned 11 swine during a state of hyperperfusion with acetylcholine and a saline bolus and subsequently scanned during a state of hypoperfusion with the prolonged use of isoflurane anesthesia. For each time point, measurements of perfusion, oxygen bioavailability and TRBF were acquired. Measurements of perfusion and oxygen bioavailability were compared with measurements of TRBF for all swine across all time points. Cortical perfusion, cortical oxygen bioavailability, medullary oxygen bioavailability and TRBF significantly increased with the acetylcholine challenge. Cortical perfusion, medullary perfusion, cortical oxygen bioavailability and TRBF significantly decreased during isoflurane anesthesia. Cortical perfusion (Spearman's correlation coefficient = 0.68; P < 1 × 10(-6)) and oxygen bioavailability (Spearman's correlation coefficient = -0.60; P < 0.0001) correlated significantly with TRBF, whereas medullary perfusion and oxygen bioavailability did not correlate with TRBF. Our results demonstrate expected changes given the pharmacologically induced changes in renal function. Maintenance of the medullary oxygen bioavailability in low blood flow states may reflect the autoregulation particular to this region of the kidney. The ability to non-invasively measure all three parameters of kidney function in a single MRI examination and to evaluate the relationships between these functional parameters is potentially useful for evaluating the state of the human kidneys in situ in future studies.

Transplantation outcomes in primary hyperoxaluria.

PubMed

Bergstralh, E J; Monico, C G; Lieske, J C; Herges, R M; Langman, C B; Hoppe, B; Milliner, D S

2010-11-01

Optimal transplantation strategies are uncertain in primary hyperoxaluria (PH) due to potential for recurrent oxalosis. Outcomes of different transplantation approaches were compared using life-table methods to determine kidney graft survival among 203 patients in the International Primary Hyperoxaluria Registry. From 1976-2009, 84 kidney alone (K) and combined kidney and liver (K + L) transplants were performed in 58 patients. Among 58 first kidney transplants (32 K, 26 K + L), 1-, 3- and 5-year kidney graft survival was 82%, 68% and 49%. Renal graft loss occurred in 26 first transplants due to oxalosis in ten, chronic allograft nephropathy in six, rejection in five and other causes in five. Delay in PH diagnosis until after transplant favored early graft loss (p = 0.07). K + L had better kidney graft outcomes than K with death-censored graft survival 95% versus 56% at 3 years (p = 0.011). Among 29 year 2000-09 first transplants (24 K + L), 84% were functioning at 3 years compared to 55% of earlier transplants (p = 0.05). At 6.8 years after transplantation, 46 of 58 patients are living (43 with functioning grafts). Outcomes of transplantation in PH have improved over time, with recent K + L transplantation highly successful. Recurrent oxalosis accounted for a minority of kidney graft losses. ©2010 The Authors Journal compilation©2010 The American Society of Transplantation and the American Society of Transplant Surgeons.

Aortoiliac aneurysm with congenital right pelvic kidney.

PubMed

Date, Kazuma; Okada, Shuuichi; Ezure, Masahiko; Takihara, Hitomi; Okonogi, Shuuichi; Hasegawa, Yutaka; Sato, Yasushi; Kaneko, Tatsuo

2015-05-01

The association of congenital pelvic kidney with abdominal aortoiliac aneurysm is an extremely rare clinical finding. Previous reports have described various methods of aneurysm repair with successful preservation of the function of pelvic kidney. However, to our knowledge, reconstruction of more than two renal arteries has not been established. We report a case of abdominal aortic aneurysm complicated by congenital right pelvic kidney in a 72-year-old man. Computed tomography (CT) revealed an abdominal aortic aneurysm with a maximum diameter of 54 mm and a right common iliac aneurysm of 45 mm. In addition, he had a congenital right pelvic kidney and CT angiography identified three right pelvic renal arteries. The upper artery originated from the bifurcation of the terminal aorta and the lower two originated from the right common iliac artery. Three-dimensional CT was helpful for the accurate planning of the operation. Open surgical repair of the aortoiliac aneurysm with a Dacron bifurcated graft replacement was decided and reimplantation of all three right pelvic kidney arteries to the right limb of the graft was also performed. For renal preservation, the right pelvic kidney arteries were perfused with cold Ringer's lactate using a rapid infusion pump and coronary perfusion cannula. The patient's postoperative course was uneventful, and worsening of renal function was not observed. The perfusion of renal arteries with cold Ringer's solution was thought to be a simple and appropriate procedure for renal protection.

Correlation of Point Shear Wave Velocity and Kidney Function in Chronic Kidney Disease.

PubMed

Grosu, Iulia; Bob, Flaviu; Sporea, Ioan; Popescu, Alina; Şirli, Roxana; Schiller, Adalbert

2018-04-24

Point shear wave elastography is a quantitative ultrasound-based imaging method used in the assessment of renal disease. Among point shear wave elastographic options, 2 techniques have been studied considerably: Virtual Touch quantification (VTQ; Siemens AG, Erlangen, Germany) and ElastPQ (EPQ; Philips Healthcare, Bothell, WA). Both rely on the tissue response to an acoustic beam generated by the ultrasound transducer. The data on renal VTQ are more extensive, whereas EPQ has been used less thus far in the assessment of the kidneys. This study aimed to evaluate the performance of EPQ in the kidney and compare it with VTQ. We studied 124 participants using EPQ: 22 with no renal disease and 102 with chronic kidney disease (CKD). Ninety-one were studied with both the EPQ and VTQ methods. We obtained 5 valid measurements in each kidney, expressed in meters per second. The mean kidney stiffness measurements ± SD obtained with EPQ in the healthy control group were as follows: right kidney, 1.23 ± 0.33 m/s; and left kidney, 1.26 ± 0.32 m/s (P = .6). In the patients with CKD (all stages), the mean kidney stiffness measurements obtained were significantly lower: right kidney, 1.09 ± 0.39 m/s; and left kidney, 1.04 ± 0.38 m/s (P = .4). We observed that, similar to VTQ, EPQ values decreased with CKD progression, based on analysis of variance results using different CKD stages. From a receiver operating characteristic curve analysis, the cutoff value for an estimated glomerular filtration rate of less than 45 mL/min was 1.24 m/s, and the value for an estimated glomerular filtration rate of less than 30 mL/min was 1.07 m/s. When using EPQ, the kidney shear wave velocity is decreased in patients with CKD, an observation similar to that obtained by using the VTQ method. © 2018 by the American Institute of Ultrasound in Medicine.

Arterial flow regulator enables transplantation and growth of human fetal kidneys in rats.

PubMed

Chang, N K; Gu, J; Gu, S; Osorio, R W; Concepcion, W; Gu, E

2015-06-01

Here we introduce a novel method of transplanting human fetal kidneys into adult rats. To overcome the technical challenges of fetal-to-adult organ transplantation, we devised an arterial flow regulator (AFR), consisting of a volume adjustable saline-filled cuff, which enables low-pressure human fetal kidneys to be transplanted into high-pressure adult rat hosts. By incrementally withdrawing saline from the AFR over time, blood flow entering the human fetal kidney was gradually increased until full blood flow was restored 30 days after transplantation. Human fetal kidneys were shown to dramatically increase in size and function. Moreover, rats which had all native renal mass removed 30 days after successful transplantation of the human fetal kidney were shown to have a mean survival time of 122 days compared to 3 days for control rats that underwent bilateral nephrectomy without a prior human fetal kidney transplant. These in vivo human fetal kidney models may serve as powerful platforms for drug testing and discovery. © Copyright 2015 The American Society of Transplantation and the American Society of Transplant Surgeons.

Ipsilateral renal function preservation after robot-assisted partial nephrectomy (RAPN): an objective analysis using mercapto-acetyltriglycine (MAG3) renal scan data and volumetric assessment.

PubMed

Zargar, Homayoun; Akca, Oktay; Autorino, Riccardo; Brandao, Luis Felipe; Laydner, Humberto; Krishnan, Jayram; Samarasekera, Dinesh; Stein, Robert J; Kaouk, Jihad H

2015-05-01

To objectively assess ipsilateral renal function (IRF) preservation and factors influencing it after robot-assisted partial nephrectomy (RAPN). Our database was queried to identify patients who had undergone RAPN from 2007 to 2013 and had complete pre- and postoperative mercapto-acetyltriglycine (MAG3) renal scan assessment. The estimated glomerular filtration rate (eGFR) for the operated kidney was calculated by multiplying the percentage of contribution from the renal scan by the total eGFR. IRF preservation was defined as a ratio of the postoperative eGFR for the operated kidney to the preoperative eGFR for the operated kidney. The percentage of total eGFR preservation was calculated in the same manner (postoperative eGFR/preoperative eGFR × 100). The amount of healthy rim of renal parenchyma removed was assessed by deducting the volume of tumour from the volume of the PN specimen assessed on pathology. Multivariable linear regression was used for analysis. In all, 99 patients were included in the analysis. The overall median (interquartile range) total eGFR preservation and IRF preservation for the operated kidney was 83.83 (75.2-94.1)% and 72 (60.3-81)%, respectively (P < 0.01). On multivariable analysis, volume of healthy rim of renal parenchyma removed, warm ischaemia time (WIT) > 30 min, body mass index (BMI) and operated kidney preoperative eGFR were predictive of IRF preservation. Using total eGFR tends to overestimate the degree of renal function preservation after RAPN. This is particularly relevant when studying factors affecting functional outcomes after nephron-sparing surgery. IRF may be a more precise assessment method in this setting. Operated kidney baseline renal function, BMI, WIT >30 min, and amount of resected healthy renal parenchyma represent the factors with a significant impact on the IRF preservation. RAPN provides significant preservation of renal function as shown by objective assessment criteria. © 2014 The Authors. BJU International © 2014 BJU International.

Challenges and opportunities for stem cell therapy in patients with chronic kidney disease

PubMed Central

Hickson, LaTonya J.; Eirin, Alfonso; Lerman, Lilach O.

2016-01-01

Chronic kidney disease (CKD) is a global healthcare burden affecting billions of individuals worldwide. The kidney has limited regenerative capacity from chronic insults, and for the most common causes of CKD, no effective treatment exists to prevent progression to end-stage kidney failure. Therefore, novel interventions, such as regenerative cell-based therapies, need to be developed for CKD. Given the risk of allosensitization, autologous transplantation of cells to boost regenerative potential is preferred. Therefore, verification of cell function and vitality in CKD patients is imperative. Two cell types have been most commonly applied in regenerative medicine. Endothelial progenitor cells contribute to neovasculogenesis primarily through paracrine angiogenic activity and partly by differentiation into mature endothelial cells in situ. Mesenchymal stem cells also exert paracrine effects, including pro-angiogenic, anti-inflammatory, and anti-fibrotic activity. However, in CKD, multiple factors may contribute to reduced cell function, including older age, coexisting cardiovascular disease, diabetes, chronic inflammatory states, and uremia, which may limit the effectiveness of an autologous cell-based therapy approach. This review highlights current knowledge on stem and progenitor cell function and vitality, aspects of the uremic milieu that may serve as a barrier to therapy, and novel methods to improve stem cell function for potential transplantation. PMID:26924058

Challenges and opportunities for stem cell therapy in patients with chronic kidney disease.

PubMed

Hickson, LaTonya J; Eirin, Alfonso; Lerman, Lilach O

2016-04-01

Chronic kidney disease (CKD) is a global health care burden affecting billions of individuals worldwide. The kidney has limited regenerative capacity from chronic insults, and for the most common causes of CKD, no effective treatment exists to prevent progression to end-stage kidney failure. Therefore, novel interventions, such as regenerative cell-based therapies, need to be developed for CKD. Given the risk of allosensitization, autologous transplantation of cells to boost regenerative potential is preferred. Therefore, verification of cell function and vitality in CKD patients is imperative. Two cell types have been most commonly applied in regenerative medicine. Endothelial progenitor cells contribute to neovasculogenesis primarily through paracrine angiogenic activity and partly by differentiation into mature endothelial cells in situ. Mesenchymal stem cells also exert paracrine effects, including proangiogenic, anti-inflammatory, and antifibrotic activity. However, in CKD, multiple factors may contribute to reduced cell function, including older age, coexisting cardiovascular disease, diabetes, chronic inflammatory states, and uremia, which may limit the effectiveness of an autologous cell-based therapy approach. This Review highlights current knowledge on stem and progenitor cell function and vitality, aspects of the uremic milieu that may serve as a barrier to therapy, and novel methods to improve stem cell function for potential transplantation. Copyright © 2016 International Society of Nephrology. Published by Elsevier Inc. All rights reserved.

Low-level cadmium exposure and effects on kidney function

PubMed Central

Wallin, Maria; Sallsten, Gerd; Lundh, Thomas; Barregard, Lars

2014-01-01

Objectives The nephrotoxicity of cadmium at low levels of exposure, measured by urinary cadmium, has recently been questioned since co-excretion of cadmium and proteins may have causes other than cadmium toxicity. The aim of this study was to explore the relation between kidney function and low or moderate cadmium levels, measured directly in kidney biopsies. Methods We analysed cadmium in kidney biopsies (K-Cd), blood (B-Cd) and urine (U-Cd) from 109 living kidney donors in a cross-sectional study. We measured glomerular filtration rate (GFR), cystatin C in serum, albumin, β-2-microglobulin (B2M), retinol-binding protein (RBP), α-1-microglobulin (A1M), N-acetyl-β-d-glucosaminidase and kidney injury molecule 1 (KIM-1) in 24 h and overnight urine. Results We found significant positive associations between A1M excretion and K-Cd in multiple regression models including age, sex, weight, smoking and urinary flow rate. This association was also present in never-smokers. A1M was also positively associated with B-Cd and U-Cd. GFR and the other biomarkers of kidney function were not associated with K-Cd. GFR estimated from serum cystatin C showed a very poor correlation with measured GFR. KIM-1, RBP and possibly albumin were positively associated with U-Cd, but only in overnight urine. No associations were found with B2M. Conclusions Our results suggest that A1M in urine is a sensitive biomarker for effects of low-level cadmium exposure. A few associations between other renal biomarkers and U-Cd, but not K-Cd, were probably caused by physiological co-excretion or chance. PMID:25286916

Predonation Volume of Future Remnant Cortical Kidney Helps Predict Postdonation Renal Function in Live Kidney Donors.

PubMed

Fananapazir, Ghaneh; Benzl, Robert; Corwin, Michael T; Chen, Ling-Xin; Sageshima, Junichiro; Stewart, Susan L; Troppmann, Christoph

2018-07-01

Purpose To determine whether the predonation computed tomography (CT)-based volume of the future remnant kidney is predictive of postdonation renal function in living kidney donors. Materials and Methods This institutional review board-approved, retrospective, HIPAA-compliant study included 126 live kidney donors who had undergone predonation renal CT between January 2007 and December 2014 as well as 2-year postdonation measurement of estimated glomerular filtration rate (eGFR). The whole kidney volume and cortical volume of the future remnant kidney were measured and standardized for body surface area (BSA). Bivariate linear associations between the ratios of whole kidney volume to BSA and cortical volume to BSA were obtained. A linear regression model for 2-year postdonation eGFR that incorporated donor age, sex, and either whole kidney volume-to-BSA ratio or cortical volume-to-BSA ratio was created, and the coefficient of determination (R 2 ) for the model was calculated. Factors not statistically additive in assessing 2-year eGFR were removed by using backward elimination, and the coefficient of determination for this parsimonious model was calculated. Results Correlation was slightly better for cortical volume-to-BSA ratio than for whole kidney volume-to-BSA ratio (r = 0.48 vs r = 0.44, respectively). The linear regression model incorporating all donor factors had an R 2 of 0.66. The only factors that were significantly additive to the equation were cortical volume-to-BSA ratio and predonation eGFR (P = .01 and P < .01, respectively), and the final parsimonious linear regression model incorporating these two variables explained almost the same amount of variance (R 2 = 0.65) as did the full model. Conclusion The cortical volume of the future remnant kidney helped predict postdonation eGFR at 2 years. The cortical volume-to-BSA ratio should thus be considered for addition as an important variable to living kidney donor evaluation and selection guidelines. © RSNA, 2018.

Milrinone Dosing Issues in Critically Ill Children With Kidney Injury: A Review.

PubMed

Gist, Katja M; Goldstein, Stuart L; Joy, Melanie S; Vinks, Alexander A

2016-02-01

Milrinone is an inotropic drug used in a variety of clinical settings in adults and children. The efficacy of milrinone in pediatric low-cardiac output syndrome after cardiac surgery is reported. Its primary route of removal from the body is through the kidney as unchanged drug in the urine. Milrinone is not known to be efficiently removed by extracorporeal dialytic therapies and thus has the potential to cause serious adverse effects and potentially worsens renal function in patients experiencing acute kidney injury (AKI). AKI is an important public health issue that is associated with increased morbidity, mortality, and cost. It is a known risk factor for the development of chronic kidney disease. There are no specific therapies to mitigate AKI once it has developed, and interventions are focused on supportive care and dose adjustment of medications. Estimating glomerular filtration rate based on height and serum creatinine is the most commonly used clinical method for assessing kidney function and modification of medication doses. The purpose of this review is to discuss our current understanding of milrinone pharmacokinetics and pharmacodynamics in children with AKI and to describe the potential use of urinary biomarkers to guide therapeutic decision making for milrinone dosing.

Prevalence of chronic kidney disease and its determinants in coronary heart disease patients in 24 European countries: Insights from the EUROASPIRE IV survey of the European Society of Cardiology.

PubMed

Wagner, Martin; Wanner, Christoph; Kotseva, Kornelia; Wood, David; De Bacquer, Dirk; Rydén, Lars; Störk, Stefan; Heuschmann, Peter U

2017-07-01

Aims Chronic kidney disease (CKD) is associated with the development and progression of coronary heart disease (CHD), in addition to classic cardiovascular risk factors. We analysed the prevalence of CKD in CHD patients from 24 European countries in the ambulatory setting and in a preceding hospital stay for CHD (index). Methods and results A total of 7998 EUROASPIRE IV participants (median 65 years of age, 76% male) attended a study visit 6-36 months after the index hospitalisation. CKD was classified according to stages of estimated glomerular filtration rate (eGFR) and albuminuria (urinary albumin/creatinine ratio). In stable CHD conditions (study visit), 17.3% had CKD (eGFR <60 mL/min/1.73 m 2 ) with variation among participating countries (range 13.1-26.4%). A further 12% presented with preserved eGFR but significant albuminuria. During the hospital stay due to a coronary event, impaired kidney function was observed in 17.6% (range 7.5-38.2%). Risk factors for impaired kidney function included older age, female gender, classic cardiovascular (CV) risk factors, details of CHD history and congestive heart failure (multivariate regression). Of all patients, 38.9% had declined, 31.3% were stable and 29.8% had improved kidney function between hospital discharge and the study visit, dependent on age, gender, CV risk factors, CHD history and cardiac dysfunction (multivariate regression). Conclusions Every fifth CHD patient had CKD, while every tenth exhibited albuminuria as the sole indicator of kidney damage. These subjects are at increased risk of progression of CKD and CHD complications. After hospital stays due to CHD, there is potential of recovery of kidney function, but our findings underline the importance of identifying patients who are at high risk of developing CKD in order to counteract disease progression.

Comparison of the long-term outcomes of kidney transplantation: USA versus Spain

PubMed Central

Ojo, Akinlolu O.; Morales, José María; González-Molina, Miguel; Steffick, Diane E.; Luan, Fu L.; Merion, Robert M.; Ojo, Tammy; Moreso, Francesc; Arias, Manuel; Campistol, Josep María; Hernandez, Domingo; Serón, Daniel

2013-01-01

Background The long-term outcomes of kidney transplantation are suboptimal because many patients lose their allografts or experience premature death. Cross-country comparisons of long-term outcomes of kidney transplantation may provide insight into factors contributing to premature graft failure and death. We evaluated the rates of late graft failure and death among US and Spanish kidney recipients. Methods This is a cohort study of US (n = 9609) and Spanish (n = 3808) patients who received a deceased donor kidney transplant in 1990, 1994, 1998 or 2002 and had a functioning allograft 1 year after transplantation with follow-up through September 2006. Ten-year overall and death-censored graft survival and 10-year overall recipient survival and death with graft function (DWGF) were estimated with multivariate Cox models. Results Among recipients alive with graft function 1 year after transplant, the 10-year graft survival was 71.3% for Spanish and 53.4% for US recipients (P < 0.001). The 10-year, death-censored graft survival was 75.6 and 76.0% for Spanish and US recipients, respectively (P = 0.73). The 10-year recipient survival was 86.2% for Spanish and 67.4% for US recipients (P < 0.001). In recipients with diabetes as the cause of ESRD, the adjusted DWGF rates at 10 years were 23.9 and 53.8 per 1000 person-years for Spanish and US recipients, respectively (P < 0.001). Among recipients whose cause of ESRD was not diabetes mellitus, the adjusted 10-year DWGF rates were 11.0 and 25.4 per 1000 person-years for Spanish and US recipients, respectively. Conclusions US kidney transplant recipients had more than twice the long-term hazard of DWGF compared with Spanish kidney transplant recipients and similar levels of death-censored graft function. Pre-transplant medical care, comorbidities, such as cardiovascular disease, and their management in each country's health system are possible explanations for the differences between the two countries. PMID:22759384

Application of the statistical process control method for prospective patient safety monitoring during the learning phase: robotic kidney transplantation with regional hypothermia (IDEAL phase 2a-b).

PubMed

Sood, Akshay; Ghani, Khurshid R; Ahlawat, Rajesh; Modi, Pranjal; Abaza, Ronney; Jeong, Wooju; Sammon, Jesse D; Diaz, Mireya; Kher, Vijay; Menon, Mani; Bhandari, Mahendra

2014-08-01

Traditional evaluation of the learning curve (LC) of an operation has been retrospective. Furthermore, LC analysis does not permit patient safety monitoring. To prospectively monitor patient safety during the learning phase of robotic kidney transplantation (RKT) and determine when it could be considered learned using the techniques of statistical process control (SPC). From January through May 2013, 41 patients with end-stage renal disease underwent RKT with regional hypothermia at one of two tertiary referral centers adopting RKT. Transplant recipients were classified into three groups based on the robotic training and kidney transplant experience of the surgeons: group 1, robot trained with limited kidney transplant experience (n=7); group 2, robot trained and kidney transplant experienced (n=20); and group 3, kidney transplant experienced with limited robot training (n=14). We employed prospective monitoring using SPC techniques, including cumulative summation (CUSUM) and Shewhart control charts, to perform LC analysis and patient safety monitoring, respectively. Outcomes assessed included post-transplant graft function and measures of surgical process (anastomotic and ischemic times). CUSUM and Shewhart control charts are time trend analytic techniques that allow comparative assessment of outcomes following a new intervention (RKT) relative to those achieved with established techniques (open kidney transplant; target value) in a prospective fashion. CUSUM analysis revealed an initial learning phase for group 3, whereas groups 1 and 2 had no to minimal learning time. The learning phase for group 3 varied depending on the parameter assessed. Shewhart control charts demonstrated no compromise in functional outcomes for groups 1 and 2. Graft function was compromised in one patient in group 3 (p<0.05) secondary to reasons unrelated to RKT. In multivariable analysis, robot training was significantly associated with improved task-completion times (p<0.01). Graft function was not adversely affected by either the lack of robotic training (p=0.22) or kidney transplant experience (p=0.72). The LC and patient safety of a new surgical technique can be assessed prospectively using CUSUM and Shewhart control chart analytic techniques. These methods allow determination of the duration of mentorship and identification of adverse events in a timely manner. A new operation can be considered learned when outcomes achieved with the new intervention are at par with outcomes following established techniques. Statistical process control techniques allowed for robust, objective, and prospective monitoring of robotic kidney transplantation and can similarly be applied to other new interventions during the introduction and adoption phase. Copyright © 2014 European Association of Urology. Published by Elsevier B.V. All rights reserved.

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.

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.

Association of pulse wave velocity and pulse pressure with decline in kidney function.

PubMed

Kim, Chang Seong; Kim, Ha Yeon; Kang, Yong Un; Choi, Joon Seok; Bae, Eun Hui; Ma, Seong Kwon; Kim, Soo Wan

2014-05-01

The association between arterial stiffness and decline in kidney function in patients with mild to moderate chronic kidney disease (CKD) is not well established. This study investigated whether pulse wave velocity (PWV) and pulse pressure (PP) are independently associated with glomerular filtration rate (GFR) and rapid decline in kidney function in early CKD. Carotid femoral PWV (cfPWV), brachial-ankle PWV (baPWV), and PP were measured in a cohort of 913 patients (mean age, 63±10 years; baseline estimated GFR, 84±18 mL/min/1.73 m(2) ). Estimated GFR was measured at baseline and at follow-up. The renal outcome examined was rapid decline in kidney function (estimated GFR loss, >3 mL/min/1.73 m(2) per year). The median follow-up duration was 3.2 years. Multivariable adjusted linear regression model indicated that arterial PWV (both cfPWV and baPWV) and PP increased as estimated GFR declined, but neither was associated with kidney function after adjustment for various covariates. Multivariable logistic regression analysis found that cfPWV and baPWV were not associated with rapid decline in kidney function (odds ratio [OR], 1.39, 95% confidence interval [CI], 0.41-4.65; OR, 2.51, 95% CI, 0.66-9.46, respectively), but PP was (OR, 1.22, 95% CI, 1.01-1.48; P=.045). Arterial stiffness assessed using cfPWV and baPWV was not correlated with lower estimated GFR and rapid decline in kidney function after adjustment for various confounders. Thus, PP is an independent risk factor for rapid decline in kidney function in populations with relatively preserved kidney function (estimated GFR ≥30 mL/min/1.73 m(2) ). ©2014 Wiley Periodicals, Inc.

Thyroid function, reduced kidney function and incident chronic kidney disease in a community-based population: the Atherosclerosis Risk in Communities study.

PubMed

Schultheiss, Ulla T; Daya, Natalie; Grams, Morgan E; Seufert, Jochen; Steffes, Michael; Coresh, Josef; Selvin, Elizabeth; Köttgen, Anna

2017-11-01

Reduced kidney function is a common public health problem that increases risk for a wide variety of adverse outcomes, making the identification of potentially modifiable factors associated with the development of incident chronic kidney disease (CKD) important. Alterations in the hypothalamic-pituitary-thyroid axis have been linked to reduced kidney function, but the association of thyroid function with the development of incident CKD is largely uncharacterized. Concentrations of thyroid stimulating hormone (TSH), free thyroxine (FT4), triiodothyronine (T3) and thyroid peroxidase antibody (TPOAb) were quantified in 12 785 black and white participants of the ongoing community-based prospective Atherosclerosis Risk in Communities study. Thyroid markers and clinical categories of thyroid dysfunction (euthyroidism, combined subclinical and overt hypothyroidism, combined subclinical and overt hyperthyroidism) were also evaluated for their association with reduced kidney function (estimated glomerular filtration rate <60 mL/min/1.73 m2) at study baseline and with incident CKD over a median follow-up time of 19.6 years. Higher TSH and FT4 as well as lower T3 concentrations were strongly and independently associated with reduced kidney function at study baseline. The clinical entities hypothyroidism and hyperthyroidism were also associated with higher odds of baseline reduced kidney function, but this was not significant. However, none of the markers of thyroid function nor different clinical categories of thyroid dysfunction (hypothyroidism, hyperthyroidism or TPOAb positivity) were associated with incident CKD in adjusted analyses. Elevated TSH, FT4 and reduced T3 concentrations were associated with reduced kidney function cross-sectionally. The lack of association with the development of incident CKD suggests that altered thyroid function in the general population is not causally related to CKD development, but screening for thyroidal status may be especially relevant in persons with reduced kidney function. © The Author 2016. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved.

A method to facilitate and monitor expression of exogenous genes in the rat kidney using plasmid and viral vectors

PubMed Central

Corridon, Peter R.; Rhodes, George J.; Leonard, Ellen C.; Basile, David P.; Gattone, Vincent H.; Bacallao, Robert L.

2013-01-01

Gene therapy has been proposed as a novel alternative to treat kidney disease. This goal has been hindered by the inability to reliably deliver transgenes to target cells throughout the kidney, while minimizing injury. Since hydrodynamic forces have previously shown promising results, we optimized this approach and designed a method that utilizes retrograde renal vein injections to facilitate transgene expression in rat kidneys. We show, using intravital fluorescence two-photon microscopy, that fluorescent albumin and dextrans injected into the renal vein under defined conditions of hydrodynamic pressure distribute broadly throughout the kidney in live animals. We found injection parameters that result in no kidney injury as determined by intravital microscopy, histology, and serum creatinine measurements. Plasmids, baculovirus, and adenovirus vectors, designed to express EGFP, EGFP-actin, EGFP-occludin, EGFP-tubulin, tdTomato-H2B, or RFP-actin fusion proteins, were introduced into live kidneys in a similar fashion. Gene expression was then observed in live and ex vivo kidneys using two-photon imaging and confocal laser scanning microscopy. We recorded widespread fluorescent protein expression lasting more than 1 mo after introduction of transgenes. Plasmid and adenovirus vectors provided gene transfer efficiencies ranging from 50 to 90%, compared with 10–50% using baculovirus. Using plasmids and adenovirus, fluorescent protein expression was observed 1) in proximal and distal tubule epithelial cells; 2) within glomeruli; and 3) within the peritubular interstitium. In isolated kidneys, fluorescent protein expression was observed from the cortex to the papilla. These results provide a robust approach for gene delivery and the study of protein function in live mammal kidneys. PMID:23467422

Kidney regeneration: Where we are and future perspectives

PubMed Central

Zambon, Joao Paulo; Magalhaes, Renata S; Ko, Inkap; Ross, Christina L; Orlando, Giuseppe; Peloso, Andrea; Atala, Anthony; Yoo, James J

2014-01-01

In 2012, about 16487 people received kidney transplants in the United States, whereas 95022 candidates were on the waiting list by the end of the year. Despite advances in renal transplant immunology, approximately 40% of recipients will die or lose graft within 10 years. The limitations of current therapies for renal failure have led researchers to explore the development of modalities that could improve, restore, or replace the renal function. The aim of this paper is to describe a reasonable approach for kidney regeneration and review the current literature regarding cell sources and mechanisms to develop a bioengineering kidney. Due to kidneys peculiar anatomy, extracellular matrix based scaffolds are rational starting point for their regeneration. The perfusion of detergents through the kidney vasculature is an efficient method for delivering decellularizing agents to cells and for removing of cellular material from the tissue. Many efforts have focused on the search of a reliable cell source to provide enrichment for achieving stable renal cell systems. For an efficient bioengineered kidney, these cells must be attached to the organ and then maturated into the bioractors, which simulates the human body environment. A functional bioengineered kidney is still a big challenge for scientists. In the last ten years we have got many improvements on the field of solid organ regeneration; however, we are still far away from the main target. Currently, regenerative centers worldwide have been striving to find feasible strategies to develop bioengineered kidneys. Cell-scaffold technology gives hope to end-stage renal disease patients who struggle with morbidity and mortality due to extended periods on dialysis or immunosupression. The potential of bioengineered organ is to provide a reliable source of organs, which can be refunctionalized and transplanted. PMID:25332894

Safety evaluation of mercury based Ayurvedic formulation (Sidh Makardhwaj) on brain cerebrum, liver & kidney in rats

PubMed Central

Kumar, Gajendra; Srivastava, Amita; Sharma, Surinder Kumar; Gupta, Yogendra Kumar

2014-01-01

Background & objectives: Sidh Makardhwaj (SM) is a mercury based Ayurvedic formulation used in rheumatoid arthritis and neurological disorders. However, toxicity concerns due to mercury content are often raised. Therefore, the present study was carried out to evaluate the effect of SM on brain cerebrum, liver and kidney in rats. Methods: Graded doses of SM (10, 50, 100 mg/kg), mercuric chloride (1 mg/kg) and normal saline were administered orally to male Wistar rats for 28 days. Behavioural parameters were assessed on days 1, 7, 14 and 28 using Morris water maze, passive avoidance, elevated plus maze and rota rod. Liver and kidney function tests were done on day 28. Animals were sacrificed and brain cerebrum acetylcholinesterase activity, levels of malondialdehyde (MDA), reduced glutathione (GSH) in brain cerebrum, liver, kidney were estimated. The levels of mercury in brain cerebrum, liver and kidney were estimated and histopathology of these tissues was also performed. Results: SM in the doses used did not cause significant change in neurobehavioural parameters, brain cerebrum AChE activity, liver (ALT, AST, ALP bilirubin) and kidney (serum urea and creatinine) function tests as compared to control. The levels of mercury in brain cerebrum, liver, and kidney were found to be raised in dose dependent manner. However, the levels of MDA and GSH in these tissues did not show significant changes at doses of 10 and 50 mg/kg. Also, there was no histopathological change in cytoarchitecture of brain cerebrum, liver, and kidney tissues at doses of 10 and 50 mg/kg. Interpretation & conclusions: The findings of the present study suggest that Sidh Makardhwaj upto five times the equivalent human dose administered for 28 days did not show any toxicological effects on rat brain cerebrum, liver and kidney. PMID:24927349

[Banff score changes in kidneys from marginal donors].

PubMed

Borda, Bernadett; Szederkényi, Edit; Ottlakán, Aurél; Kemény, Éva; Szabó, Viktor; Hódi, Zoltán; Lázár, György

2016-02-21

Despite an increase in the number of cadaver donors and the number of overall organ transplantations, the dramatic increase in the waiting list makes it necessary to reconsider donor criteria. The authors examined whether differences could exist in the function and/or morphology of transplanted kidneys originated from marginal and ideal donors one and five years after transplantation. Kidney function and histopathologic findings were analysed and compared one and 5 years after transplantation in 97 patients having marginal donor kidneys and 178 patients who received ideal donor kidneys. Serum creatinine level was significantly higher (p = 0.0001) and estimated glomerular filtration rate was significantly lower (p = 0.003) in patients having marginal donor kidneys as compared to those with ideal donor kidneys 5 years after transplantation. Morphological changes in the transplanted kidneys such as tubulitis (p = 0.014) and interstitial inflammation (p = 0.025) were significantly more frequently present in patients with marginal donor kidneys than in those with ideal donor kidneys one year after transplantation. Despite an absence of differences in kidney function one year after kidney transplantation between patients having marginal and ideal donor kidneys, morphologic differences in the transplanted kidneys can be detected between the two groups of patients.

Correction of differential renal function for asymmetric renal area ratio in unilateral hydronephrosis.

PubMed

Aktaş, Gul Ege; Sarıkaya, Ali

2015-11-01

Children with unilateral hydronephrosis are followed up with anteroposterior pelvic diameter (APD), hydronephrosis grade, mercaptoacetyltriglycine (MAG-3) drainage pattern and differential renal function (DRF). Indeterminate drainage preserved DRF in higher grades of hydronephrosis, in some situations, complicating the decision-making process. Due to an asymmetric renal area ratio, falsely negative DRF estimations can result in missed optimal surgery times. This study was designed to assess whether correcting the DRF estimation according to kidney area could reflect the clinical situation of a hydronephrotic kidney better than a classical DRF calculation, concurrently with the hydronephrosis grade, APD and MAG-3 drainage pattern. We reviewed the MAG-3, dimercaptosuccinic acid (DMSA) scans and ultrasonography (US) of 23 children (6 girls, 17 boys, mean age: 29 ± 50 months) with unilateral hydronephrosis. MAG-3 and DMSA scans were performed within 3 months (mean 25.4 ± 30.7 days). The closest US findings (mean 41.5 ± 28.2 days) were used. DMSA DRF estimations were obtained using the geometric mean method. Secondary calculations were performed to correct the counts (the total counts divided by the number of pixels in ROI) according to kidney area. The renogram patterns of patients were evaluated and separated into subgroups. The visual assessment of DMSA scans was noted and the hydronephrotic kidney was classified in comparison to the normal contralateral kidney's uptake. The correlations of the DRF values of classical and area-corrected methods with MAG-3 renogram patterns, the visual classification of DMSA scan, the hydronephrosis grade and the APD were assessed. DRF estimations of two methods were statistically different (p: 0.001). The categories of 12 hydronephrotic kidneys were changed. There were no correlations between classical DRF estimations and the hydronephrosis grade, APD, visual classification of the DMSA scan and uptake evaluation. The DRF distributions according to MAG-3 drainage patterns were not different. Area-corrected DRF estimations correlated with all: with an increasing hydronephrosis grade and APD, DRF estimations decreased and MAG-3 drainage patterns worsened. A decrease in DRF (< 45 %) was determined when APD was ≥ 10 mm. When APD was ≥ 26 mm, a reduction of DRF below 40 % was determined. Our results suggest that correcting DRF estimation for asymmetric renal area ratio in unilateral hydronephrosis can be more robust than the classical method, especially for higher grades of hydronephrotic kidneys, under equivocal circumstances.

Telomere attrition, kidney function, and prevalent chronic kidney disease in the United States.

PubMed

Mazidi, Moshen; Rezaie, Peyman; Covic, Adriac; Malyszko, Jolanta; Rysz, Jacek; Kengne, Andre Pascal; Banach, Maciej

2017-10-06

Telomere length is an emerging novel biomarker of biologic age, cardiovascular risk and chronic medical conditions. Few studies have focused on the association between telomere length (TL) and kidney function. We investigated the association between TL and kidney function/prevalent chronic kidney disease (CKD) in US adults. The National Health and Nutrition Examination Survey (NHANES) participants with measured data on kidney function and TL from 1999 to 2002 were included. Estimated glomerular filtration rate (eGFR) was based on CKD Epidemiology Collaboration (CKD-EPI) equation. Urinary albumin excretion was assessed using urinary albumin-creatinine ratio (ACR). We used multivariable adjusted linear and logistic regression models, accounting for the survey design and sample weights. Of the 10568 eligible participants, 48.0% ( n =5020) were men. Their mean age was 44.1 years. eGFR significantly decreased and ACR significantly increased across increasing quarters of TL (all p <0.001). The association between TL and kidney function remained robust even after adjusting for potential confounding factors, but the association between TL and ACR was only borderline significant (β-coefficient= -0.012, p =0.056). The association of kidney function with a marker of cellular senescence suggests an underlying mechanism influencing the progression of nephropathy.

Hypothermic machine perfusion permits extended cold ischemia times with improved early graft function.

PubMed

Guy, Alison; McGrogan, Damian; Inston, Nicholas; Ready, Andrew

2015-04-01

The logistics of deceased-donor renal transplants are largely affected by cold ischemia time. However, to attain successful outcomes, other issues must be considered. Extending cold ischemia time to accommodate these issues would be valuable. We investigated the role of hypothermic machine perfusion to extend cold ischaemia time. Deceased-donor kidneys were allocated to a storage method, depending on predicted time to operation. Kidneys to be transplanted from 8:00 AM to 8:00 PM in the transplant room remained in static cold storage. If predicted operating time was out of hours, the kidney was transferred to hypothermic machine perfusion and transplanted at the earliest opportunity on the dedicated transplant list. There were 74 kidneys transplanted from hypothermic machine perfusion and 101 kidneys from static cold storage. Median cold ischemia time was 23.85 hours in the hypothermic machine perfusion group, compared with 13 hours in the static cold storage group (P ≤ .0001). There were 20 kidneys (27%) from hypothermic machine perfusion that had delayed graft function, compared with 47 kidneys (47%) in the static cold storage group (P = .012). There were no other significant differences in graft or postoperative complications. This study demonstrated that improved early graft outcomes can be achieved following longer cold ischemia time by using hypothermic machine perfusion rather than static cold storage. This effect is likely multifactorial including the inherent effects of hypothermic machine perfusion, improved recipient preparation, and possibly better perioperative conditions.

What Is Atherosclerosis?

MedlinePlus

... builds up in the renal arteries. These arteries supply oxygen-rich blood to your kidneys. Over time, chronic kidney disease causes a slow loss of kidney function. The main function of the kidneys is to remove waste and extra water from the body. Overview The cause of atherosclerosis ...

(Re)Building a Kidney

PubMed Central

Carroll, Thomas J.; Cleaver, Ondine; Gossett, Daniel R.; Hoshizaki, Deborah K.; Hubbell, Jeffrey A.; Humphreys, Benjamin D.; Jain, Sanjay; Jensen, Jan; Kaplan, David L.; Kesselman, Carl; Ketchum, Christian J.; Little, Melissa H.; McMahon, Andrew P.; Shankland, Stuart J.; Spence, Jason R.; Valerius, M. Todd; Wertheim, Jason A.; Wessely, Oliver; Zheng, Ying; Drummond, Iain A.

2017-01-01

(Re)Building a Kidney is a National Institute of Diabetes and Digestive and Kidney Diseases-led consortium to optimize approaches for the isolation, expansion, and differentiation of appropriate kidney cell types and the integration of these cells into complex structures that replicate human kidney function. The ultimate goals of the consortium are two-fold: to develop and implement strategies for in vitro engineering of replacement kidney tissue, and to devise strategies to stimulate regeneration of nephrons in situ to restore failing kidney function. Projects within the consortium will answer fundamental questions regarding human gene expression in the developing kidney, essential signaling crosstalk between distinct cell types of the developing kidney, how to derive the many cell types of the kidney through directed differentiation of human pluripotent stem cells, which bioengineering or scaffolding strategies have the most potential for kidney tissue formation, and basic parameters of the regenerative response to injury. As these projects progress, the consortium will incorporate systematic investigations in physiologic function of in vitro and in vivo differentiated kidney tissue, strategies for engraftment in experimental animals, and development of therapeutic approaches to activate innate reparative responses. PMID:28096308

Bardoxolone Methyl Improves Kidney Function in Patients with Chronic Kidney Disease Stage 4 and Type 2 Diabetes: Post-Hoc Analyses from Bardoxolone Methyl Evaluation in Patients with Chronic Kidney Disease and Type 2 Diabetes Study

PubMed Central

Chin, Melanie P.; Bakris, George L.; Block, Geoffrey A.; Chertow, Glenn M.; Goldsberry, Angie; Inker, Lesley A.; Heerspink, Hiddo J.L.; O'Grady, Megan; Pergola, Pablo E.; Wanner, Christoph; Warnock, David G.; Meyer, Colin J.

2018-01-01

Background Increases in measured inulin clearance, measured creatinine clearance, and estimated glomerular filtration rate (eGFR) have been observed with bardoxolone methyl in 7 studies enrolling approximately 2,600 patients with type 2 diabetes (T2D) and chronic kidney disease (CKD). The largest of these studies was Bardoxolone Methyl Evaluation in Patients with Chronic Kidney Disease and Type 2 Diabetes (BEACON), a multinational, randomized, double-blind, placebo-controlled phase 3 trial which enrolled patients with T2D and CKD stage 4. The BEACON trial was terminated after preliminary analyses showed that patients randomized to bardoxolone methyl experienced significantly higher rates of heart failure events. We performed post-hoc analyses to characterize changes in kidney function induced by bardoxolone methyl. Methods Patients in ­BEACON (n = 2,185) were randomized 1: 1 to receive once-daily bardoxolone methyl (20 mg) or placebo. We compared the effects of bardoxolone methyl and placebo on a post-hoc composite renal endpoint consisting of ≥30% decline from baseline in eGFR, eGFR <15 mL/min/1.73 m2, and end-stage renal disease (ESRD) events (provision of dialysis or kidney transplantation). Results Consistent with prior studies, patients randomized to bardoxolone methyl experienced mean increases in eGFR that were sustained through study week 48. Moreover, increases in eGFR from baseline were sustained 4 weeks after cessation of treatment. Patients randomized to bardoxolone methyl were significantly less likely to experience the composite renal endpoint (hazards ratio 0.48 [95% CI 0.36–0.64]; p < 0.0001). Conclusions Bardoxolone methyl preserves kidney function and may delay the onset of ESRD in patients with T2D and stage 4 CKD. PMID:29402767

Uncontrolled Donors with Controlled Reperfusion after Sixty Minutes of Asystole: A Novel Reliable Resource for Kidney Transplantation

PubMed Central

Reznik, Oleg N.; Skvortsov, Andrei E.; Reznik, Alexander O.; Ananyev, Alexey N.; Tutin, Alexey P.; Kuzmin, Denis O.; Bagnenko, Sergey F.

2013-01-01

Background Organ shortage leads to usage of kidneys from donors after sudden cardiac death, or uncontrolled donors (UDCD). Ischemic injury due to cessation of circulation remains a crucial problem that limits adoption of UDCD. Our clinical investigation was to determine the applicability of kidneys obtained from UDCD and resuscitated by extracorporeal perfusion in situ after 60 minutes of asystole. Methods In 2009–2011, organ procurement service of St. Petersburg, obtained kidneys from 22 UDCD with critically expanded warm ischemic time (WIT). No patients were considered as potential organ donors initially. All donors died after sudden irreversible cardiac arrest. Mean WIT was 61.4±4.5 minutes. For kidney resuscitation, the subnormothermic extracorporeal abdominal perfusion with thrombolytics and leukocyte depletion was employed. Grafts were transplanted into 44 recipients. The outcomes of transplantation of resuscitated kidneys were compared to outcomes of 87 KTx from 74 brain death donors (BDDs). Results Immediate functioning of kidney grafts was observed in 21 of the 44 recipients, with no cases of primary non function. By the end of the first post-transplant year there was an acute rejection rate of 9.1% (4 episodes of rejection) in the UDCD group versus 14.2% (13 episodes of rejection) in the BDD group. The actual 1-year graft survival rate was 95.5% (n = 42) in UDCD group, and 94.6% (n = 87) in BDD group. Creatinine levels at the end of the first year were 0.116±0.008 and 0.115±0.004 mmol/l in UDCD and BDD groups, respectively. Conclusions UDCD kidneys with critically expanded WIT could be succefully used for transplantation if in situ organ “resuscitation” perfusion is included into procurement protocol. The results of 1-year follow-up meet the generally accepted criteria for graft survival and function. In situ reperfusion may exert a therapeutic effect on grafts before procurement. This approach could substantially expand the organ donors' pool. PMID:23737973

Adaptive functional change of the contralateral kidney after partial nephrectomy.

PubMed

Choi, Se Young; Yoo, Sangjun; You, Dalsan; Jeong, In Gab; Song, Cheryn; Hong, Bumsik; Hong, Jun Hyuk; Ahn, Hanjong; Kim, Choung-Soo

2017-08-01

Partial nephrectomy aims to maintain renal function by nephron sparing; however, functional changes in the contralateral kidney remain unknown. We evaluate the functional change in the contralateral kidney using a diethylene triamine penta-acetic acid (DTPA) renal scan and determine factors predicting contralateral kidney function after partial nephrectomy. A total of 699 patients underwent partial nephrectomy, with a DTPA scan before and after surgery to assess the separate function of each kidney. Patients were divided into three groups according to initial contralateral glomerular filtration rate (GFR; group 1 : <30 ml·min -1 ·1.73 m -2 , group 2 : 30-45 ml·min -1 ·1.73 m -2 , and group 3 : ≥45 ml·min -1 ·1.73 m -2 ). Multiple-regression analysis was used to identify the factors associated with increased GFR of the contralateral kidney over a 4-yr postoperative period. Patients in group 1 had a higher mean age and hypertension history, worse American Society of Anesthesiologists score, and larger tumor size than in the other two groups. The ipsilateral GFR changes at 4 yr after partial nephrectomy were -18.9, -3.6, and 3.9% in groups 1 , 2 , and 3 , respectively, whereas the contralateral GFR changes were 10.8, 25.7, and 38.8%. Age [β: -0.105, 95% confidence interval (CI): -0.213; -0.011, P < 0.05] and preoperative contralateral GFR (β: -0.256, 95% CI: -0.332; -0.050, P < 0.01) were significant predictive factors for increased GFR of the contralateral kidney after 4 yr. The contralateral kidney compensated for the functional loss of the ipsilateral kidney. The increase of GFR in contralateral kidney is more prominent in younger patients with decreased contralateral renal function. Copyright © 2017 the American Physiological Society.

Poly[ADP-Ribose] Polymerase-1 Expression Is Related To Cold Ischemia, Acute Tubular Necrosis, and Delayed Renal Function In Kidney Transplantation

PubMed Central

O'Valle, Francisco; Del Moral, Raimundo G. M.; Benítez, María del Carmén; Martín-Oliva, David; Gómez-Morales, Mercedes; Aguilar, David; Aneiros-Fernández, José; Hernández-Cortés, Pedro; Osuna, Antonio; Moreso, Francesc; Serón, Daniel; Oliver, Francisco J.; Del Moral, Raimundo G.

2009-01-01

Cold ischemia time especially impacts on outcomes of expanded-criteria donor (ECD) transplantation. Ischemia-reperfusion (IR) injury produces excessive poly[ADP-Ribose] Polymerase-1 (PARP-1) activation. The present study explored the hypothesis that increased tubular expression of PARP-1 contributes to delayed renal function in suboptimal ECD kidney allografts and in non-ECD allografts that develop posttransplant acute tubular necrosis (ATN). Materials and Methods Nuclear PARP-1 immunohistochemical expression was studied in 326 paraffin-embedded renal allograft biopsies (193 with different degrees of ATN and 133 controls) and in murine Parp-1 knockout model of IR injury. Results PARP-1 expression showed a significant relationship with cold ischemia time (r coefficient = 0.603), time to effective diuresis (r = 0.770), serum creatinine levels at biopsy (r = 0.649), and degree of ATN (r = 0.810) (p = 0.001, Pearson test). In the murine IR model, western blot showed an increase in PARP-1 that was blocked by Parp-1 inhibitor. Immunohistochemical study of PARP-1 in kidney allograft biopsies would allow early detection of possible delayed renal function, and the administration of PARP-1 inhibitors may offer a therapeutic option to reduce damage from IR in donor kidneys by preventing or minimizing ATN. In summary, these results suggest a pivotal role for PARP-1 in the ATN of renal transplantation. We propose the immunohistochemical assessment of PARP-1 in kidney allograft biopsies for early detection of a possible delayed renal function. PMID:19784367

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.

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.

Four decades of the kidney transplantation program at the Institute Nacional de Ciencias Médicas y Nutrición Salvador Zubirán in Mexico City.

PubMed

Morales-Buenrostro, Luis E; Marino-Vázquez, Lluvia A; Alberú, Josefina

2009-01-01

This is a retrospective study that includes four decades of kidney transplant program at our Institute, with a total of 923 kidney transplants in 872 recipients. In this report, the effect of variables in recipient, donor, and transplant on long-term graft survival was analyzed using the Kaplan Meier method with log-rank test for survival comparisons. Global graft survival at our center-analyzed by censoring for death-with-functioning-graft-for 1, 5 and 10 years was 93%, 83% and 74%, respectively, with median survival of 24.5 years. When analyzed for all-cause graft loss, 1, 5 and 10 year survival was 90%, 76% and 61%, with 12.8-year median survival. Variables associated with lower graft survival censored for death-with-functioning-graft were transplantation in an earlier decade, less histocompatibility, younger kidney transplant recipients, no induction therapy, and double drug initial immunosuppression. After Cox's regression multivariate analysis, the risk factors that remained associated with worse survival were younger recipient, earlier transplant decade, and deceased donor.

Oxidative Stress in Kidney Diseases: The Cause or the Consequence?

PubMed

Krata, Natalia; Zagożdżon, Radosław; Foroncewicz, Bartosz; Mucha, Krzysztof

2018-06-01

Exaggerated oxidative stress (OS) is usually considered as a disturbance in regular function of an organism. The excessive levels of OS mediators may lead to major damage within the organism's cells and tissues. Therefore, the OS-associated biomarkers may be considered as new diagnostic tools of various diseases. In nephrology, researchers are looking for alternative methods replacing the renal biopsy in patients with suspicion of chronic kidney disease (CKD). Currently, CKD is a frequent health problem in world population, which can lead to progressive loss of kidney function and eventually to end-stage renal disease. The course of CKD depends on the primary disease. It is assumed that one of the factors influencing the course of CKD might be OS. In the current work, we review whether monitoring the OS-associated biomarkers in nephrology patients can support the decision-making process regarding diagnosis, prognostication and treatment initiation.

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.

Anatomy guided automated SPECT renal seed point estimation

NASA Astrophysics Data System (ADS)

Dwivedi, Shekhar; Kumar, Sailendra

2010-04-01

Quantification of SPECT(Single Photon Emission Computed Tomography) images can be more accurate if correct segmentation of region of interest (ROI) is achieved. Segmenting ROI from SPECT images is challenging due to poor image resolution. SPECT is utilized to study the kidney function, though the challenge involved is to accurately locate the kidneys and bladder for analysis. This paper presents an automated method for generating seed point location of both kidneys using anatomical location of kidneys and bladder. The motivation for this work is based on the premise that the anatomical location of the bladder relative to the kidneys will not differ much. A model is generated based on manual segmentation of the bladder and both the kidneys on 10 patient datasets (including sum and max images). Centroid is estimated for manually segmented bladder and kidneys. Relatively easier bladder segmentation is followed by feeding bladder centroid coordinates into the model to generate seed point for kidneys. Percentage error observed in centroid coordinates of organs from ground truth to estimated values from our approach are acceptable. Percentage error of approximately 1%, 6% and 2% is observed in X coordinates and approximately 2%, 5% and 8% is observed in Y coordinates of bladder, left kidney and right kidney respectively. Using a regression model and the location of the bladder, the ROI generation for kidneys is facilitated. The model based seed point estimation will enhance the robustness of kidney ROI estimation for noisy cases.

Kidney growth and renal functions under the growth hormone replacement therapy in children.

PubMed

Ece, Aydın; Çetinkaya, Semra; Ekşioğlu, Seçil; Şenel, Saliha; Özkasap, Serdar; Giniş, Tayfur; Sen, Velat; Şahin, Cahit

2014-05-01

The aim of this study was to investigate the kidney growth and renal functions in children receiving recombinant human growth hormone (rhGH) treatment. A total of 37 children who received rhGH for 1.5 years before the study was started and 48 healthy controls were included at first evaluation. Hormone levels were determined and kidney sizes were measured by ultrasound. Kidney functions were assessed by serum creatinine and estimated glomerular filtration rate (eGFR). After 3 years of first evaluation, 23 patients were re-assessed. Kidney sizes were found to be lower in rhGH received children compared with controls at first evaluation (p<0.05). Significant positive correlations were found between anthropometric measurements and kidney length and kidney volume (p<0.05). Height was the most significant predictor of kidney volume in rhGH received children (p<0.001). After 3-years of follow-up significantly increases were found in kidney length and volume compared with the first measurements (p<0.05). Increase percentage of body height was similar to increasing percent of kidney length and liver long axis (14.2%, 11.7.1% and 7.7%, respectively, p>0.05). Although no abnormal renal function test results were found at first and second evaluations; rhGH received children had significantly lower eGFR, at first evaluation, compared with controls; however, renal functions significantly increased after 3 years of follow-up (p<0.05). In conclusion, effect rhGH treatment on kidney growth is parallel to growth in body height and other visceral organs. A 3-years rhGH treatment resulted in significant increases in renal functions.

Abrupt Decline in Kidney Function Before Initiating Hemodialysis and All-Cause Mortality: The Chronic Renal Insufficiency Cohort (CRIC) Study.

PubMed

Hsu, Raymond K; Chai, Boyang; Roy, Jason A; Anderson, Amanda H; Bansal, Nisha; Feldman, Harold I; Go, Alan S; He, Jiang; Horwitz, Edward J; Kusek, John W; Lash, James P; Ojo, Akinlolu; Sondheimer, James H; Townsend, Raymond R; Zhan, Min; Hsu, Chi-Yuan

2016-08-01

It is not clear whether the pattern of kidney function decline in patients with chronic kidney disease (CKD) may relate to outcomes after reaching end-stage renal disease (ESRD). We hypothesize that an abrupt decline in kidney function prior to ESRD predicts early death after initiating maintenance hemodialysis therapy. Prospective cohort study. The Chronic Renal Insufficiency Cohort (CRIC) Study enrolled men and women with mild to moderate CKD. For this study, we studied 661 individuals who developed chronic kidney failure that required hemodialysis therapy initiation. The primary predictor was the presence of an abrupt decline in kidney function prior to ESRD. We incorporated annual estimated glomerular filtration rates (eGFRs) into a mixed-effects model to estimate patient-specific eGFRs at 3 months prior to initiation of hemodialysis therapy. Abrupt decline was defined as having an extrapolated eGFR≥30mL/min/1.73m(2) at that time point. All-cause mortality within 1 year after initiating hemodialysis therapy. Multivariable Cox proportional hazards. Among 661 patients with CKD initiating hemodialysis therapy, 56 (8.5%) had an abrupt predialysis decline in kidney function and 69 died within 1 year after initiating hemodialysis therapy. After adjustment for demographics, cardiovascular disease, diabetes, and cancer, abrupt decline in kidney function was associated with a 3-fold higher risk for death within the first year of ESRD (adjusted HR, 3.09; 95% CI, 1.65-5.76). Relatively small number of outcomes; infrequent (yearly) eGFR determinations; lack of more granular clinical data. Abrupt decline in kidney function prior to ESRD occurred in a significant minority of incident hemodialysis patients and predicted early death in ESRD. Copyright © 2016 National Kidney Foundation, Inc. All rights reserved.

Kidney function and blood pressure in preschool-aged children exposed to cadmium and arsenic - potential alleviation by selenium

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

Skröder, Helena; Hawkesworth, Sophie; Kippler, Maria

Background: Early-life exposure to toxic compounds may cause long-lasting health effects, but few studies have investigated effects of childhood exposure to nephrotoxic metals on kidney and cardiovascular function. Objectives: To assess effects of exposure to arsenic and cadmium on kidney function and blood pressure in pre-school-aged children, and potential protection by selenium. Methods: This cross-sectional study was part of the 4.5 years of age (range: 4.4–5.4 years) follow-up of the children from a supplementation trial in pregnancy (MINIMat) in rural Bangladesh, and nested studies on early-life metal exposures. Exposure to arsenic, cadmium and selenium from food and drinking water wasmore » assessed by concentrations in children's urine, measured by ICP-MS. Kidney function was assessed by the estimated glomerular filtration rate (eGFR, n=1106), calculated from serum cystatin C, and by kidney volume, measured by ultrasound (n=375). Systolic and diastolic blood pressure was measured (n=1356) after five minutes rest. Results: Multivariable-adjusted regression analyzes showed that exposure to cadmium, but not arsenic, was inversely associated with eGFR, particularly in girls. A 0.5 µg/L increase in urinary cadmium among the girls (above spline knot at 0.12) was associated with a decrease in eGFR of 2.6 ml/min/1.73 m{sup 2}, corresponding to 0.2SD (p=0.022). A slightly weaker inverse association with cadmium was also indicated for kidney volume, but no significant associations were found with blood pressure. Stratifying on children's urinary selenium (below or above median of 12.6 µg/L) showed a three times stronger inverse association of U-Cd with eGFR (all children) in the lower selenium stratum (B=−2.8; 95% CI: −5.5, −0.20; p=0.035), compared to those with higher selenium (B=−0.79; 95% CI: −3.0, 1.4; p=0.49). Conclusions: Childhood cadmium exposure seems to adversely affect kidney function, but not blood pressure, in this population of young children in rural Bangladesh. Better selenium status appears to be protective. However, it is important to follow up these children to assess potential long-term consequences of these findings. - Highlights: • Bangladesh has high levels of arsenic and cadmium in drinking water and food • We assessed toxic exposure, kidney and cardiovascular function in Bangladeshi children • Cadmium appeared to decrease estimated glomerular filtration rate in girls • These effects were somewhat alleviated by selenium.« less

Mature induced-pluripotent-stem-cell-derived human podocytes reconstitute kidney glomerular-capillary-wall function on a chip

PubMed Central

Musah, Samira; Mammoto, Akiko; Ferrante, Thomas C.; Jeanty, Sauveur S. F.; Hirano-Kobayashi, Mariko; Mammoto, Tadanori; Roberts, Kristen; Chung, Seyoon; Novak, Richard; Ingram, Miles; Fatanat-Didar, Tohid; Koshy, Sandeep; Weaver, James C.; Church, George M.; Ingber, Donald E.

2017-01-01

An in vitro model of the human kidney glomerulus — the major site of blood filtration — could facilitate drug discovery and illuminate kidney-disease mechanisms. Microfluidic organ-on-a-chip technology has been used to model the human proximal tubule, yet a kidney-glomerulus-on-a-chip has not been possible because of the lack of functional human podocytes — the cells that regulate selective permeability in the glomerulus. Here, we demonstrate an efficient (> 90%) and chemically defined method for directing the differentiation of human induced pluripotent stem (hiPS) cells into podocytes that express markers of the mature phenotype (nephrin+, WT1+, podocin+, Pax2−) and that exhibit primary and secondary foot processes. We also show that the hiPS-cell-derived podocytes produce glomerular basement-membrane collagen and recapitulate the natural tissue/tissue interface of the glomerulus, as well as the differential clearance of albumin and inulin, when co-cultured with human glomerular endothelial cells in an organ-on-a-chip microfluidic device. The glomerulus-on-a-chip also mimics adriamycin-induced albuminuria and podocyte injury. This in vitro model of human glomerular function with mature human podocytes may facilitate drug development and personalized-medicine applications. PMID:29038743

The protective effect of baicalin against renal ischemia-reperfusion injury through inhibition of inflammation and apoptosis

PubMed Central

2014-01-01

Background Renal ischemia-reperfusion injury (IRI) increases the rates of acute kidney failure, delayed graft function, and early mortality after kidney transplantation. The pathophysiology involved includes oxidative stress, mitochondrial dysfunction, and immune-mediated injury. The anti-oxidation, anti-apoptosis, and anti-inflammation properties of baicalin, a flavonoid glycoside isolated from Scutellaria baicalensis, have been verified. This study therefore assessed the effects of baicalin against renal IRI in rats. Methods Baicalin was intraperitoneally injected 30 min before renal ischemia. Serum and kidneys were harvested 24 h after reperfusion. Renal function and histological changes were assessed. Markers of oxidative stress, the Toll-like receptor (TLR)2 and TLR4 signaling pathway, mitochondrial stress, and cell apoptosis were also evaluated. Results Baicalin treatment decreased oxidative stress and histological injury, and improved kidney function, as well as inhibiting proinflammatory responses and tubular apoptosis. Baicalin pretreatment also reduced the expression of TLR2, TLR4, MyD88, p-NF-κB, and p-IκB proteins, as well as decreasing caspase-3 activity and increasing the Bcl-2/Bax ratio. Conclusions Baicalin may attenuate renal ischemia-reperfusion injury by inhibiting proinflammatory responses and mitochondria-mediated apoptosis. These effects are associated with the TLR2/4 signaling pathway and mitochondrial stress. PMID:24417870

Quantification of single-kidney glomerular filtration rate with electron-beam computed tomography

NASA Astrophysics Data System (ADS)

Lerman, Lilach O.; Ritman, Erik L.; Pelaez, Laura I.; Sheedy, Patrick F., II; Krier, James D.

2000-04-01

The ability to accurately and noninvasively quantify single- kidney GFR could be invaluable for assessment of renal function. We developed a model that enables this measurement with EBCT. To examine the reliability of this method, EBCT renal flow and volume studies after contrast media administration were performed in pigs with unilateral renal artery stenosis (Group 1), controls (Group 2), and simultaneously with inulin clearance (Group 3). Renal flow curves, obtained from the bilateral renal cortex and medulla, depicted transit of the contrast through the vascular and tubular compartments, and were fitted using extended gamma- variate functions. Renal blood flow was calculated as the sum of products of cortical and medullary perfusions and volumes. Normalized GFR (mL/min/cc) was calculated using the rate (maximal slope) of proximal tubular contrast accumulation, and EBCT-GFR as normalized GFR* cortical volume. In Group 1, the decreased GFR of the stenotic kidney correlated well with its decreased volume and RBF, and with the degree of stenosis (r equals -0.99). In Group 3, EBCT-GFR correlated well with inulin clearance (slope 1.1, r equals 0.81). This novel approach can be very useful for quantification of concurrent regional hemodynamics and function in the intact kidneys, in a manner potentially applicable to humans.

Use and isolation of urinary exosomes as biomarkers for diabetic nephropathy.

PubMed

Musante, Luca; Tataruch, Dorota Ewa; Holthofer, Harry

2014-01-01

Diabetes represents a major threat to public health and the number of patients is increasing alarmingly in the global scale. Particularly, the diabetic kidney disease (nephropathy, DN) together with its cardiovascular complications cause immense human suffering, highly increased risk of premature deaths, and lead to huge societal costs. DN is first detected when protein appears in urine (microalbuminuria). As in other persisting proteinuric diseases (like vasculitis) it heralds irreversible damage of kidney functions up to non-functional (end-stage) kidney and ultimately calls for kidney replacement therapy (dialysis or kidney transplantation). While remarkable progress has been made in understanding the genetic and molecular factors associating with chronic kidney diseases, breakthroughs are still missing to provide comprehensive understanding of events and mechanisms associated. Non-invasive diagnostic tools for early diagnostics of kidney damage are badly needed. Exosomes - small vesicular structures present in urine are released by all cell types along kidney structures to present with distinct surface assembly. Furthermore, exosomes carry a load of special proteins and nucleic acids. This "cargo" faithfully reflects the physiological state of their respective cells of origin and appears to serve as a new pathway for downstream signaling to target cells. Accordingly, exosome vesicles are emerging as a valuable source for disease stage-specific information and as fingerprints of disease progression. Unfortunately, technical issues of exosome isolation are challenging and, thus, their full potential remains untapped. Here, we review the molecular basis of exosome secretion as well as their use to reveal events along the nephron. In addition to novel molecular information, the new methods provide the needed accurate, personalized, non-invasive, and inexpensive future diagnostics.

Use and Isolation of Urinary Exosomes as Biomarkers for Diabetic Nephropathy

PubMed Central

Musante, Luca; Tataruch, Dorota Ewa; Holthofer, Harry

2014-01-01

Diabetes represents a major threat to public health and the number of patients is increasing alarmingly in the global scale. Particularly, the diabetic kidney disease (nephropathy, DN) together with its cardiovascular complications cause immense human suffering, highly increased risk of premature deaths, and lead to huge societal costs. DN is first detected when protein appears in urine (microalbuminuria). As in other persisting proteinuric diseases (like vasculitis) it heralds irreversible damage of kidney functions up to non-functional (end-stage) kidney and ultimately calls for kidney replacement therapy (dialysis or kidney transplantation). While remarkable progress has been made in understanding the genetic and molecular factors associating with chronic kidney diseases, breakthroughs are still missing to provide comprehensive understanding of events and mechanisms associated. Non-invasive diagnostic tools for early diagnostics of kidney damage are badly needed. Exosomes – small vesicular structures present in urine are released by all cell types along kidney structures to present with distinct surface assembly. Furthermore, exosomes carry a load of special proteins and nucleic acids. This “cargo” faithfully reflects the physiological state of their respective cells of origin and appears to serve as a new pathway for downstream signaling to target cells. Accordingly, exosome vesicles are emerging as a valuable source for disease stage-specific information and as fingerprints of disease progression. Unfortunately, technical issues of exosome isolation are challenging and, thus, their full potential remains untapped. Here, we review the molecular basis of exosome secretion as well as their use to reveal events along the nephron. In addition to novel molecular information, the new methods provide the needed accurate, personalized, non-invasive, and inexpensive future diagnostics. PMID:25309511

Pediatric Renal Transplantation in Oman: A Single-center Experience

PubMed Central

Al Riyami, Mohamed S.; Al Saidi, Sulaiman; Al Ghaithi, Badria; Al Maskari, Anisa; Lala, Sadiq; Mohsin, Nabil; Hirshikesan, Lekha; Al Kalbani, Naifain

2018-01-01

Objectives This study sought to report 22 years experience in pediatric kidney transplantation in Oman. Methods Electronic charts of all Omani children below 13 years of age who received a kidney transplant from January 1994 to December 2015 were reviewed. Data collected included patient demographics, etiology of end-stage kidney disease, modality and duration of dialysis, donor type, complication of kidney transplantation (including surgical complications, infections, graft rejection) graft and patient survival, and duration of follow-up. Results During the study period transplantation from 27 living related donors (LRDs), 42 living unrelated donors (LURDs), also referred to as commercial transplant, and one deceased donor were performed. The median age at transplantation was nine years for both groups. The most common primary diagnosis was congenital anomalies of the kidney and urinary tract in 32.8% of patients followed by familial nephrotic syndrome in 20.0% and polycystic kidney disease in 18.5%. Almost half the patients were on hemodialysis before transplantation, 35.7% were on peritoneal dialysis, and 14.2% received preemptive renal transplantation. Children who received LURD kidneys had high surgical complications (42.8%) compared to the LRDs group (17.8%). Five patients from LURDs group had early graft nephrectomy and four patients developed non-graft function or delayed graft function. In addition, patients in the LURDs group had a higher incidence of hypertension and acute rejection. Graft and patient survival were both better in the LRDs than the LURDs group. Conclusions Although our pediatric kidney transplant program is a young program it has had successful patient outcomes comparable to international programs. Our study provides evidence that in addition to legal and ethical issues with commercial transplant, it also carries significantly higher morbidity and reduced graft and patient survival. PMID:29467993

Sirolimus in kidney transplant donors and clinical and histologic improvement in recipients: rat model.

PubMed

Cicora, F; Lausada, N; Vasquez, D N; Cicora, P; Zalazar, G; Gonzalez, P; Palti, G; Raimondi, C

2010-01-01

Ischemia-reperfusion (I/R) injury is one of the risk factors for delayed graft function, acute rejection episodes, and impaired long-term allograft survival after kidney transplantation. This antigen-independent inflammatory process produces tissue damage. Isogeneic transplantation in a rat model is a useful method for study of nonimmunologic risk factors for kidney damage. To study the effect of sirolimus on I/R injury using only 1 dose of the drug in the donor. Eighteen rats were allocated to 3 groups of 6 rats each: sham group, control group, and rapamycin group. Improved renal function and systemic inflammatory response were observed in the rapamycin group compared with the control group (Deltaurea, Deltacreatinine, and DeltaC3, all P < .01). The number of apoptotic nuclei in the renal medulla in the control group was higher than in the rapamycin group (P < .01). Tubular damage was less severe in the rapamycin group compared with the control group (P < .01). Complement 3 and tumor necrosis factor-alpha expression in the kidney samples were significantly decreased when rapamycin was given to the donor rats (P > .01). Bcl-2 protein was upregulated in the rapamycin group compared with the control group (P < .01). Administration of rapamycin in donors attenuates the I/R injury process after kidney transplantation in a rat model.

Determination of split renal function using dynamic CT-angiography: preliminary results.

PubMed

Helck, Andreas; Schönermarck, Ulf; Habicht, Antje; Notohamiprodjo, Mike; Stangl, Manfred; Klotz, Ernst; Nikolaou, Konstantin; la Fougère, Christian; Clevert, Dirk Andrè; Reiser, Maximilian; Becker, Christoph

2014-01-01

To determine the feasibility of a dynamic CT angiography-protocol with regard to simultaneous assessment of renal anatomy and function. 7 healthy potential kidney donors (58 ± 7 years) underwent a dynamic computed tomography angiography (CTA) using a 128-slice CT-scanner with continuous bi-directional table movement, allowing the coverage of a scan range of 18 cm within 1.75 sec. Twelve scans of the kidneys (n = 14) were acquired every 3.5 seconds with the aim to simultaneously obtain CTA and renal function data. Image quality was assessed quantitatively (HU-measurements) and qualitatively (grade 1-4, 1 = best). The glomerular filtration rate (GFR) was calculated by a modified Patlak method and compared with the split renal function obtained with renal scintigraphy. Mean maximum attenuation was 464 ± 58 HU, 435 ± 48 HU and 277 ± 29 HU in the aorta, renal arteries, and renal veins, respectively. The abdominal aorta and all renal vessels were depicted excellently (grade 1.0). The image quality score for cortex differentiation was 1.6 ± 0.49, for the renal parenchyma 2.4 ± 0.49. GFR obtained from dynamic CTA correlated well with renal scintigraphy with a correlation coefficient of r = 0.84; P = 0.0002 (n = 14). The average absolute deviation was 1.6 mL/min. The average effective dose was 8.96 mSv. Comprehensive assessment of renal anatomy and function is feasible using a single dynamic CT angiography examination. The proposed protocol may help to improve management in case of asymmetric kidney function as well as to simplify evaluation of potential living kidney donors.

Effects of feline hyperthyroidism on kidney function: a review.

PubMed

Vaske, Heather H; Schermerhorn, Thomas; Grauer, Gregory F

2016-02-01

Chronic kidney disease and hyperthyroidism are two commonly diagnosed conditions in the geriatric feline population, and are often seen concurrently. Management of both diseases is recommended; however, the physiologic implications of both diseases must be understood to ensure the most favorable outcome for each patient. This report reviews the complex interplay between hyperthyroidism and kidney function, as well as the effects of hyperthyroid therapy on kidney function. © ISFM and AAFP 2015.

Delayed Graft Function in Living-Donor Kidney Transplant: A Middle Eastern Perspective.

PubMed

Al Otaibi, Torki; Ahmadpoor, Pedram; Allawi, Ali Abdulmajid Dyab; Habhab, Wael Taher; Khatami, Mohammad Reza; Nafar, Mohsen; Glotz, Denis

2016-02-01

With an increased incidence of living-donor kidney transplants, in response to increasing unmet needs for renal transplant, a clear understanding of determinants of posttransplant outcomes is essential. The importance of delayed graft function in deceased-donor kidney transplant is now part of conventional medical wisdom, due to the large amount of evidence focused on this aspect. However, the same is not true for living-donor kidney transplant, partly due to lack of evidence on this crucial clinical question and partly due to lack of awareness about this issue. The current review aims to highlight the importance of delayed graft function as a crucial determinant of outcomes in living-donor kidney transplant. An exhaustive search of online medical databases was performed with appropriate search criteria to collect evidence about delayed graft function after living-donor kidney transplant, with a special focus on studies from the Middle East. Data on incidence, impact, risk factors, and possible prevention modalities of delayed graft function in patients undergoing living-donor kidney transplant are presented. A key finding of this review is that contemporary incidence rates reported from the Middle East are comparatively higher than those reported from outside the region. Although in absolute terms the incidence is lower than deceased donor kidney transplant, the effects of delayed graft function on graft rejection and graft and patient survival are sufficiently large to warrant the formulation of specific treatment protocols. Key to formulating prevention and treatment strategies is identifying discrete risk factors for delayed graft function. Although this evidence is scant, an overview has been provided. Further studies examining different aspects of delayed graft function incidence after living-donor kidney transplant are urgently needed to address a so far little known clinical question.

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.

Prevalence of Hypertension in Children with Early-Stage ADPKD.

PubMed

Massella, Laura; Mekahli, Djalila; Paripović, Dušan; Prikhodina, Larisa; Godefroid, Nathalie; Niemirska, Anna; Ağbaş, Ayşe; Kalicka, Karolina; Jankauskiene, Augustina; Mizerska-Wasiak, Malgorzata; Afonso, Alberto Caldas; Salomon, Rémi; Deschênes, Georges; Ariceta, Gema; Özçakar, Z Birsin; Teixeira, Ana; Duzova, Ali; Harambat, Jérôme; Seeman, Tomáš; Hrčková, Gabriela; Lungu, Adrian Catalin; Papizh, Svetlana; Peco-Antic, Amira; De Rechter, Stéphanie; Giordano, Ugo; Kirchner, Marietta; Lutz, Teresa; Schaefer, Franz; Devuyst, Olivier; Wühl, Elke; Emma, Francesco

2018-04-19

Autosomal dominant polycystic kidney disease is the most common inheritable kidney disease, frequently thought to become symptomatic in adulthood. However, patients with autosomal dominant polycystic kidney disease may develop signs or symptoms during childhood, in particular hypertension. Although ambulatory BP monitoring is the preferred method to diagnose hypertension in pediatrics, data in children with autosomal dominant polycystic kidney disease are limited. Our retrospective multicenter study was conducted to collect ambulatory BP monitoring recordings from patients with autosomal dominant polycystic kidney disease age <18 years old. Basic anthropometric parameters as well as data on kidney function, BP treatment, and kidney ultrasound were also collected. Data from 310 children with autosomal dominant polycystic kidney disease with a mean age of 11.5±4.1 years old were collected at 22 European centers. At the time when ambulatory BP monitoring was performed, 95% of children had normal kidney function. Reference data for ambulatory BP monitoring were available for 292 patients. The prevalence rates of children with hypertension and/or those who were treated with antihypertensive drugs were 31%, 42%, and 35% during daytime, nighttime, or the entire 24-hour cycle, respectively. In addition, 52% of participants lacked a physiologic nocturnal BP dipping, and 18% had isolated nocturnal hypertension. Logistic regression analysis showed a significant association between a categorical cyst score that was calculated on the basis of the number of cysts >1 cm per kidney and daytime hypertension (odds ratio, 1.70; 95% confidence interval, 1.21 to 2.4; P =0.002), nighttime hypertension (odds ratio, 1.31; 95% confidence interval, 1.05 to 1.63; P =0.02), or 24-hour hypertension (odds ratio, 1.39; 95% confidence interval, 1.08 to 1.81; P =0.01). Kidney length, expressed as SD score, was also significantly associated with nighttime hypertension (odds ratio, 1.23; 95% confidence interval, 1.06 to 1.42; P =0.10). These data indicate high prevalence of hypertension in children with autosomal dominant polycystic kidney disease starting at young ages. Copyright © 2018 by the American Society of Nephrology.

Human Urine-Derived Renal Progenitors for Personalized Modeling of Genetic Kidney Disorders

PubMed Central

Ronconi, Elisa; Angelotti, Maria Lucia; Peired, Anna; Mazzinghi, Benedetta; Becherucci, Francesca; Conti, Sara; Sansavini, Giulia; Sisti, Alessandro; Ravaglia, Fiammetta; Lombardi, Duccio; Provenzano, Aldesia; Manonelles, Anna; Cruzado, Josep M.; Giglio, Sabrina; Roperto, Rosa Maria; Materassi, Marco; Lasagni, Laura

2015-01-01

The critical role of genetic and epigenetic factors in the pathogenesis of kidney disorders is gradually becoming clear, and the need for disease models that recapitulate human kidney disorders in a personalized manner is paramount. In this study, we describe a method to select and amplify renal progenitor cultures from the urine of patients with kidney disorders. Urine-derived human renal progenitors exhibited phenotype and functional properties identical to those purified from kidney tissue, including the capacity to differentiate into tubular cells and podocytes, as demonstrated by confocal microscopy, Western blot analysis of podocyte-specific proteins, and scanning electron microscopy. Lineage tracing studies performed with conditional transgenic mice, in which podocytes are irreversibly tagged upon tamoxifen treatment (NPHS2.iCreER;mT/mG), that were subjected to doxorubicin nephropathy demonstrated that renal progenitors are the only urinary cell population that can be amplified in long-term culture. To validate the use of these cells for personalized modeling of kidney disorders, renal progenitors were obtained from (1) the urine of children with nephrotic syndrome and carrying potentially pathogenic mutations in genes encoding for podocyte proteins and (2) the urine of children without genetic alterations, as validated by next-generation sequencing. Renal progenitors obtained from patients carrying pathogenic mutations generated podocytes that exhibited an abnormal cytoskeleton structure and functional abnormalities compared with those obtained from patients with proteinuria but without genetic mutations. The results of this study demonstrate that urine-derived patient-specific renal progenitor cultures may be an innovative research tool for modeling of genetic kidney disorders. PMID:25568173

Increased resistin in brain dead organ donors is associated with delayed graft function after kidney transplantation

PubMed Central

2013-01-01

Introduction Resistin increases during several inflammatory diseases and after intracerebral bleeding or head trauma. Resistin activates the endothelium and may initiate an inflammatory response. No data are available on resistin in brain dead donors (DBD) that regularly manifest a pronounced inflammatory state. Methods We analyzed plasma resistin in 63 DBDs and correlated results with donor variables and the postoperative course following kidney transplantation using organs from these donors. Endocan and monocyte chemotactic protein (MCP)-1 were also studied. Twenty-six live kidney donors (LD) and the corresponding kidney transplantations were used as controls. Results DBDs had higher resistin (median/range 30.75 ng/ml, 5.41–173.6) than LD (7.71 ng/ml, 2.41–15.74, p < 0.0001). Resistin in DBD correlated with delayed graft function (DGF) in the kidney recipients (r = 0.321, p < 0.01); receiver operating characteristic curve revealed an area under the curve of 0.765 (95% confidence interval [CI] 0.648–0.881, p < 0.01) and a cut-off value for resistin of 25 ng/ml; MCP-1 and endocan were higher in DBDs (p < 0.0001) but did not correlate with DGF or acute rejection. No relationship was found between the studied molecules and the postoperative course of LD kidney transplants. Conclusions High resistin levels in the DBD before organ retrieval are associated with DGF after kidney transplantation. The resistin increase seems related to the inflammatory state after brain death but not to the cause of death. PMID:24070260

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

Automatic detection of kidney in 3D pediatric ultrasound images using deep neural networks

NASA Astrophysics Data System (ADS)

Tabrizi, Pooneh R.; Mansoor, Awais; Biggs, Elijah; Jago, James; Linguraru, Marius George

2018-02-01

Ultrasound (US) imaging is the routine and safe diagnostic modality for detecting pediatric urology problems, such as hydronephrosis in the kidney. Hydronephrosis is the swelling of one or both kidneys because of the build-up of urine. Early detection of hydronephrosis can lead to a substantial improvement in kidney health outcomes. Generally, US imaging is a challenging modality for the evaluation of pediatric kidneys with different shape, size, and texture characteristics. The aim of this study is to present an automatic detection method to help kidney analysis in pediatric 3DUS images. The method localizes the kidney based on its minimum volume oriented bounding box) using deep neural networks. Separate deep neural networks are trained to estimate the kidney position, orientation, and scale, making the method computationally efficient by avoiding full parameter training. The performance of the method was evaluated using a dataset of 45 kidneys (18 normal and 27 diseased kidneys diagnosed with hydronephrosis) through the leave-one-out cross validation method. Quantitative results show the proposed detection method could extract the kidney position, orientation, and scale ratio with root mean square values of 1.3 +/- 0.9 mm, 6.34 +/- 4.32 degrees, and 1.73 +/- 0.04, respectively. This method could be helpful in automating kidney segmentation for routine clinical evaluation.

Automated Segmentation of Kidneys from MR Images in Patients with Autosomal Dominant Polycystic Kidney Disease

PubMed Central

Kim, Youngwoo; Ge, Yinghui; Tao, Cheng; Zhu, Jianbing; Chapman, Arlene B.; Torres, Vicente E.; Yu, Alan S.L.; Mrug, Michal; Bennett, William M.; Flessner, Michael F.; Landsittel, Doug P.

2016-01-01

Background and objectives Our study developed a fully automated method for segmentation and volumetric measurements of kidneys from magnetic resonance images in patients with autosomal dominant polycystic kidney disease and assessed the performance of the automated method with the reference manual segmentation method. Design, setting, participants, & measurements Study patients were selected from the Consortium for Radiologic Imaging Studies of Polycystic Kidney Disease. At the enrollment of the Consortium for Radiologic Imaging Studies of Polycystic Kidney Disease Study in 2000, patients with autosomal dominant polycystic kidney disease were between 15 and 46 years of age with relatively preserved GFRs. Our fully automated segmentation method was on the basis of a spatial prior probability map of the location of kidneys in abdominal magnetic resonance images and regional mapping with total variation regularization and propagated shape constraints that were formulated into a level set framework. T2–weighted magnetic resonance image sets of 120 kidneys were selected from 60 patients with autosomal dominant polycystic kidney disease and divided into the training and test datasets. The performance of the automated method in reference to the manual method was assessed by means of two metrics: Dice similarity coefficient and intraclass correlation coefficient of segmented kidney volume. The training and test sets were swapped for crossvalidation and reanalyzed. Results Successful segmentation of kidneys was performed with the automated method in all test patients. The segmented kidney volumes ranged from 177.2 to 2634 ml (mean, 885.4±569.7 ml). The mean Dice similarity coefficient ±SD between the automated and manual methods was 0.88±0.08. The mean correlation coefficient between the two segmentation methods for the segmented volume measurements was 0.97 (P<0.001 for each crossvalidation set). The results from the crossvalidation sets were highly comparable. Conclusions We have developed a fully automated method for segmentation of kidneys from abdominal magnetic resonance images in patients with autosomal dominant polycystic kidney disease with varying kidney volumes. The performance of the automated method was in good agreement with that of manual method. PMID:26797708

Automated Segmentation of Kidneys from MR Images in Patients with Autosomal Dominant Polycystic Kidney Disease.

PubMed

Kim, Youngwoo; Ge, Yinghui; Tao, Cheng; Zhu, Jianbing; Chapman, Arlene B; Torres, Vicente E; Yu, Alan S L; Mrug, Michal; Bennett, William M; Flessner, Michael F; Landsittel, Doug P; Bae, Kyongtae T

2016-04-07

Our study developed a fully automated method for segmentation and volumetric measurements of kidneys from magnetic resonance images in patients with autosomal dominant polycystic kidney disease and assessed the performance of the automated method with the reference manual segmentation method. Study patients were selected from the Consortium for Radiologic Imaging Studies of Polycystic Kidney Disease. At the enrollment of the Consortium for Radiologic Imaging Studies of Polycystic Kidney Disease Study in 2000, patients with autosomal dominant polycystic kidney disease were between 15 and 46 years of age with relatively preserved GFRs. Our fully automated segmentation method was on the basis of a spatial prior probability map of the location of kidneys in abdominal magnetic resonance images and regional mapping with total variation regularization and propagated shape constraints that were formulated into a level set framework. T2-weighted magnetic resonance image sets of 120 kidneys were selected from 60 patients with autosomal dominant polycystic kidney disease and divided into the training and test datasets. The performance of the automated method in reference to the manual method was assessed by means of two metrics: Dice similarity coefficient and intraclass correlation coefficient of segmented kidney volume. The training and test sets were swapped for crossvalidation and reanalyzed. Successful segmentation of kidneys was performed with the automated method in all test patients. The segmented kidney volumes ranged from 177.2 to 2634 ml (mean, 885.4±569.7 ml). The mean Dice similarity coefficient ±SD between the automated and manual methods was 0.88±0.08. The mean correlation coefficient between the two segmentation methods for the segmented volume measurements was 0.97 (P<0.001 for each crossvalidation set). The results from the crossvalidation sets were highly comparable. We have developed a fully automated method for segmentation of kidneys from abdominal magnetic resonance images in patients with autosomal dominant polycystic kidney disease with varying kidney volumes. The performance of the automated method was in good agreement with that of manual method. Copyright © 2016 by the American Society of Nephrology.

Effects of uric acid on kidney function decline differ depending on baseline kidney function in type 2 diabetic patients.

PubMed

Hanai, Ko; Tauchi, Eriko; Nishiwaki, Yui; Mori, Tomomi; Yokoyama, Yoichi; Uchigata, Yasuko; Babazono, Tetsuya

2018-05-30

Most existing data regarding effects of uric acid (UA) on diabetic kidney disease have considered patients with preserved kidney function. We examined a hypothesis that there are differences in the effects of serum UA levels on the decline in kidney function depending on baseline kidney function in diabetic patients. In this historical cohort study, 7033 type 2 diabetic patients were analyzed and classified into two groups as follows: nonchronic kidney disease (non-CKD), with an estimated glomerular filtration rate (eGFR) ≥60 mL/min/1.73 m2 (n = 4994), and CKD, with an eGFR <60 mL/min/1.73 m2 (n = 2039). The composite endpoint was a ≥30% decrease in eGFR from baseline or the initiation of renal replacement therapy. The hazard ratio (HR) of serum UA levels at baseline was estimated using multivariate Cox proportional hazards models. There was a significant interaction between UA levels and baseline eGFR with respect to the endpoint (P < 0.001). The HRs of 1 mg/dL increase in UA levels were 1.13 [95% confidence interval (CI) 1.05-1.22, P = 0.002] and 0.93 (95% CI 0.88-0.99, P = 0.02) in the non-CKD and CKD groups, respectively. When patients were classified by quintile of UA levels, the HRs of those in the 5th quintile (versus 1st quintile) were 1.64 (95% CI 1.23-2.18, P < 0.001) and 0.76 (95% CI 0.58-0.99, P = 0.05) in the non-CKD and CKD groups, respectively. The effects of UA on kidney function decline might differ depending on baseline kidney function in type 2 diabetic patients. High UA levels are the prognostic factor only in patients with preserved kidney function.

Prognostic Value of Improved Kidney Function After Transcatheter Aortic Valve Implantation for Aortic Stenosis.

PubMed

Nijenhuis, Vincent Johan; Peper, Joyce; Vorselaars, Veronique M M; Swaans, Martin J; De Kroon, Thom; Van der Heyden, Jan A S; Rensing, Benno J W M; Heijmen, Robin; Bos, Willem-Jan W; Ten Berg, Jurrien M

2018-05-15

Transcatheter aortic valve implantation (TAVI) is associated with acute kidney injury (AKI), but can also improve the kidney function (IKF). We assessed the effects of kidney function changes in relation to baseline kidney function on 2-year clinical outcomes after TAVI. In total, 639 consecutive patients with aortic stenosis who underwent TAVI were stratified into 3 groups according to the ratio of serum creatinine post- to pre-TAVI: IKF (≤0.80; n = 95 [15%]), stable kidney function (0.80 to 1.5; n = 477 [75%]), and AKI (≥1.5; n = 67 [10%]). Different AKI risk scores were compared using receiving-operator characteristics. Median follow-up was 24 (8 to 44) months. At 3 months, the increase in estimated glomerular filtration rate in the IKF group remained, and the decreased estimated glomerular filtration rate in the AKI group recovered. Compared with a stable kidney function, AKI showed a higher 2-year mortality rate (adjusted hazard ratio [HR] 3.69, 95% confidence interval [CI] 2.43 to 5.62) and IKF a lower mortality rate (adjusted hazard ratio 0.53, 95% CI 0.30 to 0.93). AKI also predicted major and life-threatening bleeding (adjusted odds ratio 2.94, 95% CI 1.27 to 6.78). Independent predictors of AKI were chronic kidney disease and pulmonary hypertension. Independent predictors of IKF were female gender, a preserved kidney function, absence of atrial fibrillation, and hemoglobin level. Established AKI risk scores performed moderately and did not differentiate between AKI and IKF. In conclusion, AKI is transient and is independently associated with a higher mortality rate, whereas IKF is sustained and is associated with a lower mortality rate. These effects are independent of baseline kidney function. Further studies are warranted to investigate the role of IKF and generate a dedicated prediction model. Copyright © 2018 Elsevier Inc. All rights reserved.

Compensatory Structural and Functional Adaptation after Radical Nephrectomy for Renal Cell Carcinoma According to Preoperative Stage of Chronic Kidney Disease.

PubMed

Choi, Don Kyoung; Jung, Se Bin; Park, Bong Hee; Jeong, Byong Chang; Seo, Seong Il; Jeon, Seong Soo; Lee, Hyun Moo; Choi, Han-Yong; Jeon, Hwang Gyun

2015-10-01

We investigated structural hypertrophy and functional hyperfiltration as compensatory adaptations after radical nephrectomy in patients with renal cell carcinoma according to the preoperative chronic kidney disease stage. We retrospectively identified 543 patients who underwent radical nephrectomy for renal cell carcinoma between 1997 and 2012. Patients were classified according to preoperative glomerular filtration rate as no chronic kidney disease--glomerular filtration rate 90 ml/minute/1.73 m(2) or greater (230, 42.4%), chronic kidney disease stage II--glomerular filtration rate 60 to less than 90 ml/minute/1.73 m(2) (227, 41.8%) and chronic kidney disease stage III--glomerular filtration rate 30 to less than 60 ml/minute/1.73 m(2) (86, 15.8%). Computerized tomography performed within 2 months before surgery and 1 year after surgery was used to assess functional renal volume for measuring the degree of hypertrophy of the remnant kidney, and the preoperative and postoperative glomerular filtration rate per unit volume of functional renal volume was used to calculate the degree of hyperfiltration. Among all patients (mean age 56.0 years) mean preoperative glomerular filtration rate, functional renal volume and glomerular filtration rate/functional renal volume were 83.2 ml/minute/1.73 m(2), 340.6 cm(3) and 0.25 ml/minute/1.73 m(2)/cm(3), respectively. The percent reduction in glomerular filtration rate was statistically significant according to chronic kidney disease stage (no chronic kidney disease 31.2% vs stage II 26.5% vs stage III 12.8%, p <0.001). However, the degree of hypertrophic functional renal volume in the remnant kidney was not statistically significant (no chronic kidney disease 18.5% vs stage II 17.3% vs stage III 16.5%, p=0.250). The change in glomerular filtration rate/functional renal volume was statistically significant (no chronic kidney disease 18.5% vs stage II 20.1% vs stage III 45.9%, p <0.001). Factors that increased glomerular filtration rate/functional renal volume above the mean value were body mass index (p=0.012), diabetes mellitus (p=0.023), hypertension (p=0.015) and chronic kidney disease stage (p <0.001). Patients with a lower preoperative glomerular filtration rate had a smaller reduction in postoperative renal function than those with a higher preoperative glomerular filtration rate due to greater degrees of functional hyperfiltration. Copyright © 2015 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

Bioprinting of 3D Convoluted Renal Proximal Tubules on Perfusable Chips

NASA Astrophysics Data System (ADS)

Homan, Kimberly A.; Kolesky, David B.; Skylar-Scott, Mark A.; Herrmann, Jessica; Obuobi, Humphrey; Moisan, Annie; Lewis, Jennifer A.

2016-10-01

Three-dimensional models of kidney tissue that recapitulate human responses are needed for drug screening, disease modeling, and, ultimately, kidney organ engineering. Here, we report a bioprinting method for creating 3D human renal proximal tubules in vitro that are fully embedded within an extracellular matrix and housed in perfusable tissue chips, allowing them to be maintained for greater than two months. Their convoluted tubular architecture is circumscribed by proximal tubule epithelial cells and actively perfused through the open lumen. These engineered 3D proximal tubules on chip exhibit significantly enhanced epithelial morphology and functional properties relative to the same cells grown on 2D controls with or without perfusion. Upon introducing the nephrotoxin, Cyclosporine A, the epithelial barrier is disrupted in a dose-dependent manner. Our bioprinting method provides a new route for programmably fabricating advanced human kidney tissue models on demand.

Bioprinting of 3D Convoluted Renal Proximal Tubules on Perfusable Chips

PubMed Central

Homan, Kimberly A.; Kolesky, David B.; Skylar-Scott, Mark A.; Herrmann, Jessica; Obuobi, Humphrey; Moisan, Annie; Lewis, Jennifer A.

2016-01-01

Three-dimensional models of kidney tissue that recapitulate human responses are needed for drug screening, disease modeling, and, ultimately, kidney organ engineering. Here, we report a bioprinting method for creating 3D human renal proximal tubules in vitro that are fully embedded within an extracellular matrix and housed in perfusable tissue chips, allowing them to be maintained for greater than two months. Their convoluted tubular architecture is circumscribed by proximal tubule epithelial cells and actively perfused through the open lumen. These engineered 3D proximal tubules on chip exhibit significantly enhanced epithelial morphology and functional properties relative to the same cells grown on 2D controls with or without perfusion. Upon introducing the nephrotoxin, Cyclosporine A, the epithelial barrier is disrupted in a dose-dependent manner. Our bioprinting method provides a new route for programmably fabricating advanced human kidney tissue models on demand. PMID:27725720

Stomatal cell wall composition: distinctive structural patterns associated with different phylogenetic groups

PubMed Central

Shtein, Ilana; Shelef, Yaniv; Marom, Ziv; Zelinger, Einat; Schwartz, Amnon; Popper, Zoë A.; Bar-On, Benny

2017-01-01

Background and Aims Stomatal morphology and function have remained largely conserved throughout ∼400 million years of plant evolution. However, plant cell wall composition has evolved and changed. Here stomatal cell wall composition was investigated in different vascular plant groups in attempt to understand their possible effect on stomatal function. Methods A renewed look at stomatal cell walls was attempted utilizing digitalized polar microscopy, confocal microscopy, histology and a numerical finite-elements simulation. The six species of vascular plants chosen for this study cover a broad structural, ecophysiological and evolutionary spectrum: ferns (Asplenium nidus and Platycerium bifurcatum) and angiosperms (Arabidopsis thaliana and Commelina erecta) with kidney-shaped stomata, and grasses (angiosperms, family Poaceae) with dumbbell-shaped stomata (Sorghum bicolor and Triticum aestivum). Key Results Three distinct patterns of cellulose crystallinity in stomatal cell walls were observed: Type I (kidney-shaped stomata, ferns), Type II (kidney-shaped stomata, angiosperms) and Type III (dumbbell-shaped stomata, grasses). The different stomatal cell wall attributes investigated (cellulose crystallinity, pectins, lignin, phenolics) exhibited taxon-specific patterns, with reciprocal substitution of structural elements in the end-walls of kidney-shaped stomata. According to a numerical bio-mechanical model, the end walls of kidney-shaped stomata develop the highest stresses during opening. Conclusions The data presented demonstrate for the first time the existence of distinct spatial patterns of varying cellulose crystallinity in guard cell walls. It is also highly intriguing that in angiosperms crystalline cellulose appears to have replaced lignin that occurs in the stomatal end-walls of ferns serving a similar wall strengthening function. Such taxon-specific spatial patterns of cell wall components could imply different biomechanical functions, which in turn could be a consequence of differences in environmental selection along the course of plant evolution. PMID:28158449

Effects of a restricted fetal growth environment on human kidney morphology, cell apoptosis and gene expression.

PubMed

Wang, Yan-Ping; Chen, Xu; Zhang, Zhi-Kun; Cui, Hong-Yan; Wang, Peng; Wang, Yue

2015-12-01

Kidney development is key to the onset of hypertension and cardiovascular diseases in adults, and in the fetal stage will be impaired by a lack of nutrients in utero in animal models. However, few human studies have been performed. Kidney samples from fetuses in a fetal growth restriction (FGR) environment were collected and the morphological characteristics were observed. Potentially molecular mechanisms were explored by analyzing apoptosis and kidney-development related gene expression. The results indicated that no malformations were observed in the kidney samples of the FGR group, but the mean kidney weight and volume were significantly decreased. Moreover, the ratio of apoptotic cells and Bax-positive cells was increased and the ratio of Bcl-2-positive cells was decreased in the FGR group, indicating potential apoptosis induction under an in utero FGR environment. Finally, aberrant expression of renin and angiotensinogen indicated potential kidney functional abnormalities in the FGR group. Our study suggested increased apoptosis and decreased renin and angiotensinogen expression during human kidney development in an FGR environment. The current results will be helpful to further explore the molecular mechanism of FGR and facilitate future studies of hypertension and cardiovascular diseases and the establishment of preventive methods. © The Author(s) 2014.

Urinary Biomarkers at Early ADPKD Disease Stage

PubMed Central

Petzold, Katja; Poster, Diane; Krauer, Fabienne; Spanaus, Katharina; Andreisek, Gustav; Nguyen-Kim, Thi Dan Linh; Pavik, Ivana; Ho, Thien Anh; Serra, Andreas L.; Rotar, Laura

2015-01-01

Background Autosomal dominant polycystic kidney disease (ADPKD) is characterized by a decline in renal function at late disease stage when the majority of functional renal parenchyma is replaced by cystic tissue. Thus, kidney function, assessed by estimated glomerular filtration rate (eGFR) does not well represent disease burden in early disease. Here, we investigated various urinary markers for tubular injury and their association with disease burden in ADPKD patients at early disease course. Methods ADPKD patients between 18 and 40 years with an eGFR greater or equal to 70 ml per min per 1.73m2 were eligible for this cross-sectional study. Urinary Neutrophil Gelatinase-Associated Lipocalin (NGAL), Kidney Injury Molecule-1 (KIM-1), and Uromodulin (UMOD) were investigated by Enzyme-Linked Immunosorbent Assay. Clara Cell Protein 16 (CC16) was investigated by Latex Immuno Assay. Cryoscopy was performed to assess urine osmolality and Urinary Albumin-to-Creatinine Ratio (UACR) was calculated. The association and the predictive properties of the markers on eGFR and height adjusted total kidney volume (htTKV) was evaluated using multiple regression analysis, incorporating different control variables for adjustment. Internal bootstrapping validated the obtained results. Results In 139 ADPKD patients (age 31 ±7 years, mean eGFR of 93 ± 19 ml per min per 1.73 m2) the total kidney volume was negatively correlated with eGFR and UMOD and positive associated with age, UACR, KIM-1 and urine osmolality after adjustment for possible confounders. Urine osmolality and htTKV were also associated with eGFR, whereas no association of CC16, NGAL and UMOD with eGFR or htTKV was found. Conclusion UACR and urinary KIM-1 are independently associated with kidney size but not with renal function in our study population. Urine osmolality was associated with eGFR and kidney volume following adjustment for multiple confounders. Despite statistical significance, the clinical value of our results is not yet conceivable. Further studies are needed to evaluate the property of the aforementioned biomarkers to assess disease state at early ADPKD stage. PMID:25875363

Simultaneous liver, pancreas-duodenum and kidney transplantation in a patient with hepatitis B cirrhosis, uremia and insulin dependent diabetes mellitus.

PubMed

Li, Jiang; Guo, Qing-Jun; Cai, Jin-Zhen; Pan, Cheng; Shen, Zhong-Yang; Jiang, Wen-Tao

2017-12-07

Simultaneous liver, pancreas-duodenum, and kidney transplantation has been rarely reported in the literature. Here we present a new and more efficient en bloc technique that combines classic orthotopic liver and pancreas-duodenum transplantation and heterotopic kidney transplantation for a male patient aged 44 years who had hepatitis B related cirrhosis, renal failure, and insulin dependent diabetes mellitus (IDDM). A quadruple immunosuppressive regimen including induction with basiliximab and maintenance therapy with tacrolimus, mycophenolate mofetil, and steroids was used in the early stage post-transplant. Postoperative recovery was uneventful and the patient was discharged on the 15 th postoperative day with normal liver and kidney function. The insulin treatment was completely withdrawn 3 wk after operation, and the blood glucose level remained normal. The case findings support that abdominal organ cluster and kidney transplantation is an effective method for the treatment of end-stage liver disease combined with uremia and IDDM.

Disruption of Hox9,10,11 function results in cellular level lineage infidelity in the kidney.

PubMed

Drake, Keri A; Adam, Mike; Mahoney, Robert; Potter, S Steven

2018-04-20

Hox genes are important regulators of development. The 39 mammalian Hox genes have considerable functional overlap, greatly confounding their study. In this report, we generated mice with multiple combinations of paralogous and flanking Abd-B Hox gene mutations to investigate functional redundancies in kidney development. The resulting mice developed a number of kidney abnormalities, including hypoplasia, agenesis, and severe cysts, with distinct Hox functions observed in early metanephric kidney formation and nephron progenitor maintenance. Most surprising, however, was that extensive removal of Hox shared function in these kidneys resulted in cellular level lineage infidelity. Strikingly, mutant nephron tubules consisted of intermixed cells with proximal tubule, loop of Henle, and collecting duct identities, with some single cells expressing markers associated with more than one nephron segment. These results indicate that Hox genes are required for proper lineage selection/maintenance and full repression of genes involved in cell fate restriction in the developing kidney.

Endovascular Repair of Abdominal Aortic Aneurysms in the Presence of a Transplanted Kidney

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

Silverberg, Daniel, E-mail: silverberg-d@msn.com; Yalon, Tal; Halak, Moshe

PurposeTo present our experience performing endovascular repair of abdominal aortic aneurysms in kidney transplanted patients.MethodsA retrospective review of all patients who underwent endovascular aneurysm repair (EVAR) for abdominal aortic aneurysms (AAA) performed at our institution from 2007 to 2014. We identified all patients who had previously undergone a kidney transplant. Data collected included: comorbidities, preoperative imaging modalities, indication for surgery, stent graft configurations, pre- and postoperative renal function, perioperative complications, and survival rates.ResultsA total of 267 EVARs were performed. Six (2 %) had a transplanted kidney. Mean age was 74 (range, 64–82) years; five were males. Mean time from transplantation tomore » EVAR was 7.5 (range, 2–12) years. Five underwent preoperative planning with noncontrast modalities only. Devices used included bifurcated (n = 3), aortouniiliac (n = 2), and tube (n = 1) stent grafts. Technical success was achieved in all patients. None experienced deterioration in renal function. Median follow-up was 39 (range, 6–51) months. Four patients were alive at the time of the study. Two patients expired during the period of follow-up from unrelated causes.ConclusionsEVAR is an effective modality for the management of AAAs in the coexistence of a transplanted kidney. It can be performed with minimal morbidity and mortality without harming the transplanted kidney. Special consideration should be given to device configuration to minimize damage to the renal graft.« less

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.

Association of serum albumin levels with kidney function decline and incident chronic kidney disease in elders.

PubMed

Lang, Joshua; Katz, Ronit; Ix, Joachim H; Gutierrez, Orlando M; Peralta, Carmen A; Parikh, Chirag R; Satterfield, Suzanne; Petrovic, Snezana; Devarajan, Prasad; Bennett, Michael; Fried, Linda F; Cummings, Steven R; Sarnak, Mark J; Shlipak, Michael G

2018-06-01

Previous studies in HIV-infected individuals have demonstrated serum albumin to be strongly associated with kidney function decline, independent of urine albumin and inflammatory markers. Lower serum albumin concentrations may be an under-appreciated risk factor for kidney function decline in elders. We performed a cohort analysis in the Health Aging and Body Composition Study, a cohort of well-functioning, bi-racial, community-dwelling elders between the age of 70 and 79 years. We examined the associations of serum albumin concentration with longitudinal kidney function decline by estimated glomerular filtration rate (eGFR). Outcomes included linear eGFR decline, rapid kidney function decline defined as >30% decrease in eGFR, defined as a final eGFR <60 mL/min/1.73 m2 in those with an eGFR >60 mL/min/1.73 m2 at baseline. Cystatin C-based eGFR was calculated at baseline, Year 3 and Year 10. Mean age was 74 years, and mean eGFR was 73 mL/min/1.73 m2 at baseline. The mean rate of eGFR change was 1.81 mL/min/1.73 m2 per year. After multivariate adjustment, lower serum albumin concentrations were strongly and independently associated with kidney function decline (-0.11 mL/min/1.73 m2 per year for each standard deviation decrease serum albumin; -0.01 to - 0.20) with no attenuation after adjustment for urine albumin and inflammatory markers (-0.12, -0.03 to - 0.22). When divided into quartiles, serum albumin levels ≤3.80 g/dL were associated with increased odds of rapid kidney function decline (odds ratio 1.59; 1.12-2.26) and increased risk of incident chronic kidney disease (incident rate ratio 1.29; 1.03-1.62) relative to levels >4.21g/dL. Urine albumin to creatinine ratio (ACR) was also significantly and independently associated with kidney function decline (-0.08 mL/min/1.73 m2 per year for urine ACR >30 mg/g; -0.82 to - 0.13). Lower serum albumin levels are strongly and independently associated with kidney function decline in elders, independent of clinical risk factors, urine albumin and measured inflammatory markers.

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.

Using optical coherence tomography (OCT) to evaluate the status of human donor kidneys (Conference Presentation)

NASA Astrophysics Data System (ADS)

Andrews, Peter M.; Konkel, Brandon; Anderson, Erik; Stein, Matthew; Cooper, Matthew; Verbesey, Jennifer E.; Ghasemian, Seyed; Chen, Yu

2016-02-01

The main cause of delayed renal function following the transplant of donor kidneys is ischemic induced acute tubular necrosis (ATN). The ability to determine the degree of ATN suffered by donor kidneys prior to their transplant would enable transplant surgeons to use kidneys that might otherwise be discarded and better predict post-transplant renal function. Currently, there are no reliable tests to determine the extent of ATN of donor kidneys prior to their transplant. In ongoing clinical trials, we have been using optical coherence tomography (OCT) to non-invasively image the superficial proximal tubules of human donor kidneys prior to and following transplant, and correlate these observations with post-transplant renal function. Thus far we have studied over 40 living donor kidneys and 10 cadaver donor kidneys, and demonstrated that this imaging can be performed in a sterile and expeditious fashion in the operating room (OR). Because of many variables associated with a diverse population of donors/recipients and transplant operation parameters, more transplant data must be collected prior to drawing definite conclusions. Nevertheless, our observations have thus far mirrored our previously published laboratory results indicating that damage to the kidney proximal tubules as indicated by tubule swelling is a good measure of post-transplant ATN and delayed graft function. We conclude that OCT is a useful procedure for analyzing human donor kidneys.

Trajectories of eGFR decline over a four year period in an Indigenous Australian population at high risk of CKD-the eGFR follow up study.

PubMed

Barzi, Federica; Jones, Graham R D; Hughes, Jaquelyne T; Lawton, Paul D; Hoy, Wendy; O'Dea, Kerin; Jerums, George; MacIsaac, Richard J; Cass, Alan; Maple-Brown, Louise J

2018-03-01

Being able to estimate kidney decline accurately is particularly important in Indigenous Australians, a population at increased risk of developing chronic kidney disease and end stage kidney disease. The aim of this analysis was to explore the trend of decline in estimated glomerular filtration rate (eGFR) over a four year period using multiple local creatinine measures, compared with estimates derived using centrally-measured enzymatic creatinine and with estimates derived using only two local measures. The eGFR study comprised a cohort of over 600 Aboriginal Australian participants recruited from over twenty sites in urban, regional and remote Australia across five strata of health, diabetes and kidney function. Trajectories of eGFR were explored on 385 participants with at least three local creatinine records using graphical methods that compared the linear trends fitted using linear mixed models with non-linear trends fitted using fractional polynomial equations. Temporal changes of local creatinine were also characterized using group-based modelling. Analyses were stratified by eGFR (<60; 60-89; 90-119 and ≥120ml/min/1.73m 2 ) and albuminuria categories (<3mg/mmol; 3-30mg/mmol; >30mg/mmol). Mean age of the participants was 48years, 64% were female and the median follow-up was 3years. Decline of eGFR was accurately estimated using simple linear regression models and locally measured creatinine was as good as centrally measured creatinine at predicting kidney decline in people with an eGFR<60 and an eGFR 60-90ml/min/1.73m 2 with albuminuria. Analyses showed that one baseline and one follow-up locally measured creatinine may be sufficient to estimate short term (up to four years) kidney function decline. The greatest yearly decline was estimated in those with eGFR 60-90 and macro-albuminuria: -6.21 (-8.20, -4.23) ml/min/1.73m 2 . Short term estimates of kidney function decline can be reliably derived using an easy to implement and simple to interpret linear mixed effect model. Locally measured creatinine did not differ to centrally measured creatinine, thus is an accurate cost-efficient and timely means to monitoring kidney function progression. Copyright © 2018 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved.

Cold preservation with hyperbranched polyglycerol-based solution improves kidney functional recovery with less injury at reperfusion in rats

PubMed Central

Li, Shadan; Liu, Bin; Guan, Qiunong; Chafeeva, Irina; Brooks, Donald E; Nguan, Christopher YC; Kizhakkedathu, Jayachandran N; Du, Caigan

2017-01-01

Minimizing donor organ injury during cold preservation (including cold perfusion and storage) is the first step to prevent transplant failure. We recently reported the advantages of hyperbranched polyglycerol (HPG) as a novel substitute for hydroxyethyl starch in UW solution for both cold heart preservation and cold kidney perfusion. This study evaluated the functional recovery of the kidney at reperfusion after cold preservation with HPG solution. The impact of HPG solution compared to conventional UW and HTK solutions on tissue weight and cell survival at 4°C was examined using rat kidney tissues and cultured human umbilical vein endothelial cells (HUVECs), respectively. The kidney protection by HPG solution was tested in a rat model of cold kidney ischemia-reperfusion injury, and was evaluated by histology and kidney function. Here, we showed that preservation with HPG solution prevented cell death in cultured HUVECs and edema formation in kidney tissues at 4°C similar to UW solution, whereas HTK solution was less effective. In rat model of cold ischemia-reperfusion injury, the kidneys perfused and subsequently stored 1-hour with cold HPG solution showed less leukocyte infiltration, less tubular damage and better kidney function (lower levels of serum creatinine and blood urea nitrogen) at 48 h of reperfusion than those treated with UW or HTK solution. In conclusion, our data show the superiority of HPG solution to UW or HTK solution in the cold perfusion and storage of rat kidneys, suggesting that the HPG solution may be a promising candidate for improved donor kidney preservation prior to transplantation. PMID:28337272

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

Kidney volume measurement methods for clinical studies on autosomal dominant polycystic kidney disease

PubMed Central

Sharma, Kanishka; Caroli, Anna; Quach, Le Van; Petzold, Katja; Bozzetto, Michela; Serra, Andreas L.; Remuzzi, Giuseppe; Remuzzi, Andrea

2017-01-01

Background In autosomal dominant polycystic kidney disease (ADPKD), total kidney volume (TKV) is regarded as an important biomarker of disease progression and different methods are available to assess kidney volume. The purpose of this study was to identify the most efficient kidney volume computation method to be used in clinical studies evaluating the effectiveness of treatments on ADPKD progression. Methods and findings We measured single kidney volume (SKV) on two series of MR and CT images from clinical studies on ADPKD (experimental dataset) by two independent operators (expert and beginner), twice, using all of the available methods: polyline manual tracing (reference method), free-hand manual tracing, semi-automatic tracing, Stereology, Mid-slice and Ellipsoid method. Additionally, the expert operator also measured the kidney length. We compared different methods for reproducibility, accuracy, precision, and time required. In addition, we performed a validation study to evaluate the sensitivity of these methods to detect the between-treatment group difference in TKV change over one year, using MR images from a previous clinical study. Reproducibility was higher on CT than MR for all methods, being highest for manual and semiautomatic contouring methods (planimetry). On MR, planimetry showed highest accuracy and precision, while on CT accuracy and precision of both planimetry and Stereology methods were comparable. Mid-slice and Ellipsoid method, as well as kidney length were fast but provided only a rough estimate of kidney volume. The results of the validation study indicated that planimetry and Stereology allow using an importantly lower number of patients to detect changes in kidney volume induced by drug treatment as compared to other methods. Conclusions Planimetry should be preferred over fast and simplified methods for accurately monitoring ADPKD progression and assessing drug treatment effects. Expert operators, especially on MR images, are required for performing reliable estimation of kidney volume. The use of efficient TKV quantification methods considerably reduces the number of patients to enrol in clinical investigations, making them more feasible and significant. PMID:28558028

Association between physical activity and kidney function: National Health and Nutrition Examination Survey.

PubMed

Hawkins, Marquis S; Sevick, Mary Ann; Richardson, Caroline R; Fried, Linda F; Arena, Vincent C; Kriska, Andrea M

2011-08-01

Chronic kidney disease is a condition characterized by the deterioration of the kidney's ability to remove waste products from the body. Although treatments to slow the progression of the disease are available, chronic kidney disease may eventually lead to a complete loss of kidney function. Previous studies have shown that physical activities of moderate intensity may have renal benefits. Few studies have examined the effects of total movement on kidney function. The purpose of this study was to determine the association between time spent at all levels of physical activity intensity and sedentary behavior and kidney function. Data were obtained from the 2003-2004 and 2005-2006 National Health and Nutrition Examination Survey, a cross-sectional study of a complex, multistage probability sample of the US population. Physical activity was assessed using an accelerometer and questionnaire. Glomerular filtration rate (eGFR) was estimated using the Modification of Diet in Renal Disease study formula. To assess linear associations between levels of physical activity and sedentary behavior with log-transformed estimated GFR (eGFR), linear regression was used. In general, physical activity (light and total) was related to log eGFR in females and males. For females, the association between light and total physical activity with log eGFR was consistent regardless of diabetes status. For males, the association between light and total physical activity and log eGFR was only significant in males without diabetes. When examining the association between physical activity, measured objectively with an accelerometer, and kidney function, total and light physical activities were found to be positively associated with kidney function.

Pathogenesis of renal failure in multiple myeloma: any role of contrast media?

PubMed

Mussap, Michele; Merlini, Giampaolo

2014-01-01

The spectrum of kidney disease-associated monoclonal immunoglobulin and plasma cell malignancies is remarkably broad and encompasses nearly all nephropathologic entities. Multiple myeloma with kidney impairment at presentation is a medical emergency since the recovery of kidney function is associated with survival benefits. In most cases, kidney impairment may be the first clinical manifestation of malignant plasma cell dyscrasias like multiple myeloma and light chain amyloidosis. Multiple myeloma per se cannot be considered a main risk factor for developing acute kidney injury following intravascular administration of iodinated contrast media. The risk is increased by comorbidities such as chronic kidney disease, diabetes, hypercalcemia, dehydration, and use of nephrotoxic drugs. Before the administration of contrast media, the current recommended laboratory tests for assessing kidney function are serum creatinine measurement and the estimation of glomerular filtration rate by using the CKD-EPI equation. The assessment of Bence Jones proteinuria is unnecessary for evaluating the risk of kidney failure in patients with multiple myeloma, since this test cannot be considered a surrogate biomarker of kidney function.

Pathogenesis of Renal Failure in Multiple Myeloma: Any Role of Contrast Media?

PubMed Central

Mussap, Michele; Merlini, Giampaolo

2014-01-01

The spectrum of kidney disease-associated monoclonal immunoglobulin and plasma cell malignancies is remarkably broad and encompasses nearly all nephropathologic entities. Multiple myeloma with kidney impairment at presentation is a medical emergency since the recovery of kidney function is associated with survival benefits. In most cases, kidney impairment may be the first clinical manifestation of malignant plasma cell dyscrasias like multiple myeloma and light chain amyloidosis. Multiple myeloma per se cannot be considered a main risk factor for developing acute kidney injury following intravascular administration of iodinated contrast media. The risk is increased by comorbidities such as chronic kidney disease, diabetes, hypercalcemia, dehydration, and use of nephrotoxic drugs. Before the administration of contrast media, the current recommended laboratory tests for assessing kidney function are serum creatinine measurement and the estimation of glomerular filtration rate by using the CKD-EPI equation. The assessment of Bence Jones proteinuria is unnecessary for evaluating the risk of kidney failure in patients with multiple myeloma, since this test cannot be considered a surrogate biomarker of kidney function. PMID:24877060

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.

Kidneys: Key Modulators of HDL Levels and Function

PubMed Central

Yang, Haichun; Fogo, Agnes B.; Kon, Valentina

2016-01-01

Purpose of review This review will examine advances in our understanding of the role kidneys play in HDL metabolism and the effect on levels, composition, and function of HDL particles. Recent findings Components of the HDL particles can cross the glomerular filtration barrier. Some of these components, including apolipoproteins and enzymes involved in lipid metabolism, are taken up by the proximal tubule and degraded, modified, salvaged/returned to the circulation, or lost in the urine. Injury of the glomerular capillaries or tubules can affect these intrarenal processes and modify HDL. Changes in the plasma and urine levels of HDL may be novel markers of kidney damage and/or mechanism(s) of kidney disease. Summary The kidneys have a significant role in metabolism of individual HDL components, which in turn modulate HDL levels, composition and functionality of HDL particles. These intrarenal effects may be useful markers of kidney damage and have consequences on kidney-related perturbations in HDL. PMID:27008596

Cardiorenal syndrome: new developments in the understanding and pharmacologic management.

PubMed

House, Andrew A

2013-10-01

Cardiorenal syndromes (CRSs) with bidirectional heart-kidney signaling are increasingly being recognized for their association with increased morbidity and mortality. In acute CRS, recognition of the importance of worsening kidney function complicating management of acute decompensated heart failure has led to the examination of this specific outcome in the context of acute heart failure clinical trials. In particular, the role of fluid overload and venous congestion has focused interest in the most effective use of diuretic therapy to relieve symptoms of heart failure while at the same time preserving kidney function. Additionally, many novel vasoactive therapies have been studied in recent years with the hopes of augmenting cardiac function, improving symptoms and patient outcomes, while maintaining or improving kidney function. Similarly, recent advances in our understanding of the pathophysiology of chronic CRS have led to reanalysis of kidney outcomes in pivotal trials in chronic congestive heart failure, and newer trials are including changes in kidney function as well as kidney injury biomarkers as prospectively monitored and adjudicated outcomes. This paper provides an overview of some new developments in the pharmacologic management of acute and chronic CRS, examines several reports that illustrate a key management principle for each subtype, and discusses opportunities for future research.

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

Four-dimensional MRI of renal function in the developing mouse.

PubMed

Xie, Luke; Subashi, Ergys; Qi, Yi; Knepper, Mark A; Johnson, G Allan

2014-09-01

The major roles of filtration, metabolism and high blood flow make the kidney highly vulnerable to drug-induced toxicity and other renal injuries. A method to follow kidney function is essential for the early screening of toxicity and malformations. In this study, we acquired high spatiotemporal resolution (four dimensional) datasets of normal mice to follow changes in kidney structure and function during development. The data were acquired with dynamic contrast-enhanced MRI (via keyhole imaging) and a cryogenic surface coil, allowing us to obtain a full three-dimensional image (isotropic resolution, 125 microns) every 7.7 s over a 50-min scan. This time course permitted the demonstration of both contrast enhancement and clearance. Functional changes were measured over a 17-week course (at 3, 5, 7, 9, 13 and 17 weeks). The time dimension of the MRI dataset was processed to produce unique image contrasts to segment the four regions of the kidney: cortex (CO), outer stripe (OS) of the outer medulla (OM), inner stripe (IS) of the OM and inner medulla (IM). Local volumes, time-to-peak (TTP) values and decay constants (DC) were measured in each renal region. These metrics increased significantly with age, with the exception of DC values in the IS and OS. These data will serve as a foundation for studies of normal renal physiology and future studies of renal diseases that require early detection and intervention. Copyright © 2014 John Wiley & Sons, Ltd.

Analysis of Changes in the Glomerular Filtration Rate as Measured by the Cockroft-Gault Formula in the Early Period after Percutaneous Nephrolithotomy

PubMed Central

Seckiner, Ilker; Erturhan, Sakip M.; Mizrak, Sedat; Erbagci, Ahmet

2012-01-01

Purpose We aimed to analyze the changes in kidney function during the postoperative early period caused by the application of percutaneous nephrolithotomy (PNL), which is commonly used in kidney stone surgery. Materials and Methods PNL was performed in 80 patients (48 men, 32 women) with kidney stones. The mean age of the patients was 43.71 years (range, 18 to 71 years). Preoperative and postoperative values for stone size, glomerular filtration rate (GFR), serum creatinine, urea, electrolytes (Na, K, Cl), and Hb were compared in 80 patients in whom PNL surgery was performed. The formula of Cockroft-Gault was used to calculate the GFR during the early postoperative period (72 to 96 hours). Results Statistically significant decreases after PNL were observed in average stone size (preoperative, 627.75±375.10 mm2; postoperative, 81.70±16.15 mm2), serum urea (preoperative, 38.40±17.26 mg/dl; postoperative, 33.28±16.98 mg/dl), and creatinine (preoperative, 1.03±0.53 mg/dl; postoperative, 0.97±0.55 mg/dl) and an increase was observed in GFR (preoperative, 104.30±37.30 ml/min; postoperative, 112.38±40.1 ml/min). No changes were detected in the serum electrolyte values (Na, K, Cl). Multiple access, operation time, and type of lithotripter did not have any significant effects on the change in the GFR. Conclusions In light of our results, PNL for kidney stone operations appears to be a reliable and efficient method that provides recovery of kidney functions in the early post-operative period by increasing the GFR and with high stone-free rates. PMID:22950000

Computed Tomography Volumetry in Preoperative Living Kidney Donor Assessment for Prediction of Split Renal Function.

PubMed

Wahba, Roger; Franke, Mareike; Hellmich, Martin; Kleinert, Robert; Cingöz, Tülay; Schmidt, Matthias C; Stippel, Dirk L; Bangard, Christopher

2016-06-01

Transplant centers commonly evaluate split renal function (SRF) with Tc-99m-mercapto-acetyltriglycin (MAG3) scintigraphy in living kidney donation. Alternatively, the kidney volume can be measured based on predonation CT scans. The aim of this study was to identify the most accurate CT volumetry technique for SRF and the prediction of postdonation kidney function (PDKF). Three CT volumetry techniques (modified ellipsoid volume [MELV], smart region of interest [ROI] volume, renal cortex volume [RCV]) were performed in 101 living kidney donors. Preoperation CT volumetric SRF was determined and compared with MAG3-SRF, postoperation donor kidney function, and graft function. The correlation between donors predonation total kidney volume and predonation kidney function was the highest for RCV (0.58 with creatine clearance, 0.54 with estimated glomerular filtration rate-Cockcroft-Gault). The predonation volume of the preserved kidney was (ROI, MELV, RCV) 148.0 ± 29.1 cm, 151.2 ± 35.4 and 93.9 ± 25.2 (P < 0.005 MELV vs RCV and ROI vs RCV). Bland-Altman analysis showed agreement between CT volumetry SRF and MAG3-SRF (bias, 95% limits of agreement: ROI vs MAG3 0.4%, -7.7% to 8.6%; MELV vs MAG3 0.4%, -8.9% to 9.7%; RCV vs MAG3 0.8%, -9.1% to 10.7%). The correlation between predonation CT volumetric SRF of the preserved kidney and PDKF at day 3 was r = 0.85 to 0.88, between MAG3-SRF and PDKF (r = 0.84). The difference of predonation SRF between preserved and donated kidney was the lowest for ROI and RCV (median, 3% and 4%; 95th percentile, 9% and 13%). Overall renal cortex volumetry seems to be the most accurate technique for the evaluation of predonation SRF and allows a reliable prediction of donor's PDKF.

Mechanisms for an effect of acetylcysteine on renal function after exposure to radio-graphic contrast material: study protocol

PubMed Central

2012-01-01

Background Contrast-induced nephropathy is a common complication of contrast administration in patients with chronic kidney disease and diabetes. Its pathophysiology is not well understood; similarly the role of intravenous or oral acetylcysteine is unclear. Randomized controlled trials to date have been conducted without detailed knowledge of the effect of acetylcysteine on renal function. We are conducting a detailed mechanistic study of acetylcysteine on normal and impaired kidneys, both with and without contrast. This information would guide the choice of dose, route, and appropriate outcome measure for future clinical trials in patients with chronic kidney disease. Methods/Design We designed a 4-part study. We have set up randomised controlled cross-over studies to assess the effect of intravenous (50 mg/kg/hr for 2 hrs before contrast exposure, then 20 mg/kg/hr for 5 hrs) or oral acetylcysteine (1200 mg twice daily for 2 days, starting the day before contrast exposure) on renal function in normal and diseased kidneys, and normal kidneys exposed to contrast. We have also set up a parallel-group randomized controlled trial to assess the effect of intravenous or oral acetylcysteine on patients with chronic kidney disease stage III undergoing elective coronary angiography. The primary outcome is change in renal blood flow; secondary outcomes include change in glomerular filtration rate, tubular function, urinary proteins, and oxidative balance. Discussion Contrast-induced nephropathy represents a significant source of hospital morbidity and mortality. Over the last ten years, acetylcysteine has been administered prior to contrast to reduce the risk of contrast-induced nephropathy. Randomized controlled trials, however, have not reliably demonstrated renoprotection; a recent large randomized controlled trial assessing a dose of oral acetylcysteine selected without mechanistic insight did not reduce the incidence of contrast-induced nephropathy. Our study should reveal the mechanism of effect of acetylcysteine on renal function and identify an appropriate route for future dose response studies and in time randomized controlled trials. Trial registration Clinical Trials.gov: NCT00558142; EudraCT: 2006-003509-18. PMID:22305183

Gaining the Patient Reported Outcomes Measurement Information System (PROMIS) Perspective in Chronic Kidney Disease: a Midwest Pediatric Nephrology Consortium study

PubMed Central

Selewski, David T.; Massengill, Susan F.; Troost, Jonathan P.; Wickman, Larysa; Messer, Kassandra L.; Herreshoff, Emily; Bowers, Corinna; Ferris, Maria E.; Mahan, John D.; Greenbaum, Larry A.; MacHardy, Jackie; Kapur, Gaurav; Chand, Deepa H.; Goebel, Jens; Barletta, Gina Marie; Geary, Denis; Kershaw, David B.; Pan, Cynthia G.; Gbadegesin, Rasheed; Hidalgo, Guillermo; Lane, Jerome C.; Leiser, Jeffrey D.; Song, Peter X.; Thissen, David; Liu, Yang; Gross, Heather E.; DeWalt, Darren A.; Gipson, Debbie S.

2014-01-01

Background and Objectives Chronic kidney disease is a persistent chronic health condition commonly seen in pediatric nephrology programs. Our study aims to evaluate the sensitivity of the Patient Reported Outcomes Measurement Information System (PROMIS) pediatric instrument to indicators of disease severity and activity in pediatric chronic kidney disease. Methods This cross sectional study included 233 children 8–17 years old with chronic kidney disease from 16 participating institutions in North America. Disease activity indicators, including hospitalization in the previous 6 months, edema, and number of medications consumed daily, as well as disease severity indicators of kidney function and coexisting medical conditions were captured. PROMIS domains, including depression, anxiety, social-peer relationships, pain interference, fatigue, mobility, and upper extremity function, were administered via web-based questionnaires. Absolute effect sizes (AES) were generated to demonstrate the impact of disease on domain scores. Four children were excluded because of missing GFR estimations. Results 221 of the 229 children included in the final analysis completed the entire PROMIS questionnaire. Unadjusted PROMIS domains were responsive to chronic kidney disease activity indicators and number of coexisting conditions. PROMIS domain scores were worse in the presence of recent hospitalizations (depression AES 0.33, anxiety AES 0.42, pain interference AES 0.46, fatigue AES 0.50, mobility AES 0.49), edema (depression AES 0.50, anxiety AES 0.60, pain interference AES 0.77, mobility AES 0.54) and coexisting medical conditions (social peer-relationships AES 0.66, fatigue AES 0.83, mobility AES 0.60, upper extremity function AES 0.48). Conclusions The PROMIS pediatric domains of depression, anxiety, social-peer relationships, pain interference, and mobility were sensitive to the clinical status of children with chronic kidney disease in this multi-center cross sectional study. We demonstrated that a number of important clinical characteristics including recent history of hospitalization and edema affected patient perceptions of depression, anxiety, pain interference, fatigue and mobility. The PROMIS instruments provide a potentially valuable tool to study the impact of chronic kidney disease. Additional studies will be required to assess responsiveness in PROMIS score with changes in disease status over time. PMID:24908324

Effects of complete water fasting and regeneration diet on kidney function, oxidative stress and antioxidants.

PubMed

Mojto, V; Gvozdjakova, A; Kucharska, J; Rausova, Z; Vancova, O; Valuch, J

2018-01-01

The aim of the study was to observe the influence of 11-days complete water fasting (WF) and regeneration diet (RD) on renal function, body weight, blood pressure and oxidative stress. Therapeutic WF is considered a healing method. Ten volunteers drank only water for 11 days, followed by RD for the next 11 days. Data on body weight, blood pressure, kidney functions, antioxidants, lipid peroxidation, cholesterols, triacylglycerols and selected biochemical parameters were obtained. WF increased uric acid and creatinine and decreased glomerular filtration rate. After RD, the parameters were comparable to baseline values. Urea was not affected. Lipid peroxidation (TBARS) decreased and maintained stable after RD. Fasting decreased α-tocopherol and increased γ-tocopherol, no significant changes were found after RD. Coenzyme Q10 decreased after RD. HDL-cholesterol decreased in WF. Total- and LDL-cholesterol decreased after RD. Other biochemical parameters were within the range of reference values. The effect of the complete fasting on kidney function was manifested by hyperuricemia. Renal function was slightly decreased, however maintained within the reference values. After RD, it returned to baseline values. The positive effect of the complete water fasting was in the reduction of oxidative stress, body weight and blood pressure (Tab. 3, Ref. 25).

When Your Child Needs a Kidney Transplant

MedlinePlus

... Search English Español When Your Child Needs a Kidney Transplant KidsHealth / For Parents / When Your Child Needs ... to monitor their new kidney function. About the Kidneys Kidneys are bean-shaped organs located near the ...

The effects of weight change on glomerular filtration rate

PubMed Central

Chang, Alex; Greene, Tom H.; Wang, Xuelei; Kendrick, Cynthia; Kramer, Holly; Wright, Jackson; Astor, Brad; Shafi, Tariq; Toto, Robert; Lewis, Julia; Appel, Lawrence J.; Grams, Morgan

2015-01-01

Background Little is known about the effect of weight loss/gain on kidney function. Analyses are complicated by uncertainty about optimal body surface indexing strategies for measured glomerular filtration rate (mGFR). Methods Using data from the African-American Study of Kidney Disease and Hypertension (AASK), we determined the association of change in weight with three different estimates of change in kidney function: (i) unindexed mGFR estimated by renal clearance of iodine-125-iothalamate, (ii) mGFR indexed to concurrently measured BSA and (iii) GFR estimated from serum creatinine (eGFR). All models were adjusted for baseline weight, time, randomization group and time-varying diuretic use. We also examined whether these relationships were consistent across a number of subgroups, including tertiles of baseline 24-h urine sodium excretion. Results In 1094 participants followed over an average of 3.6 years, a 5-kg weight gain was associated with a 1.10 mL/min/1.73 m2 (95% CI: 0.87 to 1.33; P < 0.001) increase in unindexed mGFR. There was no association between weight change and mGFR indexed for concurrent BSA (per 5 kg weight gain, 0.21; 95% CI: −0.02 to 0.44; P = 0.1) or between weight change and eGFR (−0.09; 95% CI: −0.32 to 0.14; P = 0.4). The effect of weight change on unindexed mGFR was less pronounced in individuals with higher baseline sodium excretion (P = 0.08 for interaction). Conclusion The association between weight change and kidney function varies depending on the method of assessment. Future clinical trials should examine the effect of intentional weight change on measured GFR or filtration markers robust to changes in muscle mass. PMID:26085555

Effect of N-Acetylcysteine Pretreatment of Deceased Organ Donors on Renal Allograft Function: A Randomized Controlled Trial

PubMed Central

Orban, Jean-Christophe; Quintard, Hervé; Cassuto, Elisabeth; Jambou, Patrick; Samat-Long, Corine; Ichai, Carole

2015-01-01

Background Antioxidant donor pretreatment is one of the pharmacologic strategy proposed to prevent renal ischemia-reperfusion injuries and delayed graft function (DGF). The aim of the study was to investigate whether a donor pretreatment with N-acetylcysteine (NAC) reduces the incidence of DGF in adult human kidney transplant recipients. Methods In this randomized, open-label, monocenter trial, 160 deceased heart-beating donors were allowed to perform 236 renal transplantations from September 2005 to December 2010. Donors were randomized to receive, in a single-blind controlled fashion, 600 mg of intravenous NAC 1 hr before and 2 hr after cerebral angiography performed to confirm brain death. Primary endpoint was DGF defined by the need for at least one dialysis session within the first week or a serum creatinine level greater than 200 μmol/L at day 7 after kidney transplantation. Results The incidence of DGF was similar between donors pretreated with or without NAC (39/118; 33% vs. 30/118; 25.4%; P = 0.19). Requirement for at least one dialysis session was not different between the NAC and No NAC groups (17/118; 14.4% vs. 14/118; 11.8%, P = 0.56). The two groups had comparable serum creatinine levels, estimated glomerular filtration rates, and daily urine output at days 1, 7, 15, and 30 after kidney transplantation as well as at hospital discharge. No difference in recipient mortality nor in 1-year kidney graft survival was observed. Conclusion Donor pretreatment with NAC does not improve delayed graft function after kidney transplantation. PMID:25250647

Long-Term Renal Function in Living Kidney Donors who had Histological Abnormalities at Donation

PubMed Central

Fahmy, Lara M.; Massie, Allan B.; Muzaale, Abimereki D.; Bagnasco, Serena M.; Orandi, Babak J.; Alejo, Jennifer L.; Boyarsky, Brian J.; Anjum, Saad K.; Montgomery, Robert A.; Dagher, Nabil N.; Segev, Dorry L.

2016-01-01

Background Recent evidence suggests that living kidney donors are at an increased risk of end-stage renal disease. However, predicting which donors will have renal dysfunction remains challenging, particularly among those with no clinical evidence of disease at the time of donation. Although renal biopsies are not routinely performed as part of the donor evaluation process, they may yield valuable information that improves the ability to predict renal function in donors. Methods We used implantation protocol biopsies to evaluate the association between histological abnormalities in the donated kidney and postdonation renal function (estimated glomerular filtration rate, eGFR) of the remaining kidney in living kidney donors. Longitudinal analysis using mixed-effects linear regression was used to account for multiple eGFR measures per donor. Results Among 310 donors between 1997 and 2012, median (IQR) follow-up was 6.2 (2.5–8.7; maximum 14.0) years. In this cohort, the overall prevalence of histological abnormalities was 65.8% (19.7% abnormal glomerulosclerosis, 23.9% abnormal interstitial fibrosis and tubular atrophy (IFTA), 4.8% abnormal mesangial matrix increase, 32.0% abnormal arteriolar hyalinosis, and 32.9% abnormal vascular intimal thickening). IFTA was associated with a 5-mL/min/1.73m2 decrease of postdonation eGFR after adjusting for donor age at donation, sex, race, preoperative systolic blood pressure, preoperative eGFR, and time since donation (p<0.01). Conclusions In this single-center study, among healthy individuals cleared for living donation, IFTA was associated with decreased postdonation eGFR, while no other subclinical histological abnormalities provided additional information. PMID:27152920

Increasing access to kidney transplantation for sensitized recipient through three-way kidney paired donation with desensitization: The first Indian report

PubMed Central

Kute, Vivek B; Patel, Himanshu V; Shah, Pankaj R; Modi, Pranjal R; Shah, Veena R; Rizvi, Sayyed J; Pal, Bipin C; Modi, Manisha P; Shah, Priya S; Varyani, Umesh T; Wakhare, Pavan S; Shinde, Saiprasad G; Ghodela, Viajay A; Patel, Minaxi H; Trivedi, Varsha B; Trivedi, Hargovind L

2016-01-01

The combination of kidney paired donation (KPD) with desensitization represents a promising method of increasing the rate of living donor kidney transplantation (LDKT) in immunologically challenging patients. Patients who are difficult to match and desensitize due to strong donor specific antibody are may be transplanted by a combination of desensitization and KPD protocol with more immunologically favorable donor. We present our experience of combination of desensitization protocol with three-way KPD which contributed to successful LDKT in highly sensitized end stage renal disease patient. All recipients were discharged with normal and stable allograft function at 24 mo follow up. We believe that this is first report from India where three-way KPD exchange was performed with the combination of KPD and desensitization. The combination of desensitization protocol with KPD improves access and outcomes of LDKT. PMID:27803919

Endovascular treatment of cerebral aneurysm after renal transplantation in polycystic kidney disease.

PubMed

Demartini, Zeferino; Galdino, Jennyfer; Koppe, Gelson L; Bignelli, Alexandre T; Francisco, Alexandre N; Gatto, Luana Am

2018-06-01

Background Patients with polycystic kidney disease have a higher prevalence of intracranial aneurysms and may progress to renal failure requiring transplantation. The endovascular treatment of intracranial aneurysms may improve prognosis, since rupture often causes premature death or disability, but the nephrotoxicity risk associated with contrast medium must be always considered in cases of renal impairment. Methods A 55-year-old female patient with polycystic kidney disease and grafted kidney associated with anterior communicant artery aneurysm was successfully treated by embolization. Results The renal function remained normal after the procedure. To the authors' knowledge, this is the first case of endovascular treatment of brain aneurysm in a transplanted patient reported in the medical literature. Conclusions The endovascular procedure in renal transplant patients is feasible and can be considered to treat this population. Further studies and cases are needed to confirm its safety.

In vivo three-dimensional photoacoustic imaging of the renal vasculature in preclinical rodent models.

PubMed

Ogunlade, Olumide; Connell, John J; Huang, Jennifer L; Zhang, Edward; Lythgoe, Mark F; Long, David A; Beard, Paul

2018-06-01

Noninvasive imaging of the kidney vasculature in preclinical murine models is important for the assessment of renal development, studying diseases and evaluating new therapies but is challenging to achieve using existing imaging modalities. Photoacoustic imaging is a promising new technique that is particularly well suited to visualizing the vasculature and could provide an alternative to existing preclinical imaging methods for studying renal vascular anatomy and function. To investigate this, an all-optical Fabry-Perot-based photoacoustic scanner was used to image the abdominal region of mice. High-resolution three-dimensional, noninvasive, label-free photoacoustic images of the mouse kidney and renal vasculature were acquired in vivo. The scanner was also used to visualize and quantify differences in the vascular architecture of the kidney in vivo due to polycystic kidney disease. This study suggests that photoacoustic imaging could be utilized as a novel preclinical imaging tool for studying the biology of renal disease.

Simultaneous evaluation of renal morphology and function in live kidney donors using dynamic magnetic resonance imaging.

PubMed

Artunc, F; Yildiz, S; Rossi, C; Boss, A; Dittmann, H; Schlemmer, H P; Risler, T; Heyne, N

2010-06-01

Evaluation of potential kidney donors requires the assessment of both kidney anatomy and function. In this prospective study, we sought to expand the diagnostic yield of magnetic resonance (MR) by adding functional measurements of glomerular filtration rate (GFR) and split renal function. Between 2007 and 2009, all potential kidney donors presenting to our facility underwent a comprehensive single-stop MR study that included an assessment of anatomy, angiography and functional measurements. GFR was measured after a bolus injection of gadobutrol (4 ml, approximately 0.05 mmol/kg) and calculated from the washout of the signal intensity obtained over the liver. Split renal function was calculated from the increase of signal intensity over the renal cortex. Values were compared to renal scintigraphy with (99m)Tc-DTPA from the same day. The MR investigation was successfully performed in 21 participants. The GFR derived from MR (MR-GFR) correlated well (r = 0.84) with the GFR derived from scintigraphy (DTPA-GFR). The mean value of the paired differences was 4 +/- 13 [SD] ml/min/1.73 m(2) and was not significantly different from zero. The ratio between right and left kidney function was similar with both techniques (1.01 +/- 0.17 with MR and 1.06 +/- 0.12 with scintigraphy, P = 0.20). We demonstrate an MR-based approach to comprehensively evaluate both kidney anatomy and function in a single investigation, thereby facilitating the evaluation of potential kidney donors.

Left Ventricular Mass Progression Despite Stable Blood Pressure and Kidney Function in Stage 3 CKD

PubMed Central

Seifert, Michael E.; Fuentes, Lisa de las; Ginsberg, Charles; Rothstein, Marcos; Dietzen, Dennis J.; Cheng, Steven C.; Ross, Will; Windus, David; Dávila-Román, Victor G.; Hruska, Keith A.

2014-01-01

Background/Aims Progressive chronic kidney disease (CKD) is associated with worsening cardiovascular risk not explained by traditional risk factors. Left ventricular hypertrophy (LVH) is an important cardiovascular risk factor, but its progression has not been documented in early CKD. We explored whether progression of LVH in early CKD would occur despite stable kidney function. Methods We conducted a post hoc analysis of a 12-m nth study of lanthanum carbonate in stage 3 CKD, which included longitudinal assessments of cardiovascular biomarkers. Primary outcome for the analysis was the change in LV mass indexed to height in meters2.7 (LVM/Ht2.7). Secondary outcomes were changes in blood pressure (BP), pulse-wave velocity, LV systolic/diastolic function, fibroblast growth factor-23 (FGF23), klotho, and eGFR. Results 31 of 38 original subjects had sufficient data for analysis. LVM/Ht2.7 increased (47 ± 13 vs. 53 ± 13 g/m2.7, P=0.006) over 12 months despite stable BP, stable eGFR and normal LV systolic function. Vascular stiffness and LV diastolic dysfunction persisted throughout the study. Klotho levels decreased (748 ± 289 to 536 ± 410 pg/ml, P=0.03) but were unrelated to changes in LVM/Ht2.7. The change in FGF23/klotho ratio was strongly correlated with changes in LVM/Ht2.7 (r2 0.582, P=0.03). Conclusion Subjects with stage 3 CKD exhibited increasing LV mass, persistent LV diastolic dysfunction and vascular stiffness despite stable kidney function, BP and LV systolic function. Abnormal FGF23 signaling due to reduced klotho expression may be associated with increasing LV mass. These findings deserve further evaluation in a larger population, given the adverse prognostic value of these cardiovascular biomarkers. PMID:24818573

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

Association of Kidney Function and Albuminuria With Prevalent and Incident Hypertension: The Atherosclerosis Risk in Communities (ARIC) Study

PubMed Central

Huang, Minxuan; Matsushita, Kunihiro; Sang, Yingying; Ballew, Shoshana H.; Astor, Brad C.; Coresh, Josef

2014-01-01

Background Decreased kidney function and kidney damage may predate hypertension, but only a few studies have investigated both types of markers simultaneously, and these studies have obtained conflicting results. Study Design Cross-sectional for prevalent and prospective observational study for incident hypertension. Setting & Participants 9,593 participants from the Atherosclerosis Risk in Communities (ARIC) Study, aged 53-75 years during 1996-1998. Predictors Several markers of kidney function (estimated glomerular filtration rate [eGFR] using serum creatinine and/or cystatin C and two novel markers [β-trace protein and β2-microglobulin]) and one marker of kidney damage (urinary albumin-creatinine ratio [ACR]). Every kidney marker was categorized by its quintiles (top quintile as a reference for eGFRs and bottom quintile for the rest). Outcomes Prevalent and incident hypertension. Measurements Prevalence and HRs of hypertension based on modified Poisson regression and Cox proportional hazards models, respectively. Results There were 4,378 participants (45.6%) with prevalent hypertension at baseline and 2,175 incident hypertension cases during a median follow-up of 9.8 years. While all five kidney function markers were significantly associated with prevalent hypertension, prevalent hypertension was most notably associated with higher ACR (adjusted prevalence ratio, 1.60 [95% CI, 1.50-1.71] for the highest vs lowest ACR quintile). Similarly, ACR was consistently associated with incident hypertension in all models tested (adjusted HR, 1.28 [95% CI, 1.10-1.49] for top quintile), while kidney function markers demonstrated significant associations in some, but not all, models. Even mildly increased ACR (9.14-14.0 mg/g) was significantly associated with incident hypertension. Limitations Self-reported use of antihypertensive medication for defining incident hypertension, single assessment of kidney markers, and relatively narrow age range. Conclusions Although all kidney markers were associated with prevalent hypertension, only elevated albuminuria was consistently associated with incident hypertension, suggesting that kidney damage is more closely related to hypertension than moderate reduction in overall kidney function. PMID:25151408

Acoustic radiation force impulse (ARFI) elastography for detection of renal damage in children.

PubMed

Göya, Cemil; Hamidi, Cihad; Ece, Aydın; Okur, Mehmet Hanifi; Taşdemir, Bekir; Çetinçakmak, Mehmet Güli; Hattapoğlu, Salih; Teke, Memik; Şahin, Cahit

2015-01-01

Acoustic radiation force impulse (ARFI) imaging is a promising method for noninvasive evaluation of the renal parenchyma. To investigate the contribution of ARFI quantitative US elastography for the detection of renal damage in kidneys with and without vesicoureteral reflux (VUR). One hundred seventy-six kidneys of 88 children (46 male, 42 female) who had been referred for voiding cystourethrography and 20 healthy controls were prospectively investigated. Patients were assessed according to severity of renal damage on dimercaptosuccinic acid (DMSA) scintigraphy. Ninety-eight age- and gender-matched healthy children constituted the control group. Quantitative shear wave velocity (SWV) measurements were performed in the upper and lower poles and in the interpolar region of each kidney. DMSA scintigraphy was performed in 62 children (124 kidneys). Comparisons of SWV values of kidneys with and without renal damage and/or VUR were done. Significantly higher SWV values were found in non-damaged kidneys. Severely damaged kidneys had the lowest SWV values (P < 0.001). High-grade (grade V-IV) refluxing kidneys had the lowest SWV values, while non-refluxing kidneys had the highest values (P < 0.05). Significant negative correlations were found between the mean quantitative US elastography values and DMSA scarring score (r = -0.788, P < 0.001) and VUR grade (r = -0.634, P < 0.001). SWV values of the control kidneys were significantly higher than those of damaged kidneys (P < 0.05). Our findings suggest decreasing SWV of renal units with increasing grades of vesicoureteric reflux, increasing DMSA-assessed renal damage and decreasing DMSA-assessed differential function.

Clinical proof-of-concept trial to assess the therapeutic effect of sirolimus in patients with autosomal dominant polycystic kidney disease: SUISSE ADPKD study

PubMed Central

Serra, Andreas L; Kistler, Andreas D; Poster, Diane; Struker, Marian; Wüthrich, Rudolf P; Weishaupt, Dominik; Tschirch, Frank

2007-01-01

Background Currently there is no effective treatment available to retard cyst growth and to prevent the progression to end-stage renal failure in patients with autosomal dominant polycystic kidney disease (ADPKD). Evidence has recently been obtained from animal experiments that activation of the mammalian target of rapamycin (mTOR) signaling pathway plays a crucial role in cyst growth and renal volume expansion, and that the inhibition of mTOR with rapamycin (sirolimus) markedly slows cyst development and renal functional deterioration. Based on these promising results in animals we have designed and initiated the first randomized controlled trial (RCT) to examine the effectiveness, safety and tolerability of sirolimus to retard disease progression in ADPKD. Method/design This single center, randomised controlled, open label trial assesses the therapeutic effect, safety and tolerability of the mTOR inhibitor sirolimus (Rapamune®) in patients with autosomal dominant polycystic kidney disease and preserved renal function. The primary outcome will be the inhibition of kidney volume growth measured by magnetic resonance imaging (MRI) volumetry. Secondary outcome parameters will be preservation of renal function, safety and tolerability of sirolimus. Discussion The results from this proof-of-concept RCT will for the first time show whether treatment with sirolimus effectively retards cyst growth in patients with ADPKD. Trial registration NCT00346918 PMID:17868472

Male kidney allograft recipients at risk for urinary tract infection?

PubMed Central

Schuette-Nuetgen, Katharina; Vogl, Thomas; Dobrindt, Ulrich; Kahl, Barbara C.; Brand, Marcus; Pavenstädt, Hermann; Suwelack, Barbara

2017-01-01

Background Urinary tract infection (UTI) is the most common infection after renal transplantation (RTx). Although female sex is a well-known risk factor for the development of UTI after RTx, the role of the donor sex in this context remains unclear. Methods In this case control study 6,763 RTx cases were screened for UTI when presenting at our transplant outpatient clinics. 102 different RTx patients fulfilled the inclusion criteria and were compared to 102 controls. Data on renal function was prospectively followed for 12 months. Results were compared to a previous RTx cohort from our transplant center. Additionally, we assessed the immunological response of leukocytes from 58 kidney recipients and 16 controls to lipopolysaccharide stimulation. Result After identification by univariate analysis, multivariate logistic regression analysis indicated female sex, minor height, advanced age and male kidney allograft sex to be associated with the occurrence of UTI after RTx. Female recipients who received male grafts had the best renal function 12 months after presentation. However, leukocyte response of recipients to lipopolysaccharide was impaired irrespective of donor and recipient sex to the same extend. Conclusions We conclude from our data that male kidney allografts are associated with the occurrence of UTI after RTx but did not influence the response of leukocytes to lipopolysaccharide. Further prospective studies are needed to identify the underlying mechanisms of higher male kidney donor dependent UTI. PMID:29145515

Monosodium Glutamate (MSG) Consumption Is Associated with Urolithiasis and Urinary Tract Obstruction in Rats

PubMed Central

Sharma, Amod; Prasongwattana, Vitoon; Cha’on, Ubon; Selmi, Carlo; Hipkaeo, Wiphawi; Boonnate, Piyanard; Pethlert, Supattra; Titipungul, Tanin; Intarawichian, Piyapharom; Waraasawapati, Sakda; Puapiroj, Anucha; Sitprija, Visith; Reungjui, Sirirat

2013-01-01

Background The peritoneal injection of monosodium glutamate (MSG) can induce kidney injury in adult rats but the effects of long-term oral intake have not been determined. Methods We investigated the kidney histology and function in adult male Wistar rats that were fed ad libitum with a standard rat chow pellet and water with or without the addition of 2 mg/g body weight MSG/day in drinking water (n=10 per group). Both MSG-treated and control animals were sacrificed after 9 months when renal function parameters, blood and urine electrolytes, and tissue histopathology were determined. Results MSG-treated rats were more prone to kidney stone formation, as represented by the alkaline urine and significantly higher activity product of calcium phosphate. Accordingly, 3/10 MSG-treated rats developed kidney stones over 9 months versus none of the control animals. Further, 2/10 MSG-treated rats but none (0/10) of the controls manifested hydronephrosis. MSG-treated rats had significantly higher levels of serum creatinine and potassium including urine output volume, urinary excretion sodium and citrate compared to controls. In contrast, MSG-treated rats had significantly lower ammonium and magnesium urinary excretion. Conclusion Oral MSG consumption appears to cause alkaline urine and may increase the risks of kidney stones with hydronephrosis in rats. Similar effects in humans must be verified by dedicated studies. PMID:24086562

Volume estimation of small phantoms and rat kidneys using three-dimensional ultrasonography and a position sensor.

PubMed

Strømmen, Kenneth; Stormark, Tor André; Iversen, Bjarne M; Matre, Knut

2004-09-01

To evaluate the accuracy of small volume estimation, both in vivo and in vitro, measurements with a three-dimensional (3D) ultrasound (US) system were carried out. A position sensor was used and the transmitting frequency was 10 MHz. Balloons with known volumes were scanned while rat kidneys were scanned in vivo and in vitro. The Archimedes' principle was used to estimate the true volume. For balloons, the 3D US system gave very good agreement with true volumes in the volume range 0.1 to 10.0 mL (r = 0.999, n = 45, mean difference +/- 2SD = 0.245 +/- 0.370 mL). For rat kidneys in vivo (volume range 0.6 to 2.7 mL) the method was less accurate (r = 0.800, n = 10, mean difference +/- 2SD = -0.288 +/- 0.676 mL). For rat kidneys in vitro (volume range 0.3 to 2.7 mL) the results showed good agreement (r = 0.981, n = 23, mean difference +/- 2SD = 0.039 +/- 0.254 mL). For balloons, kidneys in vivo and in vitro, the mean percentage error was 9.3 +/- 4.8%, -17.1 +/- 17.4%, and 4.6 +/- 11.5%, respectively. This method can estimate the volume of small phantoms and rat kidneys and opens new possibilities for volume measurements of small objects and the study of organ function in small animals. (E-mail ).

A Dynamic Graph Cuts Method with Integrated Multiple Feature Maps for Segmenting Kidneys in 2D Ultrasound Images.

PubMed

Zheng, Qiang; Warner, Steven; Tasian, Gregory; Fan, Yong

2018-02-12

Automatic segmentation of kidneys in ultrasound (US) images remains a challenging task because of high speckle noise, low contrast, and large appearance variations of kidneys in US images. Because texture features may improve the US image segmentation performance, we propose a novel graph cuts method to segment kidney in US images by integrating image intensity information and texture feature maps. We develop a new graph cuts-based method to segment kidney US images by integrating original image intensity information and texture feature maps extracted using Gabor filters. To handle large appearance variation within kidney images and improve computational efficiency, we build a graph of image pixels close to kidney boundary instead of building a graph of the whole image. To make the kidney segmentation robust to weak boundaries, we adopt localized regional information to measure similarity between image pixels for computing edge weights to build the graph of image pixels. The localized graph is dynamically updated and the graph cuts-based segmentation iteratively progresses until convergence. Our method has been evaluated based on kidney US images of 85 subjects. The imaging data of 20 randomly selected subjects were used as training data to tune parameters of the image segmentation method, and the remaining data were used as testing data for validation. Experiment results demonstrated that the proposed method obtained promising segmentation results for bilateral kidneys (average Dice index = 0.9446, average mean distance = 2.2551, average specificity = 0.9971, average accuracy = 0.9919), better than other methods under comparison (P < .05, paired Wilcoxon rank sum tests). The proposed method achieved promising performance for segmenting kidneys in two-dimensional US images, better than segmentation methods built on any single channel of image information. This method will facilitate extraction of kidney characteristics that may predict important clinical outcomes such as progression of chronic kidney disease. Copyright © 2018 The Association of University Radiologists. Published by Elsevier Inc. All rights reserved.

Association of mGFR of the Remaining Kidney Divided by Its Volume before Donation with Functional Gain in mGFR among Living Kidney Donors.

PubMed

Courbebaisse, Marie; Gaillard, François; Tissier, Anne-Marie; Fournier, Catherine; Le Nestour, Alexis; Corréas, Jean-Michel; Slimani-Thevenet, Hind; Martinez, Frank; Léon, Carine; Eladari, Dominique; Timsit, Marc-Olivier; Otal, Philippe; Hignette, Chantal; Friedlander, Gérard; Méjean, Arnaud; Houillier, Pascal; Kamar, Nassim; Legendre, Christophe

2016-08-08

The predictors of long-term renal function in living kidney donors are currently discussed. Our objectives were to describe the predictors of functional gain of the remaining kidney after kidney donation. We hypothesized that GFR of the remaining kidney divided by volume of this kidney (rk-GFR/vol) would reflect the density of functional nephrons and be inversely associated with functional gain of the remaining kidney. We conducted a prospective monocentric study including 63 living donors (26 men; 50.3±11.8 years old) who had been evaluated for (51)Cr-EDTA and measured GFR, split renal function by scintigraphy before donation (between 2004 and 2009), and measured GFR at 5.7±0.5 years after donation. For 52 donors, volume of the remaining kidney (measured and estimated with the ellipsoid formula using renal computed tomography scannography) was determined before donation. We tested our hypothesis in an external validation cohort of 39 living donors (13 men; 51.0±9.4 years old) from another single center during the same time period. For the main cohort, the mean measured GFR was 97.6±13.0 ml/min per 1.73 m(2) before donation and 63.8±9.4 ml/min per 1.73 m(2) at 5 years. Functional gain averaged 16.2±7.2 ml/min per 1.73 m(2) (+35.3%±16.7%). Multivariate analysis showed that age, body mass index, and rk-GFR/vol at donation were negatively correlated with functional gain and had strong predictive power of the 5-year functional gain (adjusted 5-year functional gain for age: -0.4 [95% confidence interval (95% CI), -0.5 to -0.1]; body mass index: -0.3 [95% CI, -0.6 to -0.1]; rk-GFR/vol: -55.1 [95% CI, -92.3 to -17.9]). We tested this model in the external validation cohort (adjusted 5-year functional gain for age: -0.1 [95% CI, -0.5 to 0.3]; body mass index: -0.9 [95% CI, -1.8 to -0.1]; rk-GFR/vol: -97.6 [95% CI, -137.5 to -57.6]) and confirmed that rk-GFR/vol was inversely associated with 5-year functional gain. For given age and body mass index, the long-term functional gain of the remaining kidney is inversely associated with the new variable rk-GFR/vol at donation. Copyright © 2016 by the American Society of Nephrology.

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).

Effect of maternal diabetes on female offspring

PubMed Central

Martins, Juliana de Oliveira; Panício, Maurício Isaac; Dantas, Marcos Paulo Suehiro; Gomes, Guiomar Nascimento

2014-01-01

Objective To evaluate the effect of maternal diabetes on the blood pressure and kidney function of female offspring, as well as if such changes exacerbate during pregnancy. Methods Diabetes mellitus was induced in female rats with the administration of streptozotocin in a single dose, one week before mating. During pregnancy, blood pressure was measured through plethysmography. On the 20th day of pregnancy, the animals were placed for 24 hours in metabolic cages to obtain urine samples. After the animals were removed from the cages, blood samples were withdrawn. One month after pregnancy, new blood and urine sample were collected. Kidney function was evaluated through proteinuria, plasma urea, plasma creatinine, creatinine excretion rate, urinary flow, and creatinine clearance. Results The female offspring from diabetic mothers showed an increase in blood pressure, and a decrease in glomerular filtration rate in relation to the control group. Conclusion Hyperglycemia during pregnancy was capable of causing an increase in blood pressure and kidney dysfunction in the female offspring. PMID:25628190

Long-term prognosis after acute kidney injury (AKI): what is the role of baseline kidney function and recovery? A systematic review.

PubMed

Sawhney, Simon; Mitchell, Mhairi; Marks, Angharad; Fluck, Nick; Black, Corrinda

2015-01-06

To summarise the evidence from studies of acute kidney injury (AKI) with regard to the effect of pre-AKI renal function and post-AKI renal function recovery on long-term mortality and renal outcomes, and to assess whether these factors should be taken into account in future prognostic studies. A systematic review of observational studies listed in Medline and EMBASE from 1990 to October 2012. All AKI studies in adults with data on baseline kidney function to identify AKI; with outcomes either stratified by pre-AKI and/or post-AKI kidney function, or described by the timing of the outcomes. Long-term mortality and worsening chronic kidney disease (CKD). Of 7385 citations, few studies met inclusion criteria, reported baseline kidney function and stratified by pre-AKI or post-AKI function. For mortality outcomes, three studies compared patients by pre-AKI renal function and six by post-AKI function. For CKD outcomes, two studies compared patients by pre-AKI function and two by post-AKI function. The presence of CKD pre-AKI (compared with AKI alone) was associated with doubling of mortality and a fourfold to fivefold increase in CKD outcomes. Non-recovery of kidney function was associated with greater mortality and CKD outcomes in some studies, but findings were inconsistent varying with study design. Two studies also reported that risk of poor outcome reduced over time post-AKI. Meta-analysis was precluded by variations in definitions for AKI, CKD and recovery. The long-term prognosis after AKI varies depending on cause and clinical setting, but it may also, in part, be explained by underlying pre-AKI and post-AKI renal function rather than the AKI episode itself. While carefully considered in clinical practice, few studies address these factors and with inconsistent study design. Future AKI studies should report pre-AKI and post-AKI function consistently as additional factors that may modify AKI prognosis. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

Systematic review of kidney transplantation functional predictors.

PubMed

Miret Alomar, E; Trilla Herrera, E; Lorente Garcia, D; Regis Placido, L; López Del Campo, R; Cuadras Solé, M; Pont Castellana, T; Moreso Mateos, F; Serón Micas, D; Morote Robles, J

2018-05-01

Kidney transplantation from donors with expanded criteria has increased the pool of kidneys at the cost of a higher risk of short and long-term graft dysfunction. The main issue lies in determining which kidneys will offer acceptable function and survival compared with the risk represented by surgery and subsequent immunosuppression. The objective of our article is to review the current evidence on the tools for predicting the functionality of kidney transplantation from cadaveric donors with expanded criteria and determining the validity for their use in standard practice. We conducted a systematic literature review according to the PRISM criteria, through Medline (http://www.ncbi.nlm.nih.gov) and using the keywords (in isolation or in conjunction) "cadaveric renal transplantation; kidney graft function appraisal, graft function predictors". We selected prospective and retrospective series and review articles. A total of 375 articles were analysed, 39 of which were ultimately selected for review. The predictors of functionality include the following: The donor risk indices; the calculation of the renal functional weight or the assessment of the nephronic mass; the measurement of vascular resistances during perfusion in hypothermia; the measurement of the donor's biomarkers in urine and in the perfusion liquid; the measurement of functional and reperfusion parameters in normothermia; and the measurement of morphological parameters (microscopic and macroscopic) of the target organ. In this article, we present an explanatory summary of each of these parameters, as well as their most recent evidence on this issue. None of the reviewed parameters in isolation could reliably predict renal function and graft survival. There is a significant void in terms of the macroscopic assessment of kidney transplantation. We need to continue developing predictors of renal functionality to accurately define the distribution of each currently available donor kidney. Copyright © 2017 AEU. Publicado por Elsevier España, S.L.U. All rights reserved.

Hydration Status, Kidney Function, and Kidney Injury in Florida Agricultural Workers.

PubMed

Mix, Jacqueline; Elon, Lisa; Vi Thien Mac, Valerie; Flocks, Joan; Economos, Eugenia; Tovar-Aguilar, Antonio J; Stover Hertzberg, Vicki; McCauley, Linda A

2018-05-01

Recent findings suggest that laboring in hot occupational environments is related to kidney damage in agricultural workers. We examined hydration status and kidney function in 192 Florida agricultural workers. Blood and urine samples were collected over 555 workdays during the summers of 2015 and 2016. Urine-specific gravity (USG), serum creatinine, and other kidney function markers were examined pre- and post-shift on each workday. Multivariable mixed modeling was used to examine the association of risk factors with hydration status and acute kidney injury (AKI). Approximately 53% of workers were dehydrated (USG ≥1.020) pre-shift and 81% post-shift; 33% of participants had AKI on at least one workday. The odds of AKI increased 47% for each 5-degree (°F) increase in heat index. A strikingly high prevalence of dehydration and AKI exists in Florida agricultural workers.

Impaired Kidney Function and Associated Factors Among Rural Adults With Disabilities in Taiwan.

PubMed

Chen, Chu-Yeh; Chiu, Wen-Nan; Lin, Yu-Chen; Jane, Sui-Hwi; Chiang, Hsin-Hung; Chen, Mei-Yen

2017-04-01

The results of numerous studies indicate that people with disabilities seek more healthcare than those who are not disabled, particularly for conditions such as chronic kidney disease, cardiovascular disease, and obesity. However, little is known about the incidence of impaired kidney function and its associated factors among adults with disabilities in Taiwan. The aim of this study was to explore the prevalence and factors associated with impaired kidney function among adults with disabilities. This descriptive study was nurse led and was conducted as part of a health promotion program for disadvantaged rural adults with disabilities in Chiayi County, Taiwan. Health screening and a health needs survey were conducted between July and December 2013. Kidney function, physiological biomarkers, health-related behaviors, and demographic characteristics were examined. Eight hundred ten rural adults with disabilities were enrolled. The most common disabilities included physical-related disability (33.1%), intellectual-related disability (26.7%), and hearing and vision impairment (18.6%). The prevalence of impaired kidney function in this population was 85%. According to classification for chronic kidney disease, 68.6% were in Stages 1-2, and 16.8% were in Stages 3-4. Univariate analysis showed that impaired kidney function was significantly associated with lower educational level (p < .001), hearing or vision impairment (p < .001), being overweight or obese (p < .05), high systolic blood pressure (p < .01), fasting blood glucose (p < .001), total cholesterol (p < .001), total triglyceride (p < .05), older age (p < .001), smoking (p < .05), chewing betel nuts (p = .001), and low levels of participation in social activities (p < .05). The final logistic regression model showed that residents with disabilities who were older or had less education, high fasting blood glucose, and high total cholesterol tended to have impaired kidney function after adjustment for other potential confounding variables. Most participants showed impaired kidney function. The factors that were found to relate significantly to this impairment include being overweight, having hyperlipidemia, having hypertension, having high fasting blood glucose, and having an unhealthy lifestyle. Because of the lack of symptoms during the early stages of chronic kidney disease, a community-based health promotion program for these factors is an important element in health advocacy for this vulnerable population.

Cardiorenal Syndrome: New Developments in the Understanding and Pharmacologic Management

PubMed Central

2013-01-01

Summary Cardiorenal syndromes (CRSs) with bidirectional heart-kidney signaling are increasingly being recognized for their association with increased morbidity and mortality. In acute CRS, recognition of the importance of worsening kidney function complicating management of acute decompensated heart failure has led to the examination of this specific outcome in the context of acute heart failure clinical trials. In particular, the role of fluid overload and venous congestion has focused interest in the most effective use of diuretic therapy to relieve symptoms of heart failure while at the same time preserving kidney function. Additionally, many novel vasoactive therapies have been studied in recent years with the hopes of augmenting cardiac function, improving symptoms and patient outcomes, while maintaining or improving kidney function. Similarly, recent advances in our understanding of the pathophysiology of chronic CRS have led to reanalysis of kidney outcomes in pivotal trials in chronic congestive heart failure, and newer trials are including changes in kidney function as well as kidney injury biomarkers as prospectively monitored and adjudicated outcomes. This paper provides an overview of some new developments in the pharmacologic management of acute and chronic CRS, examines several reports that illustrate a key management principle for each subtype, and discusses opportunities for future research. PMID:23929925

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.

Comparison of Recipient Outcomes After Kidney Transplantation: In-House Versus Imported Deceased Donors.

PubMed

Lim, S Y; Gwon, J G; Kim, M G; Jung, C W

2018-05-01

Increased cold ischemia time in cadaveric kidney transplants has been associated with a high rate of delayed graft function (DGF), and even with graft survival. Kidney transplantation using in-house donors reduces cold preservation time. The purpose of this study was to compare the clinical outcomes after transplantation in house and externally. We retrospectively reviewed the medical records of donors and recipients of 135 deceased-donor kidney transplantations performed in our center from March 2009 to March 2016. Among the 135 deceased donors, 88 (65.2%) received the kidneys from in-house donors. Median cold ischemia time of transplantation from in-house donors was shorter than for imported donors (180.00 vs 300.00 min; P < .001). The risks of DGF and slow graft function were increased among the imported versus in-house donors. Imported kidney was independently associated with greater odds of DGF in multivariate regression analysis (odds ratio, 4.165; P = .038). However, the renal function of recipients at 1, 3, 5, and 7 years after transplantation was not significantly different between the 2 groups. Transplantation with in-house donor kidneys was significantly associated with a decreased incidence of DGF, but long-term graft function and survival were similar compared with imported donor kidneys. Copyright © 2018 Elsevier Inc. All rights reserved.

Absence of chloride intracellular channel 4 (CLIC4) predisposes to acute kidney injury but has minimal impact on recovery

PubMed Central

2014-01-01

Background CLIC4, a member of the CLIC family of proteins, was recently demonstrated to translocate to the nucleus in differentiating keratinocytes where it potentiates TGFβ-driven gene regulation. Since TGFβ signaling is known to play important roles in the fibrotic response to acute kidney injury, and since CLIC4 is abundantly expressed in kidney, we hypothesized that CLIC4 may play a role in the response to acute kidney injury. Methods Previously described Clic4 null mice were analyzed for the effect of absence of CLIC4 on growth, development and response to kidney injury. Kidney size, glomerular counts and density of peritubular capillaries of matched WT and Clic4 null mice were determined. Cohorts of WT and Clic4 null mice were subjected to the folic acid model of acute kidney injury. Extent of acute injury and long term functional recovery were assessed by plasma blood urea nitrogen (BUN); long term fibrosis/scarring was determined by histochemical assessment of kidney sections and by residual renal mass. Activation of the TGFβ signaling pathway was assessed by semi-quantitative western blots of phosphorylated SMADs 2 and 3. Results CLIC4 is abundantly expressed in the apical pole of renal proximal tubule cells, and in endothelial cells of glomerular and peritubular capillaries. CLIC4 null mice are small, have smaller kidneys with fewer glomeruli and less dense peritubular capillary networks, and have increased proteinuria. The Clic4 null mice show increased susceptibility to folic acid-induced acute kidney injury but no difference in recovery from acute injury, no nuclear redistribution of CLIC4 following injury, and no significant difference in activation of the TGFβ-signaling pathway as reflected in the level of phosphorylation of SMADs 2 and 3. Conclusions Absence of CLIC4 results in morphologic changes consistent with its known role in angiogenesis. These changes may be at least partially responsible for the increased susceptibility to acute kidney injury. However, the absence of CLIC4 has no significant impact on the extent of functional recovery or fibrosis following acute injury, indicating that CLIC4 does not play a major non-redundant role in the TGFβ signaling involved in response to acute kidney injury. PMID:24708746

Red Kidney: Kidney Transplant From a Deceased Donor Who Received Massive Blood Transfusion During Cardiopulmonary Bypass.

PubMed

Bell, Richard; Hanif, Faisal; Prasad, Padmini; Ahmad, Niaz

2016-06-01

Here, we present a case of a deceased-donor kidney transplant. The brain-dead donor had received a massive blood transfusion during cardiopulmonary bypass, which lead to hemolysis, hemoglobinuria, acute kidney injury, and renal replacement therapy. The kidney appeared red after in situ flush. Postoperatively, the recipient developed delayed graft function. Protocol biopsy during the postoperative period revealed the widespread deposition of heme pigment in the renal tubules. Massive blood transfusion and cardiopulmonary bypass surgery are associated with hemolysis and heme pigment deposition in the renal tubules, which subsequently lead to acute kidney injury. Kidneys from such donors appear red and, while this does not preclude transplant, are likely to develop delayed graft function.

Stem cells in kidney regeneration.

PubMed

Yokote, Shinya; Yokoo, Takashi

2012-01-01

Currently many efforts are being made to apply regenerative medicine to kidney diseases using several types of stem/progenitor cells, such as mesenchymal stem cells, renal stem/progenitor cells, embryonic stem cells and induced pluripotent stem cells. Stem cells have the ability to repair injured organs and ameliorate damaged function. The strategy for kidney tissue repair is the recruitment of stem cells and soluble reparative factors to the kidney to elicit tissue repair and the induction of dedifferentiation of resident renal cells. On the other hand, where renal structure is totally disrupted, absolute kidney organ regeneration is needed to rebuild a whole functional kidney. In this review, we describe current advances in stem cell research for kidney tissue repair and de novo organ regeneration.

Association of Proteinuria and Incident Atrial Fibrillation in Patients With Intact and Reduced Kidney Function.

PubMed

Molnar, Amber O; Eddeen, Anan Bader; Ducharme, Robin; Garg, Amit X; Harel, Ziv; McCallum, Megan K; Perl, Jeffrey; Wald, Ron; Zimmerman, Deborah; Sood, Manish M

2017-07-06

Early evidence suggests proteinuria is independently associated with incident atrial fibrillation (AF). We sought to investigate whether the association of proteinuria with incident AF is altered by kidney function. Retrospective cohort study using administrative healthcare databases in Ontario, Canada (2002-2015). A total of 736 666 patients aged ≥40 years not receiving dialysis and with no previous history of AF were included. Proteinuria was defined using the urine albumin-to-creatinine ratio (ACR) and kidney function by the estimated glomerular filtration rate (eGFR). The primary outcome was time to AF. Cox proportional models were used to determine the hazard ratio for AF censored for death, dialysis, kidney transplant, or end of follow-up. Fine and Grey models were used to determine the subdistribution hazard ratio for AF, with death as a competing event. Median follow-up was 6 years and 44 809 patients developed AF. In adjusted models, ACR and eGFR were associated with AF ( P <0.0001). The association of proteinuria with AF differed based on kidney function (ACR × eGFR interaction, P <0.0001). Overt proteinuria (ACR, 120 mg/mmol) was associated with greater AF risk in patients with intact (eGFR, 120) versus reduced (eGFR, 30) kidney function (adjusted hazard ratios, 4.5 [95% CI, 4.0-5.1] and 2.6 [95% CI, 2.4-2.8], respectively; referent ACR 0 and eGFR 120). Results were similar in competing risk analyses. Proteinuria increases the risk of incident AF markedly in patients with intact kidney function compared with those with decreased kidney function. Screening and preventative strategies should consider proteinuria as an independent risk factor for AF. © 2017 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley.

Outcomes of ureteroscopy for patients with stones in a solitary kidney: evidence from a systematic review

PubMed Central

Rai, Bhavan Prasad; Somani, Bhaskar K.

2016-01-01

Introduction Management of urolithiasis in a solitary functioning kidney can be clinically challenging. The aim of this article was to review the outcomes of URS for patients with stone disease in a solitary kidney and critically appraise the existing evidence and outcome reporting standards. Material and methods We conducted a systematic review in line with PRISMA checklist and Cochrane guidelines between January 1980 and February 2015. Our inclusion criteria were all English language articles reporting on a minimum of 10 patients with a solitary kidney undergoing ureteroscopy for stone disease. Results A total of 116 patients (mean age 50 years) underwent URS for stones in solitary kidney. For a mean stone size of 16.8 mm (range: 5–60 mm) and 1.23 procedures/patient, the mean stone free rate was 87%. No significant change in renal function was recorded in any of the studies although a transient elevation in creatinine was reported in 10 (8.6%) patients. A total of 33 (28%) complications were recorded a majority (n = 21) of which were Clavien grade I. The Clavien grade II/III complications as reported by authors were urosepsis, steinstrasse and renal colic. None of the procedures required conversion to open surgery with no cases of renal haematoma or ureteric perforation. Conclusions This contemporary review highlights URS as a viable treatment option for stone disease in patients with a solitary kidney. It is associated with superior clearance rates to SWL and fewer high-risk complications compared to PCNL. PMID:27123332

An unusual case of acute kidney injury due to vancomycin lessons learnt from reliance on eGFR.

PubMed

Barraclough, Katherine; Harris, Marianne; Montessori, Val; Levin, Adeera

2007-08-01

We present a case of renal impairment in an emaciated HIV-infected male that initially went unrecognized because of reliance on serum creatinine and estimated glomerular filtration rate (eGFR). Inaccurate vancomycin dosing led to toxic drug levels (66 mg/l), associated with acute and severe worsening of kidney function. This occurred in the context of escalating doses of vancomycin given in the presence of changing kidney function, albeit kidney function that always remained well within the normal range (serum creatinine 29 - 42 mumol/l). In the absence of other plausible explanations, a presumptive diagnosis of vancomycin nephrotoxicity was made. Given the rarity of this diagnosis in the current era, we discuss the pathophysiology of vancomycin nephrotoxicity. We also explore the potential reasons for inaccuracy of GFR prediction equations in the HIV population, and discuss the potential pitfalls associated with application of eGFR or even serum creatinine without appropriate understanding of their limitations. We believe our case highlights a number of important teaching points: Vancomycin nephrotoxitiy is rare but can occur in the setting of kidney dysfunction. Current assessment of kidney function using creatinine and eGFR requires awareness of the clinical caveats in which these measures may be misleading. Acute changes in kidney function, irrespective of the test used, should be contextualized to the individual situation. Persons with HIV and low muscle mass constitute a specific subgroup in whom assessment of kidney function may be problematic using creatinine. We support ongoing efforts to develop or refine equations for specific unique and easily identifiable populations.

The Impact of the Nitric Oxide (NO)/Soluble Guanylyl Cyclase (sGC) Signaling Cascade on Kidney Health and Disease: A Preclinical Perspective.

PubMed

Krishnan, Shalini M; Kraehling, Jan R; Eitner, Frank; Bénardeau, Agnès; Sandner, Peter

2018-06-09

Chronic Kidney Disease (CKD) is a highly prevalent disease with a substantial medical need for new and more efficacious treatments. The Nitric Oxide (NO), soluble guanylyl cyclase (sGC), cyclic guanosine monophosphate (cGMP) signaling cascade regulates various kidney functions. cGMP directly influences renal blood flow, renin secretion, glomerular function, and tubular exchange processes. Downregulation of NO/sGC/cGMP signaling results in severe kidney pathologies such as CKD. Therefore, treatment strategies aiming to maintain or increase cGMP might have beneficial effects for the treatment of progressive kidney diseases. Within this article, we review the NO/sGC/cGMP signaling cascade and its major pharmacological intervention sites. We specifically focus on the currently known effects of cGMP on kidney function parameters. Finally, we summarize the preclinical evidence for kidney protective effects of NO-donors, PDE inhibitors, sGC stimulators, and sGC activators.

Biosignals Analysis for Kidney Function Effect Analysis of Fennel Aromatherapy

PubMed Central

Kim, Bong-Hyun; Cho, Dong-Uk; Seo, Ssang-Hee

2015-01-01

Human effort in order to enjoy a healthy life is diverse. IT technology to these analyzes, the results of development efforts, it has been applied. Therefore, I use the care and maintenance diagnostic health management and prevention than treatment. In particular, the aromatherapy treatment easy to use without the side effects there is no irritation, are widely used in modern society. In this paper, we measured the aroma effect by applying a biosignal analysis techniques; an experiment was performed to analyze. In particular, we design methods and processes of research based on the theory aroma that affect renal function. Therefore, in this paper, measuring the biosignals and after fennel aromatherapy treatment prior to the enforcement of the mutual comparison, through the analysis, studies were carried out to analyze the effect of fennel aromatherapy therapy on kidney function. PMID:25977696

[Kidney function and liver transplantation].

PubMed

Gámán, György; Gelley, Fanni; Gerlei, Zsuzsa; Dabasi, Eszter; Görög, Dénes; Fehérvári, Imre; Kóbori, László; Lengyel, Gabriella; Zádori, Gergely; Fazakas, János; Doros, Attila; Sárváry, Enikő; Nemes, Balázs

2013-06-30

In liver cirrhosis renal function decreases as well. Hepatorenal syndrome is the most frequent cause of the decrease, but primary kidney failure, diabetes mellitus and some diseases underlying endstage liver failure (such as hepatitis C virus infection) can also play an important role. In liver transplantation several further factors (total cross-clamping of vena cava inferior, polytransfusion, immunosuppression) impair the renal function, too. The aim of this study was to analyse the changes in kidney function during the first postoperative year after liver transplantation. Retrospective data analysis was performed after primary liver transplantations (n = 319). impaired preoperative renal function increased the devepolment of postoperative complications and the first year cumulative patient survival was significantly worse (91,7% vs 69,9%; p<0,001) in this group. If renal function of the patients increased above 60 ml/min/1,73 m2 after the first year, patient survival was better. Independently of the preoperative kidney function, 76% of the patients had impaired kidney function at the first postoperative year. In this group, de novo diabetes mellitus was more frequently diagnosed (22,5% vs 9,5%; p = 0,023). Selection of personalized immunosuppressive medication has a positive effect on renal function.

Chronic Kidney Disease Epidemiology Collaboration versus Modification of Diet in Renal Disease equations for renal function evaluation in patients undergoing partial nephrectomy.

PubMed

Shikanov, Sergey; Clark, Melanie A; Raman, Jay D; Smith, Benjamin; Kaag, Matthew; Russo, Paul; Wheat, Jeffrey C; Wolf, J Stuart; Huang, William C; Shalhav, Arieh L; Eggener, Scott E

2010-11-01

A novel equation, the Chronic Kidney Disease Epidemiology Collaboration, has been proposed to replace the Modification of Diet in Renal Disease for estimated glomerular filtration rate due to higher accuracy, particularly in the setting of normal renal function. We compared these equations in patients with 2 functioning kidneys undergoing partial nephrectomy. We assembled a cohort of 1,158 patients from 5 institutions who underwent partial nephrectomy between 1991 and 2009. Only subjects with 2 functioning kidneys were included in the study. The end points were baseline estimated glomerular filtration rate, last followup estimated glomerular filtration rate (3 to 18 months), absolute and percent change estimated glomerular filtration rate ([absolute change/baseline] × 100%), and proportion of newly developed chronic kidney disease stage III. The agreement between the equations was evaluated using Bland-Altman plots and the McNemar test for paired observations. Mean baseline estimated glomerular filtration rate derived from the Modification of Diet in Renal Disease and Chronic Kidney Disease Epidemiology Collaboration equations were 73 and 77 ml/minute/1.73 m(2), respectively, and following surgery were 63 and 67 ml/minute/1.73 m(2), respectively. Mean percent change estimated glomerular filtration rate was -12% for both equations (p = 0.2). The proportion of patients with newly developed chronic kidney disease stage III following surgery was 32% and 25%, according to the Modification of Diet in Renal Disease and Chronic Kidney Disease Epidemiology Collaboration equations, respectively (p = 0.001). For patients with 2 functioning kidneys undergoing partial nephrectomy the Chronic Kidney Disease Epidemiology Collaboration equation provides slightly higher glomerular filtration rate estimates compared to the Modification of Diet in Renal Disease equation, with 7% fewer patients categorized as having chronic kidney disease stage III or worse. Copyright © 2010 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

Interactive effects of diabetes and impaired kidney function on cognitive performance in old age: a population-based study.

PubMed

Yin, Zhaoxue; Yan, Zhongrui; Liang, Yajun; Jiang, Hui; Cai, Chuanzhu; Song, Aiqin; Feng, Lei; Qiu, Chengxuan

2016-01-12

The interactive effect between diabetes and impaired kidney function on cognitive impairment in older adults has not yet been reported. The aim of this study was to investigate the association of diabetes and impaired kidney function with cognitive impairment among Chinese older people living in a rural area. This cross-sectional study included 1,358 participants (age ≥60 years; 60.5% women) in the population-based Confucius Hometown Aging Project in Shandong, China. Data on demographics, lifestyle factors, health history, use of medications, global cognitive function, and kidney function were collected through structured interviews, clinical examinations, and blood tests. We defined diabetes as a fasting plasma glucose level ≥7.0 mmol/l or use of hypoglycemic agents, impaired kidney function as glomerular filtration rate estimated from cystatin C (eGFRcys) <60 ml/min/1.73 m(2). Cognitive impairment was defined using the education-based cut-off scores of Mini-Mental State Examination (MMSE). Data were analyzed using multiple general linear and logistic regression models. Cognitive impairment was defined in 197 (14.5%) persons. The multi-adjusted β coefficient of MMSE score associated with diabetes was -0.06 (95% confidence interval [CI], -0.16, 0.03); the corresponding figures associated with eGFRcys <60, 60-89.9, and ≥90 ml/min/1.73 m(2) were -0.15 (-0.28, -0.02), -0.01 (-0.10, 0.08), and 0 (reference) (Ptrend = 0.046), respectively. Diabetes and impaired kidney function showed an interactive effect on cognitive impairment ( interaction = 0.02). Compared with individuals having neither diabetes nor impaired kidney function, those with both conditions had a multi-adjusted odds ratio of 4.23 (95% CI, 2.10-8.49) for cognitive impairment. The relative excess risk due to interaction was 2.74. This study suggests that concurrent presence of diabetes and impaired kidney function is associated with a substantial likelihood for cognitive impairment in older adults.

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

Kidney function endpoints in kidney transplant trials: a struggle for power.

PubMed

Ibrahim, A; Garg, A X; Knoll, G A; Akbari, A; White, C A

2013-03-01

Kidney function endpoints are commonly used in randomized controlled trials (RCTs) in kidney transplantation (KTx). We conducted this study to estimate the proportion of ongoing RCTs with kidney function endpoints in KTx where the proposed sample size is large enough to detect meaningful differences in glomerular filtration rate (GFR) with adequate statistical power. RCTs were retrieved using the key word "kidney transplantation" from the National Institute of Health online clinical trial registry. Included trials had at least one measure of kidney function tracked for at least 1 month after transplant. We determined the proportion of two-arm parallel trials that had sufficient sample sizes to detect a minimum 5, 7.5 and 10 mL/min difference in GFR between arms. Fifty RCTs met inclusion criteria. Only 7% of the trials were above a sample size of 562, the number needed to detect a minimum 5 mL/min difference between the groups should one exist (assumptions: α = 0.05; power = 80%, 10% loss to follow-up, common standard deviation of 20 mL/min). The result increased modestly to 36% of trials when a minimum 10 mL/min difference was considered. Only a minority of ongoing trials have adequate statistical power to detect between-group differences in kidney function using conventional sample size estimating parameters. For this reason, some potentially effective interventions which ultimately could benefit patients may be abandoned from future assessment. © Copyright 2013 The American Society of Transplantation and the American Society of Transplant Surgeons.

Outcome of organs procured from donors on extracorporeal membrane oxygenation support: an analysis of kidney and liver allograft data.

PubMed

Carter, Timothy; Bodzin, Adam S; Hirose, Hitoshi; West, Sharon; Hasz, Richard; Maley, Warren R; Cavarocchi, Nicholas C

2014-07-01

Extracorporeal membrane oxygenation has become rescue therapy for adults with overwhelming cardiac and/or respiratory failure. Not all patients are saved, creating a new cohort of potential organ donors. This study examines the outcomes of liver and kidney allografts procured from donors on extracorporeal membrane oxygenation (ECMO). A retrospective review was conducted through the local organ procurement organization. Donors on ECMO prior to notification were classified into donation after brain death (DBD) and donation after cardiac death (DCD). We compared short-term outcome data against published standards. Between 1995 and 2012, 97 organs were procured from 41 donors supported on ECMO. There were 68 kidneys donated, 51 were transplanted and 17 discarded. Excluding extended criteria donors, 29 DBD and 13 DCD kidneys were transplanted from donors supported on ECMO. Delayed graft function occurred in 34% of DBD kidneys and 38% of DCD kidneys. Kidney allograft survival at one yr was 93%. Twenty-four livers were procured, nine discarded, and 15 transplanted. Ninety-three percent of liver transplant recipients were alive with graft function at one yr. Donation after brain death kidneys procured from donors on ECMO perform similarly to non-ECMO organs with regard to delayed graft function (DGF), one-yr graft survival and function. Livers from ECMO donors have a higher discard rate than non-ECMO donors, but function similarly at six months and one yr. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Silent ureteral stones: impact on kidney function--can treatment of silent ureteral stones preserve kidney function?

PubMed

Marchini, Giovanni S; Vicentini, Fabio C; Mazzucchi, Eduardo; Brito, Arthur; Ebaid, Gustavo; Srougi, Miguel

2012-02-01

To report our experience with silent ureteral stones and expose their true influence on renal function. We analyzed 506 patients who had undergone ureterolithotripsy from January 2005 to May 2010. Silent ureteral stones were calculi found in the absence of any specific or subjective ureteral stone-related symptoms. Of the 506 patients, 27 (5.3%) met these criteria (global cohort). All patients were assessed postoperatively with dimercaptosuccinic acid scintigraphy (DMSA). A difference in relative kidney function of >10% was considered abnormal. Pre- and postoperative comparative DMSA analyses were electively obtained for 9 patients (kidney function cohort). A t test was used to assess the numeric variables, and the chi-square test or Fisher's exact test was used for categorical variables. Two-tailed P<.05 was considered statistically significant. Stones were diagnosed by radiologic abdominal evaluation for nonurologic diseases in 40% and after previous nephrolithiasis treatment in 33%. The primary therapy was ureterolithotripsy in 88%. The mean follow-up time was 23 months. The overall ureteral stone-free rate after 1 and 2 procedures was 96% and 100%, respectively. In the global cohort, the mean pre- and postoperative serum creatinine levels were similar (P=.39), and the mean postoperative function on DMSA was 31%. In the kidney function cohort, no difference was found between the pre- and postoperative DMSA findings (22%±12.1% vs 20%±11.8%; P=.83) and serum creatinine (0.8±0.13 mg/dL vs 1.0±0.21 mg/dL; P=.45). Silent ureteral stones are associated with decreased kidney function present at the diagnosis. Hydronephrosis tends to diminish after stone removal, and kidney function remains unaltered. Copyright © 2012 Elsevier Inc. All rights reserved.

Dissecting hematopoietic and renal cell heterogeneity in adult zebrafish at single-cell resolution using RNA sequencing.

PubMed

Tang, Qin; Iyer, Sowmya; Lobbardi, Riadh; Moore, John C; Chen, Huidong; Lareau, Caleb; Hebert, Christine; Shaw, McKenzie L; Neftel, Cyril; Suva, Mario L; Ceol, Craig J; Bernards, Andre; Aryee, Martin; Pinello, Luca; Drummond, Iain A; Langenau, David M

2017-10-02

Recent advances in single-cell, transcriptomic profiling have provided unprecedented access to investigate cell heterogeneity during tissue and organ development. In this study, we used massively parallel, single-cell RNA sequencing to define cell heterogeneity within the zebrafish kidney marrow, constructing a comprehensive molecular atlas of definitive hematopoiesis and functionally distinct renal cells found in adult zebrafish. Because our method analyzed blood and kidney cells in an unbiased manner, our approach was useful in characterizing immune-cell deficiencies within DNA-protein kinase catalytic subunit ( prkdc ), interleukin-2 receptor γ a ( il2rga ), and double-homozygous-mutant fish, identifying blood cell losses in T, B, and natural killer cells within specific genetic mutants. Our analysis also uncovered novel cell types, including two classes of natural killer immune cells, classically defined and erythroid-primed hematopoietic stem and progenitor cells, mucin-secreting kidney cells, and kidney stem/progenitor cells. In total, our work provides the first, comprehensive, single-cell, transcriptomic analysis of kidney and marrow cells in the adult zebrafish. © 2017 Tang et al.

Dissecting hematopoietic and renal cell heterogeneity in adult zebrafish at single-cell resolution using RNA sequencing

PubMed Central

Iyer, Sowmya; Lobbardi, Riadh; Chen, Huidong; Hebert, Christine; Shaw, McKenzie L.; Neftel, Cyril; Suva, Mario L.; Bernards, Andre; Aryee, Martin; Drummond, Iain A.

2017-01-01

Recent advances in single-cell, transcriptomic profiling have provided unprecedented access to investigate cell heterogeneity during tissue and organ development. In this study, we used massively parallel, single-cell RNA sequencing to define cell heterogeneity within the zebrafish kidney marrow, constructing a comprehensive molecular atlas of definitive hematopoiesis and functionally distinct renal cells found in adult zebrafish. Because our method analyzed blood and kidney cells in an unbiased manner, our approach was useful in characterizing immune-cell deficiencies within DNA–protein kinase catalytic subunit (prkdc), interleukin-2 receptor γ a (il2rga), and double-homozygous–mutant fish, identifying blood cell losses in T, B, and natural killer cells within specific genetic mutants. Our analysis also uncovered novel cell types, including two classes of natural killer immune cells, classically defined and erythroid-primed hematopoietic stem and progenitor cells, mucin-secreting kidney cells, and kidney stem/progenitor cells. In total, our work provides the first, comprehensive, single-cell, transcriptomic analysis of kidney and marrow cells in the adult zebrafish. PMID:28878000

Influence of fluid resuscitation on renal microvascular PO2 in a normotensive rat model of endotoxemia

PubMed Central

Johannes, Tanja; Mik, Egbert G; Nohé, Boris; Raat, Nicolaas JH; Unertl, Klaus E; Ince, Can

2006-01-01

Introduction Septic renal failure is often seen in the intensive care unit but its pathogenesis is only partly understood. This study, performed in a normotensive rat model of endotoxemia, tests the hypotheses that endotoxemia impairs renal microvascular PO2 (μPO2) and oxygen consumption (VO2,ren), that endotoxemia is associated with a diminished kidney function, that fluid resuscitation can restore μPO2, VO2,ren and kidney function, and that colloids are more effective than crystalloids. Methods Male Wistar rats received a one-hour intravenous infusion of lipopolysaccharide, followed by resuscitation with HES130/0.4 (Voluven®), HES200/0.5 (HES-STERIL® ® 6%) or Ringer's lactate. The renal μPO2 in the cortex and medulla and the renal venous PO2 were measured by a recently published phosphorescence lifetime technique. Results Endotoxemia induced a reduction in renal blood flow and anuria, while the renal μPO2 and VO2,ren remained relatively unchanged. Resuscitation restored renal blood flow, renal oxygen delivery and kidney function to baseline values, and was associated with oxygen redistribution showing different patterns for the different compounds used. HES200/0.5 and Ringer's lactate increased the VO2,ren, in contrast to HES130/0.4. Conclusion The loss of kidney function during endotoxemia could not be explained by an oxygen deficiency. Renal oxygen redistribution could for the first time be demonstrated during fluid resuscitation. HES130/0.4 had no influence on the VO2,ren and restored renal function with the least increase in the amount of renal work. PMID:16784545

Semiparametric methods to contrast gap time survival functions: Application to repeat kidney transplantation.

PubMed

Shu, Xu; Schaubel, Douglas E

2016-06-01

Times between successive events (i.e., gap times) are of great importance in survival analysis. Although many methods exist for estimating covariate effects on gap times, very few existing methods allow for comparisons between gap times themselves. Motivated by the comparison of primary and repeat transplantation, our interest is specifically in contrasting the gap time survival functions and their integration (restricted mean gap time). Two major challenges in gap time analysis are non-identifiability of the marginal distributions and the existence of dependent censoring (for all but the first gap time). We use Cox regression to estimate the (conditional) survival distributions of each gap time (given the previous gap times). Combining fitted survival functions based on those models, along with multiple imputation applied to censored gap times, we then contrast the first and second gap times with respect to average survival and restricted mean lifetime. Large-sample properties are derived, with simulation studies carried out to evaluate finite-sample performance. We apply the proposed methods to kidney transplant data obtained from a national organ transplant registry. Mean 10-year graft survival of the primary transplant is significantly greater than that of the repeat transplant, by 3.9 months (p=0.023), a result that may lack clinical importance. © 2015, The International Biometric Society.

Resveratrol Rescues Kidney Mitochondrial Function Following Hemorrhagic Shock

PubMed Central

Wang, Hao; Guan, Yuxia; Karamercan, Mehmet Akif; Ye, Lan; Bhatti, Tricia; Becker, Lance B.; Baur, Joseph A.; Sims, Carrie A.

2015-01-01

Objective Hemorrhagic shock may contribute to acute kidney injury by profoundly altering renal mitochondrial function. Resveratrol (RSV), a naturally occurring sirtuin-1 (SIRT1) activator, has been shown to promote mitochondrial function and reduce oxidative damage in a variety of aging-related disease states. We hypothesized that RSV treatment during resuscitation would ameliorate kidney mitochondrial dysfunction and decrease oxidative damage following hemorrhagic shock. Method Using a decompensated hemorrhagic shock model, male Long-Evans rats (n=6 per group) were sacrificed prior to hemorrhage (Sham), at severe shock, and following either lactated Ringer’s (LR) Resuscitation or LR+RSV Resuscitation (RSV: 30mg/kg). At each time point, blood samples were assayed for arterial blood gases, lactate, blood urea nitrogen (BUN) and serum creatinine. Mitochondria were also isolated from kidney samples in order to assess individual electron transport complexes (CI, CII, and CIV) using high-resolution respirometry. Total mitochondria reactive oxygen species (ROS) were measured using fluorometry and lipid peroxidation was assessed by measuring 4-hydroxynonenal by Western blot. qPCR was used quantify mRNA from PGC1-α, SIRT1, and proteins known to mitigate oxidative damage and promote mitochondrial biogenesis. Results RSV supplementation during resuscitation restored mitochondrial respiratory capacity, decreased mitochondrial ROS and lipid peroxidation. Compared to standard LR resuscitation, RSV treatment significantly increased SIRT1 and PGC1-α expression and significantly increased both SOD2 and catalase expression. Although RSV was associated with decreased lactate production, pH, BUN and serum creatinine values did not differ between resuscitation strategies. Conclusions Resuscitation with RSV significantly restored renal mitochondrial function and decreased oxidative damage following hemorrhagic shock. PMID:25895148

Effects of Sugammadex and Neostigmine on Renal Biomarkers

PubMed Central

Isik, Yasemin; Palabiyik, Onur; Cegin, Bilal Muhammed; Goktas, Ugur; Kati, Ismail

2016-01-01

Background Neostigmine, the currently commonly used agent for reversal of neuromuscular blockade. Sugammadex is a novel and unique compound designed as an antagonist of steroidal neuromuscular blockers. In this study, we evaluated the effects of sugammadex or neostigmine on kidney functions in patients scheduled for elective surgery. Material/Methods Patients scheduled for a surgical procedure under desflurane/opioid anesthesia received an intubating dose rocuronium. Patients were divided into 2 groups receiving either sugammadex or neostigmine atropine to reverse neuromuscular blockade. Cystatin C, creatinine, urea, blood urea nitrogen, sodium, potassium, and calcium levels in the blood and α1microglobulin, β2microglobulin, and microalbumin levels in the urine were measured. Results There was no significant difference between the groups with regard to the demographic data. In the Neostigmine Group, although β2microglobulin and microalbumin were similar, a significant increase was found in the postoperative α1microglobulin and cystatin C values. In the Sugammadex Group, although β2-microglobulin and cystatin C were similar, a significant increase was found in the postoperative α1-microglobulin and microalbumin values. The only significant difference was cystatin C value variation in the Neostigmine Group compared to the Sugammadex Group. Conclusions We believe that the use of more specific and sensitive new-generation markers like cystatin C to evaluate kidney function will provide a better understanding and interpretation of our results. Sugammadex has more tolerable effects on kidney function in patients than does neostigmine. However, when compared to preoperative values, there is a negative alteration of postoperative values. Neostigmine and sugammadex do not cause renal failure but they may affect kidney function. PMID:26963316

Neural regulation of the kidney function in rats with cisplatin induced renal failure

PubMed Central

Goulding, Niamh E.; Johns, Edward J.

2015-01-01

Aim: Chronic kidney disease (CKD) is often associated with a disturbed cardiovascular homeostasis. This investigation explored the role of the renal innervation in mediating deranged baroreflex control of renal sympathetic nerve activity (RSNA) and renal excretory function in cisplatin-induced renal failure. Methods: Rats were either intact or bilaterally renally denervated 4 days prior to receiving cisplatin (5 mg/kg i.p.) and entered a chronic metabolic study for 8 days. At day 8, other groups of rats were prepared for acute measurement of RSNA or renal function with either intact or denervated kidneys. Results: Following the cisplatin challenge, creatinine clearance was 50% lower while fractional sodium excretion and renal cortical and medullary TGF-β1 concentrations were 3–4 fold higher in both intact and renally denervated rats compared to control rats. In cisplatin-treated rats, the maximal gain of the high-pressure baroreflex curve was only 20% that of control rats, but following renal denervation not different from that of renally denervated control rats. Volume expansion reduced RSNA by 50% in control and in cisplatin-treated rats but only following bilateral renal denervation. The volume expansion mediated natriuresis/diuresis was absent in the cisplatin-treated rats but was normalized following renal denervation. Conclusions: Cisplatin-induced renal injury impaired renal function and caused a sympatho-excitation with blunting of high and low pressure baroreflex regulation of RSNA, which was dependent on the renal innervation. It is suggested that in man with CKD there is a dysregulation of the neural control of the kidney mediated by its sensory innervation. PMID:26175693

Does long-term creatine supplementation impair kidney function in resistance-trained individuals consuming a high-protein diet?

PubMed Central

2013-01-01

Background The aim of this study was to determine the effects of creatine supplementation on kidney function in resistance-trained individuals ingesting a high-protein diet. Methods A randomized, double-blind, placebo-controlled trial was performed. The participants were randomly allocated to receive either creatine (20 g/d for 5 d followed by 5 g/d throughout the trial) or placebo for 12 weeks. All of the participants were engaged in resistance training and consumed a high-protein diet (i.e., ≥ 1.2 g/Kg/d). Subjects were assessed at baseline (Pre) and after 12 weeks (Post). Glomerular filtration rate was measured by 51Cr-EDTA clearance. Additionally, blood samples and a 24-h urine collection were obtained for other kidney function assessments. Results No significant differences were observed for 51Cr-EDTA clearance throughout the trial (Creatine: Pre 101.42 ± 13.11, Post 108.78 ± 14.41 mL/min/1.73m2; Placebo: Pre 103.29 ± 17.64, Post 106.68 ± 16.05 mL/min/1.73m2; group x time interaction: F = 0.21, p = 0.64). Creatinine clearance, serum and urinary urea, electrolytes, proteinuria, and albuminuria remained virtually unchanged. Conclusions A 12-week creatine supplementation protocol did not affect kidney function in resistance-trained healthy individuals consuming a high-protein diet; thus reinforcing the safety of this dietary supplement. Trial registration ClinicalTrials.gov NCT01817673 PMID:23680457

[Considerations when using creatinine as a measure of kidney function].

PubMed

Drion, I Iefke; Fokkert, M J Marion; Bilo, H J G Henk

2013-01-01

Reported serum creatinine concentrations can sometimes vary considerably, even when the renal function does less so or even not. This variation is partly due to true changes in actual serum concentration, and partly due to interferences in the measurement technique, thus not reflecting a true change in concentration. Increased or decreased endogenous creatinine production, ingested creatinine sources through meat eating or certain creatine formulations, and interference by either browning of chromogenic substances in Jaffe measurement techniques or promotors and inhibitors of enzymatic reaction methods do play a role. Reliable serum creatinine measurements are needed for renal function estimating equations. In screening circumstances and daily practice, chronic kidney disease staging is based on these estimated glomerular filtration rate values. Given the possible influences on reported serum creatinine concentrations, it is important for health care workers to remain critical when interpreting outcomes of renal function estimating equations and to not see every reported result based on an equation as a true reflection of renal function.

Cystatin C-Based Equation Does Not Accurately Estimate the Glomerular Filtration in Japanese Living Kidney Donors.

PubMed

Tsujimura, Kazuma; Ota, Morihito; Chinen, Kiyoshi; Adachi, Takayuki; Nagayama, Kiyomitsu; Oroku, Masato; Nishihira, Morikuni; Shiohira, Yoshiki; Iseki, Kunitoshi; Ishida, Hideki; Tanabe, Kazunari

2017-06-23

BACKGROUND Precise evaluation of a living donor's renal function is necessary to ensure adequate residual kidney function after donor nephrectomy. Our aim was to evaluate the feasibility of estimating glomerular filtration rate (GFR) using serum cystatin-C prior to kidney transplantation. MATERIAL AND METHODS Using the equations of the Japanese Society of Nephrology, we calculated the GFR using serum creatinine (eGFRcre) and cystatin C levels (eGFRcys) for 83 living kidney donors evaluated between March 2010 and March 2016. We compared eGFRcys and eGFRcre values against the creatinine clearance rate (CCr). RESULTS The study population included 27 males and 56 females. The mean eGFRcys, eGFRcre, and CCr were, 91.4±16.3 mL/min/1.73 m² (range, 59.9-128.9 mL/min/1.73 m²), 81.5±14.2 mL/min/1.73 m² (range, 55.4-117.5 mL/min/1.73 m²) and 108.4±21.6 mL/min/1.73 m² (range, 63.7-168.7 mL/min/1.73 m²), respectively. eGFRcys was significantly lower than CCr (p<0.001). The correlation coefficient between eGFRcys and CCr values was 0.466, and the mean difference between the two values was -17.0 (15.7%), with a root mean square error of 19.2. Thus, eGFRcre was significantly lower than CCr (p<0.001). The correlation coefficient between eGFRcre and CCr values was 0.445, and the mean difference between the two values was -26.9 (24.8%), with a root mean square error of 19.5. CONCLUSIONS Although eGFRcys provided a better estimation of GFR than eGFRcre, eGFRcys still did not provide an accurate measure of kidney function in Japanese living kidney donors.

Low serum bicarbonate and kidney function decline: the Multi-Ethnic Study of Atherosclerosis (MESA).

PubMed

Driver, Todd H; Shlipak, Michael G; Katz, Ronit; Goldenstein, Leonard; Sarnak, Mark J; Hoofnagle, Andrew N; Siscovick, David S; Kestenbaum, Bryan; de Boer, Ian H; Ix, Joachim H

2014-10-01

Among populations with established chronic kidney disease (CKD), metabolic acidosis is associated with more rapid progression of kidney disease. The association of serum bicarbonate concentrations with early declines in kidney function is less clear. Retrospective cohort study. 5,810 participants in the Multi-Ethnic Study of Atherosclerosis (MESA) with a baseline estimated glomerular filtration rate (eGFR) > 60mL/min/1.73 m(2) using the CKD-EPI (CKD Epidemiology Collaboration) creatinine-cystatin C equation. Serum bicarbonate concentrations. Rapid kidney function decline (eGFR decline > 5% per year) and incident reduced eGFR (eGFR < 60mL/min/1.73 m(2) with minimum rate of eGFR loss of 1 mL/min/1.73 m(2) per year). Average bicarbonate concentration was 23.2 ± 1.8mEq/L. 1,730 (33%) participants had rapid kidney function decline, and 487 had incident reduced eGFR during follow-up. Each 1-SD lower baseline bicarbonate concentration was associated with 12% higher adjusted odds of rapid kidney function decline (95% CI, 6%-20%) and higher risk of incident reduced eGFR (adjusted incidence rate ratio, 1.11; 95% CI, 1.03-1.20) in models adjusting for demographics, baseline eGFR, albuminuria, and CKD risk factors. The OR for the associations of bicarbonate level < 21 mEq/L relative to 23-24 mEq/L was 1.35 (95% CI, 1.05-1.73) for rapid kidney function decline, and the incidence rate ratio was 1.16 (95% CI, 0.83-1.62) for incident reduced eGFR. Cause of metabolic acidosis cannot be determined in this study. Lower serum bicarbonate concentrations are associated independently with rapid kidney function decline independent of eGFR or albuminuria in community-living persons with baseline eGFR > 60 mL/min/1.73 m(2). If confirmed, our findings suggest that metabolic acidosis may indicate either early kidney disease that is not captured by eGFR or albuminuria or may have a causal role in the development of eGFR < 60 mL/min/1.73 m(2). Copyright © 2014 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.

Prokineticin Receptor‐1 Is a New Regulator of Endothelial Insulin Uptake and Capillary Formation to Control Insulin Sensitivity and Cardiovascular and Kidney Functions

PubMed Central

Dormishian, Mojdeh; Turkeri, Gulen; Urayama, Kyoji; Nguyen, Thu Lan; Boulberdaa, Mounia; Messaddeq, Nadia; Renault, Gilles; Henrion, Daniel; Nebigil, Canan G.

2013-01-01

Background Reciprocal relationships between endothelial dysfunction and insulin resistance result in a vicious cycle of cardiovascular, renal, and metabolic disorders. The mechanisms underlying these impairments are unclear. The peptide hormones prokineticins exert their angiogenic function via prokineticin receptor‐1 (PKR1). We explored the extent to which endothelial PKR1 contributes to expansion of capillary network and the transcapillary passage of insulin into the heart, kidney, and adipose tissues, regulating organ functions and metabolism in a specific mice model. Methods and Results By combining cellular studies and studies in endothelium‐specific loss‐of‐function mouse model (ec‐PKR1−/−), we showed that a genetically induced PKR1 loss in the endothelial cells causes the impaired capillary formation and transendothelial insulin delivery, leading to insulin resistance and cardiovascular and renal disorders. Impaired insulin delivery in endothelial cells accompanied with defective expression and activation of endothelial nitric oxide synthase in the ec‐PKR1−/− aorta, consequently diminishing endothelium‐dependent relaxation. Despite having a lean body phenotype, ec‐PKR1−/− mice exhibited polyphagia, polydipsia, polyurinemia, and hyperinsulinemia, which are reminiscent of human lipodystrophy. High plasma free fatty acid levels and low leptin levels further contribute to the development of insulin resistance at the later age. Peripheral insulin resistance and ectopic lipid accumulation in mutant skeletal muscle, heart, and kidneys were accompanied by impaired insulin‐mediated Akt signaling in these organs. The ec‐PKR1−/− mice displayed myocardial fibrosis, low levels of capillary formation, and high rates of apoptosis, leading to diastolic dysfunction. Compact fibrotic glomeruli and high levels of phosphate excretion were found in mutant kidneys. PKR1 restoration in ec‐PKR1−/− mice reversed the decrease in capillary recruitment and insulin uptake and improved heart and kidney function and insulin resistance. Conclusions We show a novel role for endothelial PKR1 signaling in cardiac, renal, and metabolic functions by regulating transendothelial insulin uptake and endothelial cell proliferation. Targeting endothelial PKR1 may serve as a therapeutic strategy for ameliorating these disorders. PMID:24152983

Kidney transplantation: a systematic review of interventional and observational studies of physical activity on intermediate outcomes.

PubMed

Macdonald, Jamie Hugo; Kirkman, Danielle; Jibani, Mahdi

2009-11-01

Kidney transplant patients have decreased quality and longevity of life. Whether exercise can positively affect associated outcomes such as physical functioning, metabolic syndrome, kidney function, and immune function, has only been addressed in relatively small studies. Thus the aim of this systematic review was to determine effects of physical activity level on these intermediate outcomes in kidney transplant patients. We electronically and hand searched to identify 21 studies (6 retrospective assessments of habitual physical activity and 15 intervention studies including 6 controlled trials). After study quality assessment, intermediate outcomes associated with quality and longevity of life were expressed as correlations or percentage changes in addition to effect sizes. Habitual physical activity level was positively associated with quality of life and aerobic fitness and negatively associated with body fat (medium to large effect sizes). Exercise interventions also showed medium to large positive effects on aerobic capacity (10%-114% increase) and muscle strength (10%-22% increase). However, exercise programs had minimal or contradictory effects on metabolic syndrome and immune and kidney function. In kidney transplant patients, physical activity intervention is warranted to enhance physical functioning. Whether exercise impacts on outcomes associated with longevity of life requires further study.

Genomic integration of ERRγ-HNF1β regulates renal bioenergetics and prevents chronic kidney disease.

PubMed

Zhao, Juanjuan; Lupino, Katherine; Wilkins, Benjamin J; Qiu, Chengxiang; Liu, Jian; Omura, Yasuhiro; Allred, Amanda L; McDonald, Caitlin; Susztak, Katalin; Barish, Grant D; Pei, Liming

2018-05-22

Mitochondrial dysfunction is increasingly recognized as a critical determinant of both hereditary and acquired kidney diseases. However, it remains poorly understood how mitochondrial metabolism is regulated to support normal kidney function and how its dysregulation contributes to kidney disease. Here, we show that the nuclear receptor estrogen-related receptor gamma (ERRγ) and hepatocyte nuclear factor 1 beta (HNF1β) link renal mitochondrial and reabsorptive functions through coordinated epigenomic programs. ERRγ directly regulates mitochondrial metabolism but cooperatively controls renal reabsorption via convergent binding with HNF1β. Deletion of ERRγ in renal epithelial cells (RECs), in which it is highly and specifically expressed, results in severe renal energetic and reabsorptive dysfunction and progressive renal failure that recapitulates phenotypes of animals and patients with HNF1β loss-of-function gene mutations. Moreover, ERRγ expression positively correlates with renal function and is decreased in patients with chronic kidney disease (CKD). REC-ERRγ KO mice share highly overlapping renal transcriptional signatures with human patients with CKD. Together these findings reveal a role for ERRγ in directing independent and HNF1β-integrated programs for energy production and use essential for normal renal function and the prevention of kidney disease.

Renal volume assessed by magnetic resonance imaging volumetry correlates with renal function in living kidney donors pre- and postdonation: a retrospective cohort study.

PubMed

Lange, Daniel; Helck, Andreas; Rominger, Axel; Crispin, Alexander; Meiser, Bruno; Werner, Jens; Fischereder, Michael; Stangl, Manfred; Habicht, Antje

2018-07-01

Renal function of potential living kidney donors is routinely assessed with scintigraphy. Kidney anatomy is evaluated by imaging techniques such as magnetic resonance imaging (MRI). We evaluated if a MRI-based renal volumetry is a good predictor of kidney function pre- and postdonation. We retrospectively analyzed the renal volume (RV) in a MRI of 100 living kidney donors. RV was correlated with the tubular excretion rate (TER) of MAG3-scintigraphy, a measured creatinine clearance (CrCl), and the estimated glomerular filtration rate (eGFR) by Cockcroft-Gault (CG), CKD-EPI, and modification of diet in renal disease (MDRD) formula pre- and postdonation during a follow-up of 3 years. RV correlated significantly with the TER (total: r = 0.6735, P < 0.0001). Correlation between RV and renal function was the highest for eGFR by CG (r = 0.5595, P < 0.0001), in comparison with CrCl, MDRD-GFR, and CKD-EPI-GFR predonation. RV significantly correlated with CG-GFR postdonation and predicted CG-GFR until 3 years after donation. MRI renal volumetry might be an alternative technique for the evaluation of split renal function and prediction of renal function postdonation in living kidney donors. © 2018 Steunstichting ESOT.

Dynamic Analysis of Kidney Function and Its Correlation with Nutritional Indicators in a Large Sample of Hospitalized Elderly Patients.

PubMed

Qingping, Li; Ribao, Wei; Yang, Wang; Tingyu, Su; Xi, Yang; Mengjie, Huang; Hui, Miao; Xiangmei, Chen

2017-04-23

BACKGROUND The aim of this study was to analyze changes in kidney function and its correlation with nutritional metabolism indicators in hospitalized elderly patients in a large medical center over the past 7 years. MATERIAL AND METHODS The renal function of patients over 60 years old in the Chinese PLA General Hospital in 2008, 2011, and 2014 were comparatively analyzed. The hemoglobin, serum albumin, triglycerides, cholesterol, uric acid, and urea nitrogen data were collected and used as the nutritional metabolism indicators. In addition, the correlation between these indicators and the eGFR was analyzed. RESULTS The numbers of patients who received kidney function assessments in the 3 years were 15 752, 23 539, and 49 828; their mean ages were 69.97±6.99, 69.51±7.11, and 69.45±7.74 years. The median values of serum creatinine were 75.4, 76.5, and 77.5 μmol/L in the men and 59.6, 60.7, and 62.1 μmol/L in the women. The eGFR in both sexes demonstrated a gradual decreasing trend over the 3 years. According to the CKD staging method, analysis of the different percentages of eGFR intervals in the patients showed that the percentages of the 3 groups with an eGFR lower than 60 mL/min/1.73 m² exhibited a rising trend annually. Correlational analysis of the nutritional indicators showed that the correlations between Hb, ALB, TG, TC, Ur, and BUN with an eGFR lower than 60 mL/min/1.73 m² were 0.582, 0.780, 1.219, 1.364, 2.180, and 3.677, respectively. CONCLUSIONS Serum creatinine showed a gradually increasing trend over the 3 study years. The CKD-EPI equation calculation results showed that the eGFR in elderly people of both sexes gradually decreased. Reduction of hemoglobin and albumin was a risk factor for decreased kidney function, while increases in uric acid and blood lipids affected the progression of renal insufficiency.

Association of mGFR of the Remaining Kidney Divided by Its Volume before Donation with Functional Gain in mGFR among Living Kidney Donors

PubMed Central

Gaillard, François; Tissier, Anne-Marie; Fournier, Catherine; Le Nestour, Alexis; Corréas, Jean-Michel; Slimani-Thevenet, Hind; Martinez, Frank; Léon, Carine; Eladari, Dominique; Timsit, Marc-Olivier; Otal, Philippe; Hignette, Chantal; Friedlander, Gérard; Méjean, Arnaud; Houillier, Pascal; Kamar, Nassim; Legendre, Christophe

2016-01-01

Background and objectives The predictors of long–term renal function in living kidney donors are currently discussed. Our objectives were to describe the predictors of functional gain of the remaining kidney after kidney donation. We hypothesized that GFR of the remaining kidney divided by volume of this kidney (rk-GFR/vol) would reflect the density of functional nephrons and be inversely associated with functional gain of the remaining kidney. Design, setting, participants, & measurements We conducted a prospective monocentric study including 63 living donors (26 men; 50.3±11.8 years old) who had been evaluated for 51Cr-EDTA and measured GFR, split renal function by scintigraphy before donation (between 2004 and 2009), and measured GFR at 5.7±0.5 years after donation. For 52 donors, volume of the remaining kidney (measured and estimated with the ellipsoid formula using renal computed tomography scannography) was determined before donation. We tested our hypothesis in an external validation cohort of 39 living donors (13 men; 51.0±9.4 years old) from another single center during the same time period. Results For the main cohort, the mean measured GFR was 97.6±13.0 ml/min per 1.73 m2 before donation and 63.8±9.4 ml/min per 1.73 m2 at 5 years. Functional gain averaged 16.2±7.2 ml/min per 1.73 m2 (+35.3%±16.7%). Multivariate analysis showed that age, body mass index, and rk-GFR/vol at donation were negatively correlated with functional gain and had strong predictive power of the 5-year functional gain (adjusted 5-year functional gain for age: −0.4 [95% confidence interval (95% CI), −0.5 to −0.1]; body mass index: −0.3 [95% CI, −0.6 to −0.1]; rk-GFR/vol: −55.1 [95% CI, −92.3 to −17.9]). We tested this model in the external validation cohort (adjusted 5-year functional gain for age: −0.1 [95% CI, −0.5 to 0.3]; body mass index: −0.9 [95% CI, −1.8 to −0.1]; rk-GFR/vol: −97.6 [95% CI, −137.5 to −57.6]) and confirmed that rk-GFR/vol was inversely associated with 5-year functional gain. Conclusions For given age and body mass index, the long–term functional gain of the remaining kidney is inversely associated with the new variable rk-GFR/vol at donation. PMID:27189317

Dietary fiber, kidney function, inflammation, and mortality risk.

PubMed

Xu, Hong; Huang, Xiaoyan; Risérus, Ulf; Krishnamurthy, Vidya M; Cederholm, Tommy; Arnlöv, Johan; Lindholm, Bengt; Sjögren, Per; Carrero, Juan Jesús

2014-12-05

In the United States population, high dietary fiber intake has been associated with a lower risk of inflammation and mortality in individuals with kidney dysfunction. This study aimed to expand such findings to a Northern European population. Dietary fiber intake was calculated from 7-day dietary records in 1110 participants aged 70-71 years from the Uppsala Longitudinal Study of Adult Men (examinations performed during 1991-1995). Dietary fiber was adjusted for total energy intake by the residual method. Renal function was estimated from the concentration of serum cystatin C, and deaths were registered prospectively during a median follow-up of 10.0 years. Dietary fiber independently and directly associated with eGFR (adjusted difference, 2.6 ml/min per 1.73 m(2) per 10 g/d higher; 95% confidence interval [95% CI], 0.3 to 4.9). The odds of C-reactive protein >3 mg/L were lower (linear trend, P=0.002) with higher fiber quartiles. During follow-up, 300 participants died (incidence rate of 2.87 per 100 person-years at risk). Multiplicative interactions were observed between dietary fiber intake and kidney dysfunction in the prediction of mortality. Higher dietary fiber was associated with lower mortality in unadjusted analysis. These associations were stronger in participants with kidney dysfunction (eGFR<60 ml/min per 1.73 m(2)) (hazard ratio [HR], 0.58; 95% CI, 0.35 to 0.98) than in those without (HR, 1.30; 95% CI, 0.76 to 2.22; P value for interaction, P=0.04), and were mainly explained by a lower incidence of cancer-related deaths (0.25; 95% CI, 0.10 to 0.65) in individuals with kidney dysfunction versus individuals with an eGFR≥60 ml/min per 1.73 m(2) (1.61; 95% CI, 0.69 to 3.74; P value for interaction, P=0.01). High dietary fiber was associated with better kidney function and lower inflammation in community-dwelling elderly men from Sweden. High dietary fiber was also associated with lower (cancer) mortality risk, especially in individuals with kidney dysfunction. Copyright © 2014 by the American Society of Nephrology.

Dietary Fiber, Kidney Function, Inflammation, and Mortality Risk

PubMed Central

Xu, Hong; Huang, Xiaoyan; Risérus, Ulf; Krishnamurthy, Vidya M.; Cederholm, Tommy; Ärnlöv, Johan; Lindholm, Bengt; Sjögren, Per

2014-01-01

Background and objectives In the United States population, high dietary fiber intake has been associated with a lower risk of inflammation and mortality in individuals with kidney dysfunction. This study aimed to expand such findings to a Northern European population. Design, setting, participants, & measurements Dietary fiber intake was calculated from 7-day dietary records in 1110 participants aged 70–71 years from the Uppsala Longitudinal Study of Adult Men (examinations performed during 1991–1995). Dietary fiber was adjusted for total energy intake by the residual method. Renal function was estimated from the concentration of serum cystatin C, and deaths were registered prospectively during a median follow-up of 10.0 years. Results Dietary fiber independently and directly associated with eGFR (adjusted difference, 2.6 ml/min per 1.73 m2 per 10 g/d higher; 95% confidence interval [95% CI], 0.3 to 4.9). The odds of C-reactive protein >3 mg/L were lower (linear trend, P=0.002) with higher fiber quartiles. During follow-up, 300 participants died (incidence rate of 2.87 per 100 person-years at risk). Multiplicative interactions were observed between dietary fiber intake and kidney dysfunction in the prediction of mortality. Higher dietary fiber was associated with lower mortality in unadjusted analysis. These associations were stronger in participants with kidney dysfunction (eGFR<60 ml/min per 1.73 m2) (hazard ratio [HR], 0.58; 95% CI, 0.35 to 0.98) than in those without (HR, 1.30; 95% CI, 0.76 to 2.22; P value for interaction, P=0.04), and were mainly explained by a lower incidence of cancer-related deaths (0.25; 95% CI, 0.10 to 0.65) in individuals with kidney dysfunction versus individuals with an eGFR≥60 ml/min per 1.73 m2 (1.61; 95% CI, 0.69 to 3.74; P value for interaction, P=0.01). Conclusions High dietary fiber was associated with better kidney function and lower inflammation in community-dwelling elderly men from Sweden. High dietary fiber was also associated with lower (cancer) mortality risk, especially in individuals with kidney dysfunction. PMID:25280496

Changes in urine volume and serum albumin in incident hemodialysis patients.

PubMed

Eriguchi, Rieko; Obi, Yoshitsugu; Rhee, Connie M; Chou, Jason A; Tortorici, Amanda R; Mathew, Anna T; Kim, Taehee; Soohoo, Melissa; Streja, Elani; Kovesdy, Csaba P; Kalantar-Zadeh, Kamyar

2017-10-01

Hypoalbuminemia is a predictor of poor outcomes in dialysis patients. Among hemodialysis patients, there has not been prior study of whether residual kidney function or decline over time impacts serum albumin levels. We hypothesized that a decline in residual kidney function is associated with an increase in serum albumin levels among incident hemodialysis patients. In a large national cohort of 38,504 patients who initiated hemodialysis during 1/2007-12/2011, we examined the association of residual kidney function, ascertained by urine volume and renal urea clearance, with changes in serum albumin over five years across strata of baseline residual kidney function, race, and diabetes using case-mix adjusted linear mixed effects models. Serum albumin levels increased over time. At baseline, patients with greater urine volume had higher serum albumin levels: 3.44 ± 0.48, 3.50 ± 0.46, 3.57 ± 0.44, 3.59 ± 0.45, and 3.65 ± 0.46 g/dL for urine volume groups of <300, 300-<600, 600-<900, 900-<1,200, and ≥1,200 mL/day, respectively (P trend  < 0.001). Over time, urine volume and renal urea clearance declined and serum albumin levels rose, while the baseline differences in serum albumin persisted across groups of urinary volume. In addition, the rate of decline in residual kidney function was not associated with the rate of change in albumin. Hypoalbuminemia in hemodialysis patients is associated with lower residual kidney function. Among incident hemodialysis patients, there is a gradual rise in serum albumin that is independent of the rate of decline in residual kidney function, suggesting that preservation of residual kidney function does not have a deleterious impact on serum albumin levels. © 2016 International Society for Hemodialysis.

Serum Calcitriol Concentrations and Kidney Function Decline, Heart Failure, and Mortality in Elderly Community-Living Adults: The Health, Aging, and Body Composition Study.

PubMed

Selamet, Umut; Katz, Ronit; Ginsberg, Charles; Rifkin, Dena E; Fried, Linda F; Kritchevsky, Stephen B; Hoofnagle, Andrew N; Bibbins-Domingo, Kirsten; Drew, David; Harris, Tamara; Newman, Anne; Gutiérrez, Orlando M; Sarnak, Mark J; Shlipak, Michael G; Ix, Joachim H

2018-06-06

Lower 25-hydroxyvitamin D concentrations have been associated with risk for kidney function decline, heart failure, and mortality. However, 25-hydroxyvitamin D requires conversion to its active metabolite, calcitriol, for most biological effects. The associations of calcitriol concentrations with clinical events have not been well explored. Case-cohort study. Well-functioning community-living older adults aged 70 to 79 years at inception who participated in the Health, Aging, and Body Composition (Health ABC) Study. Serum calcitriol measured using positive ion electrospray ionization-tandem mass spectrometry. Major kidney function decline (≥30% decline in estimated glomerular filtration rate from baseline), incident heart failure (HF), and all-cause mortality during 10 years of follow-up. Baseline calcitriol concentrations were measured in a random subcohort of 479 participants and also in cases with major kidney function decline [n=397]) and incident HF (n=207) during 10 years of follow-up. Associations of serum calcitriol concentrations with these end points were evaluated using weighted Cox regression to account for the case-cohort design, while associations with mortality were assessed in the subcohort alone using unweighted Cox regression. During 8.6 years of mean follow-up, 212 (44%) subcohort participants died. In fully adjusted models, each 1-standard deviation lower calcitriol concentration was associated with 30% higher risk for major kidney function decline (95% CI, 1.03-1.65; P=0.03). Calcitriol was not significantly associated with incident HF (HR, 1.16; 95% CI, 0.94-1.47) or mortality (HR, 1.01; 95% CI, 0.81-1.26). We observed no significant interactions between calcitriol concentrations and chronic kidney disease status, baseline intact parathyroid or fibroblast factor 23 concentrations. Observational study design, calcitriol measurements at a single time point, selective study population of older adults only of white or black race. Lower calcitriol concentrations are independently associated with kidney function decline in community-living older adults. Future studies will be needed to clarify whether these associations reflect lower calcitriol concentrations resulting from abnormal kidney tubule dysfunction or direct mechanisms relating lower calcitriol concentrations to more rapid loss of kidney function. Published by Elsevier Inc.

MECHANISMS IN ENDOCRINOLOGY: Kidney involvement in patients with primary hyperparathyroidism: an update on clinical and molecular aspects.

PubMed

Verdelli, C; Corbetta, S

2017-01-01

Primary hyperparathyroidism (PHPT) is the third most common endocrine disease. Kidney is a target of both chronic elevated PTH and calcium in PHPT. The classic PHPT complications of symptomatic kidney stones and nephrocalcinosis have become rare and the PHPT current presentation is asymptomatic with uncertain and long-lasting progression. Nonetheless, the routine use of imaging and of biochemical determinations have revealed the frequent occurrence of asymptomatic kidney stones, hypercalciuria and reduced kidney function in asymptomatic PHPT patients. Though the pathogenesis is far from being elucidated, PHPT is associated with reduced renal function, in terms of estimated glomerular filtration rate, and related increased morbidity and mortality. In the last decade, the effort of the Kidney Disease: Improving Global Outcomes (KDIGO) panel of experts highlighted that even mild reduction of kidney function is associated with increased risk of cardiovascular disease. These considerations provided the basis for the Fourth Workshop recommendations of a more extensive diagnostic workout about kidney features and of wider criteria for parathyroid surgery including asymptomatic kidney disease. Moreover, kidney involvement in PHPT is likely to be affected by variants of genes coding the key molecules regulating the calcium and ions renal handling; these features might have clinical relevance and should be considered both during diagnostic workout and follow-up. Finally, the effects of parathyroid surgery and of medical treatment on kidney involvement of PHPT are reviewed. © 2017 European Society of Endocrinology.

Deleterious effects of incense smoke exposure on kidney function and architecture in male albino rats.

PubMed

Hussain, Tajamul; Al-Attas, Omar S; Alrokayan, Salman A; Ahmed, Mukhtar; Al-Daghri, Nasser M; Al-Ameri, Salman; Pervez, Shamsh; Dewangan, Shippi; Mohammed, Arif; Gambhir, Dikshit; Sumague, Terrance S

2016-07-01

Previous studies, including ours, have shown adverse effects of incense smoke on human health. However, the effect of incense smoke on kidney function and structure remains unknown. To evaluate possible adverse effects of incense smoke on kidney function and architecture in albino rats after chronic exposure to Arabian incense. Emission characteristics including particle size distribution, volatile organic compounds (VOCs) and polycyclic aromatic hydrocarbons (PAHs) were determined by gravimetric and GCMS analyses. Kidney functional markers, oxidative stress and inflammatory markers were measured by standard or ELISA based procedures. Ultrastructural changes in kidney were examined by transmission electron microscope (TEM) and the gene expression of xenobiotic metabolizing enzymes including cytochrome P-450-1A1 (CYP1A1) and CYP1A2 were studied by real time PCR. Rats exposed to incense smoke demonstrated a significant increase in serum creatinine, uric acid, blood urea nitrogen (BUN), tissue malondialdehyde (MDA), tumor necrosis factor-alpha (TNF-α) and interleukin-4 (IL-4) levels and a significant decline in tissue reduced glutathione (GSH) and catalase activity. Incense smoke exposed rats also displayed marked ultrastructural changes in kidney tissue. Further, a significant increase in tissue gene expression of both CYP1A1 and CYP1A2 was noted in exposed rats. Changes to kidney functional markers and architecture appear to be mediated through augmented oxidative stress and inflammation. Long-term exposure to incense smoke may have deleterious effects on kidney function and architecture. Though, inhalation is the rout of exposure, findings of this study underscore that incense smoke may also have an effect on non-pulmonary tissues.

TH-EF-207A-04: A Dynamic Contrast Enhanced Cone Beam CT Technique for Evaluation of Renal Functions

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

Wang, Z; Shi, J; Yang, Y

Purpose: To develop a simple but robust method for the early detection and evaluation of renal functions using dynamic contrast enhanced cone beam CT technique. Methods: Experiments were performed on an integrated imaging and radiation research platform developed by our lab. Animals (n=3) were anesthetized with 20uL Ketamine/Xylazine cocktail, and then received 200uL injection of iodinated contrast agent Iopamidol via tail vein. Cone beam CT was acquired following contrast injection once per minute and up to 25 minutes. The cone beam CT was reconstructed with a dimension of 300×300×800 voxels of 130×130×130um voxel resolution. The middle kidney slices in themore » transvers and coronal planes were selected for image analysis. A double exponential function was used to fit the contrast enhanced signal intensity versus the time after contrast injection. Both pixel-based and region of interest (ROI)-based curve fitting were performed. Four parameters obtained from the curve fitting, namely the amplitude and flow constant for both contrast wash in and wash out phases, were investigated for further analysis. Results: Robust curve fitting was demonstrated for both pixel based (with R{sup 2}>0.8 for >85% pixels within the kidney contour) and ROI based (R{sup 2}>0.9 for all regions) analysis. Three different functional regions: renal pelvis, medulla and cortex, were clearly differentiated in the functional parameter map in the pixel based analysis. ROI based analysis showed the half-life T1/2 for contrast wash in and wash out phases were 0.98±0.15 and 17.04±7.16, 0.63±0.07 and 17.88±4.51, and 1.48±0.40 and 10.79±3.88 minutes for the renal pelvis, medulla and cortex, respectively. Conclusion: A robust method based on dynamic contrast enhanced cone beam CT and double exponential curve fitting has been developed to analyze the renal functions for different functional regions. Future study will be performed to investigate the sensitivity of this technique in the detection of radiation induced kidney dysfunction.« less

The Interaction Between Thyroid and Kidney Disease: An Overview of the Evidence

PubMed Central

Rhee, Connie M.

2016-01-01

Purpose of Review Hypothyroidism is highly prevalent in chronic kidney disease (CKD) patients, including those receiving dialysis. This review examines potential mechanistic links between thyroid and kidney disease; current evidence for hypothyroidism as a risk factor for de novo CKD and CKD progression; and studies of thyroid functional disorders, cardiovascular disease, and death in the CKD population. Recent Findings Epidemiologic data have demonstrated an incrementally higher prevalence of hypothyroidism with increasing severity of kidney dysfunction. Various thyroid functional test abnormalities are also commonly observed in CKD, due to alterations in thyroid hormone synthesis, metabolism, and regulation. While the mechanistic link between thyroid and kidney disease remains unclear, observational studies suggest hypothyroidism is associated with abnormal kidney structure and function. Previously thought to be a physiologic adaptation, recent studies show that hypothyroidism is associated with higher risk of cardiovascular disease and death in CKD. Summary A growing body of evidence suggests that hypothyroidism is a risk factor for incident CKD, CKD progression, and higher death risk in kidney disease patients. Rigorous studies are needed to determine impact of thyroid hormone replacement upon kidney disease progression, cardiovascular disease, and mortality, which may shed light into the causal implications of hypothyroidism in CKD. PMID:27428519

Role of AMP-activated protein kinase in kidney tubular transport, metabolism, and disease.

PubMed

Rajani, Roshan; Pastor-Soler, Nuria M; Hallows, Kenneth R

2017-09-01

AMP-activated protein kinase (AMPK) is a metabolic sensor that regulates cellular energy balance, transport, growth, inflammation, and survival functions. This review explores recent work in defining the effects of AMPK on various renal tubular epithelial ion transport proteins as well as its role in kidney injury and repair in normal and disease states. Recently, several groups have uncovered additional functions of AMPK in the regulation of kidney and transport proteins. These new studies have focused on the role of AMPK in the kidney in the setting of various diseases such as diabetes, which include evaluation of the effects of the hyperglycemic state on podocyte and tubular cell function. Other recent studies have investigated how reduced kidney mass, polycystic kidney disease (PKD), and fibrosis affect AMPK activation status. A general theme of several conditions that lead to chronic kidney disease (CKD) is that AMPK activity is abnormally suppressed relative to that in normal kidneys. Thus, the idea that AMPK activation may be a therapeutic strategy to slow down the progression of CKD has emerged. In addition to drugs such as metformin and 5-aminoimidazole-4-carboxamide ribonucleotide that are classically used as AMPK activators, recent studies have identified the therapeutic potential of other compounds that function at least partly as AMPK activators, such as salicylates, statins, berberine, and resveratrol, in preventing the progression of CKD. AMPK in the kidney plays a unique role at the crossroads of energy metabolism, ion and water transport, inflammation, and stress. Its potential role in modulating recovery from vs. progression of acute and chronic kidney injury has been the topic of recent research findings. The continued study of AMPK in kidney physiology and disease has improved our understanding of these physiological and pathological processes and offers great hope for therapeutic avenues for the increasing population at risk to develop kidney failure.

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

Early Renal Changes in 45° Hdt Rats

NASA Astrophysics Data System (ADS)

R. Pettis, Chris; Drake, Matt; Witten, Mark L.; Truitt, Jill; Braun, Eldon; Lindberg, Kim; McNeil, George; Hall, Jack N.

Background: Both microgravity and simulated microgravity models, such as the 45HDT (45 ∘ head-down tilt), cause a redistribution of body fluids indicating a possible adaptive process to the microgravity stressor. Understanding the physiological processes that occur in microgravity is a first step to developing countermeasures to stop its harmful effects, i.e., (edema, motion sickness) during long-term space flights. Hypothesis: Because of the kidneys' functional role in the regulation of fluid volume in the body, it plays a key role in the body's adaptation to microgravity. Methods: Rats were injected intramuscularly with a radioactive tracer and then lightly anesthetized in order to facilitate their placement in the 45HDT position. They were then placed in the 45HDT position using a specially designed ramp (45HDT group) or prone position (control group) for an experimental time period of 1 h. During this period, the 99mTc-DTPA (technetium-labeled diethylenepentaacetate, MW=492 amu, physical half-life of 6.02 h) radioactive tracer clearance rate was determined by measuring gamma counts per minute. The kidneys were then fixed and sectioned for electron microscopy. A point counting method was used to quantitate intracellular spaces of the kidney proximal tubules. Results: 45HDT animals show a significantly ( p=0.0001) increased area in the interstitial space of the proximal tubules. Conclusions: There are significant changes in the kidneys during a 1 h exposure to a simulated microgravity environment that consist primarily of anatomical alterations in the kidney proximal tubules. The kidneys also appear to respond differently to the initial periods of head-down tilt.

Awareness, self-management behaviors, health literacy and kidney function relationships in specialty practice

PubMed Central

Devraj, Radhika; Borrego, Matthew E; Vilay, A Mary; Pailden, Junvie; Horowitz, Bruce

2018-01-01

AIM To determine the relationship between chronic kidney disease (CKD) awareness (CKD-A), self-management behaviors (CKD-SMB) knowledge, performance of CKD-SMBs, health literacy (HL) and kidney function. METHODS Participants were eligible patients attending an outpatient nephrology clinic. Participants were administered: Newest Vital Sign to measure HL, CKD self-management knowledge tool (CKD-SMKT) to assess knowledge, past performance of CKD-SMB, CKD-A. Estimated GFR (eGFR) was determined using the MDRD-4 equation. Duration of clinic participation and CKD cause were extracted from medical charts. RESULTS One-hundred-fifty patients participated in the study. eGFRs ranged from 17-152 mL/min per 1.73 m2. Majority (83%) of respondents had stage 3 or 4 CKD, low HL (63%), and were CKD aware (88%). Approximately 40% (10/25) of patients in stages 1 and 2 and 6.4% (8/125) in stages 3 and 4 were unaware of their CKD. CKD-A differed with stage (P < 0.001) but not by HL level, duration of clinic participation, or CKD cause. Majority of respondents (≥ 90%) correctly answered one or more CKD-SMKT items. Knowledge of one behavior, “controlling blood pressure” differed significantly by CKD-A. CKD-A was associated with past performance of two CKD-SMBs, “controlling blood pressure” (P = 0.02), and “keeping healthy body weight” (P = 0.01). Adjusted multivariate analyses between CKD-A and: (1) HL; and (2) CKD-SMB knowledge were non-significant. However, there was a significant relationship between CKD-A and kidney function after controlling for demographics, HL, and CKD-SMB (P < 0.05). CONCLUSION CKD-A is not associated with HL, or better CKD-SMBs. CKD-A is significantly associated with kidney function and substantially lower eGFR, suggesting the need for focused patient education in CKD stages 1. PMID:29359119

Novel roles of complement in renal diseases and their therapeutic consequences.

PubMed

Wada, Takehiko; Nangaku, Masaomi

2013-09-01

The complement system functions as a part of the innate immune system. Inappropriate activation of the complement pathways has a deleterious effect on kidneys. Recent advances in complement research have provided new insights into the pathogenesis of glomerular and tubulointerstitial injury associated with complement activation. A new disease entity termed 'C3 glomerulopathy' has recently been proposed and is characterized by isolated C3 deposition in glomeruli without positive staining for immunoglobulins. Genetic and functional studies have demonstrated that several different mutations and disease variants, as well as the generation of autoantibodies, are potentially associated with its pathogenesis. The data from comprehensive analyses suggest that complement dysregulation can also be associated with hemolytic uremic syndrome and more common glomerular diseases, such as IgA nephropathy and diabetic kidney disease. In addition, animal studies utilizing genetically modified mice have begun to elucidate the molecular pathomechanisms associated with the complement system. From a diagnostic point of view, a noninvasive, MRI-based method for detecting C3 has recently been developed to serve as a novel tool for diagnosing complement-mediated kidney diseases. While novel therapeutic tools related to complement regulation are emerging, studies evaluating the precise roles of the complement system in kidney diseases will still be useful for developing new therapeutic approaches.

Diagnostic accuracy of urinary creatinine concentration in the estimation of differential renal function in patients with obstructive uropathy.

PubMed

Al-Hunayan, A; Al-Ateeqi, A; Kehinde, E O; Thalib, L; Loutfi, I; Mojiminiyi, O A

2008-01-01

To determine the diagnostic accuracy of spot urine creatinine concentration (UCC) as a new test for the evaluation of differential renal function in obstructed kidneys (DRF(ok)) drained by percutaneous nephrostomy tube (PCNT). In patients with obstructed kidneys drained by PCNT, DRF(ok) was derived from UCC by comparing the value of UCC in the obstructed kidney to the value in the contralateral kidney, and was derived from dimercaptosuccinic acid (DMSA) renal scans and creatinine clearance (CCr) using standard methods. Subsequently, the results of UCC were compared to the results of DMSA and CCr. 61 patients were enrolled. Bland-Altman plots to compare DMSA and UCC showed that the upper limit of agreement was 14.8% (95% CI 10.7-18.5) and the lower limit was -19.9% (95% CI -23.8 to -16.1). The sensitivity and specificity of detecting DMSA DRF(ok) < or = 35% using UCC was 85.2 and 91.2%, respectively. When UCC was compared to CCr, Bland-Altman tests gave an upper limit of agreement of 10.4% (95% CI 7.9-12.8) and a lower limit of agreement of -11.3% (95% CI -13.8 to -8.9). UCC is accurate in the estimation of DRF(ok) drained by PCNT. 2008 S. Karger AG, Basel

The role of oxidative stress in streptozotocin-induced diabetic nephropathy in rats.

PubMed

Fernandes, Sheila Marques; Cordeiro, Priscilla Mendes; Watanabe, Mirian; Fonseca, Cassiane Dezoti da; Vattimo, Maria de Fatima Fernandes

2016-10-01

The objective of this study was to evaluate the role of oxidative stress in an experimental model of streptozotocin-induced diabetic nephropathy in rats. Wistar, adult, male rats were used in the study. Animals were divided in the following groups: Citrate (control, citrate buffer 0.01M, pH 4.2 was administrated intravenously - i.v - in the caudal vein), Uninephrectomy+Citrate (left uninephrectomy-20 days before the study), DM (streptozotocin, 65 mg/kg, i.v, on the 20th day of the study), Uninephrectomy+DM. Physiological parameters (water and food intake, body weight, blood glucose, kidney weight, and relative kidney weight); renal function (creatinine clearance), urine albumin (immunodiffusion method); oxidative metabolites (urinary peroxides, thiobarbituric acid reactive substances, and thiols in renal tissue), and kidney histology were evaluated. Polyphagia, polydipsia, hyperglycemia, and reduced body weight were observed in diabetic rats. Renal function was reduced in diabetic groups (creatinine clearance, p < 0.05). Uninephrectomy potentiated urine albumin and increased kidney weight and relative kidney weight in diabetic animals (p < 0.05). Urinary peroxides and thiobarbituric acid reactive substances were increased, and the reduction in thiol levels demonstrated endogenous substrate consumption in diabetic groups (p < 0.05). The histological analysis revealed moderate lesions of diabetic nephropathy. This study confirms lipid peroxidation and intense consumption of the antioxidant defense system in diabetic rats. The association of hyperglycemia and uninephrectomy resulted in additional renal injury, demonstrating that the model is adequate for the study of diabetic nephropathy.

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

Automatic 3D kidney segmentation based on shape constrained GC-OAAM

NASA Astrophysics Data System (ADS)

Chen, Xinjian; Summers, Ronald M.; Yao, Jianhua

2011-03-01

The kidney can be classified into three main tissue types: renal cortex, renal medulla and renal pelvis (or collecting system). Dysfunction of different renal tissue types may cause different kidney diseases. Therefore, accurate and efficient segmentation of kidney into different tissue types plays a very important role in clinical research. In this paper, we propose an automatic 3D kidney segmentation method which segments the kidney into the three different tissue types: renal cortex, medulla and pelvis. The proposed method synergistically combines active appearance model (AAM), live wire (LW) and graph cut (GC) methods, GC-OAAM for short. Our method consists of two main steps. First, a pseudo 3D segmentation method is employed for kidney initialization in which the segmentation is performed slice-by-slice via a multi-object oriented active appearance model (OAAM) method. An improved iterative model refinement algorithm is proposed for the AAM optimization, which synergistically combines the AAM and LW method. Multi-object strategy is applied to help the object initialization. The 3D model constraints are applied to the initialization result. Second, the object shape information generated from the initialization step is integrated into the GC cost computation. A multi-label GC method is used to segment the kidney into cortex, medulla and pelvis. The proposed method was tested on 19 clinical arterial phase CT data sets. The preliminary results showed the feasibility and efficiency of the proposed method.

Prevalence and Determinants of Physical Activity and Fluid Intake in Kidney Transplant Recipients

PubMed Central

Gordon, Elisa J.; Prohaska, Thomas R.; Gallant, Mary P.; Sehgal, Ashwini R.; Strogatz, David; Conti, David; Siminoff, Laura A.

2009-01-01

Background and Significance Self-care for kidney transplantation is recommended to maintain kidney function. Little is known about levels of self-care practices, and demographic, psychosocial, and health-related correlates. Aim We investigated patients’ self-reported exercise and fluid intake, demographic and psychosocial factors associated with these self-care practices, and health-related quality of life. Methods Eighty-eight of 158 kidney recipients from two academic medical centers completed a semi-structured interview and surveys 2 months post-transplant. Results Most patients were sedentary (76%) with a quarter exercising either regularly (11%) or not at current recommendations (13%). One third (35%) reported drinking the recommended three liters of fluid daily. Multivariate analyses indicated that private insurance, high self-efficacy, and better physical functioning were significantly associated with engaging in physical activity (p<0.05); while male gender, private insurance, high self-efficacy, and not attributing oneself responsible for transplant success were significant predictors of adherence to fluid intake (p<0.05). Despite the significance of these predictors, models for physical activity and fluid intake explained 10–15% of the overall variance in these behaviors. Multivariate analyses indicated that younger age, high value of exercise, and higher social functioning significantly (p<0.05) predicted high self-efficacy for physical activity, while being married significantly (p<0.05) predicted high self-efficacy for fluid intake. Conclusion Identifying patients at risk of inadequate self-care practice is essential for educating patients about the importance of self-care. PMID:19925468

New Insights into the Effects of Chronic Kidney Failure and Dialysate Exposure on the Peritoneum.

PubMed

Vlahu, Carmen A; Aten, Jan; de Graaff, Marijke; van Veen, Henk; Everts, Vincent; de Waart, Dirk R; Struijk, Dirk G; Krediet, Raymond T

♦ INTRODUCTION: Chronic uremia and the exposure to dialysis solutions during peritoneal dialysis (PD) induce peritoneal alterations. Using a long-term peritoneal exposure model, we compared the effects of chronic kidney failure (CKD) itself and exposure to either a 'conventional' or a 'biocompatible' dialysis solution on peritoneal morphology and function. ♦ METHODS: Wistar rats (Harlan, Zeist, the Netherlands) were grouped into: normal kidney function (NKF), CKD induced by 70% nephrectomy, CKD receiving daily peritoneal infusions with 3.86% glucose Dianeal (CKDD), or Physioneal (both solutions from Baxter Healthcare, Castlebar, Ireland) (CKDP). At 16 weeks, a peritoneal function test was performed, and histology, ultrastructure, and hydroxyproline content of peritoneal tissue were assessed. ♦ RESULTS: Comparing CKD with NKF, peritoneal transport rates were higher, mesothelial cells (MC) displayed increased number of microvilli, blood and lymph vasculature expanded, vascular basal lamina appeared thicker, with limited areas of duplication, and fibrosis had developed. All alterations, except lymphangiogenesis, were enhanced by exposure to both dialysis fluids. Distinct MC alterations were observed in CKDD and CKDP, the latter displaying prominent basolateral protrusions. In addition, CKDP was associated with a trend towards less fibrosis compared to CKDD. ♦ CONCLUSIONS: Chronic kidney failure itself induced peritoneal alterations, which were in part augmented by exposure to glucose-based dialysis solutions. Overall, the conventional and biocompatible solutions had similar long-term effects on the peritoneum. Importantly, the latter may attenuate the development of fibrosis. Copyright © 2016 International Society for Peritoneal Dialysis.

Creatinine blood test

MedlinePlus

Serum creatinine; Kidney function - creatinine; Renal function - creatinine ... kidney damage or failure, infection, or reduced blood flow Loss of ... medicine overdose. Your provider will tell you more, if needed.

THE KNOCKED-OUT UNILATERAL KIDNEY! CAUSES AND PRESENTATION.

PubMed

Bangash, Kashif; Alam, Asaf; Amin, Mohammed; Anwar, Khursheed

2015-01-01

Due to lack of awareness and non-availability of proper medical facilities in Pakistan, patients with kidney problems tend to seek urological consultation very late when their kidney has already knocked-out. The aim of the study was to find the various presenting complaints of patients having unilateral loss of kidney function and their aetiologies. The study also targeted the patient's awareness regarding their disease. This descriptive case-series of 103 consecutive patients who were diagnosed as having less than 20% of function on DTPA Renal Scan were evaluated. The aetiology of the non-functioning kidney (NFK) was made on either imaging findings or during the exploration, and/or on histopathology if necessary. The results were analysed using SPSS 16.0. Results: The aetiology of the unilateral renal failure included those that were secondary to nephro-pelvic stones in 39.8% and ureteric stones in 14.6%. Of the other aetiologies culminating in a unilateral NFK, 7.8% of the patients had chronic pyelonephritis, 20.4% had PUJO and 5.8% were Genito-urinary Tuberculosis; 3.9% had VUR and were found incidentally, 3.9% developed non-functioning kidney iatrogenically. About 39.8% of the patients knew about their primary disease causing destruction of renal function since long. The remaining 60.2% were unaware that they had developed NFK already when they presented. Proper education through awareness program both for the public and general practitioners can detect early threats to the kidney and hence decrease the loss of a kidney. This will also decrease the number of nephrectomies carried out for the benign condition.

77 FR 6130 - National Institute of Diabetes and Digestive and Kidney Diseases Notice of Closed Meeting

Federal Register 2010, 2011, 2012, 2013, 2014

2012-02-07

... Diabetes and Digestive and Kidney Diseases Notice of Closed Meeting Pursuant to section 10(d) of the... Diabetes and Digestive and Kidney Diseases Special Emphasis Panel; Cellular Biology of Kidney Function and... Research; 93.849, Kidney Diseases, Urology and Hematology Research, National Institutes of Health, HHS...

Notes on the Problems of the Transplantation of Kidneys in Dogs

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

Puza, A.; Drahovsky, V.; Neubauer, E.

1963-01-01

In a group of 29 mongrel dogs kidney homotransplantation was performed. In five dogs an autograft was performed to check the suitability of the surgical technique. In the remaining 24 dogs kidney homografts were carried out, Five dogs served as controls; in these animals the functioning of the homografted kidney stopped after 8 days on the average, In 12 animals an attempt at the induction of immunological tolerance by exsanguinotransfusion, whole-body irradiation and 6-MP-administration was made. Induction of immunological tolerance by total exsanguinotransfusion immediately after birth may render possible a successful homograft even in adult life. The transplanted organ thenmore » exhibits a permanent take and takes over the function of the recipient's removed kidneys. One dog is alive with its single kidney homograft after almost two years. 6-MP administration may lead to such a degree of induced tolerance that the function of a kidney homograft is prolonged by a factor of two to three. Whole-body irradiation within a range of 400 rad (Co 60 source) does not significantly prolong homograft survival.« less

Cerebral Small Vessel Disease and Chronic Kidney Disease

PubMed Central

2015-01-01

Chronic kidney disease, defined by a decreased glomerular filtration rate or albuminuria, is recognized as a major global health burden, mainly because it is an established risk factor for cardiovascular and cerebrovascular diseases. The magnitude of the effect of chronic kidney disease on incident stroke seems to be higher in persons of Asian ethnicity. Since the kidney and brain share unique susceptibilities to vascular injury due to similar anatomical and functional features of small artery diseases, kidney impairment can be predictive of the presence and severity of cerebral small vessel diseases. Chronic kidney disease has been reported to be associated with silent brain infarcts, cerebral white matter lesions, and cerebral microbleeds, independently of vascular risk factors. In addition, chronic kidney disease affects cognitive function, partly via the high prevalence of cerebral small vessel diseases. Retinal artery disease also has an independent relationship with chronic kidney disease and cognitive impairment. Stroke experts are no longer allowed to be ignorant of chronic kidney disease. Close liaison between neurologists and nephrologists can improve the management of cerebral small vessel diseases in kidney patients. PMID:25692105

The assessment of cognitive function in older adult patients with chronic kidney disease: an integrative review.

PubMed

Hannan, Mary; Steffen, Alana; Quinn, Lauretta; Collins, Eileen G; Phillips, Shane A; Bronas, Ulf G

2018-05-25

Chronic kidney disease (CKD) is a common chronic condition in older adults that is associated with cognitive decline. However, the exact prevalence of cognitive impairment in older adults with CKD is unclear likely due to the variety of methods utilized to assess cognitive function. The purpose of this integrative review is to determine how cognitive function is most frequently assessed in older adult patients with CKD. Five electronic databases were searched to explore relevant literature related to cognitive function assessment in older adult patients with CKD. Inclusion and exclusion criteria were created to focus the search to the assessment of cognitive function with standardized cognitive tests in older adults with CKD, not on renal replacement therapy. Through the search methods, 36 articles were found that fulfilled the purpose of the review. There were 36 different types of cognitive tests utilized in the included articles, with each study utilizing between one and 12 tests. The most commonly utilized cognitive test was the Mini Mental State Exam (MMSE), followed by tests of digit symbol substitution and verbal fluency. The most commonly assessed aspect of cognitive function was global cognition. The assessment of cognitive function in older adults with CKD with standardized tests is completed in various ways. Unfortunately, the common methods of assessment of cognitive function may not be fully examining the domains of impairment commonly found in older adults with CKD. Further research is needed to identify the ideal cognitive test to best assess older adults with CKD for cognitive impairment.

Treatment Methods for Kidney Failure: Transplantation

MedlinePlus

... Right Financial Help for Treatment of Kidney Failure Kidney Transplant Some people with kidney failure may be ... transplant . What is the process for getting a kidney transplant? If you want a kidney transplant, the ...

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.

An intelligent knowledge mining model for kidney cancer using rough set theory.

PubMed

Durai, M A Saleem; Acharjya, D P; Kannan, A; Iyengar, N Ch Sriman Narayana

2012-01-01

Medical diagnosis processes vary in the degree to which they attempt to deal with different complicating aspects of diagnosis such as relative importance of symptoms, varied symptom pattern and the relation between diseases themselves. Rough set approach has two major advantages over the other methods. First, it can handle different types of data such as categorical, numerical etc. Secondly, it does not make any assumption like probability distribution function in stochastic modeling or membership grade function in fuzzy set theory. It involves pattern recognition through logical computational rules rather than approximating them through smooth mathematical functional forms. In this paper we use rough set theory as a data mining tool to derive useful patterns and rules for kidney cancer faulty diagnosis. In particular, the historical data of twenty five research hospitals and medical college is used for validation and the results show the practical viability of the proposed approach.

Peritransplant Soluble CD30 as a Risk Factor for Slow Kidney Allograft Function, Early Acute Rejection, Worse Long-Term Allograft Function, and Patients' Survival

PubMed Central

Ostapenko, Tetyana I.; Nykonenko, Tamara N.; Nesterenko, Svitlana N.; Nykonenko, Olexandr S.

2017-01-01

Background We aimed to determine whether serum soluble CD30 (sCD30) could identify recipients at high risk for unfavorable early and late kidney transplant outcomes. Methods Serum sCD30 was measured on the day of kidney transplantation and on the 4th day posttransplant. We assessed the value of these measurements in predicting delayed graft function, slow graft function (SGF), acute rejection (AR), pyelonephritis, decline of allograft function after 6 months, and graft and patient survival during 5 years of follow-up in 45 recipients. Results We found the association between low pretransplant serum levels of sCD30 and SGF. The absence of significant decrease of sCD30 on the 4th day posttransplant was characteristic for SGF, early AR (the 8th day–6 months), late AR (>6 months), and early pyelonephritis (the 8th day–2 months). Lower pretransplant and posttransplant sCD30 predicted worse allograft function at 6 months and 2 years, respectively. Higher pretransplant sCD30 was associated with higher frequency of early AR, and worse patients' survival, but only in the recipients of deceased-donor graft. Pretransplant sCD30 also allowed to differentiate patients with early pyelonephritis and early AR. Conclusions Peritransplant sCD30 is useful in identifying patients at risk for unfavorable early and late transplant outcomes. PMID:28694560

[Kidney allotransplantation from the AB0-incompatible donors].

PubMed

Goriaĭnov, V A; Kaabak, M M; Babenko, N N; Shishlo, L A; Morozova, M M; Ragimov, A A; Dazhkova, N G; Salimov, E L

2013-01-01

The experience of 28 kidney allotransplantations from the AB0-incompatible donors was analyzed. The comparative group consisted of 38 patients, who received the AB0-compatible organ. The results were assessed using the following parameters: renal function, morphology of the biopsy samples of the transplanted kidney and actuary survival of the recipients with functioning transplants in both groups. The comparative analysis showed no significant difference between the two groups, giving the right to consider the kidney allotransplantation from the AB0-incompatible donors safe and effective.

The role of the immune system in kidney disease.

PubMed

Tecklenborg, J; Clayton, D; Siebert, S; Coley, S M

2018-05-01

The immune system and the kidneys are closely linked. In health the kidneys contribute to immune homeostasis, while components of the immune system mediate many acute forms of renal disease and play a central role in progression of chronic kidney disease. A dysregulated immune system can have either direct or indirect renal effects. Direct immune-mediated kidney diseases are usually a consequence of autoantibodies directed against a constituent renal antigen, such as collagen IV in anti-glomerular basement membrane disease. Indirect immune-mediated renal disease often follows systemic autoimmunity with immune complex formation, but can also be due to uncontrolled activation of the complement pathways. Although the range of mechanisms of immune dysregulation leading to renal disease is broad, the pathways leading to injury are similar. Loss of immune homeostasis in renal disease results in perpetual immune cell recruitment and worsening damage to the kidney. Uncoordinated attempts at tissue repair, after immune-mediated disease or non-immune mediated injury, result in fibrosis of structures important for renal function, leading eventually to kidney failure. As renal disease often manifests clinically only when substantial damage has already occurred, new diagnostic methods and indeed treatments must be identified to inhibit further progression and promote appropriate tissue repair. Studying cases in which immune homeostasis is re-established may reveal new treatment possibilities. © 2018 British Society for Immunology.

Effect of mesenchymal stem cells on anti-Thy1,1 induced kidney injury in albino rats

PubMed Central

Sakr, Saber; Rashed, Laila; Zarouk, Waheba; El-Shamy, Rania

2013-01-01

Objective To evaluate the effect of mesenchymal stem cells (MSCs) in rats with anti-Thy1,1 nephritis. Methods Female albino rats were divided into three groups, control group, anti-Thy1,1 group and treatment with i.v. MSCs group. MSCs were derived from bone marrow of male albino rats, Y-chromosome gene was detected by polymerase chain reaction in the kidney. Serum urea and creatinine were estimated for all groups. Kidney of all studied groups was examined histologically and histochemically (total carbohydrates and total proteins). DNA fragmentation and expression of α-SMA were detected. Results Kidney of animals injected with anti-Thy1,1 showed inflammatory leucocytic infiltration, hypertrophied glomeruli, tubular necrosis and congestion in the renal blood vessels. The kidney tissue also showed reduction of carbohydrates and total proteins together with increase in apoptosis and in expression of α-SMA. Moreover, the levels of urea and creatinine were elevated. Treating animals with MSCs revealed that kidney tissue displayed an improvement in the histological and histochemical changes. Apoptosis and α-SMA expression were decreased, and the levels of urea and creatinine decreased. Conclusions The obtained results demonstrated the potential of MSCs to ameliorate the structure and function of the kidney in rats with anti-Thy1,1 nephritis possibly through the release of paracrine growth factor(s). PMID:23620833

[Kidney transplant experience at the Specialty Hospital Bernardo Sepulveda National Medical Center Century XXI, Mexican Institute of Social Security].

PubMed

Gracida-Juárez, Carmen; Espinoza-Pérez, Ramón; Cancino-López, Jorge David; Ibarra-Villanueva, Araceli; Cedillo-López, Urbano; Villegas-Anzo, Fernando; Martínez-Alvarez, Julio

2011-09-01

The first kidney transplant in Mexico was done on October 22, 1963 at the General Hospital of National Medical Center (CMN) of the Mexican Institute of Social Security. After the earthquake in 1985, the transplantation activity was continued at the Specialty Hospital of National Medical Center Century XXI. Our program has a continue activity for almost 48 years and a total of 2019 kidney transplants from October 1963 to December 2010. We describe our experience in 20 years. Retrospective cohort study that includes all kidney transplants performed in the period from January 1991 to December 2010. Descriptive statistics were used. The survival analysis was performed using the Kaplan Meier method. We show the patient survival, graft survival censored for death with functional graft and total graft survival (uncensored). We analyzed a total of 1544 kidney transplants. The percentage of living donor was 82.9 vs. deceased donor of 17.1%. Patient survival at 1, 5, 10, 15 and 20 years was 95.0, 91.8, 87.2, 81.1 and 70.1%, respectively; allograft survival rate censored for death with functional allograft at 1, 5, 10, 15 and 20 years was 93.0, 86.2, 76.2, 63.7 and 50.9%, respectively. Our Transplant center also take care of around 1300 living donors in the long term, looking for morbidities as risk factors for the unique kidney as metabolic syndrome, diabetes, hypertension and others. In our program, the main source of renal allografts was living donors. Our transplant center has to increase the organ procurement from deceased donors. An important contribution of our center has been the long follow up of living donors according to international consensus.

Serum uric acid is a GFR-independent long-term predictor of acute and chronic renal insufficiency: the Jerusalem Lipid Research Clinic cohort study

PubMed Central

Kark, Jeremy D.

2011-01-01

Background. Kidney disease is commonly accompanied by hyperuricemia. However, the contribution of serum uric acid (SUA) to kidney injury is debated. Our objective was to assess the long-term prediction of renal failure by SUA. Methods. Visit 2 participants in the Jerusalem Lipid Research Clinic cohort with normal baseline kidney function were followed for 24–28 years. SUA levels were assessed for associations with acute renal failure (ARF) and chronic renal failure (CRF) as defined by hospital discharge records, and mortality, ascertained through linkage with the national population registry. Results. Among 2449 eligible participants (1470 men, 979 women aged 35–78 years in 1976–79), SUA was positively linked with male sex, serum creatinine and components of the metabolic syndrome but was lower in smokers and in diabetic subjects. The 22- to 25-year incidence of hospital-diagnosed kidney failure (145 first events, 67% CRF) and the 24- to 28-year mortality (587 events) were higher in subject with hyperuricemia (>6.5 mg/dL in men and >5.3 mg/dL in women, reflecting the upper quintiles), independent of baseline kidney function and covariates. Hyperuricemia conferred adjusted hazard ratios of 1.36 (P = 0.003), 2.14 (P < 0.001) and 2.87 (P = 0.003) for mortality, CRF and ARF, respectively. Conclusions. SUA predicts renal failure incidence and all-cause mortality independently of demographic and clinical covariates. These results lend support to the undertaking of clinical trials to examine the effect of uric acid-lowering strategies on kidney outcomes. PMID:21220750

Interleukin-1β Activates a MYC-Dependent Metabolic Switch in Kidney Stromal Cells Necessary for Progressive Tubulointerstitial Fibrosis.

PubMed

Lemos, Dario R; McMurdo, Michael; Karaca, Gamze; Wilflingseder, Julia; Leaf, Irina A; Gupta, Navin; Miyoshi, Tomoya; Susa, Koichiro; Johnson, Bryce G; Soliman, Kirolous; Wang, Guanghai; Morizane, Ryuji; Bonventre, Joseph V; Duffield, Jeremy S

2018-06-01

Background Kidney injury is characterized by persisting inflammation and fibrosis, yet mechanisms by which inflammatory signals drive fibrogenesis remain poorly defined. Methods RNA sequencing of fibrotic kidneys from patients with CKD identified a metabolic gene signature comprising loss of mitochondrial and oxidative phosphorylation gene expression with a concomitant increase in regulators and enzymes of glycolysis under the control of PGC1 α and MYC transcription factors, respectively. We modeled this metabolic switch in vivo , in experimental murine models of kidney injury, and in vitro in human kidney stromal cells (SCs) and human kidney organoids. Results In mice, MYC and the target genes thereof became activated in resident SCs early after kidney injury, suggesting that acute innate immune signals regulate this transcriptional switch. In vitro , stimulation of purified human kidney SCs and human kidney organoids with IL-1 β recapitulated the molecular events observed in vivo , inducing functional metabolic derangement characterized by increased MYC-dependent glycolysis, the latter proving necessary to drive proliferation and matrix production. MYC interacted directly with sequestosome 1/p62, which is involved in proteasomal degradation, and modulation of p62 expression caused inverse effects on MYC expression. IL-1 β stimulated autophagy flux, causing degradation of p62 and accumulation of MYC. Inhibition of the IL-1R signal transducer kinase IRAK4 in vivo or inhibition of MYC in vivo as well as in human kidney organoids in vitro abrogated fibrosis and reduced tubular injury. Conclusions Our findings define a connection between IL-1 β and metabolic switch in fibrosis initiation and progression and highlight IL-1 β and MYC as potential therapeutic targets in tubulointerstitial diseases. Copyright © 2018 by the American Society of Nephrology.

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.

Wavelet-based segmentation of renal compartments in DCE-MRI of human kidney: initial results in patients and healthy volunteers.

PubMed

Li, Sheng; Zöllner, Frank G; Merrem, Andreas D; Peng, Yinghong; Roervik, Jarle; Lundervold, Arvid; Schad, Lothar R

2012-03-01

Renal diseases can lead to kidney failure that requires life-long dialysis or renal transplantation. Early detection and treatment can prevent progression towards end stage renal disease. MRI has evolved into a standard examination for the assessment of the renal morphology and function. We propose a wavelet-based clustering to group the voxel time courses and thereby, to segment the renal compartments. This approach comprises (1) a nonparametric, discrete wavelet transform of the voxel time course, (2) thresholding of the wavelet coefficients using Stein's Unbiased Risk estimator, and (3) k-means clustering of the wavelet coefficients to segment the kidneys. Our method was applied to 3D dynamic contrast enhanced (DCE-) MRI data sets of human kidney in four healthy volunteers and three patients. On average, the renal cortex in the healthy volunteers could be segmented at 88%, the medulla at 91%, and the pelvis at 98% accuracy. In the patient data, with aberrant voxel time courses, the segmentation was also feasible with good results for the kidney compartments. In conclusion wavelet based clustering of DCE-MRI of kidney is feasible and a valuable tool towards automated perfusion and glomerular filtration rate quantification. Copyright © 2011 Elsevier Ltd. All rights reserved.

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.

Soy Protein Alleviates Hypertension and Fish Oil Improves Diastolic Heart Function in the Han:SPRD-Cy Rat Model of Cystic Kidney Disease.

PubMed

Ibrahim, Naser H M; Thandapilly, Sijo J; Jia, Yong; Netticadan, Thomas; Aukema, Harold

2016-05-01

Abnormalities in cardiac structure and function are very common among people with chronic kidney disease, in whom cardiovascular disease is the major cause of death. Dietary soy protein and fish oil reduce kidney disease progression in the Han:SPRD-Cy model of cystic renal disease. However, the effects of these dietary interventions in preventing alterations in cardiac structure and function due to kidney disease (reno-cardiac syndrome) in a cystic kidney disease model are not known. Therefore, weanling Han:SPRD-Cy diseased (Cy/+) and normal (+/+) rats were given diets containing either casein or soy protein, and either soy or fish oil in a three-way design for 8 weeks. Diseased rats had larger hearts, augmented left ventricular mass, and higher systolic and mean arterial blood pressure compared to the normal rats. Assessment of cardiac function using two-dimensional guided M-mode and pulse-wave Doppler echocardiography revealed that isovolumic relaxation time was prolonged in the diseased compared to normal rats, reflecting a diastolic heart dysfunction, and fish oil prevented this elevation. Soy protein resulted in a small improvement in systolic and mean arterial pressure but did not improve diastolic heart function, while fish oil prevented diastolic heart dysfunction in this model of cystic kidney disease.

The effect of prolonged of warm ischaemic injury on renal function in an experimental ex vivo normothermic perfusion system.

PubMed

Hosgood, Sarah A; Shah, K; Patel, M; Nicholson, M L

2015-06-30

Donation after circulatory death (DCD) kidney transplants inevitably sustain a degree of warm ischaemic injury, which is manifested clinically as delayed graft function. The aim of this study was to define the effects of prolonged periods of warm ischaemic injury on renal function in a normothermic haemoperfused kidney model. Porcine kidneys were subjected to 15, 60, 90 (n = 6 per group) and 120 min (n = 4) of in situ warm ischaemia (WI) and then retrieved, flushed with cold preservation fluid and stored in ice for 2 h. Kidneys then underwent 3 h of normothermic reperfusion with a whole blood-based perfusate using an ex vivo circuit developed from clinical grade cardiopulmonary bypass technology. Creatinine clearance, urine output and fractional excretion of sodium deteriorated sequentially with increasing warm time. Renal function was severely compromised after 90 or 120 min of WI but haemodynamic, metabolic and histological parameters demonstrated the viability of kidneys subjected to prolonged warm ischaemia. Isolated kidney perfusion using a warm, oxygenated, red cell-based perfusate allows an accurate ex vivo assessment of the potential for recovery from warm ischaemic injury. Prolonged renal warm ischaemic injury caused a severe decrement in renal function but was not associated with tissue necrosis.

Increased primary non-function in transplanted deceased-donor kidneys flushed with histidine-tryptophan-ketoglutarate solution.

PubMed

Stevens, R B; Skorupa, J Y; Rigley, T H; Yannam, G R; Nielsen, K J; Schriner, M E; Skorupa, A J; Murante, A; Holdaway, E; Wrenshall, L E

2009-05-01

Histidine-Tryptophan-Ketoglutarate (HTK) solution is increasingly used to flush and preserve organ donor kidneys, with efficacy claimed equivalent to University of Wisconsin (UW) solution. We observed and reported increased graft pancreatitis in pancreata flushed with HTK solution, which prompted this review of transplanting HTK-flushed kidneys. We analyzed outcomes of deceased-donor kidneys flushed with HTK and UW solutions with a minimum of 12 months follow-up, excluding pediatric and multi-organ recipients. We evaluated patient and graft survival and rejection rates, variables that might constitute hazards to graft survival and renal function. Two-year patient survival, rejection, renal function and graft survival were not different, but early graft loss (<6 months) was worse in HTK-flushed kidneys (p < 0.03). A Cox analysis of donor grade, cold ischemic time, panel reactive antibodies (PRA), donor race, first vs. repeat transplant, rejection and flush solution showed that only HTK use predicted early graft loss (p < 0.04; relative risk = 3.24), almost exclusively attributable to primary non-function (HTK, n = 5 (6.30%); UW, n = 1 (0.65%); p = 0.02). Delayed graft function and early graft loss with HTK occurred only in lesser grade kidneys, suggesting it should be used with caution in marginal donors.

Low Serum Bicarbonate and Kidney Function Decline: The Multi-Ethnic Study of Atherosclerosis (MESA)

PubMed Central

Driver, Todd H.; Shlipak, Michael G.; Katz, Ronit; Goldenstein, Leonard; Sarnak, Mark J.; Hoofnagle, Andrew N.; Siscovick, David S.; Kestenbaum, Bryan; de Boer, Ian H.; Ix, Joachim H.

2014-01-01

Background Among populations with established chronic kidney disease (CKD), metabolic acidosis is associated with more rapid progression of kidney disease. The association of serum bicarbonate concentrations with early declines in kidney function is less clear. Study Design Retrospective cohort study. Setting & Participants 6380 participants in the Multi-Ethnic Study of Atherosclerosis (MESA) with a baseline estimated glomerular filtration rate (eGFR) >60 mL/min/1.73m2 using the CKD-EPI (CKD Epidemiology Collaboration) creatinine–cystatin C equation. Predictors Serum bicarbonate concentrations. Outcomes Rapid kidney function decline (eGFR decline >5% per year) and incident reduced eGFR (eGFR<60 mL/min/1.73 m2 with minimum rate of eGFR loss of 1 mL/min/1.73 m2 per year). Results The average bicarbonate concentration was 23.2 ± 1.8 mEq/L. 1730 (33%) participants had rapid kidney function decline, and 487 had incident reduced eGFR during follow-up. Each 1-SD lower baseline bicarbonate concentration was associated with 12% higher adjusted odds of rapid kidney function decline (95% CI, 6%–20%) and higher risk of incident reduced eGFR (adjusted incidence rate ratio, 1.11; 95% CI, 1.03–1.20) in models adjusting for demographics, baseline eGFR, albuminuria, and CKD risk factors. The OR for the associations of bicarbonate <21mEq/L relative to 23–24 mEq/L was 1.35 (95% CI, 1.05–1.73) for rapid kidney function decline, and the incidence rate ratio was 1.16 (95% CI, 0.83–1.62) for incident reduced eGFR. Limitations Etiology of metabolic acidosis cannot be determined in this study. Conclusions Lower serum bicarbonate concentrations are independently associated with rapid kidney function decline independent of eGFR or albuminuria in community-living persons with a baseline eGFR >60 mL/min/1.73 m2. If confirmed, our findings suggest that metabolic acidosis may indicate either early kidney disease that is not captured by eGFR or albuminuria, or may have a causal role in the development of an eGFR <60 mL/min/1.73 m2. PMID:24953891

Suramin protects from cisplatin-induced acute kidney injury

PubMed Central

Dupre, Tess V.; Doll, Mark A.; Shah, Parag P.; Sharp, Cierra N.; Kiefer, Alex; Scherzer, Michael T.; Saurabh, Kumar; Saforo, Doug; Siow, Deanna; Casson, Lavona; Arteel, Gavin E.; Jenson, Alfred Bennett; Megyesi, Judit; Schnellmann, Rick G.; Beverly, Levi J.

2015-01-01

Cisplatin, a commonly used cancer chemotherapeutic, has a dose-limiting side effect of nephrotoxicity. Approximately 30% of patients administered cisplatin suffer from kidney injury, and there are limited treatment options for the treatment of cisplatin-induced kidney injury. Suramin, which is Federal Drug Administration-approved for the treatment of trypanosomiasis, improves kidney function after various forms of kidney injury in rodent models. We hypothesized that suramin would attenuate cisplatin-induced kidney injury. Suramin treatment before cisplatin administration reduced cisplatin-induced decreases in kidney function and injury. Furthermore, suramin attenuated cisplatin-induced expression of inflammatory cytokines and chemokines, endoplasmic reticulum stress, and apoptosis in the kidney cortex. Treatment of mice with suramin 24 h after cisplatin also improved kidney function, suggesting that the mechanism of protection is not by inhibition of tubular cisplatin uptake or its metabolism to nephrotoxic species. If suramin is to be used in the context of cancer, then it cannot prevent cisplatin-induced cytotoxicity of cancer cells. Suramin did not alter the dose-response curve of cisplatin in lung adenocarcinoma cells in vitro. In addition, suramin pretreatment of mice harboring lung adenocarcinomas did not alter the initial cytotoxic effects of cisplatin (DNA damage and apoptosis) on tumor cells. These results provide evidence that suramin has potential as a renoprotective agent for the treatment/prevention of cisplatin-induced acute kidney injury and justify future long-term preclinical studies using cotreatment of suramin and cisplatin in mouse models of cancer. PMID:26661653

Kidney function and plasma copeptin levels in healthy kidney donors and autosomal dominant polycystic kidney disease patients.

PubMed

Zittema, Debbie; van den Berg, Else; Meijer, Esther; Boertien, Wendy E; Muller Kobold, Anneke C; Franssen, Casper F M; de Jong, Paul E; Bakker, Stephan J L; Navis, Gerjan; Gansevoort, Ron T

2014-09-05

Plasma copeptin, a marker of arginine vasopressin, is elevated in patients with autosomal dominant polycystic kidney disease and predicts disease progression. It is unknown whether elevated copeptin levels result from decreased kidney clearance or as compensation for impaired concentrating capacity. Data from patients with autosomal dominant polycystic kidney disease and healthy kidney donors before and after donation were used, because after donation, overall GFR decreases with a functionally normal kidney. Data were obtained between October of 2008 and January of 2012 from healthy kidney donors who visited the institution for routine measurements predonation and postdonation and patients with autosomal dominant polycystic kidney disease who visited the institution for kidney function measurement. Plasma copeptin levels were measured using a sandwich immunoassay, GFR was measured as (125)I-iothalamate clearance, and urine concentrating capacity was measured as urine-to-plasma ratio of urea. In patients with autosomal dominant polycystic kidney disease, total kidney volume was measured with magnetic resonance imaging. Patients with autosomal dominant polycystic kidney disease (n=122, age=40 years, men=56%) had significantly higher copeptin levels (median=6.8 pmol/L; interquartile range=3.4-15.7 pmol/L) compared with donors (n=134, age=52 years, men=49%) both predonation and postdonation (median=3.8 pmol/L; interquartile range=2.8-6.3 pmol/L; P<0.001; median=4.4 pmol/L; interquartile range=3.6-6.1 pmol/L; P<0.001). In donors, copeptin levels did not change after donation, despite a significant fall in GFR (from 105 ± 17 to 66 ± 10; P<0.001). Copeptin and GFR were significantly associated in patients with autosomal dominant polycystic kidney disease (β=-0.45, P<0.001) but not in donors. In patients with autosomal dominant polycystic kidney disease, GFR and total kidney volume were both associated significantly with urine-to-plasma ratio of urea (β=0.84, P<0.001; β=-0.51, P<0.001, respectively). On the basis of the finding in donors that kidney clearance is not a main determinant of plasma copeptin levels, it was hypothesized that, in patients with autosomal dominant polycystic kidney disease, kidney damage and associated impaired urine concentration capacity determine copeptin levels. Copyright © 2014 by the American Society of Nephrology.

Adverse effects of meglumine diatrizoate on renal function in the early post-transplant period.

PubMed

Light, J A; Perloff, L J; Etheredge, E E; Hill, G; Spees, E K

1975-11-01

Thirty-four renal transplant recipients received drip infusion urograms from 2-24 days post-transplantation. Twenty-two patients exhibited changes in renal function within 1-4 days of the urogram that were indistinguishable from allograft rejection: a tender, swollen kidney, elevation of serum creatinine, oliguria, decreased urine sodium concentration, weight gain, and hypertension. Two patients developed acute tubular necrosis and required hemodialysis, but renal function in the remaining 20 patients improved after therapy for "graft rejection" with i.v. methyprednisolone sodium succinnate. Kidneys from older-age donors that were functioning suboptimally and kidneys which exhibited subsequent clinical allograft rejection were more at risk for contrast media toxicity. This suggests that occult vascular lesions may have been present in the allograft which were exacerbated when exposed to the irritant vascular effects of contrast media, producing a mild, reversible toxic nephritis. However, several kidneys with normal function and several kidneys which never exhibited rejection activity were also adversely affected by exposure to contrast media. It appears these agents should be used cautiously, if at all, in the early post-transplant period.

Radionuclides in nephrology

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

Lausanne, A.B.D.

In 47 expert contributions, this volume provides a summary of the latest research on radionuclides in nephro-urology together with current and new clinical applications especially in renovascular hypertension, kidney transplantation, and metabolic and urological diseases. In addition, attention is given to aspects of basic renal physiology and function and possible applications of nuclear magnetic resonance and spectroscopy in nephro-urology. New testing procedures which promise to improve diagnosis, and new radiopharmaceuticals are described. The reports are divided into eight sections, the first of which features studies on the renin-angiotensin system, cisplatin, atrial natriuretic factor and determining plasma oxalate. Four papers describemore » a number of new radiopharmaceuticals which have the potential to replace hippuran. In the third section, radionuclide methods for the measurement of renal function parameters are discussed. The book then focuses on the potential role of captopril in the improved diagnosis of renovascular hypertension. Applications of nuclear magnetic resonance and spectroscopy are demonstrated in the diagnosis of acute pyelonephritis, kidney assessment after lithotripsy, kidney evaluation prior to transplantation, and in monitoring renal ischemia during hypotension.« less

Novel in vivo techniques to visualize kidney anatomy and function.

PubMed

Peti-Peterdi, János; Kidokoro, Kengo; Riquier-Brison, Anne

2015-07-01

Intravital imaging using multiphoton microscopy (MPM) has become an increasingly popular and widely used experimental technique in kidney research over the past few years. MPM allows deep optical sectioning of the intact, living kidney tissue with submicron resolution, which is unparalleled among intravital imaging approaches. MPM has solved a long-standing critical technical barrier in renal research to study several complex and inaccessible cell types and anatomical structures in vivo in their native environment. Comprehensive and quantitative kidney structure and function MPM studies helped our better understanding of the cellular and molecular mechanisms of the healthy and diseased kidney. This review summarizes recent in vivo MPM studies with a focus on the glomerulus and the filtration barrier, although select, glomerulus-related renal vascular and tubular functions are also mentioned. The latest applications of serial MPM of the same glomerulus in vivo, in the intact kidney over several days, during the progression of glomerular disease are discussed. This visual approach, in combination with genetically encoded fluorescent markers of cell lineage, has helped track the fate and function (e.g., cell calcium changes) of single podocytes during the development of glomerular pathologies, and provided visual proof for the highly dynamic, rather than static, nature of the glomerular environment. Future intravital imaging applications have the promise to further push the limits of optical microscopy, and to advance our understanding of the mechanisms of kidney injury. Also, MPM will help to study new mechanisms of tissue repair and regeneration, a cutting-edge area of kidney research.

[A cohort study of longer-term impact of melamine contaminated formula on infant health].

PubMed

Wang, Pei-xin; Li, Hong-tian; Wang, Lin-lin; Zhang, Long; Zhou, Yu-bo; Liu, Jian-meng

2013-10-15

To prospectively evaluate the health status of infants with exposure to melamine-contaminated milk formula prior to September 2008. The cohort study was conducted in an area close to the manufacturer of Sanlu dairy products. There were three groups (n = 47 each). In September 2008, the exposure group I included infants with exposure to melamine and a diagnosis of renal abnormalities, the exposure group IIhad exposure to melamine but there was no diagnosis of renal abnormalities and the non-exposure group had no exposure to melamine. The exposure II and non-exposure groups were matched with those of exposure group I by birthplaces, gender and date of birth ( ± 3 months). Kidney function tests (urea nitrogen, serum creatinine, uric acid, serum albumin, β2-microglobulin and cystatin C), liver function tests (alanine aminotransferase and aspartate aminotransferase), growth and development assessment and urinary system ultrasonography were implemented between November 2011 and June 2012. The analysis of covariance (least significant difference method) was performed to compare the differences of relevant variables among three groups. The urinary system ultrasonography showed that all abnormalities disappeared in exposure group I and all infants of another two groups had normal ultrasonography. There were statistically significant differences in serum uric acid and albumin of kidney function in exposure group I, exposure group II and non-exposure group ((344 ± 75) and (338 ± 98) and (282 ± 69) µmol/L , (47 ± 5) and (47 ± 6) and (43 ± 5) g/L, all P < 0.05) among three groups. However the differences in the remaining markers of kidney function, markers of liver function and Z scores of weight-for-age and height-for age were all statistically insignificant (all P > 0.05). Further pair-wise comparisons showed that the levels of serum uric acid and albumin in exposure group I were higher than those in non-exposure group (P = 0.001 and 0.010). And the levels of serum uric acid and albumin in exposure group II were also higher than those in non-exposure group (P = 0.003 and 0.005). All affected infants have recovered from kidney abnormalities. Early infant exposure to melamine-contaminated milk formula appears to have no obvious impact on liver function and growth. But its potential impact on kidney function should be further assessed.

The use of fibrous, supramolecular membranes and human tubular cells for renal epithelial tissue engineering: towards a suitable membrane for a bioartificial kidney.

PubMed

Dankers, Patricia Y W; Boomker, Jasper M; Huizinga-van der Vlag, Ali; Smedts, Frank M M; Harmsen, Martin C; van Luyn, Marja J A

2010-11-10

A bioartificial kidney, which is composed of a membrane cartridge with renal epithelial cells, can substitute important kidney functions in patients with renal failure. A particular challenge is the maintenance of monolayer integrity and specialized renal epithelial cell functions ex vivo. We hypothesized that this can be improved by electro-spun, supramolecular polymer membranes which show clear benefits in ease of processability. We found that after 7 d, in comparison to conventional microporous membranes, renal tubular cells cultured on top of our fibrous supramolecular membranes formed polarized monolayers, which is prerequisite for a well-functioning bioartificial kidney. In future, these supramolecular membranes allow for incorporation of peptides that may increase cell function even further.

The Aristotelian kidney.

PubMed

Marandola, P; Musitelli, S; Jallous, H; Speroni, A; de Bastiani, T

1994-01-01

Aristotle incorrectly observed the absence of the kidney in fish and birds and deduced that it was not essential for the existence of a living organism. This underlies his observations on structure and function of the kidney. From examination of rhesus monkeys he generalized that the right kidney is higher than the left. Aristotle did not consider that the renal pelvis is divided by a filter membrane into 2 chambers, and wrote that no blood reaches the renal pelvis. The theory of the 'filter kidney' cannot thus be attributed to Aristotle. The function of the kidney was described as being to separate the surplus liquid from the blood inside the renal meat (not in the renal pelvis) and to transform this liquid into what Aristotle called residuum, i.e. the urine. Aristotle also considered that the kidneys acted to anchor the blood vessels to the body. He only briefly considered renal pathology.

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

Functional Renal Imaging with 2-Deoxy-2-18F-Fluorosorbitol PET in Rat Models of Renal Disorders.

PubMed

Werner, Rudolf A; Wakabayashi, Hiroshi; Chen, Xinyu; Hirano, Mitsuru; Shinaji, Tetsuya; Lapa, Constantin; Rowe, Steven P; Javadi, Mehrbod S; Higuchi, Takahiro

2018-05-01

Precise regional quantitative assessment of renal function is limited with conventional 99m Tc-labeled renal radiotracers. A recent study reported that the PET radiotracer 2-deoxy-2- 18 F-fluorosorbitol ( 18 F-FDS) has ideal pharmacokinetics for functional renal imaging. Furthermore, 18 F-FDS is available via simple reduction from routinely used 18 F-FDG. We aimed to further investigate the potential of 18 F-FDS PET as a functional renal imaging agent using rat models of kidney disease. Methods: Two different rat models of renal impairment were investigated: induction of acute renal failure by intramuscular administration of glycerol in the hind legs, and induction of unilateral ureteral obstruction by ligation of the left ureter. At 24 h after these procedures, dynamic 30-min 18 F-FDS PET data were acquired using a dedicated small-animal PET system. Urine 18 F-FDS radioactivity 30 min after radiotracer injection was measured together with coinjected 99m Tc-diethylenetriaminepentaacetic acid urine activity. Results: Dynamic PET imaging demonstrated rapid 18 F-FDS accumulation in the renal cortex and rapid radiotracer excretion via the kidneys in healthy control rats. On the other hand, significantly delayed renal radiotracer uptake (continuous slow uptake) was observed in acute renal failure rats and unilateral ureteral obstruction kidneys. Measured urine radiotracer concentrations of 18 F-FDS and 99m Tc-diethylenetriaminepentaacetic acid correlated well with each other ( R = 0.84, P < 0.05). Conclusion: 18 F-FDS PET demonstrated favorable kinetics for functional renal imaging in rat models of kidney diseases. 18 F-FDS PET imaging, with its advantages of high spatiotemporal resolution and simple tracer production, could potentially complement or replace conventional renal scintigraphy in select cases and significantly improve the diagnostic performance of renal functional imaging. © 2018 by the Society of Nuclear Medicine and Molecular Imaging.

Chronic Kidney Disease Is Associated With White Matter Hyperintensity Volume

PubMed Central

Khatri, Minesh; Wright, Clinton B.; Nickolas, Thomas L.; Yoshita, Mitsuhiro; Paik, Myunghee C.; Kranwinkel, Grace; Sacco, Ralph L.; DeCarli, Charles

2010-01-01

Background and Purpose White matter hyperintensities have been associated with increased risk of stroke, cognitive decline, and dementia. Chronic kidney disease is a risk factor for vascular disease and has been associated with inflammation and endothelial dysfunction, which have been implicated in the pathogenesis of white matter hyperintensities. Few studies have explored the relationship between chronic kidney disease and white matter hyperintensities. Methods The Northern Manhattan Study is a prospective, community-based cohort of which a subset of stroke-free participants underwent MRIs. MRIs were analyzed quantitatively for white matter hyperintensities volume, which was log-transformed to yield a normal distribution (log-white matter hyperintensity volume). Kidney function was modeled using serum creatinine, the Cockcroft-Gault formula for creatinine clearance, and the Modification of Diet in Renal Disease formula for estimated glomerular filtration rate. Creatinine clearance and estimated glomerular filtration rate were trichotomized to 15 to 60 mL/min, 60 to 90 mL/min, and >90 mL/min (reference). Linear regression was used to measure the association between kidney function and log-white matter hyperintensity volume adjusting for age, gender, race–ethnicity, education, cardiac disease, diabetes, homocysteine, and hypertension. Results Baseline data were available on 615 subjects (mean age 70 years, 60% women, 18% whites, 21% blacks, 62% Hispanics). In multivariate analysis, creatinine clearance 15 to 60 mL/min was associated with increased log-white matter hyperintensity volume (β 0.322; 95% CI, 0.095 to 0.550) as was estimated glomerular filtration rate 15 to 60 mL/min (β 0.322; 95% CI, 0.080 to 0.564). Serum creatinine, per 1-mg/dL increase, was also positively associated with log-white matter hyperintensity volume (β 1.479; 95% CI, 1.067 to 2.050). Conclusions The association between moderate–severe chronic kidney disease and white matter hyperintensity volume highlights the growing importance of kidney disease as a possible determinant of cerebrovascular disease and/or as a marker of microangiopathy. PMID:17962588

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

Marques da Silva, A; Narciso, L

Purpose: Commercial workstations usually have their own software to calculate dynamic renal functions. However, usually they have low flexibility and subjectivity on delimiting kidney and background areas. The aim of this paper is to present a public domain software, called RenalQuant, capable to semi-automatically draw regions of interest on dynamic renal scintigraphies, extracting data and generating renal function quantification parameters. Methods: The software was developed in Java and written as an ImageJ-based plugin. The preprocessing and segmentation steps include the user’s selection of one time frame with higher activity in kidney’s region, compared with background, and low activity in themore » liver. Next, the chosen time frame is smoothed using a Gaussian low pass spatial filter (σ = 3) for noise reduction and better delimitation of kidneys. The maximum entropy thresholding method is used for segmentation. A background area is automatically placed below each kidney, and the user confirms if these regions are correctly segmented and positioned. Quantitative data are extracted and each renogram and relative renal function (RRF) value is calculated and displayed. Results: RenalQuant plugin was validated using retrospective 20 patients’ 99mTc-DTPA exams, and compared with results produced by commercial workstation software, referred as reference. The renograms intraclass correlation coefficients (ICC) were calculated and false-negative and false-positive RRF values were analyzed. The results showed that ICC values between RenalQuant plugin and reference software for both kidneys’ renograms were higher than 0.75, showing excellent reliability. Conclusion: Our results indicated RenalQuant plugin can be trustingly used to generate renograms, using DICOM dynamic renal scintigraphy exams as input. It is user friendly and user’s interaction occurs at a minimum level. Further studies have to investigate how to increase RRF accuracy and explore how to solve limitations in the segmentation step, mainly when background region has higher activity compared to kidneys. Financial support by CAPES.« less

Comprehensive morphometric analysis of mononuclear cell infiltration during experimental renal allograft rejection.

PubMed

Hoffmann, Ute; Bergler, Tobias; Jung, Bettina; Steege, Andreas; Pace, Claudia; Rümmele, Petra; Reinhold, Stephan; Krüger, Bernd; Krämer, Bernhard K; Banas, Bernhard

2013-01-01

The role of specific subtypes of infiltrating cells in acute kidney allograft rejection is still not clear and was so far not examined by different analyzing methods under standardized conditions of an experimental kidney transplantation model. Immunohistochemical staining of CD3, CD20 and CD68 was performed in rat allografts, in syngeneically transplanted rats and in control rats with a test duration of 6 and 28 days. The detailed expression and localization of infiltrating cells were analyzed manually in different kidney compartments under light microscope and by the two different morphometric software programs. Data were correlated with the corresponding kidney function as well as with histopathological classification. The information provided by the morphometric software programs on the infiltration of the specific cell types after renal transplantation was in accordance with the manual analysis. Morphometric methods were solid to analyze reliably the induction of cellular infiltrates after renal transplantation. By manual analysis we could clearly demonstrate the detailed localization of the specific cell infiltrates in the different kidney compartments. Besides infiltration of CD3 and CD68 infiltrating cells, a robust infiltration of CD20 B-cells in allogeneically transplanted rats, even at early time points after transplantation was detected. Additionally an MHC class I expression could reliable be seen in allogeneically transplanted rats. The infiltration of B-cells and the reliable antigen presentation might act as a silent subclinical trigger for subsequent chronic rejection and premature graft loss. Copyright © 2012 Elsevier B.V. All rights reserved.

Vitamin D in the Pathophysiology of Hypertension, Kidney Disease, and Diabetes: Examining the Relationship Between Vitamin D and the Renin-Angiotensin System in Human Diseases

PubMed Central

Vaidya, Anand; Williams, Jonathan S.

2011-01-01

Objective Vitamin D has been implicated in the pathophysiology of extra-skeletal conditions such as hypertension, kidney disease, and diabetes, via its ability to negatively regulate the renin-angiotensin system (RAS). This article reviews the evidence supporting a link between vitamin D and the RAS in these conditions, with specific emphasis on translational observations and their limitations. Methods Literature review of animal and human studies evaluating the role of vitamin D in hypertension, kidney disease, and diabetes. Results Excess activity of the RAS has been implicated in the pathogenesis of hypertension, chronic kidney disease, decreased insulin secretion, and insulin resistance. Animal studies provide strong support for 1,25(OH)2D mediated down-regulation of renin expression and RAS activity via its interaction with the vitamin D receptor. Furthermore, the activity of vitamin D metabolites in animals is associated with reductions in blood pressure, proteinuria and renal injury, and with improved β–cell function. Many observational, and a few interventional, studies in humans have supported these findings; however, there is a lack of well designed prospective human interventional studies to definitively assess clinical outcomes. Conclusion Animal studies implicate vitamin D receptor agonist therapy to lower RAS activity as a potential method to reduce the risk of hypertension, kidney disease, and diabetes. There is a need for more well designed prospective interventional studies to validate this hypothesis in human clinical outcomes. PMID:22075270

Hyperuricemia, Acute and Chronic Kidney Disease, Hypertension, and Cardiovascular Disease: Report of a Scientific Workshop Organized by the National Kidney Foundation.

PubMed

Johnson, Richard J; Bakris, George L; Borghi, Claudio; Chonchol, Michel B; Feldman, David; Lanaspa, Miguel A; Merriman, Tony R; Moe, Orson W; Mount, David B; Sanchez Lozada, Laura Gabriella; Stahl, Eli; Weiner, Daniel E; Chertow, Glenn M

2018-06-01

Urate is a cause of gout, kidney stones, and acute kidney injury from tumor lysis syndrome, but its relationship to kidney disease, cardiovascular disease, and diabetes remains controversial. A scientific workshop organized by the National Kidney Foundation was held in September 2016 to review current evidence. Cell culture studies and animal models suggest that elevated serum urate concentrations can contribute to kidney disease, hypertension, and metabolic syndrome. Epidemiologic evidence also supports elevated serum urate concentrations as a risk factor for the development of kidney disease, hypertension, and diabetes, but differences in methodologies and inpacts on serum urate concentrations by even subtle changes in kidney function render conclusions uncertain. Mendelian randomization studies generally do not support a causal role of serum urate in kidney disease, hypertension, or diabetes, although interpretation is complicated by nonhomogeneous populations, a failure to consider environmental interactions, and a lack of understanding of how the genetic polymorphisms affect biological mechanisms related to urate. Although several small clinical trials suggest benefits of urate-lowering therapies on kidney function, blood pressure, and insulin resistance, others have been negative, with many trials having design limitations and insufficient power. Thus, whether uric acid has a causal role in kidney and cardiovascular diseases requires further study. Copyright © 2018 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.

Older kidneys donor transplantation: five years' experience without biopsy and using clinical laboratory and macroscopic anatomy evaluation.

PubMed

Santangelo, M; Zuccaro, M; De Rosa, P; Tammaro, V; Grassia, S; Federico, S; Ciotola, A L; Spinosa, G; Renda, A

2007-01-01

The exponential increase in organ demand is not associated with a similar increase of available kidneys. This emergency led to expanded criteria to consider a kidney transplantable. The aim of this retrospective study was to explain our use of older donor kidneys without biopsy. Between 2000 and 2005, 58 older kidneys were harvested: 27 were transplanted in our center; 13 were discarded; and 18 were transplanted in other centers. We considered 3 factors to define kidney quality: macroscopic anatomy, multiple factors linked to the donor, and clinical-laboratory data. After transplantation, we observed the patients for at least 1 year and up to 6 years. At 1 year, 24/27 (89%) patients had a functional kidney, 2 patients showed an initial renal failure and 1 patient lost the kidney. At maximum follow-up, 19 patients (70%) had functional kidneys, 4 with initial renal failure. These results compared with the kidneys harvested using Standard Donor Kidney Criteria are acceptable. Obviously we need long-term follow-up to increase, the amount of data and obtain a definitive outcome. Biopsy is the gold standard for the definition of an older kidney's quality. When a biopsy is not feasible, the study of the macroscopic anatomy the kidney's donor and of some donor's parameters represent an acceptable biopsy alternative, being able to rescue some organs that would be otherwise lost.

[The kidney transplantation from the ABO-incompatible donors].

PubMed

Goriaĭnov, V A; Kaabak, M M; Babenko, N N; Shishlo, L A; Morozova, M M; Ragimov, A A; Dashkova, N G; Salimov, É L

2012-01-01

The experience of 28 allotransplantations of ABO-incompatible kidneys was compared with the treatment results of 38 ABO-compatible renal transplantations. The transplanted kidney function, morphological changes of the transplanted kidney and the comparative analysis of actuary survival in both groups showed no significant difference. The results of the study prove the validity of the kidney transplantation from the ABO-incompatible donors.

Successful outcome of transplant of kidneys recovered from a brain-dead liver transplant recipient: case report.

PubMed

Domagała, Piotr; Kwiatkowski, Artur; Drozdowski, Jakub; Ostrowski, Krzysztof; Wszola, Michal; Diuwe, Piotr; Durlik, Magdalena; Paczek, Leszek; Chmura, Andrzej

2012-12-01

Few reports describing the use of organs donated by transplant recipients have been published. In this case report, kidneys procured from a brain-dead liver recipient were transplanted successfully. A 21-year-old man was referred for liver transplant after an overdose of acetaminophen. The patient's kidney function was initially normal, with proper urine production and normal kidney laboratory parameters. On the third day after admission, the patient's kidney laboratory parameters became elevated and hepatic encephalopathy requiring mechanical ventilation developed. An orthotopic liver transplant was performed the next day. The patient did not recover consciousness, and brain death was diagnosed on the third day after the liver transplant surgery. The maximum serum concentration of creatinine was 5.8 mg/dL (513 μmol/L) before kidney recovery, and urine production was normal. The kidneys were recovered with organ-perfusion support and were preserved by using machine perfusion. The kidneys were transplanted into 2 male recipients. Twelve months after transplant, the recipients remained in good health with satisfactory kidney function. This case demonstrates that transplanting kidneys recovered from liver transplant recipients is possible and beneficial, thus expanding the pool of potential donors.

Predicting the relative binding affinity of mineralocorticoid receptor antagonists by density functional methods

NASA Astrophysics Data System (ADS)

Roos, Katarina; Hogner, Anders; Ogg, Derek; Packer, Martin J.; Hansson, Eva; Granberg, Kenneth L.; Evertsson, Emma; Nordqvist, Anneli

2015-12-01

In drug discovery, prediction of binding affinity ahead of synthesis to aid compound prioritization is still hampered by the low throughput of the more accurate methods and the lack of general pertinence of one method that fits all systems. Here we show the applicability of a method based on density functional theory using core fragments and a protein model with only the first shell residues surrounding the core, to predict relative binding affinity of a matched series of mineralocorticoid receptor (MR) antagonists. Antagonists of MR are used for treatment of chronic heart failure and hypertension. Marketed MR antagonists, spironolactone and eplerenone, are also believed to be highly efficacious in treatment of chronic kidney disease in diabetes patients, but is contra-indicated due to the increased risk for hyperkalemia. These findings and a significant unmet medical need among patients with chronic kidney disease continues to stimulate efforts in the discovery of new MR antagonist with maintained efficacy but low or no risk for hyperkalemia. Applied on a matched series of MR antagonists the quantum mechanical based method gave an R2 = 0.76 for the experimental lipophilic ligand efficiency versus relative predicted binding affinity calculated with the M06-2X functional in gas phase and an R2 = 0.64 for experimental binding affinity versus relative predicted binding affinity calculated with the M06-2X functional including an implicit solvation model. The quantum mechanical approach using core fragments was compared to free energy perturbation calculations using the full sized compound structures.

A case of unilateral nephrectomy performed for autosomal dominant polycystic kidney disease with marked unilateral enlargement.

PubMed

Makabe, Shiho; Kataoka, Hiroshi; Kondo, Tsunenori; Tanabe, Kazunari; Tsuchiya, Ken; Nitta, Kosaku; Mochizuki, Toshio

2018-05-01

Autosomal dominant polycystic kidney disease (ADPKD) is characterized by the occurrence of multiple cysts that increase the size of both kidneys, progressively reducing kidney function. Usually the cysts occur bilaterally, and there is no difference in the degree of cyst enlargement between the left and right. Here, we report a case of ADPKD in which kidney size increased markedly on the left side and was accompanied by severe abdominal distension and discomfort. Renal dynamic scintigraphy revealed a severe reduction in function of the left kidney compared with the right. Open left nephrectomy was performed. No change in renal function was observed postoperatively [preoperative estimated glomerular filtration rate (eGFR): 57.6 mL/min/1.73 m 2 , 3-month postoperative eGFR: 56.4 mL/min/1.73 m 2 ], and the abdominal symptoms subsided. When one kidney is markedly larger than the other, the cause and status of the laterality should be evaluated by using renal dynamic scintigraphy in addition to other examinations such as computed tomography or magnetic resonance imaging. Unilateral nephrectomy should be considered as a potential treatment.

Pretransplantation recipient regulatory T cell suppressive function predicts delayed and slow graft function after kidney transplantation.

PubMed

Nguyen, Minh-Tri J P; Fryml, Elise; Sahakian, Sossy K; Liu, Shuqing; Michel, Rene P; Lipman, Mark L; Mucsi, Istvan; Cantarovich, Marcelo; Tchervenkov, Jean I; Paraskevas, Steven

2014-10-15

Delayed graft function (DGF) and slow graft function (SGF) are a continuous spectrum of ischemia-reperfusion-related acute kidney injury (AKI) that increases the risk for acute rejection and graft loss after kidney transplantation. Regulatory T cells (Tregs) are critical in transplant tolerance and attenuate murine AKI. In this prospective observational cohort study, we evaluated whether pretransplantation peripheral blood recipient Treg frequency and suppressive function are predictors of DGF and SGF after kidney transplantation. Deceased donor kidney transplant recipients (n=53) were divided into AKI (n=37; DGF, n=10; SGF, n=27) and immediate graft function (n=16) groups. Pretransplantation peripheral blood CD4CD25FoxP3 Treg frequency was quantified by flow cytometry. Regulatory T-cell suppressive function was measured by suppression of autologous effector T-cell proliferation by Treg in co-culture. Pretransplantation Treg suppressive function, but not frequency, was decreased in AKI recipients (P<0.01). In univariate and multivariate analyses accounting for the effects of cold ischemic time and donor age, Treg suppressive function discriminated DGF from immediate graft function recipients in multinomial logistic regression (odds ratio, 0.77; P<0.01), accurately predicted AKI in receiver operating characteristic curve (area under the curve, 0.82; P<0.01), and predicted 14-day estimated glomerular filtration rate in linear regression (P<0.01). Our results indicate that recipient peripheral blood Treg suppressive function is a potential independent pretransplantation predictor of DGF and SGF.

[Paired kidneys in transplant].

PubMed

Regueiro López, Juan C; Leva Vallejo, Manuel; Prieto Castro, Rafael; Anglada Curado, Francisco; Vela Jiménez, Francisco; Ruiz García, Jesús

2009-02-01

Many factors affect the graft and patient survival on the renal transplant outcome. These factors depend so much of the recipient and donor. We accomplished a study trying to circumvent factors that depend on the donor. We checked the paired kidneys originating of a same donor cadaver. We examined the risk factors in the evolution and follow-up in 278 couples of kidney transplant. We describe their differences, significance, the graft and patient survival, their functionality in 3 and 5 years and the risk factors implicated in their function. We study immunogenic and no immunogenic variables, trying to explain the inferior results in the grafts that are established secondly. We regroup the paired kidneys in those that they did not show paired initial function within the same couple. The results yield a discreet deterioration in the graft and patient survival for second group establish, superior creatinina concentration, without obtaining statistical significance. The Cox regression study establishes the early rejection (inferior to three months) and DR incompatibility values like risk factors. This model of paired kidneys would be able to get close to best-suited form for risk factors analysis in kidney transplant from cadaver donors, if more patients examine themselves in the same way. The paired kidneys originating from the same donor do not show the same function in spite of sharing the same conditions of the donor and perioperative management.

[Morphological characteristics of kidneys connective tissue of mature fetuses and newborns from mothers, whose pregnancy was complicated by preeclampsia of varying degrees of severity].

PubMed

Sorokina, Iryna V; Myroshnychenko, Mykhailo S; Kapustnyk, Nataliia V; Khramova, Tetyana O; Dehtiarova, Oksana V; Danylchenko, Svitlana I

2018-01-01

Introduction: The kidneys connective tissue condition in the antenatal period affects the formation of tissues and it changes with the development of various general pathological processes in this organ. The aim of the study was to identify the morphological features of kidneys connective tissue of fetuses and newborns from mothers whose pregnancy was complicated by preeclampsia of varying degrees of severity. Materials and methods: The material of the study was the tissue of kidneys of mature fetuses and newborns from mothers with physiological pregnancy (28 cases), as well as from mothers whose pregnancy was complicated by preeclampsia of varying degrees of severity (78 cases). Immunohistochemical study was performed by an indirect Coons method according to M. Brosman's technique using monoclonal antibodies to collagen type I, III and IV. Results: The kidneys connective tissue of fetuses and newborns developing under the maternal preeclampsia conditions is characterized by the qualitative and quantitative changes that indicate the development of sclerotic processes in this organ, the severity of which increase with the age and with the increase of the maternal preeclampsia severity. Qualitative changes are characterized by an increase of the fibrous component, thickening of the bundles of connective tissue fibers, and a decrease in the distance between them. Quantitative changes are characterized by a pronounced predominance of collagen fibers over elastic fibers, almost total absence in some field of view elastic fibers and the violation of the content of collagen type I, III and IV. Conclusion: Maternal preeclampsia underlies the development of qualitative and quantitative changes in kidneys connective tissue of fetuses and newborns, which as a result will lead to disruption of the functions of these organs in such children.

Disease Progression Modeling to Evaluate the Effects of Enzyme Replacement Therapy on Kidney Function in Adult Patients with the Classic Phenotype of Fabry Disease.

PubMed

Nowak, Albina; Koch, Gilbert; Huynh-Do, Uyen; Siegenthaler, Martin; Marti, Hans-Peter; Pfister, Marc

2017-01-01

Fabry disease (FD) is a rare inherited lysosomal storage disease with common and serious kidney complications. Enzyme replacement therapies (ERT) with agalsidase-α and -β were investigated to characterize their therapeutic effect on kidney function in FD patients with Classic phenotype. The prospective FD cohort consisted of 98 genetically confirmed patients (females, n = 61, males, n = 37). The median [interquartile range] follow-up time (time difference from first to last visit) was 9 [6, 12] years. The median age of ERT start was 36 [21 - 54] years for females and 39 [28 - 49] years for males. A disease progression model was developed to (i) characterize the time course of estimated glomerular filtration rate (eGFR) and (ii) evaluate therapeutic effects of ERT on kidney function. Change in eGFR over time was best described by the linear model. Females had stable kidney function with and without ERT (eGFR slopes of -0.07 ml/min/1.73m^2 per year and 0.52 ml/min/1.73m^2 per year, respectively). Males with ERT showed an eGFR decrease of -3.07 ml/min/1.73m^2 per year. Mathematical disease progression modeling indicates that there is no clear therapeutic effect of ERT on kidney function in adult patients with Classic Phenotype of FD. Interpretation of these findings should take into account that the study is not randomized and lacks a placebo controlled group. Further investigations are warranted to clarify whether earlier ERT initiation before 18 years of age, higher ERT dose or more intensive therapies can preserve kidney function. © 2017 The Author(s)Published by S. Karger AG, Basel.

4D MRI of polycystic kidneys from rapamycin-treated Glis3-deficient mice

PubMed Central

Xie, Luke; Qi, Yi; Subashi, Ergys; Liao, Grace; Miller DeGraff, Laura; Jetten, Anton M.; Johnson, G. Allan

2015-01-01

Polycystic kidney disease (PKD) is a life-threatening disease that leads to a grotesque enlargement of the kidney and significant lose of function. Several imaging studies with MRI have demonstrated that cyst size in polycystic kidneys can determine disease severity and progression. In the present study, we found that while kidney volume and cyst volume decreased with drug treatment, renal function did not improve with treatment. Here, we applied dynamic contrast-enhanced MRI to study PKD in a Glis3-deficient mouse model. Cysts from this model have a wide range of sizes and develop at an early age. To capture this crucial stage and assess cysts in detail, we imaged during early development (3 to 17 weeks) and applied high spatiotemporal resolution MRI (125×125×125 cubic microns every 7.7 seconds). A drug treatment with rapamycin (also known as sirolimus) was applied to determine whether disease progression could be halted. The effect and synergy (interaction) of aging and treatment were evaluated using an analysis of variance (ANOVA). Structural measurements including kidney volume, cyst volume, and cyst-kidney volume ratio changed significantly with age. Drug treatment significantly decreased these metrics. Functional measurements of time-to-peak (TTP) mean and TTP variance were determined. TTP mean did not change with age, while TTP variance increased with age. The treatment of rapamycin generally did not affect these functional metrics. Synergistic effects of treatment and age were not found for any measurements. Together, the size and volume ratio of cysts decreased with drug treatment, while renal function remained the same. Quantifying renal structure and function with MRI can comprehensively assess the pathophysiology of PKD and response to treatment. PMID:25810360

Hypothermic machine perfusion in kidney transplantation.

PubMed

De Deken, Julie; Kocabayoglu, Peri; Moers, Cyril

2016-06-01

This article summarizes novel developments in hypothermic machine perfusion (HMP) as an organ preservation modality for kidneys recovered from deceased donors. HMP has undergone a renaissance in recent years. This renewed interest has arisen parallel to a shift in paradigms; not only optimal preservation of an often marginal quality graft is required, but also improved graft function and tools to predict the latter are expected from HMP. The focus of attention in this field is currently drawn to the protection of endothelial integrity by means of additives to the perfusion solution, improvement of the HMP solution, choice of temperature, duration of perfusion, and machine settings. HMP may offer the opportunity to assess aspects of graft viability before transplantation, which can potentially aid preselection of grafts based on characteristics such as perfusate biomarkers, as well as measurement of machine perfusion dynamics parameters. HMP has proven to be beneficial as a kidney preservation method for all types of renal grafts, most notably those retrieved from extended criteria donors. Large numbers of variables during HMP, such as duration, machine settings and additives to the perfusion solution are currently being investigated to improve renal function and graft survival. In addition, the search for biomarkers has become a focus of attention to predict graft function posttransplant.

[Evaluation of immune status of kidney transplant recipients by combined HLA-G5 and sCD30].

PubMed

JIN, Zhan-kui; TIAN, Pu-xun; XUE, Wu-jun; DING, Xiao-ming; PAN, Xiao-ming; DING, Chen-guang; JIA, Li-ning; GE, Guan-qun; HAO, Jun-jun

2010-09-28

to study the relationship between the expression of serum human leucocyte antigen-G5 (HLA-G5)/soluble CD30 (sCD30) and the function of renal graft in kidney transplant recipients and investigate the immune status of recipients with combined HLA-G5 and sCD30. from January 2002 to November 2008, a total of 66 kidney transplant recipients in our centre were selected as subjects and divided into three groups: stable function of renal graft (n = 38), acute rejection (n = 15) and chronic rejection (n = 13). The expressions of serum HLA-G5 and sCD30 were detected. There were two different immune conditions with acute/chronic allograft rejection and normal renal graft in kidney transplant recipients as evaluated by combined HLA-G5 and sCD30. The sensitivity, specificity and critical value of the method were analyzed by the curve of receiver operating characteristic. the levels of HLA-G5 and sCD30 were significantly correlated with serum creatinine (r = -0.493, 0.691, both P < 0.01). Within the first year post-transplantation, the sensitivity was 78.6% and the specificity 85.7% when HLA-G5 critical value 82 microg/L and sCD30 critical value 12.2 microg/L. After one year post-transplantation: the sensitivity was 92.3% and the specificity 84.6% when HLA-G5 critical value 141 microg/L and sCD30 critical value 10.3 microg/L. the immune state of recipients are evaluated by combine HLA-G5 and sCD30 which may be a simple and valid method.

History of Childhood Kidney Disease and Risk of Adult End-Stage Renal Disease.

PubMed

Calderon-Margalit, Ronit; Golan, Eliezer; Twig, Gilad; Leiba, Adi; Tzur, Dorit; Afek, Arnon; Skorecki, Karl; Vivante, Asaf

2018-02-01

The long-term risk associated with childhood kidney disease that had not progressed to chronic kidney disease in childhood is unclear. We aimed to estimate the risk of future end-stage renal disease (ESRD) among adolescents who had normal renal function and a history of childhood kidney disease. We conducted a nationwide, population-based, historical cohort study of 1,521,501 Israeli adolescents who were examined before compulsory military service in 1967 through 1997; data were linked to the Israeli ESRD registry. Kidney diseases in childhood included congenital anomalies of the kidney and urinary tract, pyelonephritis, and glomerular disease; all participants included in the primary analysis had normal renal function and no hypertension in adolescence. Cox proportional-hazards models were used to estimate the hazard ratio for ESRD associated with a history of childhood kidney disease. During 30 years of follow-up, ESRD developed in 2490 persons. A history of any childhood kidney disease was associated with a hazard ratio for ESRD of 4.19 (95% confidence interval [CI], 3.52 to 4.99). The associations between each diagnosis of kidney disease in childhood (congenital anomalies of the kidney and urinary tract, pyelonephritis, and glomerular disease) and the risk of ESRD in adulthood were similar in magnitude (multivariable-adjusted hazard ratios of 5.19 [95% CI, 3.41 to 7.90], 4.03 [95% CI, 3.16 to 5.14], and 3.85 [95% CI, 2.77 to 5.36], respectively). A history of kidney disease in childhood was associated with younger age at the onset of ESRD (hazard ratio for ESRD among adults <40 years of age, 10.40 [95% CI, 7.96 to 13.59]). A history of clinically evident kidney disease in childhood, even if renal function was apparently normal in adolescence, was associated with a significantly increased risk of ESRD, which suggests that kidney injury or structural abnormality in childhood has long-term consequences.

Dietary Potential Renal Acid Load and Risk of Albuminuria and Reduced Kidney Function in the Jackson Heart Study.

PubMed

Banerjee, Tanushree; Tucker, Katherine; Griswold, Michael; Wyatt, Sharon B; Harman, Jane; Young, Bessie; Taylor, Herman; Powe, Neil R

2018-07-01

Diets high in sulfur-rich protein and low in fruit and vegetables affect human acid-base balance adversely and may have a harmful effect on progression of chronic kidney disease (CKD). Little is known about the relationship of participant characteristics, dietary acid load (DAL), and kidney injury in African-Americans with high risk of CKD progression. We examined the association of DAL with CKD in 3,257 African-Americans aged >20 years in Jackson Heart Study. DAL was measured with nutrient intakes assessed with a food frequency questionnaire, using a model described by Remer and Manz. We tested associations of participant characteristics with DAL using median regression, and associations of DAL with albuminuria (>17 mg/g for men, >25 mg/g for women), reduced kidney function (eGFR <60 mL/minute/1.73 m 2 ), or CKD defined as albuminuria or reduced kidney function using logistic regression. We further explored whether endothelin and aldosterone production in participants with hypertension mediated risk of albuminuria or reduced kidney function due to the intake of an acid-inducing diet. Younger adults, men, and those with higher body mass index had higher DAL. Higher DAL, compared with lower, was associated with greater odds of reduced kidney function (OR [95% CI]: 2.82 [1.40-4.75]). Higher DAL was also associated with greater risk of CKD, and this persisted after adjustment for confounders. Results were similar in adults with hypertension; the OR [95% CI] for highest, versus lowest, tertile of DAL with albuminuria was 1.66 [1.01-2.59]. Aldosterone and endothelin mediated the association between DAL and albuminuria; the OR [95% CI] in the highest tertile was no longer significant 1.53 [0.97-2.40] after their inclusion. Higher DAL was associated with higher prevalence of CKD and with reduced kidney function. DAL may be an important target for future interventions in African-Americans at high risk of CKD. Copyright © 2018 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.

Metabolomic Profiling in Individuals with a Failing Kidney Allograft

PubMed Central

Biancone, Luigi; Bussolino, Stefania; Merugumala, Sai; Tezza, Sara; D’Addio, Francesca; Ben Nasr, Moufida; Valderrama-Vasquez, Alessandro; Usuelli, Vera; De Zan, Valentina; El Essawy, Basset; Venturini, Massimo; Secchi, Antonio; De Cobelli, Francesco; Lin, Alexander; Chandraker, Anil; Fiorina, Paolo

2017-01-01

Background Alteration of certain metabolites may play a role in the pathophysiology of renal allograft disease. Methods To explore metabolomic abnormalities in individuals with a failing kidney allograft, we analyzed by liquid chromatography-mass spectrometry (LC-MS/MS; for ex vivo profiling of serum and urine) and two dimensional correlated spectroscopy (2D COSY; for in vivo study of the kidney graft) 40 subjects with varying degrees of chronic allograft dysfunction stratified by tertiles of glomerular filtration rate (GFR; T1, T2, T3). Ten healthy non-allograft individuals were chosen as controls. Results LC-MS/MS analysis revealed a dose-response association between GFR and serum concentration of tryptophan, glutamine, dimethylarginine isomers (asymmetric [A]DMA and symmetric [S]DMA) and short-chain acylcarnitines (C4 and C12), (test for trend: T1-T3 = p<0.05; p = 0.01; p<0.001; p = 0.01; p = 0.01; p<0.05, respectively). The same association was found between GFR and urinary levels of histidine, DOPA, dopamine, carnosine, SDMA and ADMA (test for trend: T1-T3 = p<0.05; p<0.01; p = 0.001; p<0.05; p = 0.001; p<0.001; p<0.01, respectively). In vivo 2D COSY of the kidney allograft revealed significant reduction in the parenchymal content of choline, creatine, taurine and threonine (all: p<0.05) in individuals with lower GFR levels. Conclusions We report an association between renal function and altered metabolomic profile in renal transplant individuals with different degrees of kidney graft function. PMID:28052095

[Kidney transplantation: consecutive one thousand transplants at National Institute of Medical Sciences and Nutrition Salvador Zubirán in Mexico City].

PubMed

Marino-Vazquez, Lluvia Aurora; Sánchez-Ugarte, Regina; Morales-Buenrostro, Luis Eduardo

2011-09-01

The National Institute of Medical Sciences and Nutrition Salvador Zubiran (INCMNSZ) is a specialty hospital for adults and a teaching hospital, which performed the first kidney transplant in 1967; in 1971 it began the formal program of renal transplantation. Recently, it was performed the kidney transplant number 1000, so this article presents the information of these thousand kidney transplants, with special emphasis on survival. Retrospective cohort study which included 1000 consecutive transplants performed at the INCMNSZ between 1967 and June 2011. It describes the general characteristics of kidney transplant recipients, transplant-related variables, initial immunosuppression and complications. Descriptive statistics were used. The survival analysis was performed using the Kaplan-Meier method. It shows the patient survival, graft survival censored for death with functional graft and total graft survival (uncensored). Patient survival at 1, 3, 5, 10, 15, and 20 years was 94.9, 89.6, 86.8, 76.9, 66.1, and 62.2%, respectively. Graft survival censored for death with functional graft at 1, 3, 5, 10, 15, and 20 years was 93.1, 87.1, 83.5, 73.9, 62.7, and 52.5% respectively. Risk factors associated with poorer graft survival were younger age of the recipient, transplant during the first period (1967-1983), and a HLA mismatch. Patient and graft survival have improved over time through the use of better immunosuppression and use of induction therapy. Identification of risk factors affecting graft survival, allows each center to set their strategies to improve the patient's outcome.

Impact of transplant nephrectomy on peak PRA levels and outcome after kidney re-transplantation

PubMed Central

Tittelbach-Helmrich, Dietlind; Pisarski, Przemyslaw; Offermann, Gerd; Geyer, Marcel; Thomusch, Oliver; Hopt, Ulrich Theodor; Drognitz, Oliver

2014-01-01

AIM: To determine the impact of transplant nephrectomy on peak panel reactive antibody (PRA) levels, patient and graft survival in kidney re-transplants. METHODS: From 1969 to 2006, a total of 609 kidney re-transplantations were performed at the University of Freiburg and the Campus Benjamin Franklin of the University of Berlin. Patients with PRA levels above (5%) before first kidney transplantation were excluded from further analysis (n = 304). Patients with graft nephrectomy (n = 245, NE+) were retrospectively compared to 60 kidney re-transplants without prior graft nephrectomy (NE-). RESULTS: Peak PRA levels between the first and the second transplantation were higher in patients undergoing graft nephrectomy (P = 0.098), whereas the last PRA levels before the second kidney transplantation did not differ between the groups. Age adjusted survival for the second kidney graft, censored for death with functioning graft, were comparable in both groups. Waiting time between first and second transplantation did not influence the graft survival significantly in the group that underwent nephrectomy. In contrast, patients without nephrectomy experienced better graft survival rates when re-transplantation was performed within one year after graft loss (P = 0.033). Age adjusted patient survival rates at 1 and 5 years were 94.1% and 86.3% vs 83.1% and 75.4% group NE+ and NE-, respectively (P < 0.01). CONCLUSION: Transplant nephrectomy leads to a temporary increase in PRA levels that normalize before kidney re-transplantation. In patients without nephrectomy of a non-viable kidney graft timing of re-transplantation significantly influences graft survival after a second transplantation. Most importantly, transplant nephrectomy is associated with a significantly longer patient survival. PMID:25032103

Incidence and Risk Factors for Leukopenia in Kidney Transplant Recipients Receiving Valganciclovir for Cytomegalovirus Prophylaxis.

PubMed

Liang, Xinyun; Famure, Olusegun; Li, Yanhong; Kim, S Joseph

2018-06-01

Valganciclovir is used not only for cytomegalovirus prophylaxis after kidney transplantation but can also induce leukopenia, thereby making patients more susceptible to other infections. The epidemiology of leukopenia in patients on valganciclovir remains poorly understood. To determine the incidence and risk factors for leukopenia in patients receiving valganciclovir for cytomegalovirus prophylaxis after kidney transplantation. In this single-center, retrospective, cohort study, we included kidney recipients transplanted from January 1, 2003, to December 31, 2010, to determine the incidence and risk factors for leukopenia in patients who received valganciclovir for cytomegalovirus prophylaxis. The Kaplan-Meier product limit method was used to graphically assess time to leukopenia, and risk factors were assessed using Cox proportional hazards models. A total of 542 kidney transplant recipients were included in the study cohort. The cumulative incidence of leukopenia at 6 months posttransplant was 39.3% (11.0% for neutropenia). Low baseline white blood cell count (hazard ratio [HR] 2.34 [95% confidence interval [CI], 1.37-4.00]) and high baseline body mass index (HR 1.05 [95% CI, 1.02-1.09]) were independently associated with an increased risk of leukopenia, while higher Cockcroft-Gault creatinine clearance (HR 0.87 [95% CI, 0.78-0.97]) was significantly associated with a decreased risk of leukopenia. These data suggest that recipient baseline white blood cell count, baseline body mass index, and kidney function are clinical predictors of new-onset leukopenia after kidney transplantation. Our results may inform the approach to cytomegalovirus prophylaxis to reduce the risk of valganciclovir-induced leukopenia in kidney transplant recipients.

Association between Delayed graft function (DGF) biomarkers and long-term outcomes after living donor kidney transplantation.

PubMed

Sahraei, Zahra; Mehdizadeh, Mona; Salamzadeh, Jamshid; Nafar, Mohsen; Eshraghi, Azadeh

2018-05-21

The Association between preoperative Urine Neutrophil Gelatinase-associated Lipocalin (uNGAL) and interlukin-18 (uIL-18) with poor 1-year allograft function has been shown in deceased-donor kidney transplant recipients previously, and also these markers could predict 3-month allograft function. However, it is unknown whether there is any association between these postoperative biomarkers with important recipient outcomes beyond this time in live-donor transplants. NGAL and IL-18 four and 24 hours were measured in live-donor kidney transplant recipients after transplantation. The relationships between changes in these markers with clinical outcomes as well as kidney function were examined at 1 month and 2 years. Also, the association between delayed graft function with clinical outcome and serum creatinine (SrCr) were evaluated during this period. The Mean age for kidney recipients was 23.9 years. There was significant interaction between uNGAL 24 hr (pvalue=0.01) and uIL-18 four and 24 hr after transplantation (pvalue=0.04, 0.03; respectively) with patients' outcome after 1 month and changes in uNGAL with outcomes after 2 years (pvalue= 0.04). Changes in urine NGAL postoperative is associated with worse outcome 2 years after kidney transplantation, suggesting its potential role for identifying patients that are at high risk for diminished allograft function, outcome and survival. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

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.

Association between biomarkers of carbonyl stress with increased systemic inflammatory response in different stages of chronic kidney disease and after renal transplantation.

PubMed

Aveles, Paulo R; Criminácio, Ciro R; Gonçalves, Simone; Bignelli, Alexandre T; Claro, Ligia Maria; Siqueira, Sérgio S; Nakao, Lia S; Pecoits-Filho, Roberto

2010-01-01

Chronic kidney disease (CKD) is characterized by progressive kidney dysfunction accompanied by accumulation of uremic toxins and a potential disequilibrium between the redox status and the generation of prooxidants, resulting in oxidative stress and chronic inflammation which is associated with complications (particularly cardiovascular disease) in this population. We aimed to analyze the concentration of total plasma thiols (indicator of antioxidant capacity) and the protein carbonyl content (a marker of carbonyl stress) in relation to kidney function and inflammation in a group of patients with CKD. A group of 68 patients with CKD (stages 2-5; mean age 57 ± 12 years, 46% male, 34% diabetics) and another group of 21 patients who underwent living donor kidney transplantation (mean age 36 ± 17 years, 50% male, 10% diabetics, and 9 ± 2 months after renal transplantation) were included in the study. Total plasma thiol and protein carbonyl levels were determined by the DTNB and DNPH methods, respectively, and were adjusted to the plasma albumin concentrations. Plasma levels of fibrinogen and C-reactive protein (CRP) were measured by routine methods and used as markers of inflammation. Mean glomerular filtration rate (GFR) was 48 ml/min, and there was a positive correlation between GFR and thiol (r = 0.25, p < 0.05) and a negative correlation between GFR and carbonyl (r = -0.26, p < 0.05), fibrinogen (r = -0.45, p < 0.0001) and CRP (r = -0.14, p = ns). Carbonyl strongly correlated with CRP (0.49, p < 0.0001) and fibrinogen (0.30, p < 0.01). There was a significant reduction in plasma carbonyl after renal transplantation (1.4 ± 0.4 nmol/mg albumin), compared with the levels before the procedure (2.0 ± 1.4 nmol/mg albumin, p < 0.05), which parallels an improvement in thiol levels (15 ± 4 vs. 21 ± 5 nmol/mg albumin, p < 0.001). In addition, there was a significant correlation between CRP and carbonyl after the transplantation (r = 0.65; p < 0.005). We observed that patients with CKD present an altered redox status and increased signs of carbonyl stress and inflammatory activity as kidney function deteriorates, which was partially but significantly improved after renal transplantation. These findings indicate the importance of renal function in the complications of CKD related to oxidative stress and inflammation. Copyright © 2010 S. Karger AG, Basel.

MELAS Syndrome and Kidney Disease Without Fanconi Syndrome or Proteinuria: A Case Report.

PubMed

Rudnicki, Michael; Mayr, Johannes A; Zschocke, Johannes; Antretter, Herwig; Regele, Heinz; Feichtinger, René G; Windpessl, Martin; Mayer, Gert; Pölzl, Gerhard

2016-12-01

Mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes (MELAS syndrome) represents one of the most frequent mitochondrial disorders. The majority of MELAS cases are caused by m.3243A>G mutation in the mitochondrial MT-TL1 gene, which encodes the mitochondrial tRNA Leu(UUR) . Kidney involvement usually manifests as Fanconi syndrome or focal segmental glomerulosclerosis. We describe a patient with MELAS mutation, cardiomyopathy, and chronic kidney disease without Fanconi syndrome, proteinuria, or hematuria. While the patient was waitlisted for heart transplantation, her kidney function deteriorated from an estimated glomerular filtration rate of 33 to 20mL/min/1.73m 2 within several months. Kidney biopsy was performed to distinguish decreased kidney perfusion from intrinsic kidney pathology. Histologic examination of the biopsy specimen showed only a moderate degree of tubular atrophy and interstitial fibrosis, but quantitative analysis of the m.3243A>G mitochondrial DNA mutation revealed high heteroplasmy levels of 89% in the kidney. Functional assessment showed reduced activity of mitochondrial enzymes in kidney tissue, which was confirmed by immunohistology. In conclusion, we describe an unusual case of MELAS syndrome with chronic kidney disease without apparent proteinuria or tubular disorders associated with Fanconi syndrome, but widespread interstitial fibrosis and a high degree of heteroplasmy of the MELAS specific mutation and low mitochondrial activity in the kidney. Copyright © 2016 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.

Lack of Correlation between Periodontitis and Renal Dysfunction in Systemically Healthy Patients

PubMed Central

Brotto, Renata Squariz; Vendramini, Regina Célia; Brunetti, Iguatemy Lourenço; Marcantonio, Rosemary Adriana Chierici; Ramos, Adriana Pelegrino Pinho; Pepato, Maria Teresa

2011-01-01

Objectives: The aim of this study was to assess a suggested association between periodontitis and renal insufficiency by assaying kidney disease markers. Methods: Variables used to diagnose periodontitis were: (i) probing pocket depth (PPD), (ii) attachment loss (AL), (iii) bleeding on probing (BOP), (iv) plaque index (PI) and (v) extent and severity index. Blood and urine were collected from 60 apparently healthy non-smokers (men and women), consisting of a test group of 30 subjects with periodontitis (age 46±6 yrs) and a control group of 30 healthy subjects (age 43±5 yrs). Kidney function markers (urea, creatinine, uric acid and albumin contents) were measured in the serum and urine. Also, the glomerular filtration rate was estimated from creatinine clearance, from the abbreviated Modification of Diet in Renal Disease formula and from the albumin : creatinine ratio in a 24–h sample of urine. Results: It was found that the control group had a greater mean number of teeth than the test group and that the two groups also differed in PPD, AL, BOP and PI, all these variables being higher in the test group (P=0.006). For the extent and severity index of both PPD and AL, the test group had much higher medians of both extent and severity than the control group (P=0.001). With regard to kidney function, none of the markers revealed a significant difference between the control and test groups and all measured values fell within the reference intervals. Conclusions: It is proposed that severe periodontitis is not associated with any alteration in kidney function. PMID:21228952

Autosomal Dominant Polycystic Kidney Disease

MedlinePlus

... replacement therapies—hemodialysis and kidney transplantation, developed through fundamental NIH research in the 1960s—were increasingly available ... possible to restore lost kidney function. More aggressive management of diabetes and high blood pressure, as well ...

Frailty, Kidney Function, and Polypharmacy: The Atherosclerosis Risk in Communities (ARIC) Study.

PubMed

Ballew, Shoshana H; Chen, Yan; Daya, Natalie R; Godino, Job G; Windham, B Gwen; McAdams-DeMarco, Mara; Coresh, Josef; Selvin, Elizabeth; Grams, Morgan E

2017-02-01

Frail individuals are at increased risk for poor outcomes, including adverse drug events. Kidney function is often compromised in frailty and is a key consideration in medication choice and dosing; however, creatinine-based measures of kidney function may be biased in frail individuals. Observational study. 4,987 community-dwelling older men and women with complete data who participated in visit 5 of the Atherosclerosis Risk in Communities (ARIC) Study (2011-2013). Kidney measures included glomerular filtration rate (GFR) estimated using serum creatinine (eGFR cr ) and serum cystatin C level (eGFR cys ) and urine albumin-creatinine ratio. Frailty, defined using established criteria of 3 or more frailty characteristics (weight loss, slowness, exhaustion, weakness, and low physical activity). 341 (7%) participants were classified as frail, 1,475 (30%) had eGFR cr <60mL/min/1.73m 2 , 2,480 (50%) had eGFR cys <60mL/min/1.73m 2 , and 1,006 (20%) had albuminuria with albumin excretion ≥ 30mg/g. Among frail participants, prevalences of eGFR cr and eGFR cys <60mL/min/1.73m 2 were 45% and 77%, respectively. Adjusted for covariates, frailty showed a moderate association with eGFR cr and a strong association with eGFR cys and albumin-creatinine ratio. Frail individuals with eGFR cr of 60 to <75mL/min/1.73m 2 were frequently reclassified to lower eGFR categories using eGFR cys (49% to 45-<60, 32% to 30-<45, and 3% to <30mL/min/1.73m 2 ). Hyperpolypharmacy (taking ≥10 classes of medications) was more common in frail individuals (54% vs 38% of nonfrail), including classes requiring kidney clearance (eg, digoxin) and associated with falls and subsequent complications (eg, hypnotic/sedatives and anticoagulants). Cross-sectional study design. Frail individuals had a high prevalence of reduced kidney function, with large discrepancies when reduced kidney function was classified by eGFR cys versus eGFR cr . Given the substantial medication burden and uncertainty in chronic kidney disease classification, confirmation of kidney function with alternative biomarkers may be warranted to ensure careful prescribing practices in this vulnerable population. Copyright © 2016 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.

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.

Intermediate-Term Outcomes of Dual Adult versus Single-Kidney Transplantation: Evolution of a Surgical Technique.

PubMed

Islam, Ana K; Knight, Richard J; Mayer, Wesley A; Hollander, Adam B; Patel, Samir; Teeter, Larry D; Graviss, Edward A; Saharia, Ashish; Podder, Hemangshu; Asham, Emad H; Gaber, A Osama

2016-01-01

Background. Acceptance of dual kidney transplantation (DKT) has proven difficult, due to surgical complexity and concerns regarding long-term outcomes. We herein present a standard technique for ipsilateral DKT and compare outcomes to single-kidney transplant (SKT) recipients. Methods. A retrospective single-center comparison of DKT and SKT performed between February 2007 and July 2013. Results. Of 516 deceased donor kidney transplants, 29 were DKT and 487 were SKT. Mean follow-up was 43 ± 67 months. DKT recipients were older and more likely than SKT recipients to receive an extended criteria graft (p < 0.001). For DKT versus SKT, the rates of delayed graft function (10.3 versus 9.2%) and acute rejection (20.7 versus 22.4%) were equivalent (p = ns). A higher than expected urologic complication rate in the DKT cohort (14 versus 2%, p < 0.01) was reduced through modification of the ureteral anastomosis. Graft survival was equivalent between DKT and SKT groups (p = ns) with actuarial 3-year DKT patient and graft survivals of 100% and 93%. At 3 years, the groups had similar renal function (p = ns). Conclusions. By utilizing extended criteria donor organs as DKT, the donor pool was enlarged while providing excellent patient and graft survival. The DKT urologic complication rate was reduced by modification of the ureteral anastomosis.

Intermediate-Term Outcomes of Dual Adult versus Single-Kidney Transplantation: Evolution of a Surgical Technique

PubMed Central

Islam, Ana K.; Mayer, Wesley A.; Hollander, Adam B.; Patel, Samir; Teeter, Larry D.; Graviss, Edward A.; Saharia, Ashish; Podder, Hemangshu; Asham, Emad H.; Gaber, A. Osama

2016-01-01

Background. Acceptance of dual kidney transplantation (DKT) has proven difficult, due to surgical complexity and concerns regarding long-term outcomes. We herein present a standard technique for ipsilateral DKT and compare outcomes to single-kidney transplant (SKT) recipients. Methods. A retrospective single-center comparison of DKT and SKT performed between February 2007 and July 2013. Results. Of 516 deceased donor kidney transplants, 29 were DKT and 487 were SKT. Mean follow-up was 43 ± 67 months. DKT recipients were older and more likely than SKT recipients to receive an extended criteria graft (p < 0.001). For DKT versus SKT, the rates of delayed graft function (10.3 versus 9.2%) and acute rejection (20.7 versus 22.4%) were equivalent (p = ns). A higher than expected urologic complication rate in the DKT cohort (14 versus 2%, p < 0.01) was reduced through modification of the ureteral anastomosis. Graft survival was equivalent between DKT and SKT groups (p = ns) with actuarial 3-year DKT patient and graft survivals of 100% and 93%. At 3 years, the groups had similar renal function (p = ns). Conclusions. By utilizing extended criteria donor organs as DKT, the donor pool was enlarged while providing excellent patient and graft survival. The DKT urologic complication rate was reduced by modification of the ureteral anastomosis. PMID:27478630

Glomerular Podocytes Express Type 1 Adenylate Cyclase: Inactivation Results in Susceptibility to Proteinuria

PubMed Central

Xiao, Zhijie; He, Liqun; Takemoto, Minoru; Jalanko, Hannu; Chan, Guy C.; Storm, Daniel R.; Betsholtz, Christer; Tryggvason, Karl; Patrakka, Jaakko

2011-01-01

Background/Aims The organization of actin cytoskeleton in podocyte foot processes plays a critical role in the maintenance of the glomerular filtration barrier. The cAMP pathway is an important regulator of the actin network assembly in cells. However, the role of the cAMP pathway in podocytes is not well understood. Type 1 adenylate cyclase (Adcy1), previously thought to be specific for neuronal tissue, is a member of the family of enzymes that catalyses the formation of cAMP. In this study, we characterized the expression and role of Adcy1 in the kidney. Methods Expression of Adcy1 was studied by RT-PCR, Northern blotting and in situ hybridization. The role of Adcy1 in podocytes was investigated by analyzing Adcy1 knockout mice (Adcy1–/–). Results and Conclusion: Adcy1 is expressed in the kidney specifically by podocytes. In the kidney, Adcy1 does not have a critical role in normal physiological functioning as kidney histology and function are normal in Adcy1–/– mice. However, albumin overload resulted in severe albuminuria in Adcy1–/– mice, whereas wild-type control mice showed only mild albumin leakage to urine. In conclusion, we have identified Adcy1 as a novel podocyte signaling protein that seems to have a role in compensatory physiological processes in the glomerulus. PMID:21196775

[Contribution of X-ray computed tomography in the evaluation of kidney performance].

PubMed

Lemoine, Sandrine; Rognant, Nicolas; Collet-Benzaquen, Diane; Juillard, Laurent

2012-07-01

X-ray computer assisted tomography scanner is an imaging method based on the use of X-ray attenuation in tissue. This attenuation is proportional to the density of the tissue (without or after contrast media injection) in each pixel image of the image. Spiral scanner, the electron beam computed tomography (EBCT) scanner and multidetector computed tomography scanner allow renal anatomical measurements, such as cortical and medullary volume, but also the measurement of renal functional parameters, such as regional renal perfusion, renal blood flow and glomerular filtration rate. These functional parameters are extracted from the modeling of the kinetics of the contrast media concentration in the vascular space and the renal tissue, using two main mathematical models (the gamma variate model and the Patlak model). Renal functional imaging allows measuring quantitative parameters on each kidney separately, in a non-invasive manner, providing significant opportunities in nephrology, both for experimental and clinical studies. However, this method uses contrast media that may alter renal function, thus limiting its use in patients with chronic renal failure. Moreover, the increase irradiation delivered to the patient with multi detector computed tomography (MDCT) should be considered. Copyright © 2011 Association Société de néphrologie. Published by Elsevier SAS. All rights reserved.

Cordyceps sinensis (a traditional Chinese medicine) for kidney transplant recipients.

PubMed

Hong, Tao; Zhang, Minghua; Fan, Junming

2015-10-12

Kidney transplantation is the treatment of choice for patients with end-stage kidney disease (ESKD). Rising ESKD prevalence has substantially increased numbers of kidney transplants performed. Maintenance immunosuppression is long-term treatment to prevent acute rejection and deterioration of graft function. Although immunosuppressive treatment using drugs such as calcineurin inhibitors (CNIs, such as cyclosporin A (CsA) or tacrolimus) reduce acute rejection rates, long-term allograft survival rates are not significantly enhanced. CNI-related adverse effects contribute to reduced quality of life among kidney transplant recipients. Adjuvant immunosuppressive therapies that could offer a synergetic immunosuppressive effect, while minimising toxicity and reducing side effects, have been explored recently. Cordyceps sinensis, (Cordyceps) a traditional Chinese medicine, is used as an adjuvant immunosuppressive agent in maintenance treatment for kidney transplantation recipients in China, but there is no consensus about its use as an adjuvant immunosuppressive treatment for kidney transplantation recipients. This review aimed to evaluate the benefits and potential adverse effects of Cordyceps as an adjuvant immunosuppressive treatment for kidney transplant recipients. We searched the Cochrane Kidney and Transplant Specialised Register through contact with the Trials Search Co-ordinator to 7 September 2015 using search terms relevant to this review. We also searched Chinese language databases and other resources. We included all randomised controlled trials (RCTs) and quasi-RCTs evaluating the benefits and potential side effects of Cordyceps sinensis for kidney transplant recipients, irrespective of blinding or publication language. An inclusion criterion was that baseline immunosuppressive therapy must be the same in all study arms. Two authors extracted data. We derived risk ratios (RR) for dichotomous data and mean differences (MD) for continuous data with 95% confidence intervals (CI). Our review included five studies (six reports; 447 participants) that assessed Cordyceps. Limited reporting of study methods and data meant that all included studies were assessed as having unclear risks of bias. The studies investigated Cordyceps compared with azathioprine (AZA) (4 studies, 265 participants) and Cordyceps plus low dose CsA versus standard dose CsA (1 study, 182 participants).Compared with AZA, Cordyceps showed no significant difference in graft or patient survival, but improved graft function and may reduce acute rejection episodes. Anaemia, leucopenia, and liver function improved, and incidence of infection may also be reduced.Compared with low dose CsA versus standard dose CsA, Cordyceps did not demonstrate any statistically significant differences in patient survival, graft loss, acute rejection or allograft function. There was limited low quality evidence to suggest benefits in pulmonary infection, serum albumin, serum uric acid levels, CNI nephrotoxicity and hepatotoxicity.None of the included studies reported on quality of life, and follow-up was short-term (three months to one year). Given the limited number of small studies, and high risk of bias, results should be interpreted with caution. Although there were some favourable aspects associated with Cordyceps, longer-term studies are needed to clarify any benefit-harm trade-off. Future studies should investigate the use of Cordyceps in combination with other immunosuppressive agents such as tacrolimus, mycophenolate mofetil or induction therapy. Such studies also need to be appropriately sized and powered.

The pathologic physiology of chronic Bright's disease. An exposition of the "intact nephron hypothesis".

PubMed

Bricker, N S; Morrin, P A; Kime, S W

1997-09-01

Clinical and experimental data relating to the functional capacity of the surviving nephrons of the chronically diseased kidney for the most part support the thesis that these nephrons retain their essential functional integrity regardless of the nature of the underlying form of chronic Bright's disease. There are instances in which specific alterations of function correlate with pathologic involvement of a particular site of the nephron but these appear to represent the exceptions, and in general the more advanced the disease becomes, the less evident are the differentiating features. Studies on dogs with unilateral renal disease indicate that the functional capacity of the nephrons of the diseased kidney parallels that of the nephrons of the contralateral normal kidney. These data tend to exclude widespread intrinsic damage to the functioning nephrons by the underlying pathologic processes. From these observations, as well as from certain supporting clinical and experimental observations, it is suggested that the majority of surviving nephrons in the patient with bilateral renal disease similarly are functionally intact. Concepts of the pathologic physiology of the kidney, based on the "intact nephron hypothesis", are presented. Within the framework of this hypothesis it is concluded that (1) the diseased kidney consists of a diminished number of nephrons, most of which retain essentially normal functional abilities; (2) certain of the apparent abnormalities in function in bilateral renal disease may relate to adaptive changes imposed by the decreased nephron population and the attendant derangements in body fluids rather than to structural distortion of nephrons; (3) the over-all flexibility of the diseased kidney decreases as the number of constituent nephrons decreases; but (4) there is an orderly and predictable pattern of excretion for all substances.

Supplementing diet with Manitoba lingonberry juice reduces kidney ischemia-reperfusion injury.

PubMed

Isaak, Cara K; Wang, Pengqi; Prashar, Suvira; O, Karmin; Brown, Daniel Cw; Debnath, Samir C; Siow, Yaw L

2017-07-01

Lingonberry (Vaccinium vitis-idaea L.) contains high levels of anthocyanins which are bioavailable in the kidney and may be protective against ischemia-reperfusion (IR)-induced acute kidney injury. This study investigated the effect of lingonberry juice on the IR-induced stress-activated signalling pathway and inflammatory response in the kidney. Sprague-Dawley rats subjected to kidney IR had significantly impaired kidney function, with increased activation of the JNK signalling pathway and increased inflammatory response, measured using a multiplex panel containing an extensive array of inflammatory biomarkers. In rats fed 1 mL lingonberry juice daily for 3 weeks prior to IR, kidney function was protected and attenuation of inflammatory response and JNK signalling was reflected in the reduction of the measured biomarkers. In vitro results in cultured HK-2 cells confirmed that lingonberry anthocyanins reduced JNK signalling and inflammatory gene expression after IR. This study shows, for the first time, that daily supplementation with lingonberry juice may protect against loss of kidney function induced by IR injury by modulating JNK signalling and inhibiting the subsequent inflammatory response. © 2017 Her Majesty the Queen in Right of Canada. Journal of the Science of Food and Agriculture © 2017 Society of Chemical Industry. © 2017 Her Majesty the Queen in Right of Canada. Journal of the Science of Food and Agriculture © 2017 Society of Chemical Industry.

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.

Successful Dual Kidney Transplantation After Hypothermic Oxygenated Perfusion of Discarded Human Kidneys

PubMed Central

Ravaioli, Matteo; De Pace, Vanessa; Comai, Giorgia; Busutti, Marco; Gaudio, Massimo Del; Amaduzzi, Annalisa; Cucchetti, Alessandro; Siniscalchi, Antonio; La Manna, Gaetano; D’Errico, Antonietta A.D.; Pinna, Antonio Daniele

2017-01-01

Patient: Female, 58 Final Diagnosis: Nephroangiosclerosis Symptoms: Renal failure Medication: — Clinical Procedure: Resuscitation of grafts by hypothermic oxygenated perfusion Specialty: Transplantology Objective: Challenging differential diagnosis Background: The recovery of discarded human kidneys has increased in recent years and impels to use of unconventional organ preservation strategies that improve graft function. We report the first case of human kidneys histologically discarded and transplanted after hypothermic oxygenated perfusion (HOPE). Case Report: Marginal kidneys from a 78-year-old woman with brain death were declined by Italian transplant centers due to biopsy score (right kidney: 6; left kidney: 7). We recovered and preserved both kidneys through HOPE and we revaluated their use for transplantation by means of perfusion parameters. The right kidney was perfused for 1 h 20 min and the left kidney for 2 h 30 min. During organ perfusion, the renal flow increased progressively. We observed an increase of 34% for the left kidney (median flow 52 ml/min) and 50% for the right kidney (median flow 24 ml/min). Both kidneys had low perfusate’s lactate levels. We used perfusion parameters as important determinants of the organ discard. Based on our previous organ perfusion experience, the increase of renal flow and the low level of lactate following 1 h of HOPE lead us to declare both kidneys as appropriate for dual kidney transplantation (DKT). No complications were reported during the transplant and in the post-transplant hospital stay. The recipient had immediate graft function and serum creatinine value of 0.95 mg/dL at 3 months post-transplant. Conclusions: HOPE provides added information in the organ selection process and may improve graft quality of marginal kidneys. PMID:28928357

Biological Effect of Cynara cardunculus on Kidney Status of Hypercholesterolemic Rats

PubMed Central

Alkushi, Abdullah Glil

2017-01-01

Context: Cynara cardunculus or artichoke thistle belongs to the sunflower family and has a variety of cultivable forms. Historically, it was cultivated as a vegetable, but more recently, it is being used in cheese and biofuel preparation. Artichoke leaf extracts are also known for its medicinal purposes, particularly in reducing the elevated cholesterol levels in blood. Hypercholesterolemia (HC) is also associated with other complications such as impaired renal function and diabetes mellitus. A remedy without major side effects for HC and its associated complications is highly desirable. Aims: We explored the effect of artichoke on the kidneys of hypercholesterolemic adult male Sprague–Dawley albino rats. Subjects and Methods: Oral administration of 200 mg/kg and 400 mg/kg body weight (b.wt.) of C. cardunculus leaf extract (CCL) and C. cardunculus pulp extract (CCP) was made to male Sprague–Dawley albino hypercholesterolemic rats and investigated the levels of glucose, creatinine, uric acid, and urea in their blood. Results: We observed that both CCL and CCP significantly reduced the creatinine and uric acid levels in the blood in a dose-dependent manner (P < 0.05). Both CCL and CCP significantly reduced the blood glucose levels (P < 0.05). Further, the histopathological investigation of the kidney sections showed that CCL treatment resolved HC-associated kidney damage. Conclusion: CCL not only has cholesterol-reducing capacity but also reduces the blood glucose levels and repairs the impaired kidney functions and damages. These findings are significant particularly because HC results in further complications such as diabetes and kidney damage, both of which can be treated effectively with artichoke. SUMMARY C. cardunculus leaf extract (CCL) not only has cholesterol-reducing capacity but also reduces the blood glucose levels and repairs the impaired kidney functions and damages. This study evaluated the nephroprotective role of CCL and CCP in hypercholesterolemic rats and observed that both CCL and CCP significantly reduced the creatinine and uric acid levels in hypercholesterolemic rats in a dose-dependent manner. Abbreviations used: HC: Hypercholesterolemia, WHO: World Health Organization, BAS: Bile acid sequestrant, PCSK9: Proprotein convertase subtilisin kexin type 9, ALE: Artichoke leaf extract, CCL: Cynara cardunculus leaf extract, CCP: Cynara cardunculus pulp extract, BWG%: Body weight gain%, FER: Food-efficiency ratio. PMID:29142395

Sleep Characteristics in Early Stages of Chronic Kidney Disease in the HypnoLaus Cohort

PubMed Central

Ogna, Adam; Forni Ogna, Valentina; Haba Rubio, José; Tobback, Nadia; Andries, Dana; Preisig, Martin; Tafti, Mehdi; Vollenweider, Peter; Waeber, Gerard; Marques-Vidal, Pedro; Heinzer, Raphaël

2016-01-01

Study Objectives: To evaluate the association between early stages of chronic kidney disease (CKD) and sleep disordered breathing (SDB), restless legs syndrome (RLS), and subjective and objective sleep quality (SQ). Methods: Cross-sectional analysis of a general population-based cohort (HypnoLaus). 1,760 adults (862 men, 898 women; age 59.3 (± 11.4) y) underwent complete polysomnography at home. Results: 8.2% of participants had mild CKD (stage 1–2, estimated glomerular filtration rate [eGFR] ≥ 60 mL/min/1.73 m2 with albuminuria) and 7.8% moderate CKD (stage 3, eGFR 30–60 mL/min/1.73 m2). 37.3% of our sample had moderate-to-severe SDB (apnea-hypopnea index [AHI] ≥ 15/h) and 15.3% had severe SDB (AHI ≥ 30/h). SDB prevalence was positively associated with CKD stages and negatively with eGFR. In multivariate analysis, age, male sex, and body mass index were independently associated with SDB (all P < 0.001), but kidney function was not. The prevalence of RLS was 17.5%, without difference between CKD stages. Periodic leg movements index (PLMI) was independently associated with CKD stages. Subjective and objective SQ decreased and the use of sleep medication was more frequent with declining kidney function. Older age, female sex, and the severity of SDB were the strongest predictors of poor SQ in multivariate regression analysis but CKD stage was also independently associated with reduced objective SQ. Conclusions: Patients with early stages of CKD have impaired SQ, use more hypnotic drugs, and have an increased prevalence of SDB and PLM. After controlling for confounders, objective SQ and PLMI were still independently associated with declining kidney function. Citation: Ogna A, Forni Ogna V, Haba Rubio J, Tobback N, Andries D, Preisig M, Tafti M, Vollenweider P, Waeber G, Marques-Vidal P, Heinzer R. Sleep characteristics in early stages of chronic kidney disease in the HypnoLaus cohort. SLEEP 2016;39(4):945–953. PMID:26715230

76 FR 42716 - Effects of Ischemia Reperfusion Injury on Outcomes in Kidney Transplantation; Public Workshop

Federal Register 2010, 2011, 2012, 2013, 2014

2011-07-19

...] Effects of Ischemia Reperfusion Injury on Outcomes in Kidney Transplantation; Public Workshop AGENCY: Food... outcomes in kidney transplantation. This public workshop is intended to obtain information from health care... for the prophylaxis and/or treatment of delayed graft function (DGF) and related conditions in kidney...

[Lithium treatment in patients with impaired kidney function: Between Scylla and Charybdis].

PubMed

Dehning, Julia; Grunze, Heinz; Born, Christoph; Hausmann, Armand

2017-05-01

Introduction In quite a few patients with bipolar disorder there is no real alternative to lithium treatment despite impaired kidney function. Is it possible to continue lithium treatment despite kidney malfunction by changing dosage and/or frequency of administration? Case Report We report on a 65-year-old woman suffering from bipolar-I disorder who had been on lithium treatment for many decades. While on lithium, the glomerular filtration rate (GFR) decreased constantly. A decision had to be made whether to switch to a more tolerable o.d. administration or to taper off lithium. Conclusion With a single dose at bedtime, the serum levels remained stable; however, kidney function unfortunately did not improve. A relevant increase of GFR above the level of 60 mL/min/1,73 m 2 was only achieved after a 50% dose reduction leading also to a substantial decrease of lithium serum levels. A kidney protective lithium application in patients with reduced renal function is like sailing between Scylla and Charybdis. Georg Thieme Verlag KG Stuttgart · New York.

The biomechanics of the kidney: the isothermal function of the capsule adipose renis.

PubMed

Rados, N; Keros, P; Trnski, D; Muftić, O

1993-01-01

The paper describes the research in the field of thermodynamics. It deals with the function of capsule adipose renis. This homogenous tissue of low temperature acts as an independent thermal conductor. In fact, by encapsulating the kidney, it acts as a vacuum-flask, providing insulation for the kidney from two surrounding thermal areas, the warmer being on the interperitoneum and the cooler on the skin surface.

Recurrent clot anuria following laparoscopic pyeloplasty in a solitary functioning kidney: managing with double guide wire technique

PubMed Central

Kumar, Santosh; Singh, Shivanshu; Parmar, Kalpesh Mahesh; Garg, Nitin

2014-01-01

Clot anuria in a solitary functioning kidney is an emergency situation. Haematuria with clot anuria in an early postoperative period represents a challenge, as treatment options are limited. Manipulation of the anastomotic site may lead to anastomotic disruption and urinoma while use of thrombolytic therapy poses the danger of increasing haematuria. We report a case of anuria due to clot retention in the upper tract following laparoscopic dismembered pyeloplasty in a solitary functioning kidney, managed successfully with double guide wire technique. PMID:25540210

Association of Metabolic Syndrome With Kidney Function and Histology in Living Kidney Donors

PubMed Central

Ohashi, Y.; Thomas, G.; Nurko, S.; Stephany, B.; Fatica, R.; Chiesa, A.; Rule, A. D.; Srinivas, T.; Schold, J. D.; Navaneethan, S. D.; Poggio, E. D.

2013-01-01

The selection of living kidney donors is based on a formal evaluation of the state of health. However, this spectrum of health includes subtle metabolic derangements that can cluster as metabolic syndrome. We studied the association of metabolic syndrome with kidney function and histology in 410 donors from 2005 to 2012, of whom 178 donors were systematically followed after donation since 2009. Metabolic syndrome was defined as per the NCEP ATPIII criteria, but using a BMI > 25 kg/m2 instead of waist circumference. Following donation, donors received counseling on lifestyle modification. Metabolic syndrome was present in 50 (12.2%) donors. Donors with metabolic syndrome were more likely to have chronic histological changes on implant biopsies than donors with no metabolic syndrome (29.0% vs. 9.3%, p < 0.001). This finding was associated with impaired kidney function recovery following donation. At last follow-up, reversal of metabolic syndrome was observed in 57.1% of donors with predonation metabolic syndrome, while only 10.8% of donors developed de novo metabolic syndrome (p < 0.001). In conclusion, metabolic syndrome in donors is associated with chronic histological changes, and nephrectomy in these donors was associated with subsequent protracted recovery of kidney function. Importantly, weight loss led to improvement of most abnormalities that define metabolic syndrome. PMID:23865821

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

Preeclampsia Risks in Kidney Donors and Recipients.

PubMed

Shah, Pratik B; Samra, Manpreet; Josephson, Michelle A

2018-06-08

To review the studies and practice guidelines on the preeclampsia risks in kidney donors and recipients. There is a small increased risk of gestational hypertension and preeclampsia in pregnancies that follow kidney donation. Kidney Disease Improving Global Outcomes (KDIGO) Clinical Practice Guideline (2017) and the 2015 American Society of Transplantation (AST) consensus conference statement recommends counseling kidney donors about this increased risk. There is no observed increase in fetal complications or eclampsia post-kidney donation. Preeclampsia is more commonly observed in kidney transplant recipients than the general population and these patients should be co-managed with an obstetrician with experience in managing high risk pregnancies. Although preeclampsia has not been found to have a deleterious effect on renal graft function, it can cause premature delivery. Risk calculators have been proposed and an elevated pre-pregnancy creatinine seems to be an important risk. KDIGO Clinical Practice Guidelines (2009) recommends attempting pregnancy when kidney function is stable with proteinuria of less than 1 g per day. The use of novel biomarkers for preeclampsia has not been published in this population. Preeclampsia is an important concern for female kidney donors and recipients of child-bearing age. These individuals should be appropriately counseled.

The protective role of bee honey against the toxic effect of melamine in the male rat kidney.

PubMed

Al-Seeni, Madeha N; El Rabey, Haddad A; Al-Solamy, Suad M

2015-06-01

This study aimed to test the protective role of natural bee honey against melamine toxicity in the kidney of male albino rats. The dietary supplementation of melamine at a dose of 20,000 ppm for 28 days induced renal dysfunction, as reflected by a significant increase in kidney function parameters (urea, creatinine, and uric acid) and an increase in potassium levels. In addition, a decrease in catalase and glutathione-S-transferase and an increase in lipid peroxide in the kidney tissue homogenate were also observed. Histological changes in the melamine-treated group revealed hyperplasia and damage in kidney cells and the accumulation of melamine crystals in kidney tissues. Honey treatment for 28 days in rats concurrently administered melamine at a dose of 2.5 g/kg body weight for 28 days improved the kidney function, increased antioxidant enzymes, and decreased lipid peroxide levels. The morphology of the kidney cells of the melamine-fed rats was also improved as a result of honey treatment. In conclusion, this study revealed that natural bee honey protects the kidney against the adverse effects induced by melamine toxicity in male albino rats. © The Author(s) 2014.

Natural killer cell function predicts severe infection in kidney transplant recipients.

PubMed

Dendle, Claire; Gan, Poh-Yi; Polkinghorne, Kevan R; Ngui, James; Stuart, Rhonda L; Kanellis, John; Thursky, Karin; Mulley, William R; Holdsworth, Stephen

2018-04-30

The aim of this study was to determine if natural killer cell number (CD3 - /CD16 ± /CD56 ± ) and cytotoxic killing function predicts severity and frequency of infection in kidney transplant recipients. A cohort of 168 kidney transplant recipients with stable graft function underwent assessment of natural killer cell number and functional killing capacity immediately prior to entry into this prospective study. Participants were followed for 2 years for development of severe infection, defined as hospitalization for infection. Area under receiver operating characteristic (AUROC) curves were used to evaluate the accuracy of natural killer cell number and function for predicting severe infection. Adjusted odds ratios were determined by logistic regression. Fifty-nine kidney transplant recipients (35%) developed severe infection and 7 (4%) died. Natural killer cell function was a better predictor of severe infection than natural killer cell number: AUROC 0.84 and 0.75, respectively (P = .018). Logistic regression demonstrated that after adjustment for age, transplant function, transplant duration, mycophenolate use, and increasing natural killer function (odds ratio [OR] 0.82, 95% confidence interval [CI] 0.74-0.90; P < .0001) but not natural killer number (OR 0.96, 95% CI 0.93-1.00; P = .051) remained significantly associated with a reduced likelihood of severe infection. Natural killer cell function predicts severe infection in kidney transplant recipients. © 2018 The American Society of Transplantation and the American Society of Transplant Surgeons.

Case Report: First Reported Combined Heart-Liver Transplant in a Patient With a Congenital Solitary Kidney.

PubMed

Hanna, R M; Kamgar, M; Hasnain, H; Khorsan, R; Nsair, A; Kaldas, F; Baas, A; Bunnapradist, S; Wilson, J M

2018-04-01

We report a case of successful combined heart liver transplant in a patient with a congenital solitary kidney. The patient had normal renal function before combined heart-liver transplantation and developed acute kidney injury requiring slow continuous dialysis and subsequent intermittent dialysis for almost 8 weeks post transplantation. Her renal function recovered and she remains off dialysis now 7 months post transplantation. She only currently has mild chronic renal insufficiency. We believe this is the first reported case of successful heart liver transplant in a patient with a congenital solitary kidney. Published by Elsevier Inc.

[The method of tonifying kidneys and activating blood circulation increases testosterone secretion index in late-onset hypogonadism males with kidney deficiency].

PubMed

Zhou, Shao-Hu; Weng, Zhi-Wei; Li, Tang-Lin

2013-07-01

To investigate the effect of the method of tonifying the kidney and activating blood circulation on the testosterone secretion index (TSI) in late-onset hypogonadism (LOH) male patients with kidney deficiency and its possible mechanisms. We screened 60 LOH male patients with kidney deficiency based on the scores on Partial Androgen Deficiency in Aging Males (PADAM), the levels of serum total testosterone (TT) and luteinizing hormone (LH), and TSI (TT/LH). We randomly divided the patients into a Nan Geng Ning (NGN) group (n = 40, aged 55.02 +/- 11.37 years) and a control group (n = 20, aged 54.56 +/- 12.12 years) to be treated orally with NGN decoction and testosterone undecanoate capsules, respectively, both for 12 consecutive weeks. We obtained the scores on psychological status, physical status and sexual function and observed the changes in serum TT, LH and TSI after 4, 8 and 12 weeks of treatment. Compared with the baseline, both the NGN and control groups showed a significant reduction after 12 weeks of medication in the LH level ([5.32 +/- 2.08] vs [4.89 +/- 1.46] IU/L and [5.36 +/- 2.07] vs [4.81 +/- 1.75] IU/L, P < 0.05), psychological status score (5.2 +/- 1.3 vs 2.7 +/- 1.4 and 4.8 +/- 2.2 vs 2.9 +/- 1.2, P < 0.05), physical status score (6.9 +/- 2.5 vs 2.9 +/- 1.6 and 7.1 +/- 2.7 vs 3.1 +/- 1.5, P < 0.05) and sexual function score (10.2 +/- 3.3 vs 4.5 +/- 2.9 and 9.8 +/- 3.1 vs 4.8 +/- 3.0, P < 0.05), but a remarkable increase in the TT level ([11.13 +/- 0.69] vs [14.55 +/- 0.75] nmol/L and [10.99 +/- 0.74] vs [14.74 +/- 0.83] nmol/L, P < 0.05) and TSI ([2.14 +/- 0.65] vs [2.99 +/- 0.72] nmol/IU and ([2.05 +/- 0.73] vs [3.11 +/- 0.65] nmol/IU, P < 0.05). However, no significant differences were found between the NGN and control groups at 12 weeks in LH ([4.89 +/- 1.46] vs [4.81 +/- 1.75] IU/L, P > 0.05), TT ([14.55 +/- 0.75] vs [14.74 +/- 0.83] nmol/L, P > 0.05), TSI ([2.99 +/- 0.72] vs [3.11 +/- 0.65] nmol/IU, P > 0.05), psychological status score (2.7 +/- 1.4 vs 2.9 +/- 1.2, P > 0.05), physi- cal status score (2.9 +/- 1.6 vs 3.1 +/- 1.5, P > 0.05) and sexual function score (4.5 +/- 2.9 vs 4.8 +/- 3.0, P > 0.05). There were no adverse events in either of the two groups throughout the whole experiment. The method of tonifying the kidney and activating blood circulation could significantly improve the clinical symptoms of LOH with kidney deficiency and increase the patient's serum TT level and TSI. NGN decoction works on LOH by acting on the hypothalamic-pituitary-gonad axis.

Impact of Stone Removal on Renal Function: A Review

PubMed Central

Wood, Kyle; Keys, Tristan; Mufarrij, Patrick; Assimos, Dean G

2011-01-01

Stone removal can improve renal function by eradicating obstruction and, in certain cases, an underlying infection. Stone-removing procedures, however, may negatively impact functional integrity. Many things may impact the latter, including the procedures used, the methods of assessing function, the time when these assessments are made, the occurrence of complications, the baseline condition of the kidney, and patient-related factors. In the majority of cases, little significant functional impairment occurs. However, there are gaps in our knowledge of this subject, including the cumulative effects of multiple procedures violating the renal parenchyma and long-term functional outcomes. PMID:21935339

The impact of gut microbiota on kidney function and pathogenesis.

PubMed

Mahmoodpoor, Fariba; Rahbar Saadat, Yalda; Barzegari, Abolfazl; Ardalan, Mohammadreza; Zununi Vahed, Sepideh

2017-09-01

Chronic kidney diseases (CKDs) are a global health problem. Besides diverse leading reasons in initiation and progression of CKDs, it is evident that they might largely originate from changes in the gut microbial community (microbiota). Mounting evidence indicates that a bidirectional relationship exists between host and microbiome in humans and animals with CKDs. Changes in the microbiota composition and structure (dysbiosis) produce excessive amounts of uremic toxins (e.g. indoxyl sulfate, p-cresyl sulfate and trimethylamine-N-oxide) but less reno-protective metabolites that are implicated in oxidative stress, uremia, inflammation, deterioration of kidney function, kidney diseases progression, a higher prevalence of cardiovascular risk, and mortality in patients with CKD. The present review focuses on the pathogenic association between gut microbiota and kidney diseases like CKD, IgA nephropathy, and kidney stone disease. Certainly, novel insights into the impact of the gut microbiota in kidney diseases can be helpful to develop therapeutic strategies in order to avoid and/or treat aforementioned conditions. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

SECRETED KLOTHO AND CHRONIC KIDNEY DISEASE

PubMed Central

Hu, Ming Chang; Kuro-o, Makoto; Moe, Orson W.

2013-01-01

Soluble Klotho (sKl) in the circulation can be generated directly by alterative splicing of the Klotho transcript or the extracellular domain of membrane Klotho can be released from membrane-anchored Klotho on the cell surface. Unlike membrane Klotho which functions as a coreceptor for fibroblast growth factor-23 (FGF23), sKl, acts as hormonal factor and plays important roles in anti-aging, anti-oxidation, modulation of ion transport, and Wnt signaling. Emerging evidence reveals that Klotho deficiency is an early biomarker for chronic kidney diseases as well as a pathogenic factor. Klotho deficiency is associated with progression and chronic complications in chronic kidney disease including vascular calcification, cardiac hypertrophy, and secondary hyperparathyroidism. In multiple experimental models, replacement of sKl, or manipulated up-regulation of endogenous Klotho protect the kidney from renal insults, preserve kidney function, and suppress renal fibrosis, in chronic kidney disease. Klotho is a highly promising candidate on the horizon as an early biomarker, and as a novel therapeutic agent for chronic kidney disease. PMID:22396167

What happens to the heart in chronic kidney disease?

PubMed

Rutherford, E; Mark, P B

2017-03-01

Cardiovascular disease is common in patients with chronic kidney disease. The increased risk of cardiovascular disease seen in this population is attributable to both traditional and novel vascular risk factors. Risk of sudden cardiac or arrhythmogenic death is greatly exaggerated in chronic kidney disease, particularly in patients with end stage renal disease where the risk is roughly 20 times that of the general population. The reasons for this increased risk are not entirely understood and while atherosclerosis is accelerated in the presence of chronic kidney disease, premature myocardial infarction does not solely account for the excess risk. Recent work demonstrates that the structure and function of the heart starts to alter early in chronic kidney disease, independent of other risk factors. The implications of cardiac remodelling and hypertrophy may predispose chronic kidney disease patients to heart failure, arrhythmia and myocardial ischaemia. Further research is needed to minimise cardiovascular risk associated with structural and functional heart disease associated with chronic kidney disease.

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.

Curcumin attenuates high glucose-induced podocyte apoptosis by regulating functional connections between caveolin-1 phosphorylation and ROS

PubMed Central

Sun, Li-na; Liu, Xiang-chun; Chen, Xiang-jun; Guan, Guang-ju; Liu, Gang

2016-01-01

Aim: Caveolin-1 (cav-1) is a major multifunctional scaffolding protein of caveolae. Cav-1 is primarily expressed in mesangial cells, renal proximal tubule cells and podocytes in kidneys. Recent evidence shows that the functional connections between cav-1 and ROS play a key role in many diseases. In this study we investigated whether regulating the functional connections between cav-1 and ROS in kidneys contributed to the beneficial effects of curcumin in treating diabetic nephropathy in vitro and in vivo. Methods: Cultured mouse podocytes (mpc5) were incubated in a high glucose (HG, 30 mmol/L) medium for 24, 48 or 72 h. Male rats were injected with STZ (60 mg/kg, ip) to induce diabetes. ROS generation, SOD activity, MDA content and caspase-3 activity in the cultured cells and kidney cortex homogenate were determined. Apoptotic proteins and cav-1 phosphorylation were analyzed using Western blot analyses. Results: Incubation in HG-containing medium time-dependently increased ROS production, oxidative stress, apoptosis, and cav-1 phosphorylation in podocytes. Pretreatment with curcumin (1, 5, and 10 μmol/L) dose-dependently attenuated these abnormalities in HG-treated podocytes. Furthermore, in HG-containing medium, the podocytes transfected with a recombinant plasmid GFP-cav-1 Y14F (mutation at a cav-1 phosphorylation site) exhibited significantly decreased ROS production and apoptosis compared with the cells transfected with empty vector. In diabetic rats, administration of curcumin (100 or 200 mg/kg body weight per day, ig, for 8 weeks) not only significantly improved the renal function, but also suppressed ROS levels, oxidative stress, apoptosis and cav-1 phosphorylation in the kidneys. Conclusion: Curcumin attenuates high glucose-induced podocyte apoptosis in vitro and diabetic nephropathy in vivo partly through regulating the functional connections between cav-1 phosphorylation and ROS. PMID:26838071

The endoderm indirectly influences morphogenetic movements of the zebrafish head kidney through the posterior cardinal vein and VegfC.

PubMed

Chou, Chih-Wei; Hsu, Hsiao-Chu; You, May-Su; Lin, Jamie; Liu, Yi-Wen

2016-08-01

Integration of blood vessels and organ primordia determines organ shape and function. The head kidney in the zebrafish interacts with the dorsal aorta (DA) and the posterior cardinal vein (PCV) to achieve glomerular filtration and definitive hematopoiesis, respectively. How the head kidney co-develops with both the axial artery and vein remains unclear. We found that in endodermless sox32-deficient embryos, the head kidney associated with the PCV but not the DA. Disrupted convergent migration of the PCV and the head kidney in sox32-deficient embryos was rescued in a highly coordinated fashion through the restoration of endodermal cells. Moreover, grafted endodermal cells abutted the host PCV endothelium in the transplantation assay. Interestingly, the severely-disrupted head kidney convergence in the sox32-deficient embryo was suppressed by both the cloche mutation and the knockdown of endothelial genes, indicating that an interaction between the endoderm and the PCV restricts the migration of the head kidney. Furthermore, knockdown of either vegfC or its receptor vegfr3 suppressed the head kidney convergence defect in endodermless embryos and perturbed the head kidney-PCV association in wild-type embryos. Our findings thus underscore a role for PCV and VegfC in patterning the head kidney prior to organ assembly and function.

Arterial wave reflections and kidney function decline among persons with preserved estimated glomerular filtration rate: the Multi-Ethnic Study of Atherosclerosis.

PubMed

Hsu, Jeffrey J; Katz, Ronit; Chirinos, Julio A; Jacobs, David R; Duprez, Daniel A; Peralta, Carmen A

2016-05-01

Differences in arterial wave reflections have been associated with increased risk for heart failure and mortality. Whether these measures are also associated with kidney function decline is not well established. Reflection magnitude (RM, defined as the ratio of the backward wave [Pb] to that of the forward wave [Pf]), augmentation index (AIx), and pulse pressure amplification (PPA) were derived from radial tonometry measures among 5232 participants free of cardiovascular disease who were enrolled in the Multiethnic Study of Atherosclerosis. Kidney function was estimated by creatinine and cystatin C measurements, as well as albumin-to-creatinine ratio. We evaluated the associations of Pb, Pf, RM, AIx, and PPA with annualized estimated glomerular filtration rate (eGFR) change and rapid kidney function decline over 5 years, using generalized linear mixed models and logistic regression, respectively. Of the study participants, 48% were male, mean age was 62 years, mean eGFR and median albumin-to-creatinine ratio at baseline were 84 mL/min/1.73 m(2) and 5.3 mg/g, respectively. In demographically adjusted models, both Pb and Pf had similarly strong associations with kidney function decline; compared to those in the lowest tertiles, the persons in the highest tertiles of Pb and Pf had a 1.01 and 0.99 mL/min/1.73 m(2)/year faster eGFR decline, respectively (P < .05). However, these associations were attenuated after adjustment for systolic blood pressure. We found no significant associations between RM, AIx, or PPA and kidney function decline. In conclusion, the reflected and forward wave components were similarly associated with kidney function decline, and these associations were explained by differences in systolic blood pressure. Copyright © 2016 American Society of Hypertension. Published by Elsevier Inc. All rights reserved.

First Clinical Experience with Extracorporeally Induced Destruction of Kidney Stones by Shock Waves.

PubMed

Chaussy, Christian; Schmiedt, Egbert; Jocham, Dieter; Brendel, Walter; Forssmann, Bernd; Walther, Volker

2017-02-01

We performed extracorporeally induced destruction of kidney stones on 72 patients. No complications have resulted from the tissue exposure to high energy shock waves. Clearance studies before and after the shock wave treatment indicate no changes in renal function. The method was used successfully in all patients with stones in the renal pelvis. In none of these patients was an open operation required. Two patients with ureteral stones also were treated with shock waves but had to be operated upon because of insufficient destruction of the stone. Copyright © 2002 American Urological Association, Inc.®. Published by Elsevier Inc. All rights reserved.

Tolerance in Kidney Transplantation: What Is on the B Side?

PubMed Central

Borràs, Francesc E.

2016-01-01

Regulatory B cells (Breg) are in the spotlight for their role in immune homeostasis maintenance and tolerance achievement as in the last years the correlation with functional and increased Breg numbers in autoimmune diseases and transplantation has been extensively proven. Their study is, however, in its infancy with still little knowledge and consensus on their origin, phenotype, and mechanism of action. All this hampers the pursuit of an effective Breg induction method for therapeutic purposes. In this review we aim to summarize the studies on human Breg and their implication in kidney transplantation and to further discuss the issues surrounding therapeutic applications of this cell subset. PMID:27956762

Embryonic kidney function in a chronic renal failure model in rodents.

PubMed

Fujimoto, Eisuke; Yamanaka, Shuichiro; Kurihara, Sho; Tajiri, Susumu; Izuhara, Luna; Katsuoka, Yuichi; Yokote, Shinya; Matsumoto, Kei; Kobayashi, Eiji; Okano, Hirotaka James; Chikaraishi, Tatsuya; Yokoo, Takashi

2017-08-01

Rapid advancements have been made in alternative treatments for renal diseases. Our goal for renal regeneration is to establish a kidney graft derived from human embryonic tissues. In this study, we investigated the effects of host renal failure on the structure and activity of transplanted embryonic kidney and bladder, and found that diuretics effectively induced urine production in the transplanted kidney. Uremic conditions were reproduced using a 5/6 renal infarction rat model. An embryonic kidney plus bladder (embryonic day 15) was isolated from a pregnant Lewis rat and transplanted into the para-aortic area of a 5/6 renal-infarcted Lewis rat. Following growth, the embryonic bladder was successfully anastomosed to the host ureter. We assessed graft function in terms of survival rates and found no differences between normal (n = 5) and renal failure (n = 8) groups (median survival: 70.5 vs 74.5 h; p = 0.331) in terms of survival, indicating that the grafts prolonged rat survival, even under renal failure conditions. Furosemide (n = 9) significantly increased urine volume compared with saline-treated controls (n = 7; p < 0.05), confirming that the grafts were functional. We also demonstrated the possibilities of an in vivo imaging system for determining the viability of transplanted embryonic kidney with bladder. The results of this study demonstrate that transplanted embryonic kidney and bladder can grow and function effectively, even under uremic conditions.

[Modern biomaterials as hemostatic dressings in kidney nephron sparing surgery (NSS)--murine model. A preliminary report].

PubMed

Nowacki, Maciej; Jundziłł, Arkadiusz; Bieniek, Miłosz; Kowalczyk, Tomasz; Kloskowski, Tomasz; Drewa, Tomasz

2012-01-01

Kidney cancer is now days, one of the main problems in oncological urology. More frequent cases detection of this type of cancer and the implementation of modern methods of treatment, involves the public and good diagnostic radiological imaging methods. Approximately 40% of renal tumors are detected clinically as a changes in T1N0M0 stage. This means that in these patients, surgery can be performed using the method of nephron sparing surgery (NSS), far from consisting the implementation of radical nephrectomy. Unfortunately, despite the saving nature of this type of treatment, NSS methods are associated with local recurrence of tumor formation. Another problem is intra operative bleeding, that's why in order to stop this negative process surgeons currently use hemostatic dressings. Potentially and clinically significant solution could be a combination of this two main problematics points of concern, through the use of modern biomaterials coated on oncostatic substances as a haemostatic dressings, to the prevention of tumor recurrence. The aim of this work, was to present preliminary report of the use of advanced biomaterials, as haemostatic dressings in an experimental technique of nephron sparing surgery on an murine model. In the experiment we use two types of biomaterials and the standard haemostatic dressing used in the nephron sparing surgery (NSS) as a control. We use a polycaprolactone biomaterial obtained by electrospinning. As a second type of biomaterial, we use a homogeneous material with a structure similar to wool, also obtained from medical polycaprolactone by electrospinning. As an murine (in vivo) model in the study, we use 10 C57BL/J mice (with the local ethical committee permission). 8 mice were used in the present study, 2 mice were constituted as a separate control for obtaining the bleeding data. Kidney melanoma cells were implanted under the C57B1/J B16 mouse kidney fibrous capsule, one week before NSS. After 3 weeks the animals were sacrificed for comparison of hemostatic dressings function. Used biomaterials fulfilled their role as a hameostatic dresings. The material (Type I) was convenient and good for suturing. Haemostatic action times were as follows: (Type I) - 30 seconds. (Type III) - 50 seconds. In the control group were also observed, a proper hemostatic function after 30 seconds. In sectional observation was also found in 3 kidneys section preparation samples, a local tumor recurrence and metastasis to the other tissues of the abdomen. The tested biomaterials fulfill their hemostatic effect on kidney after NSS, without any significant difference acording to a standard hemostatic dressing used clinically. This data may be a potential factor for use in further studies to determine their continued relevance in the prevention of local tumor recurrence after nephron sparing surgery.

Primary Hyperparathyroidism

MedlinePlus

... blood calcium (above a certain level) • Impaired kidney function Non-surgical treatment: checkups and medicines For some patients without signs or symptoms, doctors recommend regular checkups instead of surgery. ... to check kidney function, and checks of bone density. A doctor may ...

Serum Neutrophil Gelatinase-Associated Lipocalin and Urinary Kidney Injury Molecule-1 as Potential Biomarkers of Subclinical Nephrotoxicity After Gadolinium-Based and Iodinated-Based Contrast Media Exposure in Pediatric Patients with Normal Kidney Function

PubMed Central

Spasojević-Dimitrijeva, Brankica; Kotur-Stevuljević, Jelena; Đukić, Milan; Paripović, Dušan; Miloševski-Lomić, Gordana; Spasojević-Kalimanovska, Vesna; Pavićević, Polina; Mitrović, Jadranka; Kostić, Mirjana

2017-01-01

Background New renal biomarkers such as neutrophil gelatinase-associated lipocalin (NGAL) and kidney injury molecule-1 (KIM-1) show promise in early diagnosis of contrast media induced acute kidney injury (CI-AKI). The purpose of our study was to compare the subclinical nephrotoxicity (a condition without changes in standard renal biomarkers) of gadolinium-based contrast media (Gd-DTPA, gadopentetate dimeglumine) and iodinated-based contrast media (iopromide) in pediatric patients with normal kidney function. Material/Methods The first group (n=58) of patients included in the study were undergoing angiography with iopromide, and the second group (n=65) were undergoing magnetic resonance (MR) angiography/urography with Gd-DTPA administration. The concentrations of NGAL and KIM-1 were measured four times in the urine (pre-contrast, then at four hours, 24 hours, and 48 hours after contrast administration), and serum NGAL was measured at 0 (baseline), 24 hours, and 48 hours after contrast exposure. Results After 24 hours, serum NGAL increase of ≥25% was noticed in 32.6% of the patients in the iopromide group and in 25.45% of the patients in the gadolinium group, with significantly higher average percent of this increase in first group (62.23% vs. 36.44%, p=0.002). In the Gd-DTPA group, we observed a statistically significant increase in urinary KIM-1 24 hours after the procedure. Normalized urinary KIM-1, 24 hours after contrast exposure, was a better predictive factor for CI-AKI than other biomarkers (AUC 0.757, cut off 214 pg/mg, sensitivity 83.3%, specificity 54.2%, p=0.035). Conclusions In children with normal renal function, exposure to iodinated-based and gadolinium-based media might lead to subclinical nephrotoxicity, which could be detected using serum NGAL and urinary KIM-1. PMID:28874655

Retinopathy and chronic kidney disease in the Chronic Renal Insufficiency Cohort (CRIC) study.

PubMed

Grunwald, Juan E; Alexander, Judith; Ying, Gui-Shuang; Maguire, Maureen; Daniel, Ebenezer; Whittock-Martin, Revell; Parker, Candace; McWilliams, Kathleen; Lo, Joan C; Go, Alan; Townsend, Raymond; Gadegbeku, Crystal A; Lash, James P; Fink, Jeffrey C; Rahman, Mahboob; Feldman, Harold; Kusek, John W; Xie, Dawei; Jaar, Bernard G

2012-09-01

To investigate the association between retinopathy and chronic kidney disease. In this observational, cross-sectional study, 2605 patients of the Chronic Renal Insufficiency Cohort (CRIC) study, a multicenter study of chronic kidney disease, were offered participation. Nonmydriatic fundus photographs of the disc and macula in both eyes were obtained in 1936 of these subjects. The photographs were reviewed in a masked fashion at a central photograph reading center using standard protocols. Presence and severity of retinopathy (diabetic, hypertensive, or other) and vessel diameter caliber were assessed by trained graders and a retinal specialist using protocols developed for large epidemiologic studies. Kidney function measurements and information on traditional and nontraditional risk factors for decreased kidney function were obtained from the CRIC study. Greater severity of retinopathy was associated with lower estimated glomerular filtration rate after adjustment for traditional and nontraditional risk factors. The presence of vascular abnormalities usually associated with hypertension was also associated with lower estimated glomerular filtration rate. We found no strong direct relationship between estimated glomerular filtration rate and average arteriolar or venular calibers. Our findings show a strong association between severity of retinopathy and its features and level of kidney function after adjustment for traditional and nontraditional risk factors for chronic kidney disease, suggesting that retinovascular pathology reflects renal disease.

Kidney regeneration by xeno-embryonic nephrogenesis.

PubMed

Yokoo, Takashi; Fukui, Akira; Matsumoto, Kei; Kawamura, Tetsuya

2008-03-01

Establishment of a functional whole kidney de novo has not received much attention because of the formidable challenges and the slow pace of advances in this field of research. This situation has changed recently with publication of data revealing the catastrophic nature of Medicaid costs for dialysis-related diseases. An innovative approach is needed in our search for therapies for kidney diseases and to provide a substitute for dialysis as soon as possible. Regenerative medicine offers great hope for realizing this goal. We established a system by which human mesenchymal stem cells can differentiate into a functional renal unit using a program of nephrogenesis in a developing xeno-embryo. In this article, recent research in the field of developing whole kidneys is reviewed, and possible therapeutic applications for kidney diseases are proposed in combination with our knowledge of the emerging field of kidney stem cell biology.

Combined heart-kidney transplantation after total artificial heart insertion.

PubMed

Ruzza, A; Czer, L S C; Ihnken, K A; Sasevich, M; Trento, A; Ramzy, D; Esmailian, F; Moriguchi, J; Kobashigawa, J; Arabia, F

2015-01-01

We present the first single-center report of 2 consecutive cases of combined heart and kidney transplantation after insertion of a total artificial heart (TAH). Both patients had advanced heart failure and developed dialysis-dependent renal failure after implantation of the TAH. The 2 patients underwent successful heart and kidney transplantation, with restoration of normal heart and kidney function. On the basis of this limited experience, we consider TAH a safe and feasible option for bridging carefully selected patients with heart and kidney failure to combined heart and kidney transplantation. Recent FDA approval of the Freedom driver may allow outpatient management at substantial cost savings. The TAH, by virtue of its capability of providing pulsatile flow at 6 to 10 L/min, may be the mechanical circulatory support device most likely to recover patients with marginal renal function and advanced heart failure. Copyright © 2015 Elsevier Inc. All rights reserved.

Kidney Transplantation Is Superior to Hemodialysis and Peritoneal Dialysis in Terms of Cognitive Function, Anxiety, and Depression Symptoms in Chronic Kidney Disease.

PubMed

Ozcan, H; Yucel, A; Avşar, U Z; Cankaya, E; Yucel, N; Gözübüyük, H; Eren, F; Keles, M; Aydınlı, B

2015-06-01

Cognitive impairment, anxiety and depression are important problems for patients with chronic kidney failure. Cognitive impairment, anxiety, and depression may be related to various factors, such as complications of hemo/peritoneal dialysis, uremic encephalopathy, psychosocial burden of the disease, and various comorbidities in patients with chronic kidney failure. Successful kidney transplantation (KT) improves kidney, endocrine, metabolic, and vascular systems, mental functions, and the quality of life of the patients. A total of 181 patients with chronic kidney failure were studied: 54 currently on hemodialysis, 58 on peritoneal dialysis, and 69 with KT. All participants were given a detailed sociodemographic form, including data about the reason of kidney failure, duration of treatment (hemodialysis, peritoneal dialysis, and KT), and comorbid illnesses. Participants were evaluated with the use of the Hospital Anxiety and Depression Scale (HADS) for evaluating depressive and anxiety symptoms and the Brief Cognitive State Examination (BCSE) for detecting possible cognitive impairment. Patients with KT had lower levels of anxiety and depression symptoms than patients with hemodialysis and peritoneal dialysis. The KT group scored better than the hemodialysis and peritoneal dialysis groups on the BCSE. The peritoneal dialysis group scored higher on the BCSE than the hemodialysis group. The hemodialysis group scored higher on the HADS than the peritoneal dialysis group. In this study it was found that KT patients have better cognitive and mood regulation outcomes than hemodialysis and peritoneal dialysis patients with chronic kidney failure. With this knowledge we suggest that patients with kidney failure should have KT for having better cognitive functions and mood state as soon as possible. Copyright © 2015 Elsevier Inc. All rights reserved.

Acute Kidney Injury in Pediatric Severe Sepsis: An Independent Risk Factor for Death and New Disability.

PubMed

Fitzgerald, Julie C; Basu, Rajit K; Akcan-Arikan, Ayse; Izquierdo, Ledys M; Piñeres Olave, Byron E; Hassinger, Amanda B; Szczepanska, Maria; Deep, Akash; Williams, Duane; Sapru, Anil; Roy, Jason A; Nadkarni, Vinay M; Thomas, Neal J; Weiss, Scott L; Furth, Susan

2016-12-01

The prevalence of septic acute kidney injury and impact on functional status of PICU survivors are unknown. We used data from an international prospective severe sepsis study to elucidate functional outcomes of children suffering septic acute kidney injury. Secondary analysis of patients in the Sepsis PRevalence, OUtcomes, and Therapies point prevalence study: acute kidney injury was defined on the study day using Kidney Disease Improving Global Outcomes definitions. Patients with no acute kidney injury or stage 1 acute kidney injury ("no/mild acute kidney injury") were compared with those with stage 2 or 3 acute kidney injury ("severe acute kidney injury"). The primary outcome was a composite of death or new moderate disability at discharge defined as a Pediatric Overall Performance Category score of 3 or higher and increased by 1 from baseline. One hundred twenty-eight PICUs in 26 countries. Children with severe sepsis in the Sepsis PRevalence, OUtcomes, and Therapies study. None. One hundred two (21%) of 493 patients had severe acute kidney injury. More than twice as many patients with severe acute kidney injury died or developed new moderate disability compared with those with no/mild acute kidney injury (64% vs 30%; p < 0.001). Severe acute kidney injury was independently associated with death or new moderate disability (adjusted odds ratio, 2.5; 95% CI, 1.5-4.2; p = 0.001) after adjustment for age, region, baseline disability, malignancy, invasive mechanical ventilation, albumin administration, and the pediatric logistic organ dysfunction score. In a multinational cohort of critically ill children with severe sepsis and high mortality rates, septic acute kidney injury is independently associated with further increased death or new disability.

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.

Predictive assessment of kidney functional recovery following ischemic injury using optical spectroscopy

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

Raman, Rajesh N.; Pivetti, Christopher D.; Ramsamooj, Rajendra

Functional changes in rat kidneys during the induced ischemic injury and recovery phases were explored using multimodal autofluorescence and light scattering imaging. We aim to evaluate the use of noncontact optical signatures for rapid assessment of tissue function and viability. Specifically, autofluorescence images were acquired in vivo under 355, 325, and 266 nm illumination while light scattering images were collected at the excitation wavelengths as well as using relatively narrowband light centered at 500 nm. The images were simultaneously recorded using a multimodal optical imaging system. We also analyzed to obtain time constants, which were correlated to kidney dysfunction asmore » determined by a subsequent survival study and histopathological analysis. This analysis of both the light scattering and autofluorescence images suggests that changes in tissue microstructure, fluorophore emission, and blood absorption spectral characteristics, coupled with vascular response, contribute to the behavior of the observed signal, which may be used to obtain tissue functional information and offer the ability to predict posttransplant kidney function.« less

Predictive assessment of kidney functional recovery following ischemic injury using optical spectroscopy

DOE PAGES

Raman, Rajesh N.; Pivetti, Christopher D.; Ramsamooj, Rajendra; ...

2017-05-03

Functional changes in rat kidneys during the induced ischemic injury and recovery phases were explored using multimodal autofluorescence and light scattering imaging. We aim to evaluate the use of noncontact optical signatures for rapid assessment of tissue function and viability. Specifically, autofluorescence images were acquired in vivo under 355, 325, and 266 nm illumination while light scattering images were collected at the excitation wavelengths as well as using relatively narrowband light centered at 500 nm. The images were simultaneously recorded using a multimodal optical imaging system. We also analyzed to obtain time constants, which were correlated to kidney dysfunction asmore » determined by a subsequent survival study and histopathological analysis. This analysis of both the light scattering and autofluorescence images suggests that changes in tissue microstructure, fluorophore emission, and blood absorption spectral characteristics, coupled with vascular response, contribute to the behavior of the observed signal, which may be used to obtain tissue functional information and offer the ability to predict posttransplant kidney function.« less

Revisiting double kidney transplantation: two kidneys provide better graft survival than one.

PubMed

Cruzado, J M; Fernandez, L; Riera, L; Bestard, O; Carrera, M; Torras, J; Gil Vernet, S; Melilli, E; Ngango, L; Grinyó, J M

2011-01-01

Double kidney transplantation is an accepted strategy to increase the donor pool. Regarding older donor kidneys, protocols for deciding to perform a dual or a single transplantation are mainly based on preimplantation biopsies. The aim of our study was to evaluate the long-term graft and patient survivals of our "Dual Kidney Transplant program." Patients who lost one of their grafts peritransplantation were used as controls. A total of 203 patients underwent kidney transplantation from December 1996 to January 2008 in our "old for old" renal transplantation program. We excluded 21 patients because of a nonfunctioning kidney, hyperacute rejection, or patient death with a functioning graft within the first month. Seventy-nine among 182 kidney transplantation the "old for old" program were dual kidney transplantation (DKT). Fifteen of 79 patients lost one of their kidney grafts (the uninephrectomized (UNX) UNX group). At 1 year, renal function was lower and proteinuria greater among the UNX than the DKT group. Patient survival was similar in both groups. However, death-censored graft survival was lower in UNX than DKT patients. The 5-year graft survival rate was 70% in UNX versus 93% in DKT cohorts (P = .04). In conclusion, taking into account the kidney shortage, our results may question whether the excellent transplant outcomes with DKT counter balance the reduced donor pool obviating acceptable transplant outcomes for more patients with single kidney transplantation. Copyright © 2011 Elsevier Inc. All rights reserved.

Cardiovascular and Renal Outcomes With Canagliflozin According to Baseline Kidney Function: Data from the CANVAS Program.

PubMed

Neuen, Brendon L; Ohkuma, Toshiaki; Neal, Bruce; Matthews, David R; de Zeeuw, Dick; Mahaffey, Kenneth W; Fulcher, Greg; Desai, Mehul; Li, Qiang; Deng, Hsiaowei; Rosenthal, Norm; Jardine, Meg J; Bakris, George; Perkovic, Vlado

2018-06-25

Background : Canagliflozin is approved for glucose lowering in type 2 diabetes and confers cardiovascular and renal benefits. We sought to assess whether it had benefits in people with chronic kidney disease (CKD), including those with an estimated glomerular filtration rate (eGFR) between 30 and 45 mL/min/1.73 m 2 in whom the drug is not currently approved for use. Methods : The CANagliflozin cardioVascular Assessment Study Program (CANVAS) randomized 10,142 participants with type 2 diabetes and eGFR greater than 30 mL/min/1.73 m 2 to canagliflozin or placebo. The primary outcome was a composite of cardiovascular death, nonfatal myocardial infarction, or nonfatal stroke, with other cardiovascular, renal, and safety outcomes. This secondary analysis describes outcomes in participants with and without CKD, defined as eGFR <60 and ≥60 mL/min/1.73 m 2 , and according to baseline kidney function (eGFR <45, 45-<60, 60-<90, and ≥90 mL/min/1.73 m 2 ). Results : At baseline, 2039 (20.1%) participants had an eGFR <60 mL/min/1.73 m 2 , of whom 71.6% had a history of cardiovascular disease. The effect of canagliflozin on the primary outcome was similar in people with CKD (HR 0.70, 95% CI 0.55-0.90) and those with preserved kidney function (HR 0.92, 95% CI 0.79-1.07, P heterogeneity = 0.08). Relative effects on most cardiovascular and renal outcomes were similar across eGFR subgroups, with possible heterogeneity suggested only for the outcome of fatal/nonfatal stroke ( P heterogeneity = 0.01), as were results for almost all safety outcomes. Conclusions : The effect of canagliflozin on cardiovascular and renal outcomes was not modified by baseline level of kidney function in people with type 2 diabetes and a history or high risk of cardiovascular disease down to eGFR levels of 30 mL/min/1.73 m 2 Reassessing current limitations on the use of canagliflozin in CKD may allow additional individuals to benefit from this therapy. Clinical Trial Registration : URL: https://clinicaltrials.gov. Unique identifiers: NCT01032629, NCT01989754.

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

Laparoscopic kidney orthotopic transplant: preclinical study in the pig model.

PubMed

He, B; Musk, G C; Mou, L; Waneck, G L; Delriviere, L

2013-06-01

Laparoscopic surgery has rapidly expanded in clinical practice replacing conventional open surgery over the last three decades. Laparoscopic donor nephrectomy has been favored due to its multiple benefits. The aim of this study was to explore the safety and feasibility of kidney transplantation by a laparoscopic technique in a pig model. The study was approved by the university animal ethics committee. Eight female pigs (Sus Scrofra, weighing 45-50 kg) were divided into 2 groups: group I included 4 animals that underwent laparoscopic kidney orthotopic transplantation on the left side. The right kidney was remained functional in situ. The pigs recovered and were observed for 1 week. In the 4 hosts group II pigs underwent a laparoscopic kidney transplantation on the left side. With simultaneous clipping of the right ureter. After recovery, the pigs were observed for 4 weeks. A laparotomy for examination was performed prior to euthanasia. All 4 group I pigs survived for 1 week. The laparotomy showed normal graft perfusion with wall patent renal artery and vein as well as satisfactory urine output upon transection of ureter in 3 hosts. Renal artery stenosis occurred in one pig. In The Immediate kidney graft function was achieved in 3 group II pigs. The fourth died following extubation due to laryngospasm despite a functional graft. The average creatinine levels were 195.5 μmol/L on day 3; 224.5 μmol/L at week 1; 127 μmol/L at week 2; 182.7 umol/L at week 3; and 154.7 umol/L at week 4. Laparoscopic kidney transplantation was feasible and safe in a pig model with immediate graft function. This study will provide further evidence to support application of laparoscopic technique to human kidney transplant. Copyright © 2013 Elsevier Inc. All rights reserved.

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.

Serum uric acid to creatinine ratio: A predictor of incident chronic kidney disease in type 2 diabetes mellitus patients with preserved kidney function.

PubMed

Gu, Liubao; Huang, Liji; Wu, Haidi; Lou, Qinglin; Bian, Rongwen

2017-05-01

Serum uric acid has shown to be a predictor of renal disease progression in most but not all studies. This study aims to test whether renal function-normalized serum uric acid is superior to serum uric acid as the predictor of incident chronic kidney disease in type 2 diabetes mellitus patients. In this study, 1339 type 2 diabetes mellitus patients with estimated glomerular filtration rate ⩾60 mL/min/1.73 m 2 and normouricemia were included. Renal function-normalized serum uric acid was calculated using serum uric acid/creatinine. Cox regression analysis was used to estimate the association between serum uric acid, renal function-normalized serum uric acid and incident chronic kidney disease. In total, 74 (5.53%) patients developed to chronic kidney disease 3 or greater during a median follow-up of 4 years, with older ages, longer diabetes duration and lower estimated glomerular filtration rate at baseline. The decline rate of estimated glomerular filtration rate was positively correlated with serum uric acid/creatinine ( r = 0.219, p < 0.001), but not serum uric acid ( r = 0.005, p = 0.858). Moreover, multivariate analysis revealed that serum uric acid was not an independent risk factor for incident chronic kidney disease ( p = 0.055), whereas serum uric acid to creatinine ratio was significantly associated with incident chronic kidney disease independently of potential confounders including baseline estimated glomerular filtration rate. serum uric acid to creatinine ratio might be a better predictor of incident chronic kidney disease in type 2 diabetes mellitus patients.

A Novel Therapy to Attenuate Acute Kidney Injury and Ischemic Allograft Damage after Allogenic Kidney Transplantation in Mice

PubMed Central

Gueler, Faikah; Shushakova, Nelli; Mengel, Michael; Hueper, Katja; Chen, Rongjun; Liu, Xiaokun; Park, Joon-Keun; Haller, Hermann

2015-01-01

Ischemia followed by reperfusion contributes to the initial damage to allografts after kidney transplantation (ktx). In this study we tested the hypothesis that a tetrapeptide EA-230 (AQGV), might improve survival and attenuate loss of kidney function in a mouse model of renal ischemia/reperfusion injury (IRI) and ischemia-induced delayed graft function after allogenic kidney transplantation. IRI was induced in male C57Bl/6N mice by transient bilateral renal pedicle clamping for 35 min. Treatment with EA-230 (20–50mg/kg twice daily i.p. for four consecutive days) was initiated 24 hours after IRI when acute kidney injury (AKI) was already established. The treatment resulted in markedly improved survival in a dose dependent manner. Acute tubular injury two days after IRI was diminished and tubular epithelial cell proliferation was significantly enhanced by EA-230 treatment. Furthermore, CTGF up-regulation, a marker of post-ischemic fibrosis, at four weeks after IRI was significantly less in EA-230 treated renal tissue. To learn more about these effects, we measured renal blood flow (RBF) and glomerular filtration rate (GFR) at 28 hours after IRI. EA-230 improved both GFR and RBF significantly. Next, EA-230 treatment was tested in a model of ischemia-induced delayed graft function after allogenic kidney transplantation. The recipients were treated with EA-230 (50 mg/kg) twice daily i.p. which improved renal function and allograft survival by attenuating ischemic allograft damage. In conclusion, EA-230 is a novel and promising therapeutic agent for treating acute kidney injury and preventing IRI-induced post-transplant ischemic allograft injury. Its beneficial effect is associated with improved renal perfusion after IRI and enhanced regeneration of tubular epithelial cells. PMID:25617900

A novel therapy to attenuate acute kidney injury and ischemic allograft damage after allogenic kidney transplantation in mice.

PubMed

Gueler, Faikah; Shushakova, Nelli; Mengel, Michael; Hueper, Katja; Chen, Rongjun; Liu, Xiaokun; Park, Joon-Keun; Haller, Hermann; Wensvoort, Gert; Rong, Song

2015-01-01

Ischemia followed by reperfusion contributes to the initial damage to allografts after kidney transplantation (ktx). In this study we tested the hypothesis that a tetrapeptide EA-230 (AQGV), might improve survival and attenuate loss of kidney function in a mouse model of renal ischemia/reperfusion injury (IRI) and ischemia-induced delayed graft function after allogenic kidney transplantation. IRI was induced in male C57Bl/6N mice by transient bilateral renal pedicle clamping for 35 min. Treatment with EA-230 (20-50mg/kg twice daily i.p. for four consecutive days) was initiated 24 hours after IRI when acute kidney injury (AKI) was already established. The treatment resulted in markedly improved survival in a dose dependent manner. Acute tubular injury two days after IRI was diminished and tubular epithelial cell proliferation was significantly enhanced by EA-230 treatment. Furthermore, CTGF up-regulation, a marker of post-ischemic fibrosis, at four weeks after IRI was significantly less in EA-230 treated renal tissue. To learn more about these effects, we measured renal blood flow (RBF) and glomerular filtration rate (GFR) at 28 hours after IRI. EA-230 improved both GFR and RBF significantly. Next, EA-230 treatment was tested in a model of ischemia-induced delayed graft function after allogenic kidney transplantation. The recipients were treated with EA-230 (50 mg/kg) twice daily i.p. which improved renal function and allograft survival by attenuating ischemic allograft damage. In conclusion, EA-230 is a novel and promising therapeutic agent for treating acute kidney injury and preventing IRI-induced post-transplant ischemic allograft injury. Its beneficial effect is associated with improved renal perfusion after IRI and enhanced regeneration of tubular epithelial cells.

Decline of kidney function during the pre-dialysis period in chronic kidney disease patients: a systematic review and meta-analysis.

PubMed

Janmaat, Cynthia J; van Diepen, Merel; van Hagen, Cheyenne Ce; Rotmans, Joris I; Dekker, Friedo W; Dekkers, Olaf M

2018-01-01

Substantial heterogeneity exists in reported kidney function decline in pre-dialysis chronic kidney disease (CKD). By design, kidney function decline can be studied in CKD 3-5 cohorts or dialysis-based studies. In the latter, patients are selected based on the fact that they initiated dialysis, possibly leading to an overestimation of the true underlying kidney function decline in the pre-dialysis period. We performed a systematic review and meta-analysis to compare the kidney function decline during pre-dialysis in CKD stage 3-5 patients, in these two different study types. We searched PubMed, EMBASE, Web of Science and Cochrane to identify eligible studies reporting an estimated glomerular filtration rate (eGFR) decline (mL/min/1.73 m 2 ) in adult pre-dialysis CKD patients. Random-effects meta-analysis was performed to obtain weighted mean annual eGFR decline. We included 60 studies (43 CKD 3-5 cohorts and 17 dialysis-based studies). The meta-analysis yielded a weighted annual mean (95% CI) eGFR decline during pre-dialysis of 2.4 (95% CI: 2.2, 2.6) mL/min/1.73 m 2 in CKD 3-5 cohorts compared to 8.5 (95% CI: 6.8, 10.1) in dialysis-based studies (difference 6.0 [95% CI: 4.8, 7.2]). To conclude, dialysis-based studies report faster mean annual eGFR decline during pre-dialysis than CKD 3-5 cohorts. Thus, eGFR decline data from CKD 3-5 cohorts should be used to guide clinical decision making in CKD patients and for power calculations in randomized controlled trials with CKD progression during pre-dialysis as the outcome.

Some Biochemical and Hematological Parameters among Petrol Station Attendants: A Comparative Study

PubMed Central

Abou-ElWafa, Hala Samir; Albadry, Ahmed A.; Bazeed, Fagr B.

2015-01-01

Objective. To describe selected biochemical and hematological parameters (blood picture, liver enzymes, and kidney functions) in petrol station attendants in Mansoura city. Methods. This is a comparative cross-sectional study. The exposed group included 102 petrol station attendants. They were compared to a matched group of healthy 102 male service and office workers at the Faculty of Medicine, Mansoura University. The results of blood picture, liver enzymes, and kidney functions were compared between both groups. Results. Mean Red Blood Cells (RBCs) count, hemoglobin level, and Hematocrit (HCT) level were significantly lower in petrol station attendants than the comparison group. All other blood picture parameters showed nonsignificant difference between both groups. Liver enzymes, renal functions, serum albumin, and total protein showed statistically nonsignificant difference between both groups except for alanine aminotransferase (ALT) which was significantly higher in petrol station attendants. Conclusions. Some laboratory parameters among petrol station attendants showed changes that could be attributed to workplace exposure and should be given attention at preemployment and periodic medical examination. PMID:26634207

Mineralocorticoid receptor antagonists in kidney transplantation: time to consider?

PubMed

Girerd, Sophie; Jaisser, Frédéric

2018-04-17

Although patient survival is significantly improved by kidney transplantation (KT) in comparison with dialysis, it remains significantly lower than that observed in the general population. Graft function is one of the major determinants of patient survival after KT. Mineralocorticoid receptor antagonists (MRAs) could be of particular interest in this population to improve graft function and treat or prevent cardiovascular (CV) complications. In KT, ischaemia/reperfusion injury is a major factor involved in delayed graft function, which is often associated with inferior long-term graft survival. Preclinical studies suggest that MRAs may prevent ischaemia/reperfusion-related lesions in addition to having a protective effect in preventing calcineurin inhibitor-induced nephrotoxicity. Clinical data also support the anti-proteinuric effect of MRAs in chronic kidney disease (CKD). Taken together, MRAs may hence be of particular benefit in improving short- and long-term graft function. Numerous randomized controlled trials (RCTs) have shown the efficacy of MRAs in both heart failure and resistant hypertension. As these comorbidities are frequent in kidney transplant recipients before transplantation or during follow-up, MRAs could represent a useful therapeutic option in those with mild renal function impairment. However, CKD patients are under-represented in RCTs and the CV effects of MRAs in kidney transplant recipients have yet to be specifically assessed in large-scale trials. Available evidence indicates a good safety profile for MRAs in patients with a glomerular filtration rate (GFR) >30 mL/min/1.73 m2. However, as for all patients prescribed an MRA, creatinine and potassium should also be closely monitored following MRA initiation in kidney transplant patients. Given the current evidence suggesting that MRAs prevent ischaemia/reperfusion-related lesions and calcineurin inhibitor-induced nephrotoxicity in kidney transplant recipients as well as CV events in patients at high risk of CV complications (such as those in kidney transplant recipients), trials are urgently needed to fully assess the clinical impact of MRA use in this population.

Polycystin-1 Binds Par3/aPKC and Controls Convergent Extension During Renal Tubular Morphogenesis

PubMed Central

Castelli, Maddalena; Boca, Manila; Chiaravalli, Marco; Ramalingam, Harini; Rowe, Isaline; Distefano, Gianfranco; Carroll, Thomas; Boletta, Alessandra

2013-01-01

Several organs, including lungs and kidneys, are formed by epithelial tubes whose proper morphogenesis ensures correct function. This is best exemplified by the kidney, where defective establishment or maintanance of tubular diameter results in polycystic kidney disease, a common genetic disorder. Most polycystic kidney disease cases result from loss-of-function mutations in the PKD1 gene, encoding Polycystin-1 (PC-1), a large receptor of unknown function. Here we demonstrate that PC-1 plays an essential role in establishment of correct tubular diameter during nephron development. PC-1 associates with Par3 favoring the assembly of a pro-polarizing Par3/aPKC complex and it regulates a program of cell polarity important for oriented cell migration and for a convergent extension-like process during tubular morphogenesis. Par3 inactivation in the developing kidney results in defective convergent extension and tubular morphogenesis and in renal cyst formation. Our data define PC-1 as central to cell polarization and to epithelial tube morphogenesis and homeostasis. PMID:24153433

Polycystin-1 binds Par3/aPKC and controls convergent extension during renal tubular morphogenesis

NASA Astrophysics Data System (ADS)

Castelli, Maddalena; Boca, Manila; Chiaravalli, Marco; Ramalingam, Harini; Rowe, Isaline; Distefano, Gianfranco; Carroll, Thomas; Boletta, Alessandra

2013-10-01

Several organs, including the lungs and kidneys, are formed by epithelial tubes whose proper morphogenesis ensures correct function. This is best exemplified by the kidney, where defective establishment or maintenance of tubular diameter results in polycystic kidney disease, a common genetic disorder. Most polycystic kidney disease cases result from loss-of-function mutations in the PKD1 gene, encoding Polycystin-1, a large receptor of unknown function. Here we demonstrate that PC-1 has an essential role in the establishment of correct tubular diameter during nephron development. Polycystin-1 associates with Par3 favouring the assembly of a pro-polarizing Par3/aPKC complex and it regulates a programme of cell polarity important for oriented cell migration and for a convergent extension-like process during tubular morphogenesis. Par3 inactivation in the developing kidney results in defective convergent extension and tubular morphogenesis, and in renal cyst formation. Our data define Polycystin-1 as central to cell polarization and to epithelial tube morphogenesis and homeostasis.

Is percutaneous nephrolithotomy in solitary kidneys safe?

PubMed

Wong, Kathie Alexina; Sahai, Arun; Patel, Amit; Thomas, Kay; Bultitude, Matthew; Glass, Jonathan

2013-11-01

To review our experience from a high volume stone center with a focus on efficacy, safety, and renal function. Stones requiring percutaneous nephrolithotomy (PCNL) in patients with solitary kidneys can pose significant anxiety to the urologist. Limited data are available in published reports in this setting. A comprehensive retrospective review of medical records was performed on patients who underwent PCNL and had a solitary kidney or a single functioning renal unit. Data were collected on patient demographics, stone burden, outcomes, complications, and renal function. Of 378 PCNLs performed between January 2003 and September 2011, 22 were performed in 17 patients with a single functioning kidney. Three procedures were performed in a transplanted kidney. In those with solitary calculus, the longest mean length and stone surface area were 37 mm and 825 mm(2), respectively. Stone-free rate was 59%. Auxiliary procedures were required in 6 cases, resulting in a stone-free rate of 77%. Median inpatient stay was 4 days. Serum creatinine values improved from 144 to 126 umol/L before and after the procedure and mean estimated glomerular filtration rate improved similarly from 51 to 59 mls/minute, respectively. Blood transfusion was required in 1 patient, sepsis developed in 3, and 2 patients required a stent for obstruction. PCNL in solitary kidneys is safe with an acceptable complication rate if performed in a high volume center. Outcomes are good, although auxiliary procedures may be necessary. Renal function remains stable or improves after procedure. Copyright © 2013 Elsevier Inc. All rights reserved.

Using OCT to predict post-transplant renal function

NASA Astrophysics Data System (ADS)

Andrews, Peter M.; Chen, Yu; Wierwille, Jeremiah; Joh, Daniel; Alexandrov, Peter; Rogalsky, Derek; Moody, Patrick; Chen, Allen; Cooper, Matthew; Verbesey, Jennifer E.; Gong, Wei; Wang, Hsing-Wen

2013-03-01

The treatment of choice for patients with end-stage renal disease is kidney transplantation. However, acute tubular necrosis (ATN) induced by an ischemic insult (e.g., from prolonged ex vivo storage times, or non-heart beating cadavers) is a major factor limiting the availability of donor kidneys. In addition, ischemic induced ATN is a significant risk factor for eventual graft survival and can be difficult to discern from rejection. Currently, there are no rapid and reliable tests to determine ATN suffered by donor kidneys and whether or not donor kidneys might exhibit delayed graft function. OCT (optical coherence tomography) is a rapidly emerging imaging modality that can function as a type of "optical biopsy", providing cross-sectional images of tissue morphology in situ and in real-time. In a series of recent clinical trials, we evaluated the ability of OCT to image those features of the renal microstructure that are predictive of ATN. Specifically, we found that OCT could effectively image through the intact human renal capsule and determine the extent of acute tubular necrosis. We also found that Doppler based OCT (i.e., DOCT) revealed renal blood flow dynamics that is also reported to be a determiner of post-transplant renal function. This kind of information will allow transplant surgeons to make the most efficient use of available donor kidneys, eliminate the possible use of bad donor kidneys, provide a measure of expected post-transplant renal function, and allow better distinction between post-transplant immunological rejection and ischemic-induced acute renal failure.

Comparison of different agar diffusion methods for the detection of residues in the kidneys of pigs treated with antimicrobial drugs.

PubMed

Korkeala, H; Sorvettula, O; Mäki-Petäys, O; Hirn, J

1983-01-01

Residue analyses of the kidneys of twenty-six pigs treated with various antimicrobial drugs 20 h before slaughter and of eleven untreated pigs were performed. The effects of storage temperature of the kidneys, and of sampling location, on the residue analysis were also studied. No method alone was sufficient for the detection of residues. Oxytetracycline residues could be detected at pH 6, dihydrostreptomycin residues at pH 8, and sulphonamide residues if trimethoprim was present in the medium. Chloramphenicol, penicillin G procaine, tylosin and lincomycin residues were not detectable with the methods used. The concentration of ampicillin decreased during the storage of samples at +4°C. Most methods also yielded zones of inhibition for the frozen kidneys from untreated pigs. It seems necessary to use agar media of two different pH values: the addition of trimethoprim to the medium is also needed. The use of fresh pig kidneys, and samples containing both kidney medulla and kidney cortex, is recommended in residue analysis. Copyright © 1983. Published by Elsevier Ltd.

Short communication: timeline of radiation-induced kidney function loss after stereotactic ablative body radiotherapy of renal cell carcinoma as evaluated by serial (99m)Tc-DMSA SPECT/CT.

PubMed

Jackson, Price; Foroudi, Farshad; Pham, Daniel; Hofman, Michael S; Hardcastle, Nicholas; Callahan, Jason; Kron, Tomas; Siva, Shankar

2014-11-26

Stereotactic ablative body radiotherapy (SABR) has been proposed as a definitive treatment for patients with inoperable primary renal cell carcinoma. However, there is little documentation detailing the radiobiological effects of hypofractionated radiation on healthy renal tissue. In this study we describe a methodology for assessment of regional change in renal function in response to single fraction SABR of 26 Gy. In a patient with a solitary kidney, detailed follow-up of kidney function post-treatment was determined through 3-dimensional SPECT/CT imaging and (51)Cr-EDTA measurements. Based on measurements of glomerular filtration rate, renal function declined rapidly by 34% at 3 months, plateaued at 43% loss at 12 months, with minimal further decrease to 49% of baseline by 18 months. The pattern of renal functional change in (99m)Tc-DMSA uptake on SPECT/CT imaging correlates with dose delivered. This study demonstrates a dose effect relationship of SABR with loss of kidney function.

[Fetal urology].

PubMed

Jakobovits, Akos; Jakobovits, Antal

2009-06-14

Although it becomes vitally important only after birth, renal function already plays significant role in maintaining fetal metabolic equilibrium. The kidneys significantly contribute to production of amniotic fluid. Adequate amount of amniotic fluid is needed to stimulate the intrauterine fetal respiratory activity. Intrauterine breathing is essential for lung development. As a result, oligohydramnion is conducive to pulmonary hypoplasia. The latter may lead to neonatal demise soon after birth. In extrauterine life kidneys eliminate nitrogen containing metabolic byproducts. Inadequate renal function results therefore lethal uremia. Integrity of ureters and the urethra is essential for the maintenance of renal function. Retention of urine causes degeneration of the functional units of the kidneys and ensuing deterioration of renal function. Intrauterine kidney puncture or shunt procedure may delay this process in some cases. On the other hand, once renal function has been damaged, no therapy can restart it. Certain anomalies of renal excretory pathways may also be associated with other congenital abnormalities, making the therapeutic efforts pointless. Presence of these associated intrauterine defects makes early pregnancy termination a management alternative, as well as it affects favorably perinatal mortality rates.

A Case Report of Successful Kidney Donation After Brain Death Following Nicotine Intoxication.

PubMed

Räsänen, M; Helanterä, I; Kalliomäki, J; Savikko, J; Parry, M; Lempinen, M

Nicotine intoxication is a rare cause of death and can lead to brain death after respiratory arrest and hypoxic-ischemic encephalopathy. To our knowledge, no previous reports regarding organ donation after nicotine intoxication have been described. We present a successful case of kidney donation after brain death caused by subcutaneous nicotine overdose from liquid nicotine from an e-cigarette cartridge in an attempted suicide. Both kidneys were transplanted successfully with immediate graft function, and both recipients were discharged at postoperative day 9 with normal plasma creatinine levels. Graft function has remained excellent in follow-up. This case suggests that kidneys from a donor with fatal nicotine intoxication may be successfully used for kidney transplantation in the absence of other contraindications for donation. Copyright © 2016 Elsevier Inc. All rights reserved.

Quantification of vascular damage in acute kidney injury with fluorine magnetic resonance imaging and spectroscopy.

PubMed

Moore, Jeremy K; Chen, Junjie; Pan, Hua; Gaut, Joseph P; Jain, Sanjay; Wickline, Samuel A

2018-06-01

To design a fluorine MRI/MR spectroscopy approach to quantify renal vascular damage after ischemia-reperfusion injury, and the therapeutic response to antithrombin nanoparticles (NPs) to protect kidney function. A total of 53 rats underwent 45 min of bilateral renal artery occlusion and were treated at reperfusion with either plain perfluorocarbon NPs or NPs functionalized with a direct thrombin inhibitor (PPACK:phenyalanine-proline-arginine-chloromethylketone). Three hours after reperfusion, kidneys underwent ex vivo fluorine MRI/MR spectroscopy at 4.7 T to quantify the extent and volume of trapped NPs, as an index of vascular damage and ischemia-reperfusion injury. Microscopic evaluation of structural damage and NP trapping in non-reperfused renal segments was performed. Serum creatinine was quantified serially over 7 days. The damaged renal cortico-medullary junction trapped a significant volume of NPs (P = 0.04), which correlated linearly (r = 0.64) with the severity of kidney injury 3 h after reperfusion. Despite global large vessel reperfusion, non-reperfusion in medullary peritubular capillaries was confirmed by MRI and microscopy, indicative of continuing hypoxia due to vascular compromise. Treatment of animals with PPACK NPs after acute kidney injury did not accelerate kidney functional recovery. Quantification of ischemia-reperfusion injury after acute kidney injury with fluorine MRI/MR spectroscopy of perfluorocarbon NPs objectively depicts the extent and severity of vascular injury and its linear relationship to renal dysfunction. The lack of kidney function improvement after early posttreatment thrombin inhibition confirms the rapid onset of ischemia-reperfusion injury as a consequence of vascular damage and non-reperfusion. The prolongation of medullary ischemia renders cortico-medullary tubular structures susceptible to continued necrosis despite restoration of large vessel flow, which suggests limitations to acute interventions after acute kidney injury, designed to interdict renal tubular damage. Magn Reson Med 79:3144-3153, 2018. © 2017 International Society for Magnetic Resonance in Medicine. © 2017 International Society for Magnetic Resonance in Medicine.

Comparison of Tissue Injury from Focused Ultrasonic Propulsion of Kidney Stones Versus Extracorporeal Shock Wave Lithotripsy

PubMed Central

Connors, Bret A.; Evan, Andrew P.; Blomgren, Philip M.; Hsi, Ryan S.; Harper, Jonathan D.; Sorensen, Mathew D.; Wang, Yak-Nam; Simon, Julianna C.; Paun, Marla; Starr, Frank; Cunitz, Bryan W.; Bailey, Michael R.; Lingeman, James E.

2013-01-01

Purpose Focused ultrasonic propulsion is a new non-invasive technique designed to move kidney stones and stone fragments out of the urinary collecting system. However, the extent of tissue injury associated with this technique is not known. As such, we quantitated the amount of tissue injury produced by focused ultrasonic propulsion under simulated clinical treatment conditions, and under conditions of higher power or continuous duty cycles, and compared those results to SWL injury. Materials and Methods A human calcium oxalate monohydrate stone and/or nickel beads were implanted (with ureteroscopy) into 3 kidneys of live pigs (45–55 kg) and repositioned using focused ultrasonic propulsion. Additional pig kidneys were exposed to SWL level pulse intensities or continuous ultrasound exposure of 10 minutes duration (ultrasound probe either transcutaneous or on the kidney). These kidneys were compared to 6 kidneys treated with an unmodified Dornier HM3 Lithotripter (2400 shocks, 120 SWs/min and 24 kV). Histological analysis was performed to assess the volume of hemorrhagic tissue injury created by each technique (% functional renal volume, FRV). Results SWL produced a lesion of 1.56±0.45% FRV. Ultrasonic propulsion produced no detectable lesion with the simulated clinical treatment. A lesion of 0.46±0.37% FRV or 1.15±0.49% FRV could be produced if excessive treatment parameters were used while the ultrasound probe was placed on the kidney. Conclusions Focused ultrasonic propulsion produced no detectable morphological injury to the renal parenchyma when using clinical treatment parameters and produced injury comparable in size to SWL when using excessive treatment parameters. PMID:23917165

Estimated Nephron Number of the Donor Kidney: Impact on Allograft Kidney Outcomes.

PubMed

Schachtner, T; Reinke, P

Low birth weights have been associated with a reduction in nephron number with compensatory hypertrophy of existing glomeruli. The impact of donor birth weight as an estimate of nephron number on allograft function, however, has not been examined. We collected donor birth weight, kidney weight, and volume from 91 living kidney donor-recipient pairs before nephrectomy and after 12, 36, and 60 months. Nephron number was calculated from donor birth weight and age. Donor birth weight, kidney weight/body surface area (BSA), and kidney volume showed a moderate positive correlation with allograft estimated glomerular filtration rate (eGFR) at 12 months (P < .05). Donor age showed a negative moderate correlation with allograft eGFR at 12 months (P = .015). The strongest correlation with allograft eGFR was observed for calculated donor kidney nephron number at 12, 36, and 60 months (R, 0.340, 0.305, and 0.476, respectively; P < .05). No impact was observed on allograft daily proteinuria of any investigated marker (P > .05). Recipients of donors with birth weight <2.5 kg had need of a significantly greater number of antihypertensive drugs (P < .05). Calculated nephron number from donor birth weight and age is suggested to be superior to donor kidney weight/BSA and volume regarding allograft function. Calculated nephron number could estimate expected eGFR and guide decision making in cases of impaired allograft function. Copyright © 2017 Elsevier Inc. All rights reserved.

The association between vitamin B12, albuminuria and reduced kidney function: an observational cohort study

USDA-ARS?s Scientific Manuscript database

Background: Variants in CUBN, the gene encoding cubilin, a proximal tubular transport protein, have been associated with albuminuria and vitamin B12 (B12) deficiency. We hypothesized that low levels of B12 would be associated with albuminuria in a population-based cohort. Methods: We analyzed parti...

A semi-automated region of interest detection method in the scintigraphic glomerular filtration rate determination for patients with abnormal low renal function.

PubMed

Tian, Cancan; Zheng, Xiujuan; Han, Yuan; Sun, Xiaoguang; Chen, Kewei; Huang, Qiu

2013-11-01

This work presents a novel semi-automated renal region-of-interest (ROI) determination method that is user friendly, time saving, and yet provides a robust glomerular filtration rate (GFR) estimation highly consistent with the reference method. We reviewed data from 57 patients who underwent (99m)Tc-diethylenetriaminepentaacetic acid renal scintigraphy and were diagnosed with abnormal renal function. The renal and background ROIs were delineated by the proposed multi-step, semi-automated method, which integrates temporal/morphologic information via visual inspection and computer-aided calculations. The total GFR was estimated using the proposed method (sGFR) performed by 2 junior clinicians (A and B) with 1 and 3 years of experience, respectively (sGFR_a, sGFR_b), and compared with the reference total GFR (rGFR) estimated by a senior clinician with 20 years of experience who manually delineated the kidney and background ROIs. All GFR calculations herein were conducted using the Gates method. Data from 10 patients with unilateral or non-functioning kidneys were excluded from the analysis. For the remaining patients, sGFR correlated well with rGFR (r(s/rGFR_a) = 0.957, P < 0.001 and r(s/rGFR_b) = 0.951, P < 0.001) and sGFR_a correlated well with sGFR_b (r(a/b) = 0.997, P < 0.001). Moreover, the Bland-Altman plots for sGFR_a and sGFR_b confirm the high reproducibility of the proposed method between different operators. Finally, the proposed procedure is almost 3 times faster than the routinely used procedure in clinical practice. The results suggest that this method is easy to use, highly reproducible, and accurate in measuring the GFR of patients with low renal function. The method is being further extended to a fully automated procedure.

Loin pain hematuria syndrome.

PubMed

Taba Taba Vakili, Sahar; Alam, Tausif; Sollinger, Hans

2014-09-01

Loin pain hematuria syndrome is a rare disease with a prevalence of ∼0.012%. The most prominent clinical features include periods of severe intermittent or persistent unilateral or bilateral loin pain accompanied by either microscopic or gross hematuria. Patients with loin pain hematuria syndrome initially present with hematuria, flank pain, or most often both hematuria and flank pain. Kidney biopsies from patients with loin pain hematuria typically reveal only minor pathologic abnormalities. Further, loin pain hematuria syndrome is not associated with loss of kidney function or urinary tract infections. Loin pain hematuria syndrome-associated hematuria and pain are postulated to be linked to vascular disease of the kidney, coagulopathy, renal vasospasm with microinfarction, hypersensitivity, complement activation on arterioles, venocalyceal fistula, abnormal ureteral peristalsis, and intratubular deposition of calcium or uric acid microcrystals. Many patients with loin pain hematuria syndrome also meet criteria for a somatoform disorder, and analgesic medications, including narcotics, commonly are used to treat loin pain hematuria syndrome-associated pain. Interventional treatments include renal denervation, kidney autotransplantation, and nephrectomy; however, these methods should be used only as a last resort when less invasive measures have been tried unsuccessfully. In this review article, we discuss and critique current clinical practices related to loin pain hematuria syndrome pathophysiology, diagnosis, treatment, and prognosis. Copyright © 2014 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.

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

Aburano, T.; Takayama, T.; Nakajima, K.

The three different methods to evaluate the alterations of split renal function following continued captopril treatment were studied in patients with hypertension. Five patients had unilateral and 2 had bilateral renal artery stenosis, and 13 had normal renal arteries. The studies were performed the day prior to receiving captopril (baseline), and 6th or 7th day following continued captorpril treatment (37.5mg or 75mg/day): Split effective renal plasma flow (ERPF) and glomerular filtration rate (GFR) after injections of I-131 iodohippuran and Tc-99m DTPA were measured respectively by the methods using kidney counting corrected for depth and dose, described by Schlegel and Gates.more » And Tc-99m DMSA uptake was also evaluated qualitatively. In most of patients with renal artery stenosis, split GFR and Tc-99m DMSA uptake in the affected kidney were markedly decreased 6th or 7th day following continued captorpril treatment. These findings suggest that the captopril induced alterations of split renal function may be of importance for the diagnosis of renovascular hypertension. For this purpose, split GFR determination and Tc-99m DMSA study are more useful than split ERPF determination.« less

RENAL MICROVASCULAR DISEASE DETERMINES THE RESPONSES TO REVASCULARIZATION IN EXPERIMENTAL RENOVASCULAR DISEASE

PubMed Central

Chade, Alejandro R.; Kelsen, Silvia

2011-01-01

Background Percutaneous trasluminal renal angioplasty (PTRA) is the most frequent therapeutic approach to resolve renal artery stenosis (RAS). However, renal function recovers in only 30% of the cases. The causes of these poor outcomes are still unknown. We hypothesize that preserving the renal microcirculation distal to RAS will improve the responses to PTRA. Methods and Results RAS was induced in 28 pigs. In 14, vascular endothelial growth factor (VEGF)-165 was infused intra-renally (RAS+VEGF, 0.05 µg/kg). Single-kidney function was assessed in all pigs in vivo using ultra-fast CT after 6 weeks. Half of the RAS/RAS+VEGF completed their observation, and the other half underwent PTRA, VEGF was repeated, and CT studies repeated 4 weeks later. Pigs were then euthanized, the stenotic kidney removed, renal microvascular (MV) architecture reconstructed ex-vivo using 3D micro-CT, and renal fibrosis quantified. Degree of RAS and hypertension were similar in RAS and RAS+VEGF. Renal function and MV density were decreased in RAS but improved in RAS+VEGF. PTRA largely resolved RAS, but the improvements of hypertension and renal function were greater in RAS+VEGF+PTRA than in RAS+PTRA, accompanied by a 34% increase in MV density and decreased fibrosis. Conclusion Preservation of the MV architecture and function in the stenotic kidney improved the responses to PTRA, indicating that renal MV integrity plays a role in determining the responses to PTRA. This study indicates that damage and early loss of renal MV is an important determinant of the progression of renal injury in RAS and instigates often irreversible damage. PMID:20587789

Radiographic kidney measurements in captive cheetahs (Acinonyx jubatus).

PubMed

Hackendahl, Nicole C; Citino, Scott B

2005-06-01

The prevalence of chronic renal disease is substantial among captive cheetahs (Acinonyx jubatus). The purpose of this study was to determine kidney measurements from radiographs of captive cheetahs (n = 15) with normal renal function. The ratio of kidney length to length of the body of the second lumbar vertebrae has been established for domestic cats with normal renal function. The mean ratio of renal length to length of the second lumbar vertebra was 1.81 +/- 0.14 in cheetahs. This baseline data may allow an objective evaluation of radiographic kidney size in cheetahs. However, evaluation of a small number of cheetahs with confirmed renal failure resulted in a similar ratio.

Insights into cellular and molecular basis for urinary tract infection in autosomal-dominant polycystic kidney disease.

PubMed

Gao, Chao; Zhang, Long; Zhang, Ye; Wallace, Darren P; Lopez-Soler, Reynold I; Higgins, Paul J; Zhang, Wenzheng

2017-11-01

Urinary tract infection (UTI) is a broad term referring to an infection of the kidneys, ureters, bladder, and/or urethra. Because of its prevalence, frequent recurrence, and rising resistance to antibiotics, UTI has become a challenge in clinical practice. Autosomal-dominant polycystic kidney disease (ADPKD) is the most common monogenic disorder of the kidney and is characterized by the growth of fluid-filled cysts in both kidneys. Progressive cystic enlargement, inflammation, and interstitial fibrosis result in nephron loss with subsequent decline in kidney function. ADPKD patients frequently develop UTI; however, the cellular and molecular mechanisms responsible for the high UTI incidence in ADPKD patients remain virtually unaddressed. Emerging evidence suggests that α-intercalated cells (α-ICs) of the collecting ducts function in the innate immune defense against UTI. α-ICs inhibit bacterial growth by acidifying urine and secreting neutrophil gelatinase-associated lipocalin (NGAL) that chelates siderophore-containing iron. It is necessary to determine, therefore, if ADPKD patients with recurrent UTI have a reduced number and/or impaired function of α-ICs. Identification of the underlying cellular and molecular mechanisms may lead to the development of novel strategies to reduce UTI in ADPKD. Copyright © 2017 the American Physiological Society.

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.

Frailty, Kidney Function, and Polypharmacy: The Atherosclerosis Risk in Communities (ARIC) Study

PubMed Central

Ballew, Shoshana H.; Chen, Yan; Daya, Natalie R.; Godino, Job G.; Windham, B. Gwen; McAdams-DeMarco, Mara; Coresh, Josef; Selvin, Elizabeth; Grams, Morgan E.

2016-01-01

Background Frail individuals are at increased risk for poor outcomes, including adverse drug events. Kidney function is often compromised in frailty and is a key consideration in medication choice and dosing; however, creatinine-based measures of kidney function may be biased in frail individuals. Study Design Observational study. Setting & Participants 4,987 community-dwelling older men and women with complete data who participated in visit 5 of the Atherosclerosis Risk in Communities (ARIC) Study (2011–2013). Predictor Kidney measures included glomerular filtration rate (GFR) estimated using serum creatinine (eGFRcr) and serum cystatin C (eGFRcys) and urine albumin-creatinine ratio (ACR). Outcomes Frailty, defined using established criteria of 3 or more frailty characteristics (weight loss, slowness, exhaustion, weakness, and low physical activity). Results In total, 341 participants (7%) were classified as frail, 1475 (30%) had eGFRcr <60 ml/min/1.73 m2, 2480 (50%) had eGFRcys <60 ml/min/1.73 m2, and 1006 (20%) had albuminuria ≥30 mg/g. Among frail participants, prevalences of eGFRcr and eGFRcys <60 ml/min/1.73 m2 were 45% and 77%, respectively. Adjusted for covariates, frailty showed a moderate association with eGFRcr and a strong association with eGFRcys and ACR. Frail individuals with eGFRcr 60–<75 ml/min/1.73 m2 were frequently reclassified to lower eGFR categories using eGFRcys (49% to 45–<60, 32% to 30–<45, and 3% to <30 ml/min/1.73 m2). Hyperpolypharmacy (taking ≥10 classes of medications) was more common in frail individuals (54% vs 38% of non-frail), including classes requiring kidney clearance (e.g., digoxin) and associated with falls and subsequent complications (e.g., hypnotic/sedatives, anticoagulants). Limitations Cross-sectional study design. Conclusions Frail individuals had a high prevalence of reduce kidney function, with large discrepancies when reduced kidney function was classified by eGFRcys versus eGFRcr. Given the substantial medication burden and uncertainty in CKD classification, confirmation of kidney function with alternative biomarkers may be warranted to ensure careful prescribing practices in this vulnerable population. PMID:27884475

Incremental short daily home hemodialysis: a case series.

PubMed

Toth-Manikowski, Stephanie M; Mullangi, Surekha; Hwang, Seungyoung; Shafi, Tariq

2017-07-05

Patients starting dialysis often have substantial residual kidney function. Incremental hemodialysis provides a hemodialysis prescription that supplements patients' residual kidney function while maintaining total (residual + dialysis) urea clearance (standard Kt/Vurea) targets. We describe our experience with incremental hemodialysis in patients using NxStage System One for home hemodialysis. From 2011 to 2015, we initiated 5 incident hemodialysis patients on an incremental home hemodialysis regimen. The biochemical parameters of all patients remained stable on the incremental hemodialysis regimen and they consistently achieved standard Kt/Vurea targets. Of the two patients with follow-up >6 months, residual kidney function was preserved for ≥2 years. Importantly, the patients were able to transition to home hemodialysis without automatically requiring 5 sessions per week at the outset and gradually increased the number of treatments and/or dialysate volume as the residual kidney function declined. An incremental home hemodialysis regimen can be safely prescribed and may improve acceptability of home hemodialysis. Reducing hemodialysis frequency by even one treatment per week can reduce the number of fistula or graft cannulations or catheter connections by >100 per year, an important consideration for patient well-being, access longevity, and access-related infections. The incremental hemodialysis approach, supported by national guidelines, can be considered for all home hemodialysis patients with residual kidney function.

Renal Atrophy Secondary to Chemoradiotherapy of Abdominal Malignancies

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

Yang, Gary Y., E-mail: Gary.Yang@RoswellPark.or; May, Kilian Salerno; Iyer, Renuka V.

2010-10-01

Purpose: To identify factors predictive of renal atrophy after chemoradiotherapy of gastrointestinal malignancies. Methods and Materials: Patients who received chemotherapy and abdominal radiotherapy (RT) between 2002 and 2008 were identified for this study evaluating change in kidney size and function after RT. Imaging and biochemical data were obtained before and after RT in 6-month intervals. Kidney size was defined by craniocaudal measurement on CT images. The primarily irradiated kidney (PK) was defined as the kidney that received the greater mean kidney dose. Receiver operating characteristic (ROC) curves were generated to predict risk for renal atrophy. Results: Of 130 patients, medianmore » age was 64 years, and 51.5% were male. Most primary disease sites were pancreas and periampullary tumors (77.7%). Median follow-up was 9.4 months. Creatinine clearance declined 20.89%, and size of the PK decreased 4.67% 1 year after completion of chemoradiation. Compensatory hypertrophy of the non-PK was not seen. Percentage volumes of the PK receiving {>=}10 Gy (V{sub 10}), 15 Gy (V{sub 15}), and 20 Gy (V{sub 20}) were significantly associated with renal atrophy 1 year after RT (p = 0.0030, 0.0029, and 0.0028, respectively). Areas under the ROC curves for V{sub 10}, V{sub 15}, and V{sub 20} to predict >5% decrease in PK size were 0.760, 0.760, and 0.762, respectively. Conclusions: Significant detriments in PK size and renal function were seen after abdominal RT. The V{sub 10}, V{sub 15}, and V{sub 20} were predictive of risk for PK atrophy 1 year after RT. Analyses suggest the association of lower-dose renal irradiation with subsequent development of renal atrophy.« less

Oral Hydration for Prevention of Contrast-Induced Acute Kidney Injury in Elective Radiological Procedures: A Systematic Review and Meta-Analysis of Randomized Controlled Trials

PubMed Central

Cheungpasitporn, Wisit; Thongprayoon, Charat; Brabec, Brady A.; Edmonds, Peter J.; O'Corragain, Oisin A.; Erickson, Stephen B.

2014-01-01

Background: The reports on efficacy of oral hydration treatment for the prevention of contrast-induced acute kidney injury (CIAKI) in elective radiological procedures and cardiac catheterization remain controversial. Aims: The objective of this meta-analysis was to assess the use of oral hydration regimen for prevention of CIAKI. Materials and Methods: Comprehensive literature searches for randomized controlled trials (RCTs) of outpatient oral hydration treatment was performed using MEDLINE, EMBASE, Cochrane Database of Systematic Reviews, Cochrane Central Register of Controlled Trials Systematic Reviews, and clinicaltrials.gov from inception until July 4th, 2014. Primary outcome was the incidence of CIAKI. Results: Six prospective RCTs were included in our analysis. Of 513patients undergoing elective procedures with contrast exposures,45 patients (8.8%) had CIAKI. Of 241 patients with oral hydration regimen, 23 (9.5%) developed CIAKI. Of 272 patients with intravenous (IV) fluid regimen, 22 (8.1%) had CIAKI. Study populations in all included studies had relatively normal kidney function to chronic kidney disease (CKD) stage 3. There was no significant increased risk of CIAKI in oral fluid regimen group compared toIV fluid regimen group (RR = 0.94, 95% confidence interval, CI = 0.38-2.31). Conclusions: According to our analysis,there is no evidence that oral fluid regimen is associated with more risk of CIAKI in patients undergoing elective procedures with contrast exposures compared to IV fluid regimen. This finding suggests that the oral fluid regimen might be considered as a possible outpatient treatment option for CIAKI prevention in patients with normal to moderately reduced kidney function. PMID:25599049

Efficacy of Cordyceps sinensis as an adjunctive treatment in kidney transplant patients: A systematic-review and meta-analysis.

PubMed

Ong, Bee Yean; Aziz, Zoriah

2017-02-01

Cordyceps sinensis (cordyceps) is a fungus used in traditional Chinese medicine as adjuvant immunosuppressive agent in patients with kidney transplant. This review evaluates current evidence on the efficacy and safety of natural and fermented cordyceps preparations in patients with kidney transplant. English and Chinese electronic databases including The Cochrane Central Register of Controlled Trials, EMBASE, MEDLINE, and CNKI (China National Knowledge Infrastructure) were searched up to December 2015 for relevant randomized controlled trials. Journals and conference proceedings were also searched. Two review authors independently selected trials for inclusion, extracted data, and assessed methodological quality. The primary outcome measures were incidence of acute graft rejection in the first year post-transplantation, one-year graft survival rate (defined as the percentage of patients with functioning grafts) and patient survival rate (or all-cause mortality). Nine studies were eligible for inclusion. These studies were considered to be at moderate risk of bias due to poor reporting of methods. Four studies that compared cordyceps-based therapy with azathioprine-based therapy gave comparable acute rejection rates, and graft and patient survival. The cordyceps-treated group however showed better kidney function and lower incidences of hyperuricemia, hyperlipidemia, hyperglycemia and liver injury. Cordyceps used with different combinations of immunosuppressant therapy showed significant reduction in proteinuria after 6-12 months. Compared to the group receiving cyclosporine A monotherapy, treatment with a combination of cordyceps and cyclosporine A showed less treatment-induced nephrotoxicity. Adverse events were either not monitored or poorly documented in most trials. Current evidence shows that cordyceps as an adjuvant to routine immunosuppressant therapy may benefit kidney transplant patient, however, better quality evidence is still required. Copyright © 2016 Elsevier Ltd. All rights reserved.

Preoperative angiotensin-converting enzyme inhibitors and angiotensin receptor blocker use and acute kidney injury in patients undergoing cardiac surgery

PubMed Central

Coca, Steven G.; Garg, Amit X.; Swaminathan, Madhav; Garwood, Susan; Hong, Kwangik; Thiessen-Philbrook, Heather; Passik, Cary; Koyner, Jay L.; Parikh, Chirag R.; Jai, Raman; Jeevanandam, Valluvan; Akhter, Shahab; Devarajan, Prasad; Bennett, Michael; Edelsteinm, Charles; Patel, Uptal; Chu, Michael; Goldbach, Martin; Guo, Lin Ruo; McKenzie, Neil; Myers, Mary Lee; Novick, Richard; Quantz, Mac; Zappitelli, Michael; Dewar, Michael; Darr, Umer; Hashim, Sabet; Elefteriades, John; Geirsson, Arnar

2013-01-01

Background Using either an angiotensin-converting enzyme inhibitor (ACEi) or an angiotensin receptor blocker (ARB) the morning of surgery may lead to ‘functional’ postoperative acute kidney injury (AKI), measured by an abrupt increase in serum creatinine. Whether the same is true for ‘structural’ AKI, measured with new urinary biomarkers, is unknown. Methods The TRIBE-AKI study was a prospective cohort study of 1594 adults undergoing cardiac surgery at six hospitals between July 2007 and December 2010. We classified the degree of exposure to ACEi/ARB into three categories: ‘none’ (no exposure prior to surgery), ‘held’ (on chronic ACEi/ARB but held on the morning of surgery) or ‘continued’ (on chronic ACEi/ARB and taken the morning of surgery). The co-primary outcomes were ‘functional’ AKI based upon changes in pre- to postoperative serum creatinine, and ‘structural AKI’, based upon peak postoperative levels of four urinary biomarkers of kidney injury. Results Across the three levels (none, held and continued) of ACEi/ARB exposure there was a graded increase in functional AKI, as defined by AKI stage 1 or worse; (31, 34 and 42%, P for trend 0.03) and by percentage change in serum creatinine from pre- to postoperative (25, 26 and 30%, P for trend 0.03). In contrast, there were no differences in structural AKI across the strata of ACEi/ARB exposure, as assessed by four structural AKI biomarkers (neutrophil gelatinase-associated lipocalin, kidney injury molecule-1, interleukin-18 or liver-fatty acid-binding protein). Conclusions Preoperative ACEi/ARB usage was associated with functional but not structural acute kidney injury. As AKI from ACEi/ARB in this setting is unclear, interventional studies testing different strategies of perioperative ACEi/ARB use are warranted. PMID:24081864

A Soft Computing Approach to Kidney Diseases Evaluation.

PubMed

Neves, José; Martins, M Rosário; Vilhena, João; Neves, João; Gomes, Sabino; Abelha, António; Machado, José; Vicente, Henrique

2015-10-01

Kidney renal failure means that one's kidney have unexpectedly stopped functioning, i.e., once chronic disease is exposed, the presence or degree of kidney dysfunction and its progression must be assessed, and the underlying syndrome has to be diagnosed. Although the patient's history and physical examination may denote good practice, some key information has to be obtained from valuation of the glomerular filtration rate, and the analysis of serum biomarkers. Indeed, chronic kidney sickness depicts anomalous kidney function and/or its makeup, i.e., there is evidence that treatment may avoid or delay its progression, either by reducing and prevent the development of some associated complications, namely hypertension, obesity, diabetes mellitus, and cardiovascular complications. Acute kidney injury appears abruptly, with a rapid deterioration of the renal function, but is often reversible if it is recognized early and treated promptly. In both situations, i.e., acute kidney injury and chronic kidney disease, an early intervention can significantly improve the prognosis. The assessment of these pathologies is therefore mandatory, although it is hard to do it with traditional methodologies and existing tools for problem solving. Hence, in this work, we will focus on the development of a hybrid decision support system, in terms of its knowledge representation and reasoning procedures based on Logic Programming, that will allow one to consider incomplete, unknown, and even contradictory information, complemented with an approach to computing centered on Artificial Neural Networks, in order to weigh the Degree-of-Confidence that one has on such a happening. The present study involved 558 patients with an age average of 51.7 years and the chronic kidney disease was observed in 175 cases. The dataset comprise twenty four variables, grouped into five main categories. The proposed model showed a good performance in the diagnosis of chronic kidney disease, since the sensitivity and the specificity exhibited values range between 93.1 and 94.9 and 91.9-94.2 %, respectively.

Renal stress and kidney injury biomarkers in response to endurance cycling in the heat with and without ibuprofen.

PubMed

McDermott, Brendon P; Smith, Cody R; Butts, Cory L; Caldwell, Aaron R; Lee, Elaine C; Vingren, Jakob L; Munoz, Colleen X; Kunces, Laura J; Williamson, Keith; Ganio, Matthew S; Armstrong, Lawrence E

2018-05-16

Exercise, especially in the heat, can contribute to acute kidney injury, which can expedite chronic kidney disease onset. The additional stress of ibuprofen use is hypothesized to increase renal stress. To observe the effects of endurance cycling in the heat on renal function. Secondarily, we investigated the effect of ibuprofen ingestion on kidney stress. Randomized, placebo controlled and observational methods were utilized. Forty cyclists (52±9y, 21.7±6.5% body fat) volunteered and completed an endurance cycling event (5.7±1.2h) in the heat (33.2±5.0°C, 38.4±10.7% RH). Thirty-five participants were randomized to ingest a placebo (n=17) or 600mg ibuprofen (n=18) pre-event. A blood sample was drawn before and following the event. Serum creatinine was assessed by colorimetric assay. An ELISA was used to measure serum neutrophil gelatinase-associated lipocalin. Fractional excretion of sodium was calculated after urinary and serum electrolyte analyses. Placebo versus ibuprofen groups contributed no significant difference in any variable (p>0.05). Serum creatinine significantly increased from pre- (0.52±0.14mg/dL) to post-event (0.88±0.21mg/dL; p<0.001). Serum neutrophil gelatinase-associated lipocalin significantly increased (pre: 68.51±17.54ng/mL; post: 139.12±36.52ng/mL; p<0.001) and fractional excretion of sodium was significantly reduced from pre- (0.52±0.24%) to post-event (0.27±0.18%; p<0.001). Changes in renal biomarkers suggest mild acute kidney injury and reduced kidney function during a single bout of endurance cycling in the heat, without influence from moderate ibuprofen ingestion. Copyright © 2018 Sports Medicine Australia. Published by Elsevier Ltd. All rights reserved.

Similar 5-Year Estimated Glomerular Filtration Rate Between Kidney Transplants From Uncontrolled and Controlled Donors After Circulatory Death—A Dutch Cohort Study

PubMed Central

Peters-Sengers, Hessel; Homan van der Heide, Jaap J.; Heemskerk, Martin B. A.; ten Berge, Ineke J. M.; Ultee, Fred C. W.; Idu, Mirza M.; Betjes, Michiel G. H.; van Zuilen, Arjan D.; Christiaans, Maarten H. L.; Hilbrands, Luuk H.; de Vries, Aiko P. J.; Nurmohamed, Azam S.; Berger, Stefan P.; Bemelman, Frederike J.

2017-01-01

Background Organ shortage persists despite a high rate of donation after circulatory death (DCD) in the Netherlands. The median waiting time for a deceased donor kidney in 2013 was 3.5 years. Most DCD kidneys are from controlled DCD (cDCD; Maastricht category III). Experience with uncontrolled donors after cardiac death (uDCD), that is, donors with an unexpected and irreversible cardiac arrest (Maastricht categories I and II), is increasing; and its effect on transplant outcomes needs evaluation. Methods We used the Dutch Organ Transplantation Registry to include recipients (≥18 years old) from all Dutch centers who received transplants from 2002 to 2012 with a first DCD kidney. We compared transplant outcome in uDCD (n = 97) and cDCD (n = 1441). Results Primary nonfunction in uDCD was higher than in the cDCD (19.6% vs 9.6%, P < 0.001, respectively). Delayed graft function was also higher in uDCD than in cDCD, but not significantly (73.7% vs 63.3%, P = .074, respectively). If censored for primary nonfunction, estimated glomerular filtration rates after 1 year and 5 years were comparable between uDCD and cDCD (1 year: uDCD, 44.3 (23.4) mL/min/m2 and cDCD, 45.8 (24.1) mL/min/m2; P = 0.621; 5 years: uDCD, 49.1 (25.6) mL/min/m2 and cDCD, 47.7 (21.7) mL/min/m2; P = 0.686). The differences in primary nonfunction between kidneys from uDCD and cDCD were explained by differences in the first warm ischemic period, cold ischemic time, and donor age. Conclusions We conclude that uDCD kidneys have potential for excellent function and can constitute a valuable extension of the donor pool. However, further efforts are necessary to address the high rate of primary nonfunction. PMID:27257998

Intensity of Renal Support in Critically Ill Patients with Acute Kidney Injury

PubMed Central

2008-01-01

BACKGROUND The optimal intensity of renal-replacement therapy in critically ill patients with acute kidney injury is controversial. METHODS We randomly assigned critically ill patients with acute kidney injury and failure of at least one nonrenal organ or sepsis to receive intensive or less intensive renal-replacement therapy. The primary end point was death from any cause by day 60. In both study groups, hemodynamically stable patients underwent intermittent hemodialysis, and hemodynamically unstable patients underwent continuous venovenous hemodiafiltration or sustained low-efficiency dialysis. Patients receiving the intensive treatment strategy underwent intermittent hemodialysis and sustained low-efficiency dialysis six times per week and continuous venovenous hemodiafiltration at 35 ml per kilogram of body weight per hour; for patients receiving the less-intensive treatment strategy, the corresponding treatments were provided thrice weekly and at 20 ml per kilogram per hour. RESULTS Baseline characteristics of the 1124 patients in the two groups were similar. The rate of death from any cause by day 60 was 53.6% with intensive therapy and 51.5% with less-intensive therapy (odds ratio, 1.09; 95% confidence interval, 0.86 to 1.40; P = 0.47). There was no significant difference between the two groups in the duration of renalreplacement therapy or the rate of recovery of kidney function or nonrenal organ failure. Hypotension during intermittent dialysis occurred in more patients randomly assigned to receive intensive therapy, although the frequency of hemodialysis sessions complicated by hypotension was similar in the two groups. CONCLUSIONS Intensive renal support in critically ill patients with acute kidney injury did not decrease mortality, improve recovery of kidney function, or reduce the rate of nonrenal organ failure as compared with less-intensive therapy involving a defined dose of intermittent hemodialysis three times per week and continuous renal-replacement therapy at 20 ml per kilogram per hour. (ClinicalTrials.gov number, NCT00076219.) PMID:18492867

odd skipped related1 reveals a novel role for endoderm in regulating kidney vs. vascular cell fate

PubMed Central

Mudumana, Sudha P.; Hentschel, Dirk; Liu, Yan; Vasilyev, Aleksandr; Drummond, Iain A.

2009-01-01

Summary The kidney and vasculature are intimately linked functionally and during development, where nephric and blood/vascular progenitor cells occupy adjacent bands of mesoderm in zebrafish and frog embryos. Developmental mechanisms underlying the differentiation of kidney vs. blood/vascular lineages remain unknown. The odd skipped related1 (osr1) gene encodes a zinc finger transcription factor that is expressed in the germ ring mesendoderm and subsequently in the endoderm and intermediate mesoderm, prior to the expression of definitive kidney or blood/vascular markers. Knockdown of osr1 in zebrafish embryos resulted in a complete, segment-specific loss of anterior kidney progenitors and a compensatory increase in the number of angioblast cells in the same trunk region. Histology revealed a subsequent absence of kidney tubules, enlarged cardinal vein, and expansion of the posterior venous plexus. Altered kidney vs. vascular development correlated with expanded endoderm development in osr1 knockdowns. Combined osr1 loss of function and blockade of endoderm development by knockdown of sox32/casanova rescued anterior kidney development. The results indicate that osr1 activity is required to limit endoderm differentiation from mesendoderm and, in the absence of osr1, excess endoderm alters mesoderm differentiation, shifting the balance from kidney toward vascular development. PMID:18787069

Tolvaptan and Kidney Pain in Patients With Autosomal Dominant Polycystic Kidney Disease: Secondary Analysis From a Randomized Controlled Trial

PubMed Central

Casteleijn, Niek F.; Blais, Jaime D.; Chapman, Arlene B.; Czerwiec, Frank S.; Devuyst, Olivier; Higashihara, Eiji; Leliveld, Anna M.; Ouyang, John; Perrone, Ronald D.; Torres, Vicente E.; Gansevoort, Ron T.

2017-01-01

Background Kidney pain is a common complication in patients with autosomal dominant polycystic kidney disease (ADPKD), and data from the TEMPO 3:4 trial suggested that tolvaptan, a vasopressin V2 receptor antagonist, may have a positive effect on kidney pain in this patient group. Because pain is difficult to measure, the incidence of kidney pain leading to objective medical interventions was used in the present study to assess pain. Study Design Secondary analysis from a randomized controlled trial. Setting & Participants Patients with ADPKD with preserved kidney function. Intervention Tolvaptan or placebo. Outcomes Kidney pain events defined by objective medical interventions. Measurements Kidney pain events were recorded and independently adjudicated. Incidence of a first kidney pain event was assessed overall and categorized into 5 subgroups according to severity. Results Of 1,445 participating patients (48.4% women; mean age, 39 ± 7 [SD] years; mean estimated glomerular filtration rate, 81 ± 22 mL/min/1.73 m2; median total kidney volume, 1,692 [IQR, 750–7,555] mL), 50.9% reported a history of kidney pain at baseline. History of urinary tract infections, kidney stones, or hematuria (all P < 0.001) and female sex (P < 0.001) were significantly associated with history of kidney pain. Tolvaptan use resulted in a significantly lower incidence of kidney pain events when compared to placebo: 10.1% versus 16.8% (P < 0.001), with a risk reduction of 36% (HR, 0.64; 95% CI, 0.48–0.86). The reduction in pain event incidence by tolvaptan was found in all groups irrespective of pain severity and was independent of predisposing factors (P for interaction > 0.05). The effect of tolvaptan was explained at least in part by a decrease in incidence of urinary tract infections, kidney stones, and hematuria when compared to placebo. Limitations Trial has specific inclusion criteria for total kidney volume and kidney function. Conclusions Tolvaptan decreased the incidence of kidney pain events independent of patient characteristics predisposing for kidney pain and possibly in part due to reductions in ADPKD-related complications. PMID:27856088

Caenorhabditis elegans as a model to study renal development and disease: sexy cilia.

PubMed

Barr, Maureen M

2005-02-01

The nematode Caenorhabditis elegans has no kidney per se, yet "the worm" has proved to be an excellent model to study renal-related issues, including tubulogenesis of the excretory canal, membrane transport and ion channel function, and human genetic diseases including autosomal dominant polycystic kidney disease (ADPKD). The goal of this review is to explain how C. elegans has provided insight into cilia development, cilia function, and human cystic kidney diseases.

Polycystin 1 loss of function is directly linked to an imbalance in G-protein signaling in the kidney.

PubMed

Zhang, Bo; Tran, Uyen; Wessely, Oliver

2018-03-22

The development of the kidney relies on the establishment and maintenance of a precise tubular diameter of its functional units, the nephrons. This process is disrupted in polycystic kidney disease (PKD), resulting in dilations of the nephron and renal cyst formation. In the course of exploring G-protein-coupled signaling in the Xenopus pronephric kidney, we discovered that loss of the G-protein α subunit, Gnas, results in a PKD phenotype. Polycystin 1, one of the genes mutated in human PKD, encodes a protein resembling a G-protein-coupled receptor. Furthermore, deletion of the G-protein-binding domain present in the intracellular C terminus of polycystin 1 impacts functionality. A comprehensive analysis of all the G-protein α subunits expressed in the Xenopus pronephric kidney demonstrates that polycystin 1 recruits a select subset of G-protein α subunits and that their knockdown - as in the case of Gnas - results in a PKD phenotype. Mechanistically, the phenotype is caused by increased endogenous G-protein β/γ signaling and can be reversed by pharmacological inhibitors as well as knocking down Gnb1. Together, our data support the hypothesis that G proteins are recruited to the intracellular domain of PKD1 and that this interaction is crucial for its function in the kidney. © 2018. Published by The Company of Biologists Ltd.

Association of metabolic syndrome with kidney function and histology in living kidney donors.

PubMed

Ohashi, Y; Thomas, G; Nurko, S; Stephany, B; Fatica, R; Chiesa, A; Rule, A D; Srinivas, T; Schold, J D; Navaneethan, S D; Poggio, E D

2013-09-01

The selection of living kidney donors is based on a formal evaluation of the state of health. However, this spectrum of health includes subtle metabolic derangements that can cluster as metabolic syndrome. We studied the association of metabolic syndrome with kidney function and histology in 410 donors from 2005 to 2012, of whom 178 donors were systematically followed after donation since 2009. Metabolic syndrome was defined as per the NCEP ATPIII criteria, but using a BMI > 25 kg/m(2) instead of waist circumference. Following donation, donors received counseling on lifestyle modification. Metabolic syndrome was present in 50 (12.2%) donors. Donors with metabolic syndrome were more likely to have chronic histological changes on implant biopsies than donors with no metabolic syndrome (29.0% vs. 9.3%, p < 0.001). This finding was associated with impaired kidney function recovery following donation. At last follow-up, reversal of metabolic syndrome was observed in 57.1% of donors with predonation metabolic syndrome, while only 10.8% of donors developed de novo metabolic syndrome (p < 0.001). In conclusion, metabolic syndrome in donors is associated with chronic histological changes, and nephrectomy in these donors was associated with subsequent protracted recovery of kidney function. Importantly, weight loss led to improvement of most abnormalities that define metabolic syndrome. © Copyright 2013 The American Society of Transplantation and the American Society of Transplant Surgeons.

Optical Coherence Tomography in Kidney Transplantation

NASA Astrophysics Data System (ADS)

Andrews, Peter M.; Wierwille, Jeremiah; Chen, Yu

End-stage renal disease (ESRD) is associated with both high mortality rates and an enormous economic burden [1]. The preferred treatment option for ESRD that can extend patients' lives and improve their quality of life is kidney transplantation. However, organ shortages continue to pose a major problem in kidney transplantation. Most kidneys for transplantation come from heart-beating cadavers. Although non-heart-beating cadavers represent a potentially large pool of donor kidneys, these kidneys are not often used due to the unknown extent of damage to the renal tubules (i.e., acute tubular necrosis or "ATN") induced by ischemia (i.e., lack of blood flow). Also, ischemic insult suffered by kidneys awaiting transplantation frequently causes ATN that leads to varying degrees of delayed graft function (DGF) after transplantation. Finally, ATN represents a significant risk for eventual graft and patient survival [2, 3] and can be difficult to discern from rejection. In present clinical practice, there is no reliable real-time test to determine the viability of donor kidneys and whether or not donor kidneys might exhibit ATN. Therefore, there is a critical need for an objective and reliable real-time test to predict ATN to use these organs safely and utilize the donor pool optimally. In this review, we provided preliminary data indicating that OCT can be used to predict the post-transplant function of kidneys used in transplantation.

Hand-assisted Laparoscopic Nephrectomy in Living-donor Kidneys With Multiple Arteries: Experience of a Transplant Center.

PubMed

Bandín Musa, Alfonso Ricardo; Montes de Oca, Jorge

2016-04-01

Hand-assisted laparoscopic nephrectomy is a relatively new procedure in our country. This article reports on one of the largest number of this procedure in kidneys with multiple vessels. We reviewed all cases of hand-assisted laparoscopic nephrectomy from July 2002 to February 2009. Results were then descriptive, with statistical analyses performed with SPSS software (SPSS: An IBM Company, version 10.0, IBM Corporation, Armonk, NY, USA). From July 2002 to February 2009, 165 patients had hand-assisted laparoscopic nephrectomy, with 96.9% being the left kidney. We found a prevalence of 18.7% (n = 31) of kidneys with multiple arteries, with 8 of these having multiple principal arteries, 9 with superior polar artery, and 14 with inferior polar artery. Twenty-nine donors (17.57%) presented with more than 1 principal vein. Warm ischemia was longer in kidneys with multiple arteries (4.16 vs 3.96 min); recipient renal function (evaluated by creatinine levels at day 5 after transplant) was 1.63 mg/dL in kidneys with single artery versus 1.27 mg/dL in kidneys with multiple arteries. There were no significant differences for time of surgery, bleeding, and discharge of the donor. We found no differences in kidney function between single and multiple artery kidneys, resulting in the conclusion that hand-assisted laparoscopic nephrectomy offers an effective option for kidney donors, including those with multiple arteries.

Fibroblast Growth Factor 23: A Biomarker of Kidney Function Decline.

PubMed

Drew, David A; Katz, Ronit; Kritchevsky, Stephen; Ix, Joachim H; Shlipak, Michael G; Newman, Anne B; Hoofnagle, Andy; Fried, Linda; Sarnak, Mark J; Gutierrez, Orlando M

2018-01-01

Fibroblast growth factor 23 (FGF-23) is a hormone that regulates phosphorus levels and vitamin D metabolism. Previous studies have shown FGF-23 to be a risk factor for incident end-stage renal disease; however, there are less data on the association of FGF-23 with earlier kidney-related outcomes. Serum FGF-23 was assayed using an intact ELISA assay in 2,496 participants of the Healthy Aging and Body Composition Study, a cohort of well-functioning older adults. Kidney function was estimated by assaying cystatin C at baseline and years 3 and 10. The associations between FGF-23 and decline in kidney function (defined by estimated glomerular filtration rate (eGFR) decline ≥30% or ≥3 mL/min/year) and incident chronic kidney disease (CKD; incident eGFR <60 mL/min/1.73 m2 and ≥1 mL/min/year decline) were evaluated. Models were adjusted for demographics, baseline eGFR, urine albumin/creatinine ratio, comorbidity, and serum calcium, phosphorus, 25(OH) vitamin D and parathyroid hormone. The mean (SD) age was 75 (3) years, with 52% female and 38% black. There were 405 persons with 30% decline, 702 with >3 mL/min/year decline, and 536 with incident CKD. In fully adjusted continuous models, doubling of FGF-23 concentrations was not associated with kidney function decline (OR [95% CI] = 0.98 [0.82-1.19] for ≥30% decline and OR 1.17 [95% CI 1.00-1.37] for ≥3 mL/min/year decline), or incident CKD (incident rate ratio [IRR] 1.05 [95% CI 0.91-1.22]). In adjusted quartile analysis, the highest quartile of FGF-23 was significantly associated with incident CKD (IRR 1.27 [95% CI 1.02-1.58] for highest vs. lowest quartile). Higher FGF-23 concentrations were not consistently associated with decline in kidney function or incident CKD in community-dwelling older adults. © 2018 S. Karger AG, Basel.

Relationship of fibroblast growth factor 21 with kidney function and albuminuria: multi-ethnic study of atherosclerosis.

PubMed

Anuwatmatee, Sahapab; Allison, Matthew A; Shlipak, Michael G; McClelland, Robyn L; Kramer, Holly; Tang, Shudi; Hou, Liming; Rye, Kerry-Anne; Ong, Kwok Leung

2018-05-15

Fibroblast growth factor 21 (FGF21) may play a role in the development of chronic kidney disease (CKD). We therefore investigated the relationship of plasma FGF21 levels with kidney function and albuminuria in the Multi-Ethnic Study of Atherosclerosis (MESA). The analysis included 5724 MESA participants ages 45-84 years between 2000 and 2002, free of clinically apparent cardiovascular disease (CVD). Participants were followed up in person at four additional clinic visits over 10 years. Plasma FGF21 levels were measured at baseline examination by enzyme-linked immunosorbent assay. Kidney function was assessed by estimated glomerular filtration rate (eGFR). Outcomes were urinary albumin:creatinine ratio (UACR) progression, incident CKD by eGFR (reaching eGFR <60 mL/min/1.73 m2 with eGFR loss rate ≥1 mL/min/1.73 m2 per year) and rapid kidney function decline (eGFR decline >5%/year). At baseline, higher FGF21 levels, assessed as both continuous and categorical quartile variables, were significantly associated with lower eGFR and higher UACR, after adjusting for demographic, socioeconomic and other confounding factors [adjusted mean differences of -2.63 mL/min/1.73 m2 in eGFR and 0.134 in log normally transformed UACR (mg/g) for the highest FGF21 quartile compared with the lowest quartile, all P < 0.001]. However, in longitudinal analyses, baseline FGF21 levels did not predict incident CKD by eGFR, rapid kidney function decline or UACR progression. No significant interaction with sex and race/ethnicity was found (all P > 0.05). Our study does not support a role of FGF21 as a biomarker for predicting kidney function decline or albuminuria in adults free of clinically apparent CVD at baseline.

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 effects of weight change on glomerular filtration rate.

PubMed

Chang, Alex; Greene, Tom H; Wang, Xuelei; Kendrick, Cynthia; Kramer, Holly; Wright, Jackson; Astor, Brad; Shafi, Tariq; Toto, Robert; Lewis, Julia; Appel, Lawrence J; Grams, Morgan

2015-11-01

Little is known about the effect of weight loss/gain on kidney function. Analyses are complicated by uncertainty about optimal body surface indexing strategies for measured glomerular filtration rate (mGFR). Using data from the African-American Study of Kidney Disease and Hypertension (AASK), we determined the association of change in weight with three different estimates of change in kidney function: (i) unindexed mGFR estimated by renal clearance of iodine-125-iothalamate, (ii) mGFR indexed to concurrently measured BSA and (iii) GFR estimated from serum creatinine (eGFR). All models were adjusted for baseline weight, time, randomization group and time-varying diuretic use. We also examined whether these relationships were consistent across a number of subgroups, including tertiles of baseline 24-h urine sodium excretion. In 1094 participants followed over an average of 3.6 years, a 5-kg weight gain was associated with a 1.10 mL/min/1.73 m(2) (95% CI: 0.87 to 1.33; P < 0.001) increase in unindexed mGFR. There was no association between weight change and mGFR indexed for concurrent BSA (per 5 kg weight gain, 0.21; 95% CI: -0.02 to 0.44; P = 0.1) or between weight change and eGFR (-0.09; 95% CI: -0.32 to 0.14; P = 0.4). The effect of weight change on unindexed mGFR was less pronounced in individuals with higher baseline sodium excretion (P = 0.08 for interaction). The association between weight change and kidney function varies depending on the method of assessment. Future clinical trials should examine the effect of intentional weight change on measured GFR or filtration markers robust to changes in muscle mass. © The Author 2015. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved.

Consequences of advanced aging on renal function in chronic hyperandrogenemic female rat model: implications for aging women with polycystic ovary syndrome.

PubMed

Patil, Chetan N; Racusen, Lorraine C; Reckelhoff, Jane F

2017-11-01

Polycystic ovary syndrome (PCOS) is the most common endocrine and reproductive disorder in premenopausal women, characterized by hyperandrogenemia, metabolic syndrome, and inflammation. Women who had PCOS during their reproductive years remain hyperandrogenemic after menopause. The consequence of chronic hyperandrogenemia with advanced aging has not been studied to our knowledge. We have characterized a model of hyperandrogenemia in female rats and have aged them to 22-25 months to mimic advanced aging in hyperandrogenemic women, and tested the hypothesis that chronic exposure to hyperandrogenemia with aging has a deleterious effect on renal function. Female rats were chronically implanted with dihydrotestosterone pellets (DHT 7.5 mg/90 days) that were changed every 85 days or placebo pellets, and renal function was measured by clearance methods. Aging DHT-treated females had a threefold higher level of DHT with significantly higher body weight, mean arterial pressure, left kidney weight, proteinuria, and kidney injury molecule-1 (KIM-1), than did age-matched controls. In addition, DHT-treated-old females had a 60% reduction in glomerular filtration rate, 40% reduction in renal plasma flow, and significant reduction in urinary nitrate and nitrite excretion (UNOxV), an index of nitric oxide production. Morphological examination of kidneys showed that old DHT-treated females had significant focal segmental glomerulosclerosis, global sclerosis, and interstitial fibrosis compared to controls. Thus chronic hyperandrogenemia that persists into old age in females is associated with renal injury. These data suggest that women with chronic hyperandrogenemia such as in PCOS may be at increased risk for development of chronic kidney disease with advanced age. © 2017 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of The Physiological Society and the American Physiological Society.

[Professor LAI Xinsheng's clinical experience in the treatment of premature ovarian failure with tongyuan acupuncture technique and Chinese herbal medicine].

PubMed

Li, Xiaozhe; Zhang, Sujuan

2017-03-12

In the treatment of premature ovarian failure (POF), professor LAI Xinsheng focuses on the determination of syndrome to seek for etiology, associating with the differentiation of meridian and collateral and that of zangfu organs. Professor LAI believes that POF is mainly manifested as amenorrhea and infertility, localized in the kidney, with the dysfunction of liver, spleen and heart. It is impacted by many pathological factors, such as cold blockage, qi stagnation, blood stagnation, blood deficiency, yin deficiency, etc., which leads to the damage of the thoroughfare vessel and the conception vessel and the blockage of menstrual flow. On the basis of four diagnostic Methods and syndrome differentiation, there are four common syndromes of POF, named qi and blood deficiency, qi and blood stagnation, liver and kidney deficiency and yang deficiency of spleen and kidney. Tongyuan acupuncture technique is summarized by Professor LAI Xinsheng on the basis of yinyang theory. It is an effective and scientific method for acupoint selection along the meridians. The acupoints on the back, communicating with the governor vessel and mind regulation, acting on the brain are selected to promote yang qi of the governor vessel. The back- shu points of five zang organs are selected to regulate the functions of internal organs. The acupoints on the abdomen and the conception vessel are selected to conduce qi to the primary so as to improve reproductive function. In the guidance of tongyuan acupuncture technique, the acupoint prescription is formed and the Chinese herbal medicines are selected in combination to improve ovarian function and regulate menstruation. Hence, the satisfactory therapeutic effects have been achieved.

Intraoperative red blood cell transfusion, delayed graft function, and infection after kidney transplant: an observational cohort study.

PubMed

Mazzeffi, Michael; Jonna, Srikar; Blanco, Natalia; Mavrothalassitis, Orestes; Odekwu, Obi; Fontaine, Magali; Rock, Peter; Tanaka, Kenichi; Thom, Kerri

2018-06-01

Kidney transplant patients are frequently anemic and at risk for red blood cell (RBC) transfusion. Previous studies suggest that pre-transplant RBC transfusion may improve kidney transplant outcomes; however, RBC transfusion is also associated with infection. The purpose of our study was to characterize the relationships between intraoperative RBC transfusion, delayed graft function (DGF), postoperative surgical site infection (SSI), and sepsis. Analysis was performed on a historical cohort of adult kidney transplant patients from a single medical center during a two-year period. Crude odds ratios for DGF, superficial and deep SSI, and sepsis were calculated for transfused patients and multivariate regression was used to control for potential confounders when significant relationships were identified. Four hundred forty-one patients had kidney transplant during the study period; 27.0% had RBC transfusion, 38.8% had DGF, 7.0% had superficial SSI, 7.9% had deep SSI, and 1.8% had sepsis. High dose RBC transfusion was associated with improved graft function, but this was negated after adjusting for confounders (OR = 0.86, 95% CI  0.26 to 2.88). There was no association between RBC transfusion and SSI. RBC transfusion was independently associated with sepsis (OR = 8.98, 95% CI  1.52 to 53.22), but the confidence interval was wide. Intraoperative RBC transfusion during kidney transplant is not associated with improved allograft function or incisional SSI, but is associated with postoperative sepsis. RBCs should not be liberally transfused during kidney transplant surgery to improve graft outcomes.

Graft function assessment in mouse models of single- and dual- kidney transplantation.

PubMed

Wang, Lei; Wang, Ximing; Jiang, Shan; Wei, Jin; Buggs, Jacentha; Fu, Liying; Zhang, Jie; Liu, Ruisheng

2018-05-23

Animal models of kidney transplantation (KTX) are widely used in studying immune response of hosts to implanted grafts. Additionally, KTX can be used in generating kidney-specific knockout animal models by transplantation of kidneys from donors with global knockout of a gene to wild type recipients or vise verse. Dual kidney transplantation (DKT) provides a more physiological environment for recipients than single kidney transplantation (SKT). However, DKT in mice is rare due to technical challenges. In this study, we successfully performed DKT in mice and compared the hemodynamic response and graft function with SKT. The surgical time, complications and survival rate of DKT were not significantly different from SKT, where survival rates were above 85%. Mice with DKT showed less injury and quicker recovery with lower plasma creatinine (Pcr) and higher GFR than SKT mice (Pcr = 0.34 and 0.17 mg/dl in DKT vs. 0.50 and 0.36 mg/dl in SKT at 1 and 3 days, respectively; GFR = 215 and 131 µl/min for DKT and SKT, respectively). In addition, the DKT exhibited better renal functional reserve and long-term outcome of renal graft function than SKT based on the response to acute volume expansion. In conclusion, we have successfully generated a mouse DKT model. The hemodynamic responses of DKT better mimic physiological situations with less kidney injury and better recovery than SKT because of reduced confounding factors such as single nephron hyperfiltration. We anticipate DKT in mice will provide an additional tool for evaluation of renal significance in physiology and disease.

Differences in urine cadmium associations with kidney outcomes based on serum creatinine and cystatin C

PubMed Central

Weaver, Virginia M.; Kim, Nam-Soo; Lee, Byung-Kook; Parsons, Patrick J.; Spector, June; Fadrowski, Jeffrey; Jaar, Bernard G.; Steuerwald, Amy J.; Todd, Andrew C.; Simon, David; Schwartz, Brian S.

2011-01-01

Cadmium is a well known nephrotoxicant; chronic exposure increases risk for chronic kidney disease. Recently, however, associations between urine cadmium and higher creatinine-based estimated glomerular filtration rate (eGFR) have been reported. Analyses utilizing alternate biomarkers of kidney function allow evaluation of potential mechanisms for these observations. We compared associations of urine cadmium with kidney function measures based on serum cystatin C to those with serum creatinine in 712 lead workers. Mean (standard deviation) molybdenum-corrected urine cadmium, Modification of Diet in Renal Disease (MDRD) eGFR and multi-variable cystatin C eGFR were 1.02 (0.65) μg/g creatinine, and 97.4 (19.2) and 112.0 (17.7) mL/min/1.73 m2, respectively. The eGFR measures were moderately correlated (rs = 0.5; p less than 0.001). After adjustment, ln(urine cadmium) was not associated with serum cystatin-C-based measures. However, higher ln(urine cadmium) was associated with higher creatinine-based eGFRs including the MDRD and an equation incorporating serum cystatin C and creatinine (beta-coefficient = 4.1 ml/min/1.73 m2; 95% confidence interval =1.6, 6.6). Urine creatinine was associated with serum creatinine-based but not cystatin-C-based eGFRs. These results support a biomarker-specific, rather than a kidney function, effect underlying the associations observed between higher urine cadmium and creatinine-based kidney function measures. Given the routine use of serum and urine creatinine in kidney and biomarker research, additional research to elucidate the mechanism(s) for these associations is essential. PMID:21871619

The Relationship between Maternal Nutrition during Pregnancy and Offspring Kidney Structure and Function in Humans: A Systematic Review

PubMed Central

Lee, Yu Qi; Collins, Clare E.; Gordon, Adrienne; Rae, Kym M.; Pringle, Kirsty G.

2018-01-01

The intrauterine environment is critical for fetal growth and organ development. Evidence from animal models indicates that the developing kidney is vulnerable to suboptimal maternal nutrition and changes in health status. However, evidence from human studies are yet to be synthesised. Therefore, the aim of the current study was to systematically review current research on the relationship between maternal nutrition during pregnancy and offspring kidney structure and function in humans. A search of five databases identified 9501 articles, of which three experimental and seven observational studies met the inclusion criteria. Nutrients reviewed to date included vitamin A (n = 3), folate and vitamin B12 (n = 2), iron (n = 1), vitamin D (n = 1), total energy (n = 2) and protein (n = 1). Seven studies were assessed as being of “positive” and three of “neutral” quality. A variety of populations were studied, with limited studies investigating maternal nutrition during pregnancy, while measurements of offspring kidney outcomes were diverse across studies. There was a lack of consistency in the timing of follow-up for offspring kidney structure and/or function assessments, thus limiting comparability between studies. Deficiencies in maternal folate, vitamin A, and total energy during pregnancy were associated with detrimental impacts on kidney structure and function, measured by kidney volume, proteinuria, eGFRcystC and mean creatinine clearance in the offspring. Additional experimental and longitudinal prospective studies are warranted to confirm this relationship, especially in Indigenous populations where the risk of renal disease is greater. PMID:29466283

The effect of the use of a TNF-alpha inhibitor in hypothermic machine perfusion on kidney function after transplantation.

PubMed

Diuwe, Piotr; Domagala, Piotr; Durlik, Magdalena; Trzebicki, Janusz; Chmura, Andrzej; Kwiatkowski, Artur

2017-08-01

One of the most important problems in transplantation medicine is the ischemia/reperfusion injury of the organs to be transplanted. The aim of the present study was to assess the effect of tumor necrosis factor-alpha (TNF-alpha) inhibitor etanercept on the machine perfusion hypothermia of renal allograft kidney function and organ perfusion. No statistically significant differences were found in the impact of the applied intervention on kidney machine perfusion during which the average flow and vascular resistance were evaluated. There were no statistically significant differences in the occurrence of delayed graft function (DGF). Fewer events in patients who received a kidney from the etanercept treated Group A compared to the patients who received a kidney from the control Group B were observed when comparing the functional DGF and occurrence of acute rejection episodes, however, there was no statistically significant difference. In summary, no effect of treatment with etanercept an inhibitor of TNF-alpha in a hypothermic machine perfusion on renal allograft renal survival and its perfusion were detected in this study. However, treatment of the isolated organ may be important for the future of transplantation medicine. Copyright © 2017 Elsevier Inc. All rights reserved.

Assessment of chronic kidney disease using skin texture as a key parameter: for South Indian population.

PubMed

Udhayarasu, Madhanlal; Ramakrishnan, Kalpana; Periasamy, Soundararajan

2017-12-01

Periodical monitoring of renal function, specifically for subjects with history of diabetic or hypertension would prevent them from entering into chronic kidney disease (CKD) condition. The recent increase in numbers may be due to food habits or lack of physical exercise, necessitates a rapid kidney function monitoring system. Presently, it is determined by evaluating glomerular filtration rate (GFR) that is mainly dependent on serum creatinine value and demographic parameters and ethnic value. Attempted here is to develop ethnic parameter based on skin texture for every individual. This value when used in GFR computation, the results are much agreeable with GFR obtained through standard modification of diet in renal disease and CKD epidemiology collaboration equations. Once correlation between CKD and skin texture is established, classification tool using artificial neural network is built to categorise CKD level based on demographic values and parameter obtained through skin texture (without using creatinine). This network when tested gives almost at par results with the network that is trained with demographic and creatinine values. The results of this Letter demonstrate the possibility of non-invasively determining kidney function and hence for making a device that would readily assess the kidney function even at home.

The 6-hydroxychromanol derivative SUL-109 ameliorates renal injury after deep hypothermia and rewarming in rats.

PubMed

Vogelaar, Pieter C; Roorda, Maurits; de Vrij, Edwin L; Houwertjes, Martin C; Goris, Maaike; Bouma, Hjalmar; van der Graaf, Adrianus C; Krenning, Guido; Henning, Robert H

2018-04-11

Mitochondrial dysfunction plays an important role in kidney damage in various pathologies, including acute and chronic kidney injury and diabetic nephropathy. In addition to the well-studied ischaemia/reperfusion (I/R) injury, hypothermia/rewarming (H/R) also inflicts acute kidney injury. Substituted 6-hydroxychromanols are a novel class of mitochondrial medicines that ameliorate mitochondrial oxidative stress and protect the mitochondrial network. To identify a novel 6-hydroxychromanol that protects mitochondrial structure and function in the kidney during H/R, we screened multiple compounds in vitro and subsequently assessed the efficacy of the 6-hydroxychromanol derivatives SUL-109 and SUL-121 in vivo to protect against kidney injury after H/R in rats. Human proximal tubule cell viability was assessed following exposure to H/R for 48/4 h in the presence of various 6-hydroxychromanols. Selected compounds (SUL-109, SUL-121) or vehicle were administered to ketamine-anaesthetized male Wistar rats (IV 135 µg/kg/h) undergoing H/R at 15°C for 3 h followed by rewarming and normothermia for 1 h. Metabolic parameters and body temperature were measured throughout. In addition, renal function, renal injury, histopathology and mitochondrial fitness were assessed. H/R injury in vitro lowered cell viability by 94 ± 1%, which was counteracted dose-dependently by multiple 6-hydroxychomanols derivatives. In vivo, H/R in rats showed kidney injury molecule 1 expression in the kidney and tubular dilation, accompanied by double-strand DNA breaks and protein nitrosylation. SUL-109 and SUL-121 ameliorated tubular kidney damage, preserved mitochondrial mass and maintained cortical adenosine 5'-triphosphate (ATP) levels, although SUL-121 did not reduce protein nitrosylation. The substituted 6-hydroxychromanols SUL-109 and SUL-121 ameliorate kidney injury during in vivo H/R by preserving mitochondrial mass, function and ATP levels. In addition, both 6-hydroxychromanols limit DNA damage, but only SUL-109 also prevented protein nitrosylation in tubular cells. Therefore SUL-109 offers a promising therapeutic strategy to preserve kidney mitochondrial function.

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

Jaggi, Jaspreet Singh; Seshan, Surya V.; McDevitt, Michael R.

Purpose: Internal irradiation of kidneys as a consequence of radioimmunotherapy, radiation accidents, or nuclear terrorism can result in radiation nephropathy. We attempted to modify pharmacologically, the functional and morphologic changes in mouse kidneys after injection with the actinium ({sup 225}Ac) nanogenerator, an in vivo generator of {alpha}- and {beta}-particle emitting elements. Methods and Materials: The animals were injected with 0.35 {mu}Ci of the {sup 225}Ac nanogenerator, which delivers a dose of 27.6 Gy to the kidneys. Then, they were randomized to receive captopril (angiotensin-converting enzyme inhibitor), L-158,809 (angiotensin II receptor-1 blocker), spironolactone (aldosterone receptor antagonist), or a placebo. Results: Fortymore » weeks after the {sup 225}Ac injection, the placebo-control mice showed a significant increase in blood urea nitrogen (BUN) (87.6 {+-} 6.9 mg/dL), dilated Bowman spaces, and tubulolysis with basement membrane thickening. Captopril treatment accentuated the functional (BUN 119.0 {+-} 4.0 mg/dL; p <0.01 vs. placebo controls) and histopathologic damage. In contrast, L-158,809 offered moderate protection (BUN 66.6 {+-} 3.9 mg/dL; p = 0.02 vs. placebo controls). Spironolactone treatment, however, significantly prevented the development of histopathologic and functional changes (BUN 31.2 {+-} 2.5 mg/dL; p <0.001 vs. placebo controls). Conclusions: Low-dose spironolactone and, to a lesser extent, angiotensin receptor-1 blockade can offer renal protection in a mouse model of internal {alpha}-particle irradiation.« less

Functional capacity and cryopreservation of fetal rat pancreas in streptozotocin-diabetes. [Effectiveness of transplantation of fetal pancreas for control of diabetes in adult rats

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

Brown, J.; Clark, W.; Molnar, I.G.

1976-01-01

The fetal rat pancreas has a marked capacity for growth and maturation in glucose responsivity after transplantation under the kidney capsules of adult rats. The optimal conditions for function of the organ are a 3-week period of growth in a normal rat before transfer to a diabetic animal. Under these conditions diabetes is completely reversed by one fetal pancreas, and glucose disappearance rate and plasma insulin response to glucose are normal. Shunting of the venous drainage into the liver from fetal pancreases placed beneath the kidney capsule results in a marked improvement in diabetes control, and this technique may provemore » useful in experimental or human applications. Cryopreservation of the fetal pancreas has been successfully accomplished and will serve as a useful adjuvant to this method of reversing experimental diabetes.« less

Acute kidney injury after contrast-enhanced examination among elderly1

PubMed Central

Aoki, Beatriz Bonadio; Fram, Dayana; Taminato, Mônica; Batista, Ruth Ester Sayad; Belasco, Angélica; Barbosa, Dulce Aparecida

2014-01-01

OBJECTIVES: to assess renal function in elderly patients undergoing contrast-enhanced computed tomography and identify the preventive measures of acute kidney injury in the period before and after the examination. METHOD: longitudinal cohort study conducted at the Federal University of São Paulo Hospital, from March 2011 to March 2013. All hospitalized elderly, of both sexes, aged 60 years and above, who performed the examination, were included (n=93). We collected sociodemographic data, data related to the examination and to the care provided, and creatinine values prior and post exam. RESULTS: an alteration in renal function was observed in 51 patients (54%) with a statistically significant increase of creatinine values (p<0.04), and two patients (4.0%) required hemodialysis. CONCLUSION: There is an urgent need for protocols prior to and post contrast-enhanced examination in the elderly, and other studies to verify the prognosis of this population. PMID:25296148

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.

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.

Reversible preoperative renal dysfunction does not add to the risk of postoperative acute kidney injury after cardiac valve surgery

PubMed Central

Xu, Jia-Rui; Zhuang, Ya-Min; Liu, Lan; Shen, Bo; Wang, Yi-Mei; Luo, Zhe; Teng, Jie; Wang, Chun-Sheng; Ding, Xiao-Qiang

2017-01-01

Objective To evaluate the impact of the renal dysfunction (RD) type and change of postoperative cardiac function on the risk of developing acute kidney injury (AKI) in patients who underwent cardiac valve surgery. Method Reversible renal dysfunction (RRD) was defined as preoperative RD in patients who had not been initially diagnosed with chronic kidney disease (CKD). Cardiac function improvement (CFI) was defined as postoperative left ventricular ejection function – preoperative left ventricular ejection function (ΔEF) >0%, and cardiac function not improved (CFNI) as ΔEF ≤0%. Results Of the 4,805 (94%) cardiac valve surgery patients, 301 (6%) were RD cases. The AKI incidence in the RRD group (n=252) was significantly lower than in the CKD group (n=49) (36.5% vs 63.3%, P=0.018). The AKI and renal replacement therapy incidences in the CFI group (n=174) were significantly lower than in the CFNI group (n=127) (33.9% vs 50.4%, P=0.004; 6.3% vs 13.4%, P=0.037). After adjustment for age, gender, and other confounding factors, CKD and CKD + CFNI were identified as independent risk factors for AKI in all patients after cardiac valve surgery. Multivariate logistic regression analysis showed that the risk factors for postoperative AKI in preoperative RD patients were age, gender (male), hypertension, diabetes, chronic heart failure, cardiopulmonary bypass time (every 1 min added), and intraoperative hypotension, while CFI after surgery could reduce the risk. Conclusion For cardiac valve surgery patients, preoperative CKD was an independent risk factor for postoperative AKI, but RRD did not add to the risk. Improved postoperative cardiac function can significantly reduce the risk of postoperative AKI. PMID:29184415

Bardoxolone: augmenting the Yin in chronic kidney disease.

PubMed

Thomas, Merlin C

2011-10-01

Nrf-2 (NF-E2-related factor 2) is a regulator of anti-oxidant, anti-inflammatory and detoxification pathways. Coordinated augmentation of these key defence pathways via Nrf-2 signalling is being investigated for the treatment of chronic diseases, including diabetes and its complications. The first to reach commercial development is the triterpenoid, bardoxolone methyl. In recent clinical trial, bardoxolone rapidly improved kidney function on average by 5-10 ml/min within 4 weeks of therapy. Importantly, this improvement was sustained during one year of active treatment. This suggests that rather that overworking a failing system, bardoxolone appeared to safely augment renal function, at least to one year. If similar improvements in kidney function can be reproduced in the upcoming BEACON trial, it will represent a major advance on conventional therapy and new way to bring balance to the failing kidney.

Application of ureterorenoscope and flexible ureterorenoscope lithotripsy in removing calculus from extracorporeal living donor renal graft: a single-center experience.

PubMed

Lin, Chun-Hua; Zhang, Zuo-Fu; Wang, Jiahui; Yu, Lu-Xin; Wang, Wen-Ting; Shi, Lei; Lin, Xiang-Nan

2017-11-01

Here, we reported our clinical application of ureterorenoscope (URS) and flexible URS lithotripsy in stone removal on 10 cases of excised living donor kidney graft. After the extraction of donor kidney by retroperitoneal laparoscopy, the donor graft was perfused with 4 °C HCA solution. Calculus between 2-4 mm were removed intact with lithotomy forceps under direct vision of URS. Larger calculi of >4 mm were fractured with flexible URS combining holmium laser lithotripsy. Fragments of the calculus were extracted with basket extractor and lithotomy forceps. All operations were successful. The operation time was 14-31 min (average 21.2 ± 6.3 min). The kidneys were then transplanted to the recipients using routine procedure. The transplanted kidneys functioned well after transplantation. Gross hematuria resolved 1-4 d after operation (average 2.6 ± 0.9 d). The transplanted kidneys functioned well without early complications such as functional recovery delay and acute graft rejection. The donors and recipients were followed for 12 months. The size of the transplanted kidneys was normal and new stones or urinary obstruction was not seen upon urinary color Doppler ultrasound examination. In conclusion, we believe it is feasible, safe and effective to use URS or flexible URS combining holmium laser lithotripsy on extracorporeal living donor kidney.

Multi-color autofluorescence and scattering spectroscopy provides rapid assessment of kidney function following ischemic injury

NASA Astrophysics Data System (ADS)

Raman, Rajesh N.; Pivetti, Chris D.; Ramsamooj, Rajendra; Troppmann, Christoph; Demos, Stavros G.

2018-02-01

A major source of kidneys for transplant comes from deceased donors whose tissues have suffered an unknown amount of warm ischemia prior to retrieval, with no quantitative means to assess function before transplant. Toward addressing this need, non-contact monitoring of optical signatures in rat kidneys was performed in vivo during ischemia and reperfusion. Kidney autofluorescence images were captured under ultraviolet illumination (355 nm, 325 nm, and 266 nm) in order to provide information on related metabolic and non-metabolic response. In addition, light scattering images under 355 nm, 325 nm, and 266 nm, 500 nm illumination were monitored to report on changes in kidney optical properties giving rise to the observed autofluorescence signals during these processes. During reperfusion, various signal ratios were generated from the recorded signals and then parametrized. Time-dependent parameters derived from the ratio of autofluorescence under 355 nm excitation to that under 266 nm excitation, as well as from 500 nm scattered signal, were found capable of discriminating dysfunctional kidneys from those that were functional (p < 0.01) within hours of reperfusion. Kidney dysfunction was confirmed by subsequent survival study and histology following autopsy up to a week later. Physiologic changes potentially giving rise to the observed signals, including those in cellular metabolism, vascular response, tissue microstructure, and microenvironment chemistry, are discussed.

One or 4 h of "in-house" reconditioning by machine perfusion after cold storage improve reperfusion parameters in porcine kidneys.

PubMed

Gallinat, Anja; Efferz, Patrik; Paul, Andreas; Minor, Thomas

2014-11-01

In-house machine perfusion after cold storage (hypothermic reconditioning) has been proposed as convenient tool to improve kidney graft function. This study investigated the role of machine perfusion duration for early reperfusion parameters in porcine kidneys. Kidney function after cold preservation (4 °C, 18 h) and subsequent reconditioning by one or 4 h of pulsatile, nonoxygenated hypothermic machine perfusion (HMP) was studied in an isolated kidney perfusion model in pigs (n = 6, respectively) and compared with simply cold-stored grafts (CS). Compared with CS alone, one or 4 h of subsequent HMP similarly and significantly improved renal flow and kidney function (clearance and sodium reabsorption) upon warm reperfusion, along with reduced perfusate concentrations of endothelin-1 and increased vascular release of nitric oxide. Molecular effects of HMP comprised a significant (vs CS) mRNA increase in the endothelial transcription factor KLF2 and lower expression of endothelin that were observed already at the end of one-hour HMP after CS. Reconditioning of cold-stored kidneys is possible, even if clinical logistics only permit one hour of therapy, while limited extension of the overall storage time by in-house machine perfusion might also allow for postponing of transplantation from night to early day work. © 2014 Steunstichting ESOT.

Analysis of renal blood flow and renal volume in normal fetuses and in fetuses with a solitary functioning kidney.

PubMed

Hindryckx, An; Raaijmakers, Anke; Levtchenko, Elena; Allegaert, Karel; De Catte, Luc

2017-12-01

To evaluate renal blood flow and renal volume for the prediction of postnatal renal function in fetuses with solitary functioning kidney (SFK). Seventy-four SFK fetuses (unilateral renal agenesis [12], multicystic dysplastic kidney [36], and severe renal dysplasia [26]) were compared with 58 healthy fetuses. Peak systolic velocity (PSV), pulsatility index (PI), and resistance index (RI) of the renal artery (RA) were measured; 2D and 3D (VOCAL) volumes were calculated. Renal length and glomerular filtration rate (GFR) were obtained in SFK children (2 years). Compared with the control group, the PSV RA was significantly lower in nonfunctioning kidneys and significantly higher in SFK. Volume measurements indicated a significantly larger volume of SFK compared with healthy kidneys. All but 4 children had GFR above 70 mL/min/1.73 m 2 , and compensatory hypertrophy was present in 69% at 2 years. PSV RA and SFK volume correlated with postnatal renal hypertrophy. No correlation between prenatal and postnatal SFK volume and GFR at 2 years was demonstrated. Low PSV RA might have a predictive value for diagnosing a nonfunctioning kidney in fetuses with a SFK. We demonstrated a higher PSV RA and larger renal volume in the SFK compared with healthy kidneys. © 2017 John Wiley & Sons, Ltd.

An Active Learning Exercise to Facilitate Understanding of Nephron Function: Anatomy and Physiology of Renal Transporters

ERIC Educational Resources Information Center

Dirks-Naylor, Amie J.

2016-01-01

Renal transport is a central mechanism underlying electrolyte homeostasis, acid base balance and other essential functions of the kidneys in human physiology. Thus, knowledge of the anatomy and physiology of the nephron is essential for the understanding of kidney function in health and disease. However, students find this content difficult to…

Enhanced hepatic and kidney cytochrome p-450 activities in nandrolone decanoate treated albino mice.

PubMed

Acharjee, B K; Mahanta, R

2009-04-01

Anabolic androgenic steroids are the xenobiotic substrates that are metabolized in the body by the protective enzyme systems. Mixed function oxygenase enzymes include a group of enzymes which play an essential role in the metabolism of a broad range of xenobiotics including endogenous and exogenous substrates. Cytochrome P-450, a member of mixed function oxygenase enzymes, plays an important role in oxidative metabolism of drugs and xenobiotics entering human body. Various anabolic steroids are found either to increase or decrease the activity of cytochrome P-450. However, effect of nandrolone decanoate, most commonly abused anabolic steroid, on cytochrome P-450 activity is still fragmentary. In the present study, albino mice were administered intramuscular 2.5 mg of nandrolone decanoate injection at 15 days interval. Cytochrome P-450 activity is determined by following the method of Omura and Sato (1964) in liver and kidney tissues of both normal and experimental groups upto 90 days. Investigation shows a significant (p <0.01) increase of cytochrome P-450 (nmol/mg) activity in liver tissue as compared to that of kidney tissues. A tissue specific and dose specific increase of cytochrome P-450 activity is observed. Mean cytochrome P-450 is found highest in liver tissue on 45(th) day whereas the activity in kidney tissue is noticed on 90(th) day of treatment. From the above observation, nandrolone decanoate can be suggested as a potent inducer of cytochrome P-450 activity like other anabolic steroids.

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.

Kidney-inspired algorithm for optimization problems

NASA Astrophysics Data System (ADS)

Jaddi, Najmeh Sadat; Alvankarian, Jafar; Abdullah, Salwani

2017-01-01

In this paper, a population-based algorithm inspired by the kidney process in the human body is proposed. In this algorithm the solutions are filtered in a rate that is calculated based on the mean of objective functions of all solutions in the current population of each iteration. The filtered solutions as the better solutions are moved to filtered blood and the rest are transferred to waste representing the worse solutions. This is a simulation of the glomerular filtration process in the kidney. The waste solutions are reconsidered in the iterations if after applying a defined movement operator they satisfy the filtration rate, otherwise it is expelled from the waste solutions, simulating the reabsorption and excretion functions of the kidney. In addition, a solution assigned as better solution is secreted if it is not better than the worst solutions simulating the secreting process of blood in the kidney. After placement of all the solutions in the population, the best of them is ranked, the waste and filtered blood are merged to become a new population and the filtration rate is updated. Filtration provides the required exploitation while generating a new solution and reabsorption gives the necessary exploration for the algorithm. The algorithm is assessed by applying it on eight well-known benchmark test functions and compares the results with other algorithms in the literature. The performance of the proposed algorithm is better on seven out of eight test functions when it is compared with the most recent researches in literature. The proposed kidney-inspired algorithm is able to find the global optimum with less function evaluations on six out of eight test functions. A statistical analysis further confirms the ability of this algorithm to produce good-quality results.

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.

Donor-specific hypo-responsiveness occurs in simultaneous liver-kidney transplant recipients after the first year.

PubMed

Taner, Timucin; Gustafson, Michael P; Hansen, Michael J; Park, Walter D; Bornschlegl, Svetlana; Dietz, Allan B; Stegall, Mark D

2018-06-01

Kidney allografts of patients who undergo simultaneous liver-kidney transplantation incur less immune-mediated injury, and retain better function compared to other kidney allografts. To characterize the host alloimmune responses in 28 of these patients, we measured the donor-specific alloresponsiveness and phenotypes of peripheral blood cells after the first year. These values were then compared to those of 61 similarly immunosuppressed recipients of a solitary kidney or 31 recipients of liver allografts. Four multicolor, non-overlapping flow cytometry protocols were used to assess the immunophenotypes. Mixed cell cultures with donor or third party cells were used to measure cell proliferation and interferon gamma production. Despite a significant overlap, simultaneous liver-kidney transplant recipients had a lower overall frequency of circulating CD8 + , activated CD4 + and effector memory T cells, compared to solitary kidney transplant recipients. Simultaneous liver-kidney transplant recipient T cells had a significantly lower proliferative response to the donor cells compared to solitary kidney recipients (11.9 vs. 42.9%), although their response to third party cells was unaltered. The frequency of interferon gamma producing alloreactive T cells in simultaneous liver-kidney transplant recipients was significantly lower than that of solitary kidney transplant recipients. Flow cytometric analysis of the mixed cultures demonstrated that both alloreactive CD4 + and CD8 + compartments of the simultaneous liver-kidney transplant recipient circulating blood cells were smaller. Thus, the phenotypic and functional characteristics of the circulating blood cells of the simultaneous liver-kidney transplant recipients resembled those of solitary liver transplant recipients, and appear to be associated with donor-specific hypo-alloresponsiveness. Copyright © 2018 International Society of Nephrology. Published by Elsevier Inc. All rights reserved.

Effect of glomerular filtration rate at dialysis initiation on survival in patients with advanced chronic kidney disease: what is the effect of lead-time bias?

PubMed Central

Janmaat, Cynthia J; van Diepen, Merel; Krediet, Raymond T; Hemmelder, Marc H; Dekker, Friedo W

2017-01-01

Purpose Current clinical guidelines recommend to initiate dialysis in the presence of symptoms or signs attributable to kidney failure, often with a glomerular filtration rate (GFR) of 5–10 mL/min/1.73 m2. Little evidence exists about the optimal kidney function to start dialysis. Thus far, most observational studies have been limited by lead-time bias. Only a few studies have accounted for lead-time bias, and showed contradictory results. We examined the effect of GFR at dialysis initiation on survival in chronic kidney disease patients, and the role of lead-time bias therein. We used both kidney function based on 24-hour urine collection (measured GFR [mGFR]) and estimated GFR (eGFR). Materials and methods A total of 1,143 patients with eGFR data at dialysis initiation and 852 patients with mGFR data were included from the NECOSAD cohort. Cox regression was used to adjust for potential confounders. To examine the effect of lead-time bias, survival was counted from the time of dialysis initiation or from a common starting point (GFR 20 mL/min/1.73 m2), using linear interpolation models. Results Without lead-time correction, no difference between early and late starters was present based on eGFR (hazard ratio [HR] 1.03, 95% confidence interval [CI] 0.81–1.3). However, after lead-time correction, early initiation showed a survival disadvantage (HR between 1.1 [95% CI 0.82–1.48] and 1.33 [95% CI 1.05–1.68]). Based on mGFR, the potential survival benefit for early starters without lead-time correction (HR 0.8, 95% CI 0.62–1.03) completely disappeared after lead-time correction (HR between 0.94 [95% CI 0.65–1.34] and 1.21 [95% CI 0.95–1.56]). Dialysis start time differed about a year between early and late initiation. Conclusion Lead-time bias is not only a methodological problem but also has clinical impact when assessing the optimal kidney function to start dialysis. Therefore, lead-time bias is extremely important to correct for. Taking account of lead-time bias, this controlled study showed that early dialysis initiation (eGFR >7.9, mGFR >6.6 mL/min/1.73 m2) was not associated with an improvement in survival. Based on kidney function, this study suggests that in some patients, dialysis could be started even later than an eGFR <5.7 and mGFR <4.3 mL/min/1.73 m2. PMID:28442934

Genetic modification of mesenchymal stem cells to overexpress CXCR4 and CXCR7 does not improve the homing and therapeutic potentials of these cells in experimental acute kidney injury.

PubMed

Gheisari, Yousof; Azadmanesh, Kayhan; Ahmadbeigi, Naser; Nassiri, Seyed Mahdi; Golestaneh, Azadeh Fahim; Naderi, Mahmood; Vasei, Mohammad; Arefian, Ehsan; Mirab-Samiee, Siamak; Shafiee, Abbas; Soleimani, Masoud; Zeinali, Sirous

2012-11-01

The therapeutic potential of bone marrow mesenchymal stem cells (MSCs) in kidney failure has been examined in some studies. However, recent findings indicate that after transplantation, these cells home to kidneys at very low levels. Interaction of stromal derived factor-1 (SDF-1) with its receptor, CXCR4, is of pivotal importance in migration and homing. Recently, CXCR7 has also been recognized as another SDF-1 receptor that interacts with CXCR4 and modulates its functions. In this study, CXCR4 and CXCR7 were separately and simultaneously overexpressed in BALB/c bone marrow MSCs by using a lentiviral vector system and the homing and renoprotective potentials of these cells were evaluated in a mouse model of cisplatin-induced acute kidney injury. Using flow cytometry, immunohistochemistry, and real-time PCR methods for detection of GFP-labeled MSCs, we found that although considerably entrapped in lungs, native MSCs home very rarely to kidneys and bone marrow and this rate cannot be significantly affected by CXCR4 and/or CXCR7 upregulation. Transplantation of neither native nor genetically engineered MSCs ameliorated kidney failure. We concluded that overexpression of CXCR4 and CXCR7 receptors in murine MSCs cannot improve the homing and therapeutic potentials of these cells and it can be due to severe chromosomal abnormalities that these cells bear during ex vivo expansion.

Uric acid lowering to prevent kidney function loss in diabetes: the preventing early renal function loss (PERL) allopurinol study.

PubMed

Maahs, David M; Caramori, Luiza; Cherney, David Z I; Galecki, Andrzej T; Gao, Chuanyun; Jalal, Diana; Perkins, Bruce A; Pop-Busui, Rodica; Rossing, Peter; Mauer, Michael; Doria, Alessandro

2013-08-01

Diabetic kidney disease causes significant morbidity and mortality among people with type 1 diabetes (T1D). Intensive glucose and blood pressure control have thus far failed to adequately curb this problem and therefore a major need for novel treatment approaches exists. Multiple observations link serum uric acid levels to kidney disease development and progression in diabetes and strongly argue that uric acid lowering should be tested as one such novel intervention. A pilot of such a trial, using allopurinol, is currently being conducted by the Preventing Early Renal Function Loss (PERL) Consortium. Although the PERL trial targets T1D individuals at highest risk of kidney function decline, the use of allopurinol as a renoprotective agent may also be relevant to a larger segment of the population with diabetes. As allopurinol is inexpensive and safe, it could be cost-effective even for relatively low-risk patients, pending the completion of appropriate trials at earlier stages.

Sensitivity and specificity of a single emergency department measurement of urinary neutrophil gelatinase-associated lipocalin for diagnosing acute kidney injury.

PubMed

Nickolas, Thomas L; O'Rourke, Matthew J; Yang, Jun; Sise, Meghan E; Canetta, Pietro A; Barasch, Nicholas; Buchen, Charles; Khan, Faris; Mori, Kiyoshi; Giglio, James; Devarajan, Prasad; Barasch, Jonathan

2008-06-03

A single serum creatinine measurement cannot distinguish acute kidney injury from chronic kidney disease or prerenal azotemia. To test the sensitivity and specificity of a single measurement of urinary neutrophil gelatinase-associated lipocalin (NGAL) and other urinary proteins to detect acute kidney injury in a spectrum of patients. Prospective cohort study. Emergency department of Columbia University Medical Center, New York, New York. 635 patients admitted to the hospital with acute kidney injury, prerenal azotemia, chronic kidney disease, or normal kidney function. Diagnosis of acute kidney injury was based on the RIFLE (risk, injury, failure, loss, and end-stage) criteria and assigned by researchers who were blinded to experimental measurements. Urinary NGAL was measured by immunoblot, N-acetyl-beta-d-glucosaminidase (NAG) by enzyme measurement, alpha1-microglobulin and alpha(1)-acid glycoprotein by immunonephelometry, and serum creatinine by Jaffe kinetic reaction. Experimental measurements were not available to treating physicians. Patients with acute kidney injury had a significantly elevated mean urinary NGAL level compared with the other kidney function groups (416 microg/g creatinine [SD, 387]; P = 0.001). At a cutoff value of 130 microg/g creatinine, sensitivity and specificity of NGAL for detecting acute injury were 0.900 (95% CI, 0.73 to 0.98) and 0.995 (CI, 0.990 to 1.00), respectively, and positive and negative likelihood ratios were 181.5 (CI, 58.33 to 564.71) and 0.10 (CI, 0.03 to 0.29); these values were superior to those for NAG, alpha1-microglobulin, alpha1-acid glycoprotein, fractional excretion of sodium, and serum creatinine. In multiple logistic regression, urinary NGAL level was highly predictive of clinical outcomes, including nephrology consultation, dialysis, and admission to the intensive care unit (odds ratio, 24.71 [CI, 7.69 to 79.42]). All patients came from a single center. Few kidney biopsies were performed. A single measurement of urinary NGAL helps to distinguish acute injury from normal function, prerenal azotemia, and chronic kidney disease and predicts poor inpatient outcomes.

Sensitivity and Specificity of a Single Emergency Department Measurement of Urinary Neutrophil Gelatinase–Associated Lipocalin for Diagnosing Acute Kidney Injury

PubMed Central

Nickolas, Thomas L.; O’Rourke, Matthew J.; Yang, Jun; Sise, Meghan E.; Canetta, Pietro A.; Barasch, Nicholas; Buchen, Charles; Khan, Faris; Mori, Kiyoshi; Giglio, James; Devarajan, Prasad; Barasch, Jonathan

2010-01-01

Background A single serum creatinine measurement cannot distinguish acute kidney injury from chronic kidney disease or prerenal azotemia. Objective To test the sensitivity and specificity of a single measurement of urinary neutrophil gelatinase–associated lipocalin (NGAL) and other urinary proteins to detect acute kidney injury in a spectrum of patients. Design Prospective cohort study. Setting Emergency department of Columbia University Medical Center, New York, New York. Participants 635 patients admitted to the hospital with acute kidney injury, prerenal azotemia, chronic kidney disease, or normal kidney function. Measurements Diagnosis of acute kidney injury was based on the RIFLE (risk, injury, failure, loss, and end-stage) criteria and assigned by researchers who were blinded to experimental measurements. Urinary NGAL was measured by immunoblot, N-acetyl-β-D-glucosaminidase (NAG) by enzyme measurement, α1-microglobulin and α1-acid glycoprotein by immunonephelometry, and serum creatinine by Jaffe kinetic reaction. Experimental measurements were not available to treating physicians. Results Patients with acute kidney injury had a significantly elevated mean urinary NGAL level compared with the other kidney function groups (416 μg/g creatinine [SD, 387]; P = 0.001). At a cutoff value of 130 μg/g creatinine, sensitivity and specificity of NGAL for detecting acute injury were 0.900 (95% CI, 0.73 to 0.98) and 0.995 (CI, 0.990 to 1.00), respectively, and positive and negative likelihood ratios were 181.5 (CI, 58.33 to 564.71) and 0.10 (CI, 0.03 to 0.29); these values were superior to those for NAG, α1-microglobulin, α1-acid glycoprotein, fractional excretion of sodium, and serum creatinine. In multiple logistic regression, urinary NGAL level was highly predictive of clinical outcomes, including nephrology consultation, dialysis, and admission to the intensive care unit (odds ratio, 24.71 [CI, 7.69 to 79.42]). Limitations All patients came from a single center. Few kidney biopsies were performed. Conclusion A single measurement of urinary NGAL helps to distinguish acute injury from normal function, prerenal azotemia, and chronic kidney disease and predicts poor inpatient outcomes. PMID:18519927

Kidney Disease and the Nexus of Chronic Kidney Disease and Acute Kidney Injury: The Role of Novel Biomarkers as Early and Accurate Diagnostics.

PubMed

Yerramilli, Murthy; Farace, Giosi; Quinn, John; Yerramilli, Maha

2016-11-01

Chronic kidney disease (CKD) and acute kidney injury (AKI) are interconnected and the presence of one is a risk for the other. CKD is an important predictor of AKI after exposure to nephrotoxic drugs or major surgery, whereas persistent or repetitive injury could result in the progression of CKD. This brings new perspectives to the diagnosis and monitoring of kidney diseases highlighting the need for a panel of kidney-specific biomarkers that reflect functional as well as structural damage and recovery, predict potential risk and provide prognosis. This article discusses the kidney-specific biomarkers, symmetric dimethylarginine (SDMA), clusterin, cystatin B, and inosine. Copyright © 2016 Elsevier Inc. All rights reserved.

A comparison of the effects of oral vs. intravenous hydration on subclinical acute kidney injury in living kidney donors: a protocol of a randomised controlled trial.

PubMed

Mackinnon, Shona; Aitken, Emma; Ghita, Ryan; Clancy, Marc

2017-01-19

Optimal treatment for established renal failure is living donor kidney transplantation. However this pathway exposes healthy individuals to significant reduction in nephron mass via major surgical procedure. Laparoscopic donor nephrectomy is now the most common method for live donor transplantation, reducing both donor post-operative pain and recovery time. However this procedure exposes kidneys to additional haemodynamic stresses. It has been suggested that donor hydration-particularly the use of preoperative intravenous fluids-may counteract these stresses, reducing subclinical acute kidney injury and ultimately improving long-term renal function. This may be important in both preservation of donor renal function and recipient graft longevity. A prospective single-centre single-blinded randomized controlled trial will be carried out to determine the effects of donor preoperative intravenous fluids. The primary outcome is donor subclinical acute kidney injury (defined as plasma NGAL, >153 ng/ml) on day 1 postoperatively. Secondary outcomes include intraoperative haemodynamics, recipient subclinical acute kidney injury, perioperative complications and donor sleep quality. Donors will be randomised into two groups: the intervention group will receive active pre-hydration consisting of three litres of intravenous Hartmann's solution between midnight and 8 am before morning kidney donation, while the control group will not receive this. Both groups will receive unlimited oral fluids until midnight, as is routine. Plasma NGAL will be measured at pre-specified perioperative time points, intraoperative haemodynamic data will be collected using non-invasive cardiac output monitoring and clinical notes will be used to obtain demographic and clinical data. The researcher will be blinded to the donor fluid hydration status. Blinded statistical analysis will be performed on an intention-to-treat basis. A prospective power calculation estimates a required sample size of 86 patients. This study will provide important data, as there is currently little evidence about the use of donor preoperative fluids in laparoscopic nephrectomy. It is hoped that the results obtained will guide future clinical practice. This study has been approved by the West of Scotland Research Ethics Committee 3 (reference no. 14/WS/1160, 27 January 2015) and is registered with the International Standard Randomised Controlled Trial Number Register (reference no. ISRCTN10199225 , 20 April 2015).

Recent advances in imaging cancer of the kidney and urinary tract.

PubMed

Hilton, Susan; Jones, Lisa P

2014-10-01

Modern radiologic imaging is an aid to treatment planning for localized renal cancer, enabling characterization of mass lesions. For patients who present with advanced renal cancer, new imaging techniques enable a functional assessment of treatment response not possible using anatomic measurements alone. Multidetector CT urography permits simultaneous assessment of the kidneys and urinary tract for patients with unexplained hematuria. Both CT and MRI play a significant role in staging and follow up of patients treated for urothelial cancer. Newer imaging methods such as diffusion-weighted MRI have shown promising results for improving accuracy of staging and follow up of urothelial cancer. Copyright © 2014 Elsevier Inc. All rights reserved.

Novel biomarkers of acute kidney injury and failure: clinical applicability.

PubMed

Mårtensson, J; Martling, C-R; Bell, M

2012-12-01

Acute kidney injury (AKI) has a number of triggers, including ischaemia, nephrotoxins, radiocontrast, and bacterial endotoxins. It occurs in around one-third of patients treated in intensive care unit (ICU) and is even more prevalent in cardiac surgery patients. There is a higher mortality in patients with AKI compared with non-AKI counterparts, and in severe AKI requiring renal support, the 6 month mortality is >50%. Unlike the progressive development of biomarkers in cardiology, there have been few changes in kidney diagnostic markers. Creatinine is still used as an indicator of kidney function but not of the parenchymal kidney injury. Serum creatinine (sCr) concentration does not change until around 50% of kidney function is lost, and varies with muscle mass, age, sex, medications, and hydration status. The lag time between injury and loss of function, risks missing a therapeutic opportunity, and may explain the high associated mortality. Novel biomarkers of AKI- and failure include neutrophil gelatinase-associated lipocalin, N-acetyl-β-d-glucosaminidase, kidney injury molecule-1, interleukin-18, and cystatin C. The pathophysiology associated with accumulation of these markers in plasma and urine is not clear, but a common denominator is inflammation. Some of these new AKI biomarkers may have clinical applicability in anaesthesia and intensive care in the future. It is possible that a 'kidney biomarker panel' will become standard before and after major surgery. If elevated or positive, the anaesthetist must take special care to optimize the patients after operation on the surgical wards or ICU to avoid further nephrotoxic insults and initiate supplementary care.

Ethanolic extract of Clerodendrum violaceum Gürke leaves enhances kidney function in mouse model of malaria.

PubMed

Zailani, Ahmed H; Balogun, Elizabeth A; Adebayo, Joseph O

2009-05-01

Evaluation of the effects of daily oral administration of ethanolic extract of C. violaceum leaves (13 mg/kg body weight) for 5 days on some kidney function indices of uninfected and Plasmodium berghei-infected mice was done on days 3, 8 and 14 post-infection. The indices studied include serum urea and creatinine concentrations with the specific activities of alkaline phosphatase, aspartate aminotransferase and alanine aminotransferase in the kidney. Treatment of P. berghei-infected mice with ethanolic extract of C. violaceum leaves (13 mg/kg body weight) for 5 days was able to ameliorate significantly the alterations in the various parameters observed in infected untreated mice, comparing favourably with chloroquine treatment in most cases. Administration of extract to uninfected mice had no significant effect on both serum and kidney parameters compared to the uninfected control. The results suggest that the ethanolic extract of C. violaceum leaves does not adversely affect kidney function at the dose used in traditional medicine for the treatment of malaria but rather enhances it.

Serum Uric Acid, Kidney Function and Acute Ischemic Stroke Outcomes in Elderly Patients: A Single-Cohort, Perspective Study

PubMed Central

Falsetti, Lorenzo; Capeci, William; Tarquinio, Nicola; Viticchi, Giovanna; Silvestrini, Mauro; Catozzo, Vania; Fioranelli, Agnese; Buratti, Laura; Pellegrini, Francesco

2017-01-01

Chronic kidney disease and hyperuricemia have been associated to an increased risk and a worse prognosis in acute ischemic stroke. Several mechanisms, including platelet dysfunction, coagulation disorders, endothelial dysfunction, inflammation, and an increased risk of atrial fibrillation could be implicated. The role of serum uric acid in this setting is still object of debate. We enrolled all the consecutive patients admitted to our department for acute ischemic stroke. Cox regression analysis was used to evaluate the risk of in-hospital death considering serum uric acid levels and all the comorbidities. In the overall sample, hyperuricemia was independently associated to an increased risk of in-hospital mortality. This effect was stronger in patients with chronic kidney disease while, in the group of patients with normal renal function, the relationship between hyperuricemia and increased stroke mortality was not confirmed. Hyperuricemia could be associated to higher in-hospital mortality for ischemic stroke among elderly patients when affected by kidney disease. Survival does not seem to be affected by hyperuricemia in patients with normal kidney function. PMID:28461885

The expanding roles of microRNAs in kidney pathophysiology.

PubMed

Metzinger-Le Meuth, Valérie; Fourdinier, Ophélie; Charnaux, Nathalie; Massy, Ziad A; Metzinger, Laurent

2018-05-25

MicroRNAs (miRNAs) are short single-stranded RNAs that control gene expression through base pairing with regions within the 3'-untranslated region of target mRNAs. These small non-coding RNAs are now increasingly known to be involved in kidney physiopathology. In this review we will describe how miRNAs were in recent years implicated in cellular and animal models of kidney disease but also in chronic kidney disease, haemodialysed and grafted patients, acute kidney injury patients and so on. At the moment miRNAs are considered as potential biomarkers in nephrology, but larger cohorts as well as the standardization of methods of measurement will be needed to confirm their usefulness. It will further be of the utmost importance to select specific tissues and biofluids to make miRNAs appropriate in day-to-day clinical practice. In addition, up- or down-regulating miRNAs that were described as deregulated in kidney diseases may represent innovative therapeutic methods to cure these disorders. We will enumerate in this review the most recent methods that can be used to deliver miRNAs in a specific and suitable way in kidney and other organs damaged by kidney failure, such as the cardiovascular system.

Uromodulin: a new biomarker of fetal renal function?

PubMed

Botelho, Thais Emanuelle Faria; Pereira, Alamanda Kfoury; Teixeira, Patrícia Gonçalves; Lage, Eura Martins; Osanan, Gabriel Costa; Silva, Ana Cristina Simões E

2016-12-01

Obstructive uropathies are main diseases affecting the fetus. Early diagnosis allows to establish the appropriate therapy to minimize the risk of damage to kidney function at birth. Biochemical markers have been used to predict the prognosis of renal function in fetuses. Uromodulin, also known by Tamm-Horsfall protein (THP) is exclusively produced in the kidneys and in normal conditions is the protein excreted in larger amounts in human urine. It plays important roles in kidneys and urinary tract. Also it participates in ion transport processes, interact with various components of the immune system and has a role in defense against urinary tract infections. Moreover, this protein was proved to be a good marker of renal function in adult patients with several renal diseases. To evaluate if uromodulin is produced and eliminated by the kidneys during fetal life by analyzing fetal urine and amniotic fluid and to establish correlation with biochemical parameter of renal function already used in Fetal Medicine Center at the Clinic Hospital of UFMG (CEMEFE/HC). Between 2013 and 2015, were selected 29 fetuses with indication of invasive tests for fetal diagnosis in monitoring at the CEMEFE/HC. The determination of uromodulin was possible and measurable in all samples and showed statistically significant correlation with the osmolarity. There was a tendency of lower levels of Uromodulin values in fetuses with severe renal impairment prenatally. Thus, high levels of this protein in fetal amniotic fluid or fetal urine dosages possibly mean kidney function preserved.

The modification of renal transplantation with the usage of own polyethylene receptacle.

PubMed

Pupka, Artur; Chudoba, Paweł; Patrzałek, Dariusz; Janczak, Dariusz; Szyber, Piotr

2003-01-01

In this study a method of elimination of the second warm ischemia is shown. The method is based on the application of a specially constructed polyethylene bag, in which the transplanted kidney is placed in the time course from a removal from ice to the reconstruction of vessel flow. The bag is built of polyethylene foil HDPE of low density produced under high pressure. Own construction of the bag (three spaces and polyethylene) enables the storage of a transplanted organ at the stable temperature +4 Celsius degrees. Thanks to the separation of containers for melting ice and for the kidney, possible becomes unrestrained performance of both venous and arterial anastomosis independently of existing operative conditions. Due to the applied method of the elimination of the second warm ischemia with the usage of own construction of polyethylene bag HDPE, one can expect better early renal function after transplantation--decrease in the number of cases and shortening of the time of acute tubular necrosis (ATN--Acute Tubular Necrosis).

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.

Prenatal lead exposure and childhood blood pressure and kidney function.

PubMed

Skröder, Helena; Hawkesworth, Sophie; Moore, Sophie E; Wagatsuma, Yukiko; Kippler, Maria; Vahter, Marie

2016-11-01

Exposure to lead, a common environmental pollutant, is known to cause cardiovascular and nephrotoxic effects in adults. Potential effects of early-life lead exposure on these functions are, however, less well characterized. To assess blood pressure and kidney function in preschool-aged children in relation to prenatal lead exposure. This prospective study in rural Bangladesh measured children's systolic and diastolic blood pressure in triplicate at the follow-up at 4.5±0.11 years. Their kidney function was assessed by the estimated glomerular filtration rate (eGFR), calculated based on serum cystatin C concentrations, and by kidney volume, measured by sonography. Exposure to lead was assessed by concentrations in the mothers' blood (erythrocyte fraction; Ery-Pb) in gestational weeks (GW) 14 and 30, the effects of which were evaluated separately in multivariable-adjusted linear regression analyses. We found no associations between maternal exposure to lead [n~1500 for GW14 and 700 for GW30] and children's blood pressure or eGFR. However, we found an inverse association between late gestation lead and kidney volume, although the sample size was limited (n=117), but not with early gestation lead (n=573). An increase of 85µg/kg in Ery-Pb (median concentration at GW30) was associated with a 6.0cm 3 /m 2 decrease in kidney volume (=0.4SD; p=0.041). After stratifying on gender, there seemed to be a somewhat stronger association in girls. Prenatal lead exposure may cause long-lasting effects on the kidney. This warrants follow-up studies in older children, as well as additional studies in other populations. Copyright © 2016. Published by Elsevier Inc.

Blood transfusion improves renal oxygenation and renal function in sepsis-induced acute kidney injury in rats.

PubMed

Zafrani, Lara; Ergin, Bulent; Kapucu, Aysegul; Ince, Can

2016-12-20

The effects of blood transfusion on renal microcirculation during sepsis are unknown. This study aimed to investigate the effect of blood transfusion on renal microvascular oxygenation and renal function during sepsis-induced acute kidney injury. Twenty-seven Wistar albino rats were randomized into four groups: a sham group (n = 6), a lipopolysaccharide (LPS) group (n = 7), a LPS group that received fluid resuscitation (n = 7), and a LPS group that received blood transfusion (n = 7). The mean arterial blood pressure, renal blood flow, and renal microvascular oxygenation within the kidney cortex were recorded. Acute kidney injury was assessed using the serum creatinine levels, metabolic cost, and histopathological lesions. Nitrosative stress (expression of endothelial (eNOS) and inducible nitric oxide synthase (iNOS)) within the kidney was assessed by immunohistochemistry. Hemoglobin levels, pH, serum lactate levels, and liver enzymes were measured. Fluid resuscitation and blood transfusion both significantly improved the mean arterial pressure and renal blood flow after LPS infusion. Renal microvascular oxygenation, serum creatinine levels, and tubular damage significantly improved in the LPS group that received blood transfusion compared to the group that received fluids. Moreover, the renal expression of eNOS was markedly suppressed under endotoxin challenge. Blood transfusion, but not fluid resuscitation, was able to restore the renal expression of eNOS. However, there were no significant differences in lactic acidosis or liver function between the two groups. Blood transfusion significantly improved renal function in endotoxemic rats. The specific beneficial effect of blood transfusion on the kidney could have been mediated in part by the improvements in renal microvascular oxygenation and sepsis-induced endothelial dysfunction via the restoration of eNOS expression within the kidney.

Differences in urine cadmium associations with kidney outcomes based on serum creatinine and cystatin C

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

Weaver, Virginia M., E-mail: vweaver@jhsph.edu; Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD; Welch Center for Prevention, Epidemiology and Clinical Research, Johns Hopkins Medical Institutions, Baltimore, MD

Cadmium is a well-known nephrotoxicant; chronic exposure increases risk for chronic kidney disease. Recently, however, associations between urine cadmium and higher creatinine-based estimated glomerular filtration rate (eGFR) have been reported. Analyses utilizing alternate biomarkers of kidney function allow evaluation of potential mechanisms for these observations. We compared associations of urine cadmium with kidney function measures based on serum cystatin C to those with serum creatinine in 712 lead workers. Mean (standard deviation) molybdenum-corrected urine cadmium, Modification of Diet in Renal Disease (MDRD) eGFR and multi-variable cystatin C eGFR were 1.02 (0.65) {mu}g/g creatinine, and 97.4 (19.2) and 112.0 (17.7) mL/min/1.73more » m{sup 2}, respectively. The eGFR measures were moderately correlated (r{sub s}=0.5; p<0.001). After adjustment, ln (urine cadmium) was not associated with serum cystatin-C-based measures. However, higher ln (urine cadmium) was associated with higher creatinine-based eGFRs including the MDRD and an equation incorporating serum cystatin C and creatinine (beta-coefficient=4.1 mL/min/1.73 m{sup 2}; 95% confidence interval=1.6, 6.6). Urine creatinine was associated with serum creatinine-based but not cystatin-C-based eGFRs. These results support a biomarker-specific, rather than a kidney function, effect underlying the associations observed between higher urine cadmium and creatinine-based kidney function measures. Given the routine use of serum and urine creatinine in kidney and biomarker research, additional research to elucidate the mechanism(s) for these associations is essential.« less

Endothelial sirtuin 1 inactivation enhances capillary rarefaction and fibrosis following kidney injury through Notch activation

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

Kida, Yujiro; Zullo, Joseph A.; Renal Research Institute, Department of Physiology, New York Medical College, Valhalla, NY

Peritubular capillary (PTC) rarefaction along with tissue fibrosis is a hallmark of chronic kidney disease (CKD). However, molecular mechanisms of PTC loss have been poorly understood. Previous studies have demonstrated that functional loss of endothelial sirtuin 1 (SIRT1) impairs angiogenesis during development and tissue damage. Here, we found that endothelial SIRT1 dysfunction causes activation of endothelial Notch1 signaling, which leads to PTC rarefaction and fibrosis following kidney injury. In mice lacking functional SIRT1 in the endothelium (Sirt1 mutant), kidney injury enhanced apoptosis and senescence of PTC endothelial cells with impaired endothelial proliferation and expanded myofibroblast population and collagen deposition. Comparedmore » to wild-type kidneys, Sirt1 mutant kidneys up-regulated expression of Delta-like 4 (DLL4, a potent Notch1 ligand), Hey1 and Hes1 (Notch target genes), and Notch intracellular domain-1 (NICD1, active form of Notch1) in microvascular endothelial cells (MVECs) post-injury. Sirt1 mutant primary kidney MVECs reduced motility and vascular assembly and enhanced senescence compared to wild-type kidney MVECs. This difference in the phenotype was negated with Notch inhibition. Concurrent stimulation of DLL4 and transforming growth factor (TGF)-β1 increased trans-differentiation of primary kidney pericytes into myofibroblast more than TGF-β1 treatment alone. Collectively, these results indicate that endothelial SIRT1 counteracts PTC rarefaction by repression of Notch1 signaling and antagonizes fibrosis via suppression of endothelial DLL4 expression. - Highlights: • SIRT1 represses Notch1 signaling in capillary endothelial cells in the kidney. • Endothelial SIRT1 is depleted in the kidney following injury. • Activation of endothelial Notch impairs angiogenesis in the kidney. • Increased expression of endothelial DLL4 enhances renal fibrosis.« less

Kidney removal: the past, presence, and perspectives: a historical review.

PubMed

Poletajew, Slawomir; Antoniewicz, Artur A; Borówka, Andrzej

2010-01-01

More than 140 years have passed since the first documented planned nephrectomy. Throughout all these years, people gained significant knowledge on the renal functions and diseases, and what is more, the surgical workshop underwent considerable improvement. Initially, the kidney removal operations were performed due to ureterovaginal fistulas and renal lithiasis. Later, they were executed mainly in patients with renal tumors, whereas today, the number of these surgeries tend to decrease to the benefit of nephron sparing procedures. Current nephrectomies are more and more often performed in case of organ donation, what will probably remain the most significant indication for the kidney removal in close future. While the first surgeries were executed with classical surgical methods, nowadays, after years of studies concerning nephron sparing and minimally invasive operations, we can see surgeries carried out through natural body orifices with robotic assistance. In relation to simple surgical operation based on ligation of 3 tubular anatomic structures, we can perceive the true scope of the progress that occurred in surgery. The aim of this article is to present the evolution of indications and operating techniques utilized to remove the kidney in chronological aspect.

Quantifying creatinine and urea in human urine through Raman spectroscopy aiming at diagnosis of kidney disease

NASA Astrophysics Data System (ADS)

Saatkamp, Cassiano Junior; de Almeida, Maurício Liberal; Bispo, Jeyse Aliana Martins; Pinheiro, Antonio Luiz Barbosa; Fernandes, Adriana Barrinha; Silveira, Landulfo, Jr.

2016-03-01

Due to their importance in the regulation of metabolites, the kidneys need continuous monitoring to check for correct functioning, mainly by urea and creatinine urinalysis. This study aimed to develop a model to estimate the concentrations of urea and creatinine in urine by means of Raman spectroscopy (RS) that could be used to diagnose kidney disease. Midstream urine samples were obtained from 54 volunteers with no kidney complaints. Samples were subjected to a standard colorimetric assay of urea and creatinine and submitted to spectroscopic analysis by means of a dispersive Raman spectrometer (830 nm, 350 mW, 30 s). The Raman spectra of urine showed peaks related mainly to urea and creatinine. Partial least squares models were developed using selected Raman bands related to urea and creatinine and the biochemical concentrations in urine measured by the colorimetric method, resulting in r=0.90 and 0.91 for urea and creatinine, respectively, with root mean square error of cross-validation (RMSEcv) of 312 and 25.2 mg/dL, respectively. RS may become a technique for rapid urinalysis, with concentration errors suitable for population screening aimed at the prevention of renal diseases.

Hemolysis in a patient with alkaptonuria and chronic kidney failure.

PubMed

Heng, Anne-Elisabeth; Courbebaisse, Marie; Kemeny, Jean Louis; Matesan, Raluca; Bonniol, Claude; Deteix, Patrice; Souweine, Bertrand

2010-07-01

In alkaptonuria, the absence of homogentisic acid oxidase results in the accumulation of homogentisic acid (HGA) in the body. Fatal disease cases are infrequent, and death often results from kidney or cardiac complications. We report a 24-year-old alkaptonuric man with severe decreased kidney function who developed fatal metabolic acidosis and intravascular hemolysis. Hemolysis may have been caused by rapid and extensive accumulation of HGA and subsequent accumulation of plasma soluble melanins. Toxic effects of plasma soluble melanins, their intermediates, and reactive oxygen side products are increased when antioxidant mechanisms are overwhelmed. A decrease in serum antioxidative activity has been reported in patients with chronic decreased kidney function. However, despite administration of large doses of an antioxidant agent and ascorbic acid and intensive kidney support, hemolysis and acidosis could not be brought under control and hemolysis led to the death of the patient.

Kidney function and sudden cardiac death in the community: The Atherosclerosis Risk in Communities (ARIC) Study.

PubMed

Suzuki, Takeki; Agarwal, Sunil K; Deo, Rajat; Sotoodehnia, Nona; Grams, Morgan E; Selvin, Elizabeth; Calkins, Hugh; Rosamond, Wayne; Tomaselli, Gordon; Coresh, Josef; Matsushita, Kunihiro

2016-10-01

Individuals with chronic kidney disease, particularly those requiring dialysis, are at high risk of sudden cardiac death (SCD). However, comprehensive data for the full spectrum of kidney function and SCD risk in the community are sparse. Furthermore, newly developed equations for estimated glomerular filtration rate (eGFR) and novel filtration markers might add further insight to the role of kidney function in SCD. We investigated the associations of baseline eGFRs using serum creatinine, cystatin C, or both (eGFRcr, eGFRcys, and eGFRcr-cys); cystatin C itself; and β2-microglobulin (B2M) with SCD (205 cases through 2001) among 13,070 black and white ARIC participants at baseline during 1990-1992 using Cox regression models accounting for potential confounders. Low eGFR was independently associated with SCD risk: for example, hazard ratio for eGFR <45 versus ≥90mL/(min 1.73m(2)) was 3.71 (95% CI 1.74-7.90) with eGFRcr, 5.40 (2.97-9.83) with eGFRcr-cys, and 5.24 (3.01-9.11) with eGFRcys. When eGFRcr and eGFRcys were included together in a single model, the association was only significant for eGFRcys. When three eGFRs, cystatin C, and B2M were divided into quartiles, B2M demonstrated the strongest association with SCD (hazard ratio for fourth quartile vs first quartile 3.48 (2.03-5.96) vs ≤2.7 for the other kidney markers). Kidney function was independently and robustly associated with SCD in the community, particularly when cystatin C or B2M was used. These results suggest the potential value of kidney function as a risk factor for SCD and the advantage of novel filtration markers over eGFRcr in this context. Copyright © 2016 Elsevier Inc. All rights reserved.

Dual kidney transplants from adult marginal donors successfully expand the limited deceased donor organ pool.

PubMed

Stratta, Robert J; Farney, Alan C; Orlando, Giuseppe; Farooq, Umar; Al-Shraideh, Yousef; Palanisamy, Amudha; Reeves-Daniel, Amber; Doares, William; Kaczmorski, Scott; Gautreaux, Michael D; Iskandar, Samy S; Hairston, Gloria; Brim, Elizabeth; Mangus, Margaret; El-Hennawy, Hany; Khan, Muhammad; Rogers, Jeffrey

2016-04-01

The need to expand the organ donor pool remains a formidable challenge in kidney transplantation (KT). The use of expanded criteria donors (ECDs) represents one approach, but kidney discard rates are high because of concerns regarding overall quality. Dual KT (DKT) may reduce organ discard and optimize the use of kidneys from marginal donors. We conducted a single-center retrospective review of outcomes in adult recipients of DKTs from adult marginal deceased donors (DD) defined by limited renal functional capacity. If the calculated creatinine clearance in an adult DD was <65 mL/min, then the kidneys were transplanted as a DKT. Over 11.5 yr, 72 DKTS were performed including 45 from ECDs, 17 from donation after cardiac death (DCD) donors, and 10 from standard criteria donors (SCD). Mean adult DD and recipient ages were both 60 yr, including 29 DDs and 26 recipients ≥65 yr of age. Mean pre-DKT waiting and dialysis vintage times were 12 months and 25 months, respectively. Actual patient and graft survival rates were 84.7% and 70.8%, respectively, with a mean follow-up of 58 months. One yr and death-censored graft survival rates were 90% and 80%, respectively. Outcomes did not differ by DD category, recipient age, or presence of delayed graft function (DGF). Eleven patients died at a mean of 32 months post-DKT (eight with functioning grafts) and 13 other patients experienced graft losses at a mean of 33 months. The incidence of DGF was 25%; there were two cases (2.8%) of primary non-function. Mean length of initial hospital stay was 7.2 d. Mean serum creatinine and glomerular filtration rate levels at 12 and 24 months were 1.5 and 53 and 1.5 mg/dL and 51 mL/min/1.73 m(2) , respectively. DKT graft survival and function were superior to concurrent single ECD and similar to concurrent SCD KTs. Two patients underwent successful kidney retransplantation, so the dialysis-free rate in surviving patients was 87%. The proportion of total renal function transplanted from adult DD to DKT recipients was 77% compared to 56% for patients receiving single KTs. Dual kidney transplantation using kidneys from adult marginal DDs that otherwise might be discarded offer a viable option to counteract the growing shortage of acceptable single kidneys. Excellent medium-term outcomes can be achieved and waiting times can be reduced in a predominantly older recipient population. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

The kidney disease quality of life cognitive function subscale and cognitive performance maintenance hemodialysis patients

USDA-ARS?s Scientific Manuscript database

Background: Cognitive impairment is common but often undiagnosed in patients with end-stage renal disease, in part reflecting limited validated and easily administered tools to assess cognitive function in dialysis patients. Accordingly, we assessed the utility of the Kidney Disease Quality of Life ...

Correlates of Physical Functioning and Performance Across the Spectrum of Kidney Function.

PubMed

Segura-Ortí, E; Gordon, P L; Doyle, J W; Johansen, K L

2018-06-01

The aim of this study was to determine the extent to which poor physical functioning, low participation in physical activity, and muscle atrophy observed among patients on hemodialysis are evident in the earlier stages of chronic kidney disease (CKD). We enrolled adults in three groups: no CKD, Stages 3 to 4 CKD, and hemodialysis. Outcomes measured were physical activity, muscle size, thigh muscle strength, physical performance, and self-reported physical function. Patients with CKD had muscle area intermediate between the no CKD and hemodialysis groups, but they had low levels of physical activity that were similar to the hemodialysis group. Physical activity and muscle size were significantly associated with all outcomes. Kidney function was not significantly associated with muscle strength or physical performance after adjustment for physical activity and muscle size. In conclusion, interventions aimed to increase muscle mass and energy expenditure might have an impact on improving physical function of CKD patients.

Assessment of Renal Ischemia By Optical Spectroscopy

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

Fitzgerald, J T; Demos, S; Michalopoulou, A

2004-01-07

Introduction: No reliable method currently exists for quantifying the degree of warm ischemia in kidney grafts prior to transplantation. We describe a method for evaluating pretransplant warm ischemia time using optical spectroscopic methods. Methods: Lewis rat kidney vascular pedicles were clamped unilaterally in vivo for 0, 5, 10, 20, 30, 60, 90 or 120 minutes; 8 animals were studied at each time point. Injured and contra-lateral control kidneys were then flushed with Euro-Collins solution, resected and placed on ice. 335 nm excitation autofluorescence as well as cross polarized light scattering images were taken of each injured and control kidney usingmore » filters of various wavelengths. The intensity ratio of the injured to normal kidneys was compared to ischemia time. Results: Autofluorescence intensity ratios through a 450 nm filter and light scattering intensity ratios through an 800 nm filter both decreased significantly with increasing ischemia time (p < 0.0001 for each method, one-way ANOVA). All adjacent and non-adjacent time points between 0 and 90 minutes were distinguishable using one of these two modalities by Fisher's PLSD. Conclusions: Optical spectroscopic methods can accurately quantify warm ischemia time in kidneys that have been subsequently hypothermically preserved. Further studies are needed to correlate results with physiological damage and posttransplant performance.« less

Determination of glomerular filtration rate (GFR) from fractional renal accumulation of iodinated contrast material: a convenient and rapid single-kidney CT-GFR technique.

PubMed

Yuan, XiaoDong; Tang, Wei; Shi, WenWei; Yu, Libao; Zhang, Jing; Yuan, Qing; You, Shan; Wu, Ning; Ao, Guokun; Ma, Tingting

2018-07-01

To develop a convenient and rapid single-kidney CT-GFR technique. One hundred and twelve patients referred for multiphasic renal CT and 99mTc-DTPA renal dynamic imaging Gates-GFR measurement were prospectively included and randomly divided into two groups of 56 patients each: the training group and the validation group. On the basis of the nephrographic phase images, the fractional renal accumulation (FRA) was calculated and correlated with the Gates-GFR in the training group. From this correlation a formula was derived for single-kidney CT-GFR calculation, which was validated by a paired t test and linear regression analysis with the single-kidney Gates-GFR in the validation group. In the training group, the FRA (x-axis) correlated well (r = 0.95, p < 0.001) with single-kidney Gates-GFR (y-axis), producing a regression equation of y = 1665x + 1.5 for single-kidney CT-GFR calculation. In the validation group, the difference between the methods of single-kidney GFR measurements was 0.38 ± 5.57 mL/min (p = 0.471); the regression line is identical to the diagonal (intercept = 0 and slope = 1) (p = 0.727 and p = 0.473, respectively), with a standard deviation of residuals of 5.56 mL/min. A convenient and rapid single-kidney CT-GFR technique was presented and validated in this investigation. • The new CT-GFR method takes about 2.5 min of patient time. • The CT-GFR method demonstrated identical results to the Gates-GFR method. • The CT-GFR method is based on the fractional renal accumulation of iodinated CM. • The CT-GFR method is achieved without additional radiation dose to the patient.

Neurocognitive functions of pediatric kidney transplant recipients.

PubMed

Molnar-Varga, Marta; Novak, Marta; Szabo, Attila J; Kelen, Kata; Streja, Elani; Remport, Adam; Mucsi, Istvan; Molnar, Miklos Z; Reusz, Gyorgy

2016-09-01

End-stage renal disease (ESRD) in children is associated with impaired neurocognitive function and development. However, data on factors associated with neurocognitive dysfunctions in children with kidney transplants are limited. We conducted a cross-sectional analysis comparing cognitive functions (using the Woodcock-Johnson International Edition, WJIE) in 35 kidney transplant and 35 healthy control children. Data on laboratory measurements, comorbidities, and social characteristics were collected. Transplant children had significantly worse scores on the intelligence quotient (IQ) test compared with controls [Full Scale IQ score 85 (26) vs 107 (10), p <0.001]. Lower maternal education level was significantly associated with lower WJIE cognitive test scores; however, no association was found between laboratory values and WJIE scores. Among children with kidney transplants, those with medical comorbid conditions had significantly lower Verbal Ability and Full Scale IQ scores. Earlier age of dialysis onset and a longer total time on dialysis (>9 months) were associated with lower test scores. Age-standardized duration of hospitalization was inversely correlated with IQ (r = -0.46, p <0.01) and was an independent significant predictor (Beta = -0.38, p = 0.02) of IQ scores in transplanted children. Child kidney transplant recipients have neurocognitive function impairments that are associated with markers of socioeconomic status (SES) and factors related to disease severity.

Dietary patterns and chronic kidney disease: a cross-sectional association in the Irish Nun Eye Study.

PubMed

Paterson, Euan N; Neville, Charlotte E; Silvestri, Giuliana; Montgomery, Shannon; Moore, Evelyn; Silvestri, Vittorio; Cardwell, Christopher R; MacGillivray, Tom J; Maxwell, Alexander P; Woodside, Jayne V; McKay, Gareth J

2018-04-27

Associations between dietary patterns and chronic kidney disease are not well established, especially in European populations. We conducted a cross-sectional study of 1033 older Irish women (age range 56-100 years) with a restricted lifestyle. Dietary intake was assessed using a food frequency questionnaire. Renal function was determined by estimated glomerular filtration rate. Two dietary patterns were identified within the study population using factor analysis. A significant negative association was found between unhealthy dietary pattern adherence and renal function in both unadjusted and adjusted models controlling for potential confounding variables (p for trend <0.001), with a mean difference in estimated glomerular filtration rate of -6 ml/min/1.73 m 2 between those in the highest fifth of adherence to the unhealthy dietary pattern compared to the lowest, in the fully adjusted model. Chronic kidney disease risk was significantly greater for the highest fifth, compared to the lowest fifth of unhealthy dietary pattern adherence in adjusted models (adjusted odds ratio = 2.62, p < 0.001). Adherence to the healthy dietary pattern was not associated with renal function or chronic kidney disease in adjusted models. In this cohort, an unhealthy dietary pattern was associated with lower renal function and greater prevalence of chronic kidney disease.

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

Applying data mining techniques to determine important parameters in chronic kidney disease and the relations of these parameters to each other.

PubMed

Tahmasebian, Shahram; Ghazisaeedi, Marjan; Langarizadeh, Mostafa; Mokhtaran, Mehrshad; Mahdavi-Mazdeh, Mitra; Javadian, Parisa

2017-01-01

Introduction: Chronic kidney disease (CKD) includes a wide range of pathophysiological processes which will be observed along with abnormal function of kidneys and progressive decrease in glomerular filtration rate (GFR). According to the definition decreasing GFR must have been present for at least three months. CKD will eventually result in end-stage kidney disease. In this process different factors play role and finding the relations between effective parameters in this regard can help to prevent or slow progression of this disease. There are always a lot of data being collected from the patients' medical records. This huge array of data can be considered a valuable source for analyzing, exploring and discovering information. Objectives: Using the data mining techniques, the present study tries to specify the effective parameters and also aims to determine their relations with each other in Iranian patients with CKD. Material and Methods: The study population includes 31996 patients with CKD. First, all of the data is registered in the database. Then data mining tools were used to find the hidden rules and relationships between parameters in collected data. Results: After data cleaning based on CRISP-DM (Cross Industry Standard Process for Data Mining) methodology and running mining algorithms on the data in the database the relationships between the effective parameters was specified. Conclusion: This study was done using the data mining method pertaining to the effective factors on patients with CKD.

Applying data mining techniques to determine important parameters in chronic kidney disease and the relations of these parameters to each other

PubMed Central

Tahmasebian, Shahram; Ghazisaeedi, Marjan; Langarizadeh, Mostafa; Mokhtaran, Mehrshad; Mahdavi-Mazdeh, Mitra; Javadian, Parisa

2017-01-01

Introduction: Chronic kidney disease (CKD) includes a wide range of pathophysiological processes which will be observed along with abnormal function of kidneys and progressive decrease in glomerular filtration rate (GFR). According to the definition decreasing GFR must have been present for at least three months. CKD will eventually result in end-stage kidney disease. In this process different factors play role and finding the relations between effective parameters in this regard can help to prevent or slow progression of this disease. There are always a lot of data being collected from the patients’ medical records. This huge array of data can be considered a valuable source for analyzing, exploring and discovering information. Objectives: Using the data mining techniques, the present study tries to specify the effective parameters and also aims to determine their relations with each other in Iranian patients with CKD. Material and Methods: The study population includes 31996 patients with CKD. First, all of the data is registered in the database. Then data mining tools were used to find the hidden rules and relationships between parameters in collected data. Results: After data cleaning based on CRISP-DM (Cross Industry Standard Process for Data Mining) methodology and running mining algorithms on the data in the database the relationships between the effective parameters was specified. Conclusion: This study was done using the data mining method pertaining to the effective factors on patients with CKD. PMID:28497080

Kidney Function and Fracture Risk: The Atherosclerosis Risk in Communities (ARIC) Study.

PubMed

Daya, Natalie; Voskertchian, Annie; Schneider, Andrea L C; Ballew, Shoshana; McAdams DeMarco, Mara; Coresh, Josef; Appel, Lawrence J; Selvin, Elizabeth; Grams, Morgan E

2016-02-01

People with end-stage renal disease are at high risk for bone fracture. Less is known about fracture risk in milder chronic kidney disease and whether chronic kidney disease-associated fracture risk varies by sex or assessment with alternative kidney markers. Prospective cohort study. 10,955 participants from the Atherosclerosis Risk in Communities (ARIC) Study followed up from 1996 to 2011. Kidney function as assessed by creatinine-based estimated glomerular filtration rate (eGFRcr), urine albumin-creatinine ratio, and alternative filtration markers. Fracture-related hospitalizations determined by diagnostic code. Baseline kidney markers; hospitalizations identified by self-report during annual telephone contact and active surveillance of local hospital discharge lists. Mean age of participants was 63 years, 56% were women, and 22% were black. During a median follow-up of 13 years, there were 722 incident fracture-related hospitalizations. Older age, female sex, and white race were associated with higher risk for fracture (P<0.001). The relationship between eGFRcr and fracture risk was nonlinear: <60mL/min/1.73m(2), lower eGFRcr was associated with higher fracture risk (adjusted HR per 10mL/min/1.73m(2) lower, 1.24; 95% CI, 1.05-1.47); there was no statistically significant association for ≥60mL/min/1.73m(2) in the primary analysis. In contrast, there was a graded association between other markers of kidney function and subsequent fracture, including albumin-creatinine ratio (HR per doubling, 1.10; 95% CI, 1.06-1.14), cystatin C-based eGFR (HR per 1-SD decrease, 1.15; 95% CI, 1.06-1.25), and 1/β2-microglobulin (HR per 1-SD decrease, 1.26, 95% CI, 1.15-1.37). No bone mineral density assessment; one-time measurement of kidney function. Both low eGFR and higher albuminuria were significant risk factors for fracture in this community-based population. The shape of the association in the upper ranges of eGFR varied by the filtration marker used in estimation. Copyright © 2016 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.

Temporary renal ischemia during nephron sparing surgery is associated with short-term but not long-term impairment in renal function.

PubMed

Yossepowitch, Ofer; Eggener, Scott E; Serio, Angel; Huang, William C; Snyder, Mark E; Vickers, Andrew J; Russo, Paul

2006-10-01

The emergence of laparoscopic nephron sparing surgery has rekindled interest in the impact of warm renal ischemia on renal function. To provide data with which warm renal ischemia can be compared we analyzed short-term and long-term changes in the glomerular filtration rate after temporary cold renal ischemia. In patients undergoing open nephron sparing surgery the estimated glomerular filtration rate was assessed preoperatively, early in the postoperative hospital stay, and 1 and 12 months after surgery using the abbreviated Modification of Diet in Renal Disease Study equation. We separately analyzed 70 patients with a solitary kidney and 592 with 2 functioning kidneys. The end point was the percent change from the baseline glomerular filtration rate. A linear regression model was used to test the association between the glomerular filtration rate change, and ischemia time, patient age, tumor size, estimated blood loss and intraoperative fluid administration. Median cold ischemia time was 31 minutes in patients with a solitary kidney and 35 minutes in those with 2 kidneys. Compared to patients with 2 kidneys those with a solitary kidney had a significantly lower preoperative estimated glomerular filtration rate (p < 0.001), which decreased a median of 30% during the early postoperative period, and 15% and 32% 1 and 12 months after surgery, respectively. In patients with 2 kidneys the corresponding glomerular filtration rate decreases were 16%, 13% and 14%, respectively. On multivariate analyses in each group cold ischemia duration and intraoperative blood loss were significantly associated with early glomerular filtration rate changes. However, 12 months after surgery age was the only independent predictor of a glomerular filtration rate decrease in patients with 2 kidneys. Cold renal ischemia during nephron sparing surgery is a significant determinant of the short-term postoperative glomerular filtration rate. Longer clamping time is particularly detrimental in patients with a solitary kidney but it does not appear to influence long-term renal function. Patients of advanced age may be less likely to recover from acute ischemic renal injury.

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.

Tesevatinib ameliorates progression of polycystic kidney disease in rodent models of autosomal recessive polycystic kidney disease

PubMed Central

Sweeney, William E; Frost, Philip; Avner, Ellis D

2017-01-01

AIM To investigate the therapeutic potential of tesevatinib (TSV), a unique multi-kinase inhibitor currently in Phase II clinical trials for autosomal dominant polycystic kidney disease (ADPKD), in well-defined rodent models of autosomal recessive polycystic kidney disease (ARPKD). METHODS We administered TSV in daily doses of 7.5 and 15 mg/kg per day by I.P. to the well characterized bpk model of polycystic kidney disease starting at postnatal day (PN) 4 through PN21 to assess efficacy and toxicity in neonatal mice during postnatal development and still undergoing renal maturation. We administered TSV by oral gavage in the same doses to the orthologous PCK model (from PN30 to PN90) to assess efficacy and toxicity in animals where developmental processes are complete. The following parameters were assessed: Body weight, total kidney weight; kidney weight to body weight ratios; and morphometric determination of a cystic index and a measure of hepatic disease. Renal function was assessed by: Serum BUN; creatinine; and a 12 h urinary concentrating ability. Validation of reported targets including the level of angiogenesis and inhibition of angiogenesis (active VEGFR2/KDR) was assessed by Western analysis. RESULTS This study demonstrates that: (1) in vivo pharmacological inhibition of multiple kinase cascades with TSV reduced phosphorylation of key mediators of cystogenesis: EGFR, ErbB2, c-Src and KDR; and (2) this reduction of kinase activity resulted in significant reduction of renal and biliary disease in both bpk and PCK models of ARPKD. The amelioration of disease by TSV was not associated with any apparent toxicity. CONCLUSION The data supports the hypothesis that this multi-kinase inhibitor TSV may provide an effective clinical therapy for human ARPKD. PMID:28729967

Renal Artery Embolization - A First Line Treatment Option For End-Stage Hydronephrosis

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

Mitra, Kakali; Prabhudesai, Vikramaditya; James, R. Lester

Conventionally poorly functioning hydronephrotic kidneys have been removed if they are symptomatic. In our unit, patients are offered renal artery embolization as an alternative treatment option. Patients and Methods: Fifteen patients (11 male, 4 female) with a mean age of 32.9 yr (20-51 yrs) have undergone renal artery embolization for symptomatic hydronephrosis with poor function. Mean follow-up was 64.13 weeks (range 14-200). All patients had loin pain and hydronephrosis. Twelve patients had primary pelvi-ureteric junction obstruction (PUJO). Two patients had poorly functioning hydronephrotic kidneys secondary to chronic calculous obstruction. One patient had chronic pain in an obstructed but reasonably functioningmore » kidney following a previous pyeloplasty for PUJO which demanded intervention. Mean split function on renography was 11% (range 0-46%). Selective renal artery embolization was carried out under antibiotic cover using a 7 Fr balloon occlusion catheter and absolute alcohol, steel coils, and polyvinyl alcohol particles.Results: Nine patients developed post-embolization syndrome of self-limiting pain and pyrexia with no evidence of sepsis. One patient required readmission with this condition. One patient developed a hematoma at the puncture site. Mean hospital stay was 2.3 days. Fourteen patients are happy with the result and are completely pain free. One patient has minor discomfort but is delighted with the result. Nine patients have had follow-up ultrasound confirming resolution of the hydronephrosis. Conclusion: Renal artery embolization is an effective, safe, well-tolerated minimally invasive treatment option in end-stage hydronephrosis and we routinely offer it as an alternative to nephrectomy.« less

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.

Living unrelated donor kidney transplantation--a fourteen-year experience.

PubMed

Ignjatović, Ljiljana; Jovanović, Dragan; Kronja, Goran; Dujić, Aleksandar; Marić, Mihailo; Ignjatović, Dragan; Hrvacević, Rajko; Kovacević, Zoran; Petrović, Milija; Elaković, Dejan; Marenović, Tomislav; Lukić, Zoran; Trkuljić, Miroljub; Stanković, Bratislav; Maksić, Doko; Butorajac, Josip; Colić, Miodrag; Drasković-Pavlović, Biljana; Kapulica-Kuljić, Nada; Drasković, Nada; Misović, Sidor; Stijelja, Borislav; Milović, Novak; Tosevski, Perica; Filipović, Nikola; Romić, Predrag; Jevtić, Miodrag; Drasković, Miroljub; Vavić, Neven; Rabrenović, Violeta; Paunić, Zoran; Radojević, Milorad; Bjelanović, Zoran; Tomić, Aleksandar; Aleksić, Predrag; Kosević, Branko; Mocović, Dejan; Bancević, Vladimir; Magić, Zvonko; Vojvodić, Danilo; Balint, Bela; Ostojić, Gordana; Tukić, Ljiljana; Murgić, Jadranka; Pervulov, Svetozar; Rusović, Sinisa; Sjenicić, Goran; Vesna, Bućan; Milavić-Vujković, Merica; Jandrić, Dusan; Raicević, Ranko; Mijusković, Mirjana; Obrencević, Katarina; Pilcević, Dejan; Cukić, Zoran; Petrović, Marijana; Petrović, Milica; Tadić, Jelena; Terzić, Brankica; Karan, Zeljko; Bokonjić, Dubravko; Dobrić, Silva; Antunović, Mirjana; Bokun, Radmila; Dimitrijević, Jovan; Vukomanović-Djurdjević, Biserka

2010-12-01

In countries without a national organization for retrieval and distribution of organs of the deceased donors, problem of organ shortage is still not resolved. In order to increase the number of kidney transplantations we started with the program of living unrelated - spousal donors. The aim of this study was to compare treatment outcome and renal graft function in patients receiving the graft from spousal and those receiving ghe graft from living related donors. We retrospectively identified 14 patients who received renal allograft from spousal donors between 1996 and 2009 (group I). The control group consisted of 14 patients who got graft from related donor retrieved from the database and matched than with respect to sex, age, kidney disease, immunological and viral pretransplant status, the initial method of the end stage renal disease treatment and ABO compatibility. In the follow-up period of 41 +/- 38 months we recorded immunosuppressive therapy, surgical complications, episodes of acute rejection, CMV infection and graft function, assessed by serum creatinine levels at the beginning and in the end of the follow-up period. All patients had pretransplant negative cross-match. In ABO incompatible patients pretransplant isoagglutinine titer was zero. The patients with a spousal donor had worse HLA matching. There were no significant differences between the groups in surgical, infective, immunological complications and graft function. Two patients from the group I returned to hemodialysis after 82 and 22 months due to serious comorbidities. In spite of the worse HLA matching, graft survival and function of renal grafts from spousal donors were as good as those retrieved from related donors.

Deletion of the pH sensor GPR4 decreases renal acid excretion.

PubMed

Sun, Xuming; Yang, Li V; Tiegs, Brian C; Arend, Lois J; McGraw, Dennis W; Penn, Raymond B; Petrovic, Snezana

2010-10-01

Proton receptors are G protein-coupled receptors that accept protons as ligands and function as pH sensors. One of the proton receptors, GPR4, is relatively abundant in the kidney, but its potential role in acid-base homeostasis is unknown. In this study, we examined the distribution of GPR4 in the kidney, its function in kidney epithelial cells, and the effects of its deletion on acid-base homeostasis. We observed GPR4 expression in the kidney cortex, in the outer and inner medulla, in isolated kidney collecting ducts, and in cultured outer and inner medullary collecting duct cells (mOMCD1 and mIMCD3). Cultured mOMCD1 cells exhibited pH-dependent accumulation of intracellular cAMP, characteristic of GPR4 activation; GPR4 knockdown attenuated this accumulation. In vivo, deletion of GPR4 decreased net acid secretion by the kidney and resulted in a nongap metabolic acidosis, indicating that GPR4 is required to maintain acid-base homeostasis. Collectively, these findings suggest that GPR4 is a pH sensor with an important role in regulating acid secretion in the kidney collecting duct.

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

Association of Slow Graft Function with Long-Term Outcomes in Kidney Transplant Recipients.

PubMed

Wang, Connie J; Tuffaha, Ahmad; Phadnis, Milind A; Mahnken, Jonathan D; Wetmore, James B

2018-04-03

BACKGROUND Whether slow graft function (SGF) represents an intermediate phenotype between immediate graft function (IGF) and delayed graft function (DGF) in kidney transplant recipients is unknown. MATERIAL AND METHODS In a retrospective cohort analysis of 1,222 kidney transplant recipients, we classified patients as having IGF, SGF, and DGF using two different schemas. SGF was defined as serum creatinine (Cr) ≥3.0 mg/dL by postoperative day 5 in Schema 1, and in Schema 2, SGF was defined as Cr >1.5 mg/dL plus a creatinine reduction ratio <20% between postoperative days 1 and 3. A complementary log-log model was used to examine the association of graft function with graft survival and patient survival. RESULTS Mean age of study patients was 51.5±13.3 years, 59.9% were male, and 66.7% were white. In Schema 1, SGF and DGF were associated with comparable increases in risk of graft failure compared to IGF (hazard ratio (HR) 1.46, 95% confidence intervals (CI) 1.02-2.10 for SGF and HR 1.56, CI 1.11-2.22 for IGF); estimates were similar for Schema 2 (HR 1.52, CI 1.05-2.20 for SGF and HR 1.54, CI 1.10-2.17 for IGF). However, for mortality, outcomes for SGF were similarly to IGF, both SGF and IGF were associated with lower risk relative to DGF (HR 0.54, CI 0.36-0.80 for SGF in Schema 1; HR 0.58, CI 0.39-0.85 for SGF in Schema 2). CONCLUSIONS These findings suggest that SGF may be a marker for graft failure but not for mortality, and SGF may therefore represent a phenotype separate from IGF and DGF.

PECULIAIRITIES OF MELATONIN EFFECT ON CHONORHYTMIC ORGANIZATION OF KIDNEY ACID-REGULATING FUNCTION INFLUENCED BY NITROGEN MONOXIDE SYNTHESIS BLOCKADE UNDER CONDITIONS OF PINEAL GLAND HYPOFUNCTION.

PubMed

Semenenko, S; Tymofiychuk, I; Boreyko, L; Karatieieva, S; Slobodian, K

2017-10-01

The objective of research is to study the peculiarities of melatonin effect on chronorhythmic organization of the kidney acid-regulating function influenced by nitrogen monoxide (NO) synthesis blockade under conditions of pineal gland (PG) hypofunction. The experiments were conducted on 72 mature non-linear albino male rats with their body mass 0,15-0,18 kg. The animals were kept under vivarium conditions at a stable temperature and air humidity fed on a standard dietary intake. The control group included animals (n=36) kept under conditions of usual light regimen (12.00С:12.00Т) during 7 days. The experimental group included animals (n=36) injected with N-nitro-L-arginine (L-NNA) in the dose of 20 mg/kg during 7 days under conditions of continuous light (12.00С:12.00С) and melatonin in the dose of 0,5 mg/kg during 7 days simultaneously. On the 8th day the animals were exposed to 5% water load with heated to room temperature water supplied and the parameters of the kidney acid-regulating function under conditions of forced diuresis were investigated. Kidney functions in the control animals are subordinated to accurate circadian organization. Daily rhythms of the parameters of kidney acid-regulating functions reflect similar changes of the renal processes. Chronorhythmic transformations of the kidney acid-regulating functions in animals with blocked NO synthesis against continuous light and parallel injection of melatonin enable to suggest that NO synthesis blockade under conditions of melatonin correction reduces daily mean pH level as compared to the control. Although, it was higher than that in the animals with blocked NO synthesis against the ground of physiological function of the pineal gland, and animals with PG hypofunction under conditions of NO synthesis blockadeю Therefore, under conditions of L-NNA blockade of NO synthesis and injection of melatonin influenced by PG hypofunction chronorhythmic transformations of architectonics and phase structure of rhythms of the majority of parameters of the kidney acid-regulating function were found, which is an important diagnostic sign of exertion of adaptive possibilities on the border of transmission of adaptation into disadaptation, were detected.

Icariin protects rats against 5/6 nephrectomy-induced chronic kidney failure by increasing the number of renal stem cells.

PubMed

Huang, Zhongdi; He, Liqun; Huang, Di; Lei, Shi; Gao, Jiandong

2015-10-21

Chronic kidney disease poses a serious health problem worldwide with increasing prevalence and lack of effective treatment. This study aimed to investigate the mechanism of icariin in alleviating chronic renal failure induced by 5/6 nephrectomy in rats. The chronic renal failure model was established by a two-phased 5/6 nephrectomy procedure. The model rats were given daily doses of water or icariin for 8 weeks. The kidney morphology was checked by HE staining. The levels of blood urea nitrogen, serum creatinine, and serum uric acid were measured by colometric methods. The expression of specified genes was analyzed by quantitative real-time PCR and immunohistochemical staining. The number of renal stem/progenitor cells was analyzed by CD133 and CD24 immunohistochemical staining. Icariin protected against CDK-caused damages to kidney histology and improved renal function, significantly reduced levels of BUN, creatinine, and uric acid. Icariin inhibited the expression level of TGF-β1 whereas upregulated HGF, BMP-7, WT-1, and Pax2 expression. Moreover, ccariin significantly increased the expression of CD24, CD133, Osr1, and Nanog in remnant kidney and the numbers of CD133(+)/CD24(+) renal stem/progenitor cells. These data demonstrated that icariin effectively alleviated 5/6 nephrectomy induced chronic renal failure through increasing renal stem/progenitor cells.

CT-based renal volume and graft function after living-donor kidney transplantation: Is there a volume threshold to avoid?

PubMed

Dias, Jorge; Malheiro, Jorge; Almeida, Manuela; Dias, Leonídio; Silva-Ramos, Miguel; Martins, La Salete; Xambre, Luís; Castro-Henriques, António

2015-05-01

Donated kidney volume influences post-transplant outcomes and graft survival. We evaluated the relationship between living-donor kidney volume and recipient graft function at 12 months post-transplantation, exploring a volume threshold for a suboptimal graft function, and compared two different formulas of volume estimation. A retrospective analysis of 82 pairs of living-donor kidney transplants was conducted. Donor renal volumes were estimated from computerized tomography scans using the ellipsoid formula and the voxel counting technique. Linear and restricted cubic regression spline was used to analyze the association of volume with graft function. Additionally, we determined the correlation between the two volume estimation formulas and established a correction factor for the ellipsoid formula. Renal volume (adjusted to recipient BSA) had the strongest independent effect (B = 1.65 per 10 ml/m(2) increase, p value <0.001) on graft function at 12 months. The eGFR at 12 months was 52.5, 63.6 and 67.6 ml/min/1.73 m(2) for the low, medium and high volume ratio terciles, respectively (p value <0.001). The odds of a GFR <50 ml/min became significantly reduced with volumes above 145 cc/1.73 m(2). A strong positive correlation between the two formulas was identified (R(2) = 0.705), but the optimal correction factor for our cohort was 0.566. In a Caucasian population, higher donor kidney volumes estimated from preoperative CT scans are associated with higher recipient eGFRs at 12 months after live-donor transplantation. Using this criterion, transplant teams can potentially improve selection of living donors if multiple donors are available. However, the need for precise estimation of donor kidney volumes should not be overlooked.

Association between Soluble Klotho and Change in Kidney Function: The Health Aging and Body Composition Study.

PubMed

Drew, David A; Katz, Ronit; Kritchevsky, Stephen; Ix, Joachim; Shlipak, Michael; Gutiérrez, Orlando M; Newman, Anne; Hoofnagle, Andy; Fried, Linda; Semba, Richard D; Sarnak, Mark

2017-06-01

CKD appears to be a condition of soluble klotho deficiency. Despite known associations between low soluble klotho levels and conditions that promote kidney damage, such as oxidative stress and fibrosis, little information exists regarding the longitudinal association between soluble klotho levels and change in kidney function. We assayed serum soluble α -klotho in 2496 participants within the Health Aging and Body Composition study, a cohort of older adults. The associations between soluble klotho levels and decline in kidney function (relative decline: eGFR decline ≥30%; absolute decline: eGFR decline >3 ml/min per year) and incident CKD (incident eGFR <60 ml/min per 1.73 m 2 and >1 ml/min per year decline) were evaluated. We adjusted models for demographics, baseline eGFR, urine albumin-to-creatinine ratio, comorbidity, and measures of mineral metabolism. Among participants, the mean (SD) age was 75 (3) years, 52% were women, and 38% were black. Median (25th, 75th percentiles) klotho level was 630 (477, 817) pg/ml. In fully adjusted models, each two-fold higher level of klotho associated with lower odds of decline in kidney function (odds ratio, 0.78 [95% confidence interval, 0.66 to 0.93] for 30% decline in eGFR, and 0.85 [95% confidence interval, 0.73 to 0.98] for >3 ml/min per year decline in eGFR), but not of incident CKD (incident rate ratio, 0.90 [95% confidence interval, 0.78 to 1.04]). Overall, a higher soluble klotho level independently associated with a lower risk of decline in kidney function. Future studies should attempt to replicate these results in other cohorts and evaluate the underlying mechanism. Copyright © 2017 by the American Society of Nephrology.

Kidney Dysfunction in Adult Offspring Exposed In Utero to Type 1 Diabetes Is Associated with Alterations in Genome-Wide DNA Methylation

PubMed Central

Gautier, Jean-François; Porcher, Raphaël; Abi Khalil, Charbel; Bellili-Munoz, Naima; Fetita, Lila Sabrina; Travert, Florence; Choukem, Simeon-Pierre; Riveline, Jean-Pierre; Hadjadj, Samy; Larger, Etienne; Boudou, Philippe; Blondeau, Bertrand; Roussel, Ronan; Ferré, Pascal; Ravussin, Eric; Rouzet, François; Marre, Michel

2015-01-01

Background Fetal exposure to hyperglycemia impacts negatively kidney development and function. Objective Our objective was to determine whether fetal exposure to moderate hyperglycemia is associated with epigenetic alterations in DNA methylation in peripheral blood cells and whether those alterations are related to impaired kidney function in adult offspring. Design Twenty nine adult, non-diabetic offspring of mothers with type 1 diabetes (T1D) (case group) were matched with 28 offspring of T1D fathers (control group) for the study of their leukocyte genome-wide DNA methylation profile (27,578 CpG sites, Human Methylation 27 BeadChip, Illumina Infinium). In a subset of 19 cases and 18 controls, we assessed renal vascular development by measuring Glomerular Filtration Rate (GFR) and Effective Renal Plasma Flow (ERPF) at baseline and during vasodilatation produced by amino acid infusion. Results Globally, DNA was under-methylated in cases vs. controls. Among the 87 CpG sites differently methylated, 74 sites were less methylated and 13 sites more methylated in cases vs. controls. None of these CpG sites were located on a gene known to be directly involved in kidney development and/or function. However, the gene encoding DNA methyltransferase 1 (DNMT1)—a key enzyme involved in gene expression during early development–was under-methylated in cases. The average methylation of the 74 under-methylated sites differently correlated with GFR in cases and controls. Conclusion Alterations in methylation profile imprinted by the hyperglycemic milieu of T1D mothers during fetal development may impact kidney function in adult offspring. The involved pathways seem to be a nonspecific imprinting process rather than specific to kidney development or function. PMID:26258530

Kidney Dysfunction in Adult Offspring Exposed In Utero to Type 1 Diabetes Is Associated with Alterations in Genome-Wide DNA Methylation.

PubMed

Gautier, Jean-François; Porcher, Raphaël; Abi Khalil, Charbel; Bellili-Munoz, Naima; Fetita, Lila Sabrina; Travert, Florence; Choukem, Simeon-Pierre; Riveline, Jean-Pierre; Hadjadj, Samy; Larger, Etienne; Boudou, Philippe; Blondeau, Bertrand; Roussel, Ronan; Ferré, Pascal; Ravussin, Eric; Rouzet, François; Marre, Michel

2015-01-01

Fetal exposure to hyperglycemia impacts negatively kidney development and function. Our objective was to determine whether fetal exposure to moderate hyperglycemia is associated with epigenetic alterations in DNA methylation in peripheral blood cells and whether those alterations are related to impaired kidney function in adult offspring. Twenty nine adult, non-diabetic offspring of mothers with type 1 diabetes (T1D) (case group) were matched with 28 offspring of T1D fathers (control group) for the study of their leukocyte genome-wide DNA methylation profile (27,578 CpG sites, Human Methylation 27 BeadChip, Illumina Infinium). In a subset of 19 cases and 18 controls, we assessed renal vascular development by measuring Glomerular Filtration Rate (GFR) and Effective Renal Plasma Flow (ERPF) at baseline and during vasodilatation produced by amino acid infusion. Globally, DNA was under-methylated in cases vs. controls. Among the 87 CpG sites differently methylated, 74 sites were less methylated and 13 sites more methylated in cases vs. controls. None of these CpG sites were located on a gene known to be directly involved in kidney development and/or function. However, the gene encoding DNA methyltransferase 1 (DNMT1)--a key enzyme involved in gene expression during early development--was under-methylated in cases. The average methylation of the 74 under-methylated sites differently correlated with GFR in cases and controls. Alterations in methylation profile imprinted by the hyperglycemic milieu of T1D mothers during fetal development may impact kidney function in adult offspring. The involved pathways seem to be a nonspecific imprinting process rather than specific to kidney development or function.

The Kidney in Aging: Physiological Changes and Pathological Implications.

PubMed

Sobamowo, H; Prabhakar, S S

2017-01-01

Aging is associated with progressive decline in renal function along with concurrent morphological changes that ultimately lead to glomerulosclerosis. The mechanisms leading to such changes in the kidney with age as well as the basis of controversies that surround the physiological basis vs pathological nature of aging kidney are the focus of this in-depth review. In addition, the renal functional defects of acid-base homeostasis and electrolyte disturbances in elderly and the physiological basis of such disorders are also discussed. © 2017 Elsevier Inc. All rights reserved.

Diabetic nephropathy in Africa: A systematic review

PubMed Central

Noubiap, Jean Jacques N; Naidoo, Jashira; Kengne, Andre P

2015-01-01

AIM: To determine the prevalence and incidence of diabetic nephropathy in Africa. METHODS: We performed a systematic narrative review of published literature following the MOOSE Guidelines for Meta-Analysis and Systematic Reviews of Observational Studies. We searched PubMed-MEDLINE for all articles published in English and French languages between January 1994 and July 2014 using a predefined strategy based on the combination of relevant terms and the names of each of the 54 African countries and African sub-regions to capture the largest number of studies, and hand-searched the reference lists of retrieved articles. Included studies reported on the prevalence, incidence or determinants of chronic kidney disease (CKD) in people with diabetes within African countries. RESULTS: Overall, we included 32 studies from 16 countries; two being population-based studies and the remaining being clinic-based surveys. Most of the studies (90.6%) were conducted in urban settings. Methods for assessing and classifying CKD varied widely. Measurement of urine protein was the most common method of assessing kidney damage (62.5% of studies). The overall prevalence of CKD varied from 11% to 83.7%. Incident event rates were 94.9% for proteinuria at 10 years of follow-up, 34.7% for end-stage renal disease at 5 years of follow-up and 18.4% for mortality from nephropathy at 20 years of follow-up. Duration of diabetes, blood pressure, advancing age, obesity and glucose control were the common determinants of kidney disease. CONCLUSION: The burden of CKD is important among people with diabetes in Africa. High quality data from large population-based studies with validated measures of kidney function are still needed to better capture the magnitude and characteristics of diabetic nephropathy in Africa. PMID:26069725

Fibroblast growth factor 23, iron and inflammation - are they related in early stages of chronic kidney disease?

PubMed

Lukaszyk, Ewelina; Lukaszyk, Mateusz; Koc-Zorawska, Ewa; Bodzenta-Lukaszyk, Anna; Malyszko, Jolanta

2017-06-01

Fibroblast growth factor 23 (FGF-23) levels are elevated in impaired renal function. Inflammation and iron are potential regulators of FGF-23. The aim of the study was to evaluate the association between FGF-23 concentration, novel iron status biomarkers and inflammatory parameters among patients with early stages of chronic kidney disease (CKD). The study population included 84 patients with CKD in the early stage. Serum hemoglobin, fibrinogen, creatinine, iron, transferrin saturation and ferritin levels were measured using standard laboratory methods. Commercially available kits were used to measure: intact FGF-23, hepcidin, soluble transferrin receptor (sTfR), interleukin 6 (IL-6) and high-sensitivity C-reactive protein (hsCRP). In patients with CKD no differences in FGF-23 concentration according to iron status were observed. Lower iron concentration was associated with higher concentrations of hsCRP, IL-6 and fibrinogen. In univariate and multivariate analysis FGF-23 correlated with fibrinogen ( r = -0.23, p < 0.05) and eGFR ( r = -0.36, p < 0.05). FGF-23 is affected by kidney function and fibrinogen but not iron status parameters in the early stages of CKD. Our data are paving the way for further studies on the role of FGF-23 in iron metabolism, especially in early stages of CKD.

Effect of Erythropoietin on Postresuscitation Renal Function in a Swine Model of Ventricular Fibrillation.

PubMed

Pantazopoulos, Charalampos; Iacovidou, Nicoletta; Kouskouni, Evangelia; Pliatsika, Paraskevi; Papalois, Apostolos; Kaparos, Georgios; Barouxis, Dimitrios; Vasileiou, Panagiotis; Lelovas, Pavlos; Kotsilianou, Olympia; Pantazopoulos, Ioannis; Gkiokas, Georgios; Garosa, Clara; Faa, Gavino; Xanthos, Theodoros

2016-01-01

Purpose . To investigate the effect of EPO administration on postresuscitation renal function. Methods . Twenty-four female Landrace/Large-White piglets aged 10-15 weeks with average weight of 19 ± 2 kg were randomly assigned to 2 different groups of 12 subjects each. After the end of an 8-minute ventricular fibrillation, the control group (Group C) received saline as placebo, whereas the EPO group (Group E) received EPO 5000 U/kg. The animals were resuscitated according to the 2010 European Resuscitation Council Guidelines for Resuscitation. Results . Five animals (41.67%) from Group C and 11 animals (91.67%) from Group E achieved ROSC ( p = 0.027). Eight animals (66.67%, 5 surviving and 3 nonsurviving) from Group C suffered severe kidney damage or AKI compared to animals from Group E, in which none of the swine had evidence of severe kidney damage or AKI ( p = 0.001). There was a statistically significant difference in all tested biochemical markers between the two groups, as well as a positive correlation of creatinine with NGAL, L-FABP, and IL-18 (summed mean values' p = 0.049, 0.01, and 0.004, resp.). Conclusions . Administration of EPO protected swine from postresuscitation acute kidney injury.

Effect of Erythropoietin on Postresuscitation Renal Function in a Swine Model of Ventricular Fibrillation

PubMed Central

Kouskouni, Evangelia; Pliatsika, Paraskevi; Kaparos, Georgios; Barouxis, Dimitrios; Lelovas, Pavlos; Kotsilianou, Olympia; Pantazopoulos, Ioannis; Gkiokas, Georgios; Garosa, Clara

2016-01-01

Purpose. To investigate the effect of EPO administration on postresuscitation renal function. Methods. Twenty-four female Landrace/Large-White piglets aged 10–15 weeks with average weight of 19 ± 2 kg were randomly assigned to 2 different groups of 12 subjects each. After the end of an 8-minute ventricular fibrillation, the control group (Group C) received saline as placebo, whereas the EPO group (Group E) received EPO 5000 U/kg. The animals were resuscitated according to the 2010 European Resuscitation Council Guidelines for Resuscitation. Results. Five animals (41.67%) from Group C and 11 animals (91.67%) from Group E achieved ROSC (p = 0.027). Eight animals (66.67%, 5 surviving and 3 nonsurviving) from Group C suffered severe kidney damage or AKI compared to animals from Group E, in which none of the swine had evidence of severe kidney damage or AKI (p = 0.001). There was a statistically significant difference in all tested biochemical markers between the two groups, as well as a positive correlation of creatinine with NGAL, L-FABP, and IL-18 (summed mean values' p = 0.049, 0.01, and 0.004, resp.). Conclusions. Administration of EPO protected swine from postresuscitation acute kidney injury. PMID:27847811

Risk factors associated with post-kidney transplant malignancies: an article from the Cancer-Kidney International Network.

PubMed

Sprangers, Ben; Nair, Vinay; Launay-Vacher, Vincent; Riella, Leonardo V; Jhaveri, Kenar D

2018-06-01

In kidney transplant recipients, cancer is one of the leading causes of death with a functioning graft beyond the first year of kidney transplantation, and malignancies account for 8-10% of all deaths in the USA (2.6 deaths/1000 patient-years) and exceed 30% of deaths in Australia (5/1000 patient-years) in kidney transplant recipients. Patient-, transplant- and medication-related factors contribute to the increased cancer risk following kidney transplantation. While it is well established that the overall immunosuppressive dose is associated with an increased risk for cancer following transplantation, the contributive effect of different immunosuppressive agents is not well established. In this review we will discuss the different risk factors for malignancies after kidney transplantation.

Trends in serum creatinine testing in Oxfordshire, UK, 1993-2013: a population-based cohort study.

PubMed

Oke, Jason; Shine, Brian; McFadden, Emily; Stevens, Richard; Lasserson, Daniel; Perera, Rafael

2015-12-16

To determine how many kidney function tests are done, on whom, how frequently they are performed and how they have changed over time. Retrospective study of all serum creatinine, urine albumin and urine creatinine tests. Primary and secondary care in Oxfordshire from 1993 to 2013. Unselected population of 1,220,447 people. The total number of creatinine and urinary protein tests ordered from primary and secondary care and the number of tests per year stratified by categories of estimated glomerular filtration rate (eGFR). The frequency of testing in patients having their kidney function monitored. Creatinine requests from primary care increased steadily from 1997 and exceeded 220,000 requests in 2013. Tests corresponding to normal kidney function (eGFR >60/mL/min/1.73 m(2)) constituted 59% of all kidney function tests in 1993 and accounted for 83% of all tests in 2013. Test corresponding to chronic kidney disease (CKD) stages 3-5 declined after 2007. Reduced kidney function, albuminuria, male gender, diabetes and age were independently associated with more frequent monitoring. For a female patient between 61 and 80 years and with stage 3a CKD, the average number of serum creatinine tests (95% CI) was 3.23/year (3.19 to 3.26) and for a similar woman with diabetes, the average number of tests was 5.50 (5.44 to 5.56) tests per year. There has been a large increase in the number of kidney function tests over the past two decades. However, we found little evidence that this increase is detecting more CKD. Tests are becoming more frequent in people with and without evidence of renal impairment. Future work using a richer data source could help unravel the underlying reasons for the increased testing and determine how much is necessary and useful. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

Effects of Mediterranean diets on kidney function: a report from the PREDIMED trial.

PubMed

Díaz-López, Andrés; Bulló, Mònica; Martínez-González, Miguel Ángel; Guasch-Ferré, Marta; Ros, Emilio; Basora, Josep; Covas, María-Isabel; del Carmen López-Sabater, Maria; Salas-Salvadó, Jordi

2012-09-01

Epidemiologic observations have linked healthy dietary patterns to improved kidney function. We assessed the effects of the Mediterranean diet (MedDiet) on kidney function in both a cross-sectional assessment and after a 1-year intervention in a cohort of the PREDIMED (Prevención con Dieta Mediterránea) Study, a multicenter 3-arm randomized clinical trial to determine the efficacy of the MedDiet on primary cardiovascular prevention. Community-dwelling men aged 55-80 years and women aged 60-80 years at high risk of cardiovascular disease from Reus, Spain. Participants were randomly assigned to 3 ad libitum diets: a MedDiet supplemented with virgin olive oil (MedDiet + olive oil), a MedDiet supplemented with mixed nuts (MedDiet + nuts), or a control low-fat diet. Estimated glomerular filtration rate (eGFR) and urinary albumin-creatinine ratio (ACR). Nutrient intake, adherence to the MedDiet, lifestyle variables, cardiovascular risk factors, serum urea and creatinine concentrations, eGFR, and urinary ACR were evaluated at baseline and after intervention for 1 year. Baseline kidney function markers were similar across quartiles of adherence to the MedDiet in 785 participants (55% women; mean age, 67 years). After a 1-year intervention in 665 participants, the 3 dietary approaches were associated with improved kidney function, with similar average increases in eGFR (4.7 [95% CI, 3.2-6.2], 3.5 [95% CI, 1.9-5.0], and 4.1 [95% CI, 2.8-5.5] mL/min/1.73 m(2) for the MedDiet + olive oil, MedDiet + nuts, and control groups, respectively [P < 0.001 vs baseline for each; P = 0.9 for differences among groups]), but no changes in ACRs after adjustment for various confounders. Generalization of results to other age groups or ethnicities. GFR was not directly measured. The results do not support the notion that the MedDiet has a beneficial effect on kidney function over and above that of advice for a low-fat diet in elderly individuals at high cardiovascular risk. Copyright © 2012 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.

High-fat diet induces an initial adaptation of mitochondrial bioenergetics in the kidney despite evident oxidative stress and mitochondrial ROS production

PubMed Central

Ruggiero, Christine; Ehrenshaft, Marilyn; Cleland, Ellen

2011-01-01

Obesity and metabolic syndrome are associated with an increased risk for several diabetic complications, including diabetic nephropathy and chronic kidney diseases. Oxidative stress and mitochondrial dysfunction are often proposed mechanisms in various organs in obesity models, but limited data are available on the kidney. Here, we fed a lard-based high-fat diet to mice to investigate structural changes, cellular and subcellular oxidative stress and redox status, and mitochondrial biogenesis and function in the kidney. The diet induced characteristic changes, including glomerular hypertrophy, fibrosis, and interstitial scarring, which were accompanied by a proinflammatory transition. We demonstrate evidence for oxidative stress in the kidney through 3-nitrotyrosine and protein radical formation on high-fat diet with a contribution from iNOS and NOX-4 as well as increased generation of mitochondrial oxidants on carbohydrate- and lipid-based substrates. The increased H2O2 emission in the mitochondria suggests altered redox balance and mitochondrial ROS generation, contributing to the overall oxidative stress. No major derailments were observed in respiratory function or biogenesis, indicating preserved and initially improved bioenergetic parameters and energy production. We suggest that, regardless of the oxidative stress events, the kidney developed an adaptation to maintain normal respiratory function as a possible response to an increased lipid overload. These findings provide new insights into the complex role of oxidative stress and mitochondrial redox status in the pathogenesis of the kidney in obesity and indicate that early oxidative stress-related changes, but not mitochondrial bioenergetic dysfunction, may contribute to the pathogenesis and development of obesity-linked chronic kidney diseases. PMID:21386058

Angiotensin converting enzyme inhibition and the kidney

NASA Technical Reports Server (NTRS)

Hollenberg, N. K.

1988-01-01

Angiotensin II (Ang II) induces a marked reduction in renal blood flow at doses well below those required to induce a pressor response, and as blood flow falls there is a decline in glomerular filtration rate and sodium excretion. This striking sensitivity of the renal blood supply led many workers to consider the possibility that angiotensin functions as a local renal hormone. As angiotensin converting enzyme (ACE) was found in particular abundance in the lung, it seemed reasonable to suspect that most of the conversion occurred there, and that the function of Ang II would be primarily systemic, rather than intrarenal. In this review, I will explore the evidence that has accumulated on these two possibilities, since they have important implications for our current understanding of normal kidney function and derangements of kidney function in disease.

Pretransplant Recipient Circulating CD4+CD127lo/- Tumor Necrosis Factor Receptor 2+ Regulatory T Cells: A Surrogate of Regulatory T Cell-Suppressive Function and Predictor of Delayed and Slow Graft Function After Kidney Transplantation.

PubMed

Nguyen, Minh-Tri J P; Fryml, Elise; Sahakian, Sossy K; Liu, Shuqing; Cantarovich, Marcelo; Lipman, Mark; Tchervenkov, Jean I; Paraskevas, Steven

2016-02-01

Delayed graft function (DGF) and slow graft function (SGF) are ischemia-reperfusion-associated acute kidney injuries (AKI) that decrease long-term graft survival after kidney transplantation. Regulatory T (Treg) cells are protective in murine AKI, and their suppressive function predictive of AKI in kidney transplantation. The conventional Treg cell function coculture assay is however time-consuming and labor intensive. We sought a simpler alternative to measure Treg cell function and predict AKI. In this prospective observational cohort study, pretransplant recipient circulating CD4+CD25+CD127lo/- and CD4+CD127lo/- tumor necrosis factor receptor 2 (TNFR2)+ Treg cells were measured by flow cytometry in 76 deceased donor kidney transplant recipients (DGF, n = 18; SGF, n = 34; immediate graft function [IGF], n = 24). In a subset of 37 recipients, pretransplant circulating Treg cell-suppressive function was also quantified by measuring the suppression of autologous effector T-cell proliferation by Treg cell in coculture. The TNFR2+ expression on CD4+CD127lo/- T cells correlated with Treg cell-suppressive function (r = 0.63, P < 0.01). In receiver operating characteristic curves, percentage and absolute number of CD4+CD127lo/-TNFR2+ Treg cell predicted DGF from non-DGF (IGF + SGF) with area under the curves of 0.75 and 0.77, respectively, and also AKI (DGF + SGF) from IGF with area under the curves of 0.76 and 0.72, respectively (P < 0.01). Prediction of AKI (DGF + SGF) from IGF remained significant in multivariate logistic regression accounting for cold ischemic time, donor age, previous transplant, and pretransplant dialysis modality. Pretransplant recipient circulating CD4+CD127lo/-TNFR2+ Treg cell is potentially a simpler alternative to Treg cell function as a pretransplant recipient immune marker for AKI (DGF + SGF), independent from donor and organ procurement characteristics.