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Sample records for chronic kidney allograft

  1. Genetics and Epigenetics of Chronic Allograft Dysfunction in Kidney Transplants.

    PubMed

    Zununi Vahed, Sepideh; Samadi, Nasser; Mostafidi, Elmira; Ardalan, Mohammad Reza; Omidi, Yadollah

    2016-01-01

    Chronic allograft dysfunction is the most common cause of allograft lost. Chronic allograft dysfunction happens as a result of complex interactions at the molecular and cellular levels. Genetic and environmental factors both influence the evolution and progression of the chronic allograft dysfunction. Epigenetic modification could be considered as a therapeutically modifiable element to pause the fibrosis process through novel strategies. In this review, the PubMed database was searched for English-language articles on these new areas.

  2. Increased Expression of p-Akt correlates with Chronic Allograft Nephropathy in a Rat Kidney Model.

    PubMed

    Zhou, Li-Na; Wang, Ning; Dong, Yang; Zhang, Yiqin; Zou, Hequn; Li, Qingqin; Shi, Yangling; Chen, Ling; Zhou, Wenying; Han, Conghui; Wang, Yuxin

    2015-04-01

    Chronic allograft nephropathy (CAN) is the most common cause of chronic graft dysfunction leading to graft failure, our study investigates the expression and significance of p-Akt in the pathogenesis of CAN in rats. Kidneys of Fisher (F344) rats were orthotopically transplanted into Lewis (LEW) rats. The animals were evaluated at 4, 8, 12, 16, and 24 weeks post-transplantation for renal function and histopathology. Phosphorate Akt (p-Akt) protein expression was determined by Western blot and immunohistological assays. Our data show that 24-h urinary protein excretion in CAN rats increased significantly at week 16 as compared with F344/LEW controls. Allografts got severe interstitial infiltration of mononuclear cells at week 4 and week 8, but it was degraded as the time went on after week 16. Allografts markedly presented with severe interstitial fibrosis (IF) and tubular atrophy at 16 and 24 weeks. p-Akt expression was upregulated in rat kidneys with CAN, and the increase became more significant over time after transplantation. p-Akt expression correlated significantly with 24-h urinary protein excretion, serum creatinine levels, tubulointerstitial mononuclear cells infiltration, smooth muscle cells (SMCs) migration in vascular wall, and IF. It was concluded that p-Akt overexpression might be the key event that involved mononuclear cells infiltration and vascular SMCs migration at early stage, and IF and allograft nephroangiosclerosis at the late stage of CAN pathogenesis in rats.

  3. Relationship between European Mitochondrial Haplogroups and Chronic Renal Allograft Rejection in Patients with Kidney Transplant

    PubMed Central

    JIMÉNEZ-SOUSA, María Angeles; TAMAYO, Eduardo; GUZMÁN-FULGENCIO, María; FERNÁNDEZ-RODRÍGUEZ, Amanda; HEREDIA-RODRIGUEZ, María; GARCÍA-ÁLVAREZ, Mónica; BERMEJO-MARTIN, Jesús F; PINEDA-TENOR, Daniel; RUIZ-GRANADO, Patricia; ALVAREZ-FUENTE, Elisa; GÓMEZ-SANCHEZ, Esther; GÓMEZ-HERRERAS, José I; RESINO, Salvador

    2014-01-01

    Mitochondrial DNA variants may contribute to differences in mitochondrial function, leading to an altered immune system. The aim of this study was to analyze the relationship between mtDNA haplogroups and the development of chronic allograft dysfunction in patients with kidney transplant. A retrospective observational study was carried out on 261 patients who received kidney transplant (114 had stable transplant and 147 patients developed chronic allograft dysfunction). DNA samples were genotyped for 14 mtDNA polymorphisms by using Sequenom's MassARRAY platform (San Diego, CA, USA). Only European white patients within the N macro-cluster were included. Patients with haplogroups V (odds ratio (OR)=0.32; p=0.037) and J (OR=0.36; p=0.038) showed lower odds for developing CRAD than patients with haplogroup H. After adjusting for the most significant variables, haplogroups V and J tended to statistical significance (p=0.091 and p=0.067 respectively). This is a preliminary study in which mtDNA haplogroups seem to be implicated in susceptibility or protection for developing chronic allograft dysfunction. PMID:25170295

  4. Natural Killer Cell Subsets and IL-2, IL-15, and IL-18 Genes Expressions in Chronic Kidney Allograft Dysfunction and Graft Function in Kidney Allograft Recipients

    PubMed Central

    Assadiasl, S.; Sepanjnia, A.; Aghili, B.; Nafar, M.; Ahmadpoor, P.; Pourrezagholi, F.; Parvin, M.; Shahlaee, A.; Nicknam, M. H.; Amirzargar, A.

    2016-01-01

    Background: While acute rejection and early graft loss rates have decreased substantially over the past four decades, progressive chronic allograft dysfunction (CAD) still remains a common cause of late graft loss in kidney transplant recipients. Objective: This study was conducted to investigate the percentage of natural killer (NK) cell subsets and IL-2, 15 and 18 genes expression in two groups of CAD and well-function graft (WFG) recipients. Methods: 30 renal allograft recipients with biopsy-proven interstitial fibrosis/tubular atrophy (IF/TA) and impaired renal function, and 30 sex- and age-matched WFG patients were enrolled in this study. The percentage of NK cell subsets including NK CD56bright and NK CD56dim cells were determined by flowcytometry; IL-2, IL-15, and IL-18 genes expressions were assessed by real-time PCR. Results: Compared to WFG patients, there was a significant (p<0.05) increase in the percentage of NK CD56bright cells in CAD patients. However, the difference in percentage of NK CD56dim cells or CD56dim/CD56bright ratio between the studied groups was not significant. In addition, IL-2, 15 and 18 genes expressions were almost similar in CAD and WFG patients. Conclusion: We found higher percentages of NK CD56bright subset in kidney transplant recipients with CAD without considerable changes in related cytokines’ gene expression, suggesting a possible defect of NK cells maturation in these patients. PMID:28078060

  5. The impact of ICAM1 and VCAM1 gene polymorphisms on chronic allograft nephropathy and transplanted kidney function.

    PubMed

    Kłoda, K; Domański, L; Pawlik, A; Wiśniewska, M; Safranow, K; Ciechanowski, K

    2013-01-01

    ICAM-1 and VCAM-1 adhesion molecules play important roles in the immune response and emergence of chronic allograft nephropathy (CAN). The several polymorphisms of ICAM1 and VCAM1 genes are associated with changes in molecular expression therefore affecting allograft function and immune responses after kidney transplantation. The aim of this study was to examine the impact of polymorphisms in ICAM1 and VCAM1 genes on biopsy-proven CAN and renal allograft function. The 270 Caucasian renal transplant recipients (166 men and 104 women) were genotyped for the rs5498 ICAM1 and rs1041163 and rs3170794 VCAM1 gene polymorphisms using real-time polymerase chain reaction. There was no correlation between polymorphisms and CAN. Creatinine concentrations in the first month after transplantation differed between the rs5498 ICAM1 genotypes (P = .095), being higher for GG carriers (AA + AG vs GG, P =.07) albeit not with statistical significance. Creatinine concentrations at 12, 24, and 36 months after transplantation differed significantly among rs5498 ICAM1 genotypes (P = .0046, P =.016, and P = .02) and were higher among GG carriers (AA + AG vs GG, P = .001, P = .004, and P = .006). Rs5498 ICAM1 GG genotype and receipient male gender were independent factors associated with higher creatinine concentrations. These results suggest that the rs5498 ICAM1 GG genotype may be associated with long-term allograft function.

  6. Application of Label-free Quantitative Peptidomics for the Identification of Urinary Biomarkers of Kidney Chronic Allograft Dysfunction*

    PubMed Central

    Quintana, Luis F.; Campistol, Josep M.; Alcolea, Maria P.; Bañon-Maneus, Elisenda; Sol-González, Amandaé; Cutillas, Pedro R.

    2009-01-01

    The advent of quantitative proteomics opens new opportunities in biomedical and clinical research. Although quantitative proteomics methods based on stable isotope labeling are in general preferred for biomolecular research, biomarker discovery is a case example of a biomedical problem that may be better addressed by using label-free MS techniques. As a proof of concept of this paradigm, we report the use of label-free quantitative LC-MS to profile the urinary peptidome of kidney chronic allograft dysfunction (CAD). The aim was to identify predictive biomarkers that could be used to personalize immunosuppressive therapies for kidney transplant patients. We detected (by LC-M/MS) and quantified (by LC-MS) 6000 polypeptide ions in undigested urine specimens across 39 CAD patients and 32 control individuals. Although unsupervised hierarchical clustering differentiated between the groups when including all the identified peptides, specific peptides derived from uromodulin and kininogen were found to be significantly more abundant in control than in CAD patients and correctly identified the two groups. These peptides are therefore potential biomarkers that might be used for the diagnosis of CAD. In addition, ions at m/z 645.59 and m/z 642.61 were able to differentiate between patients with different forms of CAD with specificities and sensitivities of 90% in a training set and, significantly, of ∼70% in an independent validation set of samples. Interestingly low expression of uromodulin at m/z 638.03 coupled with high expression of m/z 642.61 diagnosed CAD in virtually all cases. Multiple reaction monitoring experiments further validated the results, illustrating the power of our label-free quantitative LC-MS approach for obtaining quantitative profiles of urinary polypeptides in a rapid, comprehensive, and precise fashion and for biomarker discovery. PMID:19357086

  7. Clinical Significance of HLA-DQ Antibodies in the Development of Chronic Antibody-Mediated Rejection and Allograft Failure in Kidney Transplant Recipients.

    PubMed

    Lee, Hyeyoung; Min, Ji Won; Kim, Ji-Il; Moon, In-Sung; Park, Ki-Hyun; Yang, Chul Woo; Chung, Byung Ha; Oh, Eun-Jee

    2016-03-01

    With the development of the single antigen beads assay, the role of donor specific alloantibody (DSA) against human leukocyte antigens in kidney transplantation (KT) has been highlighted. This study aimed to investigate the clinical significance of DQ-DSA detected at renal allograft biopsy. We evaluated 263 KT recipients who underwent allograft biopsy and DSA detection at the same time. Among them, 155 patients who were nonsensitized before transplantation were selected to investigate the role of de-novo DQ-DSA. Both the total and nonsensitized subgroup was categorized into 4 groups each according to DSA results as: DQ only, DQ + non-DQ, non-DQ, and no DSA. In the total patient group, post-KT DSA was positive in 79 (30.0%) patients and DQ-DSA was most prevalent (64.6%). In the nonsensitized subgroup, de-novo DSAs were detected in 45 (29.0%) patients and DQ-DSA was also most prevalent (73.3%). The DQ only group showed a significantly longer post-KT duration compared to the other groups (P < 0.05). The overall incidence of antibody-mediated rejection (AMR) was 17.9%. B-DSA, DR-DSA, and DQ-DSA were associated with AMR (P < 0.05), but in the analysis for chronic AMR, only DQ-DSA showed significance in both the total and the nonsensitized subgroup (P < 0.05). On comparison of Banff scores among groups, those representing humoral immunity were significantly dominant in all DSA positive groups compared to the no DSA group (P < 0.05), and higher scores of markers representing chronic tissue injury were more frequently detected in the groups with DQ-DSA. The worst postbiopsy survival was seen in the DQ + non-DQ group of the total patient group, and patients with de-novo DQ-DSA showed poorer graft survival in the nonsensitized subgroup compared to the no DSA group (P < 0.05). In the multivariate analysis, de-novo DQ-DSA was the only significant risk factor associated with late allograft failure (P < 0.05). Our study is the first to demonstrate

  8. Minimizing the risk of chronic allograft nephropathy.

    PubMed

    Weir, Matthew R; Wali, Ravinder K

    2009-04-27

    Chronic allograft nephropathy, now defined as interstital fibrosis and tubular atrophy not otherwise specified, is a near universal finding in transplant kidney biopsies by the end of the first decade posttransplantation. After excluding death with functioning graft, caused by cardiovascular disease or malignancy, chronic allograft nephropathy is the leading cause of graft failure. Original assumptions were that this was not a modifiable process but inexorable, likely due to past kidney injuries. However, newer understandings suggest that acute or subacute processes are involved, and with proper diagnosis, appropriate interventions can be instituted. Our method involved a review of the primary and secondary prevention trials in calcineurin inhibitor withdrawal. Some of the more important causes of progressive graft deterioration include subclinical cellular or humoral rejection, and chronic calcineurin inhibitor toxicity. Early graft biopsy, assessment of histology, and changes in immunosuppression may be some of the most important measures available to protect graft function. The avoidance of clinical inertia in pursuing subtle changes in graft function is critical. Modification in maintenance immunosuppression may benefit many patients with early evidence of graft deterioration.

  9. 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

  10. Chronic Kidney Diseases

    MedlinePlus

    ... los dientes Video: Getting an X-ray Chronic Kidney Diseases KidsHealth > For Kids > Chronic Kidney Diseases Print ... re talking about your kidneys. What Are the Kidneys? Your kidneys are tucked under your lower ribs ...

  11. Chronic Kidney Diseases

    MedlinePlus

    ... Room? What Happens in the Operating Room? Chronic Kidney Diseases KidsHealth > For Kids > Chronic Kidney Diseases A ... re talking about your kidneys. What Are the Kidneys? Your kidneys are tucked under your lower ribs ...

  12. Urine Proteomics to Detect Biomarkers for Chronic Allograft Dysfunction

    PubMed Central

    Quintana, Luís F.; Solé-Gonzalez, Amanda; Kalko, Susana G.; Bañon-Maneus, Elisenda; Solé, Manel; Diekmann, Fritz; Gutierrez-Dalmau, Alex; Abian, Joaquin; Campistol, Josep M.

    2009-01-01

    Despite optimal immunosuppressive therapy, more than 50% of kidney transplants fail because of chronic allograft dysfunction. A noninvasive means to diagnose chronic allograft dysfunction may allow earlier interventions that could improve graft half-life. In this proof-of-concept study, we used mass spectrometry to analyze differences in the urinary polypeptide patterns of 32 patients with chronic allograft dysfunction (14 with pure interstitial fibrosis and tubular atrophy and 18 with chronic active antibody-mediated rejection) and 18 control subjects (eight stable recipients and 10 healthy control subjects). Unsupervised hierarchical clustering showed good segregation of samples in groups corresponding mainly to the four biomedical conditions. Moreover, the composition of the proteome of the pure interstitial fibrosis and tubular atrophy group differed from that of the chronic active antibody-mediated rejection group, and an independent validation set confirmed these results. The 14 protein ions that best discriminated between these two groups correctly identified 100% of the patients with pure interstitial fibrosis and tubular atrophy and 100% of the patients with chronic active antibody-mediated rejection. In summary, this study establishes a pattern for two histologic lesions associated with distinct graft outcomes and constitutes a first step to designing a specific, noninvasive diagnostic tool for chronic allograft dysfunction. PMID:19056874

  13. Computational Biology: Modeling Chronic Renal Allograft Injury

    PubMed Central

    Stegall, Mark D.; Borrows, Richard

    2015-01-01

    New approaches are needed to develop more effective interventions to prevent long-term rejection of organ allografts. Computational biology provides a powerful tool to assess the large amount of complex data that is generated in longitudinal studies in this area. This manuscript outlines how our two groups are using mathematical modeling to analyze predictors of graft loss using both clinical and experimental data and how we plan to expand this approach to investigate specific mechanisms of chronic renal allograft injury. PMID:26284070

  14. Unique molecular changes in kidney allografts after simultaneous liver-kidney compared with solitary kidney transplantation.

    PubMed

    Taner, Timucin; Park, Walter D; Stegall, Mark D

    2017-02-20

    Kidney allografts transplanted simultaneously with liver allografts from the same donor are known to be immunologically privileged. This is especially evident in recipients with high levels of donor-specific anti-HLA antibodies. Here we investigated the mechanisms of liver's protective impact using gene expression in the kidney allograft. Select solitary kidney transplant or simultaneous liver-kidney transplant recipients were retrospectively reviewed and separated into four groups: 16 cross-match negative kidney transplants, 15 cross-match positive kidney transplants, 12 cross-match negative simultaneous liver-kidney transplants, and nine cross-match-positive simultaneous liver-kidney transplants. Surveillance biopsies of cross-match-positive kidney transplants had increased expression of genes associated with donor-specific antigens, inflammation, and endothelial cell activation compared to cross-match-negative kidney transplants. These changes were not found in cross-match-positive simultaneous liver-kidney transplant biopsies when compared to cross-match-negative simultaneous liver-kidney transplants. In addition, simultaneously transplanting a liver markedly increased renal expression of genes associated with tissue integrity/metabolism, regardless of the cross-match status. While the expression of inflammatory gene sets in cross-match-positive simultaneous liver-kidney transplants was not completely reduced to the level of cross-match-negative kidney transplants, the downstream effects of donor-specific anti-HLA antibodies were blocked. Thus, simultaneous liver-kidney transplants can have a profound impact on the kidney allograft, not only by decreasing inflammation and avoiding endothelial cell activation in cross-match-positive recipients, but also by increasing processes associated with tissue integrity/metabolism by unknown mechanisms.

  15. An unusual case of a patient who lost his native kidneys and renal allograft from cholesterol crystal emboli.

    PubMed

    Ahmed, Wasim; Al Garni, Abdulkareem; Abdelgadir, Elbadri; Khamees, Khamess Obeid; Ellouly, Mohammed Ali Ahmed; Haleem, Abdul

    2015-09-01

    Cholesterol crystal emboli (CCE) syndrome involving native kidneys is an underdiagnosed condition. CCE is rare in renal allografts. It may present with acute kidney injury, but usually not acute graft loss. CCE should be considered in patients with a history of atherosclerosis and an invasive arterial procedure who present with acute or chronic renal allograft dysfunction. Therapy for CCE is mainly supportive and carries a high rate of mortality. To the best of our knowledge, this is the first reported case of a patient who lost his native kidneys and renal allograft due to CCE arising from his own vasculature.

  16. The impact of donor-specific anti-HLA antibodies on late kidney allograft failure.

    PubMed

    Loupy, Alexandre; Hill, Gary S; Jordan, Stanley C

    2012-04-17

    Despite improvements in outcomes of renal transplantation, kidney allograft loss remains substantial, and is associated with increased morbidity, mortality and costs. Identifying the pathologic pathways responsible for allograft loss, and the attendant development of therapeutic interventions, will be one of the guiding future objectives of transplant medicine. One of the most important advances of the past decade has been the demonstration of the destructive power of anti-HLA alloantibodies and their association with antibody-mediated rejection (ABMR). Compelling evidence exists to show that donor-specific anti-HLA antibodies (DSAs) are largely responsible for the chronic deterioration of allografts, a condition previously attributed to calcineurin inhibitor toxicity and chronic allograft nephropathy. The emergence of sensitive techniques to detect DSAs, together with advances in the assessment of graft pathology, have expanded the spectrum of what constitutes ABMR. Today, subtler forms of rejection--such as indolent ABMR, C4d-negative ABMR, and transplant arteriopathy--are seen in which DSAs exert a marked pathological effect. In addition, arteriosclerosis, previously thought to be a bystander lesion related to the vicissitudes of aging, is accelerated in ABMR. Advances in our understanding of the pathological significance of DSAs and ABMR show their primacy in the mediation of chronic allograft destruction. Therapies aimed at B cells, plasma cells and antibodies will be important therapeutic options to improve the length and quality of kidney allograft survival.

  17. Chronic Kidney Disease

    MedlinePlus

    You have two kidneys, each about the size of your fist. Their main job is to filter wastes and excess water out of ... help control blood pressure, and make hormones. Chronic kidney disease (CKD) means that your kidneys are damaged ...

  18. Multifocal Primary Neoplasms in Kidney Allografts: Evaluation of Two Cases

    PubMed Central

    Ellis, Robert J.; Ng, Keng Lim; Samaratunga, Hemamali; Del Vecchio, Sharon J.; Wood, Simon T.

    2016-01-01

    Renal cell carcinoma (RCC) is the fifth most common malignancy in kidney transplant recipients, with increased risk arising due to immunosuppression. De novo RCC occurrence in kidney allografts is much less common when compared with the native kidneys. Multifocal RCC in allograft kidneys is rarely described. In this report, we discuss two cases of de novo multifocal renal neoplasms in allograft kidneys. Case 1 had three distinct neoplastic lesions of >5 mm, and case 2 had four. Using the World Health Organization 2016 classification of adult renal tumours, case 1 had one clear-cell (cc) RCC (grade 3) and two papillary adenomas; all confined to the kidney. Case 2 had a nodular lesion classified as ccRCC (grade 4) with focal rhabdoid differentiation and some infiltration of renal sinus fat; a cc tubulopapillary RCC; a multilocular cystic renal neoplasm of low malignant potential; and a mucinous tubular and spindle cell carcinoma; the last three all confined to the kidney. This is the first report of mucinous tubular and spindle cell carcinoma in a kidney allograft. When considering multifocal RCC with discordant histology, it is likely that these represent independent tumourigenic events. PMID:28326280

  19. Expression of decoy receptor 3 in kidneys is associated with allograft survival after kidney transplant rejection.

    PubMed

    Weng, Shuo-Chun; Shu, Kuo-Hsiung; Wu, Ming-Ju; Wen, Mei-Chin; Hsieh, Shie-Liang; Chen, Nien-Jung; Tarng, Der-Cherng

    2015-09-03

    Decoy receptor 3 (DcR3) expression in kidneys has been shown to predict progression of chronic kidney disease. We prospectively investigated a cohort comprising 96 renal transplant recipients (RTRs) undergoing graft kidney biopsies. Computer-assisted quantitative immunohistochemical staining value of DcR3 in renal tubular epithelial cells (RTECs) was used to determine the predictive role of DcR3 in kidney disease progression. The primary end point was doubling of serum creatinine and/or graft failure. A multivariate Cox proportional hazards model was used to assess the risk of DcR3 expression in rejected kidney grafts toward the renal end point. In total, RTRs with kidney allograft rejection were evaluated and the median follow-up was 30.9 months. The greater expression of DcR3 immunoreactivity in RTECs was correlated with a higher rate of the histopathological concordance of acute T cell-mediated rejection. Compared with 65 non-progressors, 31 progressors had higher DcR3 expression (HDE) regardless of the traditional risk factors. Cox regression analysis showed HDE was significantly associated with the risk of renal end point with a hazard ratio of 3.19 (95% confidence interval, 1.40 to 7.27; P = 0.006) after adjusting for other variables. In repetitive biopsies, HDE in tissue showed rapid kidney disease progression due to persistent inflammation.

  20. The Kidney-Vascular-Bone Axis in the Chronic Kidney Disease-Mineral Bone Disorder

    PubMed Central

    Seifert, Michael E.; Hruska, Keith A.

    2015-01-01

    The last 25 years have been characterized by dramatic improvements in short-term patient and allograft survival after kidney transplantation. Long-term patient and allograft survival remains limited by cardiovascular disease and chronic allograft injury, among other factors. Cardiovascular disease remains a significant contributor to mortality in native chronic kidney disease as well, as cardiovascular mortality in chronic kidney disease more than doubles that of the general population. The chronic kidney disease-mineral bone disorder (CKD-MBD) is a syndrome recently coined to embody the biochemical, skeletal, and cardiovascular pathophysiology that results from disrupting the complex systems biology between the kidney, skeleton, and cardiovascular system in native and transplant kidney disease. The CKD-MBD is a unique kidney disease-specific syndrome containing novel cardiovascular risk factors, with an impact reaching far beyond traditional notions of renal osteodystrophy and hyperparathyroidism. This Overview reviews current knowledge of the pathophysiology of the CKD-MBD, including emerging concepts surrounding the importance of circulating pathogenic factors released from the injured kidney that directly cause cardiovascular disease in native and transplant chronic kidney disease, with potential application to mechanisms of chronic allograft injury and vasculopathy. PMID:26356179

  1. The Kidney-Vascular-Bone Axis in the Chronic Kidney Disease-Mineral Bone Disorder.

    PubMed

    Seifert, Michael E; Hruska, Keith A

    2016-03-01

    The last 25 years have been characterized by dramatic improvements in short-term patient and allograft survival after kidney transplantation. Long-term patient and allograft survival remains limited by cardiovascular disease and chronic allograft injury, among other factors. Cardiovascular disease remains a significant contributor to mortality in native chronic kidney disease as well as cardiovascular mortality in chronic kidney disease more than doubles that of the general population. The chronic kidney disease (CKD)-mineral bone disorder (MBD) is a syndrome recently coined to embody the biochemical, skeletal, and cardiovascular pathophysiology that results from disrupting the complex systems biology between the kidney, skeleton, and cardiovascular system in native and transplant kidney disease. The CKD-MBD is a unique kidney disease-specific syndrome containing novel cardiovascular risk factors, with an impact reaching far beyond traditional notions of renal osteodystrophy and hyperparathyroidism. This overview reviews current knowledge of the pathophysiology of the CKD-MBD, including emerging concepts surrounding the importance of circulating pathogenic factors released from the injured kidney that directly cause cardiovascular disease in native and transplant chronic kidney disease, with potential application to mechanisms of chronic allograft injury and vasculopathy.

  2. Kidney allograft pyelonephritis caused by Salmonella enterica serovar Schwarzengrund.

    PubMed

    Ito, Kenta; Nishio, Haruomi; Iwatani, Yuji; Yamada, Ryo; Okawa, Takao; Yamamoto, Takumi; Murakami, Masaaki; Matsuo, Yoko; Matsuo, Ken; Tanaka, Satoshi; Mori, Kiyoshi; Mori, Noriko

    2017-03-13

    Kidney transplant recipients (KTRs) taking immunosuppressive drugs have a 20-fold greater risk of nontyphoidal Salmonella (NTS) infection than the healthy adult population. Among KTRs, the urinary tract is the most common site of infection. However, few cases of urinary tract infection caused by NTS have been documented in KTRs, and only one in Japan. Furthermore, it frequently induces acute allograft rejection with high mortality. Salmonella enterica subsp. enterica serovar Schwarzengrund (S. Schwarzengrund) is now among the more common Salmonella serovars isolated in Japan and is likely to be invasive. We present a case of a 45-year old female with vesicoureteral reflux to her transplanted kidney who developed kidney allograft pyelonephritis caused by S. Schwarzengrund. She was admitted to our hospital with fever, urodynia, lower abdominal pain, gross hematuria, and cloudy urine. Urine cultures were positive for S. Schwarzengrund. Exposure to cats, especially stray cats, were identified as the most likely source. We administered antibiotics for 4 weeks (ceftriaxone then amoxicillin, each for 2 weeks) and educated her about pet safety. She experienced no recurrence of infection or clinical kidney allograft rejection for 3 months post-treatment. NTS should be considered as a possible pathogen of urinary tract infection among KTRs, especially in cases with animal exposure or structural urologic abnormalities. When the pathogen is NTS, appropriate antibiotics and treatment periods are essential for preventing recurrence and allograft rejection after the completion of treatment.

  3. Recurrence of Acute Page Kidney in a Renal Transplant Allograft

    PubMed Central

    Zayas, Carlos; Mulloy, Laura; Jagadeesan, Muralidharan

    2016-01-01

    Acute Page Kidney (APK) phenomenon is a rare cause of secondary hypertension, mediated by activation of renin-angiotensin-aldosterone system (RAAS). Timely intervention is of great importance to prevent any end organ damage from hypertension. We present a unique case of three episodes of APK in the same renal transplant allograft. PMID:27725836

  4. Recurrence of Acute Page Kidney in a Renal Transplant Allograft.

    PubMed

    Kapoor, Rajan; Zayas, Carlos; Mulloy, Laura; Jagadeesan, Muralidharan

    2016-01-01

    Acute Page Kidney (APK) phenomenon is a rare cause of secondary hypertension, mediated by activation of renin-angiotensin-aldosterone system (RAAS). Timely intervention is of great importance to prevent any end organ damage from hypertension. We present a unique case of three episodes of APK in the same renal transplant allograft.

  5. Allograft loss from acute Page kidney secondary to trauma after kidney transplantation.

    PubMed

    Takahashi, Kazuhiro; Prashar, Rohini; Putchakayala, Krishna G; Kane, William J; Denny, Jason E; Kim, Dean Y; Malinzak, Lauren E

    2017-02-24

    We report a rare case of allograft loss from acute Page kidney secondary to trauma that occurred 12 years after kidney transplantation. A 67-year-old Caucasian male with a past surgical history of kidney transplant presented to the emergency department at a local hospital with left lower abdominal tenderness. He recalled that his cat, which weighs 15 lbs, jumped on his abdomen 7 d prior. On physical examination, a small tender mass was noticed at the incisional site of the kidney transplant. He was producing a normal amount of urine without hematuria. His serum creatinine level was slightly elevated from his baseline. Computer tomography revealed a large subscapular hematoma around the transplant kidney. The patient was observed to have renal trauma grade II at the hospital over a period of three days, and he was finally transferred to a transplant center after his urine output significantly decreased. Doppler ultrasound demonstrated an extensive peri-allograft hypoechoic area and abnormal waveforms with absent arterial diastolic flow and a patent renal vein. Despite surgical decompression, the allograft failed to respond appropriately due to the delay in surgical intervention. This is the third reported case of allograft loss from acute Page kidney following kidney transplantation. This case reinforces that kidney care differs if the kidney is solitary or a transplant. Early recognition and aggressive treatments are mandatory, especially in a case with Doppler signs that are suggestive of compression.

  6. Allograft loss from acute Page kidney secondary to trauma after kidney transplantation

    PubMed Central

    Takahashi, Kazuhiro; Prashar, Rohini; Putchakayala, Krishna G; Kane, William J; Denny, Jason E; Kim, Dean Y; Malinzak, Lauren E

    2017-01-01

    We report a rare case of allograft loss from acute Page kidney secondary to trauma that occurred 12 years after kidney transplantation. A 67-year-old Caucasian male with a past surgical history of kidney transplant presented to the emergency department at a local hospital with left lower abdominal tenderness. He recalled that his cat, which weighs 15 lbs, jumped on his abdomen 7 d prior. On physical examination, a small tender mass was noticed at the incisional site of the kidney transplant. He was producing a normal amount of urine without hematuria. His serum creatinine level was slightly elevated from his baseline. Computer tomography revealed a large subscapular hematoma around the transplant kidney. The patient was observed to have renal trauma grade II at the hospital over a period of three days, and he was finally transferred to a transplant center after his urine output significantly decreased. Doppler ultrasound demonstrated an extensive peri-allograft hypoechoic area and abnormal waveforms with absent arterial diastolic flow and a patent renal vein. Despite surgical decompression, the allograft failed to respond appropriately due to the delay in surgical intervention. This is the third reported case of allograft loss from acute Page kidney following kidney transplantation. This case reinforces that kidney care differs if the kidney is solitary or a transplant. Early recognition and aggressive treatments are mandatory, especially in a case with Doppler signs that are suggestive of compression. PMID:28280700

  7. Kidney allograft survival in dogs treated with total lymphoid irradiation

    SciTech Connect

    Howard, R.J.; Sutherland, D.E.R.; Lum, C.T.; Lewis, W.I.; Kim, T.H.; Slavin, S.; Najarian, J.S.

    1981-02-01

    Total lymphoid irradiation (TLI) is immunosuppressive and, in rodents, can induce a state where transplantation of allogenic bone marrow results in chimerism and permanent acceptance of organ allografts from the donor strain. Twelve splenectomized dogs were treated with TLI (150 rads per fraction, total dose 1950 to 3000 rads) before bilateral nephrectomy and renal allotransplantation. Eight dogs received bone marrow from the kidney donor. In 13 untreated control dogs renal allografts functioned for a mean +- (SE) of 4.7 +- 0.3 days. In the four TLI treated dogs who did not receive bone marrow the renal allografts functioned for 15 to 76 days (two dogs died with functioning grafts). In the eight TLI treated dogs who received donor bone marrow, two died immediately after transplantation, two rejected at 3 and 13 days, one died at 13 days with a functioning graft, and two have had the grafts function for longer than 500 days. Chimerism was not detected in the one dog tested. The response of peripheral blood lymphocytes to stimulation with phytohemaglutinin and in mixed lymphocyte culture was suppressed for at least one month after TLI. The results confirm the immunosuppressive effect of TLI. The absence of kidney rejection in two recipients of donor bone marrow show the potential of this approach to induce long-term immunologic unresponsiveness as to an organ allograft, but the outcome is unpredictable and further experiments are needed to define the optimal conditions for administration of TLI and bone marrow to the recipients.

  8. Allelic and Epitopic Characterization of Intra-Kidney Allograft Anti-HLA Antibodies at Allograft Nephrectomy.

    PubMed

    Milongo, D; Kamar, N; Del Bello, A; Guilbeau-Frugier, C; Sallusto, F; Esposito, L; Dörr, G; Blancher, A; Congy-Jolivet, N

    2017-02-01

    The reasons for the increased incidence of de novo anti-human leukocyte antibody (HLA) donor-specific antibodies (DSAs) observed after kidney allograft nephrectomy are not fully understood. One advocated mechanism suggests that at graft loss, DSAs are not detected in the serum because they are fixed on the nonfunctional transplant; removal of the kidney allows DSAs to then appear in the blood circulation. The aim of our study was to compare anti-HLA antibodies present in the serum and in the graft at the time of an allograft nephrectomy. Using solid-phase assays, anti-HLA antibodies were searched for in the sera of 17 kidney transplant patients undergoing allograft nephrectomy. No anti-HLA antibodies were detected in the graft if they were not also detected in the serum. Eleven of the 12 patients who had DSAs detected in their sera also had DSAs detected in the grafts. Epitopic analysis revealed that most anti-HLA antibodies detected in removed grafts were directed against the donor. In summary, our data show that all anti-HLA antibodies that were detected in grafts were also detected in the sera. These intragraft anti-HLA antibodies are mostly directed against the donor at an epitopic level but not always at an antigenic level.

  9. Cell-Free DNA and Active Rejection in Kidney Allografts.

    PubMed

    Bloom, Roy D; Bromberg, Jonathan S; Poggio, Emilio D; Bunnapradist, Suphamai; Langone, Anthony J; Sood, Puneet; Matas, Arthur J; Mehta, Shikha; Mannon, Roslyn B; Sharfuddin, Asif; Fischbach, Bernard; Narayanan, Mohanram; Jordan, Stanley C; Cohen, David; Weir, Matthew R; Hiller, David; Prasad, Preethi; Woodward, Robert N; Grskovic, Marica; Sninsky, John J; Yee, James P; Brennan, Daniel C

    2017-03-09

    Histologic analysis of the allograft biopsy specimen is the standard method used to differentiate rejection from other injury in kidney transplants. Donor-derived cell-free DNA (dd-cfDNA) is a noninvasive test of allograft injury that may enable more frequent, quantitative, and safer assessment of allograft rejection and injury status. To investigate this possibility, we prospectively collected blood specimens at scheduled intervals and at the time of clinically indicated biopsies. In 102 kidney recipients, we measured plasma levels of dd-cfDNA and correlated the levels with allograft rejection status ascertained by histology in 107 biopsy specimens. The dd-cfDNA level discriminated between biopsy specimens showing any rejection (T cell-mediated rejection or antibody-mediated rejection [ABMR]) and controls (no rejection histologically), P<0.001 (receiver operating characteristic area under the curve [AUC], 0.74; 95% confidence interval [95% CI], 0.61 to 0.86). Positive and negative predictive values for active rejection at a cutoff of 1.0% dd-cfDNA were 61% and 84%, respectively. The AUC for discriminating ABMR from samples without ABMR was 0.87 (95% CI, 0.75 to 0.97). Positive and negative predictive values for ABMR at a cutoff of 1.0% dd-cfDNA were 44% and 96%, respectively. Median dd-cfDNA was 2.9% (ABMR), 1.2% (T cell-mediated types ≥IB), 0.2% (T cell-mediated type IA), and 0.3% in controls (P=0.05 for T cell-mediated rejection types ≥IB versus controls). Thus, dd-cfDNA may be used to assess allograft rejection and injury; dd-cfDNA levels <1% reflect the absence of active rejection (T cell-mediated type ≥IB or ABMR) and levels >1% indicate a probability of active rejection.

  10. Urine Metabolite Profiles Predictive of Human Kidney Allograft Status.

    PubMed

    Suhre, Karsten; Schwartz, Joseph E; Sharma, Vijay K; Chen, Qiuying; Lee, John R; Muthukumar, Thangamani; Dadhania, Darshana M; Ding, Ruchuang; Ikle, David N; Bridges, Nancy D; Williams, Nikki M; Kastenmüller, Gabi; Karoly, Edward D; Mohney, Robert P; Abecassis, Michael; Friedewald, John; Knechtle, Stuart J; Becker, Yolanda T; Samstein, Benjamin; Shaked, Abraham; Gross, Steven S; Suthanthiran, Manikkam

    2016-02-01

    Noninvasive diagnosis and prognostication of acute cellular rejection in the kidney allograft may help realize the full benefits of kidney transplantation. To investigate whether urine metabolites predict kidney allograft status, we determined levels of 749 metabolites in 1516 urine samples from 241 kidney graft recipients enrolled in the prospective multicenter Clinical Trials in Organ Transplantation-04 study. A metabolite signature of the ratio of 3-sialyllactose to xanthosine in biopsy specimen-matched urine supernatants best discriminated acute cellular rejection biopsy specimens from specimens without rejection. For clinical application, we developed a high-throughput mass spectrometry-based assay that enabled absolute and rapid quantification of the 3-sialyllactose-to-xanthosine ratio in urine samples. A composite signature of ratios of 3-sialyllactose to xanthosine and quinolinate to X-16397 and our previously reported urinary cell mRNA signature of 18S ribosomal RNA, CD3ε mRNA, and interferon-inducible protein-10 mRNA outperformed the metabolite signatures and the mRNA signature. The area under the receiver operating characteristics curve for the composite metabolite-mRNA signature was 0.93, and the signature was diagnostic of acute cellular rejection with a specificity of 84% and a sensitivity of 90%. The composite signature, developed using solely biopsy specimen-matched urine samples, predicted future acute cellular rejection when applied to pristine samples taken days to weeks before biopsy. We conclude that metabolite profiling of urine offers a noninvasive means of diagnosing and prognosticating acute cellular rejection in the human kidney allograft, and that the combined metabolite and mRNA signature is diagnostic and prognostic of acute cellular rejection with very high accuracy.

  11. A Lifetime of Allograft Function with Kidneys from Older Donors.

    PubMed

    Rose, Caren; Schaeffner, Elke; Frei, Ulrich; Gill, Jagbir; Gill, John S

    2015-10-01

    Strategies to increase expanded criteria donor (ECD) transplantation are needed. We quantified the extent to which ECD kidneys provide recipients with a lifetime of allograft function by determining the difference between patient survival and death-censored allograft survival (graft survival). Initial analyses compared 5-year outcomes in the Eurotransplant Senior Program (European) and the United States Renal Data System. Among European recipients ≥65 years, patient survival exceeded graft survival, and ECD recipients returned to dialysis for an average of 5.2 months after transplant failure. Among United States recipients ≥60 years, graft survival exceeded patient survival. Although patient survival in elderly recipients in the United States was low (49% at 5 years), the average difference in patient survival at 10 years in elderly recipients in the United States with an ECD versus non-ECD transplant was only 7 months. The probability of patient survival with a functioning allograft at 5 years was higher with ECD transplantation within 1 year after activation to the waiting list than with delayed non-ECD transplantation ≥3 years after activation to the waiting list. Subsequent analyses demonstrated that ECD transplants do not provide a lifetime of allograft function in recipients <50 years in the United States. These findings should encourage ECD transplantation in patients ≥60 years, demonstrate that rapid ECD transplantation is superior to delayed non-ECD transplantation, and challenge the policy in the United States of allowing patients <50 years to receive an ECD transplant.

  12. Urinary proteomic analysis of chronic allograft nephropathy

    PubMed Central

    O’Riordan, Edmond; Orlova, Tatyana N.; Mendelev, Natalia; Patschan, Daniel; Kemp, Rowena; Chander, Praveen N.; Hu, Rena; Hao, Gang; Gross, Steven S.; Iozzo, Renato V.; Delaney, Veronica; Goligorsky, Michael S.

    2015-01-01

    The pathogenesis of progressive renal allograft injury, which is termed chronic allograft nephropathy (CAN), remains obscure and is currently defined by histology. Prospective protocolbiopsy trials have demonstrated that clinical and standard laboratory tests are insufficiently sensitive indicators of the development and progression of CAN. The study aim was to determine if CAN could be characterized by urinary proteomic data and identify the proteins associated with disease. The urinary proteome of 75 renal transplant recipients and 20 healthy volunteers was analyzed using surface enhanced laser desorption and ionization MS. Patients could be classified into subgroups with normal histology and Banff CAN grades 2-3 with a sensitivity of 86% and a specificity of 92% by applying the classification algorithm Adaboost to urinary proteomic data. Several urinary proteins associated with advanced CAN were identified including α1-micro-globulin, β2-micro-globulin, prealbumin, and endorepellin, the antiangiogenic C-terminal fragment of perlecan. Increased urinary endorepellin was confirmed by ELISA and increased tissue expression of the endorepellin/perlecan ratio by immunofluoresence analysis of renal biopsies. In conclusion, analysis of urinary proteomic data has further characterized the more severe CAN grades and identified urinary endorepellin, as a potential biomarker of advanced CAN. PMID:21136903

  13. Quantitative podocyte parameters predict human native kidney and allograft half-lives

    PubMed Central

    Naik, Abhijit S.; Afshinnia, Farsad; Cibrik, Diane; Hodgin, Jeffrey B.; Zhang, Min; Kikuchi, Masao; Wickman, Larysa; Samaniego, Milagros; Bitzer, Markus; Wiggins, Jocelyn E.; Ojo, Akinlolu; Li, Yi; Wiggins, Roger C.

    2016-01-01

    BACKGROUND. Kidney function decreases with age. A potential mechanistic explanation for kidney and allograft half-life has evolved through the realization that linear reduction in glomerular podocyte density could drive progressive glomerulosclerosis to impact both native kidney and allograft half-lives. METHODS. Predictions from podometrics (quantitation of podocyte parameters) were tested using independent pathologic, functional, and outcome data for native kidneys and allografts derived from published reports and large registries. RESULTS. With age, native kidneys exponentially develop glomerulosclerosis, reduced renal function, and end-stage kidney disease, projecting a finite average kidney life span. The slope of allograft failure rate versus age parallels that of reduction in podocyte density versus age. Quantitative modeling projects allograft half-life at any donor age, and rate of podocyte detachment parallels the observed allograft loss rate. CONCLUSION. Native kidneys are designed to have a limited average life span of about 100–140 years. Allografts undergo an accelerated aging-like process that accounts for their unexpectedly short half-life (about 15 years), the observation that older donor age is associated with shorter allograft half-life, and the fact that long-term allograft survival has not substantially improved. Podometrics provides potential readouts for these processes, thereby offering new approaches for monitoring and intervention. FUNDING: National Institutes of Health. PMID:27280173

  14. Commercial kidney transplantation is an important risk factor in long-term kidney allograft survival.

    PubMed

    Prasad, G V Ramesh; Ananth, Sailesh; Palepu, Sneha; Huang, Michael; Nash, Michelle M; Zaltzman, Jeffrey S

    2016-05-01

    Transplant tourism, a form of transplant commercialization, has resulted in serious short-term adverse outcomes that explain reduced short-term kidney allograft survival. However, the nature of longer-term outcomes in commercial kidney transplant recipients is less clear. To study this further, we identified 69 Canadian commercial transplant recipients of 72 kidney allografts transplanted during 1998 to 2013 who reported to our transplant center for follow-up care. Their outcomes to 8 years post-transplant were compared with 702 domestic living donor and 827 deceased donor transplant recipients during this period using Kaplan-Meier survival plots and multivariate Cox regression analysis. Among many complications, notable specific events included hepatitis B or C seroconversion (7 patients), active hepatitis and/or fulminant hepatic failure (4 patients), pulmonary tuberculosis (2 patients), and a type A dissecting aortic aneurysm. Commercial transplantation was independently associated with significantly reduced death-censored kidney allograft survival (hazard ratio 3.69, 95% confidence interval 1.88-7.25) along with significantly delayed graft function and eGFR 30 ml/min/1.73 m(2) or less at 3 months post-transplant. Thus, commercial transplantation represents an important risk factor for long-term kidney allograft loss. Concerted arguments and efforts using adverse recipient outcomes among the main premises are still required in order to eradicate transplant commercialization.

  15. Anemia in Chronic Kidney Disease

    MedlinePlus

    ... Heart Disease Mineral & Bone Disorder Anemia in Chronic Kidney Disease What is anemia? Anemia is a condition ... they should. How is anemia related to chronic kidney disease? Anemia commonly occurs in people with chronic ...

  16. High-Throughput Proteomic Approaches to the Elucidation of Potential Biomarkers of Chronic Allograft Injury (CAI)

    PubMed Central

    Cassidy, Hilary; Slyne, Jennifer; Frain, Helena; Slattery, Craig; Ryan, Michael P.; McMorrow, Tara

    2013-01-01

    This review focuses on the role of OMICs technologies, concentrating in particular on proteomics, in biomarker discovery in chronic allograft injury (CAI). CAI is the second most prevalent cause of allograft dysfunction and loss in the first decade post-transplantation, after death with functioning graft (DWFG). The term CAI, sometimes referred to as chronic allograft nephropathy (CAN), describes the deterioration of renal allograft function and structure as a result of immunological processes (chronic antibody-mediated rejection), and other non-immunological factors such as calcineurin inhibitor (CNI) induced nephrotoxicity, hypertension and infection. Current methods for assessing allograft function are costly, insensitive and invasive; traditional kidney function measurements such as serum creatinine and glomerular filtration rate (GFR) display poor predictive abilities, while the current “gold-standard” involving histological diagnosis with a renal biopsy presents its own inherent risks to the overall health of the allograft. As early as two years post-transplantation, protocol biopsies have shown more than 50% of allograft recipients have mild CAN; ten years post-transplantation more than 50% of the allograft recipients have progressed to severe CAN which is associated with diminishing graft function. Thus, there is a growing medical requirement for minimally invasive biomarkers capable of identifying the early stages of the disease which would allow for timely intervention. Proteomics involves the study of the expression, localization, function and interaction of the proteome. Proteomic technologies may be powerful tools used to identify novel biomarkers which would predict CAI in susceptible individuals. In this paper we will review the use of proteomics in the elucidation of novel predictive biomarkers of CAI in clinical, animal and in vitro studies. PMID:28250402

  17. Kidney retransplantation for BK virus nephropathy with active viremia without allograft nephrectomy.

    PubMed

    Huang, Jingbo; Danovitch, Gabriel; Pham, Phuong-Thu; Bunnapradist, Suphamai; Huang, Edmund

    2015-12-01

    BK virus nephropathy is an important cause of kidney allograft failure. Retransplantation has been successfully performed for patients with previous allograft loss due to BK virus nephropathy; however, whether allograft nephrectomy and viral clearance are required prior to retransplantation is controversial. Some recent studies have suggested that retransplantion can be successfully achieved without allograft nephrectomy if viremia is cleared prior to retransplant. The only published experience of successful retransplantation in the presence of active viremia occurred in the presence of concomitant allograft nephrectomy of the failing kidney. In this report, we describe a case of successful repeat kidney transplant in a patient with high-grade BK viremia and fulminant hepatic failure without concomitant allograft nephrectomy performed under the setting of a simultaneous liver-kidney transplant.

  18. Chronic Kidney Disease

    MedlinePlus

    ... factors. It is important to diagnose CKD early. Diagnosis & TestsHow can my doctor tell if I have CKD?There are three simple tests that your doctor might do if he or she suspects you might have chronic kidney disease:Blood pressure testUrine albumin (a test to see ...

  19. Immunohistological observations in rat kidney allografts after local steroid administration

    PubMed Central

    1987-01-01

    In this report we investigated local regulatory mechanisms in graft rejection and their response to local immunosuppressive therapy. For this purpose local immunosuppression was induced in rat kidney allografts by intrarenal infusion of prednisolone. Intrarenal drug delivery resulted in high drug levels within the graft and low systemic drug levels. Systemic drug levels were by themselves not sufficiently immunosuppressive to induce graft survival, and local prednisolone levels within the graft proved to be responsible for prolongation of graft survival. During intrarenal drug delivery, systemic responsiveness to the renal allograft proved normal, since intrarenally treated grafts were infiltrated by MHC class II-positive host cells and, except for a somewhat lower percentage of macrophages, cellular infiltration in intrarenal treated grafts was comparable to untreated grafts. However, T cells and macrophages present in intrarenally treated grafts were not able to destroy the grafted tissue. Local immunosuppressive therapy resulted in inhibition of IL-2-R expression, absence of IFN-gamma, and prevention of MHC class II induction on grafted tissue. These observations strongly indicate the presence of local regulatory mechanisms in graft rejection. The experimental model described can be used for further analysis of these intragraft events. Moreover, the results demonstrate that local immunosuppressive therapy can contribute to effective inhibition of cellular immune response in graft rejection. PMID:3119756

  20. Renal cell carcinoma in kidney allografts: histologic types, including biphasic papillary carcinoma.

    PubMed

    Troxell, Megan L; Higgins, John P

    2016-11-01

    Kidney transplant recipients are at increased risk for malignancy, with about 5% incidence of cancer in native end-stage kidneys. Carcinoma in the renal allograft is far less common. Prior studies have demonstrated a propensity for renal cell carcinomas (RCCs) of papillary subtypes in end-stage kidneys, and perhaps in allograft kidneys, but most allograft studies lack detailed pathologic review and predate the current classification system. We reviewed our experience with renal carcinoma in kidney allografts at 2 academic centers applying the International Society of Urological Pathology classification, informed by immunohistochemistry. The incidence of renal allograft carcinoma was about 0.26% in our population. Of 12 allograft carcinomas, 6 were papillary (50%), 4 were clear cell (33%), 1 was clear cell (tubulo)papillary, and 1 chromophobe. Two of the papillary carcinomas had distinctive biphasic glomeruloid architecture matching the newly named "biphasic squamoid alveolar" pattern and were difficult to classify on core biopsies. The 2 cell types had different immunophenotypes in our hands (eosinophilic cells: RCC-/CK34betaE12+ weight keratin +/cyclin D1+; clear cells: RCC+/cytokeratin high molecular weight negative to weak/cyclin D1-). None of the patients experienced cancer recurrences or metastasis. Our study confirms the predilection for papillary RCCs in kidney allografts and highlights the occurrence of rare morphologic variants. Larger studies are needed with careful pathologic review, which has been lacking in the literature.

  1. Chronic Kidney Disease.

    PubMed

    Webster, Angela C; Nagler, Evi V; Morton, Rachael L; Masson, Philip

    2017-03-25

    The definition and classification of chronic kidney disease (CKD) have evolved over time, but current international guidelines define this condition as decreased kidney function shown by glomerular filtration rate (GFR) of less than 60 mL/min per 1·73 m(2), or markers of kidney damage, or both, of at least 3 months duration, regardless of the underlying cause. Diabetes and hypertension are the main causes of CKD in all high-income and middle-income countries, and also in many low-income countries. Incidence, prevalence, and progression of CKD also vary within countries by ethnicity and social determinants of health, possibly through epigenetic influence. Many people are asymptomatic or have non-specific symptoms such as lethargy, itch, or loss of appetite. Diagnosis is commonly made after chance findings from screening tests (urinary dipstick or blood tests), or when symptoms become severe. The best available indicator of overall kidney function is GFR, which is measured either via exogenous markers (eg, DTPA, iohexol), or estimated using equations. Presence of proteinuria is associated with increased risk of progression of CKD and death. Kidney biopsy samples can show definitive evidence of CKD, through common changes such as glomerular sclerosis, tubular atrophy, and interstitial fibrosis. Complications include anaemia due to reduced production of erythropoietin by the kidney; reduced red blood cell survival and iron deficiency; and mineral bone disease caused by disturbed vitamin D, calcium, and phosphate metabolism. People with CKD are five to ten times more likely to die prematurely than they are to progress to end stage kidney disease. This increased risk of death rises exponentially as kidney function worsens and is largely attributable to death from cardiovascular disease, although cancer incidence and mortality are also increased. Health-related quality of life is substantially lower for people with CKD than for the general population, and falls as GFR

  2. Methenamine silver staining quantitative digital histochemistry in chronic allograft nephropathy.

    PubMed

    Sarioglu, S; Celik, A; Sakar, M; Sonmez, D; Tekis, D

    2004-12-01

    Renal function and final outcome of renal allografts have been correlated with irreversible damage. This study describes a quantitative histochemical method relying on periodic acid methenamine silver (PAMS) staining of all renal compartments. Among 60 renal allograft biopsies from 43 patients, 15 biopsies showing pure chronic allograft nephropathy were selected to determine PAMS-stained area percentage (SAP), using image analysis with quantitative histochemistry. Of the 15 cases, 9 (60%) were grade I and 6 (40%) were grade II chronic allograft nephropathy (CAN). The mean serum creatinine (sCr) value was 1.86 +/- 0.47 for allograft biopsies. The mean (+/-SD) SAP for the implantation biopsies was 10.58 +/- 1.87%, and for allograft biopsies 25.26 +/- 9.67 (P <.000). The serum creatinine (sCr) values for grade I versus II CAN were 1.63 +/- 0.24 versus 2.20 +/- 0.54 mg/dL, respectively (P=.019), and SAP values were 18.97 +/- 0.24 versus 34.7 +/- 5.89 (P=.003). There was a strong positive correlation between sCr values and SAP (P=.005; r=0.64). These findings show the PAMS approach to be a useful alternative method for reflecting damage in more than one compartment of the renal tissue. Also, the method can discriminated implantation and allograft biopsies as well as grade I and II CAN cases. The series is small for a multivariate analysis of the value of SAP measurements in PAMS-stained sections as a prognosticator, but the data support its use.

  3. Chronic Kidney Disease (CKD)

    MedlinePlus

    ... upcoming screening events. Kidney Action Day Kidney Action Day Learn about our signature outreach event. About AKF ... support of AKF. Kidney Action Day Kidney Action Day Learn about our signature outreach event. Free health ...

  4. Acute Page kidney following renal allograft biopsy: a complication requiring early recognition and treatment.

    PubMed

    Chung, J; Caumartin, Y; Warren, J; Luke, P P W

    2008-06-01

    The acute Page kidney phenomenon occurs as a consequence of external compression of the renal parenchyma leading to renal ischemia and hypertension. Between January 2000 and September 2007, 550 kidney transplants and 518 ultrasound-guided kidney biopsies were performed. During that time, four recipients developed acute oligo-anuria following ultrasound-guided allograft biopsy. Emergent doppler-ultrasounds were performed demonstrating absence of diastolic flow as well as a sub-capsular hematoma of the kidney. Prompt surgical exploration with allograft capsulotomy was performed in all cases. Immediately after capsulotomy, intraoperative Doppler study demonstrated robust return of diastolic flow. Three patients maintained good graft function, and one kidney was lost due to acute antibody-mediated rejection. We conclude that postbiopsy anuria associated with a subcapsular hematoma and acute absence of diastolic flow on doppler ultrasound should be considered pathognomonic of APK. All renal transplant specialists should be able to recognize this complication, because immediate surgical decompression can salvage the allograft.

  5. Lung transplantation: chronic allograft dysfunction and establishing immune tolerance.

    PubMed

    Gracon, Adam S A; Wilkes, David S

    2014-08-01

    Despite significant medical advances since the advent of lung transplantation, improvements in long-term survival have been largely unrealized. Chronic lung allograft dysfunction, in particular obliterative bronchiolitis, is the primary limiting factor. The predominant etiology of obliterative bronchiolitis involves the recipient's innate and adaptive immune response to the transplanted allograft. Current therapeutic strategies have failed to provide a definitive treatment paradigm to improve long-term outcomes. Inducing immune tolerance is an emerging therapeutic strategy that abrogates allograft rejection, avoids immunosuppression, and improves long-term graft function. The aim of this review is to discuss the key immunologic components of obliterative bronchiolitis, describe the state of establishing immune tolerance in transplantation, and highlight those strategies being evaluated in lung transplantation.

  6. T-cell alloimmunity and chronic allograft dysfunction.

    PubMed

    Safinia, Niloufar; Afzali, Behdad; Atalar, Kerem; Lombardi, Giovanna; Lechler, Robert I

    2010-12-01

    Solid organ transplantation is the standard treatment to improve both the quality of life and survival in patients with various end-stage organ diseases. The primary barrier against successful transplantation is recipient alloimmunity and the need to be maintained on immunosuppressive therapies with associated side effects. Despite such treatments in renal transplantation, after death with a functioning graft, chronic allograft dysfunction (CAD) is the most common cause of late allograft loss. Recipient recognition of donor histocompatibility antigens, via direct, indirect, and semidirect pathways, is critically dependent on the antigen-presenting cell (APC) and elicits effector responses dominated by recipient T cells. In allograft rejection, the engagement of recipient and donor cells results in recruitment of T-helper (Th) cells of the Th1 and Th17 lineage to the graft. In cases in which the alloresponse is dominated by regulatory T cells (Tregs), rejection can be prevented and the allograft tolerated with minimum or no immunosuppression. Here, we review the pathways of allorecognition that underlie CAD and the T-cell effector phenotypes elicited as part of the alloresponse. Future therapies including depletion of donor-reactive lymphocytes, costimulation blockade, negative vaccination using dendritic cell subtypes, and Treg therapy are inferred from an understanding of these mechanisms of allograft rejection.

  7. Chronic Kidney Disease in Kidney Stone Formers

    PubMed Central

    Krambeck, Amy E.; Lieske, John C.

    2011-01-01

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

  8. Genomic Analysis of Kidney Allograft Injury Identifies Hematopoietic Cell Kinase as a Key Driver of Renal Fibrosis.

    PubMed

    Wei, Chengguo; Li, Li; Menon, Madhav C; Zhang, Weijia; Fu, Jia; Kidd, Brian; Keung, Karen L; Woytovich, Christopher; Greene, Ilana; Xiao, Wenzhen; Salem, Fadi; Yi, Zhengzi; He, John Cijiang; Dudley, Joel T; Murphy, Barbara

    2016-12-07

    Renal fibrosis is the common pathway of progression for patients with CKD and chronic renal allograft injury (CAI), but the underlying mechanisms remain obscure. We performed a meta-analysis in human kidney biopsy specimens with CAI, incorporating data available publicly and from our Genomics of Chronic Renal Allograft Rejection study. We identified an Src family tyrosine kinase, hematopoietic cell kinase (Hck), as upregulated in allografts in CAI. Querying the Kinase Inhibitor Resource database revealed that dasatinib, a Food and Drug Administration-approved drug, potently binds Hck with high selectivity. In vitro, Hck overexpression activated the TGF-β/Smad3 pathway, whereas HCK knockdown inhibited it. Treatment of tubular cells with dasatinib reduced the expression of Col1a1 Dasatinib also reduced proliferation and α-SMA expression in fibroblasts. In a murine model with unilateral ureteric obstruction, pretreatment with dasatinib significantly reduced the upregulation of profibrotic markers, phosphorylation of Smad3, and renal fibrosis observed in kidneys pretreated with vehicle alone. Dasatinib treatment also improved renal function, reduced albuminuria, and inhibited expression of profibrotic markers in animal models with lupus nephritis and folic acid nephropathy. These data suggest that Hck is a key mediator of renal fibrosis and dasatinib could be developed as an antifibrotic drug.

  9. Molecular microscope strategy to improve risk stratification in early antibody-mediated kidney allograft rejection.

    PubMed

    Loupy, Alexandre; Lefaucheur, Carmen; Vernerey, Dewi; Chang, Jessica; Hidalgo, Luis G; Beuscart, Thibaut; Verine, Jerome; Aubert, Olivier; Dubleumortier, Sébastien; Duong van Huyen, Jean-Paul; Jouven, Xavier; Glotz, Denis; Legendre, Christophe; Halloran, Philip F

    2014-10-01

    Antibody-mediated rejection (ABMR) is the leading cause of kidney allograft loss. We investigated whether the addition of gene expression measurements to conventional methods could serve as a molecular microscope to identify kidneys with ABMR that are at high risk for failure. We studied 939 consecutive kidney recipients at Necker Hospital (2004-2010; principal cohort) and 321 kidney recipients at Saint Louis Hospital (2006-2010; validation cohort) and assessed patients with ABMR in the first 1 year post-transplant. In addition to conventional features, we assessed microarray-based gene expression in transplant biopsy specimens using relevant molecular measurements: the ABMR Molecular Score and endothelial donor-specific antibody-selective transcript set. The main outcomes were kidney transplant loss and progression to chronic transplant injury. We identified 74 patients with ABMR in the principal cohort and 54 patients with ABMR in the validation cohort. Conventional features independently associated with failure were donor age and humoral histologic score (g+ptc+v+cg+C4d). Adjusting for conventional features, ABMR Molecular Score (hazard ratio [HR], 2.22; 95% confidence interval [95% CI], 1.37 to 3.58; P=0.001) and endothelial donor-specific antibody-selective transcripts (HR, 3.02; 95% CI, 1.00 to 9.16; P<0.05) independently associated with an increased risk of graft loss. The results were replicated in the independent validation group. Adding a gene expression assessment to a traditional risk model improved the stratification of patients at risk for graft failure (continuous net reclassification improvement, 1.01; 95% CI, 0.57 to 1.46; P<0.001; integrated discrimination improvement, 0.16; P<0.001). Compared with conventional assessment, the addition of gene expression measurement in kidney transplants with ABMR improves stratification of patients at high risk for graft loss.

  10. Phosphocalcic Markers and Calcification Propensity for Assessment of Interstitial Fibrosis and Vascular Lesions in Kidney Allograft Recipients.

    PubMed

    Berchtold, Lena; Ponte, Belen; Moll, Solange; Hadaya, Karine; Seyde, Olivia; Bachtler, Matthias; Vallée, Jean-Paul; Martin, Pierre-Yves; Pasch, Andreas; de Seigneux, Sophie

    2016-01-01

    Renal interstitial fibrosis and arterial lesions predict loss of function in chronic kidney disease. Noninvasive estimation of interstitial fibrosis and vascular lesions is currently not available. The aim of the study was to determine whether phosphocalcic markers are associated with, and can predict, renal chronic histological changes. We included 129 kidney allograft recipients with an available transplant biopsy in a retrospective study. We analyzed the associations and predictive values of phosphocalcic markers and serum calcification propensity (T50) for chronic histological changes (interstitial fibrosis and vascular lesions). PTH, T50 and vitamin D levels were independently associated to interstitial fibrosis. PTH elevation was associated with increasing interstitial fibrosis severity (r = 0.29, p = 0.001), while T50 and vitamin D were protective (r = -0.20, p = 0.025 and r = -0.23, p = 0.009 respectively). On the contrary, fibroblast growth factor 23 (FGF23) and Klotho correlated only modestly with interstitial fibrosis (p = 0.045) whereas calcium and phosphate did not. PTH, vitamin D and T50 were predictors of extensive fibrosis (AUC: 0.73, 0.72 and 0.68 respectively), but did not add to renal function prediction. PTH, FGF23 and T50 were modestly predictive of low fibrosis (AUC: 0.63, 0.63 and 0.61) but did not add to renal function prediction. T50 decreased with increasing arterial lesions (r = -0.21, p = 0.038). The discriminative performance of T50 in predicting significant vascular lesions was modest (AUC 0.61). In summary, we demonstrated that PTH, vitamin D and T50 are associated to interstitial fibrosis and vascular lesions in kidney allograft recipients independently of renal function. Despite these associations, mineral metabolism indices do not show superiority or additive value to fibrosis prediction by eGFR and proteinuria in kidney allograft recipients, except for vascular lesions where T50 could be of relevance.

  11. Phosphocalcic Markers and Calcification Propensity for Assessment of Interstitial Fibrosis and Vascular Lesions in Kidney Allograft Recipients

    PubMed Central

    Berchtold, Lena; Ponte, Belen; Moll, Solange; Hadaya, Karine; Seyde, Olivia; Bachtler, Matthias; Vallée, Jean-Paul; Martin, Pierre-Yves; Pasch, Andreas; de Seigneux, Sophie

    2016-01-01

    Renal interstitial fibrosis and arterial lesions predict loss of function in chronic kidney disease. Noninvasive estimation of interstitial fibrosis and vascular lesions is currently not available. The aim of the study was to determine whether phosphocalcic markers are associated with, and can predict, renal chronic histological changes. We included 129 kidney allograft recipients with an available transplant biopsy in a retrospective study. We analyzed the associations and predictive values of phosphocalcic markers and serum calcification propensity (T50) for chronic histological changes (interstitial fibrosis and vascular lesions). PTH, T50 and vitamin D levels were independently associated to interstitial fibrosis. PTH elevation was associated with increasing interstitial fibrosis severity (r = 0.29, p = 0.001), while T50 and vitamin D were protective (r = -0.20, p = 0.025 and r = -0.23, p = 0.009 respectively). On the contrary, fibroblast growth factor 23 (FGF23) and Klotho correlated only modestly with interstitial fibrosis (p = 0.045) whereas calcium and phosphate did not. PTH, vitamin D and T50 were predictors of extensive fibrosis (AUC: 0.73, 0.72 and 0.68 respectively), but did not add to renal function prediction. PTH, FGF23 and T50 were modestly predictive of low fibrosis (AUC: 0.63, 0.63 and 0.61) but did not add to renal function prediction. T50 decreased with increasing arterial lesions (r = -0.21, p = 0.038). The discriminative performance of T50 in predicting significant vascular lesions was modest (AUC 0.61). In summary, we demonstrated that PTH, vitamin D and T50 are associated to interstitial fibrosis and vascular lesions in kidney allograft recipients independently of renal function. Despite these associations, mineral metabolism indices do not show superiority or additive value to fibrosis prediction by eGFR and proteinuria in kidney allograft recipients, except for vascular lesions where T50 could be of relevance. PMID:28036331

  12. Altered Expression of MicroRNAs Following Chronic Allograft Dysfunction with Interstitial Fibrosis and Tubular Atrophy.

    PubMed

    Soltaninejad, Ehsan; Nicknam, Mohammad Hossein; Nafar, Mohsen; Sharbafi, Mohammad Hossein; Keshavarz Shahbaz, Sanaz; Barabadi, Mehri; Yekaninejad, Mir Saeed; Bahrami, Tayyeb; Ahmadpoor, Pedram; Amirzargar, Aliakbar

    2015-12-01

    Chronic allograft dysfunction (CAD) remains the major cause of renal transplant loss and characterized by interstitial fibrosis and tubular atrophy (IFTA). MicroRNAs (miRNAs) are implicated in many biological processes as well as innate and adaptive immune responses. We aimed to investigate whether CAD with IFTA is associated with differential expression of miR-142-5p, miR-142-3p and miR-211 within biopsy and peripheral blood mononuclear cell (PBMC) samples and whether expression of miRNAs are diagnostic for CAD with IFTA and predicts renal allograft function. In this study, biopsy and PBMC samples of 16 CAD with IFTA and 17 normal allografts (NA) were collected. Using Taqman MicroRNA Assays the expression levels of miR-142-5p, miR-142-3p and miR-211 were determined in two groups. Our results showed that miR-142-5p and miR-142-3p were significantly (p<0.0001) up-regulated and miR-211 was significantly (p<0.0001) down-regulated in renal allograft tissues of CAD with IFTA compared with NA recipients. Moreover, miR-142-3p and miR-211 were significantly (p<0.0001) up-regulated and down-regulated respectively in PBMC samples of CAD with IFTA. According to the ROC curve analysis, miR-142-5p in biopsy samples, but miR-142-3p and miR-211 both in biopsy and PBMC samples could be used as a diagnostic biomarker of CAD with IFTA and a prediction factor of allograft function. In this study, miRNAs were differentially expressed in the kidney allograft biopsy and simultaneously in PBMC samples of patients with CAD with IFTA. We suggest that the expression of miRNAs in PBMC might be used for monitoring the post transplantation and also as potential non-invasive biomarkers of kidney graft function and CAD with IFTA.

  13. Early treatment with xenon protects against the cold ischemia associated with chronic allograft nephropathy in rats.

    PubMed

    Zhao, Hailin; Luo, Xianghong; Zhou, Zhaowei; Liu, Juying; Tralau-Stewart, Catherine; George, Andrew J T; Ma, Daqing

    2014-01-01

    Chronic allograft nephropathy (CAN) is a common finding in kidney grafts with functional impairment. Prolonged hypothermic storage-induced ischemia-reperfusion injury is associated with the early onset of CAN. As the noble gas xenon is clinically used as an anesthetic and has renoprotective properties in a rodent model of ischemia-reperfusion injury, we studied whether early treatment with xenon could attenuate CAN associated with prolonged hypothermic storage. Exposure to xenon enhanced the expression of insulin growth factor-1 (IGF-1) and its receptor in human proximal tubular (HK-2) cells, which, in turn, increased cell proliferation. Xenon treatment before or after hypothermia-hypoxia decreased cell apoptosis and cell inflammation after reoxygenation. The xenon-induced HK-2 cell proliferation was abolished by blocking the IGF-1 receptor, mTOR, and HIF-1α individually. In the Fischer-to-Lewis rat allogeneic renal transplantation model, xenon exposure of donors before graft retrieval or recipients after engraftment enhanced tubular cell proliferation and decreased tubular cell death and cell inflammation associated with ischemia-reperfusion injury. Compared with control allografts, xenon treatment significantly suppressed T-cell infiltration and fibrosis, prevented the development of CAN, and improved renal function. Thus, xenon treatment promoted recovery from ischemia-reperfusion injury and reduced susceptibility to the subsequent development of CAN in allografts.

  14. Chronic Achilles Tendon Rupture Treated with Allograft: A Case Report.

    PubMed

    Restuccia, Giuseppe; Lippi, Alessandro; Casella, Francesco; Citarelli, Carmine; Sacchetti, Federico; Benifei, Maurizio

    2017-02-07

    In clinical practice, chronic Achilles tendon ruptures are uncommon. Usually, these lesions are discovered four to six weeks after injuries. More frequently, Achilles tendon ruptures are acute and treated with tendon sutures.1 Many surgical techniques are available to treat chronic lesions such as sutures or V-Y elongation with or without augments.2-3 Our case is about a chronic Achilles tendon rupture discovered two years after injury. Our patient came to our attention with a 6 cm tendon gap. We performed tendon repair with cadaver allograft. After four years of follow-up, our patient has a complete functional recovery and he can normally perform daily and working tasks without pain.

  15. Nitration and Inactivation of Manganese Superoxide Dismutase in Chronic Rejection of Human Renal Allografts

    NASA Astrophysics Data System (ADS)

    MacMillan-Crow, L. A.; Crow, John P.; Kerby, Jeffrey D.; Beckman, Joseph S.; Thompson, John A.

    1996-10-01

    Inflammatory processes in chronic rejection remain a serious clinical problem in organ transplantation. Activated cellular infiltrate produces high levels of both superoxide and nitric oxide. These reactive oxygen species interact to form peroxynitrite, a potent oxidant that can modify proteins to form 3-nitrotyrosine. We identified enhanced immunostaining for nitrotyrosine localized to tubular epithelium of chronically rejected human renal allografts. Western blot analysis of rejected tissue demonstrated that tyrosine nitration was restricted to a few specific polypeptides. Immunoprecipitation and amino acid sequencing techniques identified manganese superoxide dismutase, the major antioxidant enzyme in mitochondria, as one of the targets of tyrosine nitration. Total manganese superoxide dismutase protein was increased in rejected kidney, particularly in the tubular epithelium; however, enzymatic activity was significantly decreased. Exposure of recombinant human manganese superoxide dismutase to peroxynitrite resulted in a dose-dependent (IC50 = 10 μ M) decrease in enzymatic activity and concomitant increase in tyrosine nitration. Collectively, these observations suggest a role for peroxynitrite during development and progression of chronic rejection in human renal allografts. In addition, inactivation of manganese superoxide dismutase by peroxynitrite may represent a general mechanism that progressively increases the production of peroxynitrite, leading to irreversible oxidative injury to mitochondria.

  16. Macrophage-to-Myofibroblast Transition Contributes to Interstitial Fibrosis in Chronic Renal Allograft Injury.

    PubMed

    Wang, Ying-Ying; Jiang, Hong; Pan, Jun; Huang, Xiao-Ru; Wang, Yu-Cheng; Huang, Hong-Feng; To, Ka-Fai; Nikolic-Paterson, David J; Lan, Hui-Yao; Chen, Jiang-Hua

    2017-02-16

    Interstitial fibrosis is an important contributor to graft loss in chronic renal allograft injury. Inflammatory macrophages are associated with fibrosis in renal allografts, but how these cells contribute to this damaging response is not clearly understood. Here, we investigated the role of macrophage-to-myofibroblast transition in interstitial fibrosis in human and experimental chronic renal allograft injury. In biopsy specimens from patients with active chronic allograft rejection, we identified cells undergoing macrophage-to-myofibroblast transition by the coexpression of macrophage (CD68) and myofibroblast (α-smooth muscle actin [α-SMA]) markers. CD68(+)/α-SMA(+) cells accounted for approximately 50% of the myofibroblast population, and the number of these cells correlated with allograft function and the severity of interstitial fibrosis. Similarly, in C57BL/6J mice with a BALB/c renal allograft, cells coexpressing macrophage markers (CD68 or F4/80) and α-SMA composed a significant population in the interstitium of allografts undergoing chronic rejection. Fate-mapping in Lyz2-Cre/Rosa26-Tomato mice showed that approximately half of α-SMA(+) myofibroblasts in renal allografts originated from recipient bone marrow-derived macrophages. Knockout of Smad3 protected against interstitial fibrosis in renal allografts and substantially reduced the number of macrophage-to-myofibroblast transition cells. Furthermore, the majority of macrophage-to-myofibroblast transition cells in human and experimental renal allograft rejection coexpressed the M2-type macrophage marker CD206, and this expression was considerably reduced in Smad3-knockout recipients. In conclusion, our studies indicate that macrophage-to-myofibroblast transition contributes to interstitial fibrosis in chronic renal allograft injury. Moreover, the transition of bone marrow-derived M2-type macrophages to myofibroblasts in the renal allograft is regulated via a Smad3-dependent mechanism.

  17. Pregnancy and chronic kidney disease.

    PubMed

    Davison, John M; Lindheimer, Marshall D

    2011-01-01

    This article reviews the association of chronic renal disease and pregnancy. Included are discussions of guidelines for counseling pregnant women with underlying chronic renal disease who are considering conceiving as well as management of those already pregnant. Specifically highlighted are recent studies that question the validity of using estimated glomerular filtration rate and other formulae and questions of whether we should strive to replace the classic counseling approaches based primarily on serum creatinine levels with guidelines based on chronic kidney disease classification. The article concludes with a review as well as a critique of recent research on the prevalence of preeclampsia in women with underlying chronic renal disease, as well as if women with preeclampsia and underlying kidney disease have accelerated courses toward end-stage renal disease.

  18. B Lymphocytes Differentially Influence Acute and Chronic Allograft Rejection in Mice1

    PubMed Central

    DiLillo, David J.; Griffiths, Robert; Seshan, Surya V.; Magro, Cynthia M.; Ruiz, Phillip; Coffman, Thomas M.; Tedder, Thomas F.

    2013-01-01

    The relative contributions of B lymphocytes and plasma cells during allograft rejection remain unclear. Therefore, the effects of B cell depletion on acute cardiac rejection, chronic renal rejection, and skin graft rejection were compared using CD20 or CD19 mAbs. Both CD20 and CD19 mAbs effectively depleted mature B cells, while CD19 mAb treatment depleted plasmablasts and some plasma cells. B cell depletion did not affect acute cardiac allograft rejection, although CD19 mAb treatment prevented allograft-specific IgG production. Strikingly, CD19 mAb treatment significantly reduced renal allograft rejection and abrogated allograft-specific IgG development, while CD20 mAb treatment did not. By contrast, B cell depletion exacerbated skin allograft rejection and augmented the proliferation of adoptively transferred alloantigen-specific CD4+ T cells, demonstrating that B cells can also negatively regulate allograft rejection. Thereby, B cells can either positively or negatively regulate allograft rejection depending on the nature of the allograft and the intensity of the rejection response. Moreover, CD19 mAb may represent a new approach for depleting both B cells and plasma cells to concomitantly impair T cell activation, inhibit the generation of new allograft-specific Abs, or reduce preexisting allograft-specific Ab levels in transplant patients. PMID:21248259

  19. Assessment of allograft function using diffusion-weighted magnetic resonance imaging in kidney transplant patients.

    PubMed

    Kaul, Anupma; Sharma, Raj Kumar; Gupta, Rakesh Kumar; Lal, Hira; Yadav, Abhishek; Bhadhuria, Dharmendra; Prasad, Narayan; Gupta, Amit

    2014-11-01

    Developing a non-invasive method such as diffusion-weighted magnetic resonance imaging (DWMRI) could be used as a feasible and reproducible modality in the differential diagnosis of allograft dysfunction. We assessed the functional status of the renal allograft by DWMRI and its applicability in assessment of graft dysfunction on all end-stage renal transplant patients who attained normal renal function on the 7th day post-transplantation. Follow-up imaging of the recipient allograft was performed at the end of 90 and 180 days and in case of graft dysfunction. Kidney biopsies were performed to correlate with the corresponding MRI. The apparent diffusion coefficient (ADC) maps of the cortex and medulla were obtained by studying the DWMRI. The ADC values were significantly lower in the medulla compared with the cortex in normal donor kidneys and normally functioning transplanted kidneys, while they decreased significantly when rejection occurred. The reduction in ADC values occurred both in the cortex and in the medulla, and correlated with the degree of rejection on the kidney biopsies. The ADC values increased significantly during the recovery from rejection. We conclude that DWMRI can be beneficial in the diagnosis and follow-up of transplant patients during acute rejection.

  20. Downregulation of T cell receptor expression by CD8(+) lymphocytes in kidney allografts.

    PubMed Central

    Mannon, R B; Kotzin, B L; Nataraj, C; Ferri, K; Roper, E; Kurlander, R J; Coffman, T M

    1998-01-01

    Allospecific CD8(+) T lymphocytes are an important component of the cellular response in allograft rejection. These cells recognize and engage MHC class I antigens, leading to allospecific cytolytic responses and graft rejection. In mouse kidney allografts that survive to 3 wk after transplantation, we noted that the majority of CD8(+) cells do not express surface alpha/beta T cell receptor alpha/beta(TCR), gamma/deltaTCR, or CD3. However, these CD8(+)TCR- cells did express surface markers characteristic of T cells, including Thy1.2, CD2, and CD5. In addition, the CD8(+)TCR- cells expressed mRNA for TCR Vbeta gene families, and nearly half stained positive for cytoplasmic Vbeta8 protein, suggesting that they are T cells that have downregulated alpha/betaTCR protein expression from their cell surfaces. When these surface TCR- cells were isolated from kidney allografts by flow cytometry and cultured in the presence of either allogeneic or syngeneic stimulators, nearly 100% of cells reacquired normal levels of alpha/betaTCR expression with disproportionate usage of Vbeta8 chains. After recovery of their surface TCR expression, the CD8(+)TCR- population demonstrated strong alloreactivity in culture. These results suggest that the substantial number of CD8(+)TCR- cells found in long-term surviving mouse kidney allografts are alpha/beta-T cells that have downregulated their cell surface expression of TCR. While in other systems this phenotype may identify cells that have engaged antigen, our results indicate that loss of TCR expression by CD8(+) kidney graft-infiltrating cells may not depend on antigen engagement and that elements in the microenvironment of the kidney graft play a key role in this process. Factors that modulate expression of TCR by graft-infiltrating lymphocytes may have an important role in regulating rejection responses. PMID:9616223

  1. Timing of Pregnancy After Kidney Transplantation and Risk of Allograft Failure.

    PubMed

    Rose, C; Gill, J; Zalunardo, N; Johnston, O; Mehrotra, A; Gill, J S

    2016-08-01

    The optimal timing of pregnancy after kidney transplantation remains uncertain. We determined the risk of allograft failure among women who became pregnant within the first 3 posttransplant years. Among 21 814 women aged 15-45 years who received a first kidney-only transplant between 1990 and 2010 captured in the United States Renal Data System, n = 729 pregnancies were identified using Medicare claims. The probability of allograft failure from any cause including death (ACGL) at 1, 3, and 5 years after pregnancy was 9.6%, 25.9%, and 36.6%. In multivariate analyses, pregnancy in the first posttransplant year was associated with an increased risk of ACGL (hazard ratio [HR]: 1.18; 95% confidence interval [CI] 1.00, 1.40) and death censored graft loss (DCGL) (HR:1.25; 95% CI 1.04, 1.50), while pregnancy in the second posttransplant year was associated with an increased risk of DCGL (HR: 1.26; 95% CI 1.06, 1.50). Pregnancy in the third posttransplant year was not associated with an increased risk of ACGL or DCGL. These findings demonstrate a higher incidence of allograft failure after pregnancy than previously reported and that the increased risk of allograft failure extends to pregnancies in the second posttransplant year.

  2. Prevalence and risk factors for early chronic allograft nephropathy in a live related renal transplant program

    PubMed Central

    Khan, Hamid; Mubarak, Muhammed; Aziz, Tahir; Ahmed, Ejaz; Fazal Akhter, Syed; Kazi, Javed; AA Naqvi, Syed; AH Rizvi, Syed

    2014-01-01

    Background: Chronic allograft nephropathy (CAN) is a common cause of delayed allograft failure throughout the world. Its prevalence and risk factors vary depending on a number of factors. There is little information on the prevalence and risk factors for early CAN in live related renal transplant patients. Objectives: We aimed to determine the prevalence and the risk factors of early CAN in our setup. Patients and Methods: The study was conducted at Sindh Institute of Urology & Transplantation (SIUT), Karachi, from 2002 to 2005 on patients who had live related kidney transplantation and underwent at least one allograft biopsy within 18 months of transplantation. The biopsies were performed and prepared in accordance with established indications and guidelines. The Banff 97 classification and its updates were used to diagnose and categorize the biopsy pathology. Patients were divided into two groups depending on the presence or absence of CAN on biopsies. Following parameters were compared among the groups: age, sex, human leukocyte antigen (HLA) match, immunosuppression used, acute rejection (AR) episodes, urinary tract infections (UTIs), viral infections, cyclosporine levels, early and late graft function monitored by serum creatinine. Results: A total of 164 patients fulfilled the study inclusion criteria. The mean age of recipients and donors was relatively young. The majority of the donors were siblings. The overall prevalence of CAN was 25.6% (42/164), between 3 and 18 months post transplantation. The median time to the appearance of CAN was 9 months post-transplant. The prevalence of CAN increased as post-transplant duration increased. In 39 (92.8%) subjects, CAN was detected on the second or subsequent graft biopsy. Only 3 (7.2%) patients showed CAN on the first graft biopsy. The majority of cases belonged to moderate degree or grade II CAN. The mean serum creatinine values were higher in the CAN group at the time of discharge and all times post

  3. Quantitative digital histochemistry with methenamine silver staining in renal allograft biopsies excluding pure chronic allograft nephropathy cases.

    PubMed

    Sarioglu, S; Sis, B; Celik, A; Tekis, D; Kavukcu, S; Bora, S; Camsari, T

    2006-03-01

    Deterioration of renal function is correlated with irreversible damage in chronic diseases. Recently we described a digital quantitative histochemistry method, relying on periodic acid methenamine silver (PAMS) staining to determine the chronic renal lesions. This index was strongly correlated with progressive deterioration of renal function in grafts with chronic allograft nephropathy (CAN). Herein the method has been applied to a cohort of renal allografts which were biopsied for various reasons, we sought to highlight its value to quantify chronic graft damage. Forty-four renal allograft biopsies from 37 patients with elevated serum creatinine values (SCr) underwent light microscopic image analysis (Mediscope, Dokuz Eylül University, Clinical Engineering Department, Izmir, Turkey) of the PAMS-stained area percentage (SAP). SCr was recorded at four intervals to overcome acute effects: the under SCr value before (SCr1) and after a biopsy within 3 months (SCr3), SCr at the time of the biopsy (SCr2), and the latest value (SCr4). The PAMS-SAP scores were strongly associated with increased interstitial fibrosis and tubular atrophy Banff scores (Kruskal-Wallis test, P = .006 and P = .003, respectively). There was a moderate positive correlation between PAMS and SCr3 (Pearson correlation test, P = .04, r = .312), and a strong positive correlation between time from transplantation to biopsy (Pearson correlation test, P < .000, r = .532). The present results show that PAMS-SAP seems to be of value to quantify renal scarring in allograft biopsies, reflecting four compartments. The strong correlation with time is noteworthy especially as a probable reflection of aging of the renal allograft.

  4. Raman-based detection of hydroxyethyl starch in kidney allograft biopsies as a potential marker of allograft quality in kidney transplant recipients

    PubMed Central

    Vuiblet, Vincent; Fere, Michael; Bankole, Ezechiel; Wynckel, Alain; Gobinet, Cyril; Birembaut, Philippe; Piot, Olivier; Rieu, Philippe

    2016-01-01

    In brain-dead donor resuscitation, hydroxyethyl starch (HES) use has been associated with presence of osmotic-nephrosis-like lesions in kidney transplant recipients. Our aim was to determine whether the presence of HES in protocol renal graft biopsies at three months (M3) after transplantation is associated with renal graft quality. According to the HES administered to the donor during the procurement procedure, two groups of patients were defined according graft exposition to HES: HES group, (N = 20) and control group (N = 6). Detection and relative quantification of HES was performed by Raman spectroscopy microimaging on M3 protocol renal graft biopsies. Statistical analyses were used to investigate the association between Raman data and graft characteristics. HES spectral signal was revealed negative in the control group, whereas it was positive in 40% of biopsies from the HES group. In the HES group, a stronger HES signal was associated with a lower risk of graft failure measured by the Kidney Donor Risk Index (KDRI) and was correlated with the allograft kidney function. Thus, HES accumulation in donor kidney, as probed by Raman biophotonic technique, is correlated with the quality of donor kidney and consequently the graft renal function and graft survival. PMID:27608775

  5. Raman-based detection of hydroxyethyl starch in kidney allograft biopsies as a potential marker of allograft quality in kidney transplant recipients

    NASA Astrophysics Data System (ADS)

    Vuiblet, Vincent; Fere, Michael; Bankole, Ezechiel; Wynckel, Alain; Gobinet, Cyril; Birembaut, Philippe; Piot, Olivier; Rieu, Philippe

    2016-09-01

    In brain-dead donor resuscitation, hydroxyethyl starch (HES) use has been associated with presence of osmotic-nephrosis-like lesions in kidney transplant recipients. Our aim was to determine whether the presence of HES in protocol renal graft biopsies at three months (M3) after transplantation is associated with renal graft quality. According to the HES administered to the donor during the procurement procedure, two groups of patients were defined according graft exposition to HES: HES group, (N = 20) and control group (N = 6). Detection and relative quantification of HES was performed by Raman spectroscopy microimaging on M3 protocol renal graft biopsies. Statistical analyses were used to investigate the association between Raman data and graft characteristics. HES spectral signal was revealed negative in the control group, whereas it was positive in 40% of biopsies from the HES group. In the HES group, a stronger HES signal was associated with a lower risk of graft failure measured by the Kidney Donor Risk Index (KDRI) and was correlated with the allograft kidney function. Thus, HES accumulation in donor kidney, as probed by Raman biophotonic technique, is correlated with the quality of donor kidney and consequently the graft renal function and graft survival.

  6. NAFLD and Chronic Kidney Disease.

    PubMed

    Marcuccilli, Morgan; Chonchol, Michel

    2016-04-14

    Non-alcoholic fatty liver disease (NAFLD) is the most common cause of chronic liver disease in developed countries and it is now considered a risk factor for cardiovascular disease. Evidence linking NAFLD to the development and progression of chronic kidney disease (CKD) is emerging as a popular area of scientific interest. The rise in simultaneous liver-kidney transplantation as well as the significant cost associated with the presence of chronic kidney disease in the NAFLD population make this entity a worthwhile target for screening and therapeutic intervention. While several cross-sectional and case control studies have been published to substantiate these theories, very little data exists on the underlying cause of NAFLD and CKD. In this review, we will discuss the most recent publications on the diagnosis of NAFLD as well new evidence regarding the pathophysiology of NAFLD and CKD as an inflammatory disorder. These mechanisms include the role of obesity, the renin-angiotensin system, and dysregulation of fructose metabolism and lipogenesis in the development of both disorders. Further investigation of these pathways may lead to novel therapies that aim to target the NAFLD and CKD. However, more prospective studies that include information on both renal and liver histology will be necessary in order to understand the relationship between these diseases.

  7. Symptomatic Respiratory Virus Infection and Chronic Lung Allograft Dysfunction

    PubMed Central

    Fisher, Cynthia E.; Preiksaitis, Carl M.; Lease, Erika D.; Edelman, Jeffrey; Kirby, Katharine A.; Leisenring, Wendy M.; Raghu, Ganesh; Boeckh, Michael; Limaye, Ajit P.

    2016-01-01

    Background. Chronic lung allograft dysfunction (CLAD) is a major cause of allograft loss post-lung transplantation. Prior studies have examined the association between respiratory virus infection (RVI) and CLAD were limited by older diagnostic techniques, study design, and case numbers. We examined the association between symptomatic RVI and CLAD using modern diagnostic techniques in a large contemporary cohort of lung transplant recipients (LTRs). Methods. We retrospectively assessed clinical variables including acute rejection, cytomegalovirus pneumonia, upper and lower RVI, and the primary endpoint of CLAD (determined by 2 independent reviewers) in 250 LTRs in a single university transplantation program. Univariate and multivariate Cox models were used to analyze the relationship between RVI and CLAD in a time-dependent manner, incorporating different periods of risk following RVI diagnosis. Results. Fifty patients (20%) were diagnosed with CLAD at a median of 95 weeks post-transplantation, and 79 (32%) had 114 episodes of RVI. In multivariate analysis, rejection and RVI were independently associated with CLAD (adjusted hazard ratio [95% confidence interval]) 2.2 (1.2–3.9), P = .01 and 1.9 (1.1–3.5), P = .03, respectively. The association of RVI with CLAD was stronger the more proximate the RVI episode: 4.8 (1.9–11.6), P < .01; 3.4 (1.5–7.5), P < .01; and 2.4 (1.2–5.0), P = .02 in multivariate analysis for 3, 6, and 12 months following RVI, respectively. Conclusions. Symptomatic RVI is independently associated with development of CLAD, with increased risk at shorter time periods following RVI. Prospective studies to characterize the virologic determinants of CLAD and define the underlying mechanisms are warranted. PMID:26565010

  8. Simultaneous pancreas and kidney transplantation with concurrent allograft nephrectomy for recipients with prior renal transplants lost to BK virus nephropathy: two case reports.

    PubMed

    Kubal, S; Powelson, J A; Taber, T E; Goble, M L; Fridell, J A

    2010-01-01

    Candidacy for retransplantation after allograft loss due to BK virus-associated nephropathy (BKVN) with or without allograft nephrectomy is controversial. This report describes 2 renal transplant recipients who lost their grafts to BKVN and subsequently underwent simultaneous kidney and pancreas transplantation with allograft nephrectomy.

  9. HIV infection in the native and allograft kidney: implications for management, diagnosis, and transplantation.

    PubMed

    Avettand-Fenoël, Véronique; Rouzioux, Christine; Legendre, Christophe; Canaud, Guillaume

    2017-02-11

    The native kidney is a reservoir for HIV-1 and a site of viral replication, similar to lymphoid tissue, gut-associated lymphoid tissue or semen. The ability of the virus to persist may result from either a true latency or sequestration in an anatomic site that is not effectively exposed to antiretroviral therapy. The presence of HIV in kidney epithelial cells will lead progressively to end-stage renal disease. For decades, HIV-infected patients were excluded from consideration for kidney transplantation. Hemodialysis and peritoneal dialysis were the only forms of treatment available to these patients. The introduction of combined antiretroviral therapy has changed the overall prognosis of these patients and allowed them to benefit from kidney transplantation without an increased risk of opportunistic infections or cancer. However, we recently established that HIV-1 can infect kidney transplant epithelial cells in the absence of detectable viremia. The presence of HIV in kidney cells can manifest itself in multiple ways, ranging from indolent nephropathy and inflammation to proteinuria with glomerular abnormalities. Because the tools that are available to diagnose the presence of HIV in kidney cells are complex, the rate of infection is certainly underestimated. This finding will certainly have implications in the management of patients, particularly for HIV-positive donors. The purpose of this review is to highlight recent evidence that the allograft kidney can be infected by the virus after transplantation as well as the associated consequences.

  10. Macrophage in chronic kidney disease

    PubMed Central

    Flaquer, Maria; Cruzado, Josep M.

    2016-01-01

    Chronic kidney disease (CKD) has become a major health problem worldwide. This review describes the role of macrophages in CKD and highlights the importance of anti-inflammatory M2 macrophage activation in both renal fibrosis and wound healing processes. Furthermore, the mechanisms by which M2 macrophages induce renal repair and regeneration are still under debate and currently demand more attention. The M1/M2 macrophage balance is related to the renal microenvironment and could influence CKD progression. In fact, an inflammatory renal environment and M2 plasticity can be the major hurdles to establishing macrophage cell-based therapies in CKD. M2 macrophage cell-based therapy is promising if the M2 phenotype remains stable and is ‘fixed’ by in vitro manipulation. However, a greater understanding of phenotype polarization is still required. Moreover, better strategies and targets to induce reparative macrophages in vivo should guide future investigations in order to abate kidney diseases. PMID:27994852

  11. Decreased chronic cellular and antibody-mediated injury in the kidney following simultaneous liver-kidney transplantation.

    PubMed

    Taner, Timucin; Heimbach, Julie K; Rosen, Charles B; Nyberg, Scott L; Park, Walter D; Stegall, Mark D

    2016-04-01

    In simultaneous liver-kidney transplantation (SLK), the liver can protect the kidney from hyperacute rejection and may also decrease acute cellular rejection rates. Whether the liver protects against chronic injury is unknown. To answer this we studied renal allograft surveillance biopsies in 68 consecutive SLK recipients (14 with donor-specific alloantibodies at transplantation [DSA+], 54 with low or no DSA, [DSA-]). These were compared with biopsies of a matched cohort of kidney transplant alone (KTA) recipients (28 DSA+, 108 DSA-). Overall 5-year patient and graft survival was not different: 93.8% and 91.2% in SLK, and 91.9% and 77.1% in KTA. In DSA+ recipients, KTA had a significantly higher incidence of acute antibody-mediated rejection (46.4% vs. 7.1%) and chronic transplant glomerulopathy (53.6% vs. 0%). In DSA- recipients at 5 years, KTA had a significantly higher cumulative incidence of T cell-mediated rejection (clinical plus subclinical, 30.6% vs. 7.4%). By 5 years, DSA+ KTA had a 44% decline in mean GFR while DSA+SLK had stable GFR. In DSA- KTA, the incidence of a combined endpoint of renal allograft loss or over a 50% decline in GFR was significantly higher (20.4% vs. 7.4%). Simultaneously transplanted liver allograft was the most predictive factor for a significantly lower incidence of cellular (odds ratio 0.13, 95% confidence interval 0.06-0.27) and antibody-mediated injury (odds ratio 0.11, confidence interval 0.03-0.32), as well as graft functional decline (odds ratio 0.22, confidence interval 0.06-0.59). Thus, SLK is associated with reduced chronic cellular and antibody-mediated alloimmune injury in the kidney allograft.

  12. [Anemia in chronic kidney disease].

    PubMed

    Amador-Medina, Lauro Fabián

    2014-01-01

    Anemia is almost unavoidable in the last stages of chronic kidney disease. It is defined as a condition where hemoglobin concentration is below 2 standard deviations from the mean hemoglobin level of the general population, corrected for age and sex (typically, hemoglobin < 13 g/dL in adults and 12 g/dL in women). Although the cause is multi-factorial, the most known is inadequate erythropoietin production. Anemia has been associated with poor prognosis in patients with several conditions such as cancer, chronic kidney disease and congestive heart failure. Treatment with erythropoiesis-stimulating agents, such as erythropoietin, is a logical strategy that has enabled clinical improvement and reduced transfusion requirements for the patients; however, total correction of anemia with erythropoiesis-stimulating agents has demonstrated an increase in the risk of mortality or cardiovascular complications associated with these agents. In randomized trials, the achievement of normal or nearly normal hemoglobin levels is not associated with improved survival and reduced cardiovascular risk; however the ideal hemoglobin level with the use of erythropoiesis-stimulating agents seems to be problematic. More information is needed in order to obtain definite conclusions; in the meantime, using the lowest possible dose of erythropoietin seems to be the most prudent approach.

  13. B-Cell-Mediated Strategies to Fight Chronic Allograft Rejection

    PubMed Central

    Dalloul, Ali

    2013-01-01

    Solid organs have been transplanted for decades. Since the improvement in graft selection and in medical and surgical procedures, the likelihood of graft function after 1 year is now close to 90%. Nonetheless even well-matched recipients continue to need medications for the rest of their lives hence adverse side effects and enhanced morbidity. Understanding Immune rejection mechanisms, is of increasing importance since the greater use of living-unrelated donors and genetically unmatched individuals. Chronic rejection is devoted to T-cells, however the role of B-cells in rejection has been appreciated recently by the observation that B-cell depletion improve graft survival. By contrast however, B-cells can be beneficial to the grafted tissue. This protective effect is secondary to either the secretion of protective antibodies or the induction of B-cells that restrain excessive inflammatory responses, chiefly by local provision of IL-10, or inhibit effector T-cells by direct cellular interactions. As a proof of concept B-cell-mediated infectious transplantation tolerance could be achieved in animal models, and evidence emerged that the presence of such B-cells in transplanted patients correlate with a favorable outcome. Among these populations, regulatory B-cells constitute a recently described population. These cells may develop as a feedback mechanism to prevent uncontrolled reactivity to antigens and inflammatory stimuli. The difficult task for the clinician, is to quantify the respective ratios and functions of “tolerant” vs. effector B-cells within a transplanted organ, at a given time point in order to modulate B-cell-directed therapy. Several receptors at the B-cell membrane as well as signaling molecules, can now be targeted for this purpose. Understanding the temporal expansion of regulatory B-cells in grafted patients and the stimuli that activate them will help in the future to implement specific strategies aimed at fighting chronic allograft

  14. Long-term gene therapy with thrombospondin 2 inhibits TGF-β activation, inflammation and angiogenesis in chronic allograft nephropathy.

    PubMed

    Daniel, Christoph; Vogelbacher, Regina; Stief, Andrea; Grigo, Christina; Hugo, Christian

    2013-01-01

    We recently identified Thrombospondin-2 (TSP-2) as a regulator of matrix remodelling and inflammation in experimental kidney disease by using TSP-2 null mice and successfully proved TSP-2 overexpression as a therapeutic concept in a short term glomerulonephritis model in the rat. In this current study, we investigated if long-term TSP-2 overexpression is also capable to ameliorate the progression of chronic kidney disease in the setting of the chronic allograft nephropathy F344-Lewis model in the rat. Two weeks after renal transplantation, two rat thigh muscles were transfected once only with either a TSP-2 overexpressing plasmid (n = 8) or a luciferase-expressing plasmid as control (n = 8). Rats were monitored for renal function, histological changes and gene expression in the graft for up to 30 weeks after transplantation. Unexpectedly, only in the TSP-2 treated group 2 rats died before the end of the experiment and renal function tended to be worsened in the TSP-2 group compared to the luciferase-treated controls. In addition, glomerular sclerosis and tubular interstitial injury as well as cortical fibronectin deposition was significantly increased in the TSP-2 treated kidneys despite reduced TGF-β activation and marked anti-inflammatory (macrophages, T-cells and B-cells) effects in this group. Long-term TSP-2 therapy impaired repair of renal endothelium, as demonstrated by significant higher glomerular and peritubular endothelial rarefaction and reduced endothelial cell proliferation in the transplanted kidneys from TSP-2 treated rats compared to controls. This TSP-2 effect was associated with decreased levels of renal VEGF but not VEGF1 receptor. In conclusion, despite its anti-inflammatory and TGF-β activation blocking effects, TSP-2 gene therapy did not ameliorate but rather worsened experimental chronic allograft nephropathy most likely via its anti-angiogenic properties on the renal microvasculature.

  15. Development of injury in a rat model of chronic renal allograft rejection: effect of dietary protein restriction.

    PubMed

    Bombas, A; Stein-Oakley, A N; Baxter, K; Thomson, N M; Jablonski, P

    1999-01-01

    Non-allogeneic factors such as increased nephron "workload" may contribute to chronic renal allograft rejection. Reducing dietary protein from 20% to 8% was tested in a model of chronic rejection: Dark Agouti kidney to Albino Surgery recipient, "tolerised" by previous donor blood transfusions. Survival, weight gain, serum creatinine concentration and creatinine clearance were similar for both groups at all times. Urinary protein was significantly (P < 0.05) lower in the low-protein (LP) group 1 month after transplantation. After 3 and 6 months, both groups demonstrated mild chronic rejection. After 6 months, tubular atrophy was significantly (P < 0.05) less in the LP group and interstitial fibrosis was marginally reduced. Glomerular hypertrophy, glomerular sclerosis, tubular dilatation, leucocyte infiltration, adhesion molecule expression and TGF-beta1 mRNA expression were similarly increased in both groups. Thus, reducing dietary protein to 8% lowered urinary protein, but did not significantly affect the development of chronic rejection in renal allografts beyond affording a degree of protection from tubulointerstitial damage.

  16. Chronic kidney disease in children

    PubMed Central

    Becherucci, Francesca; Roperto, Rosa Maria; Materassi, Marco; Romagnani, Paola

    2016-01-01

    Chronic kidney disease (CKD) is a major health problem worldwide. Although relatively uncommon in children, it can be a devastating illness with many long-term consequences. CKD presents unique features in childhood and may be considered, at least in part, as a stand-alone nosologic entity. Moreover, some typical features of paediatric CKD, such as the disease aetiology or cardiovascular complications, will not only influence the child's health, but also have long-term impact on the life of the adult that they will become. In this review we will focus on the unique issues of paediatric CKD, in terms of aetiology, clinical features and treatment. In addition, we will discuss factors related to CKD that start during childhood and require appropriate treatments in order to optimize health outcomes and transition to nephrologist management in adult life. PMID:27478602

  17. Myeloperoxidase in chronic kidney disease.

    PubMed

    Madhusudhana Rao, A; Anand, Usha; Anand, C V

    2011-01-01

    Numerous lines of evidence implicate a role of myeloperoxidase (MPO) in the pathogenesis of cardiovascular disease (CVD). It is a well accepted fact that patients with chronic kidney disease (CKD) are at an increased risk for CVD. MPO is a pro-oxidant enzyme which could be involved in the increased susceptibility of these patients to CVD. Hence, the levels of plasma MPO was determined in healthy controls as well as in patients with CKD [stratified with the level of their kidney failure as CKD stages II-V (end stage renal disease)]. Plasma MPO was assayed by a spectrophotometric method. Serum urea and creatinine were estimated on a clinical chemistry analyzer using standard laboratory procedures. The mean plasma MPO levels were significantly lower with advancing stages of renal failure (P < 0.001). There was a positive correlation between MPO and GFR (r = +0.89, P < 0.001) and a negative correlation with urea (r = -0.85, P < 0.001) and creatinine (r = -0.82, P < 0.001). While an inverse association was observed between plasma MPO and urea in CKD patients, such an association was not observed in control subjects (P = 0.43). In conclusion, the decline in plasma MPO levels may be due to the inhibitory effect of uraemic toxins on the enzyme.

  18. Hypoglycemia, chronic kidney disease, and diabetes mellitus.

    PubMed

    Alsahli, Mazen; Gerich, John E

    2014-11-01

    Hypoglycemia is a major problem associated with substantial morbidity and mortality in patients with diabetes and is often a major barrier to achieving optimal glycemic control. Chronic kidney disease not only is an independent risk factor for hypoglycemia but also augments the risk of hypoglycemia that is already present in people with diabetes. This article summarizes our current knowledge of the epidemiology, pathogenesis, and morbidity of hypoglycemia in patients with diabetes and chronic kidney disease and reviews therapeutic considerations in this situation. PubMed and MEDLINE were searched for literature published in English from January 1989 to May 2014 for diabetes mellitus, hypoglycemia, chronic kidney disease, and chronic renal insufficiency.

  19. Post-transplant anti-HLA class II antibodies as risk factor for late kidney allograft failure.

    PubMed

    Campos, E F; Tedesco-Silva, H; Machado, P G; Franco, M; Medina-Pestana, J O; Gerbase-DeLima, M

    2006-10-01

    The purpose of this study was to prospectively analyze the relationship between the post-transplant anti-HLA class I and/or class II panel reactive antibodies and graft failure due to chronic allograft nephropathy (CAN). We studied 512 first kidney recipients transplanted at a single center, with a graft functioning for at least 3 years. A single blood sample was collected from each patient for antibody evaluation. The median posttransplant time after blood collection was 4.4 years and did not differ between patients with (n = 91) or without anti-HLA antibodies (n = 421). Female gender, pregnancies and blood transfusions were associated with the presence of anti-HLA class I antibodies. Graft function deterioration was associated with anti-HLA class II antibodies. Multivariate analysis showed independent association for creatinine levels (RR = 7.5), acute rejection (RR = 2.6), recipient male gender (RR = 3.6) and anti-HLA class II antibodies (RR = 2.9) and CAN-associated graft loss. In conclusion, the presence of anti-HLA class II antibodies conferred a risk for graft loss before a decline in renal function and increased the risk of graft failure in patients who already had a decline in graft function. Thus, anti-HLA class II antibody monitoring is a useful tool for the management of long-term kidney recipients.

  20. Hepcidin as a Biomarker of Impaired Renal Function in Rat Models for Chronic Allograft Nephropathy.

    PubMed

    Xue, Dong; Zhou, Cuixing; Shi, Yunbo; Lu, Hao; He, Xiaozhou

    2016-02-23

    BACKGROUND To explore the use of hepcidin as a marker of impaired renal function in a rat model for chronic allograft nephropathy (CAN). MATERIAL AND METHODS Twenty-four models were developed and 20 models were included in this study, using Fisher (F344) rats (donors) and Lewis rats (recipients). Renal function tests were performed preoperatively and postoperatively. Hepcidin, interleukin-6 (IL-6), and erythropoietin levels in serum and urine were measured by enzyme-linked immunosorbent assay (ELISA). To observe pathological changes in the kidneys, 10 rats each were sacrificed at 2 months and 4 months after surgery. RESULTS After transplantation, the serum hepcidin and IL-6 levels increased, while urine hepcidin levels decreased. Erythropoietin levels showed a similar trend; all P<0.05. Serum creatinine (SCr) and blood urea nitrogen significantly increased post-operatively, with SCr positively correlating with serum hepcidin. Serum hepcidin positively correlated with IL-6 and negatively correlated with EPO. Histopathological results were consistent with CAN, after transplantation. CONCLUSIONS Hepcidin may be considered as a potential marker of impaired renal function.

  1. Probiotics and chronic kidney disease.

    PubMed

    Koppe, Laetitia; Mafra, Denise; Fouque, Denis

    2015-11-01

    Probiotics are the focus of a thorough investigation as a natural biotreatment due to their various health-promoting effects and inherent ability to fight specific diseases including chronic kidney disease (CKD). Indeed, intestinal microbiota has recently emerged as an important player in the progression and complications of CKD. Because many of the multifactorial physiological functions of probiotics are highly strain specific, preselection of appropriate probiotic strains based on their expression of functional biomarkers is critical. The interest in developing new research initiatives on probiotics in CKD have increased over the last decade with the goal of fully exploring their therapeutic potentials. The efficacy of probiotics to decrease uremic toxin production and to improve renal function has been investigated in in vitro models and in various animal and human CKD studies. However to date, the quality of intervention trials investigating this novel CKD therapy is still lacking. This review outlines potential mechanisms of action and efficacy of probiotics as a new CKD management tool, with a particular emphasis on uremic toxin production and inflammation.

  2. Nutrition and chronic kidney disease.

    PubMed

    Fouque, Denis; Pelletier, Solenne; Mafra, Denise; Chauveau, Philippe

    2011-08-01

    The incidence of malnutrition disorders in chronic kidney disease (CKD) appears unchanged over time, whereas patient-care and dialysis techniques continue to progress. Despite some evidence for cost-effective treatments, there are numerous caveats to applying these research findings on a daily care basis. There is a sustained generation of data confirming metabolic improvement when patients control their protein intake, even at early stages of CKD. A recent protein-energy wasting nomenclature allows a simpler approach to the diagnosis and causes of malnutrition. During maintenance dialysis, optimal protein and energy intakes have been recently challenged, and there is no longer an indication to control hyperphosphatemia through diet restriction. Recent measurements of energy expenditure in dialysis patients confirm very low physical activity, which affects energy requirements. Finally, inflammation, a common state during CKD, acts on both nutrient intake and catabolism, but is not a contraindication to a nutritional intervention, as patients do respond and improve their survival as well as do noninflamed patients.

  3. Wasting in chronic kidney disease.

    PubMed

    Mak, Robert H; Ikizler, Alp T; Kovesdy, Csaba P; Raj, Dominic S; Stenvinkel, Peter; Kalantar-Zadeh, Kamyar

    2011-03-01

    Wasting/cachexia is prevalent among patients with chronic kidney disease (CKD). It is to be distinguished from malnutrition, which is defined as the consequence of insufficient food intake or an improper diet. Malnutrition is characterized by hunger, which is an adaptive response, whereas anorexia is prevalent in patients with wasting/cachexia. Energy expenditure decreases as a protective mechanism in malnutrition whereas it remains inappropriately high in cachexia/wasting. In malnutrition, fat mass is preferentially lost and lean body mass and muscle mass is preserved. In cachexia/wasting, muscle is wasted and fat is relatively underutilized. Restoring adequate food intake or altering the composition of the diet reverses malnutrition. Nutrition supplementation does not totally reverse cachexia/wasting. The diagnostic criteria of cachexia/protein-energy wasting in CKD are considered. The association of wasting surrogates, such as serum albumin and prealbumin, with mortality is strong making them robust outcome predictors. At the patient level, longevity has consistently been observed in patients with CKD who have more muscle and/or fat, who report better appetite and who eat more. Although inadequate nutritional intake may contribute to wasting or cachexia, recent evidence indicates that other factors, including systemic inflammation, perturbations of appetite-controlling hormones from reduced renal clearance, aberrant neuropeptide signaling, insulin and insulin-like growth factor resistance, and metabolic acidosis, may be important in the pathogenesis of CKD-associated wasting. A number of novel therapeutic approaches, such as ghrelin agonists and melanocortin receptor antagonists are currently at the experimental level and await confirmation by randomized controlled clinical trials in patients with CKD-associated cachexia/wasting syndrome.

  4. Niacin and Chronic Kidney Disease.

    PubMed

    Taketani, Yutaka; Masuda, Masashi; Yamanaka-Okumura, Hisami; Tatsumi, Sawako; Segawa, Hiroko; Miyamoto, Ken-ichi; Takeda, Eiji; Yamamoto, Hironori

    2015-01-01

    Chronic kidney disease (CKD) is an increasing problem worldwide. The number of end-stage renal disease patients requiring treatment by dialysis is estimated to be increasing by 10,000 patients per year in Japan. Furthermore, an estimated 13 million people are living with CKD in Japan. Various complications are associated with CKD, including cardiovascular disease (CVD). More than one-third of CKD patients die from CVD. Thus, prevention of CVD is a primary concern for the treatment of CKD patients. CKD-mineral and bone disorder (CKD-MBD) is a serious complication that typically leads to CVD. Hyperphosphatemia is thought to be a central-risk factor for CKD-MBD. Therefore, managing hyperphosphatemia is crucial to prevent CKD-MBD and CVD. It is difficult to achieve the target serum phosphate level through dietary modifications alone in patients with hyperphosphatemia, because most foods contain phosphate. Thus, phosphate binders such as calcium carbonate are commonly prescribed to CKD patients with hyperphosphatemia, but these have undesirable side effects. Inhibition of intestinal phosphate transport activity has also been investigated as an alternative approach for controlling serum phosphate levels in CKD patients. Nicotinamide, which is the amide of niacin, can inhibit intestinal phosphate transport. Niacin and related compounds have also been developed as drugs for hyperlipidemia conditions, especially hypertriglyceridemia with low high-density lipoprotein. This type of dyslipidemia is frequently observed in CKD patients and is a modifiable risk factor for CVD. Thus, niacin and related compounds may have utility for the treatment of both hyperphosphatemia and dyslipidemia in CKD patients to prevent CVD.

  5. Long-Term Impact of Cyclosporin Reduction with MMF Treatment in Chronic Allograft Dysfunction: REFERENECE Study 3-Year Follow Up.

    PubMed

    Frimat, L; Cassuto-Viguier, E; Provôt, F; Rostaing, L; Charpentier, B; Akposso, K; Moal, M C; Lang, P; Glotz, D; Caillard, S; Ducloux, D; Pouteil-Noble, C; Girardot-Seguin, S; Kessler, M

    2010-01-01

    Calcineurin inhibitor (CNI) toxicity contributes to chronic allograft nephropathy (CAN). In the 2-year, randomized, study, we showed that 50% cyclosporin (CsA) reduction in combination with mycophenolate mofetil (MMF) treatment improves kidney function without increasing the risk for graft rejection/loss. To investigate the long-term effect of this regimen, we conducted a follow up study in 70 kidney transplant patients until 5 years after REFERENCE initiation. The improvement of kidney function was confirmed in the MMF group but not in the control group (CsA group). Four graft losses occurred, 2 in each group (graft survival in the MMF group 95.8% and 90.9% in control group). One death occurred in the control group. There was no statistically significant difference in the occurrence of serious adverse events or acute graft rejections. A limitation is the weak proportion of patient still remaining within the control group. On the other hand, REFERENCE focuses on the CsA regimen while opinions about the tacrolimus ones are still debated. In conclusion, CsA reduction in the presence of MMF treatment seems to maintain kidney function and is well tolerated in the long term.

  6. The NOX2-mediated ROS producing capacity of recipient cells is associated with reduced T cell infiltrate in an experimental model of chronic renal allograft inflammation.

    PubMed

    Kraaij, Marina D; Koekkoek, Karin M; Gelderman, Kyra A; van Kooten, Cees

    2014-03-01

    We previously showed that anti-inflammatory Mph (Mph2) can both in vitro and in vivo induce regulatory T cells (Tregs) in a reactive oxygen species (ROS)-dependent fashion. As influx of Mph is an important characteristic of chronic inflammatory responses, we investigated the impact of NOX2-mediated ROS production by recipient cells in an experimental model of chronic allograft inflammation. We used a kidney transplantation (Tx) model with Lewis (Lew) rats as donor and congenic DA.Ncf1(DA/DA) (low ROS) and DA.Ncf1(E3/E3) (normal ROS) rats as recipients. At day 7 the contralateral kidney was removed, and the animals were sacrificed four weeks after Tx. Renal function and injury were monitored in serum and urine and the composition of the infiltrate was analyzed by immunohistochemistry. Four weeks after Tx, large leukocyte clusters were observed in the allograft, in which signs of ROS production could be demonstrated. These clusters showed no difference regarding composition of myeloid cells or the number of FoxP3 positive cells. However, T cell infiltrate was significantly reduced in the DA.Ncf1(E3/E3) recipients having normal ROS production. Therefore, this study suggests a regulatory effect of ROS on T cell infiltration, but no effect on other inflammatory cells in the allograft.

  7. CXCL4 Contributes to the Pathogenesis of Chronic Liver Allograft Dysfunction

    PubMed Central

    Li, Jing; Shi, Yuan; Xie, Ke-Liang; Yin, Hai-Fang; Yan, Lu-nan; Lau, Wan-yee; Wang, Guo-Lin

    2016-01-01

    Chronic liver allograft dysfunction (CLAD) remains the most common cause of patient morbidity and allograft loss in liver transplant patients. However, the pathogenesis of CLAD has not been completely elucidated. By establishing rat CLAD models, in this study, we identified the informative CLAD-associated genes using isobaric tags for relative and absolute quantification (iTRAQ) proteomics analysis and validated these results in recipient rat liver allografts. CXCL4, CXCR3, EGFR, JAK2, STAT3, and Collagen IV were associated with CLAD pathogenesis. We validated that CXCL4 is upstream of these informative genes in the isolated hepatic stellate cells (HSC). Blocking CXCL4 protects against CLAD by reducing liver fibrosis. Therefore, our results indicated that therapeutic approaches that neutralize CXCL4, a newly identified target of fibrosis, may represent a novel strategy for preventing and treating CLAD after liver transplantation. PMID:28053995

  8. A Randomized Study Comparing Parathyroidectomy with Cinacalcet for Treating Hypercalcemia in Kidney Allograft Recipients with Hyperparathyroidism.

    PubMed

    Cruzado, Josep M; Moreno, Pablo; Torregrosa, José V; Taco, Omar; Mast, Richard; Gómez-Vaquero, Carmen; Polo, Carolina; Revuelta, Ignacio; Francos, José; Torras, Joan; García-Barrasa, Arantxa; Bestard, Oriol; Grinyó, Josep M

    2016-08-01

    Tertiary hyperparathyroidism is a common cause of hypercalcemia after kidney transplant. We designed this 12-month, prospective, multicenter, open-label, randomized study to evaluate whether subtotal parathyroidectomy is more effective than cinacalcet for controlling hypercalcemia caused by persistent hyperparathyroidism after kidney transplant. Kidney allograft recipients with hypercalcemia and elevated intact parathyroid hormone (iPTH) concentration were eligible if they had received a transplant ≥6 months before the study and had an eGFR>30 ml/min per 1.73 m(2) The primary end point was the proportion of patients with normocalcemia at 12 months. Secondary end points were serum iPTH concentration, serum phosphate concentration, bone mineral density, vascular calcification, renal function, patient and graft survival, and economic cost. In total, 30 patients were randomized to receive cinacalcet (n=15) or subtotal parathyroidectomy (n=15). At 12 months, ten of 15 patients in the cinacalcet group and 15 of 15 patients in the parathyroidectomy group (P=0.04) achieved normocalcemia. Normalization of serum phosphate concentration occurred in almost all patients. Subtotal parathyroidectomy induced greater reduction of iPTH and associated with a significant increase in femoral neck bone mineral density; vascular calcification remained unchanged in both groups. The most frequent adverse events were digestive intolerance in the cinacalcet group and hypocalcemia in the parathyroidectomy group. Surgery would be more cost effective than cinacalcet if cinacalcet duration reached 14 months. All patients were alive with a functioning graft at the end of follow-up. In conclusion, subtotal parathyroidectomy was superior to cinacalcet in controlling hypercalcemia in these patients with kidney transplants and persistent hyperparathyroidism.

  9. Effect of CTLA-4 gene polymorphisms on long-term kidney allograft function in Han Chinese recipients

    PubMed Central

    Guo, Fang

    2016-01-01

    Single nucleotide polymorphisms (SNPs) of cytotoxic T lymphocyte associated antigen-4 gene (CTLA-4) have been associated with graft rejection and long-term clinical outcome after organ transplantation. Our aim was to examine the association between CTLA-4 SNPs (rs733618, rs4553808, rs5742909, rs231775, rs3087243) and long-term allograft function in Chinese renal transplant recipients. Genotyping of CTLA-4 SNPs was performed in 292 renal transplantation recipients. To assess long-term allograft function, the estimated glomerular filtration rate (eGFR) was determined 1, 3, 6, 12, 24, 36, 48 and 60 months after renal transplantation. CTLA-4 rs733618 and rs3087243 alleles and genotypes as well as the rs5742909 and rs231775 genotypes were significantly associated with long-term allograft function after transplantation (P<0.05). Patients with favorable genotypes had higher allograft function during the 60 months after transplantation. The TACGG, CACAG and CGTAA haplotypes were also associated with long-term kidney function after renal transplantation (P<0.05 or P<0.01). In sum, the favorable CTLA-4 rs5742909TT genotype, CTLA-4 rs733618C and rs3087243A alleles, and CACAG and CGTAA haplotypes, as well as the unfavorable rs733618TT, rs3087243GG and rs231775GG genotypes and TACGG haplotype could potentially serve as effective indicators of long-term allograft function in Chinese renal transplantation recipients. PMID:27081086

  10. Intraoperative administration of inhaled carbon monoxide reduces delayed graft function in kidney allografts in Swine.

    PubMed

    Hanto, D W; Maki, T; Yoon, M H; Csizmadia, E; Chin, B Y; Gallo, D; Konduru, B; Kuramitsu, K; Smith, N R; Berssenbrugge, A; Attanasio, C; Thomas, M; Wegiel, B; Otterbein, L E

    2010-11-01

    Ischemia/reperfusion injury and delayed graft function (DGF) following organ transplantation adversely affect graft function and survival. A large animal model has not been characterized. We developed a pig kidney allograft model of DGF and evaluated the cytoprotective effects of inhaled carbon monoxide (CO). We demonstrate that donor warm ischemia time is a critical determinant of DGF as evidenced by a transient (4-6 days) increase in serum creatinine and blood urea nitrogen following transplantation before returning to baseline. CO administered to recipients intraoperatively for 1 h restored kidney function more rapidly versus air-treated controls. CO reduced acute tubular necrosis, apoptosis, tissue factor expression and P-selectin expression and enhanced proliferative repair as measured by phosphorylation of retinol binding protein and histone H3. Gene microarray analyses with confirmatory PCR of biopsy specimens showed that CO blocked proinflammatory gene expression of MCP-1 and heat shock proteins. In vitro in pig renal epithelial cells, CO blocks anoxia-reoxygenation-induced cell death while promoting proliferation. This large animal model of DGF can be utilized for testing therapeutic strategies to reduce or prevent DGF in humans. The efficacy of CO on improving graft function posttransplant validates the model and offers a potentially important therapeutic strategy to improve transplant outcomes.

  11. Common Iliac Artery Thrombosis following Pelvic Surgery Resulting in Kidney Allograft Failure Successfully Treated by Percutaneous Transluminal Angioplasty with Balloon-Expandable Covered Stent

    PubMed Central

    Golla, Maheswara S.; Acharjee, Subasit; Jaber, Bertrand L.; Garcia, Lawrence A.

    2015-01-01

    We report the case of a 66-year-old woman who developed acute kidney allograft failure due to thrombotic occlusion of the common iliac artery after hysterectomy requiring emergent allograft rescue. She underwent percutaneous transluminal angioplasty with endovascular balloon expandable covered stent graft placement in the right common iliac artery. Although there are a handful of case reports of acute limb ischemia secondary to acute common iliac artery thrombosis, this is the first case reported in the literature resulting in successful kidney allograft rescue following pelvic surgery. PMID:26355669

  12. Natural killer cells play a critical role in mediating inflammation and graft failure during antibody-mediated rejection of kidney allografts.

    PubMed

    Kohei, Naoki; Tanaka, Toshiaki; Tanabe, Kazunari; Masumori, Naoya; Dvorina, Nina; Valujskikh, Anna; Baldwin, William M; Fairchild, Robert L

    2016-06-01

    While the incidence of antibody-mediated kidney graft rejection has increased, the key cellular and molecular participants underlying this graft injury remain unclear. Rejection of kidney allografts in mice lacking the chemokine receptor CCR5 is dependent on production of donor-specific antibody. Here we determine if cells expressing cytotoxic function contributed to antibody-mediated kidney allograft rejection in these recipients. Wild-type C57BL/6, B6.CCR5(-/-), and B6.CD8(-/-)/CCR5(-/-) mice were transplanted with complete MHC-mismatched A/J kidney grafts, and intragraft inflammatory components were followed to rejection. B6.CCR5(-/-) and B6.CD8(-/-)/CCR5(-/-) recipients rejected kidney allografts by day 35, whereas 65% of allografts in wild-type recipients survived past day 80 post-transplant. Rejected allografts in wild-type C57BL/6, B6.CCR5(-/-), and B6.CD8(-/-)/CCR5(-/-) recipients expressed high levels of VCAM-1 and MMP7 mRNA that was associated with high serum titers of donor-specific antibody. High levels of perforin and granzyme B mRNA expression peaked on day 6 post-transplant in allografts in all recipients, but were absent in isografts. Depletion of natural killer cells in B6.CD8(-/-)/CCR5(-/-) recipients reduced this expression to background levels and promoted the long-term survival of 40% of the kidney allografts. Thus, natural killer cells have a role in increased inflammation during antibody-mediated kidney allograft injury and in rejection of the grafts.

  13. Exome Sequencing and Prediction of Long-Term Kidney Allograft Function

    PubMed Central

    Mesnard, Laurent; Muthukumar, Thangamani; Burbach, Maren; Li, Carol; Shang, Huimin; Dadhania, Darshana; Lee, John R.; Xiang, Jenny; Suberbielle, Caroline; Carmagnat, Maryvonnick; Ouali, Nacera; Rondeau, Eric; Abecassis, Michael M.; Suthanthiran, Manikkam

    2016-01-01

    Current strategies to improve graft outcome following kidney transplantation consider information at the human leukocyte antigen (HLA) loci. Cell surface antigens, in addition to HLA, may serve as the stimuli as well as the targets for the anti-allograft immune response and influence long-term graft outcomes. We therefore performed exome sequencing of DNA from kidney graft recipients and their living donors and estimated all possible cell surface antigens mismatches for a given donor/recipient pair by computing the number of amino acid mismatches in trans-membrane proteins. We designated this tally as the allogenomics mismatch score (AMS). We examined the association between the AMS and post-transplant estimated glomerular filtration rate (eGFR) using mixed models, considering transplants from three independent cohorts (a total of 53 donor-recipient pairs, 106 exomes, and 239 eGFR measurements). We found that the AMS has a significant effect on eGFR (mixed model, effect size across the entire range of the score: -19.4 [-37.7, -1.1], P = 0.0042, χ2 = 8.1919, d.f. = 1) that is independent of the HLA-A, B, DR matching, donor age, and time post-transplantation. The AMS effect is consistent across the three independent cohorts studied and similar to the strong effect size of donor age. Taken together, these results show that the AMS, a novel tool to quantify amino acid mismatches in trans-membrane proteins in individual donor/recipient pair, is a strong, robust predictor of long-term graft function in kidney transplant recipients. PMID:27684477

  14. Predictors and risk factors for recurrent scleroderma renal crisis in the kidney allograft: case report and review of the literature.

    PubMed

    Pham, Phuong-Thu T; Pham, Phuong-Chi T; Danovitch, Gabriel M; Gritsch, H Albin; Singer, Jennifer; Wallace, William D; Hayashi, Rick; Wilkinson, Alan H

    2005-10-01

    Scleroderma renal crisis (SRC) can lead to end-stage renal disease (ESRD) and subsequent need for dialysis and/or renal transplantation. We review all reported cases of renal transplantations in scleroderma patients from PubMed search, present UNOS data on transplant outcomes, and identify predictors for allograft SRC. Of the five cases with recurrent SRC, all developed ESRD within a year of onset of native kidney SRC, whereas none of those who developed ESRD more than 1-2 years after the onset of SRC developed recurrence. Anemia preceded allograft SRC in two cases, pericardial effusion in one, and skin tightening in two others. UNOS data (October 1987-July 2004) documented 260 transplants performed for the renal diagnosis of scleroderma, with a 5-year graft survival rate of 56.7%. The risk for allograft SRC recurrence appears to correlate with early native renal function loss following the onset of SRC. Recurrent SRC in the allograft may be heralded by multiple clinical markers known to be predictive of severe scleroderma, including progression of diffuse skin thickening, new-onset anemia and cardiac complications.

  15. Cardiovascular complications of pediatric chronic kidney disease

    PubMed Central

    2006-01-01

    Cardiovascular disease (CVD) mortality is a leading cause of death in adult chronic kidney disease (CKD), with exceptionally high rates in young adults, according to the Task Force on Cardiovascular Disease. Recent data indicate that cardiovascular complications are already present in children with CKD. This review summarizes the current literature on cardiac risk factors, mortality and morbidity in children with CKD. PMID:17120060

  16. [Chronic kidney diseases, metformin and lactic acidosis].

    PubMed

    Borbély, Zoltán

    2016-04-01

    Chronic kidney disease and diabetes mellitus represent a worldwide public health problem. The incidence of these diseases is gradually growing into epidemic proportions. In many cases they occur simultaneously, what leads to increased morbidity and mortality among the affected patients. The majority of the patients treated for diabetes mellitus are unaware of the presence of renal insufficiency. Vascular hypertrophy and diabetic kidney disease in patients with type 2 diabetes are the most common causes of kidney failure in countries with advanced healthcare systems. Metformin is a basic drug used for the treatment of type 2 diabetes mellitus. It is excreted in an unchanged form by the kidneys. When administered to patients with renal insufficiency, sepsis, dehydration or after the parenteral administration of iodinated contrast agents, metformin can cause lactic acidosis, which is also associated with an increased mortality rate.

  17. Chronic kidney disease in pregnancy.

    PubMed

    Chinnappa, V; Ankichetty, S; Angle, P; Halpern, S H

    2013-07-01

    Parturients with renal insufficiency or failure present a significant challenge for the anesthesiologist. Impaired renal function compromises fertility and increases both maternal and fetal morbidity and mortality. Close communication amongst medical specialists, including nephrologists, obstetricians, neonatologists and anesthesiologists is required to ensure the safety of mother and child. Pre-existing diseases should be optimized and close surveillance of maternal and fetal condition is required. Kidney function may deteriorate during pregnancy, necessitating early intervention. The goal is to maintain hemodynamic and physiologic stability while the demands of the pregnancy change. Drugs that may adversely affect the fetus, are nephrotoxic or are dependent on renal elimination should be avoided.

  18. Phosphorus Regulation in Chronic Kidney Disease

    PubMed Central

    Suki, Wadi N.; Moore, Linda W.

    2016-01-01

    Serum phosphorus levels stay relatively constant through the influence of multiple factors—such as parathyroid hormone, fibroblast growth factor 23, and vitamin D—on the kidney, bone, and digestive system. Whereas normal serum phosphorus ranges between 3 mg/dL to 4.5 mg/dL, large cross-sectional studies have shown that even people with normal kidney function are sometimes found to have levels ranging between 1.6 mg/dL and 6.2 mg/dL. While this may partially be due to diet and the factors mentioned above, total understanding of these atypical ranges of serum phosphorus remains uncertain. Risks for bone disease are high in people aged 50 and older, and this group comprises a large proportion of people who also have chronic kidney disease. Consuming diets low in calcium and high in phosphorus, especially foods with phosphate additives, further exacerbates bone turnover. Existing bone disease increases the risk for high serum phosphorus, and higher serum phosphorus has been associated with increased adverse events and cardiovascular-related mortality both in people with chronic kidney disease and in those with no evidence of disease. Once kidney function has deteriorated to end-stage disease (Stage 5), maintaining normal serum phosphorus requires dietary restrictions, phosphate-binding medications, and dialysis. Even so, normal serum phosphorus remains elusive in many patients with Stage 5 kidney disease, and researchers are testing novel targets that may inhibit intestinal transport of phosphorus to achieve better phosphate control. Protecting and monitoring bone health should also aid in controlling serum phosphorus as kidney disease advances. PMID:28298956

  19. Phosphorus Regulation in Chronic Kidney Disease.

    PubMed

    Suki, Wadi N; Moore, Linda W

    2016-01-01

    Serum phosphorus levels stay relatively constant through the influence of multiple factors-such as parathyroid hormone, fibroblast growth factor 23, and vitamin D-on the kidney, bone, and digestive system. Whereas normal serum phosphorus ranges between 3 mg/dL to 4.5 mg/dL, large cross-sectional studies have shown that even people with normal kidney function are sometimes found to have levels ranging between 1.6 mg/dL and 6.2 mg/dL. While this may partially be due to diet and the factors mentioned above, total understanding of these atypical ranges of serum phosphorus remains uncertain. Risks for bone disease are high in people aged 50 and older, and this group comprises a large proportion of people who also have chronic kidney disease. Consuming diets low in calcium and high in phosphorus, especially foods with phosphate additives, further exacerbates bone turnover. Existing bone disease increases the risk for high serum phosphorus, and higher serum phosphorus has been associated with increased adverse events and cardiovascular-related mortality both in people with chronic kidney disease and in those with no evidence of disease. Once kidney function has deteriorated to end-stage disease (Stage 5), maintaining normal serum phosphorus requires dietary restrictions, phosphate-binding medications, and dialysis. Even so, normal serum phosphorus remains elusive in many patients with Stage 5 kidney disease, and researchers are testing novel targets that may inhibit intestinal transport of phosphorus to achieve better phosphate control. Protecting and monitoring bone health should also aid in controlling serum phosphorus as kidney disease advances.

  20. [Chronic kidney disease in the elderly patient].

    PubMed

    Mora-Gutiérrez, José María; Slon Roblero, María Fernanda; Castaño Bilbao, Itziar; Izquierdo Bautista, Diana; Arteaga Coloma, Jesús; Martínez Velilla, Nicolás

    2016-05-06

    Chronic kidney disease (CKD) is widely prevalent worldwide, with a special impact on elderly population. Around half of people aged over 75 meet diagnostic criteria for CKD according to the recent 'Kidney disease improving global outcomes' (KDIGO) 2012 clinical practice guideline on the evaluation and management of CKD. However, geriatric patients have characteristics that may not be addressed by general guidelines. Therefore, it is important to know the natural history of the disease, symptoms, and 'red-flags' that could help in the management of these patients. In this review, a complete approach is presented on the pathophysiology, diagnosis, and treatment of CKD in the geriatric population.

  1. Gonadal dysfunction in chronic kidney disease.

    PubMed

    Palmer, Biff F; Clegg, Deborah J

    2016-09-01

    Sexual dysfunction is a common finding in both men and women with chronic kidney failure. Common disturbances include erectile dysfunction in men, menstrual abnormalities in women, and decreased libido and fertility in both sexes. These abnormalities are primarily organic in nature and are related to uremia as well as the other comorbid conditions that frequently occur in the chronic kidney failure patient. Fatigue and psycho social factors related to the presence of a chronic disease are also contributory factors. Disturbances in the hypothalamic-pituitary-gonadal axis can be detected prior to the need for dialysis but continue to worsen once dialytic therapy is initiated. Impaired gonadal function is prominent in uremic men while the disturbances in the hypothalamic-pituitary axis are more subtle. By contrast, central disturbances are more prominent in uremic women. Therapy is initially directed towards optimizing the delivery of dialysis, correcting anemia with recombinant erythropoietin, and controlling the degree of secondary hyperparathyroidism with vitamin D. For many practicing nephrologists sildenafil has become the first line therapy in the treatment of impotence. In the hypogonadal man whose only complaint is decreased libido, testosterone may be of benefit. Regular gynecologic follow up is required in uremic women to guard against potential complications of unopposed estrogen effect. Uremic women should be advised against pregnancy while on dialysis. Successful transplantation is the most effective means of restoring normal sexual function in both men and women with chronic kidney failure.

  2. Associations of Perfusate Biomarkers and Pump Parameters With Delayed Graft Function and Deceased Donor Kidney Allograft Function.

    PubMed

    Parikh, C R; Hall, I E; Bhangoo, R S; Ficek, J; Abt, P L; Thiessen-Philbrook, H; Lin, H; Bimali, M; Murray, P T; Rao, V; Schröppel, B; Doshi, M D; Weng, F L; Reese, P P

    2016-05-01

    Hypothermic machine perfusion (HMP) is increasingly used in deceased donor kidney transplantation, but controversy exists regarding the value of perfusion biomarkers and pump parameters for assessing organ quality. We prospectively determined associations between perfusate biomarkers (neutrophil gelatinase-associated lipocalin [NGAL], kidney injury molecule 1, IL-18 and liver-type fatty acid-binding protein [L-FABP]) and pump parameters (resistance and flow) with outcomes of delayed graft function (DGF) and 6-mo estimated GFR (eGFR). DGF occurred in 230 of 671 (34%) recipients. Only 1-h flow was inversely associated with DGF. Higher NGAL or L-FABP concentrations and increased resistance were inversely associated with 6-mo eGFR, whereas higher flow was associated with higher adjusted 6-mo eGFR. Discarded kidneys had consistently higher median resistance and lower median flow than transplanted kidneys, but median perfusate biomarker concentrations were either lower or not significantly different in discarded compared with transplanted kidneys. Notably, most recipients of transplanted kidneys with isolated "undesirable" biomarker levels or HMP parameters experienced acceptable 6-mo allograft function, suggesting these characteristics should not be used in isolation for discard decisions. Additional studies must confirm the utility of combining HMP measurements with other characteristics to assess kidney quality.

  3. Chronic kidney disease and premature ageing.

    PubMed

    Kooman, Jeroen P; Kotanko, Peter; Schols, Annemie M W J; Shiels, Paul G; Stenvinkel, Peter

    2014-12-01

    Chronic kidney disease (CKD) shares many phenotypic similarities with other chronic diseases, including heart failure, chronic obstructive pulmonary disease, HIV infection and rheumatoid arthritis. The most apparent similarity is premature ageing, involving accelerated vascular disease and muscle wasting. We propose that in addition to a sedentary lifestyle and psychosocial and socioeconomic determinants, four major disease-induced mechanisms underlie premature ageing in CKD: an increase in allostatic load, activation of the 'stress resistance response', activation of age-promoting mechanisms and impairment of anti-ageing pathways. The most effective current interventions to modulate premature ageing-treatment of the underlying disease, optimal nutrition, correction of the internal environment and exercise training-reduce systemic inflammation and oxidative stress and induce muscle anabolism. Deeper mechanistic insight into the phenomena of premature ageing as well as early diagnosis of CKD might improve the application and efficacy of these interventions and provide novel leads to combat muscle wasting and vascular impairment in chronic diseases.

  4. Antibody-Dependent NK Cell Activation Is Associated with Late Kidney Allograft Dysfunction and the Complement-Independent Alloreactive Potential of Donor-Specific Antibodies

    PubMed Central

    Legris, Tristan; Picard, Christophe; Todorova, Dilyana; Lyonnet, Luc; Laporte, Cathy; Dumoulin, Chloé; Nicolino-Brunet, Corinne; Daniel, Laurent; Loundou, Anderson; Morange, Sophie; Bataille, Stanislas; Vacher-Coponat, Henri; Moal, Valérie; Berland, Yvon; Dignat-George, Francoise; Burtey, Stéphane; Paul, Pascale

    2016-01-01

    Although kidney transplantation remains the best treatment for end-stage renal failure, it is limited by chronic humoral aggression of the graft vasculature by donor-specific antibodies (DSAs). The complement-independent mechanisms that lead to the antibody-mediated rejection (ABMR) of kidney allografts remain poorly understood. Increasing lines of evidence have revealed the relevance of natural killer (NK) cells as innate immune effectors of antibody-dependent cellular cytotoxicity (ADCC), but few studies have investigated their alloreactive potential in the context of solid organ transplantation. Our study aimed to investigate the potential contribution of the antibody-dependent alloreactive function of NK cells to kidney graft dysfunction. We first conducted an observational study to investigate whether the cytotoxic function of NK cells is associated with chronic allograft dysfunction. The NK-Cellular Humoral Activation Test (NK-CHAT) was designed to evaluate the recipient and antibody-dependent reactivity of NK cells against allogeneic target cells. The release of CD107a/Lamp1+ cytotoxic granules, resulting from the recognition of rituximab-coated B cells by NK cells, was analyzed in 148 kidney transplant recipients (KTRs, mean graft duration: 6.2 years). Enhanced ADCC responsiveness was associated with reduced graft function and identified as an independent risk factor predicting a decline in the estimated glomerular filtration rate over a 1-year period (hazard ratio: 2.83). In a second approach, we used the NK-CHAT to reveal the cytotoxic potential of circulating alloantibodies in vitro. The level of CD16 engagement resulting from the in vitro recognition of serum-coated allogeneic B cells or splenic cells was further identified as a specific marker of DSA-induced ADCC. The NK-CHAT scoring of sera obtained from 40 patients at the time of transplant biopsy was associated with ABMR diagnosis. Our findings indicate that despite the administration of

  5. Measurement of renal function in patients with chronic kidney disease

    PubMed Central

    Sandilands, Euan A; Dhaun, Neeraj; Dear, James W; Webb, David J

    2013-01-01

    Chronic kidney disease affects millions of people worldwide and is associated with an increased morbidity and mortality as a result of kidney failure and cardiovascular disease. Accurate assessment of kidney function is important in the clinical setting as a screening tool and for monitoring disease progression and guiding prognosis. In clinical research, the development of new methods to measure kidney function accurately is important in the search for new therapeutic targets and the discovery of novel biomarkers to aid early identification of kidney injury. This review considers different methods for measuring kidney function and their contribution to the improvement of detection, monitoring and treatment of chronic kidney disease. PMID:23802624

  6. Measurement of renal function in patients with chronic kidney disease.

    PubMed

    Sandilands, Euan A; Dhaun, Neeraj; Dear, James W; Webb, David J

    2013-10-01

    Chronic kidney disease affects millions of people worldwide and is associated with an increased morbidity and mortality as a result of kidney failure and cardiovascular disease. Accurate assessment of kidney function is important in the clinical setting as a screening tool and for monitoring disease progression and guiding prognosis. In clinical research, the development of new methods to measure kidney function accurately is important in the search for new therapeutic targets and the discovery of novel biomarkers to aid early identification of kidney injury. This review considers different methods for measuring kidney function and their contribution to the improvement of detection, monitoring and treatment of chronic kidney disease.

  7. Updated management of chronic kidney disease in patients with diabetes.

    PubMed

    Hass, Virginia McCoy

    2014-06-01

    Chronic diseases, including chronic kidney disease (CKD), are the primary threat to global public health in the 21st century. Recently updated guidelines from the National Kidney Foundation's Kidney Disease Outcomes Quality Initiative provide patient care benchmarks that physician assistants can use when caring for patients with diabetes and CKD and developing clinical performance improvement plans.

  8. Chronic kidney Disease and the Aging Population.

    PubMed

    Tonelli, Marcello; Riellae, Miguel

    2014-01-01

    Youth, which is forgiven everything, forgives itself nothing: age, which forgives itself everything, is forgiven nothing. George Bernard Shaw The proportion of older people in the general population is steadily increasing worldwide, with the most rapid growth in low-and middle-income countries [1]. This demographic change is to be celebrated, because it is the consequence of socioeconomic development and better life expectancy. However, population aging also has important implications for society - in diverse areas including health systems, labor markets, public policy, social programs, and family dynamics [2]. A successful response to the aging population will require capitalizing on the opportunities that this transition offers, as well as effectively addressing its challenges. Chronic kidney disease (CKD) is an important public health problem that is characterized by poor health outcomes and very high health care costs. CKD is a major risk multiplier in patients with diabetes, hypertension, heart disease and stroke - all of which are key causes of death and disability in older people [3]. Since the prevalence of CKD is higher in older people, the health impact of population aging will depend in part on how the kidney community responds. March 13, 2014 will mark the celebration of the 9th World Kidney Day (WKD), an annual event jointly sponsored by the International Society of Nephrology and the International Federation of Kidney Foundations. Since its inception in 2006, WKD has become the most successful effort to raise awareness among policymakers and the general public about the importance of kidney disease. The topic for WKD 2014 is "CKD in older people". This article reviews the key links between kidney function, age, health and illness - and discusses the implications of the aging population for the care of people with CKD.

  9. Soluble Urokinase Receptor and Chronic Kidney Disease

    PubMed Central

    Hayek, Salim S.; Sever, Sanja; Ko, Yi-An; Trachtman, Howard; Awad, Mosaab; Wadhwani, Shikha; Altintas, Mehmet M.; Wei, Changli; Hotton, Anna L.; French, Audrey L.; Sperling, Laurence S.; Lerakis, Stamatios; Quyyumi, Arshed A.; Reiser, Jochen

    2015-01-01

    BACKGROUND Relatively high plasma levels of soluble urokinase-type plasminogen activator receptor (suPAR) have been associated with focal segmental glomerulosclerosis and poor clinical outcomes in patients with various conditions. It is unknown whether elevated suPAR levels in patients with normal kidney function are associated with future decline in the estimated glomerular filtration rate (eGFR) and with incident chronic kidney disease. METHODS We measured plasma suPAR levels in 3683 persons enrolled in the Emory Cardiovascular Biobank (mean age, 63 years; 65% men; median suPAR level, 3040 pg per milliliter) and determined renal function at enrollment and at subsequent visits in 2292 persons. The relationship between suPAR levels and the eGFR at baseline, the change in the eGFR over time, and the development of chronic kidney disease (eGFR <60 ml per minute per 1.73 m2 of body-surface area) were analyzed with the use of linear mixed models and Cox regression after adjustment for demographic and clinical variables. RESULTS A higher suPAR level at baseline was associated with a greater decline in the eGFR during follow-up; the annual change in the eGFR was −0.9 ml per minute per 1.73 m2 among participants in the lowest quartile of suPAR levels as compared with −4.2 ml per minute per 1.73 m2 among participants in the highest quartile (P<0.001). The 921 participants with a normal eGFR (≥90 ml per minute per 1.73 m2) at baseline had the largest suPAR-related decline in the eGFR. In 1335 participants with a baseline eGFR of at least 60 ml per minute per 1.73 m2, the risk of progression to chronic kidney disease in the highest quartile of suPAR levels was 3.13 times as high (95% confidence interval, 2.11 to 4.65) as that in the lowest quartile. CONCLUSIONS An elevated level of suPAR was independently associated with incident chronic kidney disease and an accelerated decline in the eGFR in the groups studied. (Funded by the Abraham J. and Phyllis Katz Foundation

  10. When Your Child Has a Chronic Kidney Disease

    MedlinePlus

    ... Year-Old When Your Child Has a Chronic Kidney Disease KidsHealth > For Parents > When Your Child Has ... and what parents can do to help. Treating Kidney Diseases Treatment begins with dietary changes and medicines. ...

  11. Chronic Disease and Childhood Development: Kidney Disease and Transplantation.

    ERIC Educational Resources Information Center

    Klein, Susan D.; Simmons, Roberta G.

    As part of a larger study of transplantation and chronic disease and the family, 124 children (10-18 years old) who were chronically ill with kidney disease (n=72) or were a year or more post-transplant (n=52) were included in a study focusing on the effects of chronic kidney disease and transplantation on children's psychosocial development. Ss…

  12. Ghrelin and cachexia in chronic kidney disease.

    PubMed

    Suzuki, Hajime; Asakawa, Akihiro; Amitani, Haruka; Nakamura, Norifumi; Inui, Akio

    2013-04-01

    Ghrelin is a growth hormone (GH) secretagogue and a potent orexigenic factor that stimulates feeding by interacting with hypothalamic feeding-regulatory nuclei. Its multifaceted effects are potentially beneficial as a treatment in human disease states. In both adult and pediatric chronic kidney disease (CKD) patients, decreased appetite plays a major role in wasting, which in turn is linked to morbidity and mortality; wasting has also been linked to high levels of leptin and proinflammatory cytokines. The beneficial effects of ghrelin treatment in CKD are potentially mediated by multiple concurrent actions, including the stimulation of appetite-regulating centers, anti-inflammatory effects, and direct kidney effects. Further evaluation of this appetite-regulating hormone in CKD is needed to confirm previous findings and to determine the underlying mechanisms.

  13. Sexual function in chronic kidney disease.

    PubMed

    Anantharaman, Priya; Schmidt, Rebecca J

    2007-04-01

    Endocrine abnormalities are common in patients with chronic kidney disease (CKD) and lead to sexual dysfunction, anemia, hyperparathyroidism, and altered mineral metabolism. Common clinical problems include disturbances in menstruation in women, erectile dysfunction in men, and decreased libido and infertility in both sexes. Organic factors tend to be prominent and are related to uremia and other comorbid illnesses. Psychological factors and depression may exacerbate the primary problem. Alterations in the hypothalamic-pituitary axis are seen early in CKD and tend to worsen after patients start dialysis. Hypogonadism plays a dominant role in male sexual function, whereas changes in hypothalamic-pituitary function predominate in female sexual dysfunction. In patients on dialysis, treatment strategies include optimizing dose of dialysis, correction of anemia with erythropoietin, and correction of hyperparathyroidism. Successful kidney transplantation may restore normal sexual function, especially in younger patients.

  14. Statins in chronic kidney disease and kidney transplantation.

    PubMed

    Kassimatis, Theodoros I; Goldsmith, David J A

    2014-10-01

    HMG-CoA reductase inhibitors (statins) have been shown to improve cardiovascular (CV) outcomes in the general population as well as in patients with cardiovascular disease (CVD). Statins' beneficial effects have been attributed to both cholesterol-lowering and cholesterol-independent "pleiotropic" properties. By their pleiotropic effects statins have been shown to reduce inflammation, alleviate oxidative stress, modify the immunologic responses, improve endothelial function and suppress platelet aggregation. Patients with chronic kidney disease (CKD) exhibit an enormous increase in CVD rates even from early CKD stages. As considerable differences exist in dyslipidemia characteristics and the pathogenesis of CVD in CKD, statins' CV benefits in CKD patients (including those with a kidney graft) should not be considered unequivocal. Indeed, accumulating clinical evidence suggests that statins exert diverse effects on dialysis and non-dialysis CKD patients. Therefore, it seems that statins improve CV outcomes in non-dialysis patients whereas exert little (if any) benefit in the dialysis population. It has also been proposed that dyslipidemia might play a causative role or even accelerate renal injury. Moreover, ample experimental evidence suggests that statins ameliorate renal damage. However, a high quality randomized controlled trial (RCT) and metaanalyses do not support a beneficial role of statins in renal outcomes in terms of proteinuria reduction or retardation of glomerular filtration rate (GFR) decline.

  15. Growth, chronic kidney disease and pediatric kidney transplantation: is it useful to use recombinant growth hormone in Colombian children with renal transplant?

    PubMed

    Castañeda, D A; López, L F; Ovalle, D F; Buitrago, J; Rodríguez, D; Lozano, E

    2011-11-01

    Kidney transplantation has become the best treatment for children with chronic kidney disease (CKD). In recent times, knowledge concerning the effect of CKD and kidney transplantation over the normal growth rate has increased; now it is known that 40% of children with CKD do not reach the expected height for age. Growth retardation has been associated with the type of nephropathy, metabolic and endocrine disorders that are secondary to kidney disease, immunosuppressive therapy with glucocorticoids, and suboptimal function of renal allograft. Nowadays, we know better the role of the growth hormone/insulin-like growth factor 1 axis in growth retardation we can see it in children with CKD or recipients of renal allograft. Several studies have shown that administration of recombinant growth hormone (rhGH) has a positive effect on the longitudinal growth of children and teenagers who have received a kidney transplant. On the other hand, there have been reported side effects associated with using rhGH; however, these are not statistically significant. In this article, we show a small review about growth in children with CKD and/or recipients of renal allografts the growth pattern of three children who were known by the Transplant Group of National University of Colombia, and the results obtained with the use of rhGH in one of these cases. We want to show the possibility of achieving a secure use of rhGH in children with CKD and its use as a therapeutic option for treating the growth retardation in children with kidney transplantation, and set out the need of typifying the growth pattern of Colombian children with CKD and/or who are recipients of renal allografts through multicenter studies to propose and analyze the inclusion of rhGH in the therapeutic scheme of Colombian children with these two medical conditions. rhGH could be a useful tool for treating children with CKD or kidney transplantation who have not reached the expected longitudinal growth for age. However

  16. Biomarkers in chronic kidney disease, from kidney function to kidney damage

    PubMed Central

    Lopez-Giacoman, Salvador; Madero, Magdalena

    2015-01-01

    Chronic kidney disease (CKD) typically evolves over many years, with a long latent period when the disease is clinically silent and therefore diagnosis, evaluation and treatment is based mainly on biomarkers that assess kidney function. Glomerular filtration rate (GFR) remains the ideal marker of kidney function. Unfortunately measuring GFR is time consuming and therefore GFR is usually estimated from equations that take into account endogenous filtration markers like serum creatinine (SCr) and cystatin C (CysC). Other biomarkers such as albuminuria may precede kidney function decline and have demonstrated to have strong associations with disease progression and outcomes. New potential biomarkers have arisen with the promise of detecting kidney damage prior to the currently used markers. The aim of this review is to discuss the utility of the GFR estimating equations and biomarkers in CKD and the different clinical settings where these should be applied. The CKD-Epidemiology Collaboration equation performs better than the modification of diet in renal disease equation, especially at GFR above 60 mL/min per 1.73 m2. Equations combining CysC and SCr perform better than the equations using either CysC or SCr alone and are recommended in situations where CKD needs to be confirmed. Combining creatinine, CysC and urine albumin to creatinine ratio improves risk stratification for kidney disease progression and mortality. Kidney injury molecule and neutrophil gelatinase-associated lipocalin are considered reasonable biomarkers in urine and plasma to determine severity and prognosis of CKD. PMID:25664247

  17. PDL1 is required for peripheral transplantation tolerance and protection from chronic allograft rejection.

    PubMed

    Tanaka, Katsunori; Albin, Monica J; Yuan, Xueli; Yamaura, Kazuhiro; Habicht, Antje; Murayama, Takaya; Grimm, Martin; Waaga, Ana Maria; Ueno, Takuya; Padera, Robert F; Yagita, Hideo; Azuma, Miyuki; Shin, Tahiro; Blazar, Bruce R; Rothstein, David M; Sayegh, Mohamed H; Najafian, Nader

    2007-10-15

    The PD-1:PDL pathway plays an important role in regulating alloimmune responses but its role in transplantation tolerance is unknown. We investigated the role of PD-1:PDL costimulatory pathway in peripheral and a well established model of central transplantation tolerance. Early as well as delayed blockade of PDL1 but not PDL2 abrogated tolerance induced by CTLA4Ig in a fully MHC-mismatched cardiac allograft model. Accelerated rejection was associated with a significant increase in the frequency of IFN-gamma-producing alloreactive T cells and expansion of effector CD8(+) T cells in the periphery, and a decline in the percentage of Foxp3(+) graft infiltrating cells. Similarly, studies using PDL1/L2-deficient recipients confirmed the results with Ab blockade. Interestingly, while PDL1-deficient donor allografts were accepted by wild-type recipients treated with CTLA4Ig, the grafts developed severe chronic rejection and vasculopathy when compared with wild-type grafts. Finally, in a model of central tolerance induced by mixed allogeneic chimerism, engraftment was not abrogated by PDL1/L2 blockade. These novel data demonstrate the critical role of PDL1 for induction and maintenance of peripheral transplantation tolerance by its ability to alter the balance between pathogenic and regulatory T cells. Expression of PDL1 in donor tissue is critical for prevention of in situ graft pathology and chronic rejection.

  18. Impact of cyclosporine reduction with MMF: a randomized trial in chronic allograft dysfunction. The 'reference' study.

    PubMed

    Frimat, L; Cassuto-Viguier, E; Charpentier, B; Noël, C; Provôt, F; Rostaing, L; Glotz, D; Sraer, J D; Bourbigot, B; Moulin, B; Lang, P; Ducloux, D; Pouteil-Noble, C; Girardot-Seguin, S; Kessler, M

    2006-11-01

    Long-term use of calcineurine inhibitors (CNIs) may contribute to the development of chronic allograft dysfunction (CAD). We investigate the impact of the introduction of MMF combined with cyclosporine (CsA) 50% dose reduction. An open, randomized, controlled, multicenter, prospective study was conducted in 103 patients, receiving a CsA-based therapy with a serum creatinine between 1.7-3.4 mg/dL, more than 1 year after transplantation. They were randomized to receive MMF with half dose of CsA (MMF group) or to continue their maintenance CsA dose (control group). A total of 96 weeks after randomization, the evolution of renal function assessed by regression line analysis of 1/SeCr improved in the MMF group (positive slope) vs. the control group (negative slope), 4.2 x 10(-4) vs. -3.0 x 10(-4), respectively (p < 0.001). Concurrently, the absolute renal function improved significantly in the MMF group. No episode of biopsy-proven acute rejection occurred. One patient in each group lost his graft because of biopsy-proven chronic allograft nephropathy. There was a significant decrease of triglycerides level in the MMF group. Anemia and diarrhea were statistically more frequent in the MMF group. In CAD, the reduction of CsA in the presence of MMF results in significant improvement in renal function during a 2-year follow-up.

  19. Vitamin K Status in Chronic Kidney Disease

    PubMed Central

    McCabe, Kristin M.; Adams, Michael A.; Holden, Rachel M.

    2013-01-01

    The purpose of this review is to summarize the research to date on vitamin K status in chronic kidney disease (CKD). This review includes a summary of the data available on vitamin K status in patients across the spectrum of CKD as well as the link between vitamin K deficiency in CKD and bone dynamics, including mineralization and demineralization, as well as ectopic mineralization. It also describes two current clinical trials that are underway evaluating vitamin K treatment in CKD patients. These data may inform future clinical practice in this population. PMID:24212088

  20. Baroreflex dysfunction in chronic kidney disease

    PubMed Central

    Kaur, Manpreet; Chandran, Dinu S; Jaryal, Ashok Kumar; Bhowmik, Dipankar; Agarwal, Sanjay Kumar; Deepak, Kishore Kumar

    2016-01-01

    Chronic kidney disease (CKD) patients have high cardiovascular mortality and morbidity. The presence of traditional and CKD related risk factors results in exaggerated vascular calcification in these patients. Vascular calcification is associated with reduced large arterial compliance and thus impaired baroreflex sensitivity (BRS) resulting in augmented blood pressure (BP) variability and hampered BP regulation. Baroreflex plays a vital role in short term regulation of BP. This review discusses the normal baroreflex physiology, methods to assess baroreflex function, its determinants along with the prognostic significance of assessing BRS in CKD patients, available literature on BRS in CKD patients and the probable patho-physiology of baroreflex dysfunction in CKD. PMID:26788464

  1. Male Sexual Dysfunction and Chronic Kidney Disease

    PubMed Central

    Edey, Matthew M.

    2017-01-01

    Male sexual dysfunction is common in chronic kidney disease (CKD), particularly in end-stage renal disease. Historically, this cause of considerable morbidity has been under-reported and under-recognized. The ideal approach to diagnosis and management remains unclear due to a paucity of good quality data, but an understanding of the pathophysiology is necessary in order to address the burden of this important complication of CKD. This paper will review the endocrine dysfunction that occurs in renal disease, particularly the hypothalamic–pituitary–gonadal axis, discuss the causes of erectile dysfunction, infertility, and altered body image and libido in these patients and suggest appropriate treatment interventions. PMID:28382300

  2. Pregnancy and contraceptive counseling of women with chronic kidney disease and kidney transplants.

    PubMed

    Watnick, Suzanne

    2007-04-01

    Women with kidney disease of childbearing age should expect proactive counseling regarding pregnancy and contraception. Discussions should include the impact of pregnancy on their kidney disease and the impact of kidney disease on maternal and fetal outcomes. However, nephrologists rarely discuss sexual dysfunction, infertility, menstrual irregularities, and contraception with their premenopausal women patients. This review will consider pregnancy-related issues to discuss when counseling women with all stages of chronic kidney disease. Issues related to contraception in women on dialysis, women with functioning kidney transplants, and those with chronic kidney disease will also be reviewed.

  3. Sleep disorders and chronic kidney disease.

    PubMed

    Maung, Stephanie C; El Sara, Ammar; Chapman, Cherylle; Cohen, Danielle; Cukor, Daniel

    2016-05-06

    Sleep disorders have a profound and well-documented impact on overall health and quality of life in the general population. In patients with chronic disease, sleep disorders are more prevalent, with an additional morbidity and mortality burden. The complex and dynamic relationship between sleep disorders and chronic kidney disease (CKD) remain relatively little investigated. This article presents an overview of sleep disorders in patients with CKD, with emphasis on relevant pathophysiologic underpinnings and clinical presentations. Evidence-based interventions will be discussed, in the context of individual sleep disorders, namely sleep apnea, insomnia, restless leg syndrome and excessive daytime sleepiness. Limitations of the current knowledge as well as future research directions will be highlighted, with a final discussion of different conceptual frameworks of the relationship between sleep disorders and CKD.

  4. Sleep disorders and chronic kidney disease

    PubMed Central

    Maung, Stephanie C; El Sara, Ammar; Chapman, Cherylle; Cohen, Danielle; Cukor, Daniel

    2016-01-01

    Sleep disorders have a profound and well-documented impact on overall health and quality of life in the general population. In patients with chronic disease, sleep disorders are more prevalent, with an additional morbidity and mortality burden. The complex and dynamic relationship between sleep disorders and chronic kidney disease (CKD) remain relatively little investigated. This article presents an overview of sleep disorders in patients with CKD, with emphasis on relevant pathophysiologic underpinnings and clinical presentations. Evidence-based interventions will be discussed, in the context of individual sleep disorders, namely sleep apnea, insomnia, restless leg syndrome and excessive daytime sleepiness. Limitations of the current knowledge as well as future research directions will be highlighted, with a final discussion of different conceptual frameworks of the relationship between sleep disorders and CKD. PMID:27152260

  5. Management of hyperkalaemia in chronic kidney disease.

    PubMed

    Kovesdy, Csaba P

    2014-11-01

    Hyperkalaemia is common in patients with chronic kidney disease (CKD), in part because of the effects of kidney dysfunction on potassium homeostasis and in part because of the cluster of comorbidities (and their associated treatments) that occur in patients with CKD. Owing to its electrophysiological effects, severe hyperkalaemia represents a medical emergency that usually requires prompt intervention, whereas the prevention of hazardous hyperkalaemic episodes in at-risk patients requires measures aimed at the long-term normalization of potassium homeostasis. The options for effective and safe medical interventions to restore chronic potassium balance are few, and long-term management of hyperkalaemia is primarily limited to the correction of modifiable exacerbating factors. This situation can result in a difficult trade-off in patients with CKD, because drugs that are beneficial to these patients (for example, renin-angiotensin-aldosterone-system antagonists) are often the most prominent cause of their hyperkalaemia. Maintaining the use of these beneficial medications while implementing various strategies to control potassium balance is desirable; however, discontinuation rates remain high. The emergence of new medications that specifically target hyperkalaemia could lead to a therapeutic paradigm shift, emphasizing preventive management over ad hoc treatment of incidentally discovered elevations in serum potassium levels.

  6. BALF cytokines in different phenotypes of chronic lung allograft dysfunction in lung transplant patients.

    PubMed

    Berastegui, Cristina; Gómez-Ollés, Susana; Sánchez-Vidaurre, Sara; Culebras, Mario; Monforte, Victor; López-Meseguer, Manuel; Bravo, Carlos; Ramon, Maria-Antonia; Romero, Laura; Sole, Joan; Cruz, Maria-Jesus; Román, Antonio

    2017-03-01

    The long-term success of lung transplantation (LT) is limited by chronic lung allograft dysfunction (CLAD). Different phenotypes of CLAD have been described, such as bronchiolitis obliterans syndrome (BOS) and restrictive allograft syndrome (RAS). The purpose of this study was to investigate the levels of cytokines and chemokines in bronchoalveolar lavage fluid (BALF) as markers of these CLAD phenotypes. BALF was collected from 51 recipients who underwent (bilateral and unilateral) LT. The study population was divided into three groups: stable (ST), BOS, and RAS. Levels of interleukin (IL)-4, IL-5, IL-6, IL-10, IL-13, tumor necrosis factor alpha (TNF-α), interferon-gamma (IFN-γ), and granulocyte-macrophage colony-stimulating factor (GM-CSF) were measured using the multiplex technology. BALF neutrophilia medians were higher in BOS (38%) and RAS (30%) than in ST (8%) (P=.008; P=.012). Regarding BALF cytokines, BOS and RAS patients showed higher levels of INF-γ than ST (P=.02; P=.008). Only IL-5 presented significant differences between BOS and RAS (P=.001). BALF neutrophilia is as a marker for both CLAD phenotypes, BOS and RAS, and IL-5 seems to be a potential biomarker for the RAS phenotype.

  7. Inflammation and cachexia in chronic kidney disease.

    PubMed

    Cheung, Wai W; Paik, Kyung Hoon; Mak, Robert H

    2010-04-01

    Chronic inflammation is associated with cachexia and increased mortality risk in patients with chronic kidney disease (CKD) and end-stage renal disease (ESRD). Inflammation suppresses appetite and causes the loss of protein stores. In CKD patients, increased serum levels of pro-inflammatory cytokines may be caused by reduced renal function, volume overload, oxidative or carbonyl stress, decreased levels of antioxidants, increased susceptibility to infection in uremia, and the presence of comorbid conditions. Cachexia is brought about by the synergistic combination of a dramatic decrease in appetite and an increase in the catabolism of fat and lean body mass. Pro-inflammatory cytokines act on the central nervous system to alter appetite and energy metabolism and to provide a signal-through the nuclear factor-kappaB and ATP-ubiquitin-dependent proteolytic pathways-that causes muscle wasting. Further research into the molecular pathways leading to inflammation and cachexia may lead to novel therapeutic therapies for this devastating and potentially fatal complication of chronic disease.

  8. 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

  9. Cardiometabolic syndrome and chronic kidney disease.

    PubMed

    Lastra, Guido; Manrique, Camila; McFarlane, Samy I; Sowers, James R

    2006-06-01

    Chronic kidney disease (CKD) is increasingly recognized as a major risk factor for end-stage renal disease (ESRD), cardiovascular (CV) disease, and CV-related premature death. More than 8 million people in the United States have CKD; therefore, preventive stratiegies should be directed at identifying risk factors for this condition. There is growing evidence implicating the cardiometabolic syndrome, a clustering of CV risk factors that include obesity, insulin resistance, compensatory hyperinsulinemia, dysglycemia, atherogenic dyslipidemia, and hypertension. Factors mediating this relationship include increased glomerular filtration, increased vascular permeability, oxidative and endoplasmic reticulum stress, activation of the renin-angiotensin system, and inappropriate secretion of growth factors. The consequences are microalbuminuria, a marker of inflammation and endothelial dysfunction, renal vascular proliferation, extracellular matrix expansion, and CKD. Prevention of CKD should be directed at controlling all components of the cardiometabolic syndrome, with the ultimate goal of reducing the burden imposed by ESRD.

  10. Chronic kidney disease - different role for HDL?

    PubMed

    Jacek, Rysz; Anna, Gluba; Danilo, Fliser; Timo, Speer; Andrzej, Wiecek

    2014-01-01

    Chronic kidney disease (CKD) is an emerging health hazard, connected to very high cardiovascular mortality due to accelerated atherosclerosis. Increased cardiovascular risk cannot be explained only by traditional risk factors. Patients with renal dysfunction have significant disturbances in lipoprotein metabolism and HDL in these patients becomes dysfunctional. It has been documented that in patients with CKD lower plasma level of HDL cholesterol and reduced ability of HDL to bind to ABCA1 are seen, which result in slowing down the reverse cholesterol transport and disturbances in HDL maturation due to decreased lecithin cholesterol ester transfer protein. Studies demonstrated that HDL of CKD patients loses its vasoprotective, antioxidative and anti-inflammatory properties and turns into a noxious particle which promotes endothelial dysfunction via stimulating superoxide production and limiting NO bioavailability. Alterations of HDL at the 'molecular and functional level' are also seen in renal transplant recipients even in those with excellent graft function.

  11. [Iron therapy in chronic kidney disease].

    PubMed

    Graczyk, Maciej; Kohmann, Anna

    Iron deficiency is one of the main causes of anemia in patients with chronic kidney disease, and iron supplements along the erythropoietin constitute the basis of its therapy. Among hemodialysis patients a preferred method of iron supplementation is an intravenous route, but the route of administration of iron to patients with nondialysis CKD raises a lot of controversy. Treatment with oral iron is cheap, does not require vascular access, but of lower efficacy due to insufficient absorption and frequent occurrence of side effects from the gastrointestinal, with discontinuation of therapy. Intravenous iron though effective is associated with the risk of allergic reactions, oxidative stress and the risk of iron overload. Modern oral medications may constitute an alternative to intravenous iron.

  12. Chronic kidney disease in postmenopausal women.

    PubMed

    Suzuki, Hiromichi; Kondo, Kazuoki

    2012-02-01

    Menopause is derived from the Greek words men (month) and pauses (cessation) and means permanent cessation of menstruation after the loss of ovarian activity. Chronic kidney disease (CKD) has recently been associated with cardiovascular events in several studies. CKD patients have a heavy burden of traditional cardiovascular risk factors in addition to a range of nontraditional risk factors such as inflammation and abnormal metabolism of calcium and phosphate. In this review, the association of CKD and cardiovascular disease (CVD), as well as of osteoporosis in postmenopausal women is discussed. CKD mineral and bone disorder, characterized by disturbances of calcium/phosphate/parathyroid hormone, bone abnormalities and vascular and soft tissue calcification, is highly prevalent in CKD and is a strong, independent predictor of bone fracture, CVD and death. Estrogen has been shown to: (a) decrease the expression of angiotensin type 1 receptors in vasculature and kidneys; (b) reduce the expression and activity of angiotensin-converting enzyme, and (c) cause the release of angiotensinogen substrate from the liver. However, the degree of activation or suppression of the renin-angiotensin-aldosterone system by estrogen has not been clearly established. Clinical data on the effects of estrogen therapy on bone mineral densities are extremely limited in the ESRD population. CVD is the most common cause of death in postmenopausal women with CKD and many contributing factors have been explored. Future research for prevention of CVD in postmenopausal women with CKD would focus on the biology of vascular calcification as well as bone loss.

  13. [Treatment of hypertension in chronic kidney disease].

    PubMed

    Palomo-Piñón, Silvia; Rosas-Peralta, Martín; Paniagua-Sierra, José Ramón

    2016-01-01

    Systemic arterial hypertension (SAH) is a progressive cardiovascular syndrome caused by complex and interrelated causes. The early markers of this syndrome are often present even before the blood pressure (BP) elevation; therefore, SAH cannot only be classified by the BP elevation threshold, which sometimes is discreet. Its progression is strongly associated with structural and functional cardiovascular abnormalities, which lead to end-organ damage (heart, kidney, brain, blood vessels and other organs), and cause premature morbidity and death. In this sense, the BP is only a biomarker of this cardiovascular syndrome, which is why it is more useful to consider individual BP patterns of the ill patient rather than a single BP threshold. The study and treatment of hypertension in chronic kidney disease (CKD) has made some progresses, especially in patients requiring dialysis. The use of non-invasive technology to register the BP has reconfigured health care of patients in regards to the diagnosis, circadian pattern, clinical surveillance, pharmacological prescription, prognosis, and risk of cardiovascular events (as well as mortality). The opportunity in the diagnosis and treatment means a delay in the onset of complications and, also, of dialysis. The blockade of the renin-aldotensin-aldosterone system (RAAS), a regular monitoring of the dry weight of the population in dialysis, and non-pharmacological interventions to modify lifestyle are the maneuvers with greater impact on the morbidity and mortality of patients.

  14. Central blood pressure and chronic kidney disease

    PubMed Central

    Ohno, Yoichi; Kanno, Yoshihiko; Takenaka, Tsuneo

    2016-01-01

    In this review, we focused on the relationship between central blood pressure and chronic kidney diseases (CKD). Wave reflection is a major mechanism that determines central blood pressure in patients with CKD. Recent medical technology advances have enabled non-invasive central blood pressure measurements. Clinical trials have demonstrated that compared with brachial blood pressure, central blood pressure is a stronger risk factor for cardiovascular (CV) and renal diseases. CKD is characterized by a diminished renal autoregulatory ability, an augmented direct transmission of systemic blood pressure to glomeruli, and an increase in proteinuria. Any elevation in central blood pressure accelerates CKD progression. In the kidney, interstitial inflammation induces oxidative stress to handle proteinuria. Oxidative stress facilitates atherogenesis, increases arterial stiffness and central blood pressure, and worsens the CV prognosis in patients with CKD. A vicious cycle exists between CKD and central blood pressure. To stop this cycle, vasodilator antihypertensive drugs and statins can reduce central blood pressure and oxidative stress. Even in early-stage CKD, mineral and bone disorders (MBD) may develop. MBD promotes oxidative stress, arteriosclerosis, and elevated central blood pressure in patients with CKD. Early intervention or prevention seems necessary to maintain vascular health in patients with CKD. PMID:26788468

  15. Antibody-Mediated Rejection Due to Preexisting versus De Novo Donor-Specific Antibodies in Kidney Allograft Recipients.

    PubMed

    Aubert, Olivier; Loupy, Alexandre; Hidalgo, Luis; Duong van Huyen, Jean-Paul; Higgins, Sarah; Viglietti, Denis; Jouven, Xavier; Glotz, Denis; Legendre, Christophe; Lefaucheur, Carmen; Halloran, Philip F

    2017-03-02

    Antibody-mediated rejection (ABMR) can occur in patients with preexisting anti-HLA donor-specific antibodies (DSA) or in patients who develop de novo DSA. However, how these processes compare in terms of allograft injury and outcome has not been addressed. From a cohort of 771 kidney biopsy specimens from two North American and five European centers, we performed a systematic assessment of clinical and biologic parameters, histopathology, circulating DSA, and allograft gene expression for all patients with ABMR (n=205). Overall, 103 (50%) patients had preexisting DSA and 102 (50%) had de novo DSA. Compared with patients with preexisting DSA ABMR, patients with de novo DSA ABMR displayed increased proteinuria, more transplant glomerulopathy lesions, and lower glomerulitis, but similar levels of peritubular capillaritis and C4d deposition. De novo DSA ABMR was characterized by increased expression of IFNγ-inducible, natural killer cell, and T cell transcripts, but less expression of AKI transcripts compared with preexisting DSA ABMR. The preexisting DSA ABMR had superior graft survival compared with the de novo DSA ABMR (63% versus 34% at 8 years after rejection, respectively; P<0.001). After adjusting for clinical, histologic, and immunologic characteristics and treatment, we identified de novo DSA ABMR (hazard ratio [HR], 1.82 compared with preexisting DSA ABMR; 95% confidence interval [95% CI], 1.07 to 3.08; P=0.03); low eGFR (<30 ml/min per 1.73 m(2)) at diagnosis (HR, 3.27; 95% CI, 1.48 to 7.23; P<0.001); ≥0.30 g/g urine protein-to-creatinine ratio (HR, 2.44; 95% CI, 1.47 to 4.09; P<0.001); and presence of cg lesions (HR, 2.25; 95% CI, 1.34 to 3.79; P=0.002) as the main independent determinants of allograft loss. Our findings support the transplant of kidneys into highly sensitized patients and should encourage efforts to monitor patients for de novo DSA.

  16. Burden of chronic kidney disease: North Africa

    PubMed Central

    Barsoum, Rashad S

    2013-01-01

    North Africa (NAF) is composed of six countries located in the African Sahara, namely the Western Sahara, Morocco, Algeria, Tunisia, Libya, and Egypt. Common features between these countries include similar climate, ecology, population genetics, and the socioeconomic environment. This commonality reflects on the chronic kidney disease (CKD) profile in these countries. While there are some estimates on the epidemiology of end-stage kidney disease, that of earlier stages is unknown. Several national screening programs are currently addressing this issue, such as the EGIPT-CKD project in Egypt and the MAREMAR study in Morocco. Preliminary results from the former suggest a prevalence of proteinuria in 10.6% of the relatives of patients on regular dialysis treatment. Despite the lack of reliable registries, it was possible to gather information on the etiology of CKD by direct contact with leading nephrologists in those countries. It turns out that glomerulonephritis (GN) accounts for 9–20%, diabetes 11–18%, hypertensive nephrosclerosis 10–35%, chronic interstitial nephritis 7–17%, and polycystic disease 2–3%. Compared to two decades earlier, diabetes has become more common at the expense of GN, proliferative GN, and amyloidosis regressed in favor of IgA and membranous nephropathies in Tunisian adults. Conventional schistosomal nephropathies are regressing in favor of hepatitis C viral (HCV) nephropathy in Egyptians. Focal segmental glomerulosclerosis is increasing at the expense of proliferative GNs in the region at large. Access to regular dialysis has been optimized during the past decade, with favorable outcomes despite the high incidence of HCV infection, tuberculosis, and protein-calorie malnutrition. Kidney transplantation is available in all NAF countries except the Western Sahara. About 650 transplants are performed annually from live donors, the majority in Egypt, where data from the largest center in Mansoura display a 10-year graft survival of 62

  17. Neprilysin inhibition in chronic kidney disease

    PubMed Central

    Judge, Parminder; Haynes, Richard; Landray, Martin J.; Baigent, Colin

    2015-01-01

    Despite current practice, patients with chronic kidney disease (CKD) are at increased risk of progression to end-stage renal disease and cardiovascular events. Neprilysin inhibition (NEPi) is a new therapeutic strategy with potential to improve outcomes for patients with CKD. NEPi enhances the activity of natriuretic peptide systems leading to natriuresis, diuresis and inhibition of the renin–angiotensin system (RAS), which could act as a potentially beneficial counter-regulatory system in states of RAS activation such as chronic heart failure (HF) and CKD. Early NEPi drugs were combined with angiotensin-converting enzyme inhibitors but were associated with unacceptable rates of angioedema and, therefore, withdrawn. However, one such agent (omapatrilat) showed promise of NEP/RAS inhibition in treating CKD in animal models, producing greater reductions in proteinuria, glomerulosclerosis and tubulointerstitial fibrosis compared with isolated RAS inhibition. A new class of drug called angiotensin receptor neprilysin inhibitor (ARNi) has been developed. One such drug, LCZ696, has shown substantial benefits in trials in hypertension and HF. In CKD, HF is common due to a range of mechanisms including hypertension and structural heart disease (including left ventricular hypertrophy), suggesting that ARNi could benefit patients with CKD by both retarding the progression of CKD (hence delaying the need for renal replacement therapy) and reducing the risk of cardiovascular disease. LCZ696 is now being studied in a CKD population. PMID:25140014

  18. Neprilysin inhibition in chronic kidney disease.

    PubMed

    Judge, Parminder; Haynes, Richard; Landray, Martin J; Baigent, Colin

    2015-05-01

    Despite current practice, patients with chronic kidney disease (CKD) are at increased risk of progression to end-stage renal disease and cardiovascular events. Neprilysin inhibition (NEPi) is a new therapeutic strategy with potential to improve outcomes for patients with CKD. NEPi enhances the activity of natriuretic peptide systems leading to natriuresis, diuresis and inhibition of the renin-angiotensin system (RAS), which could act as a potentially beneficial counter-regulatory system in states of RAS activation such as chronic heart failure (HF) and CKD. Early NEPi drugs were combined with angiotensin-converting enzyme inhibitors but were associated with unacceptable rates of angioedema and, therefore, withdrawn. However, one such agent (omapatrilat) showed promise of NEP/RAS inhibition in treating CKD in animal models, producing greater reductions in proteinuria, glomerulosclerosis and tubulointerstitial fibrosis compared with isolated RAS inhibition. A new class of drug called angiotensin receptor neprilysin inhibitor (ARNi) has been developed. One such drug, LCZ696, has shown substantial benefits in trials in hypertension and HF. In CKD, HF is common due to a range of mechanisms including hypertension and structural heart disease (including left ventricular hypertrophy), suggesting that ARNi could benefit patients with CKD by both retarding the progression of CKD (hence delaying the need for renal replacement therapy) and reducing the risk of cardiovascular disease. LCZ696 is now being studied in a CKD population.

  19. [Chronic kidney disease : What is currently available for treatment?

    PubMed

    Fleig, S; Patecki, M; Schmitt, R

    2016-12-01

    Chronic kidney disease is common in the general population with an estimated prevalence of roughly 2 million in Germany. Typically, chronic kidney disease is progressive and in the terminal stage the patients require dialysis or kidney transplantation. In many cases the disease remains silent for a long time but early stages are already associated with increasing morbidity and mortality. Therefore early detection is very important. In recent years several new concepts have been introduced that might help to slow the progression of chronic kidney disease or improve the accompanying risks. Here, we want to provide a nephrologist's perspective on the current guidelines for the treatment and prevention of chronic kidney disease. We summarize which diagnostic approaches are useful for general practitioners and we take a pragmatic look at the existing opportunities for combating renal functional decline. We also shed light on established measures to minimize the risk of comorbidities.

  20. C1q binding is not an independent risk factor for kidney allograft loss after an acute antibody-mediated rejection episode: a retrospective cohort study.

    PubMed

    Moktefi, Anissa; Parisot, Juliette; Desvaux, Dominique; Canoui-Poitrine, Florence; Brocheriou, Isabelle; Peltier, Julie; Audard, Vincent; Kofman, Tomek; Suberbielle, Caroline; Lang, Philippe; Rondeau, Eric; Grimbert, Philippe; Matignon, Marie

    2017-03-01

    After kidney transplantation, C4d is an incomplete marker of acute antibody-mediated rejection (AMR) and C1q-binding donor-specific antibodies (DSA) have been associated with allograft survival. However, the impact on allograft survival of C1q+ DSA after clinical AMR has not been studied yet. We analysed retrospectively in clinical AMR C4d staining and C1q-binding impact on allograft survival. We compared clinical, histological and serological features of C4d- and C4d+ AMR, C1q+ and C1q- DSA AMR and analysed C4d and C1q-binding impact on allograft survival. Among 500 for-cause kidney allograft biopsies, 48 fulfilled AMR criteria. C4d+ AMR [N = 18 (37.5%)] have significantly higher number class I DSA (P = 0.02), higher microvascular score (P = 0.02) and more transplant glomerulopathy (P = 0.04). C1q+ AMR [N = 20 (44%)] presented with significantly more class I and class II DSA (P = 0.005 and 0.04) and C4d+ staining (P = 0.01). Graft losses were significantly higher in the C4d+ group (P = 0.04) but similar in C1q groups. C4d+ but not C1q+ binding was an independent risk factor for graft loss [HR = 2.65; (1.11-6.34); P = 0.028]. In our cohort of clinical AMR, C4d+ staining but not C1q+ binding is an independent risk factor for graft loss. Allograft loss and patient survival were similar in C1q+ and C1q- AMR.

  1. [Ureterostomy cytomegalovirus infection presenting as stoma ulceration in a kidney allograft receptor: a case report].

    PubMed

    Rico, J E; Cardona, X; Rodelo, J; Reino, A; Arias, L F; Arbeláez, M

    2008-06-01

    Cytomegalovirus (CMV) is the most common viral infection affecting transplant patients, but urinary tract involvement has been rare. Only a few cases of symptomatic ureteritis have been reported in renal transplant recipients. In previous reports the presentation of CMV ureteritis is obstructive nephropathy, often in the absence of systemic illness, or rarely it may also mimic allograft rejection with minimal obstructive symptoms. We describe an additional case of CMV ureteritis in a patient with cutaneous ureterostomy. The unusual clinical presentation with urinary infection symptoms and ureterostomy stoma ulceration constitute a very particular presentation. The increasing report cases with CMV ureteritis suggest an increase of this post-transplant complication.

  2. Hormones and arterial stiffness in patients with chronic kidney disease.

    PubMed

    Gungor, Ozkan; Kircelli, Fatih; Voroneanu, Luminita; Covic, Adrian; Ok, Ercan

    2013-01-01

    Cardiovascular disease constitutes the major cause of mortality in patients with chronic kidney disease. Arterial stiffness is an important contributor to the occurrence and progression of cardiovascular disease. Various risk factors, including altered hormone levels, have been suggested to be associated with arterial stiffness. Based on the background that chronic kidney disease predisposes individuals to a wide range of hormonal changes, we herein review the available data on the association between arterial stiffness and hormones in patients with chronic kidney disease and summarize the data for the general population.

  3. Chronic kidney disease and pregnancy: maternal and fetal outcomes.

    PubMed

    Fischer, Michael J

    2007-04-01

    Chronic kidney disease complicates an increasing number of pregnancies, and at least 4% of childbearing-aged women are afflicted by this condition. Although diabetic nephropathy is the most common type of chronic kidney disease found in pregnant women, a variety of other primary and systemic kidney diseases also commonly occur. In the setting of mild maternal primary chronic kidney disease (serum creatinine <1.3 mg/dL) without poorly controlled hypertension, most pregnancies result in live births and maternal kidney function is unaffected. In cases of more moderate and severe maternal primary chronic kidney disease, the incidence of fetal prematurity, low birth weight, and death increase substantially, and the risk of accelerated irreversible decline in maternal kidney function, proteinuria, and hypertensive complications rise dramatically. In addition to kidney function, maternal hypertension and proteinuria portend negative outcomes and are important factors to consider when risk stratifying for fetal and maternal complications. In the setting of diabetic nephropathy and lupus nephropathy, other systemic disease features such as disease activity, the presence of antiphospholipid antibodies, and glycemic control play important roles in determining pregnancy outcomes. Concomitant with advances in obstetrical management and kidney disease treatments, it appears that the historically dismal maternal and fetal outcomes have greatly improved.

  4. HLA Matching at the Eplet Level Protects Against Chronic Lung Allograft Dysfunction.

    PubMed

    Walton, D C; Hiho, S J; Cantwell, L S; Diviney, M B; Wright, S T; Snell, G I; Paraskeva, M A; Westall, G P

    2016-09-01

    Donor selection in lung transplantation (LTx) is historically based upon clinical urgency, ABO compatibility, and donor size. HLA matching is not routinely considered; however, the presence or later development of anti-HLA antibodies is associated with poorer outcomes, particularly chronic lung allograft dysfunction (CLAD). Using eplet mismatches, we aimed to determine whether donor/recipient HLA incompatibility was a significant predictor of CLAD. One hundred seventy-five LTx undertaken at the Alfred Hospital between 2008 and 2012 met criteria. Post-LTx monitoring was continued for at least 12 months, or until patient death. HLA typing was performed by sequence-based typing and Luminex sequence-specific oligonucleotide. Using HLAMatchmaker, eplet mismatches between each donor/recipient pairing were analyzed and correlated against incidences of CLAD. HLA-DRB1/3/4/5+DQA/B eplet mismatch was a significant predictor of CLAD (hazard ratio [HR] 3.77, 95% confidence interval [CI]: 1.71-8.29 p < 0.001). When bronchiolitis obliterans syndrome (BOS) and restrictive allograft syndrome (RAS) were analyzed independently, HLA-DRB1/3/4/5 + DQA/B eplet mismatch was shown to significantly predict RAS (HR 8.3, 95% CI: 2.46-27.97 p < 0.001) but not BOS (HR 1.92, 95% CI: 0.64-5.72, p = 0.237). HLA-A/B eplet mismatch was shown not to be a significant predictor when analyzed independently but did provide additional stratification of results. This study illustrates the importance of epitope immunogenicity in defining donor-recipient immune compatibility in LTx.

  5. Chronic cardiac allograft rejection: critical role of ED-A(+) fibronectin and implications for targeted therapy strategies.

    PubMed

    Franz, Marcus; Neri, Dario; Berndt, Alexander

    2012-03-01

    Chronic cardiac allograft rejection is characterized by cardiac allograft vasculopathy (CAV) and cardiac interstitial fibrosis (CIF) causing severe long-term complications after heart transplantation and determining allograft function and patients' prognosis. Until now, there have been no sufficient preventive or therapeutic strategies. CAV and CIF are accompanied by changes in the extracellular matrix, including re-expression of the fetal fibronectin splice variant known as ED-A(+) fibronectin. This molecule has been shown to be crucial for the development of myofibroblasts (MyoFbs) as the main cell type in CIF and for the activation of vascular smooth muscle cells (VSMCs) as the main cell type in CAV. Relevant re-expression and protein deposition of ED-A(+) fibronectin has been demonstrated in animal models of chronic rejection, with spatial association to CAV and CIF, and a quantitative correlation to the rejection grade. The paper by Booth et al published in this issue of The Journal of Pathology could prove for the first time the functional importance of ED-A(+) fibronectin for the development of CIF as a main component of chronic cardiac rejection. Thus, promising conclusions for the development of new diagnostic, preventive, and therapeutic strategies for chronic cardiac rejection focusing on ED-A(+) fibronectin can be suggested.

  6. Chronic Kidney Disease: Highlights for the General Pediatrician

    PubMed Central

    Quigley, Raymond

    2012-01-01

    Chronic kidney disease in the pediatric population has been increasing. Early detection and treatment can slow down the progression of kidney disease and help prevent the development of end stage renal disease. In addition, as the kidney function declines, there are many pathophysiologic interactions with other organ systems that need to be monitored and treated. In particular, because of impaired vitamin D metabolism, calcium and phosphorus homeostasis is dysregulated and results in secondary bone disease. Anemia is common due to a number of factors including impaired erythropoietin production. Growth is often impacted by chronic kidney disease but can be improved by proper treatment. Complications of chronic kidney disease can be minimized by proper monitoring and treatment of these parameters. The general pediatrician plays a critical role in this process. PMID:22829845

  7. Bone Marrow and Kidney Transplant for Patients With Chronic Kidney Disease and Blood Disorders

    ClinicalTrials.gov

    2017-03-21

    Chronic Kidney Disease; Acute Myeloid Leukemia (AML); Acute Lymphoblastic Leukemia (ALL); Chronic Myelogenous Leukemia (CML); Chronic Lymphocytic Leukemia (CLL); Non-Hodgkin's Lymphoma (NHL); Hodgkin Disease; Multiple Myeloma; Myelodysplastic Syndrome (MDS); Aplastic Anemia; AL Amyloidosis; Diamond Blackfan Anemia; Myelofibrosis; Myeloproliferative Disease; Sickle Cell Anemia; Autoimmune Diseases; Thalassemia

  8. Resistant Hypertension in Nondialysis Chronic Kidney Disease

    PubMed Central

    Stanzione, Giovanna; Conte, Giuseppe

    2013-01-01

    Resistant hypertension (RH) is defined as blood pressure (BP) that remains above the target of less than 140/90 mmHg in the general population and 130/80 mmHg in people with diabetes mellitus or chronic kidney disease (CKD) in spite of the use of at least three full-dose antihypertensive drugs including a diuretic or as BP that reaches the target by means of four or more drugs. In CKD, RH is a common condition due to a combination of factors including sodium retention, increased activity of the renin-angiotensin system, and enhanced activity of the sympathetic nervous system. Before defining the hypertensive patient as resistant it is mandatory to exclude the so-called “pseudoresistance.” This condition, which refers to the apparent failure to reach BP target in spite of an appropriate antihypertensive treatment, is mainly caused by white coat hypertension that is prevalent (30%) in CKD patients. Recently we have demonstrated that “true” RH represents an independent risk factor for renal and cardiovascular outcomes in CKD patients. PMID:23710342

  9. Gut microbiota in chronic kidney disease.

    PubMed

    Cigarran Guldris, Secundino; González Parra, Emilio; Cases Amenós, Aleix

    The intestinal microflora maintains a symbiotic relationship with the host under normal conditions, but its imbalance has recently been associated with several diseases. In chronic kidney disease (CKD), dysbiotic intestinal microflora has been reported with an increase in pathogenic flora compared to symbiotic flora. An enhanced permeability of the intestinal barrier, allowing the passage of endotoxins and other bacterial products to the blood, has also been shown in CKD. By fermenting undigested products that reach the colon, the intestinal microflora produce indoles, phenols and amines, among others, that are absorbed by the host, accumulate in CKD and have harmful effects on the body. These gut-derived uraemic toxins and the increased permeability of the intestinal barrier in CKD have been associated with increased inflammation and oxidative stress and have been involved in various CKD-related complications, including cardiovascular disease, anaemia, mineral metabolism disorders or the progression of CKD. The use of prebiotics, probiotics or synbiotics, among other approaches, could improve the dysbiosis and/or the increased permeability of the intestinal barrier in CKD. This article describes the situation of the intestinal microflora in CKD, the alteration of the intestinal barrier and its clinical consequences, the harmful effects of intestinal flora-derived uraemic toxins, and possible therapeutic options to improve this dysbiosis and reduce CKD-related complications.

  10. Contextual Poverty, Nutrition and Chronic Kidney Disease

    PubMed Central

    Gutiérrez, Orlando M.

    2014-01-01

    Nutrition plays an important role in chronic kidney disease (CKD) outcomes. One of the strongest factors that impacts nutrition is socioeconomic status as evidenced by the large body of epidemiologic data showing that income and education are directly associated with diet quality. Apart from individual-level markers of socioeconomic status such as income and education, contextual factors such as availability of and transportation to food outlets that provide healthy food options and the density of fast food restaurants within particular regions markedly impact the ability of individuals to comply with nutrition recommendations. This is particularly true for nutrition guidelines most specific to individuals with CKD such as the consumption of protein, saturated fat, sodium and phosphorus, all of which have been shown to impact CKD health and are influenced by the availability of healthy food options within individual neighborhood food environments. Because of the strong association of contextual poverty with the diet quality, any serious attempt to improve the diet of CKD patients must include a discussion of the environmental barriers that each individual faces in trying to access healthy foods and health care providers should take account of these barriers when tailoring specific recommendations. PMID:25573510

  11. Building the chronic kidney disease management team.

    PubMed

    Spry, Leslie

    2008-01-01

    The need to be efficient and the demands for performance-based service are changing how nephrologists deliver care. Chronic kidney disease (CKD) occurs in patients with complex medical and social problems. CKD management requires that multidisciplinary professionals provide patient education, disease management, and psychosocial support. To remain cost-efficient, many physicians are training and supervising midlevel practitioners in the delivery of specialized health care. Specialized care that meets present CKD patient needs is best delivered in a CKD clinic. Three models of CKD clinic are identified: (1) anemia management CKD clinic, (2) the basic CKD clinic, and (3) the comprehensive CKD clinic. Each clinic model is based on critical elements of staffing, billable services, and patient-focused health care. Billable services are anemia-management services, physician services that may be provided by midlevel practitioners, and medical nutrition therapy. In some cases, social worker services may be billable. Building a patient-focused clinic that offers CKD management requires planning, familiarity with federal regulations and statutes, and skillful practitioners. Making services cost-efficient and outcome oriented requires careful physician leadership, talented midlevel practitioners, and billing professionals who understand the goals of the CKD clinic. As Medicare payment reforms evolve, a well-organized CKD program can be well poised to meet the requirements of payers and congressional mandates for performance-based purchasing.

  12. Chronic kidney disease and fragility fracture.

    PubMed

    Kazama, Junichiro James

    2017-03-01

    Osteoporosis is defined simply as "a skeletal disorder characterized by compromised bone strength predisposing to an increased risk of fracture. Thus, any bone lesion that causes fragility fracture is osteoporosis, which has quite heterogeneous backgrounds. Chronic kidney disease-related bone and mineral disease (CKD-MBD) is defined as "a systemic disorder of mineral and bone metabolism due to CKD, which is manifested by abnormalities in bone and mineral metabolism and/or extra-skeletal calcification". Although CKD-MBD is one of the possible causes of osteoporosis, we do not have evidences that CKD-MBD is the only or crucial determinant of bone mechanical strength in CKD patients. The risk of hip fracture is considerably high in CKD patients. Drugs that intervene in systemic mineral metabolism, indeed, lead to the improvement on bone histology in CKD patients. However, it remains unclear whether the intervention in systemic mineral metabolism also improves bone strength, today. Thus, the use of drugs that directly act on bone and the introduction of fracture liaison concept are promising strategies for fragility fracture prevention among CKD patients, as well as treatment for CKD-MBD.

  13. Neurological complications in chronic kidney disease

    PubMed Central

    Arnold, Ria; Issar, Tushar; Krishnan, Arun V

    2016-01-01

    Patients with chronic kidney disease (CKD) are frequently afflicted with neurological complications. These complications can potentially affect both the central and peripheral nervous systems. Common neurological complications in CKD include stroke, cognitive dysfunction, encephalopathy, peripheral and autonomic neuropathies. These conditions have significant impact not only on patient morbidity but also on mortality risk through a variety of mechanisms. Understanding the pathophysiological mechanisms of these conditions can provide insights into effective management strategies for neurological complications. This review describes clinical management of neurological complications in CKD with reference to the contributing physiological and pathological derangements. Stroke, cognitive dysfunction and dementia share several pathological mechanisms that may contribute to vascular impairment and neurodegeneration. Cognitive dysfunction and dementia may be differentiated from encephalopathy which has similar contributing factors but presents in an acute and rapidly progressive manner and may be accompanied by tremor and asterixis. Recent evidence suggests that dietary potassium restriction may be a useful preventative measure for peripheral neuropathy. Management of painful neuropathic symptoms can be achieved by pharmacological means with careful dosing and side effect considerations for reduced renal function. Patients with autonomic neuropathy may respond to sildenafil for impotence. Neurological complications often become clinically apparent at end-stage disease, however early detection and management of these conditions in mild CKD may reduce their impact at later stages. PMID:27867500

  14. HLA-DRB1 and susceptibility to kidney allograft rejection in Southern Iranian patients.

    PubMed

    Gharesi-Fard, Behrouz; Rezanezhad, Leila; Karimi, Mohammad Hossein; Geramizadeh, Bita; Salehipour, Mohammad Mehdi; Hosseini, Seyed Ali Malek; Roozbeh, Jamshid

    2014-08-01

    Kidney transplantation is the best treatment option for the patients with end-stage renal disease. Viral infections and genetic factors such as HLA-II antigens may affect the kidney transplant outcome. The compatibility of HLA-DRB1 molecules in the survival of kidney transplant is important. Also, the correlation between these molecules and viral infections is significant. The current study investigates the allele frequency of HLA-DRB1 in 41 recipient kidney transplant and 203 normal healthy controls by polymerase chain reaction using sequence specific primers. Moreover the relation between HLA-DRB1 allelic groups and hepatitis B, hepatitis C and cytomegalovirus viral infections was also studied. However statistical analysis of the allele frequencies didn't show any significant association between HLA-DRB1 allelic group distributions or sharing and susceptibility to acute kidney transplant rejection (P > 0.05). Comparing the allele frequencies between HLA-DRB1*14 and DRB1*04 allelic showed a significant difference in controls and patients (P = 0.03 and P = 0.05 respectively). The results of the present study also showed a significant association between possession of HLA-DRB1*07 allele in kidney transplant recipients and hepatitis C virus infection (P = 0.009). In conclusion however the results of the present study did not showed relation between HLA-DRB1 allele's frequencies or sharing and kidney transplantation outcome, the results indicated that HLA-DRB1 alleles may susceptible individuals to renal disease or play a role in susceptibility to viral infection in kidney transplant patients.

  15. The utility of cytodiagnostic urinalysis as a tool to diagnose kidney allograft dysfunction in the era lymphocyte-depleting induction therapy.

    PubMed

    Mehta, T; Sanaei-Ardekani, M; Farooqi, A; Khan, S; Shammas, A; Boonyapredee, M; Allston, C; Wu, J; Nsouli, H; Pehlivanova, M

    2011-12-01

    Cytodiagnostic urinalysis (CDU) has been used to evaluate causes of kidney allograft dysfunction, such as an acute rejection episode (ARE), calcineurin inhibitor (CNI) toxicity, or polyoma virus infection. We examined the concordance between CDU and allograft biopsy in patients with allograft dysfunction. Between 2002 and 2006, 201 patients had CDU performed within 7 days of a biopsy. The cohort was black (73%) with, male preponderance (59.2%), and an overall mean age of 48±13 years with 46% having received a deceased donor kidney. The induction regimen consisted of either antithymocyte globulin or alemtuzumab. CDU results that demonstrated 5 to 10 lymphocytes per high-power field (HPF) and >20 lymphocytes/HPF had 2.5 increased odds of predicting acute rejection (AR) on biopsy (odds ratio [OR] 2.5; 95% confidence interval [CI] 1.12-5.79; P=.025). In the era of antithymocyte globulin induction, a CDU result demonstrating>5 lymphocytes/HPF had a 4.3 increased odds of predicting AR (CI 1.76-10.50; P=.001). This association was lost with alemtuzumab induction. A positive CDU result for calcineurin inhibitor (CNI) toxicity did not predict CNI nephrotoxcity on biopsy, but a positive CDU for polyoma virus infection predicted polyoma virus nephropathy (OR 22.18; CI: 4.41-111.63; P<.001). In conclusion, CDU is an adjunctive diagnostic tool for kidney transplantation.

  16. Genetic polymorphisms of Interleukin-18 are not associated with allograft function in kidney transplant recipients

    PubMed Central

    do Nascimento, Wenna Gleyce Araújo; Cilião, Daiani Alves; Genre, Julieta; Gondim, Dikson Dibe; Alves, Renata Gomes; Hassan, Neife Deghaide; Lima, Francisco Pignataro; Pereira, Maurício Galvão; Donadi, Eduardo Antônio; de Oliveira Crispim, Janaina Cristiana

    2014-01-01

    Interleukin 18 (IL-18) is a proinflammatory cytokine that plays a role in host defense by upregulating both innate and acquired immune responses. Analysis of IL18 polymorphisms may be clinically important since their roles have been recognized in a variety of inflammatory and autoimmune disorders. However, the role of this cytokine polymorphisms in kidney transplant still remains unclear. In this study, we evaluated the associations between IL18 polymorphisms and graft function assessed by creatinine clearance in kidney transplant recipients. A total of 82 kidney transplant recipients and 183 healthy controls were enrolled, and frequencies of alleles, genotypes and haplotypes for IL18 polymorphisms were determined and compared with creatinine clearance. The -607C/A (rs1946518) and -137C/G (rs187238) variant alleles in the IL18 gene were determined by polymerase chain reaction. In our study, no significant association was found between the IL18 variants and creatinine clearance (p > 0.05). Nonetheless, polymorphism analysis revealed an increase in the frequency of the IL18 major haplotype -607C/-137G in kidney transplant patients (odds ratio 2.57, 95% confidence interval 1.45–4.55, p = 0.0014). Finally, we found that IL18 polymorphisms did not influence the renal function and that IL18 haplotype -607C/-137G seems to be associated with kidney transplant recipients. PMID:25071398

  17. Con: Phosphate binders in chronic kidney disease

    PubMed Central

    Kestenbaum, Bryan

    2016-01-01

    Phosphate binders are prescribed to chronic kidney disease (CKD) patients based on associations of serum phosphate concentrations with mortality and calcification, experimental evidence for direct calcifying effects of phosphate on vascular smooth muscle tissue and the central importance of phosphate retention in CKD-mineral and bone disorder (CKD-MBD). Current knowledge regarding phosphate metabolism in CKD provides important insight into disease mechanisms and supports future clinical trials of phosphate binders in CKD patients to determine the impact of these medications on clinically relevant outcomes. The risks and benefits of phosphate binders cannot be inferred from association studies of serum phosphate concentrations, which are inconsistent and subject to confounding, animal-experimental data, which are based on conditions that differ from human disease, or physiological arguments, which are limited to known regulatory factors. Many interventions that targeted biochemical pathways suggested by association studies and suspected biological importance have yielded null or harmful results. Clinical trials of phosphate binders are of high clinical and scientific importance to nephrology. Demonstration of reduced rates of clinical disease in such trials could lead to important health benefits for CKD patients, whereas negative results would refocus efforts to understand and treat CKD-MBD. Clinical trials that employ highly practical or ‘pragmatic’ designs represent an optimal approach for determining the safety and effectiveness of phosphate binders in real-world settings. Absent clinical trial data, observational studies of phosphate binders in large CKD populations could provide important information regarding the benefits, risks and/or unintended side effects of these medications. PMID:26681747

  18. Con: Phosphate binders in chronic kidney disease.

    PubMed

    Kestenbaum, Bryan

    2016-02-01

    Phosphate binders are prescribed to chronic kidney disease (CKD) patients based on associations of serum phosphate concentrations with mortality and calcification, experimental evidence for direct calcifying effects of phosphate on vascular smooth muscle tissue and the central importance of phosphate retention in CKD-mineral and bone disorder (CKD-MBD). Current knowledge regarding phosphate metabolism in CKD provides important insight into disease mechanisms and supports future clinical trials of phosphate binders in CKD patients to determine the impact of these medications on clinically relevant outcomes. The risks and benefits of phosphate binders cannot be inferred from association studies of serum phosphate concentrations, which are inconsistent and subject to confounding, animal-experimental data, which are based on conditions that differ from human disease, or physiological arguments, which are limited to known regulatory factors. Many interventions that targeted biochemical pathways suggested by association studies and suspected biological importance have yielded null or harmful results. Clinical trials of phosphate binders are of high clinical and scientific importance to nephrology. Demonstration of reduced rates of clinical disease in such trials could lead to important health benefits for CKD patients, whereas negative results would refocus efforts to understand and treat CKD-MBD. Clinical trials that employ highly practical or 'pragmatic' designs represent an optimal approach for determining the safety and effectiveness of phosphate binders in real-world settings. Absent clinical trial data, observational studies of phosphate binders in large CKD populations could provide important information regarding the benefits, risks and/or unintended side effects of these medications.

  19. Non-HLA antibodies to immunogenic epitopes predict the evolution of chronic renal allograft injury.

    PubMed

    Sigdel, Tara K; Li, Li; Tran, Tim Q; Khatri, Purvesh; Naesens, Maarten; Sansanwal, Poonam; Dai, Hong; Hsieh, Szu-chuan; Sarwal, Minnie M

    2012-04-01

    Chronic allograft injury (CAI) results from a humoral response to mismatches in immunogenic epitopes between the donor and recipient. Although alloantibodies against HLA antigens contribute to the pathogenesis of CAI, alloantibodies against non-HLA antigens likely contribute as well. Here, we used high-density protein arrays to identify non-HLA antibodies in CAI and subsequently validated a subset in a cohort of 172 serum samples collected serially post-transplantation. There were 38 de novo non-HLA antibodies that significantly associated with the development of CAI (P<0.01) on protocol post-transplant biopsies, with enrichment of their corresponding antigens in the renal cortex. Baseline levels of preformed antibodies to MIG (also called CXCL9), ITAC (also called CXCL11), IFN-γ, and glial-derived neurotrophic factor positively correlated with histologic injury at 24 months. Measuring levels of these four antibodies could help clinicians predict the development of CAI with >80% sensitivity and 100% specificity. In conclusion, pretransplant serum levels of a defined panel of alloantibodies targeting non-HLA immunogenic antigens associate with histologic CAI in the post-transplant period. Validation in a larger, prospective transplant cohort may lead to a noninvasive method to predict and monitor for CAI.

  20. Better recovery of kidney function in patients with de novo chronic kidney disease after partial nephrectomy compared with those with pre-existing chronic kidney disease.

    PubMed

    Takagi, Toshio; Kondo, Tsunenori; Iizuka, Junpei; Omae, Kenji; Kobayashi, Hirohito; Hashimoto, Yasunobu; Yoshida, Kazuhiko; Tanabe, Kazunari

    2014-06-01

    We compared kidney functional recovery between patients with pre-existing chronic kidney disease, those with de novo chronic kidney disease and those with normal kidney function, after partial nephrectomy. A total of 311 patients who underwent partial nephrectomy at Tokyo Women's Medical University Hospital, Tokyo, Japan, between January 2004 and July 2011 with sufficient kidney functional data participated in the study. Patients with pre-existing chronic kidney disease (group1: 78 patients) were defined as those with estimated glomerular filtration rate under 60 mL/min/m(2) before partial nephrectomy. Patients with de novo chronic kidney disease (group 2: 49) were defined as those with estimated glomerular filtration rate over 60 mL/min/m(2) before surgery and who developed estimated glomerular filtration rate under 60 mL/min/m(2) 3 months after partial nephrectomy. Normal patients (group 3: 184) were defined as those with estimated glomerular filtration rate over 60 mL/min/m(2) both before and after partial nephrectomy. Group 1 was associated with older age and higher comorbidity, including hypertension and diabetes mellitus, compared with other groups. R.E.N.A.L. score was not significantly different between the groups. Although the percent change of estimated glomerular filtration rate between the preoperative period and 3 months after partial nephrectomy in group 2 was significantly decreased compared with that in other groups (group 1: -6.8%, group 2: -18%, group 3: -7.3%), the renal functional recovery between 3 and 12 months after partial nephrectomy in group 2 was better than that in other groups (group 1: -0.5%, group 2: 5.6%, group 3: -0.4%). Patients with de novo chronic kidney disease had better kidney functional recovery than the other two groups, which might suggest that they were surgically assaulted and developed chronic kidney disease in the early postoperative period, and were essentially different from those with pre-existing chronic kidney

  1. Early Kidney Allograft Dysfunction (Threatened Allograft): Comparative Effectiveness of Continuing Versus Discontinuation of Tacrolimus and Use of Sirolimus to Prevent Graft Failure: A Retrospective Patient-Centered Outcome Study

    PubMed Central

    Wali, Ravinder K.; Prentice, Heather A.; Reddivari, Venkata; Baffoe-Bonnie, Geroge; Drachenberg, Cinthia I.; Pappadimitriou, John C.; Ramos, Emilio; Cooper, Matthew; Jonsson, Johann; Bartlett, Stephen; Weir, Matthew R.

    2016-01-01

    Background Due to lack of treatment options for early acute allograft dysfunction in the presence of tubular-interstitial injury without histological features of rejection, kidney transplant recipients are often treated with sirolimus-based therapy to prevent cumulative calcineurin inhibitor exposure and to prevent premature graft failure. Methods We analyzed transplant recipients treated with sirolimus-based (n = 220) compared with continued tacrolimus-based (n = 276) immunosuppression in recipients of early-onset graft dysfunction (threatened allograft) with the use of propensity score-based inverse probability treatment weighted models to balance for potential confounding by indication between 2 nonrandomized groups. Results Weighted odds for death-censored graft failure (odds ratio [OR], 1.20; 95% confidence interval [95% CI], 0.66-2.19, P = 0.555) was similar in the 2 groups, but a trend for increased risk of greater than 50% loss in estimated glomerular filtration rate from baseline in sirolimus group (OR, 1.90; 95% CI, 0.96-3.76; P = 0.067) compared with tacrolimus group. Sirloimus group compared with tacrolimus group had increased risk for death with functioning graft (OR, 2.01; 95% CI, 1.29-3.14; P = 0.002) as well as increased risk of late death (death after graft failure while on dialysis) (OR, 2.39; 95% CI, 1.59-3.59; P < 0.001). Analysis of subgroups based on the absence or presence of T cell–mediated rejection or tubulointerstitial inflammation in the index biopsy, or the use of different types of induction agents, and all subgroups had increased risk of death with functioning graft and late death if exposed to sirolimus-based therapy. Conclusions Use of sirolimus compared with tacrolimus in recipients with early allograft dysfunction during the first year of transplant may not prevent worsening of allograft function and could potentially lead to poor survival along with increased risk of late death. PMID:27795990

  2. Stop chronic kidney disease progression: Time is approaching

    PubMed Central

    Sharaf El Din, Usama Abdel Azim; Salem, Mona Mansour; Abdulazim, Dina Ossama

    2016-01-01

    Progression of chronic kidney disease (CKD) is inevitable. However, the last decade has witnessed tremendous achievements in this field. Today we are optimistic; the dream of withholding this progression is about to be realistic. The recent discoveries in the field of CKD management involved most of the individual diseases leading the patients to end-stage renal disease. Most of these advances involved patients suffering diabetic kidney disease, chronic glomerulonephritis, polycystic kidney disease, renal amyloidosis and chronic tubulointerstitial disease. The chronic systemic inflammatory status and increased oxidative stress were also investigated. This inflammatory status influences the anti-senescence Klotho gene expression. The role of Klotho in CKD progression together with its therapeutic value are explored. The role of gut as a major source of inflammation, the pathogenesis of intestinal mucosal barrier damage, the role of intestinal alkaline phosphatase and the dietary and therapeutic implications add a novel therapeutic tool to delay CKD progression. PMID:27152262

  3. Chronic Ifosfamide toxicity: kidney pathology and pathophysiology.

    PubMed

    Akilesh, Shreeram; Juaire, Noemie; Duffield, Jeremy S; Smith, Kelly D

    2014-05-01

    Ifosfamide is a nitrogen mustard alkylating agent used as both a first-line and a salvage chemotherapeutic agent in the treatment of testicular germ cell tumors, various sarcomas, carcinomas, and some lymphomas. A well-known complication of ifosfamide therapy is transient acute kidney injury. However, in a minority of patients, the reduction in kidney function is progressive and permanent, sometimes occurring long after exposure to ifosfamide. Scattered reports have described the pathologic findings in kidneys permanently affected by ifosfamide toxicity. We present the findings of an illustrative case and review the pathology and molecular mechanisms of long-term ifosfamide toxicity with implications for personalized medicine.

  4. Acute Kidney Allograft Rejection Precipitated by Lenalidomide Treatment for Multiple Myeloma.

    PubMed

    Lum, Erik L; Huang, Edmund; Bunnapradist, Suphamai; Pham, Thu; Danovitch, Gabriel

    2017-02-09

    Patients who develop malignancy after kidney transplantation typically undergo a reduction in immunosuppression and referral to an oncologist for chemotherapeutic considerations for the management of their malignancy. Traditional cytotoxic chemotherapy agents can result in kidney transplant injury, but the decision about which agents to be used has largely been determined by oncologists without the involvement of nephrologists. More recently, several classes of drugs with immunomodulatory actions have been approved for the treatment of cancer, including multiple myeloma. Activation of the immune system against malignant cells may have unintended consequences in solid-organ transplant recipients, who require suppression of the immune system to avoid transplant rejection. In this report, we present a case of acute kidney transplant rejection in a 65-year-old woman following administration of the newer immunomodulatory agent lenalidomide for the treatment of multiple myeloma. A greater awareness of the mechanisms of newly introduced chemotherapy agents and discussion with the treating oncologist and patient are paramount in caring for patients who develop malignancy following transplantation.

  5. Soluble BAFF Cytokine Levels and Antibody-Mediated Rejection of the Kidney Allograft.

    PubMed

    Slavcev, Antonij; Brozova, Jitka; Slatinska, Janka; Sekerkova, Zuzana; Honsova, Eva; Skibova, Jelena; Striz, Ilja; Viklicky, Ondrej

    2016-12-01

    The B-cell activating factor (BAFF) cytokine has important functions for the survival and maturation of B lymphocytes, which implies that this cytokine might play a role in the development of antibody-mediated rejection (AMR) after kidney transplantation. In our study, we compared the concentrations of the soluble BAFF cytokine in kidney graft recipients with AMR and patients without rejection with the goal of testing the hypothesis whether BAFF level measurement might be useful as a diagnostic marker of AMR. The study included a cohort of 19 high-risk patients with diagnosed AMR and 17 control patients free of rejection. BAFF was measured in all patients before transplantation, during the rejection episodes, and three months after transplantation in patients free of rejection using the Luminex technique. Before transplantation, the serum concentrations of BAFF in patients with AMR and kidney recipients without rejection did not significantly differ. After transplantation, however, BAFF levels were significantly lower in patients with AMR and also in patients with concurrent humoral and cellular rejection compared with patients without rejection (p < 0.05 and p < 0.01, respectively). No correlation was found between BAFF and the production of donor-specific antibodies (DSA) before and after transplantation. Patients experiencing AMR and simultaneous cellular and AMR had significantly lower concentrations of BAFF in comparison with patients free of rejection.

  6. Pregnancy across the spectrum of chronic kidney disease.

    PubMed

    Hladunewich, Michelle A; Melamad, Nir; Bramham, Kate

    2016-05-01

    Management of the pregnant woman with chronic kidney disease is difficult for both nephrologists and obstetricians. Prepregnancy counselling with respect to risk stratification, optimization of maternal health prior to pregnancy, as well as management of the many potential pregnancy-associated complications in this complex patient population remains challenging due to the paucity of large, well-designed clinical studies. Furthermore, the heterogeneity of disease and the relative infrequency of pregnancy, particularly in more advanced stages of chronic kidney disease, leaves many clinicians feeling ill prepared to manage these pregnancies. As such, counselling is imprecise and management varies substantially across centers. All pregnancies in women with chronic kidney disease can benefit from a collaborative multidisciplinary approach with a team that consists of nephrologists experienced in the management of kidney disease in pregnancy, maternal-fetal medicine specialists, high-risk pregnancy nursing staff, dieticians, and pharmacists. Further access to skilled neonatologists and neonatal intensive care unit support is essential given the risks for preterm delivery in this patient population. The goal of this paper is to highlight some of the data that currently exist in the literature, provide management strategies for the practicing nephrologist at all stages of chronic kidney disease, and explore some of the knowledge gaps where future multinational collaborative research efforts should concentrate to improve pregnancy outcomes in women with kidney disease across the globe.

  7. Th-17 Alloimmune Responses in Renal Allograft Biopsies From Recipients of Kidney Transplants Using Extended Criteria Donors During Acute T Cell-Mediated Rejection.

    PubMed

    Matignon, M; Aissat, A; Canoui-Poitrine, F; Grondin, C; Pilon, C; Desvaux, D; Saadoun, D; Barathon, Q; Garrido, M; Audard, V; Rémy, P; Lang, P; Cohen, J; Grimbert, P

    2015-10-01

    Although renal transplantation using expanded criteria donors has become a common practice, immune responses related to immunosenescence in those kidney allografts have not been studied yet in humans. We performed a retrospective molecular analysis of the T cell immune response in 43 kidney biopsies from patients with acute T cell-mediated rejection including 25 from recipients engrafted with a kidney from expanded criteria donor and 18 from recipients grafted with optimal kidney allograft. The clinical, transplant and acute T cell-mediated rejection characteristics of both groups were similar at baseline. The expression of RORγt, Il-17 and T-bet mRNA was significantly higher in the elderly than in the optimal group (p = 0.02, p = 0.036, and p = 0.01, respectively). Foxp3 mRNA levels were significantly higher in elderly patients experiencing successful acute T cell-mediated rejection reversal (p = 0.03). The presence of IL-17 mRNA was strongly associated with nonsuccessful reversal in elderly patients (p = 0.008). Patients with mRNA IL17 expression detection and low mRNA Foxp3 expression experienced significantly more treatment failure (87.5%) than patients with no mRNA IL17 expression and/or high mRNA Foxp3 expression (26.7%; p = 0.017). Our study suggests that the Th17 pathway is involved in pathogenesis and prognosis of acute T cell-mediated rejection in recipients of expanded criteria allograft.

  8. Chronic kidney disease of unknown etiology should be renamed chronic agrochemical nephropathy.

    PubMed

    Jayasinghe, Saroj

    2014-04-01

    Epidemics of chronic kidney disease not attributable to common causes have recently been observed in Central America and Asia. Since the etiology is unclear, the disease is often known by terms such as chronic kidney disease of unknown etiology. There is growing evidence that risk factors include rural agricultural work and agrochemical exposure. The disease should be renamed chronic agrochemical nephropathy to highlight the most likely etiology and draw attention to the condition.

  9. The double challenge of resistant hypertension and chronic kidney disease.

    PubMed

    Rossignol, Patrick; Massy, Ziad A; Azizi, Michel; Bakris, George; Ritz, Eberhard; Covic, Adrian; Goldsmith, David; Heine, Gunnar H; Jager, Kitty J; Kanbay, Mehmet; Mallamaci, Francesca; Ortiz, Alberto; Vanholder, Raymond; Wiecek, Andrzej; Zoccali, Carmine; London, Gérard Michel; Stengel, Bénédicte; Fouque, Denis

    2015-10-17

    Resistant hypertension is defined as blood pressure above goal despite adherence to a combination of at least three optimally dosed antihypertensive medications, one of which is a diuretic. Chronic kidney disease is the most frequent of several patient factors or comorbidities associated with resistant hypertension. The prevalence of resistant hypertension is increased in patients with chronic kidney disease, while chronic kidney disease is associated with an impaired prognosis in patients with resistant hypertension. Recommended low-salt diet and triple antihypertensive drug regimens that include a diuretic, should be complemented by the sequential addition of other antihypertensive drugs. New therapeutic innovations for resistant hypertension, such as renal denervation and carotid barostimulation, are under investigation especially in patients with advanced chronic kidney disease. We discuss resistant hypertension in chronic kidney disease stages 3-5 (ie, patients with an estimated glomerular filtration rate below 60 mL/min per 1·73 m(2) and not on dialysis), in terms of worldwide epidemiology, outcomes, causes and pathophysiology, evidence-based treatment, and a call for action.

  10. Treatment of chronic periodontitis decreases serum prohepcidin levels in patients with chronic kidney disease

    PubMed Central

    Vilela, Eduardo Machado; Bastos, Jessica Amaral; Fernandes, Natalia; Ferreira, Ana Paula; Chaoubah, Alfredo; Bastos, Marcus Gomes

    2011-01-01

    OBJECTIVE: To determine the impact of periodontal treatment on serum levels of prohepcidin (the prohormone of hepcidin) and systemic inflammation markers, as well as correlations among these markers, in patients with chronic periodontitis and chronic kidney disease who were not undergoing dialysis. METHODS: We included 56 chronic periodontitis patients, 36 with chronic kidney disease and 20 without systemic diseases and with normal renal function (control group). Chronic kidney disease was defined as suggested by the clinical practice guidelines in the National Kidney Foundation. Chronic periodontitis was defined through clinical attachment level and by probing pocket depth, according to the American Association of Periodontology. The inflammatory markers ultrasensitive C-reactive protein, interleukin-6, and prohepcidin were evaluated before and 3 months after periodontal treatment. RESULTS: The efficacy of periodontal treatment was confirmed by the improvement in clinical parameters of chronic periodontitis in the control and chronic kidney disease groups. Periodontal treatment resulted in significant reductions in ultrasensitive C-reactive protein, interleukin-6 and serum prohepcidin levels in both groups. Moreover, in multivariate linear regression, the reduction in prohepcidin after periodontal treatment was significantly and independently associated with interleukin-6 levels in the control group. CONCLUSIONS: By inducing a decline in the systemic inflammatory response and a decrease in serum prohepcidin, successful periodontal treatment may represent an important means of ameliorating the inflammatory burden seen in patients with chronic kidney disease. Trial registration: ISRCTN59866656. PMID:21655762

  11. Fatigue in chronic kidney disease: Definition, assessment and treatment.

    PubMed

    Zalai, Dora; Bohra, Miqdad

    2016-01-01

    Chronic fatigue--an overwhelming subjective feeling of mental or physical exhaustion--impacts patients' everyday functioning and quality of life, delays recovery after hemodialysis, and increases mortality. There are a number of factors that may perpetuate clinically significant fatigue among individuals with chronic kidney disease, including sleep disorders, depression, sedentary lifestyle, anemia, and chronic inflammation. Some of these factors (i.e., anemia and inflammation) are in the forefront of clinical attention, whereas the other contributing factors often remain unrecognized. This article provides a pragmatic overview of the definition, assessment, maintaining factors, and management of fatigue in chronic kidney disease. Given that chronic fatigue is a major determinant of patients' quality of life, nurses can bring about a fundamental improvement in patients' well-being if they recognize the most common fatigue-perpetuating factors and facilitate fatigue management interventions.

  12. Gene Expression Profiling of Bronchoalveolar Lavage Cells Preceding a Clinical Diagnosis of Chronic Lung Allograft Dysfunction

    PubMed Central

    Wang, Xiaoyan; Palchevskiy, Vyacheslav; Gregson, Aric L.; Patel, Naman; DerHovanessian, Ariss; Shino, Michael Y.; Sayah, David M.; Birjandi, Shirin; Lynch, Joseph P.; Saggar, Rajan; Ardehali, Abbas; Ross, David J.; Palmer, Scott M.; Elashoff, David; Belperio, John A.

    2017-01-01

    Background Chronic Lung Allograft Dysfunction (CLAD) is the main limitation to long-term survival after lung transplantation. Although CLAD is usually not responsive to treatment, earlier identification may improve treatment prospects. Methods In a nested case control study, 1-year post transplant surveillance bronchoalveolar lavage (BAL) fluid samples were obtained from incipient CLAD (n = 9) and CLAD free (n = 8) lung transplant recipients. Incipient CLAD cases were diagnosed with CLAD within 2 years, while controls were free from CLAD for at least 4 years following bronchoscopy. Transcription profiles in the BAL cell pellets were assayed with the HG-U133 Plus 2.0 microarray (Affymetrix). Differential gene expression analysis, based on an absolute fold change (incipient CLAD vs no CLAD) >2.0 and an unadjusted p-value ≤0.05, generated a candidate list containing 55 differentially expressed probe sets (51 up-regulated, 4 down-regulated). Results The cell pellets in incipient CLAD cases were skewed toward immune response pathways, dominated by genes related to recruitment, retention, activation and proliferation of cytotoxic lymphocytes (CD8+ T-cells and natural killer cells). Both hierarchical clustering and a supervised machine learning tool were able to correctly categorize most samples (82.3% and 94.1% respectively) into incipient CLAD and CLAD-free categories. Conclusions These findings suggest that a pathobiology, similar to AR, precedes a clinical diagnosis of CLAD. A larger prospective investigation of the BAL cell pellet transcriptome as a biomarker for CLAD risk stratification is warranted. PMID:28103284

  13. Frailty in elderly people with chronic kidney disease.

    PubMed

    Portilla Franco, Maria Eugenia; Tornero Molina, Fernando; Gil Gregorio, Pedro

    In recent years, the concept of frailty as a "state of pre-disability" has been widely accepted by those involved in the care of the elderly. Its importance lies not only in its high prevalence - more than 25% in people over 85 years of age - but it is also considered an independent risk factor of disability, institutionalisation and mortality amongst the elderly. The study of renal function is relevant in patients with major comorbidities. Studies have shown a significant association between chronic kidney disease and the development of adverse clinical outcomes such as heart disease, heart failure, end-stage renal disease, increased susceptibility to infections and greater functional impairment. Frailty can be reversed, which is why a study of frailty in patients with chronic kidney disease is of particular interest. This article aims to describe the association between ageing, frailty and chronic kidney disease in light of the most recent and relevant scientific publications.

  14. Mechanisms by Which Dehydration May Lead to Chronic Kidney Disease.

    PubMed

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

    2015-01-01

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

  15. [Clinicopathological study of chronic kidney diseases (CKD)].

    PubMed

    Yoshida, Haruyoshi

    2012-02-01

    up-to-date information and techniques in clinical nephrology. From this hospital, I published a paper in Kidney International entitled, "Mesangiolytic glomerulopathy in severe congestive heart failure", based on the autopsy cases collected at the Pathology Department. This paper became a milestone in starting to study the role of chronic hypoxia in CKD. In 1999, I was elected as a professor of the Department of Clinical Laboratories, Faculty of Medicine, University of Fukui. In Fukui, I could extend my hypoxia study to cellular levels and diabetic mouse experiments in collaboration with Dr. Kimura, Dr. Li, Dr. Takahashi and many other doctors and technicians. When overviewing my research history, I realize that I was fortunate to be involved at the starting point of every laboratory with energetic mood and that I was supported and helped by many people.

  16. Pre-Transplant Cardiovascular Risk Factors Affect Kidney Allograft Survival: A Multi-Center Study in Korea

    PubMed Central

    Lee, Jung Pyo; Bae, Eunjin; Kang, Eunjeong; Kim, Hack-Lyoung; Kim, Yong-Jin; Oh, Yun Kyu; Kim, Yon Su; Kim, Young Hoon; Lim, Chun Soo

    2016-01-01

    Background Pre-transplant cardiovascular (CV) risk factors affect the development of CV events even after successful kidney transplantation (KT). However, the impact of pre-transplant CV risk factors on allograft failure (GF) has not been reported. Methods and Findings We analyzed the graft outcomes of 2,902 KT recipients who were enrolled in a multi-center cohort from 1997 to 2012. We calculated the pre-transplant CV risk scores based on the Framingham risk model using age, gender, total cholesterol level, smoking status, and history of hypertension. Vascular disease (a composite of ischemic heart disease, peripheral vascular disease, and cerebrovascular disease) was noted in 6.5% of the patients. During the median follow-up of 6.4 years, 286 (9.9%) patients had developed GF. In the multivariable-adjusted Cox proportional hazard model, pre-transplant vascular disease was associated with an increased risk of GF (HR 2.51; 95% CI 1.66–3.80). The HR for GF (comparing the highest with the lowest tertile regarding the pre-transplant CV risk scores) was 1.65 (95% CI 1.22–2.23). In the competing risk model, both pre-transplant vascular disease and CV risk score were independent risk factors for GF. Moreover, the addition of the CV risk score, the pre-transplant vascular disease, or both had a better predictability for GF compared to the traditional GF risk factors. Conclusions In conclusion, both vascular disease and pre-transplant CV risk score were independently associated with GF in this multi-center study. Pre-transplant CV risk assessments could be useful in predicting GF in KT recipients. PMID:27501048

  17. Clinical management of the uraemic syndrome in chronic kidney disease.

    PubMed

    Vanholder, Raymond; Fouque, Denis; Glorieux, Griet; Heine, Gunnar H; Kanbay, Mehmet; Mallamaci, Francesca; Massy, Ziad A; Ortiz, Alberto; Rossignol, Patrick; Wiecek, Andrzej; Zoccali, Carmine; London, Gérard Michel

    2016-04-01

    The clinical picture of the uraemic syndrome is a complex amalgam of accelerated ageing and organ dysfunction, which progress in parallel to chronic kidney disease. The uraemic syndrome is associated with cardiovascular disease, metabolic bone disease, inflammation, protein energy wasting, intestinal dysbiosis, anaemia, and neurological and endocrine dysfunction. In this Review, we summarise specific, modern management options for the uraemic syndrome in chronic kidney disease. Although large randomised controlled trials are scarce, based on data from randomised controlled trials and observational studies, as well as pathophysiological reasoning, a therapeutic algorithm can be developed for this complex and multifactorial condition, with interventions targeting several modifiable factors simultaneously.

  18. Use of sevelamer in chronic kidney disease: beyond phosphorus control.

    PubMed

    Rodríguez-Osorio, Laura; Zambrano, Diana Pazmiño; Gracia-Iguacel, Carolina; Rojas-Rivera, Jorge; Ortiz, Alberto; Egido, Jesus; González Parra, Emilio

    2015-01-01

    Sevelamer is a non-calcium phosphate binder used in advanced chronic kidney disease (CKD) and in dialysis for hyperphosphataemia control. Several experimental, observational studies and clinical trials have shown that sevelamer has pleiotropic effects, beyond hyperphosphataemia control, including actions on inflammation, oxidative stress, lipid profile and atherogenesis, vascular calcification, endothelial dysfunction and the reduction of several uremic toxins. This is the biological basis for its global effect on cardiovascular morbidity and mortality in patients with chronic kidney disease. This review focuses on these pleiotropic actions of sevelamer and their impact on cardiovascular health, with the experience published after more than ten years of clinical expertise.

  19. A Higher Risk of Acute Rejection of Human Kidney Allografts Can Be Predicted from the Level of CD45RC Expressed by the Recipients’ CD8 T Cells

    PubMed Central

    Ordonez, Laurence; Bernard, Isabelle; Chabod, Marianne; Augusto, Jean-François; Lauwers-Cances, Valerie; Cristini, Christelle; Cuturi, Maria-Cristina; Subra, Jean-François; Saoudi, Abdelhadi

    2013-01-01

    Although transplantation is the common treatment for end-stage renal failure, allograft rejection and marked morbidity from the use of immunosuppressive drugs remain important limitations. A major challenge in the field is to identify easy, reliable and noninvasive biomarkers allowing the prediction of deleterious alloreactive immune responses and the tailoring of immunosuppressive therapy in individuals according to the rejection risk. In this study, we first established that the expression of the RC isoform of the CD45 molecule (CD45RC) on CD4 and CD8 T cells from healthy individuals identifies functionally distinct alloreactive T cell subsets that behave differently in terms of proliferation and cytokine secretion. We then investigated whether the frequency of the recipients CD45RC T cell subsets before transplantation would predict acute graft rejection in a cohort of 89 patients who had undergone their first kidney transplantation. We showed that patients exhibiting more than 54.7% of CD8 CD45RChigh T cells before transplantation had a 6 fold increased risk of acute kidney graft rejection. In contrast, the proportions of CD4 CD45RC T cells were not predictive. Thus, a higher risk of acute rejection of human kidney allografts can be predicted from the level of CD45RC expressed by the recipients’ CD8 T cells. PMID:23894540

  20. Genetic loci influencing kidney function and chronic kidney disease in man

    PubMed Central

    Chambers, John C; Zhang, Weihua; Lord, Graham M; van der Harst, Pim; Lawlor, Debbie A; Sehmi, Joban S; Gale, Daniel P; Wass, Mark N; Ahmadi, Kourosh R; Bakker, Stephan JL; Beckmann, Jacqui; Bilo, Henk JG; Bochud, Murielle; Brown, Morris J; Caulfield, Mark J; Connell, John M C; Cook, Terence; Cotlarciuc, Ioana; Smith, George Davey; de Silva, Ranil; Deng, Guohong; Devuyst, Olivier; Dikkeschei, Lambert D.; Dimkovic, Nada; Dockrell, Mark; Dominiczak, Anna; Ebrahim, Shah; Eggermann, Thomas; Farrall, Martin; Ferrucci, Luigi; Floege, Jurgen; Forouhi, Nita G; Gansevoort, Ron T; Han, Xijin; Hedblad, Bo; van der Heide, Jaap J Homan; Hepkema, Bouke G; Hernandez-Fuentes, Maria; Hypponen, Elina; Johnson, Toby; de Jong, Paul E; Kleefstra, Nanne; Lagou, Vasiliki; Lapsley, Marta; Li, Yun; Loos, Ruth J F; Luan, Jian'an; Luttropp, Karin; Maréchal, Céline; Melander, Olle; Munroe, Patricia B; Nordfors, Louise; Parsa, Afshin; Penninx, Brenda W.; Perucha, Esperanza; Pouta, Anneli; Prokopenko, Inga; Roderick, Paul J; Ruokonen, Aimo; Samani, Nilesh; Sanna, Serena; Schalling, Martin; Schlessinger, David; Schlieper, Georg; Seelen, Marc AJ; Shuldiner, Alan R; Sjögren, Marketa; Smit, Johannes H.; Snieder, Harold; Soranzo, Nicole; Spector, Timothy D; Stenvinkel, Peter; Sternberg, Michael JE; Swaminathan, Ramasamyiyer; Tanaka, Toshiko; Ubink-Veltmaat, Lielith J.; Uda, Manuela; Vollenweider, Peter; Wallace, Chris; Waterworth, Dawn; Zerres, Klaus; Waeber, Gerard; Wareham, Nicholas J; Maxwell, Patrick H; McCarthy, Mark I; Jarvelin, Marjo-Riitta; Mooser, Vincent; Abecasis, Goncalo R; Lightstone, Liz; Scott, James; Navis, Gerjan; Elliott, Paul; Kooner., Jaspal S

    2013-01-01

    Chronic kidney disease (CKD), the result of permanent loss of kidney function, is a major global problem. We identify common genetic variants at chr2p12-p13, chr6q26, chr17q23 and chr19q13 associated with serum creatinine, a marker of kidney function (P=10−10 to 10−15). SNPs rs10206899 (near NAT8, chr2p12-p13) and rs4805834 (near SLC7A9, chr19q13) were also associated with CKD. Our findings provide new insight into metabolic, solute and drug-transport pathways underlying susceptibility to CKD. PMID:20383145

  1. 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

  2. New oral anticoagulants in patients with chronic kidney disease.

    PubMed

    Belmar Vega, Lara; de Francisco, A L M; Bada da Silva, Jairo; Galván Espinoza, Luis; Fernández Fresnedo, Gema

    2016-12-08

    Patients with chronic kidney disease (CKD) develop bleeding and thrombotic tendencies, so the indication of anticoagulation at the onset of atrial fibrillation (AF) is complex. AF is the most common chronic cardiac arrhythmia, and thromboembolism and ischemic stroke in particular are major complications. In recent years, new oral anticoagulant drugs have been developed, and they have shown superiority over the classical AVK in preventing stroke, systemic embolism and bleeding risk, constituting an effective alternative to those resources.

  3. Cancer-related outcomes in kidney allograft recipients in England versus New York State: a comparative population-cohort analysis between 2003 and 2013.

    PubMed

    Jackson-Spence, Francesca; Gillott, Holly; Tahir, Sanna; Nath, Jay; Mytton, Jemma; Evison, Felicity; Sharif, Adnan

    2017-03-01

    It is unclear whether cancer-related epidemiology after kidney transplantation is translatable between countries. In this population-cohort study, we compared cancer incidence and all-cause mortality after extracting data for every kidney-alone transplant procedure performed in England and New York State (NYS) between 2003 and 2013. Data were analyzed for 18,493 and 11,602 adult recipients from England and NYS respectively, with median follow up 6.3 years and 5.5 years respectively (up to December 2014). English patients were more likely to have previous cancer at time of transplantation compared to NYS patients (5.6% vs. 3.5%, P < 0.001). Kidney allograft recipients in England versus NYS had increased cancer incidence (12.3% vs. 5.9%, P < 0.001) but lower all-cause mortality during the immediate postoperative stay (0.7% vs. 1.0%, P = 0.011), after 30-days (0.9% vs. 1.8%, P < 0.001) and after 1-year post-transplantation (3.0% vs. 5.1%, P < 0.001). However, mortality rates among patients developing post-transplant cancer were equivalent between the two countries. During the first year of follow up, if patients had an admission with a cancer diagnosis, they were more likely to die in both England (Odds Ratio 4.28 [95% CI: 3.09-5.93], P < 0.001) and NYS (Odds Ratio 2.88 [95% CI: 1.70-4.89], P < 0.001). Kidney allograft recipients in NYS demonstrated higher hazard ratios for developing kidney transplant rejection/failure compared to England on Cox regression analysis. Our analysis demonstrates significant differences in cancer-related epidemiology between kidney allograft recipients in England versus NYS, suggesting caution in translating post-transplant cancer epidemiology between countries.

  4. Endocrine Abnormalities in Patients with Chronic Kidney Disease.

    PubMed

    Kuczera, Piotr; Adamczak, Marcin; Wiecek, Andrzej

    2015-01-01

    In patients with chronic kidney disease the alterations of the endocrine system may arise from several causes. The kidney is the site of degradation as well as synthesis of many different hormones. Moreover, a number of concomitant pathological conditions such as inflammation, metabolic acidosis and malnutrition may participate in the pathogenesis of endocrine abnormalities in this group of patients. The most pronounced endocrine abnormalities in patients with chronic kidney disease are the deficiencies of: calcitriol, testosterone, insulin-like growth factor and, erythropoietin (EPO). Additionally accumulation of several hormones, such as: prolactin, growth hormone and insulin frequently also occur. The clinical consequences of the abovementioned endocrine abnormalities are among others: anemia, infertility and bone diseases.

  5. DNA vaccination as a treatment for chronic kidney disease.

    PubMed

    Wang, Yuan Min; Alexander, Stephen I

    2014-01-01

    Chronic kidney disease is one of the major health problems worldwide. DNA vaccination delivers plasmid DNA encoding the target gene to induce both humoral and cellular immune responses. Here, we describe the methods of CD40 DNA vaccine enhanced by dendritic cell (DC) targeting on the development of Heymann nephritis (HN), a rat model of human membranous nephropathy.

  6. Nutrition interventions to address cardiovascular outcomes in chronic kidney disease.

    PubMed

    Beto, Judith A; Bansal, Vinod K

    2004-10-01

    The high mortality in chronic kidney disease has been linked to cardiovascular risk and these patients are considered at high risk. Dietary intervention can directly address nutritional risk factors in lipid management, calcium-phorphorus balance, and body composition to reduce risk of cardiovascular disease. Nutrient intake can also indirectly address less overt risks of dental health, nutritional supplements, and compliance issues.

  7. Treating chronic lower limb lymphedema with the Charles procedure in a renal allograft recipient.

    PubMed

    Wu, Hsiao-Su; Cheng, Hsu-Tang; Chen, Hung-Chi

    2012-01-01

    We report our experience in applying the Charles procedure to a female renal allograft recipient for her left lower leg lymphedema. This is a rare comorbidity in limb lymphedema victims, and the use of the Charles procedure has not been reported in such an immunocompromised patient. After surgery, infection was well controlled, and there was minimal scar in the affected limb.

  8. Pharmacological management of acute kidney injury and chronic kidney disease in neonates.

    PubMed

    Jetton, Jennifer G; Sorenson, Mark

    2017-04-01

    Both acute kidney injury (AKI) and chronic kidney disease (CKD) are seen more frequently in the neonatal intensive care unit (NICU) as advances in supportive care improve the survival of critically ill infants as well as those with severe, congenital kidney and urinary tract anomalies. Many aspects of the infant's care, including fluid balance, electrolyte and mineral homeostasis, acid-base balance, and growth and nutrition require close monitoring by and collaboration among neonatologists, nephrologists, dieticians, and pharmacologists. This educational review summarizes the therapies widely used for neonates with AKI and CKD. Use of these therapies is extrapolated from data in older children and adults or based on clinical experience and case series. There is a critical need for more research on the use of therapies in infants with kidney disease as well as for the development of drug delivery systems and preparations scaled more appropriately for these small patients.

  9. Role of Myeloperoxidase in Patients with Chronic Kidney Disease

    PubMed Central

    Kisic, Bojana; Miric, Dijana; Dragojevic, Ilija; Rasic, Julijana; Popovic, Ljiljana

    2016-01-01

    Chronic kidney disease (CKD) is a worldwide public health problem. Patients with CKD have a number of disorders in the organism, and the presence of oxidative stress and systemic inflammation in these patients is the subject of numerous studies. Chronic inflammation joined with oxidative stress contributes to the development of numerous complications: accelerated atherosclerosis process and cardiovascular disease, emergence of Type 2 diabetes mellitus, development of malnutrition, anaemia, hyperparathyroidism, and so forth, affecting the prognosis and quality of life of patients with CKD. In this review we presented the potential role of the myeloperoxidase enzyme in the production of reactive/chlorinating intermediates and their role in oxidative damage to biomolecules in the body of patients with chronic kidney disease and end-stage renal disease. In addition, we discussed the role of modified lipoprotein particles under the influence of prooxidant MPO intermediates in the development of endothelial changes and cardiovascular complications in renal failure. PMID:27127544

  10. Barriers to successful care for chronic kidney disease

    PubMed Central

    Lenz, Oliver; Mekala, Durga P; Patel, Daniel V; Fornoni, Alessia; Metz, David; Roth, David

    2005-01-01

    Background The National Kidney Foundation has formulated clinical practice guidelines for patients with chronic kidney disease (K/DOQI). However, little is know about how many patients actually achieve these goals in a dedicated clinic for chronic kidney disease. Methods We performed a cross-sectional analysis of 198 patients with an estimated glomerular filtration rate of less than 30 ml/min/1.73 m2 and determined whether K/DOQI goals were met for calcium, phosphate, calcium-phosphate product, parathyroid hormone, albumin, bicarbonate, hemoglobin, lipids, and blood pressure. Results We found that only a small number of patients achieved K/DOQI targets. Recent referral to the nephrologist, failure to attend scheduled clinic appointments, African American ethnicity, diabetes, and advanced renal failure were significant predictors of low achievement of K/DOQI goals. Conclusion We conclude that raising awareness of chronic kidney disease and K/DOQI goals among primary care providers, early referral to a nephrologist, the exploration of socioeconomic barriers and cultural differences, and both patient and physician education are critical to improve CKD care in patients with Stage 4 and 5 CKD. PMID:16250919

  11. Role of Bone Biopsy in Stages 3 to 4 Chronic Kidney Disease

    PubMed Central

    Gal-Moscovici, Anca; Sprague, Stuart M.

    2008-01-01

    Secondary hyperparathyroidism develops relatively early in chronic kidney disease as a consequence of impaired phosphate, calcium, and vitamin D homeostasis. The disease state in chronic kidney disease, which includes the histologic features of bone disease, defined as renal osteodystrophy, and the hormonal and biochemical disturbances, have recently been redefined as a disease syndrome and is referred to as “chronic kidney disease–mineral and bone disorder.” As chronic kidney disease progresses, specific histologic disturbances in the bone develop, which may or may not be predictable from the biochemical and hormonal changes that are associated with chronic kidney disease. In addition, patients may have had underlying bone disease before developing kidney failure or may have been treated with agents that will alter the classical pathologic findings of the bones in chronic kidney disease and their relation to parathyroid hormone. Thus, in stage 5 chronic kidney disease, bone biopsy with quantitative histomorphometric analysis is considered the gold standard in the diagnosis of renal osteodystrophy. In contrast to stage 5 chronic kidney disease, there are very few data on the histologic changes in bone in earlier stages of chronic kidney disease. There also is no adequate information on the etiopathogenesis of bone disease in stages 3 and 4 chronic kidney disease. Thus, because biochemical data cannot predict bone pathology in stages 3 and 4 chronic kidney disease, bone biopsy should be used to define these bone changes and to allow appropriate therapeutic approaches. PMID:18988703

  12. Local gene therapy with indoleamine 2,3-dioxygenase protects against development of transplant vasculopathy in chronic kidney transplant dysfunction.

    PubMed

    Vavrincova-Yaghi, D; Deelman, L E; van Goor, H; Seelen, M A; Vavrinec, P; Kema, I P; Gomolcak, P; Benigni, A; Henning, R H; Sandovici, M

    2016-11-01

    Chronic transplant dysfunction (CTD) is the primary cause of late allograft loss in kidney transplantation. Indoleamine 2,3-dioxygenase (IDO) is involved in fetomaternal tolerance and IDO gene therapy inhibits acute rejection following kidney transplantation. The aim of this study is to investigate whether gene therapy with IDO is able to attenuate CTD. Transplantation was performed in a rat Dark-Agouti to Wistar-Furth CTD model. Donor kidneys were incubated either with an adenovirus carrying IDO gene, a control adenovirus or saline. During the first 10 days recipients received low-dose cyclosporine. Body weight, blood pressure, serum creatinine and proteinuria were measured every 2 weeks. Rats were killed after 12 weeks. IDO had a striking beneficial effect on transplant vasculopathy at week 12. It also significantly improved body weight gain; it reduced blood pressure and decreased proteinuria during the follow-up. However, it did not affect the kidney function. In addition, IDO therapy significantly decreased the number of graft-infiltrating macrophages at week 12. The messenger RNA levels of forkhead box p3 and transforming grow factor-β were elevated in the IDO treated group at week 12. Here we show for first time a clear beneficial effect of local IDO gene therapy especially on transplant vasculopathy in a rat model of renal CTD.

  13. Pre-pregnancy counseling for women with chronic kidney disease.

    PubMed

    Bramham, Kate; Lightstone, Liz

    2012-01-01

    Pre-pregnancy counseling should be available for all women with chronic kidney disease (CKD) so that conception occurs at the right time in the course of their disease and while they are on the right medications, with the aims of minimizing risks for both mother and fetus. Key areas to consider are the factors which are associated with worse prognosis and the influence of underlying kidney conditions and their treatment, in particular lupus nephritis, advanced renal impairment and transplantation. This experience-based review provides a guide to clinicians managing women with CKD, before and during their pregnancy.

  14. Chronic kidney disease of unknown etiology in agricultural communities.

    PubMed

    Almaguer, Miguel; Herrera, Raúl; Orantes, Carlos M

    2014-04-01

    In recent years, Central America, Egypt, India and Sri Lanka have reported a high prevalence of chronic kidney disease of unknown etiology in agricultural communities, predominantly among male farmworkers. This essay examines the disease's case definitions, epidemiology (disease burden, demographics, associated risk factors) and causal hypotheses, by reviewing published findings from El Salvador, Nicaragua, Costa Rica, Sri Lanka, Egypt and India. The range of confirmed chronic kidney disease prevalence was 17.9%-21.1%. Prevalence of reduced glomerular filtration (<60 mL/min/1.73 m2 body surface area) based on a single serum creatinine measurement was 0%-67% men and 0%-57% women. Prevalence was generally higher in male farmworkers aged 20-50 years, and varied by community economic activity and altitude. Cause was unknown in 57.4%-66.7% of patients. The dominant histopathological diagnosis was chronic tubulointerstitial nephritis. Associations were reported with agricultural work, agrochemical exposure, dehydration, hypertension, homemade alcohol use and family history of chronic kidney disease. There is no strong evidence for a single cause, and multiple environmental, occupational and social factors are probably involved. Further etiological research is needed, plus interventions to reduce preventable risk factors.

  15. Cadmium, diabetes and chronic kidney disease

    SciTech Connect

    Edwards, Joshua R. Prozialeck, Walter C.

    2009-08-01

    Recent epidemiological studies suggest a positive association between exposure to the environmental pollutant cadmium (Cd) and the incidence and severity of diabetes. In this review, we examine the literature suggesting a relationship between Cd exposure, elevated blood glucose levels, and the development of diabetes. In addition we review human and animal studies indicating that Cd potentiates or exacerbates diabetic nephropathy. We also review the various possible cellular mechanisms by which Cd may alter blood glucose levels. In addition, we present some novel findings from our own laboratories showing that Cd elevates fasting blood glucose levels in an animal model of subchronic Cd exposure before overt signs of renal dysfunction are evident. These studies also show that Cd reduces insulin levels and has direct cytotoxic effects on the pancreas. Together, these findings indicate that Cd may be a factor in the development of some types of diabetes and they raise the possibility that Cd and diabetes-related hyperglycemia may act synergistically to damage the kidney.

  16. History of kidney stones and risk of chronic kidney disease: a meta-analysis

    PubMed Central

    Shang, Weifeng; Li, Lixi; Ren, Yali; Ge, Qiangqiang; Ku, Ming

    2017-01-01

    Background Although the relationship between a history of kidney stones and chronic kidney disease (CKD) has been explored in many studies, it is still far from being well understood. Thus, we conducted a meta-analysis of studies comparing rates of CKD in patients with a history of kidney stones. Methods PubMed, EMBASE, and the reference lists of relevant articles were searched to identify observational studies related to the topic. A random-effects model was used to combine the study-specific risk estimates. We explored the potential heterogeneity by subgroup analyses and meta-regression analyses. Results Seven studies were included in this meta-analysis. Pooled results suggested that a history of kidney stones was associated with an increased adjusted risk estimate for CKD [risk ratio (RR), 1.47 95% confidence interval (CI) [1.23–1.76])], with significant heterogeneity among these studies (I2 = 93.6%, P < 0.001). The observed positive association was observed in most of the subgroup analyses, whereas the association was not significant among studies from Asian countries, the mean age ≥50 years and male patients. Conclusion A history of kidney stones is associated with increased risk of CKD. Future investigations are encouraged to reveal the underlying mechanisms in the connection between kidney stones and CKD, which may point the way to more effective preventive and therapeutic measures. PMID:28149686

  17. Treatment of chronic kidney diseases with histone deacetylase inhibitors

    PubMed Central

    Liu, Na; Zhuang, Shougang

    2015-01-01

    Histone deacetylases (HDACs) induce deacetylation of both histone and non-histone proteins and play a critical role in the modulation of physiological and pathological gene expression. Pharmacological inhibition of HDAC has been reported to attenuate progression of renal fibrogenesis in obstructed kidney and reduce cyst formation in polycystic kidney disease. HDAC inhibitors (HDACis) are also able to ameliorate renal lesions in diabetes nephropathy, lupus nephritis, aristolochic acid nephropathy, and transplant nephropathy. The beneficial effects of HDACis are associated with their anti-fibrosis, anti-inflammation, and immunosuppressant effects. In this review, we summarize recent advances on the treatment of various chronic kidney diseases with HDACis in pre-clinical models. PMID:25972812

  18. Modeling Red Blood Cell and Iron Dynamics in Patients with Chronic Kidney Disease

    DTIC Science & Technology

    2012-02-10

    Abstract Chronic kidney disease causes a slow loss of kidney function over time and can even- tually lead to End Stage Renal Disease, where a patient must...AVAILABILITY STATEMENT Approved for public release; distribution unlimited 13. SUPPLEMENTARY NOTES 14. ABSTRACT Chronic kidney disease causes a slow...Standard Form 298 (Rev. 8-98) Prescribed by ANSI Std Z39-18 1 Introduction It is estimated that 31 million Americans have chronic kidney disease ( CKD

  19. Juxtarenal Mycotic Aneurysm as a Complication of Acute Exacerbation of Chronic Cholecystitis Treated by Resection and Replacement by a Fresh Allograft.

    PubMed

    Grus, Tomáš; Lambert, Lukáš; Rohn, Vilém; Klika, Tomáš; Grusová, Gabriela; Michálek, Pavel

    2016-01-01

    We present a case of a female patient with infectious (mycotic) juxtarenal abdominal aneurysm with atypical symptoms beginning as acute exacerbation of chronic cholecystitis. Apart from common antibiotic treatment, the patient successfully underwent resection of the diseased segment and replacement by a fresh allograft in order to reduce the risk of infection of the graft, but with the need of subsequent life-long immunosuppressive therapy. Perioperative monitoring of the spinal cord by near infrared spectroscopy was used to identify possible spinal ischemia. The choice of the fresh allograft was based on our experience supported by review of the literature.

  20. Vascular Stiffness in Children With Chronic Kidney Disease.

    PubMed

    Savant, Jonathan D; Betoko, Aisha; Meyers, Kevin E C; Mitsnefes, Mark; Flynn, Joseph T; Townsend, Raymond R; Greenbaum, Larry A; Dart, Allison; Warady, Bradley; Furth, Susan L

    2017-05-01

    Carotid-femoral pulse wave velocity (cfPWV) is a measure of arterial stiffness associated with cardiovascular events in the general population and in adults with chronic kidney disease. However, few data exist regarding cfPWV in children with chronic kidney disease. We compared observed cfPWV assessed via applanation tonometry in children enrolled in the CKiD cohort study (Chronic Kidney Disease in Children) to normative data in healthy children and examined risk factors associated with elevated cfPWV. cfPWV Z score for height/gender and age/gender was calculated from and compared with published pediatric norms. Multivariable linear regression was used to assess the relationship between cfPWV and age, gender, race, body mass index, diagnosis, urine protein-creatinine ratio, mean arterial pressure, heart rate, number of antihypertensive medications, uric acid, and serum low-density lipoprotein. Of the 95 participants with measured cfPWV, 60% were male, 19% were black, 46% had glomerular cause of chronic kidney disease, 22% had urine protein-creatinine ratio 0.5 to 2.0 mg/mg and 9% had >2.0 mg/mg, mean age was 15.1 years, average mean arterial pressure was 80 mm Hg, and median glomerular filtration rate was 63 mL/min per 1.73 m(2) Mean cfPWV was 5.0 m/s (SD, 0.8 m/s); mean cfPWV Z score by height/gender norms was -0.1 (SD, 1.1). cfPWV increased significantly with age, mean arterial pressure, and black race in multivariable analysis; no other variables, including glomerular filtration rate, were independently associated with cfPWV. In this pediatric cohort with mild kidney dysfunction, arterial stiffness was comparable to that of normal children. Future research is needed to examine the impact of chronic kidney disease progression on arterial stiffness and associated cardiovascular parameters in children.

  1. [Lithium and chronic kidney disease: a pathology which remains relevant].

    PubMed

    Félix, Paula; Stoermann-Chopard, Catherine; Martin, Pierre-Yves

    2010-03-03

    Lithium continues to be the standard for acute and maintenance treatment of bipolar mood disorders despite the availability of alternative agents. Lithium has a narrow therapeutic index and can result in considerable toxicity. Acute renal intoxication is well-known but chronic kidney disease should be in each doctor's mind. The main manifestations are nephrogenic diabetes insipidus (NDI) and tubulointerstitial nephritis. For NDI, the potassium sparing diuretic amiloride or a thiazide diuretic can improve polyuria. Lithium-induced ESRD in chronic tubulointerstitial nephritis is not uncommon and more prevalent (> 1% among long-term lithium patients) than previously thought. The risk of renal failure may persist even after lithium discontinuation. Additional kidney manifestations of lithium exposure include renal tubular acidosis and hypercalcemia.

  2. Sexual and gonadal dysfunction in chronic kidney disease: Pathophysiology.

    PubMed

    Rathi, Manish; Ramachandran, Raja

    2012-03-01

    Sexual and gonadal dysfunction/infertility are quite common in patients with chronic kidney disease. Forty percent of male and 55% of female dialysis patients do not achieve orgasm. The pathophysiology of gonadal dysfunction is multifactorial. It is usually a combination of psychological, physiological, and other comorbid factors. Erectile dysfunction in males is mainly due to arterial factors, venous leakage, psychological factors, neurogenic factors, endocrine factors, and drugs. Sexual dysfunction in females is mainly due to hormonal factors and manifests mainly as menstrual irregularities, amenorrhea, lack of vaginal lubrication, and failure to conceive. Treatment of gonadal dysfunction in chronic kidney disease is multipronged and an exact understanding of underlying pathology is essential in proper management of these patients.

  3. Recent developments in epigenetics of acute and chronic kidney diseases.

    PubMed

    Reddy, Marpadga A; Natarajan, Rama

    2015-08-01

    The growing epidemic of obesity and diabetes, the aging population as well as prevalence of drug abuse has led to significant increases in the rates of the closely associated acute and chronic kidney diseases, including diabetic nephropathy. Furthermore, evidence shows that parental behavior and diet can affect the phenotype of subsequent generations via epigenetic transmission mechanisms. These data suggest a strong influence of the environment on disease susceptibility and that, apart from genetic susceptibility, epigenetic mechanisms need to be evaluated to gain critical new information about kidney diseases. Epigenetics is the study of processes that control gene expression and phenotype without alterations in the underlying DNA sequence. Epigenetic modifications, including cytosine DNA methylation and covalent post-translational modifications of histones in chromatin, are part of the epigenome, the interface between the stable genome and the variable environment. This dynamic epigenetic layer responds to external environmental cues to influence the expression of genes associated with disease states. The field of epigenetics has seen remarkable growth in the past few years with significant advances in basic biology, contributions to human disease, as well as epigenomics technologies. Further understanding of how the renal cell epigenome is altered by metabolic and other stimuli can yield novel new insights into the pathogenesis of kidney diseases. In this review, we have discussed the current knowledge on the role of epigenetic mechanisms (primarily DNAme and histone modifications) in acute and chronic kidney diseases, and their translational potential to identify much needed new therapies.

  4. Toward a more collaborative federal response to chronic kidney disease.

    PubMed

    Narva, Andrew S; Briggs, Michael; Jordan, Regina; Pavkov, Meda E; Burrows, Nilka Rios; Williams, Desmond E

    2010-05-01

    Chronic kidney disease (CKD) is a significant public health problem in the United States. However, data from the United States Renal Data System and other sources suggest that care for people with CKD does not meet recommended standards. The Federal government has developed the infrastructure to promote population-based interventions which have reduced the burden of other chronic illnesses. An effective, coordinated response by Federal health agencies to the public health challenge of CKD could have a significant effect on the morbidity, mortality, and costs associated with CKD. In recent years, initiatives undertaken by three Federal agencies have made important advances in coordinating efforts. The Centers for Disease Control and Prevention has begun to develop public health infrastructure for monitoring the burden of CKD. The Centers for Medicare and Medicaid Services has, through the successful Fistula First Breakthrough Initiative (FFBI) and inclusion of CKD in the scope of work of Quality Improvement Organizations, promoted earlier diagnosis and treatment of CKD. The National Institute of Diabetes and Digestive and Kidney Diseases, through its National Kidney Disease Education Program, has reinvigorated and expanded the Kidney Interagency Coordinating Committee so that it is a robust vehicle to share information about activities, identify and disseminate promising practices and tools, and foster cross-agency collaboration. Collaboration among Federal health agencies has the potential to enhance efforts to reduce the burden of CKD.

  5. Renal resistive index and mortality in chronic kidney disease.

    PubMed

    Toledo, Clarisse; Thomas, George; Schold, Jesse D; Arrigain, Susana; Gornik, Heather L; Nally, Joseph V; Navaneethan, Sankar D

    2015-08-01

    Renal resistive index (RRI) measured by Doppler ultrasonography is associated with cardiovascular events and mortality in hypertensive, diabetic, and elderly patients. We studied the factors associated with high RRI (≥0.70) and its associations with mortality in chronic kidney disease patients without renal artery stenosis. We included 1962 patients with an estimated glomerular filtration rate of 15 to 59 mL/min per 1.73 m(2) who also had RRI measured (January 1, 2005, to October 2011) from an existing chronic kidney disease registry. Participants with renal artery stenosis (60%-99% or renal artery occlusion) were excluded. Multivariable logistic regression model was used to study factors associated with high RRI (≥0.70), and its association with mortality was studied using Kaplan-Meier plots and Cox proportional hazards model. Hypertension was prevalent in >90% of the patients. In the multivariable logistic regression, older age, female sex, diabetes mellitus, coronary artery disease, peripheral vascular disease, higher systolic blood pressure, and the use of β blockers were associated with higher odds of having RRI≥0.70. During a median follow-up of 2.2 years, 428 patients died. After adjusting for covariates, RRI≥0.70 was associated with increased mortality (adjusted hazard ratio, 1.29; 95% confidence interval, 1.02-1.65; P<0.05). This association was more pronounced among younger patients and those with stage 3 chronic kidney disease. Noncardiovascular/non-malignancy-related deaths were higher in those with RRI≥0.70. RRI≥0.70 is associated with higher mortality in hypertensive chronic kidney disease patients without clinically significant renal artery stenosis after accounting for other significant risk factors. Its evaluation may allow early identification of those who are at risk thereby potentially preventing or delaying adverse outcomes.

  6. Dietary sodium in chronic kidney disease: a comprehensive approach.

    PubMed

    Wright, Julie A; Cavanaugh, Kerri L

    2010-01-01

    Despite existing guidelines, dietary sodium intake among people worldwide often exceeds recommended limits. Research evidence is growing in both animal and human studies showing indirect and direct adverse consequences of high dietary sodium on the kidney. In patients with kidney disease, dietary sodium may have important effects on proteinuria, efficacy of antiproteinuric pharmacologic therapy, hypertension control, maintaining an optimal volume status, and immunosuppressant therapy. Dietary sodium intake is an important consideration in patients with all stages of chronic kidney disease, including those receiving dialysis therapy or those who have received a kidney transplant. We review in detail the dietary sodium recommendations suggested by various organizations for patients with kidney disease. Potential barriers to successfully translating current sodium intake guidelines into practice include poor knowledge about the sodium content of food among both patients and providers, complex labeling information, patient preferences related to taste, and limited support for modifications in public policy. Finally, we offer existing and potential solutions that may assist providers in educating and empowering patients to effectively manage their dietary sodium intake.

  7. Dietary Sodium in Chronic Kidney Disease: A Comprehensive Approach

    PubMed Central

    Wright, Julie A.; Cavanaugh, Kerri L.

    2010-01-01

    Despite existing guidelines, dietary sodium intake among people worldwide often exceeds recommended limits. Research evidence is growing in both animal and human studies showing indirect and direct adverse consequences of high dietary sodium on the kidney. In patients with kidney disease, dietary sodium may have important effects on proteinuria, efficacy of antiproteinuric pharmacologic therapy, hypertension control, maintaining an optimal volume status, and immunosuppressant therapy. Dietary sodium intake is an important consideration in patients with all stages of chronic kidney disease, including those receiving dialysis therapy or those who have received a kidney transplant. We review in detail the dietary sodium recommendations suggested by various organizations for patients with kidney disease. Potential barriers to successfully translating current sodium intake guidelines into practice include poor knowledge about the sodium content of food among both patients and providers, complex labeling information, patient preferences related to taste, and limited support for modifications in public policy. Finally, we offer existing and potential solutions that may assist providers in educating and empowering patients to effectively manage their dietary sodium intake. PMID:20557489

  8. [Resistant hypertension and chronic kidney disease: epidemiology and prognosis].

    PubMed

    Seidowsky, Alexandre; Massy, Ziad A; Metzger, Marie; Stengel, Bénédicte

    2014-06-01

    The emergence of new effective therapeutic strategies for the treatment of resistant hypertension such as renal sympathetic denervation technique has lead to a renewed interest in the screening and assessment of prognosis of this specific entity which constitutes a subset of uncontrolled hypertension. Its prevalence is unknown, but estimated between 12 and 15% among hypertensive subjects from the general population. Several factors have been associated with the development of resistant hypertension, four of which are essential: age, diabetes, chronic kidney disease and vascular structural alteration. Excessive salt intake is also a risk factor for poorly controlled hypertension in patients with salt-dependent hypertension, and may participate to the genesis of resistant hypertension. Because of population ageing and increasing prevalence of diabetes, obesity and chronic kidney disease, the prevalence of resistant hypertension is expected to rise. A better understanding of its determinants and associated risks (such as chronic kidney disease) would identify high-risk groups that may benefit from extensive diagnosis work up and more specific treatments.

  9. Metformin in patients with chronic kidney disease: strengths and weaknesses.

    PubMed

    Rocha, Ana; Almeida, Marta; Santos, Josefina; Carvalho, André

    2013-01-01

    A wide array of benefits has been attributed to metformin. These include attenuation of abnormal glucose metabolism (diabetes treatment and prevention), weight neutrality or weight loss, improvement in the pathophysiologic components of metabolic syndrome (insulin resistance, subclinical inflammation, and endothelial dysfunction), lipid-lowering properties, cardiovascular protection, and antineoplastic potential. Metformin itself is not a nephrotoxic drug. Initially appointed as the safest hypoglycemic agent in chronic kidney disease, its use has been limited in these patients because of the perceived risk of lactic acidosis. A fear perpetuated by numerous case reports in which it is implicated. Current guidelines stipulate that it must be used with caution in estimated glomerular filtration rates (eGFRs) of less than 60 mL/minute and not at all in eGFRs of less than 30 mL/minute. Identified risk factors for metformin-associated lactic acidosis include acute kidney injury, hypoxemia, sepsis, alcohol abuse, liver failure, myocardial infarction, and shock. Treatment may include supportive care and dialysis techniques. On the other hand, it is likely that the use of metformin would be beneficial in many with chronic kidney disease according to the advantages associated with attenuation of metabolic syndrome and cardiovascular protection. The reality of severe metformin-induced lactic acidosis in the absence of chronic renal impairment raises the question of limitation of its use in these patients.

  10. Metabolic syndrome and chronic kidney disease.

    PubMed

    Bhowmik, D; Tiwari, S C

    2008-01-01

    Obesity is fast becoming a bane for the present civilization, as a result of sedentary lifestyle, atherogenic diet, and a susceptible thrifty genotype. The concept of metabolic syndrome, which is a constellation of metabolic disturbances, has crystallized over the last 80 years with the aim of identifying those at greater risk of developing type 2 diabetes and cardiovascular disease. These patients have visceral obesity and insulin resistance characterized by hypertyriglyceridemia. Recently, it has been realized that they are also at an increased risk of chronic renal disease. Release of adipocytokines leads to endothelial dysfunction. There is also activation of systemic and local renin-angiotensin-aldosterone system, oxidative stress, and impaired fibrinolysis. This leads to glomerular hyperfiltration, proteinuria, focal segmental glomerulosclerosis (FSGS), and ultimately end-stage renal disease (ESRD). Treatment consists of lifestyle modifications along with optimal control of blood pressure, blood sugar and lipids. Metformin and thiazolidenidiones reduce insulin resistance; while angiotensin converting enzyme inhibitors and angiotensin receptor blockers reduce proteinuria and have a renoprotective effect. Exciting new medical therapies on the horizon include rimonabant a cannabinoid receptor type 1 antagonist, soy proteins, and peroxisome proliferator-activated receptor (PPAR) agonist. Bariatric surgery for morbid obesity has also been shown to be effective in treating metabolic syndrome.

  11. Dehydrated Amniotic Membrane Allograft for Treatment of Chronic Leg Ulcers in Patients With Multiple Comorbidities: A Case Series

    PubMed Central

    Barr, Stephen M.

    2016-01-01

    Cellular and/or tissue-based products (CTPs) are emerging treatment options for chronic non-healing wounds. Dehydrated amniotic membrane allograft (DAMA) was used in 7 patients whose wounds had not responded adequately to standard and adjuvant therapies; four VLUs, 2 surgical wounds, and 1 DFU. Patients had multiple comorbidities, including 2 with autoimmune disorders (CREST syndrome and systemic lupus erythematosus). Patients received 3–8 applications of DAMA at weekly to biweekly intervals (average, 5.4 applications). Complete wound healing was observed in 6 of 7 patients during study period, with an average time to closure of 7.9 weeks. Closure was achieved in 3 of 7 patients after 3 DAMA applications. In the patient with CREST syndrome who did not completely close, DAMA reduced the area and volume by nearly 50% and later went on to closure. These cases suggest that DAMA is a viable option for recalcitrant DFUs, VLUs, and surgical wounds. PMID:27104144

  12. Neurocognitive Outcomes in Children with Chronic Kidney Disease: Current Findings and Contemporary Endeavors

    ERIC Educational Resources Information Center

    Gerson, Arlene C.; Butler, Robert; Moxey-Mims, Marva; Wentz, Alicia; Shinnar, Shlomo; Lande, Marc B.; Mendley, Susan R.; Warady, Bradley A.; Furth, Susan L.; Hooper, Stephen R.

    2006-01-01

    Given the rise in chronic kidney disease (CKD) in both children and adults, CKD has recently been targeted as a public health priority. Childhood onset kidney disease is generally a noncurable and progressive condition that leads to kidney failure by early adulthood. Fortunately, improved identification of kidney problems allows for early…

  13. IL-34 mediates acute kidney injury and worsens subsequent chronic kidney disease.

    PubMed

    Baek, Jea-Hyun; Zeng, Rui; Weinmann-Menke, Julia; Valerius, M Todd; Wada, Yukihiro; Ajay, Amrendra K; Colonna, Marco; Kelley, Vicki R

    2015-08-03

    Macrophages (Mø) are integral in ischemia/reperfusion injury-incited (I/R-incited) acute kidney injury (AKI) that leads to fibrosis and chronic kidney disease (CKD). IL-34 and CSF-1 share a receptor (c-FMS), and both cytokines mediate Mø survival and proliferation but also have distinct features. CSF-1 is central to kidney repair and destruction. We tested the hypothesis that IL-34-dependent, Mø-mediated mechanisms promote persistent ischemia-incited AKI that worsens subsequent CKD. In renal I/R, the time-related magnitude of Mø-mediated AKI and subsequent CKD were markedly reduced in IL-34-deficient mice compared with controls. IL-34, c-FMS, and a second IL-34 receptor, protein-tyrosine phosphatase ζ (PTP-ζ) were upregulated in the kidney after I/R. IL-34 was generated by tubular epithelial cells (TECs) and promoted Mø-mediated TEC destruction during AKI that worsened subsequent CKD via 2 distinct mechanisms: enhanced intrarenal Mø proliferation and elevated BM myeloid cell proliferation, which increases circulating monocytes that are drawn into the kidney by chemokines. CSF-1 expression in TECs did not compensate for IL-34 deficiency. In patients, kidney transplants subject to I/R expressed IL-34, c-FMS, and PTP-ζ in TECs during AKI that increased with advancing injury. Moreover, IL-34 expression increased, along with more enduring ischemia in donor kidneys. In conclusion, IL-34-dependent, Mø-mediated, CSF-1 nonredundant mechanisms promote persistent ischemia-incited AKI that worsens subsequent CKD.

  14. Nonsteroidal Mineralocorticoid Receptor Antagonist Finerenone Protects Against Acute Kidney Injury-Mediated Chronic Kidney Disease: Role of Oxidative Stress.

    PubMed

    Lattenist, Lionel; Lechner, Sebastian M; Messaoudi, Smail; Le Mercier, Alan; El Moghrabi, Soumaya; Prince, Sonia; Bobadilla, Norma A; Kolkhof, Peter; Jaisser, Frédéric; Barrera-Chimal, Jonatan

    2017-05-01

    Acute kidney injury induced by ischemia/reperfusion (IR) is a frequent complication in hospitalized patients. Mineralocorticoid receptor antagonism has shown to be helpful against renal IR consequences; however, the potential benefit of novel nonsteroidal mineralocorticoid receptor antagonists such as finerenone has to be further explored. In this study, we evaluated the efficacy of finerenone to prevent the acute and chronic consequences of ischemic acute kidney injury. For the acute study (24 hours), 18 rats were divided into sham, bilateral renal ischemia of 25 minutes, and rats that received 3 doses of finerenone at 48, 24, and 1 hour before the ischemia. For the chronic study (4 months), 23 rats were divided into sham, rats that underwent 45 minutes of bilateral ischemia, and rats treated with finerenone at days 2 and 1 and 1 hour before IR. We found that after 24 hours of reperfusion, the untreated IR rats presented kidney dysfunction and tubular injury. Kidney injury molecule-1 and neutrophil gelatinase associated to lipolacin mRNA levels were increased. In contrast, the rats treated with finerenone displayed normal kidney function and significantly lesser tubular injury and kidney injury molecule-1 and neutrophil gelatinase associated to lipolacin levels. After 4 months, the IR rats developed chronic kidney disease, evidenced by kidney dysfunction, increased proteinuria and renal vascular resistance, tubular dilation, extensive tubule-interstitial fibrosis, and an increase in kidney transforming growth factor-β and collagen-I mRNA. The transition from acute kidney injury to chronic kidney disease was fully prevented by finerenone. Altogether, our data show that in the rat, finerenone is able to prevent acute kidney injury induced by IR and the chronic and progressive deterioration of kidney function and structure.

  15. Chronic kidney disease: identification and management in primary care

    PubMed Central

    Fraser, Simon DS; Blakeman, Tom

    2016-01-01

    Chronic kidney disease (CKD) is an important and common noncommunicable condition globally. In national and international guidelines, CKD is defined and staged according to measures of kidney function that allow for a degree of risk stratification using commonly available markers. It is often asymptomatic in its early stages, and early detection is important to reduce future risk. The risk of cardiovascular outcomes is greater than the risk of progression to end-stage kidney disease for most people with CKD. CKD also predisposes to acute kidney injury – a major cause of morbidity and mortality worldwide. Although only a small proportion of people with CKD progress to end-stage kidney disease, renal replacement therapy (dialysis or transplantation) represents major costs for health care systems and burden for patients. Efforts in primary care to reduce the risks of cardiovascular disease, acute kidney injury, and progression are therefore required. Monitoring renal function is an important task, and primary care clinicians are well placed to oversee this aspect of care along with the management of modifiable risk factors, particularly blood pressure and proteinuria. Good primary care judgment is also essential in making decisions about referral for specialist nephrology opinion. As CKD commonly occurs alongside other conditions, consideration of comorbidities and patient wishes is important, and primary care clinicians have a key role in coordinating care while adopting a holistic, patient-centered approach and providing continuity. This review aims to summarize the vital role that primary care plays in predialysis CKD care and to outline the main considerations in its identification, monitoring, and clinical management in this context. PMID:27822135

  16. Impact of very early high doses of recombinant erythropoietin on anemia and allograft function in de novo kidney-transplant patients.

    PubMed

    Kamar, Nassim; Reboux, Anne-Hélène; Cointault, Olivier; Esposito, Laure; Cardeau-Desangles, Isabelle; Lavayssière, Laurence; Guitard, Joëlle; Wéclawiak, Hugo; Rostaing, Lionel

    2010-03-01

    After kidney transplantation, occurrence of anemia in the early post-transplant period (<1 month) is high and arises out of issues that are multifactorial. We performed a retrospective single-center study to assess whether delivery of high doses of erythropoietin-stimulating agents (ESA) within the first week of kidney transplantation, translates at 1 month post-transplant, in to causing less anemia and whether it has an impact on allograft function. Ninety-nine patients were not given ESA (group I), whereas 82 were (250 IU/kg/week; group II). All patients had similar pretransplant and baseline (day 0) variables. Similar numbers of group II patients were still receiving ESA by day 14 (97.5%) and day 30 (89%). Respective figures for group I were 27% and 27%. Independent factors for anemia at 1 month post-transplant included: being male subject, treatment for hypertension at pretransplant, anemia at transplant, a higher mean corpuscular volume at transplant, and an induction therapy using antithymocyte globulins. Independent predictive factors for lower creatinine clearance included being female subjects, having a donor aged >50 years, being a recipient aged >50 years, not treated for hypertension at pretransplant, and no post-transplant ESA therapy. High doses of ESA within the first month of kidney transplantation have no impact on anemia or renal function by 1 month post-transplant.

  17. Management of gouty arthritis in patients with chronic kidney disease.

    PubMed

    Abdellatif, Abdul A; Elkhalili, Naser

    2014-01-01

    Chronic kidney disease (CKD) is a comorbid condition that affects, based on recent estimates, between 47% and 54% of patients with gouty arthritis. However, data from randomized controlled trials in patients with gouty arthritis and CKD are limited, and current gouty arthritis treatment guidelines do not address the challenges associated with managing this patient population. Nonsteroidal anti-inflammatory drugs and colchicine are recommended first-line treatments for acute gouty arthritis attacks. However, in patients with CKD, nonsteroidal anti-inflammatory drugs are not recommended because their use can exacerbate or cause acute kidney injury. Also, colchicine toxicity is increased in patients with CKD, and dosage reduction is required based on level of kidney function. Allopurinol, febuxostat, and pegloticase are all effective treatments for controlling elevated uric acid levels after the treatment of an acute attack. However, in patients with CKD, required allopurinol dosage reductions may limit efficacy; pegloticase requires further investigation in this population, and febuxostat has not been studied in patients with creatinine clearance<30 mL/min. This article reviews the risks and benefits associated with currently available pharmacologic agents for the management of acute and chronic gouty arthritis including urate-lowering therapy in patients with CKD. Challenges specific to primary care providers are addressed, including guidance to help them decide when to collaborate with, or refer patients to, rheumatology and nephrology specialists based on the severity of gout and CKD.

  18. SDF-1/CXCR4/CXCR7 is pivotal for vascular smooth muscle cell proliferation and chronic allograft vasculopathy.

    PubMed

    Thomas, Michael N; Kalnins, Aivars; Andrassy, Martin; Wagner, Anne; Klussmann, Sven; Rentsch, Markus; Habicht, Antje; Pratschke, Sebastian; Stangl, Manfred; Bazhin, Alexandr V; Meiser, Bruno; Fischereder, Michael; Werner, Jens; Guba, Markus; Andrassy, Joachim

    2015-12-01

    Chronic rejection remains a major obstacle in transplant medicine. Recent studies suggest a crucial role of the chemokine SDF-1 on neointima formation after injury. Here, we investigate the potential therapeutic effect of inhibiting the SDF-1/CXCR4/CXCR7 axis with an anti-SDF-1 Spiegelmer (NOX-A12) on the development of chronic allograft vasculopathy. Heterotopic heart transplants from H-2bm12 to B6 mice and aortic transplants from Balb/c to B6 were performed. Mice were treated with NOX-A12. Control animals received a nonfunctional Spiegelmer (revNOX-A12). Samples were retrieved at different time points and analysed by histology, RT-PCR and proliferation assay. Blockade of SDF-1 caused a significant decrease in neointima formation as measured by intima/media ratio (1.0 ± 0.1 vs. 1.8 ± 0.1, P < 0.001 AoTx; 0.35 ± 0.05 vs. 1.13 ± 0.27, P < 0.05 HTx). In vitro treatment of primary vascular smooth muscle cells with NOX-A12 showed a significant reduction in proliferation (0.42 ± 0.04 vs. 0.24 ± 0.03, P < 0.05). TGF-β, TNF-α and IL-6 levels were significantly reduced under SDF-1 inhibition (3.42 ± 0.37 vs. 1.67 ± 0.33, P < 0.05; 2.18 ± 0.37 vs. 1.0 ± 0.39, P < 0.05; 2.18 ± 0.26 vs. 1.6 ± 0.1, P < 0.05). SDF-1/CXCR4/CXCR7 plays a critical role in the development of chronic allograft vasculopathy (CAV). Therefore, pharmacological inhibition of SDF-1 with NOX-A12 may represent a therapeutic option to ameliorate chronic rejection changes.

  19. Epigenetics of Progression of Chronic Kidney Disease: Fact or Fantasy?

    PubMed Central

    Wing, Maria R.; Ramezani, Ali; Gill, Harindarpal S.; Devaney, Joseph M.; Raj, Dominic S.

    2013-01-01

    Summary Epigenetic modifications are important in the normal functioning of the cell, from regulating dynamic expression of essential genes and associated proteins to repressing those that are unneeded. Epigenetic changes are essential for development and functioning of the kidney, and aberrant methylation, histone modifications, and expression of microRNA could lead to chronic kidney disease (CKD). Here, epigenetic modifications modulate transforming growth factor β signaling, inflammation, profibrotic genes, and the epithelial-to-mesenchymal transition, promoting renal fibrosis and progression of CKD. Identification of these epigenetic changes is important because they are potentially reversible and may serve as therapeutic targets in the future to prevent subsequent renal fibrosis and CKD. In this review we discuss the different types of epigenetic control, methods to study epigenetic modifications, and how epigenetics promotes progression of CKD. PMID:24011578

  20. Role of leptin in reverse epidemiology in chronic kidney disease.

    PubMed

    Scholze, Alexandra; Tepel, Martin

    2007-01-01

    Leptin is mainly produced by adipocytes and metabolized in the kidney. Leptin is taken up into the central nervous system by a saturable transport system, and controls appetite in rodents and in healthy subjects. Leptin acts on peripheral tissue and increases the inflammatory response by stimulating the production of tumor necrosis factor alpha, interleukin-6 and interleukin-12. In healthy humans, serum leptin concentration is related to the size of adipose tissue mass in the body. The majority of obese subjects have inappropriately high levels of circulating plasma leptin concentrations, indicating leptin resistance. In healthy subjects increased leptin concentration constitutes a biomarker for increased cardiovascular risk. On the other hand, a recent prospective long-term study in patients with chronic kidney disease stage 5 on hemodialysis therapy showed that reduced serum leptin concentration is an independent risk factor for mortality in these patients.

  1. Evaluation of chronic kidney disease in chronic heart failure: From biomarkers to arterial renal resistances

    PubMed Central

    Iacoviello, Massimo; Leone, Marta; Antoncecchi, Valeria; Ciccone, Marco Matteo

    2015-01-01

    Chronic kidney disease and its worsening are recurring conditions in chronic heart failure (CHF) which are independently associated with poor patient outcome. The heart and kidney share many pathophysiological mechanisms which can determine dysfunction in each organ. Cardiorenal syndrome is the condition in which these two organs negatively affect each other, therefore an accurate evaluation of renal function in the clinical setting of CHF is essential. This review aims to revise the parameters currently used to evaluate renal dysfunction in CHF with particular reference to the usefulness and the limitations of biomarkers in evaluating glomerular dysfunction and tubular damage. Moreover, it is reported the possible utility of renal arterial resistance index (a parameter associated with abnormalities in renal vascular bed) for a better assesment of kidney disfunction. PMID:25610846

  2. Urotensin II levels in patients with chronic kidney disease and kidney transplants

    PubMed Central

    2012-01-01

    Objective. Urotensin II is a potent vasoactive peptide that has been implicated in the pathophysiology of many diseases. There is no study reporting the role and level of this peptide in recipients of kidney transplant. So we aimed to study the plasma levels of urotensin II in this group of patients. Methods. Plasma urotensin II levels were analyzed in 110 subjects, who were divided into three groups: group 1 (35 kidney transplant recipients), group 2 (36 patients with chronic kidney disease), and group 3 (39 healthy controls). Results. Analysis of logarithmic transformation of urotensin II, i.e. log (urotensin II × 1000) levels, with a one-way analysis of variance yielded a P value of 0.001. Post-hoc analysis showed significantly higher log (urotensin II × 1000) levels in group 1 than groups 2 and 3 (P = 0.001 and 0.017, respectively). One of the important features of the subjects of this group was that they were taking immunosuppressive drugs because of renal transplantation. Conclusions. High urotensin II levels in recipients of kidney transplants could be drug-related (immunosuppressive drugs) and may be of practical importance that may be used to improve the long-term outcome of the patients. PMID:22098077

  3. AA amyloidosis in the renal allograft: a report of two cases and review of the literature

    PubMed Central

    Rojas, Rebecca; Josephson, Michelle A.; Chang, Anthony; Meehan, Shane M.

    2012-01-01

    AA amyloidosis is a disorder characterized by the abnormal formation, accumulation and systemic deposition of fibrillary material that frequently involves the kidney. Recurrent AA amyloidosis in the renal allograft has been documented in patients with tuberculosis, familial Mediterranean fever, ankylosing spondylitis, chronic pyelonephritis and rheumatoid arthritis. De novo AA amyloidosis is rarely described. We report two cases of AA amyloidosis in the renal allograft. Our first case is a 47-year-old male with a history of ankylosing spondylitis who developed end-stage renal disease reportedly from tubulointerstitial nephritis from non-steroidal anti-inflammatory agent use. A biopsy was never performed. One year after transplantation, AA amyloidosis was identified in the femoral head and 8 years post-transplantation, AA amyloidosis was identified in the renal allograft. He was treated with colchicine and adalimumab and has stable renal function at 1 year-follow-up. Our second case is a 57-year-old male with a long history of intravenous drug use and hepatitis C infection who developed end-stage kidney disease due to AA amyloidosis. Our second patient's course was complicated by renal adenovirus, pulmonary aspergillosis and hepatitis C with AA amyloidosis subsequently being identified in the allograft 2.5 years post-transplantation. Renal allograft function remains stable 4-years post-transplantation. These reports describe clinical and pathologic features of two cases of AA amyloidosis presenting with proteinuria and focal involvement of the renal allograft. PMID:22833808

  4. 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.

  5. Chronic Kidney Disease As a Potential Indication for Renal Denervation

    PubMed Central

    Sanders, Margreet F.; Blankestijn, Peter J.

    2016-01-01

    Renal denervation is being used as a blood pressure lowering therapy for patients with apparent treatment resistant hypertension. However, this population does not represent a distinct disease condition in which benefit is predictable. In fact, the wide range in effectiveness of renal denervation could be a consequence of this heterogeneous pathogenesis of hypertension. Since renal denervation aims at disrupting sympathetic nerves surrounding the renal arteries, it seems obvious to focus on patients with increased afferent and/or efferent renal sympathetic nerve activity. In this review will be argued, from both a pathophysiological and a clinical point of view, that chronic kidney disease is particularly suited to renal denervation. PMID:27375498

  6. [Oral anticoagulation in chronic kidney disease with atrial fibrillation].

    PubMed

    Expósito, Víctor; Seras, Miguel; Fernández-Fresnedo, Gema

    2015-05-21

    Atrial fibrillation is a common finding in patients with chronic kidney disease (CKD), which increases markedly the embolism risk. The CHADS2 and HAS-BLED scales, used in the general population to assess the risk/benefit of oral anticoagulation (OAC), underestimate respectively the risk of embolism and haemorrhage in CKD, making it difficult to decide whether to use OAC or not. Based on the available evidence, it seems indicated to use OAC in stage 3 CKD, while it is controversial in advanced stages. New OAC such as dabigatran and rivaroxaban have been approved in stage 3 CKD but their role is still somewhat uncertain.

  7. [The role of zinc in chronic kidney disease].

    PubMed

    Fukushima, Tatsuo

    2016-07-01

    Renal anemia is one of the most important complication as a cause of cardiovascular event in patients with chronic kidney disease (CKD). The status of renal anemia has been ameliorated by using recombinant human erythropoietin (EPO), however, the EPO resistant anemia is sometimes seen in high stage CKD patients. Heavy metal deficiency including zinc deficiency is one of the cause of EPO resistant anemia. Recently, it is reported that zinc deficiency is seen in patients with CKD. In this article, we describe zinc deficiency in patients with CKD. The ability that zinc supplementation improves their anemia in CKD patients is also described.

  8. Nutritional treatment in chronic kidney disease: the concept of nephroprotection.

    PubMed

    Riccio, Eleonora; Di Nuzzi, Antonella; Pisani, Antonio

    2015-04-01

    Low-protein diets have been advocated for many decades as the cornerstone in the treatment of chronic kidney disease. Initially, the low intake of protein was used to reduce uremic symptoms; thereafter, albeit controversial, evidences suggested that dietary protein restriction can also slow the rate of progression of renal failure and the time until end-stage renal disease. This reviews focuses on the dietary factors and their influence on the loss of renal function and on the evidences in the literature supporting a nephroprotective role of the low-protein diet.

  9. Nutritional management and growth in children with chronic kidney disease.

    PubMed

    Rees, Lesley; Jones, Helen

    2013-04-01

    Despite continuing improvements in our understanding of the causes of poor growth in chronic kidney disease, many unanswered questions remain: why do some patients maintain a good appetite whereas others have profound anorexia at a similar level of renal function? Why do some, but not all, patients respond to increased nutritional intake? Is feed delivery by gastrostomy superior to oral and nasogastric routes? Do children who are no longer in the 'infancy' stage of growth benefit from enteral feeding? Do patients with protein energy wasting benefit from increased nutritional input? How do we prevent obesity, which is becoming so prevalent in the developed world? This review will address these issues.

  10. Aging and the Kidneys: Anatomy, Physiology and Consequences for Defining Chronic Kidney Disease.

    PubMed

    Glassock, Richard J; Rule, Andrew D

    2016-01-01

    The varied functions of the kidneys are influenced by the complex process of aging. The glomerular filtration rate (GFR) steadily declines with normal aging, and the progress of this process can be influenced by superimposed diseases. Microscopically, nephron numbers decrease as global glomerulosclerosis becomes more evident. The precise mechanisms underlying nephron loss with aging are not well understood, but derangements in podocyte biology appear to be involved. Classifications of chronic kidney disease (CKD) incorporate GFR values and attendant risk of adverse events. Arbitrary and fixed thresholds of GFR for defining CKD have led to an overdiagnosis of CKD in the elderly. An age-sensitive definition of CKD could offer a solution to this problem and more meaningfully capture the prognostic implications of CKD.

  11. The Effect of Histological CD20-Positive B Cell Infiltration in Acute Cellular Rejection on Kidney Transplant Allograft Survival

    PubMed Central

    Jiang, Yan; Wang, Rending; Wang, Huiping; Huang, Hongfeng; Peng, Wenhan; Qiu, Wenxian; Zhou, Jingyi

    2016-01-01

    Background. It is controversial whether lymphocyte infiltration exhibited in biopsy specimens is associated with transplant outcomes. This study focused on the effect of CD20-positive B cell infiltration in biopsy specimens from allografts with acute cellular rejection (ACR) in a Chinese population. Methods. Altogether, 216 patients transplanted from Sep. 2001 to Dec. 2014 with biopsy-proved ACR (Banff I or Banff II) were included in the analysis. Biopsies were immunostained for CD20 and C4d. Baseline information, serum creatinine and GFR before and after treatment, steroid resistance, response to treatment, graft loss, and survival were analyzed. Results. Eighty-three patients were classified into CD20-negative group, and 133 patients were classified into CD20-positive group. Significantly more CD20-negative patients (49/83, 59.0%) received steroid plus antibody therapy compared with the CD20-positive group (52/133, 39.1%) (P = 0.004). The response to treatment for ACR did not differ between these two groups. The CD20-positive group had less graft loss (18.8% versus 32.5%, P = 0.022) and a better graft survival rate. Further exploration of the infiltration degree suggested that it tended to be positively related to graft survival, but this did not reach statistical significance. Conclusion. CD20-positive B cell infiltration in renal allograft biopsies with ACR is associated with less steroid resistance and better graft survival. The presence of CD20-positive B cells is protective for renal allografts. PMID:28058267

  12. Uric acid metabolism of kidney and intestine in a rat model of chronic kidney disease.

    PubMed

    Nagura, Michito; Tamura, Yoshifuru; Kumagai, Takanori; Hosoyamada, Makoto; Uchida, Shunya

    2016-12-01

    Uric acid (UA) is a potential risk factor of the progression of chronic kidney disease (CKD). Recently, we reported that intestinal UA excretion might be enhanced via upregulation of the ATP-binding cassette transporter G2 (Abcg2) in a 5/6 nephrectomy (Nx) rat model. In the present study, we examined the mRNA and protein expressions of UA transporters, URAT1, GLUT9/URATv1, ABCG2 and NPT4 in the kidney and ileum in the same rat model. Additionally, we investigated the Abcg2 mRNA expression of ileum in hyperuricemic rat model by orally administering oxonic acid. Male Wistar rats were randomly assigned to three groups consisting of Nx group, oxonic acid-treated (Ox) group and sham-operated control group, and sacrificed at 8 weeks. Creatinine and UA were measured and the mRNA expressions of UA transporters in the kidney and intestine were evaluated by a real time PCR. UA transporters in the kidney sections were also examined by immunohistochemistry. Serum creatinine elevated in the Nx group whereas serum UA increased in the Ox group. Both the mRNA expression and the immunohistochemistry of the UA transporters were decreased in the Nx group, suggesting a marginal role in UA elevation in decreased kidney function. In contrast, the mRNA expression of Abcg2 in the ileum significantly increased in the Ox group. These results suggest that the upregulation of Abcg2 mRNA in the ileum triggered by an elevation of serum UA may play a compensatory role in increasing intestinal UA excretion.

  13. Risk Factors for Progression of Chronic Kidney Disease

    PubMed Central

    Staples, Amy; Wong, Craig

    2010-01-01

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

  14. Kidney EPO expression during chronic hypoxia in aged mice.

    PubMed

    Benderro, Girriso F; LaManna, Joseph C

    2013-01-01

    In order to maintain normal cellular function, mammalian tissue oxygen concentrations must be tightly regulated within a narrow physiological range. The hormone erythropoietin (EPO) is essential for maintenance of tissue oxygen supply by stimulating red blood cell production and promoting their survival. In this study we compared the effects of 290 Torr atmospheric pressure on the kidney EPO protein levels in young (4-month-old) and aged (24-month-old) C57BL/6 mice. The mice were sacrificed after being anesthetized, and kidney samples were collected and processed by Western blot analysis. Relatively low basal expression of EPO during normoxia in young mice showed significant upregulation in hypoxia and stayed upregulated throughout the hypoxic period (threefold compared to normoxic control), showing a slight decline toward the third week. Whereas, a relatively higher normoxic basal EPO protein level in aged mice did not show significant increase until seventh day of hypoxia, but showed significant upregulation in prolonged hypoxia. Hence, we confirmed that there is a progressively increased accumulation of EPO during chronic hypoxia in young and aged mouse kidney, and the EPO upregulation during hypoxia showed a similarity with the pattern of increase in hematocrit, which we have reported previously.

  15. Aggressive blood pressure control for chronic kidney disease unmasks moyamoya!

    PubMed Central

    Davis, T. Keefe; Halabi, Carmen M.; Siefken, Philp; Karmarkar, Swati; Leonard, Jeffrey

    2013-01-01

    Hypertensive crises in children or adolescents are rare, but chronic kidney disease (CKD) is a major risk factor for occurrence. Vesicoureteral reflux nephropathy is a common cause of pediatric renal failure and is associated with hypertension. Aggressive blood pressure (BP) control has been shown to delay progression of CKD and treatment is targeted for the 50th percentile for height when compared with a target below the 90th percentile for the general pediatric hypertensive patient. We present a case of an adolescent presenting with seizures and renal failure due to a hypertensive crisis. Hypertension was thought to be secondary to CKD as she had scarred echogenic kidneys due to known reflux nephropathy. However, aggressive BP treatment improved kidney function which is inconsistent with CKD from reflux nephropathy. Secondly, aggressive BP control caused transient neurological symptoms. Further imaging identified moyamoya disease. We present this case to highlight the consideration of moyamoya as a diagnosis in the setting of renal failure and hypertensive crisis. PMID:26064513

  16. Cognitive Changes in Chronic Kidney Disease and After Transplantation.

    PubMed

    Van Sandwijk, Marit S; Ten Berge, Ineke J M; Majoie, Charles B L M; Caan, Matthan W A; De Sonneville, Leo M J; Van Gool, Willem A; Bemelman, Frederike J

    2016-04-01

    Cognitive impairment is very common in chronic kidney disease (CKD) and is strongly associated with increased mortality. This review article will discuss the pathophysiology of cognitive impairment in CKD, as well as the effect of dialysis and transplantation on cognitive function. In CKD, uremic toxins, hyperparathyroidism and Klotho deficiency lead to chronic inflammation, endothelial dysfunction and vascular calcifications. This results in an increased burden of cerebrovascular disease in CKD patients, who consistently have more white matter hyperintensities, microbleeds, microinfarctions and cerebral atrophy on magnetic resonance imaging scans. Hemodialysis, although beneficial in terms of uremic toxin clearance, also contributes to cognitive decline by causing rapid fluid and osmotic shifts. Decreasing the dialysate temperature and increasing total dialysis time limits these shifts and helps maintain cognitive function in hemodialysis patients. For many patients, kidney transplantation is the preferred treatment modality, because it reverses the underlying mechanisms causing cognitive impairment in CKD. These positive effects have to be balanced against the possible neurotoxicity of infections and immunosuppressive medications, especially glucocorticosteroids and calcineurin inhibitors. A limited number of studies have addressed the overall effect of transplantation on cognitive function. These have mostly found an improvement after transplantation, but have a limited applicability to daily practice because they have only included relatively young patients.

  17. Oxidative Stress in Diabetic Nephropathy with Early Chronic Kidney Disease

    PubMed Central

    Andrade-Sierra, Jorge

    2016-01-01

    The increase in the prevalence of diabetes mellitus (DM) and the secondary kidney damage produces diabetic nephropathy (DN). Early nephropathy is defined as the presence of microalbuminuria (30–300 mg/day), including normal glomerular filtration rate (GFR) or a mildly decreased GFR (60–89 mL/min/1.73 m2), with or without overt nephropathy. The earliest change caused by DN is hyperfiltration with proteinuria. The acceptable excretion rate of albumin in urine is <30 mg/day. Albuminuria represents the excretion of >300 mg/day. Chronic kidney disease (CKD) is characterized by abnormalities in renal function that persist for >3 months with health implications. Alterations in the redox state in DN are caused by the persistent state of hyperglycemia and the increase in advanced glycation end products (AGEs) with ability to affect the renin-angiotensin system and the transforming growth factor-beta (TGF-β), producing chronic inflammation and glomerular and tubular hypertrophy and favoring the appearance of oxidative stress. In DN imbalance between prooxidant/antioxidant processes exists with an increase in reactive oxygen species (ROS). The overproduction of ROS diminishes expression of the antioxidant enzymes (manganese superoxide dismutase, glutathione peroxidase, and catalase). The early detection of CKD secondary to DN and the timely identification of patients would permit decreasing its impact on health. PMID:27525285

  18. BEYOND GENETICS: EPIGENETIC CODE IN CHRONIC KIDNEY DISEASE

    PubMed Central

    Dwivedi, Rama S.; Herman, James G.; McCaffrey, Timothy; Raj, Dominic SC

    2013-01-01

    Epigenetics refers to a heritable change in the pattern of gene expression that is mediated by a mechanism specifically not due to alterations in the primary nucleotide sequence. Well known epigenetic mechanisms encompass DNA methylation, chromatin remodeling (histone modifications) and RNA interference. Functionally, epigenetics provides an extra layer of transcriptional control and plays a crucial role in normal physiological development, as well as in pathological conditions. Aberrant DNA methylation is implicated in immune dysfunction, inflammation and insulin resistance. Epigenetic changes may be responsible for “metabolic memory” and development of micro- and macrovascular complications of diabetes. MicroRNAs are critical in the maintenance of glomerular homeostasis and hence RNA interference may be important in the progression of renal disease. Recent studies have shown that epigenetic modifications orchestrate the epithelial-mesenchymal transition and eventually fibrosis of the renal tissue. Oxidative stress, inflammation, hyperhomocysteinemia and uremic toxins could induce epimutations in chronic kidney disease. Epigenetic alterations are associated with inflammation and cardiovascular disease in patients with chronic kidney disease. Reversible nature of the epigenetic changes gives an unique opportunity to halt or even reverse the disease process through targeted therapeutic strategies. PMID:20881938

  19. [CKD-MBD (Chronic Kidney Disease-Mineral and Bone Disorder). Effect of vitamin D on kidney and cardiovascular system].

    PubMed

    Fujii, Hideki

    2010-07-01

    Recently, many investigators have reported that treatment with vitamin D improves outcomes of patients with chronic kidney disease. Though the detailed mechanisms have remained unclear, it has been speculated that such a treatment may prevent progression of chronic kidney disease and cardiovascular disease. It has been reported that Vitamin D may attenuate renal injury and ameliorate renal function and proteinuria. In addition, several studies have shown that vitamin D may prevent progression of atherosclerosis, vascular calcification and left ventricular hypertrophy. The emerging experimental and clinical evidence has suggested that vitamin D may protect kidney and cardiovascular system.

  20. Hypoxia: The Force that Drives Chronic Kidney Disease

    PubMed Central

    Fu, Qiangwei; Colgan, Sean P; Shelley, Carl Simon

    2016-01-01

    In the United States the prevalence of end-stage renal disease (ESRD) reached epidemic proportions in 2012 with over 600,000 patients being treated. The rates of ESRD among the elderly are disproportionally high. Consequently, as life expectancy increases and the baby-boom generation reaches retirement age, the already heavy burden imposed by ESRD on the US health care system is set to increase dramatically. ESRD represents the terminal stage of chronic kidney disease (CKD). A large body of evidence indicating that CKD is driven by renal tissue hypoxia has led to the development of therapeutic strategies that increase kidney oxygenation and the contention that chronic hypoxia is the final common pathway to end-stage renal failure. Numerous studies have demonstrated that one of the most potent means by which hypoxic conditions within the kidney produce CKD is by inducing a sustained inflammatory attack by infiltrating leukocytes. Indispensable to this attack is the acquisition by leukocytes of an adhesive phenotype. It was thought that this process resulted exclusively from leukocytes responding to cytokines released from ischemic renal endothelium. However, recently it has been demonstrated that leukocytes also become activated independent of the hypoxic response of endothelial cells. It was found that this endothelium-independent mechanism involves leukocytes directly sensing hypoxia and responding by transcriptional induction of the genes that encode the β2-integrin family of adhesion molecules. This induction likely maintains the long-term inflammation by which hypoxia drives the pathogenesis of CKD. Consequently, targeting these transcriptional mechanisms would appear to represent a promising new therapeutic strategy. PMID:26847481

  1. Chronic kidney disease in children and adolescents in Brunei Darussalam

    PubMed Central

    Tan, Shi Ying; Naing, Lin; Han, Aye; Khalil, Muhammad Abdul Mabood; Chong, Vui Heng; Tan, Jackson

    2016-01-01

    AIM: To determine epidemiology of Bruneian paediatric chronic kidney disease (CKD) patients and factors that affect growth and progression of disease. METHODS: A cross-sectional study conducted on all children below 18 years old who were diagnosed with CKD over a ten year period (2004 to 2013). The reference population was all children (< 18 years old) suffering from CKD and attending the tertiary paediatric nephrology clinic in Brunei Darussalam. Demographic (current age, age of diagnosis, gender, ethnicity), anthropometric (weight and height), diagnosis, laboratory data (serum creatinine and haemoglobin, urinalysis) and blood pressure were extracted from the patients’ clinical case notes and recorded using a data collection form. RESULTS: The study revealed a high national prevalence [736 per million child population (pmcp)] and incidence (91 pcmp) of CKD. If CKD was defined at Stage 1, 2, 3, 4 or 5, the associated prevalence figures were 736, 132, 83, 50 and 33 pmcp. Glomerulonephritis accounted for 69% of all prevalent cases, followed by congenital abnormalities of kidney and urinary tract (20%) and tubulointerstitial diseases (8%). Minimal change disease being the most common histological diagnosis. The median age of diagnosis was 4.5 years, with congenital disease patients experiencing an earlier onset of diagnosis. A large proportion of patients were below the 5% percentile for height and weight. Non-glomerular diseases, adolescent and female patients were significantly associated with poor growth, but not glomerular filtration rate, age of diagnosis or steroid usage. CONCLUSION: Brunei has a high prevalence of chronic kidney disease in the paediatric population with glomerulonephritis being the most common disease. PMID:26981447

  2. Albuminuria and posttransplant chronic kidney disease stage predict transplant outcomes.

    PubMed

    Lam, Ngan N; Tonelli, Marcello; Lentine, Krista L; Hemmelgarn, Brenda; Ye, Feng; Wen, Kevin; Klarenbach, Scott

    2017-03-30

    In 2012, the KDIGO guidelines updated the classification system for chronic kidney disease to include albuminuria. Whether this classification system predicts adverse clinical outcomes among kidney transplant recipients is unclear. To evaluate this, we conducted a retrospective study using linked databases in Alberta, Canada to follow kidney transplant recipients from 2002-2011. We examined the association between an estimated glomerular filtration rate (eGFR of 60 or more, 45-59, 30-44, 15-29 mL/min/1.73 m(2)) and albuminuria (normal, mild, heavy) at one year post-transplant and subsequent mortality and graft loss. There were 900 recipients with a functioning graft and at least one outpatient serum creatinine and urine protein measurement at one year post-transplant. The median age was 51.2 years, 38.7% were female, and 52% had an eGFR of 60 mL/min/1.73 m(2) or more. The risk of all-cause mortality and death-censored graft loss was increased in recipients with reduced eGFR or heavier albuminuria. The adjusted incidence rate per 1000 person-years of all-cause mortality for recipients with an eGFR of 15-29 mL/min/1.73 m(2) and heavy albuminuria vs. an eGFR 60 mL/min/1.73 m(2) or more and normal protein excretion was 117 (95% confidence interval 38-371) vs. 15 (9-23) (rate ratio 8). Corresponding rates for death-censored graft loss were 273 (88-1203) vs. 6 (3-9) (rate ratio 49). Reduced eGFR and heavier albuminuria in kidney transplant recipients are associated with an increased risk of mortality and graft loss. Thus, eGFR and albuminuria may be used together to identify, evaluate, and manage transplant recipients who are at higher risk of adverse clinical outcomes.

  3. Two-Stage, In Silico Deconvolution of the Lymphocyte Compartment of the Peripheral Whole Blood Transcriptome in the Context of Acute Kidney Allograft Rejection

    PubMed Central

    Shannon, Casey P.; Balshaw, Robert; Ng, Raymond T.; Wilson-McManus, Janet E.; Keown, Paul; McMaster, Robert; McManus, Bruce M.; Landsberg, David; Isbel, Nicole M.; Knoll, Greg; Tebbutt, Scott J.

    2014-01-01

    Acute rejection is a major complication of solid organ transplantation that prevents the long-term assimilation of the allograft. Various populations of lymphocytes are principal mediators of this process, infiltrating graft tissues and driving cell-mediated cytotoxicity. Understanding the lymphocyte-specific biology associated with rejection is therefore critical. Measuring genome-wide changes in transcript abundance in peripheral whole blood cells can deliver a comprehensive view of the status of the immune system. The heterogeneous nature of the tissue significantly affects the sensitivity and interpretability of traditional analyses, however. Experimental separation of cell types is an obvious solution, but is often impractical and, more worrying, may affect expression, leading to spurious results. Statistical deconvolution of the cell type-specific signal is an attractive alternative, but existing approaches still present some challenges, particularly in a clinical research setting. Obtaining time-matched sample composition to biologically interesting, phenotypically homogeneous cell sub-populations is costly and adds significant complexity to study design. We used a two-stage, in silico deconvolution approach that first predicts sample composition to biologically meaningful and homogeneous leukocyte sub-populations, and then performs cell type-specific differential expression analysis in these same sub-populations, from peripheral whole blood expression data. We applied this approach to a peripheral whole blood expression study of kidney allograft rejection. The patterns of differential composition uncovered are consistent with previous studies carried out using flow cytometry and provide a relevant biological context when interpreting cell type-specific differential expression results. We identified cell type-specific differential expression in a variety of leukocyte sub-populations at the time of rejection. The tissue-specificity of these differentially

  4. Short-term and long-term effects of acute kidney injury in chronic kidney disease patients: A longitudinal analysis.

    PubMed

    Asar, Özgür; Ritchie, James; Kalra, Philip A; Diggle, Peter J

    2016-11-01

    We use data from an ongoing cohort study of chronic kidney patients at Salford Royal NHS Foundation Trust, Greater Manchester, United Kingdom, to investigate the influence of acute kidney injury (AKI) on the subsequent rate of change of kidney function amongst patients already diagnosed with chronic kidney disease (CKD). We use a linear mixed effects modelling framework to enable estimation of both acute and chronic effects of AKI events on kidney function. We model the fixed effects by a piece-wise linear function with three change-points to capture the acute changes in kidney function that characterise an AKI event, and the random effects by the sum of three components: a random intercept, a stationary stochastic process with Matérn correlation structure, and measurement error. We consider both multivariate Normal and multivariate t versions of the random effects. For either specification, we estimate model parameters by maximum likelihood and evaluate the plug-in predictive distributions of the random effects given the data. We find that following an AKI event the average long-term rate of decline in kidney function is almost doubled, regardless of the severity of the event. We also identify and present examples of individual patients whose kidney function trajectories diverge substantially from the population-average.

  5. 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

  6. 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

  7. 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

  8. Interactions between cytokines, congenital anomalies of kidney and urinary tract and chronic kidney disease.

    PubMed

    Simões e Silva, Ana Cristina; Valério, Flávia Cordeiro; Vasconcelos, Mariana Affonso; Miranda, Débora Marques; Oliveira, Eduardo Araújo

    2013-01-01

    Fetal hydronephrosis is the most common anomaly detected on antenatal ultrasound, affecting 1-5% of pregnancies. Postnatal investigation has the major aim in detecting infants with severe urinary tract obstruction and clinically significant urinary tract anomalies among the heterogeneous universe of patients. Congenital uropathies are frequent causes of pediatric chronic kidney disease (CKD). Imaging techniques clearly contribute to this purpose; however, sometimes, these exams are invasive, very expensive, and not sufficient to precisely define the best approach as well as the prognosis. Recently, biomarkers have become a focus of clinical research as potentially useful diagnostic tools in pediatric urological diseases. In this regard, recent studies suggest a role for cytokines and chemokines in the pathophysiology of CAKUT and for the progression to CKD. Some authors proposed that the evaluation of these inflammatory mediators might help the management of postnatal uropathies and the detection of patients with high risk to developed chronic kidney disease. Therefore, the aim of this paper is to revise general aspects of cytokines and the link between cytokines, CAKUT, and CKD by including experimental and clinical evidence.

  9. Interactions between Cytokines, Congenital Anomalies of Kidney and Urinary Tract and Chronic Kidney Disease

    PubMed Central

    Simões e Silva, Ana Cristina; Valério, Flávia Cordeiro; Vasconcelos, Mariana Affonso; Miranda, Débora Marques; Oliveira, Eduardo Araújo

    2013-01-01

    Fetal hydronephrosis is the most common anomaly detected on antenatal ultrasound, affecting 1–5% of pregnancies. Postnatal investigation has the major aim in detecting infants with severe urinary tract obstruction and clinically significant urinary tract anomalies among the heterogeneous universe of patients. Congenital uropathies are frequent causes of pediatric chronic kidney disease (CKD). Imaging techniques clearly contribute to this purpose; however, sometimes, these exams are invasive, very expensive, and not sufficient to precisely define the best approach as well as the prognosis. Recently, biomarkers have become a focus of clinical research as potentially useful diagnostic tools in pediatric urological diseases. In this regard, recent studies suggest a role for cytokines and chemokines in the pathophysiology of CAKUT and for the progression to CKD. Some authors proposed that the evaluation of these inflammatory mediators might help the management of postnatal uropathies and the detection of patients with high risk to developed chronic kidney disease. Therefore, the aim of this paper is to revise general aspects of cytokines and the link between cytokines, CAKUT, and CKD by including experimental and clinical evidence. PMID:24066006

  10. Acute kidney injury and chronic kidney disease: an integrated clinical syndrome.

    PubMed

    Chawla, Lakhmir S; Kimmel, Paul L

    2012-09-01

    The previous conventional wisdom that survivors of acute kidney injury (AKI) tend to do well and fully recover renal function appears to be flawed. AKI can cause end-stage renal disease (ESRD) directly, and increase the risk of developing incident chronic kidney disease (CKD) and worsening of underlying CKD. In addition, severity, duration, and frequency of AKI appear to be important predictors of poor patient outcomes. CKD is an important risk factor for the development and ascertainment of AKI. Experimental data support the clinical observations and the bidirectional nature of the relationships between AKI and CKD. Reductions in renal mass and nephron number, vascular insufficiency, cell cycle disruption, and maladaptive repair mechanisms appear to be important modulators of progression in patients with and without coexistent CKD. Distinction between AKI and CKD may be artificial. Consideration should be given to the integrated clinical syndrome of diminished GFR, with acute and chronic stages, where spectrum of disease state and outcome is determined by host factors, including the balance of adaptive and maladaptive repair mechanisms over time. Physicians must provide long-term follow-up to patients with first episodes of AKI, even if they presented with normal renal function.

  11. Effect of telmisartan on kidney function in patients with chronic kidney disease: an observational study

    PubMed Central

    Agrawal, Ashish; Kamila, Shibnath; Reddy, Swetha; Lilly, Joyal; Mariyala, MS Sadhguna

    2016-01-01

    Abstract Background: Globally the burden of chronic kidney disease (CKD) is rising, an important cause of death and loss of disability-adjusted life years. Activation of the renin-angiotensin-aldosterone system is involved in its pathogenesis. The aim of the present study was to examine the effects of telmisartan (40 mg/day), an angiotensin receptor blocker (ARB) in Indian patients with CKD in real-life setting. Method: This was a prospective observational study. Fifty-six patients (>18 years) diagnosed with CKD were enrolled into the study. Serum creatinine, 24-h urinary protein, spot urine protein-to-creatinine ratio, glomerular filtration rate (GFR) and blood pressure (BP) were assessed along with safety. Results: A total of 55 patients (96.36% hypertensive; 63.61% diabetic) with mean age of 48.23 years completed the study. At the end of 3 months treatment with telmisartan, 24-h urinary protein, spot urine protein-to-creatinine, serum creatinine and BP significantly reduced (p < .05) by 806.78 mg, 0.95, 0.44 mg/dl and 8.9/4.7 mmHg in the overall population. GFR increased from the baseline value of 52.13 to 65.01 ml/min. Telmisartan was well tolerated and treatment was discontinued in one patient because of hyperkalemia. Conclusion: This study demonstrated that telmisartan effectively and safely reduces proteinuria in chronic kidney disease patients. PMID:27994942

  12. Urinary C-X-C Motif Chemokine 10 Independently Improves the Noninvasive Diagnosis of Antibody-Mediated Kidney Allograft Rejection.

    PubMed

    Rabant, Marion; Amrouche, Lucile; Lebreton, Xavier; Aulagnon, Florence; Benon, Aurélien; Sauvaget, Virginia; Bonifay, Raja; Morin, Lise; Scemla, Anne; Delville, Marianne; Martinez, Frank; Timsit, Marc Olivier; Duong Van Huyen, Jean-Paul; Legendre, Christophe; Terzi, Fabiola; Anglicheau, Dany

    2015-11-01

    Urinary levels of C-X-C motif chemokine 9 (CXCL9) and CXCL10 can noninvasively diagnose T cell-mediated rejection (TCMR) of renal allografts. However, performance of these molecules as diagnostic/prognostic markers of antibody-mediated rejection (ABMR) is unknown. We investigated urinary CXCL9 and CXCL10 levels in a highly sensitized cohort of 244 renal allograft recipients (67 with preformed donor-specific antibodies [DSAs]) with 281 indication biopsy samples. We assessed the benefit of adding these biomarkers to conventional models for diagnosing/prognosing ABMR. Urinary CXCL9 and CXCL10 levels, normalized to urine creatinine (Cr) levels (CXCL9:Cr and CXCL10:Cr) or not, correlated with the extent of tubulointerstitial (i+t score; all P<0.001) and microvascular (g+ptc score; all P<0.001) inflammation. CXCL10:Cr diagnosed TCMR (area under the curve [AUC]=0.80; 95% confidence interval [95% CI], 0.68 to 0.92; P<0.001) and ABMR (AUC=0.76; 95% CI, 0.69 to 0.82; P<0.001) with high accuracy, even in the absence of tubulointerstitial inflammation (AUC=0.70; 95% CI, 0.61 to 0.79; P<0.001). Although mean fluorescence intensity of the immunodominant DSA diagnosed ABMR (AUC=0.75; 95% CI, 0.68 to 0.82; P<0.001), combining urinary CXCL10:Cr with immunodominant DSA levels improved the diagnosis of ABMR (AUC=0.83; 95% CI, 0.77 to 0.89; P<0.001). At the time of ABMR, urinary CXCL10:Cr ratio was independently associated with an increased risk of graft loss. In conclusion, urinary CXCL10:Cr ratio associates with tubulointerstitial and microvascular inflammation of the renal allograft. Combining the urinary CXCL10:Cr ratio with DSA monitoring significantly improves the noninvasive diagnosis of ABMR and the stratification of patients at high risk for graft loss.

  13. Factors associated with chronic musculoskeletal pain in patients with chronic kidney disease

    PubMed Central

    2014-01-01

    Background Chronic musculoskeletal (MS) pain is common in patients with chronic kidney disease (CKD) undergoing haemodialysis. However, epidemiological data for chronic MS pain and factors associated with chronic MS pain in patients with early- or late-stage CKD who are not undergoing dialysis are limited. Method A cross-sectional study to evaluate the prevalence of chronic MS pain and factors associated with chronic MS pain in patients with early- and late-stage CKD who were not undergoing dialysis, was conducted. In addition, the distribution of pain severity among patients with different stages of CKD was evaluated. Results Of the 456 CKD patients studied, 53.3% (n = 243/456) had chronic MS pain. Chronic MS pain was independently and significantly associated with hyperuricemia as co-morbidity, as well as with the calcium × phosphate product levels. In CKD patients with hyperuricemia, chronic MS pain showed a negative, independent significant association with diabetes mellitus as a co-morbidity (odds ratio: 0.413, p = 0.020). However, in the CKD patients without hyperuricemia as a co-morbidity, chronic MS pain showed an independent significant association with the calcium × phosphate product levels (odds ratio: 1.093, p = 0.027). Furthermore, stage-5 CKD patients seemed to experience more severe chronic MS pain than patients with other stages of CKD. Conclusion Chronic MS pain is common in CKD patients. Chronic MS pain was independently and significantly associated with hyperuricemia as co-morbidity, and with the calcium × phosphate product levels in early- and late-stage CKD patients who were not on dialysis. PMID:24400957

  14. Prevalence of Diabetes Mellitus in Patients with Chronic Kidney Disease

    PubMed Central

    Stojceva-Taneva, Olivera; Otovic, Natasa Eftimovska; Taneva, Borjanka

    2016-01-01

    BACKGROUND: Chronic kidney disease (CKD) became a new epidemic of the twentieth and twenty-first centuries. Diabetic nephropathy is one of the leading causes of end-stage renal failure as a result of the diabetes epidemic worldwide. AIM: The aim of our study was to assess the prevalence of CKD in the Republic of Macedonia and its association with diabetes mellitus. MATERIALS AND METHODS: The study was a part of a study conducted in 2006 in terms of screening for early detection of kidney disease. It was a cross-sectional study based on a random sample of patients aged > 20, consecutively consulting their primary physician for any cause. Fifty physicians throughout the country were included in the study. A total of 2637 patients have been analyzed based on integrity data. GFR was estimated using corrected values of serum creatinine and calculating kidney function by the Cockroft & Gault formula, adjusted for body surface using the Gehan & George formula. Patients with estimated glomerular filtration rate (eGFR) less than 60 ml/min were considered as having CKD. Blood pressure, body weight, height, serum creatinine, glucose, hemoglobin, hematocrit, urinalysis and medical history for presence of cardiovascular diseases or diabetes were also assessed. RESULTS: The mean age of the subjects was 45.97 ± 16.55 SD and 17.97% were older than 60. Regarding gender, 44.14% were males. The prevalence of diabetes mellitus was 13.9%. Subjects with CKD (eGFR less than 60 ml/min) were 7.53% of the total. Subjects aged 60 or above, had 20 times higher risk of having CKD (eGFR less than 60 ml/min/1.73 m2). Out of the total group of subjects, 13.9% had diabetes mellitus and they had 3.13 times higher risk of having CKD stage 3-5 (eGFR less than 60 ml/min/1.73 m2) when compared to non-diabetics. The results showed that diabetes was significantly more associated with lower eGFR (less than 60 ml/min/1.73 m2) in younger subjects (age less than 60) compared to older ones (odds ratio 3

  15. In experimental chronic kidney disease or cancer, parathyroid hormone is a novel mediator of cachexia.

    PubMed

    Wyatt, Christina M; Mitch, William E

    2016-05-01

    Hyperparathyroidism plays a central role in the disordered bone mineral metabolism of chronic kidney disease, and has been associated with increased cardiovascular morbidity and mortality in that setting. A recent study suggests a novel role for parathyroid hormone and its receptor in muscle wasting and cachexia occurring in advanced chronic kidney disease.

  16. Fournier’s gangrene associated with chronic kidney disease in a dog

    PubMed Central

    Lee, Jung-Jin; Park, Hye-Mi; Kim, Jung-Hyun

    2016-01-01

    A dog was diagnosed with Fournier’s gangrene associated with chronic kidney disease. Clinical features included crepitant scrotal inflammation that spread to the penis; the lesion exhibited liquefactive necrosis or purulent moist gangrene. This is the first description of Fournier’s gangrene associated with chronic kidney disease in a dog. PMID:27708443

  17. Future options for the management of chronic kidney disease in Nigeria.

    PubMed

    Okafor, Chidi; Kankam, Charity

    2012-02-01

    The lack of health care infrastructure and prevalence of infectious disease in Nigeria exacerbate the growing problem of diagnosing and treating chronic kidney disease. Nigeria should place more emphasis on chronic kidney disease education, screening, and prevention; propagation of acceptance of peritoneal dialysis over hemodialysis; subsidization of renal replacement costs; and advancement of the national renal transplantation program.

  18. Pregnancy management and outcome in women with chronic kidney disease.

    PubMed

    Bili, E; Tsolakidis, D; Stangou, S; Tarlatzis, B

    2013-04-01

    An increasing number of pregnancies occur in the presence of chronic kidney diseases (CKD), mainly including chronic glomerulonephritis (GN), diabetic nephropathy (DN), and lupus nephritis (LN). The most important factor affecting fetal and maternal prognosis is the degree of renal function at conception. In the majority of patients with mild renal function impairment, and well-controlled blood pressure, pregnancy is usually successful and does not alter the natural course of maternal renal disease. Conversely, fetal outcome and long-term maternal renal function might be seriously threatened by pregnancy in women with moderate or severe renal function impairment. The last few years, advances in our knowledge about the interaction of pregnancy and renal function resulted in the improvement of fetal outcome in patients with chronic renal failure and also in the management of pregnant women with end-stage renal disease (ESRD) maintained on dialysis. However, women with impaired renal function and those on dialysis should be carefully counseled about the risks of pregnancy.

  19. Mesenchymal Stromal Cell Therapy for Chronic Lung Allograft Dysfunction: Results of a First-in-Man Study.

    PubMed

    Chambers, Daniel C; Enever, Debra; Lawrence, Sharon; Sturm, Marian J; Herrmann, Richard; Yerkovich, Stephanie; Musk, Michael; Hopkins, Peter M A

    2017-04-01

    Chronic lung transplant rejection (termed chronic lung allograft dysfunction [CLAD]) is the main impediment to long-term survival after lung transplantation. Bone marrow-derived mesenchymal stromal cells (MSCs) represent an attractive cell therapy in inflammatory diseases, including organ rejection, given their relative immune privilege and immunosuppressive and tolerogenic properties. Preclinical studies in models of obliterative bronchiolitis and human trials in graft versus host disease and renal transplantation suggest potential efficacy in CLAD. The purpose of this phase 1, single-arm study was to explore the feasibility and safety of intravenous delivery of allogeneic MSCs to patients with advanced CLAD. MSCs from unrelated donors were isolated from bone marrow, expanded and cryopreserved in a GMP-compliant facility. Patients had deteriorating CLAD and were bronchiolitis obliterans (BOS) grade ≥ 2 or grade 1 with risk factors for rapid progression. MSCs (2 x 10(6) cells per kilogram patient weight) were infused via a peripheral vein twice weekly for 2 weeks, with 52 weeks follow-up. Ten Patients (5 male, 8 bilateral, median [interquartile range] age 40 [30-59] years, 3 BOS2, 7 BOS3) participated. MSC treatment was well tolerated with all patients receiving the full dosing schedule without any procedure-related serious adverse events. The rate of decline in forced expiratory volume in one second slowed after the MSC infusions (120 ml/month preinfusion vs. 30 ml/month postinfusion, p = .08). Two patients died at 152 and 270 days post-MSC treatment, both from progressive CLAD. In conclusion, infusion of allogeneic bone marrow-derived MSCs is feasible and safe even in patients with advanced CLAD. Stem Cells Translational Medicine 2017;6:1152-1157.

  20. Soluble CD59 is a Novel Biomarker for the Prediction of Obstructive Chronic Lung Allograft Dysfunction After Lung Transplantation

    PubMed Central

    Budding, Kevin; van de Graaf, Eduard. A.; Kardol-Hoefnagel, Tineke; Kwakkel-van Erp, Johanna M.; Luijk, Bart D.; Oudijk, Erik-Jan D.; van Kessel, Diana A.; Grutters, Jan C.; Hack, C. Erik; Otten, Henderikus G.

    2016-01-01

    CD59 is a complement regulatory protein that inhibits membrane attack complex formation. A soluble form of CD59 (sCD59) is present in various body fluids and is associated with cellular damage after acute myocardial infarction. Lung transplantation (LTx) is the final treatment for end-stage lung diseases, however overall survival is hampered by chronic lung allograft dysfunction development, which presents itself obstructively as the bronchiolitis obliterans syndrome (BOS). We hypothesized that, due to cellular damage and activation during chronic inflammation, sCD59 serum levels can be used as biomarker preceding BOS development. We analyzed sCD59 serum concentrations in 90 LTx patients, of whom 20 developed BOS. We observed that BOS patients exhibited higher sCD59 serum concentrations at the time of diagnosis compared to clinically matched non-BOS patients (p = 0.018). Furthermore, sCD59 titers were elevated at 6 months post-LTx (p = 0.0020), when patients had no BOS-related symptoms. Survival-analysis showed that LTx patients with sCD59 titers ≥400 pg/ml 6 months post-LTx have a significant (p < 0.0001) lower chance of BOS-free survival than patients with titers ≤400 pg/ml, 32% vs. 80% respectively, which was confirmed by multivariate analysis (hazard ratio 6.2, p < 0.0001). We propose that circulating sCD59 levels constitute a novel biomarker to identify patients at risk for BOS following LTx. PMID:27215188

  1.  Association between hepatitis B virus and chronic kidney disease: a systematic review and meta-analysis.

    PubMed

    Fabrizi, Fabrizio; Donato, Francesca M; Messa, Piergiorgio

     Background. Hepatitis B virus infection and chronic kidney disease are prevalent and remain a major public health problem worldwide. It remains unclear how infection with hepatitis B virus impacts on the development and progression of chronic kidney disease.

  2. Treatment of hypertension in children with chronic kidney disease.

    PubMed

    Halbach, Susan; Flynn, Joseph

    2015-01-01

    Hypertension (HTN) is increasingly recognized as a common feature of pediatric chronic kidney disease (CKD). A growing body of evidence demonstrates that HTN is both underdiagnosed and undertreated in this population. The consequences of untreated HTN include adverse effects on CKD progression, markers of cardiovascular morbidity, and neurocognitive functioning. Consensus guidelines issued over the past decade have incorporated recent research on the consequences of HTN in recommendations for the diagnosis and treatment of HTN in pediatric CKD and include lower BP targets. Agents which target the renin-angiotensin-aldosterone system (RAAS) should be considered first-line therapy in CKD-associated HTN in children, though multiple medications may be required to achieve sufficient BP control.

  3. Resistant Hypertension and Chronic Kidney Disease: a Dangerous Liaison.

    PubMed

    Wolley, Martin J; Stowasser, Michael

    2016-04-01

    Treatment-resistant hypertension is an increasingly recognised problem and is markedly over-represented in patients with chronic kidney disease (CKD). Recent evidence has clarified the heightened risk for both adverse renal and cardiovascular outcomes associated with resistant hypertension, even when blood pressure control is attained. The diagnosis of resistant hypertension in CKD is reliant on accurate blood pressure measurement, and out of office measurements are important due to the high prevalence of masked hypertension in these patients. Treatment strategies include careful dietary measures to restrict sodium intake, and a focus on improving adherence to antihypertensive medications. Medication choices should focus on a sensible foundation and then diuretic titration to combat the salt and volume retention inherent in CKD. In this review, we discuss the epidemiology, pathogenesis and consequences of resistant hypertension in CKD, and then review the optimal diagnostic and management strategies.

  4. Metformin therapy in patients with chronic kidney disease.

    PubMed

    Duong, J K; Roberts, D M; Furlong, T J; Kumar, S S; Greenfield, J R; Kirkpatrick, C M; Graham, G G; Williams, K M; Day, R O

    2012-10-01

    Metformin therapy is limited in patients with chronic kidney disease (CKD) due to the potential risk of lactic acidosis. This open-label observational study investigated metformin and lactate concentrations in patients with CKD (n = 22; creatinine clearances 15-40 ml/min) and in two dialysed patients. Patients were prescribed a range of metformin doses (250-2000 mg daily) and metformin concentrations were compared with data from healthy subjects (scaled to 1500 mg twice daily). A subset of patients (n = 7) was controlled on low doses of metformin (250 or 500 mg daily). No correlation between metformin and lactate concentrations was observed. Three patients had high lactate concentrations (>2.7 mmol/l) and two had high metformin concentrations (3-5 mg/l), but none had any symptoms of lactic acidosis. Reducing metformin dosage and monitoring metformin concentrations will allow the safe use of metformin in CKD, provided that renal function is stable.

  5. Multi-Trajectory Models of Chronic Kidney Disease Progression.

    PubMed

    Burckhardt, Philipp; Nagin, Daniel S; Padman, Rema

    2016-01-01

    An ever increasing number of people are affected by chronic kidney disease (CKD). A better understanding of the progression ofCKD and its complications is needed to address what is becoming a major burden for health-care systems worldwide. Utilizing a rich data set consisting of the Electronic Health Records (EHRs) of more than 33,000 patients from a leading community nephrology practice in Western Pennsylvania, we applied group-based trajectory modeling (GBTM) in order to detect patient risk groups and uncover typical progressions of CKD and related comorbidities and complications. We have found distinct risk groups with differing trajectories and are able to classify new patients into these groups with high accuracy (up to ≈ 90%). Our results suggest that multitrajectory modeling via GBTM can shed light on the developmental course ofCKD and the interactions between related complications.

  6. Vegetarianism: advantages and drawbacks in patients with chronic kidney diseases.

    PubMed

    Chauveau, Philippe; Combe, Christian; Fouque, Denis; Aparicio, Michel

    2013-11-01

    Vegetarian diet is a very old practice that is liable to confer some health benefits. Recent studies have demonstrated that modification of the dietary pattern with a reduction of animal protein intake and increased consumption of plant-based foods could influence cardiovascular risk profile and mortality rate. Moreover, phosphate bioavailability from plant proteins is reduced. These statements could lead to some benefits for chronic kidney disease (CKD) patients. This review summarizes the characteristics and benefits of vegetarian diets in the general population and the potential beneficial effects of such a diet on phosphate balance, insulin sensitivity, and the control of metabolic acidosis in CKD patients. Potential drawbacks exist when a vegetarian diet is associated with protein intake that is too restrictive and/or insufficient energy intake, justifying an early and regular nutritional follow-up jointly assumed by a nephrologist and a renal dietitian.

  7. Multi-Trajectory Models of Chronic Kidney Disease Progression

    PubMed Central

    Burckhardt, Philipp; Nagin, Daniel S.; Padman, Rema

    2016-01-01

    An ever increasing number of people are affected by chronic kidney disease (CKD). A better understanding of the progression ofCKD and its complications is needed to address what is becoming a major burden for health-care systems worldwide. Utilizing a rich data set consisting of the Electronic Health Records (EHRs) of more than 33,000 patients from a leading community nephrology practice in Western Pennsylvania, we applied group-based trajectory modeling (GBTM) in order to detect patient risk groups and uncover typical progressions of CKD and related comorbidities and complications. We have found distinct risk groups with differing trajectories and are able to classify new patients into these groups with high accuracy (up to ≈ 90%). Our results suggest that multitrajectory modeling via GBTM can shed light on the developmental course ofCKD and the interactions between related complications. PMID:28269932

  8. Erectile dysfunction in chronic kidney disease: From pathophysiology to management

    PubMed Central

    Papadopoulou, Eirini; Varouktsi, Anna; Lazaridis, Antonios; Boutari, Chrysoula; Doumas, Michael

    2015-01-01

    Chronic kidney disease (CKD) is encountered in millions of people worldwide, with continuously rising incidence during the past decades, affecting their quality of life despite the increase of life expectancy in these patients. Disturbance of sexual function is common among men with CKD, as both conditions share common pathophysiological causes, such as vascular or hormonal abnormalities and are both affected by similar coexisting comorbid conditions such as cardiovascular disease, hypertension and diabetes mellitus. The estimated prevalence of erectile dysfunction reaches 70% in end stage renal disease patients. Nevertheless, sexual dysfunction remains under-recognized and under-treated in a high proportion of these patients, a fact which should raise awareness among clinicians. A multifactorial approach in management and treatment is undoubtedly required in order to improve patients’ quality of life and cardiovascular outcomes. PMID:26167462

  9. DNA Damage in Chronic Kidney Disease: Evaluation of Clinical Biomarkers

    PubMed Central

    Schupp, Nicole; Stopper, Helga; Heidland, August

    2016-01-01

    Patients with chronic kidney disease (CKD) exhibit an increased cancer risk compared to a healthy control population. To be able to estimate the cancer risk of the patients and to assess the impact of interventional therapies thereon, it is of particular interest to measure the patients' burden of genomic damage. Chromosomal abnormalities, reduced DNA repair, and DNA lesions were found indeed in cells of patients with CKD. Biomarkers for DNA damage measurable in easily accessible cells like peripheral blood lymphocytes are chromosomal aberrations, structural DNA lesions, and oxidatively modified DNA bases. In this review the most common methods quantifying the three parameters mentioned above, the cytokinesis-block micronucleus assay, the comet assay, and the quantification of 8-oxo-7,8-dihydro-2′-deoxyguanosine, are evaluated concerning the feasibility of the analysis and regarding the marker's potential to predict clinical outcomes. PMID:27313827

  10. Chronic kidney disease and albuminuria in arterial hypertension.

    PubMed

    Leoncini, Giovanna; Viazzi, Francesca; Pontremoli, Roberto

    2010-10-01

    Chronic kidney disease is a major public health problem worldwide: it is estimated that in the general population, 1 person in 10 has some degree of renal damage. Adequate blood pressure control represents the mainstay of treatment, to delay deterioration of renal function and prevent cardiovascular complications. Current evidence supports a target blood pressure value of 130/80 mm Hg or less (ie, <125/75 mm Hg) when proteinuria exceeds 1 g/L. Angiotensin-converting enzyme inhibitors or angiotensin II receptor blockers represent the treatment of choice, especially in the presence of proteinuria. More complete blockade of the renin-angiotensin-aldosterone system (RAAS) has been advocated, using a combination of multiple RAAS blocker drugs or supramaximal doses to maximize renal protection. Achieving recommended blood pressure target values usually requires the use of multiple antihypertensive drugs, including diuretics and calcium channel blockers.

  11. [Self-Management in Patients With Chronic Kidney Disease].

    PubMed

    Chiou, Chou-Ping; Lu, Yung-Chuan; Hung, Shih-Yuan

    2016-04-01

    Chronic kidney disease (CKD) patients typically self-manage their disease-care program. Self-management requires the investment of considerable time and energy in health management and in following the multifaceted CKD treatment regimen. CKD, a progressive disease, is classified into five stages that correspond to the five stages of decline in kidney function, as measured using the glomerular filtration rate (GRF). Each of these stages requires that a patient modify his / her lifestyle and shoulder the responsibility for day-to-day health management tasks. Key to promoting self-management is the partnership and collaboration between healthcare providers and patients. Tasks in this partnership include patient assessment and communication, regimen adherence, emotional management, negotiation of care plans, and the enhancement of self-efficacy, with the aims of creating positive changes in behavior, promoting correct symptoms interpretation and reporting, and promoting the appropriate use of resources. Nurses may help patients maneuver this initially frightening and sometimes difficult terrain with strategies that are tailored to each CKD stage.

  12. Developments in renal pharmacogenomics and applications in chronic kidney disease

    PubMed Central

    Padullés, Ariadna; Rama, Inés; Llaudó, Inés; Lloberas, Núria

    2014-01-01

    Chronic kidney disease (CKD) has shown an increasing prevalence in the last century. CKD encompasses a poor prognosis related to a remarkable number of comorbidities, and many patients suffer from this disease progression. Once the factors linked with CKD evolution are distinguished, it will be possible to provide and enhance a more intensive treatment to high-risk patients. In this review, we focus on the emerging markers that might be predictive or related to CKD progression physiopathology as well as those related to a different pattern of response to treatment, such as inhibitors of the renin–angiotensin system (including angiotensin-converting enzyme inhibitors and angiotensin II receptor blockers; the vitamin D receptor agonist; salt sensitivity hypertension; and progressive kidney-disease markers with identified genetic polymorphisms). Candidate-gene association studies and genome-wide association studies have analyzed the genetic basis for common renal diseases, including CKD and related factors such as diabetes and hypertension. This review will, in brief, consider genotype-based pharmacotherapy, risk prediction, drug target recognition, and personalized treatments, and will mainly focus on findings in CKD patients. An improved understanding will smooth the progress of switching from classical clinical medicine to gene-based medicine. PMID:25206311

  13. FGF-23 and secondary hyperparathyroidism in chronic kidney disease.

    PubMed

    Silver, Justin; Naveh-Many, Tally

    2013-11-01

    The metabolic changes that occur in patients with chronic kidney disease (CKD) have a profound influence on mineral and bone metabolism. CKD results in altered levels of serum phosphate, vitamin D, calcium, parathyroid hormone (PTH) and fibroblast growth factor 23 (FGF-23); the increased levels of serum phosphate, PTH and FGF-23 contribute to the increased cardiovascular mortality in affected patients. FGF-23 is produced by osteocytes and osteoblasts and acts physiologically in the kidney to induce phosphaturia and inhibit the synthesis of 1,25-dihydroxyvitamin D3. PTH acts directly on osteocytes to increase FGF-23 expression. In addition, the high levels of PTH associated with CKD contribute to changes in bone remodelling that result in decreased levels of dentin matrix protein 1 and the release of low-molecular-weight fibroblast growth factors from the bone matrix, which stimulate FGF-23 transcription. A prolonged oral phosphorus load increases FGF-23 expression by a mechanism that includes local changes in the ratio of inorganic phosphate to pyrophosphate in bone. Other factors such as dietary vitamin D compounds, calcium, and metabolic acidosis all increase FGF-23 levels. This Review discusses the mechanisms by which secondary hyperparathyroidism associated with CKD stimulates bone cells to overexpress FGF-23 levels.

  14. Discriminants of prevalent fractures in chronic kidney disease.

    PubMed

    Nickolas, Thomas L; Cremers, Serge; Zhang, Amy; Thomas, Valeri; Stein, Emily; Cohen, Adi; Chauncey, Ryan; Nikkel, Lucas; Yin, Michael T; Liu, Xiaowei S; Boutroy, Stephanie; Staron, Ronald B; Leonard, Mary B; McMahon, Donald J; Dworakowski, Elzbieta; Shane, Elizabeth

    2011-08-01

    Patients with chronic kidney disease (CKD) have higher rates of fracture than the general population. Increased bone remodeling, leading to microarchitectural deterioration and increased fragility, may accompany declining kidney function, but there are no reliable methods to identify patients at increased risk for fracture. In this cross-sectional study of 82 patients with predialysis CKD, high-resolution imaging revealed that the 23 patients with current fractures had significantly lower areal density at the femoral neck; total, cortical, and trabecular volumetric bone density; cortical area and thickness; and trabecular thickness. Compared with levels in the lowest tertile, higher levels of osteocalcin, procollagen type-1 N-terminal propeptide, and tartrate-resistant acid phosphatase 5b were associated with higher odds of fracture, even after adjustment for femoral neck T-score. Discrimination of fracture prevalence was best with a femoral neck T-score of -2.0 or less and a value in the upper two tertiles for osteocalcin, procollagen type-1 N-terminal propeptide, or tartrate-resistant acid phosphatase 5b; these values corresponded to the upper half of the normal premenopausal reference range. In summary, these cross-sectional data suggest that measurement of bone turnover markers may increase the diagnostic accuracy of densitometry to identify patients with CKD at high risk for fracture.

  15. Amygdalin inhibits renal fibrosis in chronic kidney disease.

    PubMed

    Guo, Junqi; Wu, Weizheng; Sheng, Mingxiong; Yang, Shunliang; Tan, Jianming

    2013-05-01

    Renal interstitial fibrosis is a common outcome of chronic renal diseases. Amygdalin is one of a number of nitrilosides, the natural cyanide‑containing substances abundant in the seeds of plants of the prunasin family that are used to treat cancer and relieve pain. However, whether amygdalin inhibits the progression of renal fibrosis or not remains unknown. The present study aimed to assess the therapeutic potential of amygdalin by investigating its effect and potential mechanism on the activation of renal interstitial fibroblast cells and renal fibrosis in rat unilateral ureteral obstruction (UUO). Treatment of the cultured renal interstitial fibroblasts with amygdalin inhibited their proliferation and the production of transforming growth factor (TGF)‑β1. In the rat model of obstructive nephropathy, following ureteral obstruction, the administration of amygdalin immediately eliminated the extracellular matrix accumulation and alleviated the renal injury on the 21st day. Collectively, amygdalin attenuated kidney fibroblast (KFB) activation and rat renal interstitial fibrosis. These results indicate that amygdalin is a potent antifibrotic agent that may have therapeutic potential for patients with fibrotic kidney diseases.

  16. Protein-Energy Wasting and Mortality in Chronic Kidney Disease

    PubMed Central

    Bonanni, Alice; Mannucci, Irene; Verzola, Daniela; Sofia, Antonella; Saffioti, Stefano; Gianetta, Ezio; Garibotto, Giacomo

    2011-01-01

    Protein-energy wasting (PEW) is common in patients with chronic kidney disease (CKD) and is associated with an increased death risk from cardiovascular diseases. However, while even minor renal dysfunction is an independent predictor of adverse cardiovascular prognosis, PEW becomes clinically manifest at an advanced stage, early before or during the dialytic stage. Mechanisms causing loss of muscle protein and fat are complex and not always associated with anorexia, but are linked to several abnormalities that stimulate protein degradation and/or decrease protein synthesis. In addition, data from experimental CKD indicate that uremia specifically blunts the regenerative potential in skeletal muscle, by acting on muscle stem cells. In this discussion recent findings regarding the mechanisms responsible for malnutrition and the increase in cardiovascular risk in CKD patients are discussed. During the course of CKD, the loss of kidney excretory and metabolic functions proceed together with the activation of pathways of endothelial damage, inflammation, acidosis, alterations in insulin signaling and anorexia which are likely to orchestrate net protein catabolism and the PEW syndrome. PMID:21655142

  17. Anticoagulation Therapy in Patients with Chronic Kidney Disease.

    PubMed

    Saheb Sharif-Askari, Fatemeh; Syed Sulaiman, Syed Azhar; Saheb Sharif-Askari, Narjes

    2017-01-01

    Patients with chronic kidney disease (CKD) are at increased risk for both thrombotic events and bleeding. The early stages of CKD are mainly associated with prothrombotic tendency, whereas in its more advanced stages, beside the prothrombotic state, platelets can become dysfunctional due to uremic-related toxin exposure leading to an increased bleeding tendency. Patients with CKD usually require anticoagulation therapy for treatment or prevention of thromboembolic diseases. However, this benefit could easily be offset by the risk of anticoagulant-induced bleeding. Treatment of patients with CKD should be based on evidence from randomized clinical trials, but usually CKD patients are excluded from these trials. In the past, unfractionated heparins were the anticoagulant of choice for patients with CKD because of its independence of kidney elimination. However, currently low-molecular-weight heparins have largely replaced the use of unfractionated heparins owing to fewer incidences of heparin-induced thrombocytopenia and bleeding. We undertook this review in order to explain the practical considerations for the management of anticoagulation in these high risk population.

  18. Systemic Redox Imbalance in Chronic Kidney Disease: A Systematic Review

    PubMed Central

    Kaltsatou, Antonia; Jamurtas, Athanasios Z.; Koutedakis, Yiannis; Stefanidis, Ioannis; Sakkas, Giorgos K.

    2016-01-01

    Patients with chronic kidney disease (CKD) experience imbalance between oxygen reactive species (ROS) production and antioxidant defenses leading to cell and tissue damage. However, it remains unclear at which stage of renal insufficiency the redox imbalance becomes more profound. The aim of this systematic review was to provide an update on recent advances in our understanding of how the redox status changes in the progression of renal disease from predialysis stages 1 to 4 to end stage 5 and whether the various treatments and dialysis modalities influence the redox balance. A systematic review was conducted searching PubMed and Scopus by using the Cochrane and PRISMA guidelines. In total, thirty-nine studies met the inclusion criteria and were reviewed. Even from an early stage, imbalance in redox status is evident and as the kidney function worsens it becomes more profound. Hemodialysis therapy per se seems to negatively influence the redox status by the elevation of lipid peroxidation markers, protein carbonylation, and impairing erythrocyte antioxidant defense. However, other dialysis modalities do not so far appear to confer advantages. Supplementation with antioxidants might assist and should be considered as an early intervention to halt premature atherogenesis development at an early stage of CKD. PMID:27563376

  19. Emerging risk factors and markers of chronic kidney disease progression.

    PubMed

    Kronenberg, Florian

    2009-12-01

    Chronic kidney disease (CKD) is a common condition with an increasing prevalence. A number of comorbidities are associated with CKD and prognosis is poor, with many patients experiencing disease progression. Recognizing the factors associated with CKD progression enables high-risk patients to be identified and given more intensive treatment if necessary. The identification of new predictive markers might improve our understanding of the pathogenesis and progression of CKD. This Review discusses a number of emerging factors and markers for which epidemiological evidence from prospective studies indicates an association with progression of CKD. The following factors and markers are discussed: asymmetric dimethylarginine, factors involved in calcium-phosphate metabolism, adrenomedullin, A-type natriuretic peptide, N-terminal pro-brain natriuretic peptide, liver-type fatty acid binding protein, kidney injury molecule 1, neutrophil gelatinase-associated lipocalin, apolipoprotein A-IV, adiponectin and some recently identified genetic polymorphisms. Additional epidemiological and experimental data are required before these markers can be broadly used for the prediction of CKD progression and before the risk factors can be considered as potential drug targets in clinical interventional trials.

  20. The Use of Targeted Biomarkers for Chronic Kidney Disease

    PubMed Central

    Devarajan, Prasad

    2010-01-01

    There is a paucity of sensitive and specific biomarkers for the early prediction of chronic kidney disease (CKD) progression. The recent application of innovative technologies such as functional genomics, proteomics, and biofluid profiling has uncovered a number of new candidates that are emerging as predictive biomarkers of CKD. The most promising among these include urinary proteins such as neutrophil gelatinase-associated lipocalin (NGAL), kidney injury molecule-1 (KIM-1), and liver-type fatty acid binding protein (L-FABP). In addition, an improved understanding of the complex pathophysiologic processes underlying CKD progression has also provided discriminatory biomarkers of CKD progression that are being actively evaluated. Candidates included in this category are plasma proteins such as asymmetric dimethylarginine (ADMA), adiponectin, apolipoprotein A-IV (apoA-IV), fibroblast growth factor 23 (FGF23), NGAL, and the natriuretic peptides, as well as urinary N-acetyl-β-D-glucosaminidase (NAG). This review represents a critical appraisal of the current status of these emerging CKD biomarkers. At the present time, none are ready for routine clinical use. Additional large, multicenter prospective studies are needed to validate the biomarkers, identify thresholds and cut-offs for prediction of CKD progression and adverse events, assess the effects of confounding variables, and establish the ideal assays. PMID:21044769

  1. Cardiovascular Pharmacogenomics – Implications for Patients with Chronic Kidney Disease

    PubMed Central

    Cavallari, Larisa H.; Mason, Darius L.

    2016-01-01

    Chronic kidney disease (CKD) is an independent risk factor for cardiovascular disease. Thus, patients with CKD often require treatment with cardiovascular drugs, such as antiplatelet, antihypertensive, anticoagulant, and lipid-lowering agents. There is significant inter-patient variability in response to cardiovascular therapies, which contributes to risk for treatment failure or adverse drug effects. Pharmacogenomics offers the potential to optimize cardiovascular pharmacotherapy and improve outcomes in patients with cardiovascular disease, though data in patients with concomitant CKD are limited. The drugs with the most pharmacogenomic evidence are warfarin, clopidogrel, and statins. There are also accumulating data for genetic contributions to β-blocker response. Guidelines are now available to assist with applying pharmacogenetic test results to optimize warfarin dosing, selection of antiplatelet therapy after percutaneous coronary intervention, and prediction of risk for statin-induced myopathy. Clinical data, such as age, body size, and kidney function have long been used to optimize drug prescribing. An increasing number of institutions are also implementing genetic testing to be considered in the context of important clinical factors to further personalize drug therapy for patients with cardiovascular disease. PMID:26979147

  2. Management of chronic kidney disease and dialysis in homeless persons.

    PubMed

    Podymow, Tiina; Turnbull, Jeff

    2013-05-01

    End-stage renal disease and dialysis are complicated illnesses to manage in homeless persons, who often suffer medical comorbidities, psychiatric disease, cognitive impairment and addictions; descriptions of this population and management strategies are lacking. A retrospective review of dialysis patients who were homeless or unstably housed was undertaken at an urban academic Canadian center from 2001 to 2011. Electronic hospital records were analyzed for demographic, housing, medical, and psychiatric history, dialysis history, adherence to treatment, and outcomes. Two detailed cases of homeless patients with chronic kidney disease are presented. Eleven homeless dialysis patients with a mean age of 52.7±12.3 years, mostly men and mostly from minority groups were dialyzed for 41.1±29.2 months. Most resided permanently in shelters, eventually obtained fistula access, and were adherent to dialysis schedules. Patients were often nonadherent to pre-dialysis management, resulting in emergency starts. Many barriers to care for homeless persons with end-stage kidney disease and on dialysis are identified, and management strategies are highlighted. Adherence is optimized with shelter-based health care and intensive team-oriented case management.

  3. Role of Vitamin D in Chronic Kidney Disease

    PubMed Central

    Patel, Tejas; Singh, Ajay K.

    2009-01-01

    Decline in renal function is directly related to cardiovascular mortality. However, traditional risk factors do not fully account for the high mortality in these patients. Activated vitamin D, a hormone produced by the proximal convoluted tubule of the kidney, appears to have beneficial effects beyond suppressing parathyroid hormone. However, activated vitamin D can also cause hypercalcemia and hyperphosphatemia in chronic kidney disease (CKD). Newer agents such as vitamin D receptor activators (VDRAs, e.g., paricalcitol) suppress PTH with reduced risk of hypercalcemia and hyperphosphatemia. Recent evidence from animal and preliminary human studies supports an association between VDRAs and reduced risk of CVD deaths, irrespective of PTH levels. New pathways of vitamin D regulation have also been discovered, namely the roles of fibroblast growth factor-23 and klotho. Although tremendous work has been done to advance our understanding of the effects of vitamin D in health and CKD, more investigations and randomized trials need to be performed to elucidate the mechanistic underpinnings of this effect. PMID:19371802

  4. Coronary artery calcification in chronic kidney disease: An update

    PubMed Central

    Stompór, Tomasz

    2014-01-01

    Arterial calcification is a well-recognized complication of advanced atherosclerosis. Chronic kidney disease (CKD) is characterized by significantly more pronounced, disseminated and fast-progressing calcification of the vascular system, including the coronary arteries. New computed tomography-based imaging techniques allow for the noninvasive assessment and monitoring of calcification in different vascular sites. Coronary artery calcification (CAC) develops early in the course of CKD and is tightly associated with mineral and bone disorders, which include but are not limited to secondary hyperparathyroidism. In this review, recent data on the pathogenesis of CAC development and progression are discussed, with a special emphasis on fibroblast growth factor 23 and its co-receptor, klotho. The prevalence, progression and prognostic significance of CAC are reviewed separately for patients with end-stage renal disease treated with dialysis, kidney transplant recipients and patients with earlier stages of CKD. In the last section, therapeutic considerations are discussed, with special attention paid to the importance of treatment that addresses mineral and bone disorders of CKD. PMID:24772252

  5. Modulation of stroke risk in chronic kidney disease

    PubMed Central

    Arnold, Julia; Sims, Don; Ferro, Charles J.

    2016-01-01

    Stroke is the second most common cause of death and the leading cause of neurological disability worldwide, with huge economic costs and tragic human consequences. Both chronic kidney disease (CKD) and end-stage kidney disease are associated with a significantly increased risk of stroke. However, to date this has generated far less interest compared with the better-recognized links between cardiac and renal disease. Common risk factors for stroke, such as hypertension, hypercholesterolaemia, smoking and atrial fibrillation, are shared with the general population but are more prevalent in renal patients. In addition, factors unique to these patients, such as disorders of mineral and bone metabolism, anaemia and its treatments as well as the process of dialysis itself, are all also postulated to further increase the risk of stroke. In the general population, advances in medical therapies mean that effective primary and secondary prevention therapies are available for many patients. The development of specialist stroke clinics and acute stroke units has also improved outcomes after a stroke. Emerging therapies such as thrombolysis and thrombectomy are showing increasingly beneficial results. However, patients with CKD and on dialysis have different risk profiles that must be taken into account when considering the potential benefits and risks of these treatments. Unfortunately, these patients are either not recruited or formally excluded from major clinical trials. There is still much work to be done to harness effective stroke treatments with an acceptable safety profile for patients with CKD and those on dialysis. PMID:26798458

  6. Fractal analysis of the retinal vasculature and chronic kidney disease.

    PubMed

    Sng, Chelvin C A; Sabanayagam, Charumathi; Lamoureux, Ecosse L; Liu, Erica; Lim, Su Chi; Hamzah, Haslina; Lee, Jeannette; Tai, E Shyong; Wong, Tien Y

    2010-07-01

    BACKGROUND. Fractal analysis provides a global index of the geometric complexity and optimality of vascular networks. In this study, we investigated the relationship between fractal measurements of the retinal vasculature and chronic kidney disease (CKD). METHODS. This was a population-based case-control study which included participants from the Singapore Prospective Study Program. We identified 261 participants with CKD, defined as estimated glomerular filtration rate of <60 mL/min/1.73 m(2), and 651 controls. The retinal fractal dimension (D(f)) was quantified from digitized fundus photographs using a computer-based programme. RESULTS. The mean D(f) was 1.43 +/- 0.048 in the participants with CKD and 1.44 +/- 0.042 in controls (P = 0.013). Suboptimal D(f) in the lowest (first) and highest (fifth) quintiles were associated with an increased prevalence of CKD after adjusting for age, systolic blood pressure, diabetes and other risk factors [odds ratio (OR) 2.10, 95% confidence interval (CI) 1.15, 3.83 and OR 1.84, 95% CI 1.06, 3.17; compared to the fourth quintile, respectively). This association was present even in participants without diabetes or hypertension. CONCLUSIONS. Our study found that an abnormal retinal vascular network is associated with an increased risk of CKD, supporting the hypothesis that deviations from optimal microvascular architecture may be related to kidney damage.

  7. Chronic kidney disease and the involvement of estrogen hormones in its pathogenesis and progression.

    PubMed

    Gluhovschi, Gh; Gluhovschi, A; Anastasiu, D; Petrica, Ligia; Gluhovschi, Cristina; Velciov, Silvia

    2012-01-01

    The kidney is under the influence of sexual hormones. Estrogens have a favourable role in the progression of some chronic renal diseases. Estrogen hormones act upon the nephron component cells, regulating several processes going on at this level. One of the most important actions of the estrogens is represented by the protective effect on the kidneys, estrogens attenuating glomerulosclerosis and tubulo-interstitial fibrosis. Thus, estrogens have nephroprotective effects. Phosphorus-calcium metabolism disturbances during chronic kidney disease are influenced by numerous regulatory factors: parathormone, vitamin D fibroblast growth factor, 23. Estrogens play an important part in disturbances of the phosphorus-calcium metabolism, co-operating with these factors. They exert favourable effects on renal osteodystrophy, the main consequence of phosphorus-calcium disturbances. Hormonal dysfunction in chronic kidney disease is clinically accompanied by sexual dysfunction that influences the life quality of these patients. In advanced stages of chronic kidney disease, especially in dialysed patients, these sexual dysfunctions can be more evident. Hormonal replacement therapy and estrogen therapy- receptor modulating therapy have an important role in correcting hormonal dysfunctions manifest in chronic kidney disease. Caution is necessary in case of a would-be pregnancy in patients with chronic kidney disease, given its risks and the complexity of the problem. Renal transplantation corrects to a great extent hormonal dysfunctions in chronic kidney disease.

  8. Chronic Kidney Disease, Fluid Overload and Diuretics: A Complicated Triangle

    PubMed Central

    Khan, Yusra Habib; Sarriff, Azmi; Adnan, Azreen Syazril; Khan, Amer Hayat; Mallhi, Tauqeer Hussain

    2016-01-01

    Background Despite promising role of diuretics to manage fluid overload among chronic kidney disease (CKD) patients, their use is associated with adverse renal outcomes. Current study aimed to determine the extent of renal deterioration with diuretic therapy. Methods A total 312 non-dialysis dependent CKD (NDD-CKD) patients were prospectively followed-up for one year. Fluid overload was assessed via bioimpedance spectroscopy. Estimated GFR (eGFR) was calculated from serum creatinine values by using Chronic Kidney Disease- Epidemiology Collaboration (CKD-EPI) equation. Results Out of 312 patients, 64 (20.5%) were hypovolemic while euvolemia and hypervolemia were observed in 113 (36.1%) and 135 (43.4%) patients. Overall 144 patients were using diuretics among which 98 (72.6%) were hypervolemic, 35 (30.9%) euvolemic and 11 (17.2%) were hypovolemic. The mean decline in estimated GFR of entire cohort was -2.5 ± 1.4 ml/min/1.73m2 at the end of follow up. The use of diuretics was significantly associated with decline in eGFR. A total of 36 (11.5%) patients initiated renal replacement therapy (RRT) and need of RRT was more profound among diuretic users. Conclusions The use of diuretics was associated with adverse renal outcomes indicated by decline in eGFR and increasing risk of RRT initiation in our cohort of NDD-CKD patients. Therefore, it is cautiously suggested to carefully prescribe diuretics by keeping in view benefit versus harm for each patient. PMID:27442587

  9. Insulin resistance in chronic kidney disease: a systematic review.

    PubMed

    Spoto, Belinda; Pisano, Anna; Zoccali, Carmine

    2016-12-01

    Insulin resistance (IR) is an early metabolic alteration in chronic kidney disease (CKD) patients, being apparent when the glomerular filtration rate is still within the normal range and becoming almost universal in those who reach the end stage of kidney failure. The skeletal muscle represents the primary site of IR in CKD, and alterations at sites beyond the insulin receptor are recognized as the main defect underlying IR in this condition. Estimates of IR based on fasting insulin concentration are easier and faster but may not be adequate in patients with CKD because renal insufficiency reduces insulin catabolism. The hyperinsulinemic euglycemic clamp is the gold standard for the assessment of insulin sensitivity because this technique allows a direct measure of skeletal muscle sensitivity to insulin. The etiology of IR in CKD is multifactorial in nature and may be secondary to disturbances that are prominent in renal diseases, including physical inactivity, chronic inflammation, oxidative stress, vitamin D deficiency, metabolic acidosis, anemia, adipokine derangement, and altered gut microbiome. IR contributes to the progression of renal disease by worsening renal hemodynamics by various mechanisms, including activation of the sympathetic nervous system, sodium retention, and downregulation of the natriuretic peptide system. IR has been solidly associated with intermediate mechanisms leading to cardiovascular (CV) disease in CKD including left ventricular hypertrophy, vascular dysfunction, and atherosclerosis. However, it remains unclear whether IR is an independent predictor of mortality and CV complications in CKD. Because IR is a modifiable risk factor and its reduction may lower CV morbidity and mortality, unveiling the molecular mechanisms responsible for the pathogenesis of CKD-related insulin resistance is of importance for the identification of novel therapeutic targets aimed at reducing the high CV risk of this condition.

  10. UPDATE ON FIBROBLAST GROWTH FACTOR 23 IN CHRONIC KIDNEY DISEASE

    PubMed Central

    Wolf, Myles

    2012-01-01

    Chronic kidney disease (CKD) is a public health epidemic that affects millions of people worldwide. Presence of CKD predisposes individuals to high risks of end-stage renal disease, cardiovascular disease and premature death. Disordered phosphate homeostasis with elevated circulating levels of fibroblast growth factor 23 (FGF23) is an early and pervasive complication of CKD. CKD is likely the most common cause of chronically elevated FGF23 levels, and the clinical condition in which levels are most markedly elevated. Although increases in FGF23 levels help maintain serum phosphate in the normal range in CKD, prospective studies in populations of pre-dialysis CKD, incident and prevalent end-stage renal disease, and kidney transplant recipients demonstrate that elevated FGF23 levels are independently associated with progression of CKD and development of cardiovascular events and mortality. It was originally thought that these observations were driven by elevated FGF23 acting as a highly sensitive biomarker of toxicity due to phosphate. However, FGF23 itself has now been shown to mediate “off-target,” direct, end-organ toxicity in the heart, which suggests that elevated FGF23 may be a novel mechanism of adverse outcomes in CKD. This report reviews recent advances in FGF23 biology relevant to CKD, the classical effects of FGF23 on mineral homeostasis, and the studies that established FGF23 excess as a biomarker and novel mechanism of cardiovascular disease. The report concludes with a critical review of the effects of different therapeutic strategies targeting FGF23 reduction and how these might be leveraged in a future randomized trial aimed at improving outcomes in CKD. PMID:22622492

  11. ADVANCE: Study to Evaluate Cinacalcet Plus Low Dose Vitamin D on Vascular Calcification in Subjects With Chronic Kidney Disease Receiving Hemodialysis

    ClinicalTrials.gov

    2014-07-14

    Chronic Kidney Disease; End Stage Renal Disease; Coronary Artery Calcification; Vascular Calcification; Calcification; Cardiovascular Disease; Chronic Renal Failure; Hyperparathyroidism; Kidney Disease; Nephrology; Secondary Hyperparathyroidism

  12. Genomic imbalances in pediatric patients with chronic kidney disease

    PubMed Central

    Verbitsky, Miguel; Sanna-Cherchi, Simone; Fasel, David A.; Levy, Brynn; Kiryluk, Krzysztof; Wuttke, Matthias; Abraham, Alison G.; Kaskel, Frederick; Köttgen, Anna; Warady, Bradley A.; Furth, Susan L.; Wong, Craig S.; Gharavi, Ali G.

    2015-01-01

    BACKGROUND. There is frequent uncertainty in the identification of specific etiologies of chronic kidney disease (CKD) in children. Recent studies indicate that chromosomal microarrays can identify rare genomic imbalances that can clarify the etiology of neurodevelopmental and cardiac disorders in children; however, the contribution of unsuspected genomic imbalance to the incidence of pediatric CKD is unknown. METHODS. We performed chromosomal microarrays to detect genomic imbalances in children enrolled in the Chronic Kidney Disease in Children (CKiD) prospective cohort study, a longitudinal prospective multiethnic observational study of North American children with mild to moderate CKD. Patients with clinically detectable syndromic disease were excluded from evaluation. We compared 419 unrelated children enrolled in CKiD to multiethnic cohorts of 21,575 children and adults that had undergone microarray genotyping for studies unrelated to CKD. RESULTS. We identified diagnostic copy number disorders in 31 children with CKD (7.4% of the cohort). We detected 10 known pathogenic genomic disorders, including the 17q12 deletion HNF1 homeobox B (HNF1B) and triple X syndromes in 19 of 419 unrelated CKiD cases as compared with 98 of 21,575 control individuals (OR 10.8, P = 6.1 × 10–20). In an additional 12 CKiD cases, we identified 12 likely pathogenic genomic imbalances that would be considered reportable in a clinical setting. These genomic imbalances were evenly distributed among patients diagnosed with congenital and noncongenital forms of CKD. In the vast majority of these cases, the genomic lesion was unsuspected based on the clinical assessment and either reclassified the disease or provided information that might have triggered additional clinical care, such as evaluation for metabolic or neuropsychiatric disease. CONCLUSION. A substantial proportion of children with CKD have an unsuspected genomic imbalance, suggesting genomic disorders as a risk factor for

  13. Retinopathy and Chronic Kidney Disease in the Chronic Renal Insufficiency Cohort Study (CRIC)

    PubMed Central

    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.

    2013-01-01

    Objectives Retinal vascular and anatomic abnormalities caused by diabetes, hypertension, and other conditions can be observed directly in the ocular fundus and may reflect severity of chronic renal insufficiency. The purpose of this study was to investigate the association between retinopathy and chronic kidney disease (CKD). Methods In this observational, cross-sectional study, 2605 participants of the Chronic Renal Insufficiency Cohort (CRIC) study, a multi-center study of CKD, were offered participation. Non-mydriatic fundus photographs of the disc and macula in both eyes were obtained in 1936 of these subjects. 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 non-traditional risk factors for decreased kidney function were obtained from the CRIC study. Results Greater severity of retinopathy was associated with lower estimated glomerular filtration rate (eGFR) after adjustment for traditional and non-traditional risk factors. Presence of vascular abnormalities usually associated with hypertension was also associated with lower eGFR. We found no strong direct relationship between eGFR and average arteriolar or venular calibers. Conclusions Our findings show a strong association between severity of retinopathy and its features and level of kidney function after adjustment for traditional and non-traditional risk factors for CKD, suggesting that retinovascular pathology reflects renal disease. PMID:22965589

  14. Stroke and Chronic Kidney Disease: Epidemiology, Pathogenesis, and Management Across Kidney Disease Stages

    PubMed Central

    Weiner, Daniel E.; Dad, Taimur

    2015-01-01

    Summary Cerebrovascular disease and stroke are very common at all stages of chronic kidney disease (CKD), likely representing both shared risk factors as well as synergy among risk factors. More subtle ischemic brain lesions may be particularly common in the CKD population, with subtle manifestations including cognitive impairment. For individuals with nondialysis CKD, the prevention, approach to, diagnosis, and management of stroke is similar to the general, non-CKD population. For individuals with end-stage renal disease, far less is known regarding the prevention of stroke. Stroke prophylaxis using warfarin in dialysis patients with atrial fibrillation in particular remains of uncertain benefit. End-stage renal disease patients can be managed aggressively in the setting of acute stroke. Outcomes after stroke at all stages of CKD are poor, and improving these outcomes should be the subject of future clinical trials. PMID:26355250

  15. Chronic kidney disease and its prevention in India.

    PubMed

    Agarwal, Sanjay K

    2005-09-01

    Chronic kidney disease (CKD) is an important, chronic, noncommunicable disease epidemic that affects the world, including India. Because of the absence of a renal registry in India, the true magnitude of CKD/end-stage renal disease (ESRD) is unknown. Two community-based studies, although methodologically different, have shown a prevalence of chronic renal failure of 0.16% and 0.79%. The cost of maintenance hemodialysis for a single session varies between 10 US dollars to 40 between government-run and private hospitals. The average cost of erythropoetin is approximately 150 US dollars to 200 per month. The cost of chronic ambulatory peritoneal dialysis with "Y" set at 3 exchanges per week, which most patients in India do, is US 400 US dollars per month. The cost of a renal transplant (RT) procedure is approximately US 700 US dollars to 800 in the government sector and 6000 US dollars in the private sector. The cost of immunosuppression with basic triple immunosuppression drugs (cyclosporine, steroid, and azathioprin) is US 250 US dollars per month. There are hardly any state-funded medical treatment and medical insurance facilities for CKD and ESRD patients in India. India has nearly 700 nephrologists and approximately 400 dialysis units with 1000 dialysis stations, with the majority being in the private sector. A maximum of 2% of patients can be subjected to maintenance hemodialysis. Until now, approximately 3000 patients have been initiated on chronic ambulatory peritoneal dialysis. India has approximately 100 RT centers, mostly in private setup, and not more than 3000 to 4000 RTs are performed annually. Thus, only 3% to 5% of all patients with ESRD in India get some form of renal replacement therapy. Thus, planning for prevention of CKD on a long-term basis is the only practical solution for India. It appears that even in India, diabetes and hypertension are responsible for 40% to 50% of all cases of chronic renal failure. Screening for these 2 diseases and CKD

  16. Predictors of chronic kidney disease in type 2 diabetes

    PubMed Central

    De Cosmo, Salvatore; Viazzi, Francesca; Pacilli, Antonio; Giorda, Carlo; Ceriello, Antonio; Gentile, Sandro; Russo, Giuseppina; Rossi, Maria C.; Nicolucci, Antonio; Guida, Pietro; Pontremoli, Roberto

    2016-01-01

    Abstract The identification of clinical predictors for the development of chronic kidney disease is a critical issue in the management of patients with type 2 diabetes mellitus. We evaluated 27,029 patients with type 2 diabetes mellitus and estimated glomerular filtration rate (eGFR) ≥60 mL/min/1.73 m2 and normoalbuminuria from the database of the Italian Association of Clinical Diabetologists network. Primary outcomes were eGFR <60 mL/min/1.73 m2 and normoalbuminuria; albuminuria and eGFR ≥60 mL/min/1.73 m2; and eGFR <60 mL/min/1.73 m2 and albuminuria. Secondary outcomes were eGFR <60 mL/min/1.73 m2 and albuminuria. Measurements: eGFR from serum creatinine by chronic kidney disease epidemiology collaboration equation (CKD-EPI), urinary albumin excretion, HbA1c, triglycerides, high-density lipoprotein cholesterol (HDL-c) and low-density lipoprotein cholesterol (LDL-c), blood pressure, and body mass index. Over a 4-year period, 33.2% of patients (n = 8973) developed chronic kidney disease, 10.3% (n = 2788) showed a decline in eGFR <60 mL/min/1.73 m2, 18.4% (n = 4978) developed albuminuria, and 4.5% (n = 1207) developed both features. Relative risk ratios (RRRs) for age (1.37, P < 0.001 by 5 years), sex (0.77, P < 0.001 for being male), body mass index (1.03, P < 0.001 by 1 kg/m2), triglycerides (1.02, P < 0.001 by 10 mg/dL), and LDL-c (0.97, P = 0.004 by 10 mg/dL) were independently related to the onset of eGFR reduction. Age (1.08, P < 0.001 by 5 years), sex (1.36, P < 0.001 for being male), body mass index (1.02, P < 0.001 by 1 kg/m2), triglycerides (1.01, P = 0.02 by 10 mg/dL), HDL-c, and LDL-c (0.97, P = 0.008 and 0.99, P = 0.003 by 5 and 10 mg/dL, respectively) were related to the onset of albuminuria. HbA1c and the intensity of antihypertensive treatment showed a weaker association with renal outcome. Reduction in eGFR and albuminuria showed distinct sets of risk factors, suggesting that

  17. Evidence-based guidelines for the management of hypertension in children with chronic kidney disease.

    PubMed

    Dionne, Janis M

    2015-11-01

    Hypertension is common in children with chronic kidney disease and early evidence suggests that it is a modifiable risk factor for renal and cardiovascular outcomes. Recommendations for blood pressure management in children with chronic kidney disease can be found in various clinical practice guidelines including the 4th Task Force Report, the European Society of Hypertension pediatric recommendations, and the National Kidney Foundation Kidney Disease Outcomes Quality Initiative (K/DOQI) and Kidney Disease: Improving Global Outcomes (KDIGO) guidelines for the management of blood pressure in chronic kidney disease. Unfortunately, as pediatric trial evidence is limited, there are discrepancies in the recommendations that may lead to inconsistent clinical care and practice variation. This article reviews the strength of evidence behind each of the clinical practice guideline recommendations regarding blood pressure assessment, treatment targets, and first-line antihypertensive medications. The benefits and cautions of use of clinical practice guidelines are described with emphasis on the importance of reading beyond the summary statements.

  18. Pregnancy in a 24 year old Nigerian woman with chronic kidney disease: challenges and outcome.

    PubMed

    Okafor, U H; Nwobodo, M U; Ezeugwu, F O

    2013-01-01

    There is increasing incidence and prevalence of chronic kidney disease worldwide. The developing countries including Nigeria are facing greater challenges because of the prevailing poverty and high burden of infectious diseases. There are various prevalent co-morbid conditions that influence and are influenced by the status of the kidney function of the patient. These conditions pose some peculiar challenges and management of the challenges will determine the outcome. The aim of this report is to highlight the chalIenges of pregnancy in women with chronic kidney disease and possible outcome. We report a 24 years Nigerian woman diagnosed with chronic kidney disease who presented with 10 weeks gestation and deteriorating kidney function. Her management was associated with various challenges including non adherance to medications and not regular to follow up visits. She later developed ecclampsia and had intra uterine fetal death. She had various interventional measures including haemodialysis. She recovered kidney function appreciably but has defaulted follow up since discharge.

  19. Plasma Uromodulin Correlates With Kidney Function and Identifies Early Stages in Chronic Kidney Disease Patients

    PubMed Central

    Steubl, Dominik; Block, Matthias; Herbst, Victor; Nockher, Wolfgang Andreas; Schlumberger, Wolfgang; Satanovskij, Robin; Angermann, Susanne; Hasenau, Anna-Lena; Stecher, Lynne; Heemann, Uwe; Renders, Lutz; Scherberich, Jürgen

    2016-01-01

    Abstract Uromodulin, released from tubular cells of the ascending limb into the blood, may be associated with kidney function. This work studies the relevance of plasma uromodulin as a biomarker for kidney function in an observational cohort of chronic kidney disease (CKD) patients and subjects without CKD (CKD stage 0). It should be further evaluated if uromodulin allows the identification of early CKD stages. Plasma uromodulin, serum creatinine, cystatin C, blood-urea-nitrogen (BUN) concentrations, and estimated glomerular filtration rate (eGFR CKD-EPIcrea-cystatin) were assessed in 426 individuals of whom 71 were CKD stage 0 and 355 had CKD. Besides descriptive statistics, univariate correlations between uromodulin and biomarkers/eGFR were calculated using Pearson-correlation coefficient. Multiple linear regression modeling was applied to establish the association between uromodulin and eGFR adjusted for demographic parameters and pharmacologic treatment. Receiver-operating-characteristic (ROC) analysis adjusted for demographic parameters was performed to test if uromodulin allows differentiation of subjects with CKD stage 0 and CKD stage I. Mean uromodulin plasma levels were 85.7 ± 60.5 ng/mL for all CKD stages combined. Uromodulin was correlated with all biomarkers/eGFR in univariate analysis (eGFR: r = 0.80, creatinine: r = −0.76, BUN: r = −0.72, and cystatin C: r = −0.79). Multiple linear regression modeling showed significant association between uromodulin and eGFR (coefficient estimate β = 0.696, 95% confidence interval [CI] 0.603–0.719, P < 0.001). In ROC analysis uromodulin was the only parameter that significantly improved a model containing demographic parameters to differentiate between CKD 0° and I° (area under the curve [AUC] 0.831, 95% CI 0.746–0.915, P = 0.008) compared to creatinine, cystatin C, BUN, and eGFR (AUC for creatinine: 0.722, P = 0.056, cystatin C: 0.668, P = 0.418, BUN: 0.653, P

  20. Hypertension in children with chronic kidney disease: pathophysiology and management.

    PubMed

    Hadtstein, Charlotte; Schaefer, Franz

    2008-03-01

    Arterial hypertension is very common in children with all stages of chronic kidney disease (CKD). While fluid overload and activation of the renin-angiotensin system have long been recognized as crucial pathophysiological pathways, sympathetic hyperactivation, endothelial dysfunction and chronic hyperparathyroidism have more recently been identified as important factors contributing to CKD-associated hypertension. Moreover, several drugs commonly administered in CKD, such as erythropoietin, glucocorticoids and cyclosporine A, independently raise blood pressure in a dose-dependent fashion. Because of the deleterious consequences of hypertension on the progression of renal disease and cardiovascular outcomes, an active screening approach should be adapted in patients with all stages of CKD. Before one starts antihypertensive treatment, non-pharmacological options should be explored. In hemodialysis patients a low salt diet, low dialysate sodium and stricter dialysis towards dry weight can often achieve adequate blood pressure control. Angiotensin-converting enzyme (ACE) inhibitors and angiotensin receptor blockers are first-line therapy for patients with proteinuria, due to their additional anti-proteinuric properties. Diuretics are a useful alternative for non-proteinuric patients or as an add-on to renin-angiotensin system blockade. Multiple drug therapy is often needed to maintain blood pressure below the 90th percentile target, but adequate blood pressure control is essential for better renal and cardiovascular long-term outcomes.

  1. Alteration of the platelet transcriptome in chronic kidney disease.

    PubMed

    Plé, Hélène; Maltais, Manon; Corduan, Aurélie; Rousseau, Guy; Madore, François; Provost, Patrick

    2012-10-01

    Bleeding and thrombotic disorders are major complications affecting patients with chronic kidney disease (CKD). Exposure of circulating platelets to uraemic toxins and contact with artificial surfaces during dialysis induce platelet abnormalities and alter the platelet proteome. We hypothesised that these changes may be subsequent to changes in the composition and/or regulation of the platelet transcriptome. In this study, we investigated the circulating platelets of 10 CKD patients (i.e. five chronic haemodialysis patients and five stage 4 CKD uraemic patients) and five age- and sex-matched healthy subjects. We observed an alteration of the platelet messenger RNA (mRNA) and microRNA transcriptome in CKD patients. Impaired in uraemic platelets, the levels of some mRNAs and of most microRNAs appeared to be corrected by dialysis, which is consistent with a beneficial effect of dialysis and a mRNA regulatory role of platelet microRNAs. Reduced in platelets of uraemic patients, phosphatidylcholine transfer protein (PCTP) and WD repeat-containing protein 1 (WDR1) were found to be regulated by microRNAs, the latter of which involving hsa-miR-19b, a microRNA increased in platelets of uraemic patients and involved in platelet reactivity. These results suggest that an alteration of microRNA-based mRNA regulatory mechanisms may underlie the platelet response to uremia and entail the development of platelet-related complications in CKD.

  2. Low expression of cyclooxygenase-2 in chronic kidney disease in young dogs.

    PubMed

    Yabuki, Akira; Miyazaki, Akiko; Ichii, Osamu; Kohyama, Moeko; Sawa, Mariko; Yamato, Osamu

    2016-12-01

    Chronic kidney disease (CKD) often results in end-stage renal failure in young dogs; however, the pathogenesis of this disease is not established. This study investigated renal expression of cyclooxygenase (COX)-1 and COX-2 proteins in three dogs with chronic kidney disease by immunohistochemistry. Histopathology showed asynchronous differentiation of renal tissues, including immature glomeruli. COX-1 signals were not detected in diseased or normal kidneys. COX-2 signals were low or undetectable in diseased kidneys, while normal kidneys showed clear positive signals in the macula densa (MD). Quantitative scores of COX-2 in diseased kidneys were significantly lower than those in normal kidneys. These findings demonstrate low renal COX-2 expression in CKD in young dogs, but whether this is correlated with disease pathogenesis remains unclear.

  3. [Wasting in chronic kidney disease: Refeeding techniques and artificial nutrition practices].

    PubMed

    Pasian, Céline; Azar, Raymond; Fouque, Denis

    2016-12-01

    Protein energy wasting (PEW) is an independent factor associated with morbi-mortality in chronic kidney disease. Wasting is particularly common in chronic diseases of organs such as kidney disease with a major impact at the stage of dialysis. It covers 20 to 70% of patients diagnosed with chronic kidney disease according to the degree of evolution of the disease and the diagnostic method used patients. Mechanisms of PEW are based mainly on anorexia and metabolic abnormalities caused by kidney disease. Nutritional treatment differs depending on the stage of the kidney disease acute or chronic treated whether or not by dialysis. Nutritional monitoring should be regular, individualized and collaborative to detect a risk of PEW or treat installed PEW. Refeeding techniques should allow all the nutritional needs. Their indications depend on the clinic, biochemical assessment and nutrient intake.

  4. Baseline donor chronic renal injury confers the same transplant survival disadvantage for DCD and DBD kidneys.

    PubMed

    Kosmoliaptsis, V; Salji, M; Bardsley, V; Chen, Y; Thiru, S; Griffiths, M H; Copley, H C; Saeb-Parsy, K; Bradley, J A; Torpey, N; Pettigrew, G J

    2015-03-01

    Histological assessment of baseline chronic kidney injury may discriminate kidneys that are suitable for transplantation, but has not been validated for appraisal of donation after circulatory death (DCD) kidneys. 'Time-zero' biopsies for 371 consecutive, solitary, deceased-donor kidneys transplanted at our center between 2006 and 2010 (65.5% DCD, 34.5% donation after brain death [DBD]) were reviewed and baseline chronic degenerative injury scored using Remuzzi's classification. High scores correlated with donor age and extended criteria donors (42% of donors), but the spectrum of scores was similar for DCD and DBD kidneys. Transplant outcomes for kidneys scoring from 0 to 4 were comparable (1 and 3 year graft survival 95% and 92%), but were much poorer for kidneys scoring ≥5, with 1 year graft survival only 73%, and 12.5% suffering primary nonfunction. Critically, high Remuzzi scores conferred the same survival disadvantage for DCD and DBD kidneys. On multi-variable regression analysis, time-zero biopsy score was the only independent predictor for graft survival, whereas one-year graft estimated glomerular filtration rate (eGFR) correlated with donor age and biopsy score. In conclusion, the relationship between severity of chronic kidney injury and transplant outcome is similar for DCD and DBD kidneys. Kidneys with Remuzzi scores of ≤4 can be implanted singly with acceptable results.

  5. Expression of growth arrest-specific gene 6 and its receptors in dysfunctional human renal allografts.

    PubMed

    Yin, Jian L; Hambly, Brett D; Bao, Shi S; Painter, Dorothy; Bishop, G Alex; Eris, Josette M

    2003-09-01

    Growth arrest-specific gene 6 (Gas6) and its receptors Rse, Axl and Mer have recently been found to be involved in a rat model of chronic allograft nephropathy (CAN). Thus, in this study we investigated the function of Gas6 and its receptors in human renal allograft dysfunction. Expression of Gas6 and its receptors was detected by immunohistochemical staining. Gas6 and its receptors were widely expressed in glomeruli, tubules and vessels of renal allografts. Gas6 expression was detected in normal-functioning allografts and was increased in acute rejection ( P<0.05), acute tubular necrosis ( P<0.05) and CAN ( P<0.01). Gas6 receptors were not upregulated in any of the allograft groups, except for the Axl receptor, which increased only in acute tubular necrosis ( P<0.01). Gas6 expression was also found to correspond with the expression of alpha-smooth muscle actin, a general marker of CAN ( r(2)=0.21, P<0.01). These findings suggest that Gas6, acting as a growth factor, is increased in the process of kidney allograft dysfunction and in CAN.

  6. Chronic kidney disease hotspots in developing countries in South Asia

    PubMed Central

    Abraham, Georgi; Varughese, Santosh; Thandavan, Thiagarajan; Iyengar, Arpana; Fernando, Edwin; Naqvi, S. A. Jaffar; Sheriff, Rezvi; Ur-Rashid, Harun; Gopalakrishnan, Natarajan; Kafle, Rishi Kumar

    2016-01-01

    In many developing countries in the South Asian region, screening for chronic diseases in the community has shown a widely varying prevalence. However, certain geographical regions have shown a high prevalence of chronic kidney disease (CKD) of unknown etiology. This predominantly affects the young and middle-aged population with a lower socioeconomic status. Here, we describe the hotspots of CKD of undiagnosed etiology in South Asian countries including the North, Central and Eastern provinces of Sri Lanka and the coastal region of the state of Andhra Pradesh in India. Screening of these populations has revealed cases of CKD in various stages. Race has also been shown to be a factor, with a much lower prevalence of CKD in whites compared to Asians, which could be related to the known influence of ethnicity on CKD development as well as environmental factors. The difference between developed and developing nations is most stark in the realm of healthcare, which translates into CKD hotspots in many regions of South Asian countries. Additionally, the burden of CKD stage G5 remains unknown due to the lack of registry reports, poor access to healthcare and lack of an organized chronic disease management program. The population receiving various forms of renal replacement therapy has dramatically increased in the last decade due to better access to point of care, despite the disproportionate increase in nephrology manpower. In this article we will discuss the nephrology care provided in various countries in South Asia, including India, Bangladesh, Pakistan, Nepal, Bhutan, Sri Lanka and Afghanistan. PMID:26798474

  7. Managing pregnancy in chronic kidney disease: improving outcomes for mother and baby

    PubMed Central

    Fitzpatrick, Alyssa; Mohammadi, Fadak; Jesudason, Shilpanjali

    2016-01-01

    Parenthood is a central focus for women with chronic kidney disease, but raises important fears and uncertainties about risks to their own and their baby’s health. Pregnancy in women with background kidney disease, women receiving dialysis, or those with a functioning kidney transplant poses a challenging clinical scenario, associated with high maternal–fetal morbidity and potential impact on maternal renal health. Improvements in care over recent decades have led to a paradigm shift with cautious optimism and growing interest regarding pregnancies in women with chronic kidney disease. In this review, we discuss obstetric and renal outcomes, and practical aspects of management of pregnancy in this complex cohort. PMID:27471410

  8. Variability of the Estimated Glomerular Filtration Rate in the First Year after Kidney Transplantation Is an Independent Risk Factor for Poor Renal Allograft Outcomes: A Retrospective Cohort Study

    PubMed Central

    Choi, Hoon Young; Huh, Kyu Ha; Lee, Jae Geun; Song, Mi Kyung; Kim, Myoung Soo; Kim, Yu Seun; Kim, Beom Seok

    2016-01-01

    Renal function in the first year after kidney transplantation (KT) can predict long-term renal graft survival. This study investigated whether estimated glomerular filtration rate (eGFR) variability during the first year after KT is a risk factor for poor renal allograft outcomes. This retrospective cohort study included 3077 patients who underwent repeated eGFR measurements for 1 year after KT at Severance Hospital Transplantation Center between 1979 and 2012. The eGFR variability during the first year after KT was the predictor. The patients were divided into four quartile groups of eGFR variability according to the coefficient of variation for eGFR (eGFR-CV). We selected a cutoff of eGFR-CV for graft failure and performed the sensitivity analyses. The graft outcome was worse in the highest quartile group of eGFR variability than in the other groups among all patients (Q4: HR 1.631, 95% CI 1.278–2.081; p < 0.0001) and among patients without AR (Q4: HR 1.425, 95% CI 1.024–1.982; p = 0.0358) after adjusting for eGFR at 1 year after KT and other covariates. Additionally, all-cause mortality was higher in this highest quartile group than in the other groups among all patients but not among patients without AR. Higher eGFR-CVs than the cutoff were significantly associated with a high risk of graft failure among all patients (HR 1.670, 95% CI 1.395–2.000; p < 0.0001) and among patients without AR (HR 1.899, 95% CI 1.457–2.477; p < 0.0001) after fully adjusting for covariates. For all-cause mortality, a higher eGFR-CV was an independent risk factor among all patients but not among patients without AR after adjusting for covariates. eGFR variability in the first year after KT is an independent risk factor for poor renal allograft outcomes. PMID:27973553

  9. Vitamin D and UV exposure in chronic kidney disease

    PubMed Central

    Krause, Rolfdieter

    2013-01-01

    With loss of renal function and decreasing glomerula filtration rate the serum levels of 25-hydroxyvitamin D [25(OH)D] as well as 1,25-dihydroxyvitamin D [1,25 (OH)2 D] often decrease simultaneously. In representative groups of German patients on renal replacement therapy (hemodialysis, peritoneal dialysis, kidney transplantation) our group retrospectively analyzed the vitamin D status over a period of 12 y (1995‒2006). Only 11% of patients had a serum level of 25(OH)D that was > 30 ng/ml, more than 70% had a level of 25(OH)D < 20 ng/ml. In clinical trials we used sun-simulating artificial lamps to produce vitamin D3 in the skin. Partial-body irradiation (15% of body surface) was used during the routine hemodialysis treatment. Whole-body UV exposure was done in a standing position three times a week before the hemodialysis treatment. With both procedures we observed an increase of the serum level of 25(OH)2D3 by approx. 35–50% over a period of 2‒3 mo, maintenance of trabecular bone mineral density and a normalization of systolic and diastolic blood pressure. Heart rate variability improved during the whole-body radiation intervention period by 20‒25%. Patients who continued the whole-body irradiation regularly two or three times before starting the routine hemodialysis session had maintained normal levels of circulating 25(OH)D3 and of 1,25(OH)2D3. Therefore, from our data it can be recommended that intermittent suberythemal UVB exposure with a sun-simulation spectrum is effective to treat and/or protect against vitamin D deficiency in chronic and end-stage kidney disease patients. PMID:24494043

  10. Smell and taste function in children with chronic kidney disease.

    PubMed

    Armstrong, Jessica E; Laing, David G; Wilkes, Fiona J; Kainer, Gad

    2010-08-01

    Loss of appetite and poor growth are common in children with chronic kidney disease (CKD), and changes in smell and/or taste function may be responsible, but the hypothesis has not been proven. This aims of this prospective age- and gender-controlled study were to determine whether: (1) changes in smell and taste function occur in children with CKD; (2) smell or taste dysfunction are associated with estimated glomerular filtration rate (eGFR); (3) there is an association between smell or taste loss and body mass index (BMI). The study cohort consisted of 72 children of whom 20 were CKD stage 3-5 patients, 12 were CKD stage 2 patients, 20 were clinical controls (CC) and 20 were healthy children (HC). The CKD patients and clinical controls were recruited from Sydney Children's Hospital and The Children's Hospital, Westmead, and healthy controls were recruited from a local school. Scores for each group from taste and smell chemosensory function tests were compared, and their relationship with renal function and BMI investigated. The CKD stage 3-5 group had a significantly lower taste identification score (85.6%, P < 0.001) than the CC (94.8%) and HC (94.8%) groups, with almost one third of the children in the CKD stage 3-5 group exhibiting taste loss. Decreased taste function was associated with decreased eGFR (r = 0.43, P < 0.01), but no association between BMI and taste function was found (r = 0.001, P > 0.9). Odour identification scores were not different; however, there was a positive relationship with BMI (r = 0.427, P = 0.006). We conclude that a loss of taste can occur in children with CKD and that when it occurs, it worsens as eGFR declines and is found early in kidney disease.

  11. Vitamin D and UV exposure in chronic kidney disease.

    PubMed

    Krause, Rolfdieter

    2013-01-01

    With loss of renal function and decreasing glomerula filtration rate the serum levels of 25-hydroxyvitamin D [25(OH)D] as well as 1,25-dihydroxyvitamin D [1,25 (OH)2 D] often decrease simultaneously. In representative groups of German patients on renal replacement therapy (hemodialysis, peritoneal dialysis, kidney transplantation) our group retrospectively analyzed the vitamin D status over a period of 12 y (1995‒2006). Only 11% of patients had a serum level of 25(OH)D that was > 30 ng/ml, more than 70% had a level of 25(OH)D < 20 ng/ml. In clinical trials we used sun-simulating artificial lamps to produce vitamin D3 in the skin. Partial-body irradiation (15% of body surface) was used during the routine hemodialysis treatment. Whole-body UV exposure was done in a standing position three times a week before the hemodialysis treatment. With both procedures we observed an increase of the serum level of 25(OH)2D3 by approx. 35-50% over a period of 2‒3 mo, maintenance of trabecular bone mineral density and a normalization of systolic and diastolic blood pressure. Heart rate variability improved during the whole-body radiation intervention period by 20‒25%. Patients who continued the whole-body irradiation regularly two or three times before starting the routine hemodialysis session had maintained normal levels of circulating 25(OH)D3 and of 1,25(OH)2D3. Therefore, from our data it can be recommended that intermittent suberythemal UVB exposure with a sun-simulation spectrum is effective to treat and/or protect against vitamin D deficiency in chronic and end-stage kidney disease patients.

  12. Sphingolipids in Genetic and Acquired Forms of Chronic Kidney Diseases.

    PubMed

    Ueda, Norishi

    2017-01-12

    Sphingolipids (SLs) regulate apoptosis, proliferation, and stress response. SLs, including ceramide, glycosphingolipids (glucosylceramide, lactosylceramide, and gangliosides) and sphingosine-1-phosphate (S1P), play a role in the pathogenesis and progression of genetic (lysosomal storage disease, congenital nephrotic syndrome and polycystic kidney disease) and non-genetic forms of chronic kidney diseases (CKDs). SLs metabolism defects promote complications (cardiovascular events, etc.) via oxidant stress in CKDs. A balancing role of apoptotic SLs and anti-apoptotic S1P is crucial in the regulation of glomerular injury and complications associated with CKDs. Interaction between SLs, endothelial function and renin-angiotensin-aldosterone system (RAAS) plays an important role in the regulation of glomerular injury. SLs affect mitochondrial function that regulate the opening of mitochondrial permeability transition (MPT) pore, mitochondrial outer membrane permeability (MOMP), generation of reactive oxygen species (ROS), Bcl-2 family proteins, leading to cytochrome c release and caspase activation, leading to apoptosis, and regulate glomerular cell proliferation or renal fibrosis. Interaction between SLs, endothelial function and RAAS plays a role in the regulation of glomerular injury. This review article summarizes the current evidence supporting a role of SLs metabolism defects in the pathogenesis and progression of glomerular injury and discusses a role of mitochondria, including MPT pore, MOMP, ROS, Bcl-2 family proteins, interaction between SLs, endothelial function and RAAS, and SLs-induced downstream signaling events in CKDs. Crosstalk between these factors plays a role in the pathogenesis and progression of CKDs. Therapeutic strategy of targeting SLs metabolism defects for CKDs through modulation of the enzymes responsible for SLs metabolism defects are also discussed.

  13. Demographics of the older adult and chronic kidney disease: a literature review.

    PubMed

    Elliott, Rowena W

    2012-01-01

    Older adults (65 years of age and older) comprised 4.1% of the population in 1900 (3.1 million), rose to 13.0% in 2010 (40.3 million), and are projected to reach 16.1% in 2020 (54.8 million). With each decade, there has been a steady increase, including older adults, in the population with chronic kidney disease. This article provides a review of the literature related to the demographics of the older adult population and older adults with chronic kidney disease. It also explores life expectancy, health promotion, and the economic impact of chronic kidney disease and its co-morbidities.

  14. Elevated endothelial HIF-1α contributes to glomerular injury and promotes hypertensive chronic kidney disease

    PubMed Central

    Luo, Renna; Zhang, Weiru; Zhao, Cheng; Zhang, Yujin; Wu, Hongyu; Jin, Jianping; Zhang, Wenzheng; Grenz, Almut; Eltzschig, Holger K.; Tao, Lijian; Kellems, Rodney E; Xia, Yang

    2016-01-01

    Hypertensive chronic kidney disease is one of the most prevalent medical conditions with high morbidity and mortality in the United States and worldwide. However, early events initiating the progression to hypertensive chronic kidney disease are poorly understood. We hypothesized that elevated endothelial hypoxia-inducible factor-1alpha is a common early insult triggering initial glomerular injury leading to hypertensive chronic kidney disease. To test our hypothesis we used an angiotensin II infusion model of hypertensive chronic kidney disease to determine the specific cell type and mechanisms responsible for elevation of HIF-1α and its role in the progression of hypertensive chronic kidney disease. Genetic studies coupled with RT-PCR profiling revealed that elevated endothelial HIF-1α is essential to initiate glomerular injury and progression to renal fibrosis by the transcriptional activation of genes encoding multiple vasoactive proteins. Mechanistically, we found that endothelial HIF-1α gene expression was induced by Ang II in a nuclear factor-κB-dependent manner. Finally, we discovered reciprocal positive transcriptional regulation of endothelial Hif-1α and Nf-κb genes is a key driving force for their persistent activation and disease progression. Overall, our findings revealed that the stimulation of HIF-1α gene expression in endothelial cells is detrimental to induce kidney injury, hypertension and disease progression. Our findings highlight early diagnostic opportunities and therapeutic approaches for hypertensive chronic kidney disease. PMID:25987665

  15. Chronic kidney disease in homeless persons in Mexico.

    PubMed

    Garcia-Garcia, Guillermo; Gutiérrez-Padilla, Alfonso J; Renoirte-Lopez, Karina; Mendoza-Garcia, Martha; Oseguera-Vizcaino, Ma C; Perez-Gomez, Hector R; Marquez-Amezcua, J Mario; Tonelli, Marcello

    2013-05-01

    Little is known about the prevalence of chronic kidney disease (CKD) among the homeless in Mexico. The role of substance abuse, alcoholism, and homelessness in CKD has not been properly evaluated. We screened 260 homeless individuals in the state of Jalisco, Mexico, for the presence of CKD and its risk factors, and compared their characteristics with those from a separate cohort of poor Jalisco residents and with a survey of the general Mexican population. CKD was more prevalent among the homeless than among the poor Jalisco population (22% vs. 15.8%, P=0.0001); 16.5% had stage 3, 4.3% stage 4, and 1.2% stage 5. All were unaware of having CKD. Only 5.8% knew they had diabetes, but 19% had fasting blood sugar >126 mg/dl; 3.5% knew they were hypertensive but 31% had systolic blood pressure ⩾140 mm Hg or diastolic blood pressure ⩾90 mm Hg. Alcoholism was less common than in the poor Jalisco population (23.5% vs. 32.3%, P=0.002), but tobacco smoking (34.6% vs. 21.5%, P=0.0001) and substance abuse (18% vs. 1.1%, P=0.0001) were more prevalent among the homeless. Likewise, chronic viral infections such as HIV (4.5% vs. 0.3%, P=0.0001) and HCV (7.7% vs. 1.4%, P=0.0001) were also significantly higher among the homeless than in the general population. In conclusion, CKD and its risk factors are highly prevalent among the homeless individuals in Jalisco, Mexico. Lack of awareness of having diabetes and hypertension is highly common, as is substance abuse. Programs aiming to prevent CKD and its risk factors in Mexico should specifically target this high-risk population.

  16. NLRP3 Inflammasome Activation in Dialyzed Chronic Kidney Disease Patients

    PubMed Central

    Granata, Simona; Masola, Valentina; Zoratti, Elisa; Scupoli, Maria Teresa; Baruzzi, Anna; Messa, Michele; Sallustio, Fabio; Gesualdo, Loreto; Lupo, Antonio; Zaza, Gianluigi

    2015-01-01

    To assess whether NLR pyrin domain-containing protein 3 (NLRP3) inflammasome, a multiprotein complex that mediates the activation of caspase-1 (CASP-1) and pro-inflammatory cytokines IL-18 and IL-1β, could be involved in the chronic inflammatory state observed in chronic kidney disease patients undergoing hemodialysis treatment (CKD-HD), we employed several biomolecular techniques including RT-PCR, western blot, FACS analysis, confocal microscopy and microarray. Interestingly, peripheral blood mononuclear cells from 15 CKD-HD patients showed higher mRNA levels of NLRP3, CASP-1, ASC, IL-1β, IL-18 and P2X7receptor compared to 15 healthy subjects. Western blotting analysis confirmed the above results. In particular, active forms of CASP-1, IL1-β and IL-18 resulted significantly up-regulated in CKD-HD versus controls. Additionally, elevated mitochondrial ROS level, colocalization of NLRP3/ASC/mitochondria in peripheral blood mononuclear cells from CKD-HD patients and down-regulation of CASP-1, IL1-β and IL-18 protein levels in immune-cells of CKD-HD patients stimulated with LPS/ATP in presence of mitoTEMPO, inhibitor of mitochondrial ROS production, suggested a possible role of this organelle in the aforementioned CKD-associated inflammasome activation. Then, microarray analysis confirmed, in an independent microarray study cohort, that NLRP3 and CASP-1, along with other inflammasome-related genes, were up-regulated in 17 CKD-HD patients and they were able to clearly discriminate these patients from 5 healthy subjects. All together these data showed, for the first time, that NLRP3 inflammasome was activated in uremic patients undergoing dialysis treatment and they suggested that this unphysiological condition could be possibly induced by mitochondrial dysfunction. PMID:25798846

  17. Recurrence of ANCA-associated vasculitis in a patient with kidney trasplant.

    PubMed

    García Cosmes, Pedro; Fraile Gómez, Pilar; Lewczuk, Kamil; Rodríguez González, Marta; Ruiz Ferreras, Elena; Tabernero Fernández, Guadalupe

    2016-01-01

    Renal disease secondary to vasculitis associated with anti-neutrophil cytoplasmic antibodies (ANCA) can lead to chronic renal disease requiring renal replacement therapy. In these patients, kidney transplantation offers excellent long-term rates of allograft and patient survival; consequently, they can be trasplanted when the clinical disease activity has remitted. However, the risk of disease relapses in the renal allograft remains, although at lower rates due to modern immunosuppressive regimens. We describe the case of a male patient with extracapillary glomerulonephritis type III C-ANCA (+) who developed a recurrence in the renal allograft 8 years after transplantation. Intensive immunosupression with plasmapheresis controlled the disease.

  18. Safety of intravenous iron use in chronic kidney disease

    PubMed Central

    Kalra, Philip A.; Bhandari, Sunil

    2016-01-01

    Purpose of review Iron deficiency anaemia (IDA) is common and associated with fatigue, reduced quality of life and poorer clinical outcomes. Treatment with oral iron is often inadequate and international guidelines recommend intravenous (i.v.) iron as the preferred option for the treatment of IDA in certain clinical situations. In this review, we assess the safety of using i.v. iron with a particular focus on patients with chronic kidney disease. Recent findings Recent publications have raised safety concerns regarding the incidence of serious reactions accompanying i.v. infusion, as well as the subsequent risk of infections and cardiovascular events. Methodological flaws influence the interpretation of these data that lack evidence from the use of modern irons. The latter have been investigated in several randomized control trials. Summary There is a need for better understanding and definition of the nature of i.v. iron reactions, as many are nonserious infusion reactions rather than true anaphylaxis. Retrospective identification of anaphylaxis is difficult and we suggest the importance of reanalysing data using fatalities or standardized terms as outcome measures. With the exception of high molecular weight iron dextran, serious or life-threatening reactions are rare with the use of i.v. irons, and they can be used safely for the treatment of IDA. PMID:27557350

  19. [Obesity in children and its relationship with chronic kidney disease].

    PubMed

    Zurita-Cruz, Jessie Nallely; Villasís-Keever, Miguel Ángel

    2016-01-01

    In the last decades, obesity and chronic kidney disease (CKD) have increased worldwide, in parallel. This article focuses on the current issues of obesity on renal damage, with special emphasis on what happens at pediatric ages. While obesity has been linked closely with type 2 diabetes mellitus and hypertension, reduced insulin sensitivity is a direct mechanism for renal damage. The pathophysiologic mechanisms on renal damage include glomerular hyperfiltration and hypertrophy, hypercellularity and broadening of the mesangial regions, while the lack of sensitivity to insulin increases the effects of angiotensin II, exacerbates proteinuria and induces the production of inflammatory cytokines. Many epidemiological studies have documented the relationship of increased BMI with the development of ERC, but most of these studies have been conducted in adults. In children, the information is scarce, but is consistent with findings in adults. In contrast, there are studies which show that interventions aimed to improve weight loss and limit renal damage and proteinuria is reduced, the blood pressure and glomerular filtration rate. Allthe above make us think on the need to improve efforts to reduce the prevalence of obesity from the early stages of life, which could reduce the number of patients with CKD in the future.

  20. Metformin in chronic kidney disease: time for a rethink.

    PubMed

    Heaf, James

    2014-06-01

    Metformin has traditionally been regarded as contraindicated in chronic kidney disease (CKD), though guidelines in recent years have been relaxed to permit therapy if the glomerular filtration rate (GFR) is > 30 mL/min. The main problem is the perceived risk of lactic acidosis (LA). Epidemiological evidence suggests that this fear is disproportionate. Lactic acidosis is a rare complication to type 2 diabetes mellitus (T2DM), with an incidence of 6/100,000 patient-years. The risk is not increased in metformin-treated patients. Metformin possesses a number of clinical effects independent of glucose reduction, including weight loss, which are beneficial to patients. The risk of death and cardiovascular disease is reduced by about a third in non-CKD patients. Since metformin intoxication undoubtedly causes LA, and metformin is renally excreted, inappropriate dosage of metformin will increase the risk of LA. It is suggested that introduction of metformin therapy to more advanced stages of CKD may bring therapeutic benefits that outweigh the possible risks.

  1. Metformin in Chronic Kidney Disease: Time for a Rethink

    PubMed Central

    Heaf, James

    2014-01-01

    Metformin has traditionally been regarded as contraindicated in chronic kidney disease (CKD), though guidelines in recent years have been relaxed to permit therapy if the glomerular filtration rate (GFR) is > 30 mL/min. The main problem is the perceived risk of lactic acidosis (LA). Epidemiological evidence suggests that this fear is disproportionate. Lactic acidosis is a rare complication to type 2 diabetes mellitus (T2DM), with an incidence of 6/100,000 patient-years. The risk is not increased in metformin-treated patients. Metformin possesses a number of clinical effects independent of glucose reduction, including weight loss, which are beneficial to patients. The risk of death and cardiovascular disease is reduced by about a third in non-CKD patients. Since metformin intoxication undoubtedly causes LA, and metformin is renally excreted, inappropriate dosage of metformin will increase the risk of LA. It is suggested that introduction of metformin therapy to more advanced stages of CKD may bring therapeutic benefits that outweigh the possible risks. PMID:24711640

  2. Cardiovascular calcifications in chronic kidney disease: Potential therapeutic implications.

    PubMed

    Bover, Jordi; Ureña-Torres, Pablo; Górriz, José Luis; Lloret, María Jesús; da Silva, Iara; Ruiz-García, César; Chang, Pamela; Rodríguez, Mariano; Ballarín, José

    Cardiovascular (CV) calcification is a highly prevalent condition at all stages of chronic kidney disease (CKD) and is directly associated with increased CV and global morbidity and mortality. In the first part of this review, we have shown that CV calcifications represent an important part of the CKD-MBD complex and are a superior predictor of clinical outcomes in our patients. However, it is also necessary to demonstrate that CV calcification is a modifiable risk factor including the possibility of decreasing (or at least not aggravating) its progression with iatrogenic manoeuvres. Although, strictly speaking, only circumstantial evidence is available, it is known that certain drugs may modify the progression of CV calcifications, even though a direct causal link with improved survival has not been demonstrated. For example, non-calcium-based phosphate binders demonstrated the ability to attenuate the progression of CV calcification compared with the liberal use of calcium-based phosphate binders in several randomised clinical trials. Moreover, although only in experimental conditions, selective activators of the vitamin D receptor seem to have a wider therapeutic margin against CV calcification. Finally, calcimimetics seem to attenuate the progression of CV calcification in dialysis patients. While new therapeutic strategies are being developed (i.e. vitamin K, SNF472, etc.), we suggest that the evaluation of CV calcifications could be a diagnostic tool used by nephrologists to personalise their therapeutic decisions.

  3. Epidemiology of acute infections among patients with chronic kidney disease.

    PubMed

    Dalrymple, Lorien S; Go, Alan S

    2008-09-01

    The objectives of this review were (1) to review recent literature on the rates, risk factors, and outcomes of infections in patients who had chronic kidney disease (CKD) and did or did not require renal replacement therapy; (2) to review literature on the efficacy and use of selected vaccines for patients with CKD; and (3) to outline a research framework for examining key issues regarding infections in patients with CKD. Infection-related hospitalizations contribute substantially to excess morbidity and mortality in patients with ESRD, and infection is the second leading cause of death in this population. Patients who have CKD and do not require renal replacement therapy seem to be at higher risk for infection compared with patients without CKD; however, data about patients who have CKD and do not require dialysis therapy are very limited. Numerous factors potentially predispose patients with CKD to infection: advanced age, presence of coexisting illnesses, vaccine hyporesponsiveness, immunosuppressive therapy, uremia, dialysis access, and the dialysis procedure. Targeted vaccination seems to have variable efficacy in the setting of CKD and is generally underused in this population. In conclusion, infection is a primary issue when caring for patients who receive maintenance dialysis. Very limited data exist about the rates, risk factors, and outcomes of infection in patients who have CKD and do not require dialysis. Future research is needed to delineate accurately the epidemiology of infections in these populations and to develop effective preventive strategies across the spectrum of CKD severity.

  4. Remote home management for chronic kidney disease: A systematic review.

    PubMed

    He, Ting; Liu, Xing; Li, Ying; Wu, Qiaoyu; Liu, Meilin; Yuan, Hong

    2017-01-01

    Background Remote home management is a new healthcare model that uses information technology to enhance patients' self-management of disease in a home setting. This study is designed to identify the effects of remote home management on patients with chronic kidney disease (CKD). Methods A comprehensive search of PubMed, MEDLINE, Embase, and the Cochrane Central Register of Controlled Trials was performed in January 2015. The reference listings of the included articles in this review were also manually examined. Randomized controlled trials (RCTs) designed to evaluate the effects of remote home management on patients with CKD were included. Results Eight trials were identified. The results of this study suggest that the quality of life (QOL) enabled by remote home management was higher than typical care in certain dimensions. However, the effects of remote home management on blood pressure (BP) remain inconclusive. The studies that assessed health service utilization demonstrated a significant decrease in hospital readmission, emergency room visits, and number of days in the hospital. Another favorable result of this study is that regardless of their gender, age or nationality, patients tend to comply with remote home management programs and the use of related technologies. Conclusions The available data indicate that remote home management may be a novel and effective disease management strategy for improving CKD patients' QOL and influencing their attitudes and behaviors. And, relatively little is known about BP and cost-effectiveness, so future research should focus on these two aspects for the entire population of patients with CKD.

  5. Sleep disorders in pediatric chronic kidney disease patients.

    PubMed

    Stabouli, Stella; Papadimitriou, Eleni; Printza, Nikoleta; Dotis, John; Papachristou, Fotios

    2016-08-01

    The prevalence of sleep disorders during childhood has been estimated to range from 25 to 43 %. The aim of this review is to determine the prevalence of sleep disorders and possible associations with chronic kidney disease (CKD)-related factors and health-related quality of life (HRQOL) in children with CKD. An electronic systematic literature search for sleep disorders in children with CKD in Pubmed, Embase and the Cochrane Library Databases identified seven relevant articles for review, all of which reported an increased prevalence of sleep disorders in children with CKD. Five studies included children with CKD undergoing dialysis, and two studies included only non-dialysis patients. In all studies the presence of sleep disturbances was assessed by questionnaires; only one study compared the results of a validated questionnaire with laboratory-based polysomnography. The prevalence of any sleep disorder ranged from 77 to 85 % in dialysis patients, to 32-50 % in transplanted patients and 40-50 % in non-dialysis patients. The most commonly studied disorder was restless legs syndrome, which presented at a prevalence of 10-35 %. Three studies showed significant associations between presence of sleep disorders and HRQOL. We found consistent evidence of an increased prevalence of sleep disturbances in children with CKD, and these seemed to play a critical role in HRQOL.

  6. Plant phosphates, phytate and pathological calcifications in chronic kidney disease.

    PubMed

    Buades Fuster, Juan Manuel; Sanchís Cortés, Pilar; Perelló Bestard, Joan; Grases Freixedas, Félix

    Phytate, or myo-inositol 1,2,3,4,5,6-hexakis dihydrogen phosphate (InsP6), is a naturally occurring phosphorus compound that is present in many foods, mainly legumes, whole grains and nuts. Patients with chronic kidney disease (CKD) have cardiovascular disease mortality up to 30times higher than the general population. Vascular calcifications (VCs) directly contribute to overall morbidity and mortality, especially in CKD. In part, this high mortality is due to elevated levels of phosphorus in the blood. Therefore, control of dietary phosphorus is essential. Dietary phosphorus can be classified according to its structure in organic phosphorus (plant and animal) and inorganic (preservatives and additives). Plant-phosphorus (legumes and nuts), mainly associated with InsP6, is less absorbable by the human gastrointestinal tract as the bioavailability of phosphorous from plant-derived foods is very low. Recent data indicate that restriction of foods containing plant phosphates may compromise the adequate supply of nutrients that have a beneficial effect in preventing cardiovascular events, such as InsP6 or fibre found in legumes and nuts. Experimental studies in animals and observational studies in humans suggest that InsP6 can prevent lithiasis and VCs and protect from osteoporosis. In conclusion, we need prospective studies to elucidate the potential benefits and risks of phytate (InsP6) through the diet and as an intravenous drug in patients on haemodialysis.

  7. Vascular calcification in chronic kidney disease: a clinical review.

    PubMed

    Eddington, Helen; Sinha, Smeeta; Kalra, Philip A

    2009-03-01

    Vascular calcification, which is associated with arterial stiffness, is now known to be an important predictor of cardiovascular and all-cause mortality in patients with renal disease. This calcification starts developing in the early stages of chronic kidney disease (CKD) and is present in over 50% of patients at the time of dialysis commencement. Once calcification is present it continues to progress, though some medications have been shown to slow this progression. Vascular calcification and bone abnormalities are now both encompassed by the term of CKD-mineral bone disorder and are thought to be part of the same disease process in CKD. Vascular calcification and arterial stiffness have been extensively researched in the renal population and many factors are known to be associated with their presence and progression. This calcification is an important factor to be considered in the management of the renal patient but there are different methods available for its measurement. These details will be discussed further in this review along with evidence available for management of this important complication of renal disease.

  8. New Strategies for Anaemia Management in Chronic Kidney Disease.

    PubMed

    Locatelli, Francesco; Del Vecchio, Lucia

    2017-01-01

    Erythropoiesis-stimulating agents (ESAs) and iron therapy are the standard of care for normocytic normochromic anaemia, which is a frequent comorbidity of patients with chronic kidney disease. In a large percentage of patients, ESAs and iron increase haemoglobin levels, thus reducing the risk of blood transfusions and improving patient quality of life. However, randomised trials have raised some concerns about higher haemoglobin targets and/or high ESA dose use. These concerns include higher cardiovascular and thrombosis risk, cancer progression, and increased mortality. A more cautious approach was then advised and partial anaemia correction (haemoglobin 10-12 g/dl) is now strongly suggested. The clinical concerns about ESAs and economic constraints have led to larger intravenous iron use. However, severe anaphylactic reactions, although infrequent, can occur and excessive iron use may be dangerous as well, possibly causing iron overload. Several attempts are being made to develop new drugs with theoretically better activity and safety, and/or easier manufacturing processes as compared to available ESAs. These include drugs manipulating the hypoxia-inducible transcription factor (HIF) system, which stimulates the endogenous erythropoietin (EPO) production and avoids unphysiological EPO plasma levels. Several phase I and II studies support the beneficial role of augmenting HIFs to stimulate erythropoiesis. Here we give an update on this new investigational strategy.

  9. Febuxostat for hyperuricemia in patients with advanced chronic kidney disease.

    PubMed

    Akimoto, Tetsu; Morishita, Yoshiyuki; Ito, Chiharu; Iimura, Osamu; Tsunematsu, Sadao; Watanabe, Yuko; Kusano, Eiji; Nagata, Daisuke

    2014-01-01

    Febuxostat is a nonpurine xanthine oxidase (XO) inhibitor, which recently received marketing approval. However, information regarding the experience with this agent among advanced chronic kidney disease (CKD) patients is limited. In the current study, we investigated the effects of oral febuxostat in patients with advanced CKD with asymptomatic hyperuricemia. We demonstrated, for the first time, that not only the serum levels of uric acid (UA) but also those of 8-hydroxydeoxyguanosine, an oxidative stress marker, were significantly reduced after six months of febuxostat treatment, with no adverse events. These results encouraged us to pursue further investigations regarding the clinical impact of lowering the serum UA levels with febuxostat in advanced CKD patients in terms of concomitantly reducing oxidative stress via the blockade of XO. More detailed studies with a larger number of subjects and assessments of the effects of multiple factors affecting hyperuricemia, such as age, sex, and dietary habits, would shed light on the therapeutic challenges of treating asymptomatic hyperuricemia in patients with various stages of CKD.

  10. Ghrelin and leptin pathophysiology in chronic kidney disease.

    PubMed

    Gunta, Sujana S; Mak, Robert H

    2013-04-01

    Ghrelin is an orexigenic hormone with additional effects on the regulation of inflammation and the cardiovascular system. It may play an important role in the pathogenesis of cachexia/protein-energy wasting (PEW), inflammation and cardiovascular complications in chronic kidney disease (CKD). There are three circulating gene products of ghrelin, namely, acyl ghrelin, des-acyl ghrelin and obestatin, each with individual distinct functions. Perturbations of these circulating ghrelin proteins impact the overall milieu of CKD. Leptin is an anorexigenic hormone which is secreted from the adipocytes and interacts with ghrelin and other appetite-regulating hormones. Leptin also plays a role in regulating inflammation and the cardiovascular system. Indeed, ghrelin and leptin may play yin-and-yang roles in CKD pathophysiology. Clinical trials involving the use of the mimetics or antagonists of these hormones are limited to short-term phase I/II studies. Further understanding of their interactions in CKD pathophysiology is needed for potential large-scale clinical trials, which may impact the quality of life and survival of patients with CKD.

  11. Linking zinc and leptin in chronic kidney disease: future directions.

    PubMed

    Lobo, Julie Calixto; Aranha, Luciana Nicolau; Moraes, Cristiane; Brito, Luciana Catunda; Mafra, Denise

    2012-04-01

    Anorexia is a common complication in patients with chronic kidney disease (CKD) and is associated with the development of malnutrition and an increased risk of mortality. Several compounds are linked to anorexia in these patients; however, the mechanisms are unknown. Zinc (Zn) deficiency is associated with decreased food intake and has been observed in CKD patients. In addition, leptin is an anorexigenic peptide, and patients with CKD present generally high levels of this hormone. Studies have suggested an association between Zn and leptin status in human and rats; however, the results are inconsistent. Some claimed that Zn supplementation does not change leptin release or that there is no significant relationship between Zn and leptin. Others have reported that Zn might be a mediator of leptin production. CKD patients have hyperleptinemia and hypozincemia, but the relationship between Zn deficiency and leptin levels in CKD patients has been poorly understood until now. The aim of this review is to integrate knowledge on leptin and Zn actions to provide a cohesive clinical perspective regarding their interactions in CKD patients.

  12. Patient education for phosphorus management in chronic kidney disease

    PubMed Central

    Kalantar-Zadeh, Kamyar

    2013-01-01

    Objectives: This review explores the challenges and solutions in educating patients with chronic kidney disease (CKD) to lower serum phosphorus while avoiding protein insufficiency and hypercalcemia. Methods: A literature search including terms “hyperphosphatemia,” “patient education,” “food fatigue,” “hypercalcemia,” and “phosphorus–protein ratio” was undertaken using PubMed. Results: Hyperphosphatemia is a strong predictor of mortality in advanced CKD and is remediated via diet, phosphorus binders, and dialysis. Dietary counseling should encourage the consumption of foods with the least amount of inorganic or absorbable phosphorus, low phosphorus-to-protein ratios, and adequate protein content, and discourage excessive calcium intake in high-risk patients. Emerging educational initiatives include food labeling using a “traffic light” scheme, motivational interviewing techniques, and the Phosphate Education Program – whereby patients no longer have to memorize the phosphorus content of each individual food component, but only a “phosphorus unit” value for a limited number of food groups. Phosphorus binders are associated with a clear survival advantage in CKD patients, overcome the limitations associated with dietary phosphorus restriction, and permit a more flexible approach to achieving normalization of phosphorus levels. Conclusion: Patient education on phosphorus and calcium management can improve concordance and adherence and empower patients to collaborate actively for optimal control of mineral metabolism. PMID:23667310

  13. Multidisciplinary strategies in the management of early chronic kidney disease.

    PubMed

    Martínez-Ramírez, Héctor R; Cortés-Sanabria, Laura; Rojas-Campos, Enrique; Hernández-Herrera, Aurora; Cueto-Manzano, Alfonso M

    2013-11-01

    Chronic kidney disease (CKD) is a worldwide epidemic especially in developing countries, with clear deficiencies in identification and treatment. Better care of CKD requires more than only economic resources, utilization of health research in policy-making and health systems changes that produce better outcomes. A multidisciplinary approach may facilitate and improve management of patients from early CKD in the primary health-care setting. This approach is a strategy for improving comprehensive care, initiating and maintaining healthy behaviors, promoting teamwork, eliminating barriers to achieve goals and improving the processes of care. A multidisciplinary intervention may include educational processes guided by health professional, use of self-help groups and the development of a CKD management plan. The complex and fragmented care management of patients with CKD, associated with poor outcome, enhances the importance of implementing a multidisciplinary approach in the management of this disease from the early stages. Multidisciplinary strategies should focus on the needs of patients (to increase their empowerment) and should be adapted to the resources and health systems prevailing in each country; its systematic implementation can help to improve patient care and slow the progression of CKD.

  14. Mechanisms of muscle wasting in chronic kidney disease

    PubMed Central

    Wang, Xiaonan H.; Mitch, William E.

    2014-01-01

    In patients with chronic kidney disease (CKD), loss of cellular proteins increases the risks of morbidity and mortality. Persistence of muscle protein catabolism in CKD results in striking losses of muscle proteins as whole-body protein turnover is great; even small but persistent imbalances between protein synthesis and degradation cause substantial protein loss. No reliable methods to prevent CKD-induced muscle wasting currently exist, but mechanisms that control cellular protein turnover have been identified, suggesting that therapeutic strategies will be developed to suppress or block protein loss. Catabolic pathways that cause protein wasting include activation of the ubiquitin–proteasome system (UPS), caspase-3, lysosomes and myostatin (a negative regulator of skeletal muscle growth). These pathways can be initiated by complications associated with CKD, such as metabolic acidosis, defective insulin signalling, inflammation, increased angiotensin II levels, abnormal appetite regulation and impaired microRNA responses. Inflammation stimulates cellular signalling pathways that activate myostatin, which accelerates UPS-mediated catabolism. Blocking this pathway can prevent loss of muscle proteins. Myostatin inhibition could yield new therapeutic directions for blocking muscle protein wasting in CKD or disorders associated with its complications. PMID:24981816

  15. [DIABETIC NEPHROPATHY AS A CAUSE OF CHRONIC KIDNEY DISEASE].

    PubMed

    Kos, Ivan; Prkačin, Ingrid

    2014-12-01

    Diabetic nephropathy is the leading cause of end-stage chronic kidney disease in most developed countries. Hyperglycemia, hypertension and genetic predisposition are the main risk factors for the development of diabetic nephropathy. Elevated serum lipids, smoking habits, and the amount and origin of dietary protein also seem to play a role as risk factors. Clinical picture includes a progressive increase in albuminuria, decline in glomerular filtration, hypertension, and a high risk of cardiovascular morbidity and mortality. Screening for albuminuria should be performed yearly, starting 5 years after diagnosis in type 1 diabetes or earlier in the presence of adolescence or poor metabolic control. In patients with type 2 diabetes, screening should be performed at diagnosis and yearly thereafter. Patients with albuminuria should undergo evaluation regarding the presence of associated comorbidities, especially retinopathy and macrovascular disease. Achieving the best metabolic control (HbA1c < 7%), treating hypertension (target blood pressure < 140/85 mm Hg), using drugs with blockade effect on the renin-angiotensin-aldosterone system, treating dyslipidemia and anemia are effective strategies for preventing the development of albuminuria, delaying the progression to more advanced stages of nephropathy and reducing cardiovascular mortality in patients with type 1 and type 2 diabetes.

  16. Clinical value of natriuretic peptides in chronic kidney disease.

    PubMed

    Santos-Araújo, Carla; Leite-Moreira, Adelino; Pestana, Manuel

    2015-01-01

    According to several lines of evidence, natriuretic peptides (NP) are the main components of a cardiac-renal axis that operate in clinical conditions of decreased cardiac hemodynamic tolerance to regulate sodium homeostasis, blood pressure and vascular function. Even though it is reasonable to assume that NP may exert a relevant role in the adaptive response to renal mass ablation, evidence gathered so far suggest that this contribution is probably complex and dependent on the type and degree of the functional mass loss. In the last years NP have been increasingly used to diagnose, monitor treatment and define the prognosis of several cardiovascular (CV) diseases. However, in many clinical settings, like chronic kidney disease (CKD), the predictive value of these biomarkers has been questioned. In fact, it is now well established that renal function significantly affects the plasmatic levels of NP and that renal failure is the clinical condition associated with the highest plasmatic levels of these peptides. The complexity of the relation between NP plasmatic levels and CV and renal functions has obvious consequences, as it may limit the predictive value of NP in CV assessment of CKD patients and be a demanding exercise for clinicians involved in the daily management of these patients. This review describes the role of NP in the regulatory response to renal function loss and addresses the main factors involved in the clinical valorization of the peptides in the context of significant renal failure.

  17. Metabolomics for clinical use and research in chronic kidney disease.

    PubMed

    Hocher, Berthold; Adamski, Jerzy

    2017-03-06

    Chronic kidney disease (CKD) has a high prevalence in the general population and is associated with high mortality; a need therefore exists for better biomarkers for diagnosis, monitoring of disease progression and therapy stratification. Moreover, very sensitive biomarkers are needed in drug development and clinical research to increase understanding of the efficacy and safety of potential and existing therapies. Metabolomics analyses can identify and quantify all metabolites present in a given sample, covering hundreds to thousands of metabolites. Sample preparation for metabolomics requires a very fast arrest of biochemical processes. Present key technologies for metabolomics are mass spectrometry and proton nuclear magnetic resonance spectroscopy, which require sophisticated biostatistic and bioinformatic data analyses. The use of metabolomics has been instrumental in identifying new biomarkers of CKD such as acylcarnitines, glycerolipids, dimethylarginines and metabolites of tryptophan, the citric acid cycle and the urea cycle. Biomarkers such as c-mannosyl tryptophan and pseudouridine have better performance in CKD stratification than does creatinine. Future challenges in metabolomics analyses are prospective studies and deconvolution of CKD biomarkers from those of other diseases such as metabolic syndrome, diabetes mellitus, inflammatory conditions, stress and cancer.

  18. A Structural Approach to Skeletal Fragility in Chronic Kidney Disease

    PubMed Central

    Leonard, Mary B.

    2009-01-01

    Renal osteodystrophy is a multifactorial disorder of bone metabolism in chronic kidney disease (CKD). As CKD progresses, ensuing abnormalities in mineral metabolism result in distortions in trabecular microarchitecture, thinning of the cortical shell, and increased cortical porosity. Recent studies have demonstrated significantly increased hip fracture rates in CKD stages 3 and 4, in dialysis patients, and in transplant recipients. The majority of studies of bone loss in CKD relied on dual energy x-ray absorptiometry (DXA) measures of bone mineral density (BMD). However, DXA summarizes the total bone mass within the projected bone area, concealing distinct structural alterations in trabecular and cortical bone. Recent data have confirmed that peripheral quantitative computed tomography (pQCT) measures of cortical density and thickness provide substantially better fracture discrimination in dialysis patients, compared with hip or spine DXA. The following review summarizes the growing evidence for bone fragility in CKD stages 3 through 5, considers the effects of CKD on trabecular and cortical bone structure as relates to fracture risk, and details the potential advantages and disadvantages of DXA and alternative measures of bone density, geometry, and microarchitecture, including pQCT, high resolution pQCT, and micro-magnetic resonance imaging for fracture risk assessment in CKD. PMID:19371804

  19. Assessment of nutritional status in children with chronic kidney disease.

    PubMed

    Paglialonga, F; Felice Civitillo, C; Groppali, E; Edefonti, A

    2010-06-01

    The achievement of a normal nutritional status, that is a normal body composition and a normal pattern of growth, is a cornerstone in the management of children with chronic kidney disease (CKD). Protein-energy wasting (PEW) which indicates the state of decreased body protein mass and fuel reserves (body protein and fat mass), is a common condition in this population, and a source of morbidity and mortality. For the diagnosis of this condition, a lot of methods have been proposed, but due to the clinical characteristics of children with CKD, the intrinsic limits of the available indices and some methodological issues concerning published pediatric studies, none of these parameters could be considered as the gold standard. Given these limitations, a general consensus exists according to which only the combination of more indices integrated in a multidisciplinary approach can give the idea of the individual nutritional status. Among these indices, recent guidelines recommend dietary intake (by means of 3-day diary or 24-hour recall), anthropometric parameters (weight, height, height velocity, body mass index, head circumference) and, only for adolescent on hemodialysis, normalized protein catabolic rate as the most accurate ones. Other methods, such as mid-arm anthropometry, bioimpedance analysis, biochemical indices, and dual-energy X-ray absorptiometry could certainly help in the nutritional evaluation, taking into account the advantages and drawbacks of each method.

  20. [Nutritional status of patients with chronic kidney disease].

    PubMed

    Brunori, Giuliano

    2012-01-01

    The population of patients with chronic kidney disease is aging, and approximately 50% of those starting renal replacement therapy are older than 65 years. Aging poses challenges to maintaining the nutritional status of these patients. As patients get older, purchasing and preparing food may become difficult if the patient is not supported by relatives or social workers. In addition, appetite may decrease as a result of depression. Furthermore, intercurrent illnesses may become more frequent, leading to changes in nutrient requirements. Mobility and cognitive function often decline in elderly patients and the combination of these factors may result in malnutrition. Since malnutrition has been demonstrated to impact on survival in dialysis patients of all ages, appropriate attention to nutritional status and its management is essential in the elderly patient, both in the predialysis phase and on dialysis. This article reviews the issues associated with the maintenance of good nutrition in elderly patients and describes the potential causes of malnutrition. It also reviews the nutrient requirements of older dialysis patients (which differ somewhat from those of younger patients) as well as the assessment of their nutritional status. Finally, recommendations for the management of nutrition in the elderly patient are discussed.

  1. [Congestive heart failure in patients with chronic kidney disease].

    PubMed

    Poskurica, Mileta; Petrović, Dejan

    2014-01-01

    Cardiovascular disorders are the most frequent cause of death (46-60%) among patients with advanced chronic renal failure (CRF), and on dialysis treatment. Uremic cardiomyopathy is the basic pathophysiologic substrate, whereas ischemic heart disease (IHD) and anemia are the most important contributing factors. Associated with well-know risk factors and specific disorders for terminal kidney failure and dialysis, the aforementioned factors instigate congestive heart failure (CHF). Suspected CHF is based on the anamnesis, clinical examination and ECG, while it is confirmed and defined more precisely on the basis of echocardiography and radiology examination. Biohumoral data (BNP, NT-proBNP) are not sufficiently reliable because of specific volemic fluctuation and reduced natural clearance. Therapy approach is similar to the one for the general population: ACEI, ARBs, β-blockers, inotropic drugs and diuretics. Hypervolemia and most of the related symptoms can be kept under control effectively by the isolated or ultrafiltation, in conjunction with dialysis, during the standard bicarbonate hemodialysis or hemodiafiltration. In the same respect peritoneal dialysis is efficient for the control of hypervolemia symptoms, mainly during the first years of its application and in case of the lower NYHA class (II°/III°). In general, heart support therapy, surgical interventions of the myocardium and valve replacement are rarely used in patients on dialysis, whereas revascularization procedures are beneficial for associated IHD. In selected cases the application of cardiac resynchronization and/or implantation of a cardioverter defibrillator are advisable.

  2. [Polycystic kidney disease in a patient using lithium chronically].

    PubMed

    Atagün, Murat Ilhan; Oral, Esad Timuçin; Sevinç, Can

    2013-01-01

    Lithium remains to be the gold standard in the treatment of mood disorders. This study presents a case treated with lithium for an extended period with a good response. Following an increase in creatinine levels, further investigation of renal dysfunction revealed polycystic kidney disease. Lithium was used prior to the diagnosis of polycystic kidney disease, resulting in the unique opportunity to examine the effects of lithium on kidneys with polycystic kidney disease. Within this context, this study also discusses the pharmacokinetics of lithium, and its possible relation to cyst formation in polycystic kidney disease.

  3. Bone mineral disorder in chronic kidney disease: Klotho and FGF23; cardiovascular implications.

    PubMed

    Salanova Villanueva, Laura; Sánchez González, Carmen; Sánchez Tomero, José Antonio; Aguilera, Abelardo; Ortega Junco, Esther

    2016-01-01

    Cardiovascular factors are one of the main causes of morbidity and mortality in patients with chronic kidney disease. Bone mineral metabolism disorders and inflammation are pathological conditions that involve increased cardiovascular risk in chronic kidney disease. The cardiovascular risk involvement of bone mineral metabolism classical biochemical parameters such as phosphorus, calcium, vitamin D and PTH is well known. The newest markers, FGF23 and klotho, could also be implicated in cardiovascular disease.

  4. The Endoplasmic Reticulum Stress Protein Calreticulin in Diabetic Chronic Kidney Disease

    DTIC Science & Technology

    2016-07-01

    AWARD NUMBER: W81XWH-14-1-0203 TITLE: The Endoplasmic Reticulum Stress Protein Calreticulin in Diabetic Chronic Kidney Disease PRINCIPAL...1 July 2015- 30 June 2016 4. TITLE AND SUBTITLE The Endoplasmic Reticulum Stress Protein Calreticulin in Diabetic Chronic Kidney Disease 5a...We hypothesize that ER stress induced by glucose in diabetes promotes diabetic CKD through CRT stimulation of TGF-beta-dependent calcium/NFAT

  5. The Endoplasmic Reticulum Stress Protein Calreticulin in Diabetic Chronic Kidney Disease

    DTIC Science & Technology

    2015-07-01

    1 AWARD NUMBER: W81XWH-14-1-0203 TITLE: The Endoplasmic Reticulum Stress Protein Calreticulin in Diabetic Chronic Kidney Disease PRINCIPAL...COVERED 07/01/2014-06/30/2015 4. TITLE AND SUBTITLE The Endoplasmic Reticulum Stress Protein Calreticulin in Diabetic Chronic Kidney Disease 5a...NUMBER(S) 13. SUPPLEMENTARY NOTES 14. ABSTRACT We hypothesize that ER stress induced by glucose in diabetes promotes diabetic CKD through CRT stimulation

  6. ABO-compatible Liver Allograft Antibody-mediated Rejection: an update

    PubMed Central

    Demetris, Anthony J.; Zeevi, Adriana; O’Leary, Jacqueline G.

    2015-01-01

    Purpose Liver allograft antibody-mediated rejection (AMR) studies have lagged behind parallel efforts in kidney and heart because of a comparative inherent hepatic resistance to AMR. Three developments, however, have increased interest: 1) solid phase antibody testing enabled more precise antibody characterization; 2) increased expectations for long-term, morbidity-free survival; and 3) immunosuppression minimization trials. Recent Findings Two overlapping liver allograft AMR phenotypic expressions are beginning to emerge: acute and chronic AMR. Acute AMR usually occurs within the several weeks after transplantation and characterized clinically by DSA persistence, allograft dysfunction, thrombocytopenia, and hypocomplementemia. Acute AMR appears histopathologically similar to acute AMR in other organs: diffuse microvascular endothelial cell hypertrophy, C4d deposits, neutrophilic, eosinophilic, and macrophage-mediated microvasculitis/capillaritis, along with liver-specific ductular reaction, centrilobular hepatocyte swelling and hepatocanalicular cholestasis often combined with T cell-mediated rejection (TCMR). Chronic AMR is less well-defined, but strongly linked to serum class II DSA and associated with late-onset acute TCMR, fibrosis, chronic rejection and decreased survival. Unlike acute AMR, chronic AMR is a slowly evolving insult with a number of potential manifestations, but most commonly appears as low-grade lymphoplasmacytic portal and perivenular inflammation accompanied by unusual fibrosis patterns and variable microvascular C4d deposition; capillaritis is more difficult to identify than in acute AMR. Summary More precise DSA characterization, increasing expectations for long-term survival, and immunosuppression weaning precipitated a re-emergence of liver allograft AMR interest. Pathophysiological similarities exist between heart, kidney, and liver allografts, but liver-specific considerations may prove critical to our ultimate understanding of all

  7. Renal allograft eosinophilia: An unusual presentation of sudden graft dysfunction

    PubMed Central

    Yuvaraj, A.; Ghosh, S.; Abraham, G.; Koshy, P.

    2017-01-01

    We present a case of sudden allograft dysfunction 11 months after renal transplantation which presented as severe peripheral and allograft eosinophilia and was managed as a case of an acute cellular rejection with significant interstitial graft eosinophilic infiltration. Patient had partial response to antirejection therapy and eventually ended up in a chronic allograft dysfunction. PMID:28356665

  8. Skeletal effects of zoledronic acid in an animal model of chronic kidney disease

    PubMed Central

    Chen, N. X.; Gattone, V. H.; Chen, X.; Carr, A. J.; LeBlanc, P.; Brown, D.; Moe, S. M.

    2014-01-01

    Summary Bisphosphonates reduce skeletal loss and fracture risk, but their use has been limited in patients with chronic kidney disease. This study shows skeletal benefits of zoledronic acid in an animal model of chronic kidney disease. Introduction Bisphosphonates are routinely used to reduce fractures but limited data exists concerning their efficacy in non-dialysis chronic kidney disease. The goal of this study was to test the hypothesis that zoledronic acid produces similar skeletal effects in normal animals and those with kidney disease. Methods At 25 weeks of age, normal rats were treated with a single dose of saline vehicle or 100 µg/kg of zoledronic acid while animals with kidney disease (approximately 30 % of normal kidney function) were treated with vehicle, low dose (20 µg/kg), or high dose (100 µg/kg) zoledronic acid, or calcium gluconate (3 % in the drinking water). Skeletal properties were assessed 5 weeks later using micro-computed tomography, dynamic histomorphometry, and mechanical testing. Results Animals with kidney disease had significantly higher trabecular bone remodeling compared to normal animals. Zoledronic acid significantly suppressed remodeling in both normal and diseased animals yet the remodeling response to zoledronic acid was no different in normal and animals with kidney disease. Animals with kidney disease had significantly lower cortical bone biomechanical properties; these were partially normalized by treatment. Conclusions Based on these results, we conclude that zoledronic acid produces similar amounts of remodeling suppression in animals with high turnover kidney disease as it does in normal animals, and has positive effects on select biomechanical properties that are similar in normal animals and those with chronic kidney disease. PMID:22907737

  9. Prevalence of chronic kidney disease in persons with undiagnosed or prehypertension in the United States.

    PubMed

    Crews, Deidra C; Plantinga, Laura C; Miller, Edgar R; Saran, Rajiv; Hedgeman, Elizabeth; Saydah, Sharon H; Williams, Desmond E; Powe, Neil R

    2010-05-01

    Hypertension is both a cause and a consequence of chronic kidney disease, but the prevalence of chronic kidney disease throughout the diagnostic spectrum of blood pressure has not been established. We determined the prevalence of chronic kidney disease within blood pressure categories in 17 794 adults surveyed by the National Health and Nutrition Examination Survey during 1999-2006. Diagnosed hypertension was defined as self-reported provider diagnosis (n=5832); undiagnosed hypertension was defined as systolic blood pressure > or = 140 mm Hg or diastolic blood pressure > or = 90 mm Hg, without report of provider diagnosis (n=3046); prehypertension was defined as systolic blood pressure > or = 120 and <140 mm Hg or diastolic blood pressure > or = 80 and <90 mm Hg (n=3719); and normal was defined as systolic blood pressure <120 mm Hg and diastolic blood pressure <80 mm Hg (n=5197). Chronic kidney disease was defined as estimated glomerular filtration rate <60 mL/min per 1.73 m(2) or urinary albumin:creatinine ratio >30 mg/g. Prevalences of chronic kidney disease among those with prehypertension and undiagnosed hypertension were 17.3% and 22.0%, respectively, compared with 27.5% with diagnosed hypertension and 13.4% with normal blood pressure, after adjustment for age, sex, and race in multivariable logistic regression. This pattern persisted with varying definitions of kidney disease; macroalbuminuria (urinary albumin:creatinine ratio >300 mg/g) had the strongest association with increasing blood pressure category (odds ratio: 2.37 [95% CI: 2.00 to 2.81]). Chronic kidney disease is prevalent in undiagnosed and prehypertension. Earlier identification and treatment of both these conditions may prevent or delay morbidity and mortality from chronic kidney disease.

  10. Glibenclamide improves kidney and heart structure and function in the adenine-diet model of chronic kidney disease.

    PubMed

    Diwan, Vishal; Gobe, Glenda; Brown, Lindsay

    2014-01-01

    The development of chronic kidney disease (CKD) and associated cardiovascular disease involves free radical damage and inflammation. Addition of adenine to the diet induces inflammation followed by CKD and cardiovascular disease. NOD-like receptor protein-3 (NLRP-3) is pro-inflammatory in the kidney; glibenclamide inhibits production of NLRP-3. Male Wistar rats were fed either control rat food or adenine (0.25%) in this food for 16 weeks. Glibenclamide (10 mg/kg/day) was administered to two groups with and without adenine for the final 8 weeks. Kidney function (blood urea nitrogen/BUN, plasma creatinine/PCr, plasma uric acid, proteinuria), kidney structure (fibrosis, inflammation), cardiovascular parameters (blood pressure, left ventricular stiffness, vascular responses and echocardiography) and protein expression of markers for oxidative stress (HO-1), and inflammation (TNF-α, NLRP-3) were assessed. In adenine-fed rats, glibenclamide decreased BUN (controls: 6±0.6; adenine: 56.6±5.4; adenine+glibenclamide: 19.4±2.7 mmol/L), PCr (controls: 42±2.8; adenine: 268±23; adenine+glibenclamide: 81±10 μmol/L), proteinuria (controls: 150±7.4; adenine: 303±19; adenine+glibenclamide: 220±13 μmol/L) (all p<0.05). Glibenclamide decreased infiltration of chronic inflammatory cells, fibrosis, tubular damage and expression of HO-1, TNF-α and NLRP-3 in the kidney. Glibenclamide did not alter plasma uric acid concentrations (controls: 38±1; adenine: 63±4; adenine+glibenclamide: 69±14 μmol/L). Cardiovascular changes included decreased systolic blood pressure and improved vascular responses although cardiac fibrosis, left ventricular stiffness and hypertrophy were not reduced. Glibenclamide improved kidney structure and function in CKD and decreased some cardiovascular parameters. Inflammatory markers and cell populations were attenuated by glibenclamide in kidneys.

  11. Physical Activity and Hemodynamic Reactivity in Chronic Kidney Disease

    PubMed Central

    Agarwal, Rajiv; Light, Robert P.

    2008-01-01

    Background and objectives: Patients with chronic kidney disease (CKD) have an elevated cardiovascular risk. This study was designed to understand better the presence and strength of the relationship between physical activity and BP and to explore determinants of hemodynamic reactivity. Design, setting, participants, & measurements: Twenty-four patients with CKD (mean age 69.5 yr; 3.1 antihypertensive drugs; estimated GFR 47 ml/min per 1.73 m2, albumin/creatinine ratio 403 mg/g) were studied on three occasions during a 6-wk period with 24-h ambulatory BP monitoring and simultaneous activity monitoring with wrist actigraphy. Results: Nondippers were found have a greater level of sleep activity compared with dippers, although the awake activity level was similar (7.06 versus 6.73) between groups (P = 0.042 for interaction). In 3587 BP activity pairs, hemodynamic reactivity was variable between individuals (systolic BP reactivity 1.06 [SD 10.50]; diastolic BP reactivity 0.89 [SD 7.80] heart rate reactivity 1.18 [SD 11.00]); those who were more sedentary had a greater increment in systolic BP compared with those who were less sedentary. Antihypertensive drugs blunted hemodynamic reactivity. Hemodynamic reactivity was greatest between 12 a.m. and 8 a.m., making this a vulnerable period for cardiovascular events. Conclusions: Greater hemodynamic reactivity in sedentary people with CKD offers a possible and thus far unrecognized mechanism of cardiovascular damage. Besides reducing BP, antihypertensive drugs reduce hemodynamic reactivity, which offers another plausible mechanism of cardiovascular protection with their use. PMID:18922983

  12. Cinacalcet in Pediatric and Adolescent Chronic Kidney Disease

    PubMed Central

    Alharthi, Abdulla A.; Kamal, Naglaa M.; Abukhatwah, Mohamed W.; Sherief, Laila M.

    2015-01-01

    Abstract Cinacalcet, a calcimimetic drug, has been shown to be efficacious in adult chronic kidney disease (CKD) patients; however, it was not fully studied in pediatric CKD patients. We aimed at assessing the effect of cinacalcet on intact parathyroid hormone (iPTH) secretion in children with CKD-4/5 with iPTH consistently ≥ 300 pg/mL refractory to conventional treatment. This is a prospective cohort analysis of 28 children with uncontrolled hyper-parathyroidism secondary to stage 4 and 5 CKD admitted to a tertiary center during the period from April 2012 to April 2014. Twenty-eight patients with CKD-4/5 were assessed prospectively regarding bone biochemistry, renal ultrasonography, serum iPTH level, and medications. Patients were classified into 3 groups: group 1, 6 patients with CKD-4 on supplemental and supportive therapy; group 2, 6 patients with CKD-5 on hemodialysis and; group 3, 16 patients with CKD-5 on automated peritoneal dialysis. Patients were between the ages of 9 months and 18 years on commencing cinacalcet at doses of 0.5 to 1.5 mg/kg. All patients showed at least a 60% reduction in iPTH (60%–97%). Highly significant reduction in iPTH and serum alkaline phosphatase levels was detected post-cinacalcet. The serum calcium (Ca), phosphate (P), and Ca × P product were unaffected. Treatment was well tolerated with no hypophosphatemia, hypocalcemia, or other adverse effects almost in all patients. Cinacalcet use was proven safe for all pediatric and adolescent patients with CKD-4/5 during the study period, and at the same time most of the patients reached the suggested iPTH target values PMID:25590845

  13. The social cost of chronic kidney disease in Italy.

    PubMed

    Turchetti, Giuseppe; Bellelli, S; Amato, M; Bianchi, S; Conti, P; Cupisti, A; Panichi, V; Rosati, A; Pizzarelli, F

    2016-10-03

    This study aims to estimate the mean annual social cost per patient with chronic kidney disease (CKD) by stages 4 and 5 pre-dialyses and cost components in Italy. The multicenter cross-sectional study included all adult outpatients in charge of the 14 main Nephrology Centers of Tuscany Region during 7 weeks from 2012 to 2013. Direct medical costs have been estimated using tariffs for laboratory tests, diagnostic exams, visits, hospitalization and prices for drugs. Non-medical costs included expenses of low-protein special foods, travel, and formal and informal care. Patients' and caregivers' losses of productivity have been estimated as indirect costs using the human capital approach. Costs have been expressed in Euros (2016). Totals of 279 patients in stage 4 and 205 patients in stage 5 have been enrolled. The estimated mean annual social cost of a patient with CKD were €7422 (±€6255) for stage 4 and €8971 (±€6503) for stage 5 (p < 0.05). Direct medical costs were higher in stage 5 as compared to stage 4; direct non-medical costs and indirect costs accounted, respectively, for 41 and 5 % of the total social cost of CKD stage 4 and for 33 and 9 % of CKD stage 5. In Italy, the overall annual social cost of CKD was €1,809,552,398 representing 0.11 % of the Gross Domestic Product. Direct non-medical costs and indirect costs were weighted on the social cost of CKD almost as much as the direct medical cost. Patients, their families and the productivity system sustain the burden of the disease almost as much as the healthcare system.

  14. Glycaemic changes in patients with chronic kidney disease.

    PubMed

    De'Marziani, Guillermo; Soler Pujol, Gervasio; Obregón, Liliana Miriam; Morales, Elisa Mabel; Gonzalez, Claudio Daniel; Gonzalez Paganti, Luciana; Cacciagiú, Leonardo; Lopez, Graciela; Schreier, Laura; Elbert, Alicia

    2016-01-01

    In Argentina, there have been no studies aimed at establishing the prevalence of dysglycaemia (impaired fasting glucose [IFG], impaired glucose tolerance [IGT] and diabetes mellitus [DM]) in patients with chronic kidney disease (CKD). Our group decided to conduct an observational study to evaluate the frequency with oral glucose tolerance test (OGTT) in CKD patients with no previous data for dysglycaemia in their medical records. OGTT was performed in 254 patients (60.62% male) with stage 3, 4 and 5 CKD under conservative treatment, haemodialysis or transplantation. Results for DM were found in 10 patients according to fasting glucose alone (3.94%; 95% CI: 1.35-6.53%), 11 patients with exclusively the second hour criterion (4.33%; 95% CI: 1.63-7.03%), 15 with both criteria (5.91%; 95% CI: 2.81-9.00%) and 36 patients with at least one criteria (14.17%; 95% CI: 9.69-18.66%). In a multivariate analysis, DM was associated with waist circumference (OR=1.033 per cm; 95% CI, 1.005 to 1.062; P=.019) and with conservative treatment vs. replacement therapy (OR=0.41; 95% CI: 0.19-0.92; P=.028). IGT was evident in 24.6% and 20.3 on conservative vs. replacement therapy, with no statistically significant difference. IFG (ADA criteria) was 19.75 vs. 9.24% in conservative vs. replacement therapy, with a statistically significant difference. OGTT is suggested for all CKD patients since it is able to detect the full range of unknown dysglycaemias, which avoids underdiagnoses and favours performing treatments to prevent progression in DM risk groups (IFG and/or IGT). It also aids in the selection of the most appropriate medication for transplantation or treatment initiation in new cases of undiagnosed DM to decrease morbidity and mortality.

  15. Energy homeostasis and cachexia in chronic kidney disease.

    PubMed

    Mak, Robert H; Cheung, Wai

    2006-12-01

    Loss of protein stores, presenting as clinical wasting, is reported to have a prevalence of 30-60% and is an important risk factor for mortality in chronic kidney disease (CKD) patients. There is debate as to whether the clinical wasting in CKD patients represents malnutrition or cachexia. Malnutrition results from inadequate intake of nutrients, despite a good appetite, and manifests as weight loss associated with adaptive metabolic responses such as decreased basic metabolic rate and preservation of lean body mass at the expense of fat mass. Furthermore, the abnormalities in malnutrition can usually be overcome simply by supplying more food or altering the composition of the diet. In contrast, cachexia is characterized by maladaptive responses such as anorexia, elevated basic metabolic rate, wasting of lean body tissue, and underutilization of fat tissue for energy. Diet supplementation and intradialytic parenteral nutrition have not been successful in reversing cachexia in CKD. The etiology of cachexia in CKD is complex and multifactorial. Two major factors causing muscle wasting in uremia are acidosis and decreased insulin responses. Inflammation secondary to cytokines may also play a significant role. The hypoalbuminemia of CKD patients is principally associated with inflammation and not changes in food intake. There is also recent evidence that hypothalamic neuropeptides may be important in the downstream signaling of cytokines in the pathogenesis of cachexia in CKD. Elevated circulating levels of cytokines, such as leptin, may be an important cause of uremia-associated cachexia via signaling through the central melanocortin system. Further research into the molecular pathways leading to cachexia may lead to novel therapeutic therapy for this devastating and potentially fatal complication of CKD.

  16. Salivary Alterations in Rats with Experimental Chronic Kidney Disease

    PubMed Central

    Romero, Ana Carolina; Bergamaschi, Cassia Toledo; de Souza, Douglas Nesadal; Nogueira, Fernando Neves

    2016-01-01

    Objective This study aimed to analyze changes in saliva composition and salivary secretion process of rats with chronic kidney disease induced by 5/6 nephrectomy to set the foundation for salivary studies related to CKD. Methods CKD was induced in Wistar rats via 5/6 nephrectomy. Blood and saliva samples were collected from Control, Sham and CKD groups at 8 and 12 weeks after the surgery. Salivation was stimulated via intraperitoneal injections of pilocarpine (1.0 mg/Kg body weight) or isoproterenol (5.0 mg/Kg body weight). Saliva was collected and immediately stored at -80°C until analysis. The salivary flow rate, total protein, amylase and peroxidase activities, and urea concentrations were measured. The blood urea nitrogen (BUN) and serum creatinine concentrations were also evaluated. Results Increases in BUN and serum creatinine concentrations were observed in the CKD groups. Amylase activity was significantly reduced in response to both stimuli in the CKD groups at 8 weeks and increased in the CKD groups at 12 weeks in response to isoproterenol stimulus. The peroxidase activities of the CKD groups were significantly reduced in response to isoproterenol stimulation and were increased at 12 weeks in response to pilocarpine stimulation. Salivary urea was significantly increased in the CKD groups at 8 weeks in response to the isoproterenol stimuli and at 12 weeks in response to both salivary agonists. Conclusions The pattern of alterations observed in this experimental model is similar to those observed in patients and clearly demonstrates the viability of 5/6 nephrectomy as an experimental model in future studies to understand the alterations in salivary compositions and in salivary glands that are elicited by CKD. PMID:26859883

  17. Serum Vitamin D levels in patients with chronic kidney disease

    PubMed Central

    Rozita, Mohd; Noorul Afidza, Mohamad; Ruslinda, Mustafar; Cader, Rizna; Halim, A. Gafor; Kong, Chiew Tong Norella; Nor Azmi, Kamaruddin; Shah, Shamsul Azhar

    2013-01-01

    Introduction: Hypovitaminosis D is reported to be associated with several medical complications. Recent studies have reported a high worldwide prevalence of Vitamin D deficiency in the general population (up to 80 %). This is even higher in patients with chronic kidney disease (CKD) and increases with advancing stages of CKD. Objectives: To determine the difference in serum Vitamin D [25-hydroxyvitamin D, 25(OH) D] levels between CKD patients and normal healthy population. Materials and Methods: A prospective cross-sectional study involving 50 normal volunteers (control) and 50 patients with CKD stages 2-4. Their demographic profiles were recorded and blood samples taken for serum 25(OH) D, intact parathyroid hormone (iPTH) and other routine blood tests. Results: All subjects regardless of renal status had hypovitaminosis D (< 30ng/mL). The mean serum 25(OH) D were comparable in the control and CKD groups (15.3 ± 4.2 ng/mL vs 16.1 ± 6.2 ng/mL, p = NS). However, within the Vitamin D deficient group, the CKD group had lower levels of serum 25(OH) D [12.6(3.7) ng/mL vs 11.2(6.5) ng/mL, p = 0.039]. Female gender [OR 22.553; CI 95 % (2.16-235.48); p = 0.009] and diabetic status [OR 6.456; CI 95 % (1.144-36.433); p = 0.035] were independent predictors for 25(OH) D deficiency. Conclusions: Vitamin D insufficiency and vitamin D deficiency are indeed prevalent and under-recognized. Although the vitamin D levels among the study subjects and their control are equally low, the CKD group had severe degree of vitamin D deficiency. Diabetic status and female gender were independent predictors of low serum 25(OH)D. PMID:26933400

  18. Subclinical cardiopulmonary dysfunction in stage 3 chronic kidney disease

    PubMed Central

    Nelson, Alexander; Otto, James; Whittle, John; Stephens, Robert C M; Martin, Daniel S; Prowle, John R

    2016-01-01

    Objective Reduced exercise capacity is well documented in end-stage chronic kidney disease (CKD), preceded by changes in cardiac morphology in CKD stage 3. However, it is unknown whether subclinical cardiopulmonary dysfunction occurs in CKD stage 3 independently of heart failure. Methods Prospective observational cross-sectional study of exercise capacity assessed by cardiopulmonary exercise testing in 993 preoperative patients. Primary outcome was peak oxygen consumption (VO2peak). Anaerobic threshold (AT), oxygen pulse and exercise-evoked measures of autonomic function were analysed, controlling for CKD stage 3, age, gender, diabetes mellitus and hypertension. Results CKD stage 3 was present in 93/993 (9.97%) patients. Diabetes mellitus (RR 2.49 (95% CI 1.59 to 3.89); p<0.001), and hypertension (RR 3.20 (95% CI 2.04 to 5.03); p<0.001)) were more common in CKD stage 3. Cardiac failure (RR 0.83 (95% CI 0.30 to 2.24); p=0.70) and ischaemic heart disease (RR 1.40 (95% CI 0.97 to 2.02); p=0.09) were not more common in CKD stage 3. Patients with CKD stage 3 had lower predicted VO2peak (mean difference: 6% (95% CI 1% to 11%); p=0.02), lower peak heart rate (mean difference:9 bpm (95% CI 3 to 14); p=0.03)), lower AT (mean difference: 1.1 mL/min/kg (95% CI 0.4 to 1.7); p<0.001) and impaired heart rate recovery (mean difference: 4 bpm (95% CI 1 to 7); p<0.001)). Conclusions Subclinical cardiopulmonary dysfunction in CKD stage 3 is common. This study suggests that maladaptive cardiovascular/autonomic dysfunction may be established in CKD stage 3, preceding pathophysiology reported in end-stage CKD. PMID:27127638

  19. Bone mineral density predicts fractures in chronic kidney disease.

    PubMed

    West, Sarah L; Lok, Charmaine E; Langsetmo, Lisa; Cheung, Angela M; Szabo, Eva; Pearce, Dawn; Fusaro, Maria; Wald, Ron; Weinstein, Jordan; Jamal, Sophie A

    2015-05-01

    Fractures are common in chronic kidney disease (CKD). The optimal methods by which to assess fracture risk are unknown, in part, due to a lack of prospective studies. We determined if bone mineral density (BMD) by dual-energy X-ray absorptiometry (DXA), and/or high-resolution peripheral quantitative computed tomography (HRpQCT) could predict fractures in men and women ≥18 years old with stages 3 to 5 CKD. BMD was measured by DXA (at the total hip, lumbar spine, ultradistal, and 1/3 radius) and by HRpQCT (at the radius), and subjects were followed for 2 years for incident morphometric spine fractures and low-trauma clinical fractures. The mean age of the subjects was 62 years with equal numbers having stages 3, 4, and 5 CKD. Over 2 years there were 51 fractures in 35 subjects. BMD by DXA at baseline was significantly lower at all sites among those with incident fractures versus those without. For example, the mean BMD at the total hip in those with incident fractures was 0.77 g/cm2 (95% confidence interval [CI], 0.73 to 0.80) and in those without fracture was 0.95 g/cm2 (95% CI, 0.92 to 0.98). Almost all baseline HRpQCT measures were lower in those with incident fracture versus those without. For example, volumetric BMD in those with incident fractures was 232 mg HA/cm3 (95% CI, 213 to 251) and in those without fracture was 317.6 mg HA/cm3 (95% CI, 306 to 329.1). Bone loss occurred in all subjects, but was significantly greater among those with incident fractures. Our data demonstrate that low BMD (by DXA and HRpQCT) and a greater annualized percent decrease in BMD are risk factors for subsequent fracture in men and women with predialysis CKD.

  20. Rescue therapy with Tanshinone IIA hinders transition of acute kidney injury to chronic kidney disease via targeting GSK3β

    PubMed Central

    Jiang, Chunming; Zhu, Wei; Yan, Xiang; Shao, Qiuyuan; Xu, Biao; Zhang, Miao; Gong, Rujun

    2016-01-01

    Acute kidney injury (AKI) remains challenging for clinical practice and poses a risk of developing progressive chronic kidney disease (CKD) with no definitive treatment available yet. Tanshinone IIA, an active ingredient of Chinese herbal Salvia miltiorrhiza, has been widely used in Asia for the remarkable organoprotective activities. Its effect on established AKI, however, remains unknown. In mice with folic acid-induced AKI, delayed treatment with Tanshinone IIA, commenced early or late after injury, diminished renal expression of kidney injury markers, reduced apoptosis and improved kidney dysfunction, concomitant with mitigated histologic signs of AKI to CKD transition, including interstitial fibrosis and tubular atrophy, and with an ameliorated inflammatory infiltration in tubulointerstitium and a favored M2-skewed macrophage polarization. Mechanistically, Tanshinone IIA blunted glycogen synthase kinase (GSK)3β overactivity and hyperactivation of its downstream mitogen-activated protein kinases that are centrally implicated in renal fibrogenesis and inflammation. Inhibition of GSK3β is likely a key mechanism mediating the therapeutic activity of Tanshinone IIA, because sodium nitroprusside, a GSK3β activator, largely offset its renoprotective effect. In confirmatory studies, rescue treatment with Tanshinone IIA likewise ameliorated ischemia/reperfusion-induced kidney destruction in mice. Our data suggest that Tanshinone IIA represents a valuable treatment that improves post-AKI kidney salvage via targeting GSK3β. PMID:27857162

  1. Lipopolysaccharide-pretreated plasmacytoid dendritic cells ameliorate experimental chronic kidney disease.

    PubMed

    Zheng, Dong; Cao, Qi; Lee, Vincent W S; Wang, Ya; Zheng, Guoping; Wang, YuanMin; Tan, Thian Kui; Wang, Changqi; Alexander, Stephen I; Harris, David C H; Wang, Yiping

    2012-05-01

    Plasmacytoid dendritic cells play important roles in inducing immune tolerance, preventing allograft rejection, and regulating immune responses in both autoimmune disease and graft-versus-host disease. In order to evaluate a possible protective effect of plasmacytoid dendritic cells against renal inflammation and injury, we purified these cells from mouse spleens and adoptively transferred lipopolysaccharide (LPS)-treated cells, modified ex vivo, into mice with adriamycin nephropathy. These LPS-treated cells localized to the kidney cortex and the lymph nodes draining the kidney, and protected the kidney from injury during adriamycin nephropathy. Glomerulosclerosis, tubular atrophy, interstitial expansion, proteinuria, and creatinine clearance were significantly reduced in mice with adriamycin nephropathy subsequently treated with LPS-activated plasmacytoid dendritic cells as compared to the kidney injury in mice given naive plasmacytoid dendritic cells. In addition, LPS-pretreated cells, but not naive plasmacytoid dendritic cells, convert CD4+CD25- T cells into Foxp3+ regulatory T cells and suppress the proinflammatory cytokine production of endogenous renal macrophages. This may explain their ability to protect against renal injury in adriamycin nephropathy.

  2. The role of the gastrointestinal tract and microbiota on uremic toxins and chronic kidney disease development.

    PubMed

    Briskey, David; Tucker, Patrick; Johnson, David W; Coombes, Jeff S

    2017-02-01

    It is well-established that uremic toxins are positively correlated with the risk of developing chronic kidney disease and cardiovascular disease. In addition, emerging data suggest that gut bacteria exert an influence over both the production of uremic toxins and the development of chronic kidney disease. As such, modifying the gut microbiota may have the potential as a treatment for chronic kidney disease. This is supported by data that suggest that rescuing microbiota dysbiosis may: reduce uremic toxin production; prevent toxins and pathogens from crossing the intestinal barrier; and, reduce gastrointestinal tract transit time allowing nutrients to reach the microbiota in the distal portion of the gastrointestinal tract. Despite emerging literature, the gut-kidney axis has yet to be fully explored. A special focus should be placed on examining clinically translatable strategies that might encourage improvements to the microbiome, thereby potentially reducing the risk of the development of chronic kidney disease. This review aims to present an overview of literature linking changes to the gastrointestinal tract with microbiota dysbiosis and the development and progression of chronic kidney disease.

  3. [Parenteral iron therapy in chronic kidney disease or chronic heart failure].

    PubMed

    Eisenga, Michele F; Diepenbroek, Adry; Swinkels, Dorine W; Bakker, Stephan J L; van der Meer, Peter; Gaillard, Carlo A J M

    2015-01-01

    Iron deficiency and anaemia occur frequently in patients with chronic kidney disease (CKD) or chronic heart failure (CHF) and are associated with lower quality of life and higher mortality. Treating anaemia with erythropoietic growth factors produces no improvement. In recent years, the focus has therefore shifted to correction of iron deficiency. Chronic inflammation in CKD increases the production of hepcidin, which blocks iron absorption from the intestine and leads to less efficient re-use of iron from the macrophages. In absolute iron deficiency the body's iron stores are depleted, whereas in functional iron deficiency the supply of iron is not sufficient to meet demand from the bone marrow. Normal or high ferritin levels do not exclude iron deficiency at tissue level. The iron saturation fraction is a more useful indicator. Parenteral iron therapy ameliorates in CHF the symptoms of iron deficiency, irrespective of the effect on haemoglobin levels. The long-term effects of intravenous iron on mortality and morbidity are still unknown.

  4. Impact of Iodinated Contrast on Renal Function and Hemodynamics in Rats with Chronic Hyperglycemia and Chronic Kidney Disease.

    PubMed

    Fernandes, Sheila Marques; Martins, Daniel Malisani; da Fonseca, Cassiane Dezoti; Watanabe, Mirian; Vattimo, Maria de Fátima Fernandes

    2016-01-01

    Iodinated contrast (IC) is clinically used in diagnostic and interventional procedures, but its use can result in contrast-induced acute kidney injury (CI-AKI). Chronic kidney disease (CKD) and chronic hyperglycemia (CH) are important predisposing factors to CI-AKI. The aim of this study was to investigate the impact of iodinated contrast on the renal function and hemodynamics in rats with chronic hyperglycemia and chronic kidney disease. A total of 30 rats were divided into six groups; Sham: control of chronic renal disease; Citrate: control of chronic hyperglycemia (CH); Nx5/6: rats with 5/6 nephrectomy; Chronic Hyperglycemia: rats receiving Streptozotocin 65 mg/kg; Nx5/6 + IC: rats Nx5/6 received 6 mL/kg of IC; CH + IC: Chronic hyperglycemia rats receiving 6 mL/kg of IC. Renal function (inulin clearance; urinary neutrophil gelatinase-associated lipocalin, NGAL) and hemodynamics (arterial blood pressure; renal blood flow; renal vascular resistance) were evaluated. Iodinated contrast significantly increased urinary NGAL and reduced inulin clearance, while the hemodynamics parameters showed changes in arterial blood pressure, renal blood flow, and renal vascular resistance in both CKD and CH groups. The results suggest that the iodinated contrast in risk factors models has important impact on renal function and hemodynamics. NGAL was confirmed to play a role of highlight in diagnosis of CI-AKI.

  5. Onco-nephrology: an appraisal of the cancer and chronic kidney disease links.

    PubMed

    Izzedine, Hassan; Perazella, Mark A

    2015-12-01

    A bidirectional relationship has been observed for kidney disease and cancer. On the one hand, cancer is an important complication noted in kidney disease as well as a major cause of morbidity and mortality in this group. On the other hand, improved cancer treatment has prolonged survival, but also increased the development of acute and chronic kidney disease. The combination of cancer and kidney disease makes it challenging for clinicians to provide comprehensive and safe therapies for this group of patients. As such, clinicians caring for this group must develop expertise and become competent in the practice of a newly evolving subspecialty of nephrology known as 'onco-nephrology'. This brief narrative review will focus on the cancer risk in patients with underlying kidney disease, the therapies such as erythropoiesis-stimulating agents on cancer progression and other outcomes, and the appropriate dosing of anti-cancer agents in patients with underlying kidney disease.

  6. Plasma Nitration of High-Density and Low-Density Lipoproteins in Chronic Kidney Disease Patients Receiving Kidney Transplants

    PubMed Central

    Bakillah, Ahmed; Tedla, Fasika; Ayoub, Isabelle; John, Devon; Norin, Allen J.; Hussain, M. Mahmood; Brown, Clinton

    2015-01-01

    Background. Functional abnormalities of high-density lipoprotein (HDL) could contribute to cardiovascular disease in chronic kidney disease patients. We measured a validated marker of HDL dysfunction, nitrated apolipoprotein A-I, in kidney transplant recipients to test the hypothesis that a functioning kidney transplant reduces serum nitrated apoA-I concentrations. Methods. Concentrations of nitrated apoA-I and apoB were measured using indirect sandwich ELISA assays on sera collected from each transplant subject before transplantation and at 1, 3, and 12 months after transplantation. Patients were excluded if they have history of diabetes, treatment with lipid-lowering medications or HIV protease inhibitors, prednisone dose > 15 mg/day, nephrotic range proteinuria, serum creatinine > 1.5 mg/dL, or active inflammatory disease. Sera from 18 transplanted patients were analyzed. Four subjects were excluded due to insufficient data. Twelve and eight patients had creatinine < 1.5 mg/dL at 3 and 12 months after transplantation, respectively. Results. Nitrated apoA-I was significantly reduced at 12 months after transplantation (p = 0.039). The decrease in apoA-I nitration was associated with significant reduction in myeloperoxidase (MPO) activity (p = 0.047). In contrast to apoA-I, nitrated apoB was not affected after kidney transplantation. Conclusions. Patients with well-functioning grafts had significant reduction in nitrated apoA-I 12 months after kidney transplantation. Further studies are needed in a large cohort to determine if nitrated apoA-I can be used as a valuable marker for cardiovascular risk stratification in chronic kidney disease. PMID:26648662

  7. Sodium glucose transporter-2 inhibition has no renoprotective effects on non-diabetic chronic kidney disease.

    PubMed

    Ma, Qiuyue; Steiger, Stefanie; Anders, Hans-Joachim

    2017-04-01

    Sodium glucose transporter (SGLT)-2 inhibition has renoprotective effects in diabetic kidney disease. Whether similar effects can be achieved also in non-diabetic kidney disease is speculative. Chronic kidney disease was induced in C57BL/6N mice by feeding an oxalate-rich diet for 14 days, known to induce nephrocalcinosis-related tubular atrophy and interstitial fibrosis without directly affecting the glomerular compartment. Empagliflozin treatment started from day 0 of oxalate feeding had no effect on the decline of glomerular filtration rate, crystal deposition, blood urea nitrogen or serum creatinine levels on day 7 and 14. Tissue morphometry of tubular injury and kidney mRNA levels of kidney injury molecule-1 or tissue inhibitor of metalloproteinase-2 were comparable between empagliflozin- and vehicle-treated mice with oxalate nephropathy on day 7 and 14. Similarly, empagliflozin did not affect markers of interstitial fibrosis, including silver, alpha smooth muscle actin (αSMA) and collagen 1 staining, and mRNA levels of fibronectin-1, collagen 1α1, fibroblast-specific protein-1, and transforming growth factor (TGF)-β2 on day 7 and 14. Thus, the specific renoprotective mechanisms-of-action of SGLT2 inhibition in diabetic kidney disease do not apply to chronic oxalosis, a non-diabetic form of chronic kidney disease.

  8. Unusual Dyslipidemia in Patients with Chronic Kidney Diseases

    PubMed Central

    Goswami, Rohini K

    2017-01-01

    Introduction Chronic Kidney Disease (CKD) is a major and globally increasing health problem in the general population arising from a spectrum of diseases. Majority of the patients die even before reaching End Stage Renal Disease (ESRD) due to cardiovascular complications which arise due to altered lipoprotein compositions. Aim Present study was aimed at evaluating the serum lipid profile in CKD patients and to find the pattern of its alteration in both haemodialyzed and conservatively treated CKD patients. Materials and Methods Seventy one randomly selected CKD patients attending a tertiary care hospital of Assam during one year of time frame (40 haemodialyzed and 31 conservatively treated) along with 50 apparently healthy controls were included in the study. Test for serum lipid profile, urea creatinine, FBS, PPBS, total protein and albumin were carried out in all the cases and controls. The results were analyzed and compared with the controls using Microsoft Excel software. Results Triglyceride Level (TGL) of CKD group 157.88±61.82, controls 96.98±37.52, Very Low Density Lipoprotein (VLDL) of CKD group 31.58±12.36, controls 19.39±7.50 was marginally elevated and High Density Lipoprotein (HDL) of CKD group 33.40±9.06, controls 45.95±10.35 was significantly reduced in the patient group as compared to the controls and the results were statistically highly significant with p-value<0.001. Total cholesterol (CKD group 128.2±53.57, controls 142.53±31.44) and LDL (CKD group 63.23±46.47, controls 77.35±26.81) were lower in the patient group as compared to the controls, however the difference was statistically not significant (p value 0.09 and 0.059 respectively). There was no statistically significant difference of lipid profile between hemodialyzed and conservatively treated CKD groups and there was no gender related variation of lipid profile too. Conclusion Increased TGL and reduced HDL, rather than increased total cholesterol and increased LDL are

  9. Risk Factors for Development and Progression of Chronic Kidney Disease

    PubMed Central

    Tsai, Wan-Chuan; Wu, Hon-Yen; Peng, Yu-Sen; Ko, Mei-Ju; Wu, Ming-Shiou; Hung, Kuan-Yu; Wu, Kwan-Dun; Chu, Tzong-Shinn; Chien, Kuo-Liong

    2016-01-01

    Abstract The risk factors influencing the natural course of chronic kidney disease (CKD) are complex and heterogeneous, and few systematic reviews to date have focused on this issue. The aim of the study is to identify the risk factors for disease development and progression in each stage of CKD. We conducted electronic literature searches of PubMed, MEDLINE, Scopus, and the Cochrane Library up to October 15, 2012, for observational studies evaluating the risk factors on the development or progression of CKD. Eligible studies should have collected repeated information that could evaluate changes in renal function. Extracted information from all the included studies was synthesized narratively. Quality assessments were performed using the Newcastle–Ottawa Scale. An exploratory random-effects meta-analysis was performed where feasible to pool effect sizes across studies for a specific risk factor in a specific outcome. We identified 38 cohort studies and 2 case-control studies from 40 articles, with a total of 318,898 participants from 14 countries. The follow-up duration ranged from 1.5 to 16 years. The majority of the included studies were of high quality. The baseline CKD stages of the included studies ranged from normal to later stages, and only 19 studies could be classified into a specific range of CKD stages during follow-up. Three risk factors from studies of the same baseline and follow-up CKD stages were eligible for the exploratory meta-analysis, including male sex, substantial proteinuria, and diabetes. The hazard ratios for the progression from CKD stages 3–5 to end-stage renal disease (ESRD) were 1.37 (95% confidence interval 1.17–1.62), 1.64 (1.01–2.66), and 1.16 (0.98–1.38) for male sex, substantial proteinuria, and diabetes, respectively. In conclusion, our analyses comprehensively summarize the initiating and perpetuating factors for CKD. Male sex and substantial proteinuria are significant perpetuating factors for the progression from

  10. Measurement of the intestinal permeability in chronic kidney disease

    PubMed Central

    Terpstra, Matty L; Singh, Ramandeep; Geerlings, Suzanne E; Bemelman, Frederike J

    2016-01-01

    AIM: To evaluate methods measuring the intestinal per-meability in chronic kidney disease (CKD) and clarify whether there is an increased intestinal permeability in CKD. METHODS: We reviewed the literature in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-analysis (PRISMA) protocol and performed a systematic literature search through MEDline and EMBASE. All controlled trials and cohort studies using non-invasive methods to assess intestinal permeability in CKD patients were included. Excluded were: Conference abstracts and studies including patients younger than 18 years or animals. From the included studies we summarized the used methods and their advantages and disadvantages. For the comparison of their results we divided the included studies in two categories based on their included patient population, either assessing the intestinal permeability in mild to moderate CKD patients or in end stage renal disease (ESRD) patients. Results were graphically displayed in two plots, one comparing the intestinal permeability in mild to moderate CKD patients to healthy controls and one comparing the intestinal permeability in ESRD patients to healthy controls. RESULTS: From the 480 identified reports, 15 met our inclusion criteria. Methods that were used to assess the intestinal permeability varied from markers measured in plasma to methods based on calculating the urinary excretion of an orally administered test substance. None of the applied methods has been validated in CKD patients and the influence of decreased renal function on the different methods remains unclear to a certain extent. Methods that seem the least likely to be influenced by decreased renal function are the quantitative PCR (qPCR) for bacterial DNA in blood and D-lactate. Considering the results published by the included studies; the studies including patients with mild to moderate CKD conducted conflicting results. Some studies did report an increase in intestinal

  11. Hepcidin: an important iron metabolism regulator in chronic kidney disease.

    PubMed

    Antunes, Sandra Azevedo; Canziani, Maria Eugênia Fernandes

    2016-01-01

    Anemia is a common complication and its impact on morbimortality in patients with chronic kidney disease (CKD) is well known. The discovery of hepcidin and its functions has contributed to a better understanding of iron metabolism disorders in CKD anemia. Hepcidin is a peptide mainly produced by hepatocytes and, through a connection with ferroportin, it regulates iron absorption in the duodenum and its release of stock cells. High hepcidin concentrations described in patients with CKD, especially in more advanced stages are attributed to decreased renal excretion and increased production. The elevation of hepcidin has been associated with infection, inflammation, atherosclerosis, insulin resistance and oxidative stress. Some strategies were tested to reduce the effects of hepcidin in patients with CKD, however more studies are necessary to assess the impact of its modulation in the management of anemia in this population. Resumo Anemia é uma complicação frequente e seu impacto na morbimortalidade é bem conhecido em pacientes com doença renal crônica (DRC). A descoberta da hepcidina e de suas funções contribuíram para melhor compreensão dos distúrbios do metabolismo de ferro na anemia da DRC. Hepcidina é um peptídeo produzido principalmente pelos hepatócitos, e através de sua ligação com a ferroportina, regula a absorção de ferro no duodeno e sua liberação das células de estoque. Altas concentrações de hepcidina descritas em pacientes com DRC, principalmente em estádios mais avançados, são atribuídas à diminuição da excreção renal e ao aumento de sua produção. Elevação de hepcidina tem sido associada à ocorrência de infecção, inflamação, aterosclerose, resistência à insulina e estresse oxidativo. Algumas estratégias foram testadas para diminuir os efeitos da hepcidina em pacientes com DRC, entretanto, serão necessários mais estudos para avaliar o impacto de sua modulação no manejo da anemia nessa população.

  12. Dyslipidemia in patients with chronic kidney disease: etiology and management

    PubMed Central

    Mikolasevic, Ivana; Žutelija, Marta; Mavrinac, Vojko; Orlic, Lidija

    2017-01-01

    Patients with chronic kidney disease (CKD), including those with end-stage renal disease, treated with dialysis, or renal transplant recipients have an increased risk for cardiovascular disease (CVD) morbidity and mortality. Dyslipidemia, often present in this patient population, is an important risk factor for CVD development. Specific quantitative and qualitative changes are seen at different stages of renal impairment and are associated with the degree of glomerular filtration rate declining. Patients with non-dialysis-dependent CKD have low high-density lipoproteins (HDL), normal or low total cholesterol (TC) and low-density lipoprotein (LDL) cholesterol, increased triglycerides as well as increased apolipoprotein B (apoB), lipoprotein(a) (Lp (a)), intermediate- and very-low-density lipoprotein (IDL, VLDL; “remnant particles”), and small dense LDL particles. In patients with nephrotic syndrome lipid profile is more atherogenic with increased TC, LDL, and triglycerides. Lipid profile in hemodialysis (HD) patients is usually similar to that in non-dialysis-dependent CKD patients. Patients on peritoneal dialysis (PD) have more altered dyslipidemia compared to HD patients, which is more atherogenic in nature. These differences may be attributed to PD per se but may also be associated with the selection of dialytic modality. In renal transplant recipients, TC, LDL, VLDL, and triglycerides are elevated, whereas HDL is significantly reduced. Many factors can influence post-transplant dyslipidemia including immunosuppressive agents. This patient population is obviously at high risk; hence, prompt diagnosis and management are required to improve their clinical outcomes. Various studies have shown statins to be effective in the cardiovascular risk reduction in patients with mild-to-moderate CKD as well as in renal transplant recipients. However, according to recent clinical randomized controlled trials (4D, A Study to Evaluate the Use of Rosuvastatin in Subjects on

  13. MiR-142-5p and miR-486-5p as biomarkers for early detection of chronic antibody-mediated rejection in kidney transplantation.

    PubMed

    Iwasaki, Kenta; Yamamoto, Takayuki; Inanaga, Yukiko; Hiramitsu, Takahisa; Miwa, Yuko; Murotani, Kenta; Narumi, Shuji; Watarai, Yoshihiko; Katayama, Akio; Uchida, Kazuharu; Kobayashi, Takaaki

    2017-02-01

    De novo donor-specific HLA antibody (DSA) would not necessarily contribute to chronic antibody-mediated rejection (CAMR) in kidney transplantation. Here, we investigated whether PBMC miRNAs could be predictable biomarkers for CAMR. Microarray profiling of 435 mature miRNAs in pooled samples was conducted. Individual analysis revealed that miR-142-5p was significantly (p < 0.01) underexpressed in patients with DSA. After DSA production, miR-486-5p and its target PTEN/foxO3 mRNA were significantly overexpressed (p < 0.01) and underexpressed (p < 0.01), respectively, in patients with biopsy-proven CAMR, compared with non-CAMR. Our studies suggest that miRNA expression patterns may serve as noninvasive diagnostic biomarkers to evaluate immune response and kidney allograft status.

  14. Chronic Kidney Disease and Medicines: What You Need to Know

    MedlinePlus

    ... how to protect your kidneys. These medicines include: n Prescription and over-the-counter (OTC) medicines—those you get without prescriptions, and n Supplements, such as vitamins and herbal or natural ...

  15. When Your Child Has a Chronic Kidney Disease

    MedlinePlus

    ... slushy beverages or ice cubes to suck on. Sodium Some kids with kidney disease, particularly those with ... pressure, may need to restrict their intake of sodium, which is found in table salt and many ...

  16. The relationships of sleep apnea, hypertension, and resistant hypertension on chronic kidney disease.

    PubMed

    Chang, Chih-Ping; Li, Tsai-Chung; Hang, Liang-Wen; Liang, Shinn-Jye; Lin, Jen-Jyn; Chou, Che-Yi; Tsai, Jeffrey J P; Ko, Po-Yen; Chang, Chiz-Tzung

    2016-06-01

    Hypertension, blood pressure variation, and resistant hypertension have close relations to sleep apnea, which lead to target organ damage, including the kidney. The complex relationships between sleep apnea and blood pressure cause their interactions with chronic kidney disease ambiguous. The aim of the study was to elucidate the separate and joint effects of sleep apnea, hypertension, and resistant hypertension on chronic kidney disease. A cross-sectional study was done to see the associations of sleep apnea, hypertension, and resistant hypertension with chronic kidney disease in 998 subjects underwent overnight polysomnography without device-therapy or surgery for their sleep-disordered breathing. Multivariate logistic regression was used to analyze the severity of SA, hypertension stage, resistant hypertension, and their joint effects on CKD. The multivariable relative odds (95% CI) of chronic kidney disease for the aged (age ≥65 years), severe sleep apnea, stage III hypertension, and resistant hypertension were 3.96 (2.57-6.09) (P < 0.001), 2.28 (1.13-4.58) (P < 0.05), 3.55 (1.70-7.42) (P < 0.001), and 9.42 (4.22-21.02) (P < 0.001), respectively. In subgroups analysis, the multivariable relative odds ratio of chronic kidney disease was highest in patients with both resistant hypertension and severe sleep apnea [13.42 (4.74-38.03)] (P < 0.001). Severe sleep apnea, stage III hypertension, and resistant hypertension are independent risk factors for chronic kidney disease. Patients with both severe sleep apnea and resistant hypertension have the highest risks.

  17. The value of needle renal allograft biopsy. I. A retrospective study of biopsies performed during putative rejection episodes.

    PubMed Central

    Matas, A J; Sibley, R; Mauer, M; Sutherland, D E; Simmons, R L; Najarian, J S

    1983-01-01

    Following renal transplantation, immunosuppression is usually increased to treat presumed rejection episodes. However, a) many conditions mimic rejection in the post-transplant period, and b) many rejection episodes are irreversible. As increased immunosuppressive therapy is associated with an increased risk of infection, it would be ideal to limit antirejection therapy to only the rejection episodes that are reversible. The role of percutaneous allograft biopsy was studied as an aid to decide which patients to treat for rejection, to limit unnecessary immunosuppression and to predict allograft survival. One hundred thirty-five patients with suspected rejection underwent 206 allograft biopsies without complication. Two hundred four biopsies were available for study. Biopsies were coded on a 1-4 scale (minimal, mild, moderate, severe) for acute and chronic tubulointerstitial infiltrate and vascular rejection, as well as no rejection (e.g., recurrence of original disease). Treatment decisions were made on the basis of the biopsy combined with clinical data. All patients have been followed two years and outcome correlated with biopsy findings (death, nephrectomy, and return to dialysis defined as kidney loss). The results were the following: 1) biopsies represented changes within the kidney. Of 16 kidneys removed within one month of biopsy, no nephrectomy specimen showed less rejection than that seen on biopsy. 2) Eighty-one biopsies (39.7%) led to tapering or not increasing immunosuppression (either no rejection, minimal rejection, or irreversible changes). 3) Kidneys having either severe acute or chronic vascular rejection (less than 30% function at three months) had significantly (p less than 0.05) decreased survival three to 24 months postbiopsy than those with minimal or mild vascular rejection or tubulointerstitial infiltrate (83% function at three months). 4) Kidneys with moderate chronic vascular rejection and those with severe acute tubulointerstitial

  18. Diagnosis of Chronic Kidney Disease Based on Support Vector Machine by Feature Selection Methods.

    PubMed

    Polat, Huseyin; Danaei Mehr, Homay; Cetin, Aydin

    2017-04-01

    As Chronic Kidney Disease progresses slowly, early detection and effective treatment are the only cure to reduce the mortality rate. Machine learning techniques are gaining significance in medical diagnosis because of their classification ability with high accuracy rates. The accuracy of classification algorithms depend on the use of correct feature selection algorithms to reduce the dimension of datasets. In this study, Support Vector Machine classification algorithm was used to diagnose Chronic Kidney Disease. To diagnose the Chronic Kidney Disease, two essential types of feature selection methods namely, wrapper and filter approaches were chosen to reduce the dimension of Chronic Kidney Disease dataset. In wrapper approach, classifier subset evaluator with greedy stepwise search engine and wrapper subset evaluator with the Best First search engine were used. In filter approach, correlation feature selection subset evaluator with greedy stepwise search engine and filtered subset evaluator with the Best First search engine were used. The results showed that the Support Vector Machine classifier by using filtered subset evaluator with the Best First search engine feature selection method has higher accuracy rate (98.5%) in the diagnosis of Chronic Kidney Disease compared to other selected methods.

  19. Relation of aortic valve calcium to chronic kidney disease (from the Chronic Renal Insufficiency Cohort Study).

    PubMed

    Guerraty, Marie A; Chai, Boyang; Hsu, Jesse Y; Ojo, Akinlolu O; Gao, Yanlin; Yang, Wei; Keane, Martin G; Budoff, Matthew J; Mohler, Emile R

    2015-05-01

    Although subjects with chronic kidney disease (CKD) are at markedly increased risk for cardiovascular mortality, the relation between CKD and aortic valve calcification has not been fully elucidated. Also, few data are available on the relation of aortic valve calcification and earlier stages of CKD. We sought to assess the relation of aortic valve calcium (AVC) with estimated glomerular filtration rate (eGFR), traditional and novel cardiovascular risk factors, and markers of bone metabolism in the Chronic Renal Insufficiency Cohort (CRIC) Study. All patients who underwent aortic valve scanning in the CRIC study were included. The relation between AVC and eGFR, traditional and novel cardiovascular risk factors, and markers of calcium metabolism were analyzed using both unadjusted and adjusted regression models. A total of 1,964 CRIC participants underwent computed tomography for AVC quantification. Decreased renal function was independently associated with increased levels of AVC (eGFR 47.11, 44.17, and 39 ml/min/1.73 m2, respectively, p<0.001). This association persisted after adjusting for traditional, but not novel, AVC risk factors. Adjusted regression models identified several traditional and novel risk factors for AVC in patients with CKD. There was a difference in AVC risk factors between black and nonblack patients. In conclusion, our study shows that eGFR is associated in a dose-dependent manner with AVC in patients with CKD, and this association is independent of traditional cardiovascular risk factors.

  20. Management of acute and post-operative pain in chronic kidney disease

    PubMed Central

    Parmar, Malvinder S

    2013-01-01

    Chronic kidney disease is common and patients with many co-morbid conditions frequently have to undergo surgical procedures and, therefore, require effective pain management. The pharmacokinetics of various analgesic agents are not well studied in patients with chronic kidney disease and the risk of accumulation of the main drug or their metabolites, resulting in serious adverse events, is a common scenario on medical and surgical wards. It is common for these patients to be cared for by 'non-nephrologists' who often prescribe the standard dose of the commonly used analgesics, without taking into consideration the patient's kidney function. It is important to recognize the problems and complications associated with the use of standard doses of analgesics, and highlight the importance of adjusting analgesic dosage based on kidney function to avoid complications while still providing adequate pain relief. PMID:24358847

  1. Chronic kidney disease, severe arterial and arteriolar sclerosis and kidney neoplasia: on the spectrum of kidney involvement in MELAS syndrome

    PubMed Central

    2012-01-01

    Background MELAS syndrome (MIM ID#540000), an acronym for Mitochondrial Encephalopathy, Lactic Acidosis and Stroke-like episodes, is a genetically heterogeneous mitochondrial disorder with protean manifestations and occasional kidney involvement. Interest in the latter is rising due to the identification of cases with predominant kidney involvement and to the hypothesis of a link between mitochondrial DNA and kidney neoplasia. Case presentation We report the case of a 41-year-old male with full blown MELAS syndrome, with lactic acidosis and neurological impairment, affected by the "classic" 3243A > G mutation of mitochondrial DNA, with kidney cancer. After unilateral nephrectomy, he rapidly developed severe kidney functional impairment, with nephrotic proteinuria. Analysis of the kidney tissue at a distance from the two tumor lesions, sampled at the time of nephrectomy was performed in the context of normal blood pressure, recent onset of diabetes and before the appearance of proteinuria. The morphological examination revealed a widespread interstitial fibrosis with dense inflammatory infiltrate and tubular atrophy, mostly with thyroidization pattern. Vascular lesions were prominent: large vessels displayed marked intimal fibrosis and arterioles had hyaline deposits typical of hyaline arteriolosclerosis. These severe vascular lesions explained the different glomerular alterations including ischemic and obsolescent glomeruli, as is commonly observed in the so-called "benign" arteriolonephrosclerosis. Some rare glomeruli showed focal segmental glomerulosclerosis; as the patient subsequently developed nephrotic syndrome, these lesions suggest that silent ischemic changes may result in the development of focal segmental glomerulosclerosis secondary to nephron loss. Conclusions Nephron loss may trigger glomerular sclerosis, at least in some cases of MELAS-related nephropathy. Thus the incidence of kidney disease in the "survivors" of MELAS syndrome may increase as the

  2. BMP-7 Signaling and its Critical Roles in Kidney Development, the Responses to Renal Injury, and Chronic Kidney Disease.

    PubMed

    Manson, Scott R; Austin, Paul F; Guo, Qiusha; Moore, Katelynn H

    2015-01-01

    Chronic kidney disease (CKD) is a significant health problem that most commonly results from congenital abnormalities in children and chronic renal injury in adults. The therapeutic potential of BMP-7 was first recognized nearly two decades ago with studies demonstrating its requirement for kidney development and ability to inhibit the pathogenesis of renal injury in models of CKD. Since this time, our understanding of CKD has advanced considerably and treatment strategies have evolved with the identification of many additional signaling pathways, cell types, and pathologic processes that contribute to disease progression. The purpose of this review is to revisit the seminal studies that initially established the importance of BMP-7, highlight recent advances in BMP-7 research, and then integrate this knowledge with current research paradigms. We will provide an overview of the evolutionarily conserved roles of BMP proteins and the features that allow BMP signaling pathways to function as critical signaling nodes for controlling biological processes, including those related to CKD. We will discuss the multifaceted functions of BMP-7 during kidney development and the potential for alterations in BMP-7 signaling to result in congenital abnormalities and pediatric kidney disease. We will summarize the renal protective effects of recombinant BMP-7 in experimental models of CKD and then propose a model to describe the potential physiological role of endogenous BMP-7 in the innate repair mechanisms of the kidneys that respond to renal injury. Finally, we will highlight emerging clinical approaches for applying our knowledge of BMP-7 toward improving the treatment of patients with CKD.

  3. Vegetarian Diet in Chronic Kidney Disease-A Friend or Foe.

    PubMed

    Gluba-Brzózka, Anna; Franczyk, Beata; Rysz, Jacek

    2017-04-10

    Healthy diet is highly important, especially in patients with chronic kidney disease (CKD). Proper nutrition provides the energy to perform everyday activities, prevents infection, builds muscle, and helps to prevent kidney disease from getting worse. However, what does a proper diet mean for a CKD patient? Nutrition requirements differ depending on the level of kidney function and the presence of co-morbid conditions, including hypertension, diabetes, and cardiovascular disease. The diet of CKD patients should help to slow the rate of progression of kidney failure, reduce uremic toxicity, decrease proteinuria, maintain good nutritional status, and lower the risk of kidney disease-related secondary complications (cardiovascular disease, bone disease, and hypertension). It has been suggested that plant proteins may exert beneficial effects on blood pressure, proteinuria, and glomerular filtration rate, as well as results in milder renal tissue damage when compared to animal proteins. The National Kidney Foundation recommends vegetarianism, or part-time vegetarian diet as being beneficial to CKD patients. Their recommendations are supported by the results of studies demonstrating that a plant-based diet may hamper the development or progression of some complications of chronic kidney disease, such as heart disease, protein loss in urine, and the progression of kidney damage. However, there are sparse reports suggesting that a vegan diet is not appropriate for CKD patients and those undergoing dialysis due to the difficulty in consuming enough protein and in maintaining proper potassium and phosphorus levels. Therefore, this review will focus on the problem as to whether vegetarian diet and its modifications are suitable for chronic kidney disease patients.

  4. Maremar, prevalence of chronic kidney disease, how to avoid over-diagnosis and under-diagnosis.

    PubMed

    De Broe, Marc E; Gharbi, Mohammed Benghanem; Elseviers, Monique

    2016-04-01

    Chronic kidney disease is considered as a major public health problem. Recent studies mention a prevalence rate between 8%-12%. Several editorials, comments, short reviews described the weaknesses (lack of confirmation of proteinuria, and of chronicity of decreased estimated glomerular filtration rate) of a substantial number of studies and the irrational of using a single arbitrary set point, i.e. diagnosis of chronic kidney disease whenever the estimated glomerular filtration rate is less than 60mL/min/1.73m(2). Maremar (Maladies rénales chroniques au Maroc) is a prevalence study of chronic kidney disease, hypertension, diabetes and obesity in a randomized, representative, high response rate (85%), sample of the adult population of Morocco, strictly applying the Kidney Disease: Improving Global Outcomes (KDIGO) criteria. Compared to the vast majority of the available studies, Maremar has a low prevalence of chronic kidney disease (2.9% adjusted to the actual adult population of Morocco). The population pyramid, and particularly the confirmation of proteinuria and "chronicity" of the decreased estimated glomerular filtration rate are the main reasons for this low prevalence of chronic kidney disease. The choice of arbitrary single threshold of estimated glomerular filtration rate for classifying stage 3-5 chronic kidney disease inevitably leads to "over-diagnosis" (false positives) of the disease in the elderly, particularly those without proteinuria, hematuria or hypertension, and to "under-diagnosed" (false negatives) in younger individuals with an estimated glomerular filtration rate above 60mL/min/1.73m(2) and below the 3rd percentile of their age/gender category. There is an urgent need for quality studies using in a correct way the recent KDIGO guidelines when investigating the prevalence of chronic kidney disease, in order to avoid a 50 to 100% overestimation of a disease state with potential dramatic consequences. The combination of the general population

  5. Acute kidney injury in children with sickle cell disease-compounding a chronic problem.

    PubMed

    Mammen, Cherry; Bissonnette, Mei Lin; Matsell, Douglas G

    2017-03-28

    In an article recently published in Pediatric Nephrology, Baddam and colleagues discuss the relatively underreported clinical problem of repeated episodes of acute kidney injury (AKI) in children with sickle cell disease (SCD). Their report is a cautionary note about the importance of repeated kidney injury on the background of underlying chronic kidney injury and its potential implications on long-term kidney outcome. In children and adults with SCD, this includes the effects of repeated vaso-occlusive crises and the management of these painful episodes with non-steroidal anti-inflammatory drugs. Here we review the scope of kidney involvement in SCD in children and discuss the potential short- and long-term consequences of AKI in children with SCD.

  6. [Efficacy and safety of lanthanum carbonate in chronic kidney disease patients with hyperphosphataemia].

    PubMed

    Laville, Maurice

    2011-06-01

    Hyperphosphataemia is a frequent complication in patients with chronic kidney disease and is associated with increased cardiovascular morbidity. Lanthanum carbonate is a calcium-free phosphate binder indicated in patients with chronic kidney disease. Its digestive absorption is minimal (<0,002%). This minimal quantity is rapidly excreted by the hepatobiliary system, but there is an initial accumulation in liver and bone, which reaches a plateau within a few weeks. Long-term follow-up until six years did not show any bone or liver toxicity. Efficacy and safety of lanthanum carbonate have been assessed in randomized trials. The most common side effects reported were gastrointestinal and occurred with a similar incidence than with placebo and other phosphate binders. Hypercalcemia was less frequent than with calcium carbonate. This review highlights pharmacokinetic, pharmacodynamic and clinical (efficacy and safety) properties of lanthanum carbonate and discusses its place in the management of hyperphosphataemia in patients with chronic kidney disease.

  7. [CHRONIC KIDNEY DISEASE AND ITS RELATIONSHIP WITH INTAKE OF TURMERIC, CATECHINS, PROANTHOCYANIDINS AND OMEGA-3].

    PubMed

    Guerrero-Wyss, Marion; Montiel P, Javiera; Jara L, Loreto; Moris U, Gabriela; Mosquera B, Mitchelle

    2015-10-01

    Chronic renal disease is characterized by decreased glomerular filtration rate (GFR) < 60 ml/min/ 1.73m2 and/or the presence of kidney damage independent of the cause for a period of 3 months or more. The treatment of more advanced stages of chronic kidney disease is dialysis, and most common form of hemodialysis. This treatment is costly in our country reaching USD 900 per person. The main cause of admission to dialysis, diabetic nephropathy remains with 34% of all revenue. This alone makes any improvement in the treatment of CKD is highly desirable. There is evidence available about the fundamental role of turmeric, proanthocyanidins, catechins and omega-3 on how these compounds are related to the response to treatment of chronic kidney disease for various reasons.

  8. The experiences of close persons caring for people with chronic kidney disease stage 5 on conservative kidney management: Contested discourses of ageing

    PubMed Central

    Myers, Jason; Smith, Glenn; Higgs, Paul; Burns, Aine; Hopkins, Katherine; Jones, Louise

    2014-01-01

    Chronic kidney disease stage 5 is a global health challenge in the context of population ageing across the world. The range of treatment options available to patients at all ages has increased and includes transplantation and dialysis. However, these options are often seen as inappropriate for older frailer patients who are now offered the option of conservative kidney management, which is presented as a non-invasive alternative to dialysis, involving symptom management and addressing psychosocial needs. In this study, we conducted qualitative interviews with 26 close persons caring for someone with chronic kidney disease stage 5 in the United Kingdom to investigate how conservative kidney management interacted with implicit ideas of ageing, in both the experience of conservative kidney management and the understanding of the prognosis and future care of the kidney disease. Our findings highlighted participant confusion about the nature of conservative kidney management, which stems from an initial lack of clarity about how conservative kidney management differed from conventional treatments for chronic kidney disease stage 5. In particular, some respondents were not aware of the implicit palliative nature of the intervention or indeed the inevitable end-of-life issues. Although these findings can be situated within the context of communication failure, we would further argue that they also bring to the surface tensions in the discourses surrounding ageing and old age, drawing on the use of a ‘natural’ and a ‘normal’ paradigm of ageing. In the context of chronic kidney disease stage 5, more patients are being dialysed at older ages, but conservative kidney management is being advanced as a better option than dialysis in terms of quality of life and experience. However, in doing so, conservative kidney management implicitly draws on a notion of older age that echoes natural ageing rather than advocate a more interventionist approach. The role of discourses

  9. The experiences of close persons caring for people with chronic kidney disease stage 5 on conservative kidney management: contested discourses of ageing.

    PubMed

    Low, Joe; Myers, Jason; Smith, Glenn; Higgs, Paul; Burns, Aine; Hopkins, Katherine; Jones, Louise

    2014-11-01

    Chronic kidney disease stage 5 is a global health challenge in the context of population ageing across the world. The range of treatment options available to patients at all ages has increased and includes transplantation and dialysis. However, these options are often seen as inappropriate for older frailer patients who are now offered the option of conservative kidney management, which is presented as a non-invasive alternative to dialysis, involving symptom management and addressing psychosocial needs. In this study, we conducted qualitative interviews with 26 close persons caring for someone with chronic kidney disease stage 5 in the United Kingdom to investigate how conservative kidney management interacted with implicit ideas of ageing, in both the experience of conservative kidney management and the understanding of the prognosis and future care of the kidney disease. Our findings highlighted participant confusion about the nature of conservative kidney management, which stems from an initial lack of clarity about how conservative kidney management differed from conventional treatments for chronic kidney disease stage 5. In particular, some respondents were not aware of the implicit palliative nature of the intervention or indeed the inevitable end-of-life issues. Although these findings can be situated within the context of communication failure, we would further argue that they also bring to the surface tensions in the discourses surrounding ageing and old age, drawing on the use of a 'natural' and a 'normal' paradigm of ageing. In the context of chronic kidney disease stage 5, more patients are being dialysed at older ages, but conservative kidney management is being advanced as a better option than dialysis in terms of quality of life and experience. However, in doing so, conservative kidney management implicitly draws on a notion of older age that echoes natural ageing rather than advocate a more interventionist approach. The role of discourses of ageing

  10. FOCAL SEGMENTAL GLOMERULOSCLEROSIS AND CHRONIC KIDNEY DISASE IN PEDIATRIC PATIENTS

    PubMed Central

    Kiffel, Jeremy; Rahimzada, Yael; Trachtman, Howard

    2011-01-01

    Focal segmental glomerulosclerosis (FSGS) is one of the most common forms of acquired glomerular disease leading to end stage kidney disease (ESKD). Its incidence is rising around the world. There is no proven therapy for those patients who do not respond to corticosteroids and it can recur in 20–25% of patients who receive a kidney transplant. The disease can be primary or secondary to various conditions including vesicoureteral reflux, obesity, medications, and infections. Recent advances have demonstrated the important role of genetic mutations in podocyte proteins as a cause of FSGS. There is an urgent need for randomized clinical trials to develop safe and effective therapy for FSGS that occurs in the native or transplanted kidney. PMID:21896374

  11. Combination of ACE inhibitor with nicorandil provides further protection in chronic kidney disease.

    PubMed

    Shiraishi, Takeshi; Tamura, Yoshifuru; Taniguchi, Kei; Higaki, Masato; Ueda, Shuko; Shima, Tomoko; Nagura, Michito; Nakagawa, Takahiko; Johnson, Richard J; Uchida, Shunya

    2014-12-15

    An inhibition in the renin-angiotensin system (RAS) is one of the most widely used therapies to treat chronic kidney disease. However, its effect is occasionally not sufficient and additional treatments may be required. Recently, we reported that nicorandil exhibited renoprotective effects in a mouse model of diabetic nephropathy. Here we examined if nicorandil can provide an additive protection on enalapril in chronic kidney disease. Single treatment with either enalapril or nicorandil significantly ameliorated glomerular and tubulointerstitial injury in the rat remnant kidney while the combination of these two compounds provided additive effects. In addition, an increase in oxidative stress in remnant kidney was also blocked by either enalapril or nicorandil while the combination of the drugs was more potent. A mechanism was likely due for nicorandil to preventing manganase superoxide dismutase (MnSOD) and sirtuin (Sirt)3 from being reduced in injured kidneys. A study with cultured podocytes indicated that the antioxidative effect could be mediated through sulfonylurea receptor (SUR) in the mitochondrial KATP channel since blocking SUR with glibenclamide reduced MnSOD and Sirt3 expression in podocytes. In conclusion, nicorandil may synergize with enalapril to provide superior protection in chronic kidney disease.

  12. Increased risk of cardiovascular complications in chronic kidney disease: a possible role of leptin.

    PubMed

    Korolczuk, Agnieszka; Dudka, Jaroslaw

    2014-01-01

    Leptin is a small peptide hormone (16 kDa), a product of the obesity gene (Ob), and is mainly synthesized and secreted by adipocytes. It is removed from the blood by the kidneys. The kidney is not only a site of leptin clearance, but also a target organ for its action in different pathophysiological states. Several studies have documented a strong relationship between chronic kidney disease (CKD) and accelerated cardiovascular disease (CVD) defined as a cardiorenal syndrome. Patients with stage 3 and 4 CKD develop cardiovascular complications and are at increased risk of death from CVD. Renal dysfunction promotes several mechanisms responsible for exacerbation of cardiovascular disease. These include activation of the renin-angiotensin system, oxidative stress, elevated asymmetric dimethylarginine (ADMA), low-grade inflammation with increased circulating cytokines, and dyslipidemia. Recently, it has been observed that plasma leptin level is elevated in patients with cardiorenal syndrome. In obesity, hyperleptinemia combined with selective leptin resistance appear to have a critical role in the development and progression of kidney disease, CVD and metabolic syndrome. This has clinical implications for the treatment of obesity-related hypertension and kidney disease. In this paper the role of leptin in chronic kidney disease and accelerated cardiovascular disease is out lined. The link between hyperleptinemia and development and progression of morphologic changes that effect kidney in obese patients is also discussed.

  13. Crosstalk between the unfolded protein response and NF-κB-mediated inflammation in the progression of chronic kidney disease.

    PubMed

    Mohammed-Ali, Zahraa; Cruz, Gaile L; Dickhout, Jeffrey G

    2015-01-01

    The chronic inflammatory response is emerging as an important therapeutic target in progressive chronic kidney disease. A key transcription factor in the induction of chronic inflammation is NF-κB. Recent studies have demonstrated that sustained activation of the unfolded protein response (UPR) can initiate this NF-κB signaling phenomenon and thereby induce chronic kidney disease progression. A key factor influencing chronic kidney disease progression is proteinuria and this condition has now been demonstrated to induce sustained UPR activation. This review details the crosstalk between the UPR and NF-κB pathways as pertinent to chronic kidney disease. We present potential tools to study this phenomenon as well as potential therapeutics that are emerging to regulate the UPR. These therapeutics may prevent inflammation specifically induced in the kidney due to proteinuria-induced sustained UPR activation.

  14. Chronic kidney disease in European patients with obstructive sleep apnea: the ESADA cohort study.

    PubMed

    Marrone, Oreste; Battaglia, Salvatore; Steiropoulos, Paschalis; Basoglu, Ozen K; Kvamme, John A; Ryan, Silke; Pepin, Jean-Louis; Verbraecken, Johan; Grote, Ludger; Hedner, Jan; Bonsignore, Maria R

    2016-12-01

    The cross-sectional relationship of obstructive sleep apnea with moderate to severe chronic kidney disease, defined as an estimated glomerular filtration rate <60 mL min(-1) ∙1.73 m(-2) , was investigated in a large cohort of patients with suspected obstructive sleep apnea studied by nocturnal polysomnography or cardiorespiratory polygraphy. Data were obtained from the European Sleep Apnea Database, where information from unselected adult patients with suspected obstructive sleep apnea afferent to 26 European sleep centres had been prospectively collected. Both the Modification of Diet in Renal Disease and the Chronic Kidney Disease-Epidemiology Collaboration equations were used for the assessment of estimated glomerular filtration rate. The analysed sample included 7700 subjects, 71% male, aged 51.9 ± 12.5 years. Severe obstructive sleep apnea (apnea-hypopnea index ≥30) was found in 34% of subjects. The lowest nocturnal oxygen saturation was 81 ± 10.2%. Chronic kidney disease prevalence in the whole sample was 8.7% or 6.1%, according to the Modification of Diet in Renal Disease or the Chronic Kidney Disease-Epidemiology Collaboration equations, respectively. Subjects with lower estimated glomerular filtration rate were older, more obese, more often female, had worse obstructive sleep apnea and more co-morbidities (P < 0.001, each). With both equations, independent predictors of estimated glomerular filtration rate <60 were: chronic heart failure; female gender; systemic hypertension; older age; higher body mass index; and worse lowest nocturnal oxygen saturation. It was concluded that in obstructive sleep apnea, chronic kidney disease is largely predicted by co-morbidities and anthropometric characteristics. In addition, severe nocturnal hypoxaemia, even for only a small part of the night, may play an important role as a risk factor for kidney dysfunction.

  15. Stress Signal Network between Hypoxia and ER Stress in Chronic Kidney Disease

    PubMed Central

    Maekawa, Hiroshi; Inagi, Reiko

    2017-01-01

    Chronic kidney disease (CKD) is characterized by an irreversible decrease in kidney function and induction of various metabolic dysfunctions. Accumulated findings reveal that chronic hypoxic stress and endoplasmic reticulum (ER) stress are involved in a range of pathogenic conditions, including the progression of CKD. Because of the presence of an arteriovenous oxygen shunt, the kidney is thought to be susceptible to hypoxia. Chronic kidney hypoxia is induced by a number of pathogenic conditions, including renal ischemia, reduced peritubular capillary, and tubulointerstitial fibrosis. The ER is an organelle which helps maintain the quality of proteins through the unfolded protein response (UPR) pathway, and ER dysfunction associated with maladaptive UPR activation is named ER stress. ER stress is reported to be related to some of the effects of pathogenesis in kidney, particularly in the podocyte slit diaphragm and tubulointerstitium. Furthermore, chronic hypoxia mediates ER stress in blood vessel endothelial cells and tubulointerstitium via several mechanisms, including oxidative stress, epigenetic alteration, lipid metabolism, and the AKT pathway. In summary, a growing consensus considers that these stresses interact via complicated stress signal networks, which leads to the exacerbation of CKD (Figure 1). This stress signal network might be a target for interventions aimed at ameliorating CKD. PMID:28228736

  16. Stress Signal Network between Hypoxia and ER Stress in Chronic Kidney Disease.

    PubMed

    Maekawa, Hiroshi; Inagi, Reiko

    2017-01-01

    Chronic kidney disease (CKD) is characterized by an irreversible decrease in kidney function and induction of various metabolic dysfunctions. Accumulated findings reveal that chronic hypoxic stress and endoplasmic reticulum (ER) stress are involved in a range of pathogenic conditions, including the progression of CKD. Because of the presence of an arteriovenous oxygen shunt, the kidney is thought to be susceptible to hypoxia. Chronic kidney hypoxia is induced by a number of pathogenic conditions, including renal ischemia, reduced peritubular capillary, and tubulointerstitial fibrosis. The ER is an organelle which helps maintain the quality of proteins through the unfolded protein response (UPR) pathway, and ER dysfunction associated with maladaptive UPR activation is named ER stress. ER stress is reported to be related to some of the effects of pathogenesis in kidney, particularly in the podocyte slit diaphragm and tubulointerstitium. Furthermore, chronic hypoxia mediates ER stress in blood vessel endothelial cells and tubulointerstitium via several mechanisms, including oxidative stress, epigenetic alteration, lipid metabolism, and the AKT pathway. In summary, a growing consensus considers that these stresses interact via complicated stress signal networks, which leads to the exacerbation of CKD (Figure 1). This stress signal network might be a target for interventions aimed at ameliorating CKD.

  17. STAT4 gene polymorphism in patients after renal allograft transplantation

    PubMed Central

    Dąbrowska-Żamojcin, Ewa; Dziedziejko, Violetta; Safranow, Krzysztof; Domański, Leszek; Słuczanowska-Głabowska, Sylwia

    2016-01-01

    Introduction STAT4 (signal transducer and activator of transcription 4) is involved in the regulation of innate and adaptive immune responses. Some studies have suggested that STAT4 may be involved in the immune response after graft transplantation. Several polymorphisms in the STAT4 gene have been identified. The most commonly studied polymorphism in the STAT4 gene is rs7574865. In our study, we examined whether this polymorphism is associated with the early and late functions of renal allografts. Material and methods A total of 270 recipients of first renal transplants were included in the study. Single nucleotide polymorphisms (SNPs) within the STAT4 gene were genotyped using TaqMan genotyping assays. Results There were no statistically significant associations between the STAT4 gene rs7574865 polymorphism and delayed graft function, acute rejection, chronic allograft dysfunction, post-transplant diabetes mellitus, or creatinine serum concentrations after transplantation. Conclusions Our results suggest a lack of association between the STAT4 rs7574865 SNP and kidney allograft function in the Polish population. PMID:27833442

  18. Plasma levels of microRNA in chronic kidney disease: patterns in acute and chronic exercise.

    PubMed

    Van Craenenbroeck, Amaryllis H; Ledeganck, Kristien J; Van Ackeren, Katrijn; Jürgens, Angelika; Hoymans, Vicky Y; Fransen, Erik; Adams, Volker; De Winter, Benedicte Y; Verpooten, Gert A; Vrints, Christiaan J; Couttenye, Marie M; Van Craenenbroeck, Emeline M

    2015-12-15

    Exercise training is an effective way to improve exercise capacity in chronic kidney disease (CKD), but the underlying mechanisms are only partly understood. In healthy subjects (HS), microRNA (miRNA or miR) are dynamically regulated following exercise and have, therefore, been suggested as regulators of cardiovascular adaptation to exercise. However, these effects were not studied in CKD before. The effect of acute exercise (i.e., an acute exercise bout) was assessed in 32 patients with CKD and 12 age- and sex-matched HS (study 1). miRNA expression in response to chronic exercise (i.e., a 3-mo exercise training program) was evaluated in 40 CKD patients (study 2). In a subgroup of study 2, the acute-exercise induced effect was evaluated at baseline and at follow-up. Plasma levels of a preselected panel miRNA, involved in exercise adaptation processes such as angiogenesis (miR-126, miR-210), inflammation (miR-21, miR-146a), hypoxia/ischemia (miR-21, miR-210), and progenitor cells (miR-150), were quantified by RT-PCR. Additionally, seven miRNA involved in similar biological processes were quantified in the subgroup of study 2. Baseline, studied miRNA were comparable in CKD and HS. Following acute exercise, miR-150 levels increased in both CKD (fold change 2.12 ± 0.39, P = 0.002; and HS: fold change 2.41 ± 0.48 P = 0.018, P for interaction > 0.05). miR-146a acutely decreased in CKD (fold change 0.92 ± 0.13, P = 0.024), whereas it remained unchanged in HS. Levels of miR-21, miR-126, and miR-210 remained unaltered. Chronic exercise did not elicit a significant change in the studied miRNA levels. However, an acute exercise-induced decrease in miR-210 was observed in CKD patients, only after training (fold change 0.76 ± 0.15). The differential expression in circulating miRNA in response to acute and chronic exercise may point toward a physiological role in cardiovascular adaptation to exercise, also in CKD.

  19. Plasma levels of microRNA in chronic kidney disease: patterns in acute and chronic exercise

    PubMed Central

    Ledeganck, Kristien J.; Van Ackeren, Katrijn; Jürgens, Angelika; Hoymans, Vicky Y.; Fransen, Erik; Adams, Volker; De Winter, Benedicte Y.; Verpooten, Gert A.; Vrints, Christiaan J.; Couttenye, Marie M.; Van Craenenbroeck, Emeline M.

    2015-01-01

    Exercise training is an effective way to improve exercise capacity in chronic kidney disease (CKD), but the underlying mechanisms are only partly understood. In healthy subjects (HS), microRNA (miRNA or miR) are dynamically regulated following exercise and have, therefore, been suggested as regulators of cardiovascular adaptation to exercise. However, these effects were not studied in CKD before. The effect of acute exercise (i.e., an acute exercise bout) was assessed in 32 patients with CKD and 12 age- and sex-matched HS (study 1). miRNA expression in response to chronic exercise (i.e., a 3-mo exercise training program) was evaluated in 40 CKD patients (study 2). In a subgroup of study 2, the acute-exercise induced effect was evaluated at baseline and at follow-up. Plasma levels of a preselected panel miRNA, involved in exercise adaptation processes such as angiogenesis (miR-126, miR-210), inflammation (miR-21, miR-146a), hypoxia/ischemia (miR-21, miR-210), and progenitor cells (miR-150), were quantified by RT-PCR. Additionally, seven miRNA involved in similar biological processes were quantified in the subgroup of study 2. Baseline, studied miRNA were comparable in CKD and HS. Following acute exercise, miR-150 levels increased in both CKD (fold change 2.12 ± 0.39, P = 0.002; and HS: fold change 2.41 ± 0.48 P = 0.018, P for interaction > 0.05). miR-146a acutely decreased in CKD (fold change 0.92 ± 0.13, P = 0.024), whereas it remained unchanged in HS. Levels of miR-21, miR-126, and miR-210 remained unaltered. Chronic exercise did not elicit a significant change in the studied miRNA levels. However, an acute exercise-induced decrease in miR-210 was observed in CKD patients, only after training (fold change 0.76 ± 0.15). The differential expression in circulating miRNA in response to acute and chronic exercise may point toward a physiological role in cardiovascular adaptation to exercise, also in CKD. PMID:26475583

  20. Cytokine and Chemokine Expression in Kidneys during Chronic Leptospirosis in Reservoir and Susceptible Animal Models

    PubMed Central

    Matsui, Mariko; Roche, Louise; Geroult, Sophie; Soupé-Gilbert, Marie-Estelle; Monchy, Didier; Huerre, Michel; Goarant, Cyrille

    2016-01-01

    Leptospirosis is caused by pathogenic spirochetes of the genus Leptospira. Humans can be infected after exposure to contaminated urine of reservoir animals, usually rodents, regarded as typical asymptomatic carriers of leptospires. In contrast, accidental hosts may present an acute form of leptospirosis with a range of clinical symptoms including the development of Acute Kidney Injury (AKI). Chronic Kidney Disease (CKD) is considered as a possible AKI-residual sequela but little is known about the renal pathophysiology consequent to leptospirosis infection. Herein, we studied the renal morphological alterations in relation with the regulation of inflammatory cytokines and chemokines, comparing two experimental models of chronic leptospirosis, the golden Syrian hamster that survived the infection, becoming carrier of virulent leptospires, and the OF1 mouse, a usual reservoir of the bacteria. Animals were monitored until 28 days after injection with a virulent L. borgpetersenii serogroup Ballum to assess chronic infection. Hamsters developed morphological alterations in the kidneys with tubulointerstitial nephritis and fibrosis. Grading of lesions revealed higher scores in hamsters compared to the slight alterations observed in the mouse kidneys, irrespective of the bacterial load. Interestingly, pro-fibrotic TGF-β was downregulated in mouse kidneys. Moreover, cytokines IL-1β and IL-10, and chemokines MIP-1α/CCL3 and IP-10/CXCL-10 were significantly upregulated in hamster kidneys compared to mice. These results suggest a possible maintenance of inflammatory processes in the hamster kidneys with the infiltration of inflammatory cells in response to bacterial carriage, resulting in alterations of renal tissues. In contrast, lower expression levels in mouse kidneys indicated a better regulation of the inflammatory response and possible resolution processes likely related to resistance mechanisms. PMID:27219334

  1. Cystatin-C is associated with partial recovery of kidney function and progression to chronic kidney disease in living kidney donors

    PubMed Central

    Bang, Ji-Yeon; Kim, Seon-Ok; Kim, Sae-Gyul; Song, Jun-Gol; Hwang, Gyu Sam

    2017-01-01

    Abstract Donor nephrectomy in living-donor kidney transplantation may result in hyperfiltration injury in remnant kidney; however, its clinical implication in partial recovery of kidney function (PRKF) in remnant kidney and chronic kidney disease (CKD) progression remains unclear. Thus, we investigated the effect of PRKF on CKD development in the residual kidney and the utility of cystatin-C (Cys-C) in evaluating renal function in living-donor kidney transplantation donors. The electronic medical records and laboratory results of 1648 kidney transplant (KT) donors and 13,834 healthy nondonors between January 2006 and November 2014 were reviewed. The predictors of PRKF and CKD diagnosed by Kidney Disease: Improving Global Outcomes (KDIGO) criteria were evaluated by multivariate analysis. CKD risk was compared between KT donors and healthy nondonors using Cox proportional hazard regression analysis following propensity score matching (PSM). The incidence of PRKF for KT donors was 49.3% (813). CKD incidence was 24.8% (408) in KT donors and 2.0% (277) in healthy nondonors. The predictors of PRKF were, male sex (odds ratio [OR], 17.32; 95% confidence interval [CI] 9.16–32.77), age (OR, 1.02; 95% CI, 1.00–1.04; P < 0.001), Cys-C concentration (OR, 1.02; 95% CI, 1.00–1.04; P = 0.02), and preoperative albumin level (OR, 0.49; 95% CI, 0.27–0.89; P = 0.02). The predictors of CKD were age (hazards ratio [HR], 1.04; 95% CI, 1.02–1.05; P < 0.001), Cys-C concentration (HR, 1.024; 95% CI, 1.012–1.037; P < 0.001), and PRKF (HR, 1.41; 95% CI, 1.04–1.92; P = 0.03). After PSM, the risk of progression to CKD was higher in KT donors than in healthy nondonors (HR, 58.4; 95% CI, 34.2–99.8; P < 0.001). Donor nephrectomy is associated with PRKF and progression to CKD. Cys-C is a useful early marker for detecting PRKF and CKD. PMID:28151912

  2. Cystatin-C is associated with partial recovery of kidney function and progression to chronic kidney disease in living kidney donors: Observational study.

    PubMed

    Bang, Ji-Yeon; Kim, Seon-Ok; Kim, Sae-Gyul; Song, Jun-Gol; Hwang, Gyu Sam

    2017-02-01

    Donor nephrectomy in living-donor kidney transplantation may result in hyperfiltration injury in remnant kidney; however, its clinical implication in partial recovery of kidney function (PRKF) in remnant kidney and chronic kidney disease (CKD) progression remains unclear. Thus, we investigated the effect of PRKF on CKD development in the residual kidney and the utility of cystatin-C (Cys-C) in evaluating renal function in living-donor kidney transplantation donors.The electronic medical records and laboratory results of 1648 kidney transplant (KT) donors and 13,834 healthy nondonors between January 2006 and November 2014 were reviewed. The predictors of PRKF and CKD diagnosed by Kidney Disease: Improving Global Outcomes (KDIGO) criteria were evaluated by multivariate analysis. CKD risk was compared between KT donors and healthy nondonors using Cox proportional hazard regression analysis following propensity score matching (PSM).The incidence of PRKF for KT donors was 49.3% (813). CKD incidence was 24.8% (408) in KT donors and 2.0% (277) in healthy nondonors. The predictors of PRKF were, male sex (odds ratio [OR], 17.32; 95% confidence interval [CI] 9.16-32.77), age (OR, 1.02; 95% CI, 1.00-1.04; P < 0.001), Cys-C concentration (OR, 1.02; 95% CI, 1.00-1.04; P = 0.02), and preoperative albumin level (OR, 0.49; 95% CI, 0.27-0.89; P = 0.02). The predictors of CKD were age (hazards ratio [HR], 1.04; 95% CI, 1.02-1.05; P < 0.001), Cys-C concentration (HR, 1.024; 95% CI, 1.012-1.037; P < 0.001), and PRKF (HR, 1.41; 95% CI, 1.04-1.92; P = 0.03). After PSM, the risk of progression to CKD was higher in KT donors than in healthy nondonors (HR, 58.4; 95% CI, 34.2-99.8; P < 0.001).Donor nephrectomy is associated with PRKF and progression to CKD. Cys-C is a useful early marker for detecting PRKF and CKD.

  3. FTY720 in combination with cyclosporine--an analysis of skin allograft survival and renal function.

    PubMed

    Silva, Francieli Ruiz; Silva, Lea Bueno Lucas; Cury, Patricia Maluf; Burdmann, Emmanuel Almeida; Bueno, Valquiria

    2006-12-20

    Acute and chronic nephrotoxicity caused by CsA continuous administration impair kidney allograft survival. Several clinical and experimental protocols have shown benefits to the kidney after decreasing CsA dose, withdrawing the drug or delaying its introduction after transplantation. FTY720 is a new compound that has immunosuppressive characteristics and increase allograft survival in animal models without causing the side effects of calcineurin inhibitors (CNIs). FTY720 described mechanism of action that consists to alter the lymphocyte migration pattern without impairment of the immune system response against pathogens. In our mice model, FTY720 administered alone or in combination with CsA during 21 days increased skin allograft survival in a fully mismatched strain combination and did not cause significant changes in renal function. Moreover, renal structure was normal in all groups suggesting that at low doses (10 mg/kg/day) CsA can be associated during short-term period to other immunosuppressive drugs, i.e. FTY720 without affecting the kidney. Combination of immunosuppressive compounds with FTY720 and/or delayed introduction of low cyclosporine dose could prevent graft rejection and avoid nephrotoxicity.

  4. Modeling a Mobile Health Management Business Model for Chronic Kidney Disease.

    PubMed

    Lee, Ying-Li; Chang, Polun

    2016-01-01

    In these decades, chronic kidney disease (CKD) has become a global public health problem. Information technology (IT) tools have been used widely to empower the patients with chronic disease (e.g., diabetes and hypertension). It is also a potential application to advance the CKD care. In this project, we analyzed the requirements of a mobile health management system for healthcare workers, patients and their families to design a health management business model for CKD patients.

  5. [Chronic kidney diseases do not always pass unnoticed].

    PubMed

    Alves, Cyrielle; Pruijma, Menno; Rotman, Samuel; Bonny, Olivier

    2016-02-24

    Kidney diseases are frequent, but most of the time, they develop unnoticed. This paucity of symptoms may lead to delayed diagnosis with important consequences on their outcome. Nevertheless, specific systemic signs such as skin lesions, joint pain or electrolytes disturbances may sometimes alert the clinician and direct the diagnosis to an underlying nephropathy. A high awareness of clinicians is warranted to recognize these red flags and diagnose these diseases early, as illustrated by two clinical cases discussed in this article.

  6. Hypertension and cardiovascular risk in chronic kidney disease patients.

    PubMed

    Luño, José; Rodriguez-Iturbe, Bernardo; Ayus, Juan Carlos

    2006-12-01

    This supplement of the Journal of American Society of Nephrology contains some of the proceedings of the Fifth International Conference on Hypertension and the Kidney. The Conference, held in Madrid, Spain, in February 2006, was organized by the Department of Nephrology of the Hospital General, Universitario Gregorio Marañón, under the sponsorship of the Universidad Complutense de Madrid, Spanish Society of Nephrology, Spanish Society of Hypertension, and European Renal Association-European Dialysis and Transplant Association.

  7. Visit-to-visit variability of blood pressure and renal function decline in patients with diabetic chronic kidney disease.

    PubMed

    Yokota, Kei; Fukuda, Masamichi; Matsui, Yoshio; Kario, Kazuomi; Kimura, Kenjiro

    2014-05-01

    The authors previously reported that the visit-to-visit variability of blood pressure is correlated with renal function decline in nondiabetic chronic kidney disease. Little is known about the association between visit-to-visit variability and renal function decline in patients with diabetic chronic kidney disease. The authors retrospectively studied 69 patients with diabetic chronic kidney disease stage 3a, 3b, or 4. The standard deviation and coefficient of variation of blood pressure in 12 consecutive visits were defined as visit-to-visit variability of blood pressure. The median observation period was 32 months. In univariate correlation, the standard deviation and coefficient of variation of blood pressure were not significantly associated with the slope of estimated glomerular filtration rate. There was no significant association between the visit-to-visit variability of blood pressure and renal function decline in patients with diabetic chronic kidney disease, in contrast with our previous study of nondiabetic patients with chronic kidney disease.

  8. Role of sodium restriction and diuretic therapy for "resistant" hypertension in chronic kidney disease.

    PubMed

    Sinnakirouchenan, Ramapriya; Kotchen, Theodore A

    2014-01-01

    In patients with chronic kidney disease, an impaired capacity of the kidney to excrete sodium is a major contributor to hypertension. We discuss the role of sodium restriction and diuretic therapy for resistant hypertension in chronic kidney disease. Independent of increasing blood pressure, a sustained high sodium intake also may affect the progression of renal disease adversely. Consequently, dietary sodium restriction and appropriate diuretic therapy are the foundation for the treatment of resistant hypertension. Thiazide-like diuretics have decreasing effectiveness in patients with advancing renal disease; however, they may augment the effectiveness of the more potent loop diuretics. Increasing evidence suggests that spironolactone is an effective adjunct for the treatment of resistant hypertension. Inclusion of other classes of antihypertensive agents to the treatment regimen generally is necessary to counterbalance other mechanisms contributing to resistant hypertension. The effectiveness of these agents is enhanced by dietary sodium restriction and diuretic therapy.

  9. Chronic diarrhea due to duodenal candidiasis in a patient with a history of kidney transplantation.

    PubMed

    Nouri-Majalan, Nader; Moghaddasi, Sarasadat; Qane, Mohammad Davud; Shefaie, Farzane; Masoumi Dehshiri, Roghayyeh; Amirbaigy, Mohammad Kassem; Baghbanian, Mahmoud

    2014-11-01

    Candida infection in the small intestine is uncommon. We report an unusual case of duodenal candidiasis that presented as chronic diarrhea in a patient who had previously undergone kidney transplantation. A 60-year-old man presented with profuse watery diarrhea that had lasted 6 months 13 years after kidney transplantation. Upper gastrointestinal endoscopy results indicated candidiasis within the esophagus and duodenum. Biopsy results revealed active duodenitis with hyphal and yeast forms of Candida overlying the duodenal epithelium in periodic acid Schiff staining. The patient was successfully treated with fluconazole. After 6 months of follow-up, the patient had no complaint of diarrhea. Duodenal candidiasis may be the result of chronic diarrhea in patients with a history of kidney transplantation.

  10. Management of chronic kidney disease in China calls for the implementation of expert patient program with traditional Chinese medical interventions.

    PubMed

    Wu, Yi-fan; Zhang, La; Hu, Xiao-xuan; Liu, Xu-sheng

    2014-10-01

    Chronic kidney disease was closely related with unhealthy lifestyle; therefore a strategy focused both on daily life and medical process, like the Expert Patients Program, was of great value in the prevention and treatment of chronic kidney disease. In China, however, obstacles still existed in the process of implementing the program. Adding traditional Chinese medical interventions to the program assisted both patients and physicians to understand and to accept this new trend in management of chronic disease better. The combination with traditional Chinese medical interventions showed a solution for successfully implementing the Expert Patients Program and provided a new strategy for prevention and control of chronic kidney disease.

  11. Optimal management of bone mineral disorders in chronic kidney disease and ESRD

    PubMed Central

    Lundquist, Andrew L.; Nigwekar, Sagar U.

    2016-01-01

    Purpose of review This review summarizes recent studies on chronic kidney disease-mineral bone disorders, with a focus on new developments in disease management. Recent findings The term chronic kidney disease-mineral bone disorder has come to describe an increasingly complex network of alterations in minerals and skeletal disorders that contribute to the significant cardiovascular morbidity and mortality seen in patients with chronic kidney disease and ESRD. Clinical studies continue to suggest associations with clinical outcomes, yet current clinical trials have failed to support causality. Variability in practice exists as current guidelines for management of bone-mineral disorders are often based on weak evidence. Recent studies implicate novel pathways for therapeutic intervention in clinical trials. Summary Mineral-bone disorders in chronic kidney disease arise from alterations in a number of molecules in an increasingly complex physiological network interconnecting bone and the cardiovascular system. Despite extensive associations with improved outcomes in a number of molecules, clinical trials have yet to prove causality and there is an absence of new therapies available to improve patient outcomes. Additional clinical trials that can incorporate the complexity of mineral bone disorders and with the ability to intervene on more than one pathway are needed to advance patient care. PMID:26785065

  12. Dietary vitamin K and therapeutic warfarin alter susceptibility to vascular calcification in experimental chronic kidney disease

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The leading cause of death in patients with chronic kidney disease (CKD) is cardiovascular disease (CVD), with vascular calcification (VC) being a key modifier of disease progression. A local regulator of vascular calcification is vitamin K. This gamma-glutamyl carboxylase substrate is an essential ...

  13. Vitamins K and D status in patients with stages 3-5 chronic kidney disease

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Background and Objectives: Vitamin K, vitamin K-dependent (VKD) proteins and vitamin D may be involved in the regulation of calcification in chronic kidney disease (CKD). Design, setting, participants and measurements: Vitamin K and D status was measured as dietary intake, plasma phylloquinone, se...

  14. Role of Adipose Tissue in Determining Muscle Mass in Patients with Chronic Kidney Disease

    Technology Transfer Automated Retrieval System (TEKTRAN)

    OBJECTIVE: Malnutrition is a powerful predictor of mortality in chronic kidney disease (CKD). However, its etiology is unclear. We hypothesized that the adipocyte-derived proteins leptin and adiponectin, inflammation (as measured by C-reactive protein, CRP), and insulin resistance (as measured by ho...

  15. Phylloquinone and vitamin D status: associations with incident chronic kidney disease in the Framingham Offspring Cohort

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Cardiovascular risk factors are associated with the development of chronic kidney disease (CKD), and CKD and vascular disease are etiologically linked. Evidence suggests deficiencies of vitamins D and K may adversely affect the cardiovascular system, but data from longitudinal studies are lacking. W...

  16. Prevalence and characteristics of patients with resistant hypertension and chronic kidney disease.

    PubMed

    Verdalles, Úrsula; Goicoechea, Marian; Garcia de Vinuesa, Soledad; Quiroga, Borja; Galan, Isabel; Verde, Eduardo; Perez de Jose, Ana; Luño, José

    Resistant hypertension (RH) is a common problem in patients with chronic kidney disease (CKD). A decline in the glomerular filtration rate (GFR) and increased albuminuria are associated with RH; however, there are few published studies about the prevalence of this entity in patients with CKD.

  17. Retention of acetylcarnitine in chronic kidney disease causes insulin resistance in skeletal muscle

    PubMed Central

    Miyamoto, Yasunori; Miyazaki, Teruo; Honda, Akira; Shimohata, Homare; Hirayama, Kouichi; Kobayashi, Masaki

    2016-01-01

    Insulin resistance occurs frequently in patients with chronic kidney disease. However, the mechanisms of insulin resistance associated with chronic kidney disease are unclear. It is known that an increase in the mitochondrial acetyl-CoA (AcCoA)/CoA ratio causes insulin resistance in skeletal muscle, and this ratio is regulated by carnitine acetyltransferase that exchanges acetyl moiety between CoA and carnitine. Because excess acetyl moiety of AcCoA is excreted in urine as acetylcarnitine, we hypothesized that retention of acetylcarnitine might be a cause of insulin resistance in chronic kidney disease patients. Serum acetylcarnitine concentrations were measured in chronic kidney disease patients, and were significantly increased with reduction of renal function. The effects of excess extracellular acetylcarnitine on insulin resistance were studied in cultured skeletal muscle cells (C2C12 and human myotubes), and insulin-dependent glucose uptake was significantly and dose-dependently inhibited by addition of acetylcarnitine. The added acetylcarnitine was converted to carnitine via reverse carnitine acetyltransferase reaction, and thus the AcCoA concentration and AcCoA/CoA ratio in mitochondria were significantly elevated. The results suggest that increased serum acetylcarnitine in CKD patients causes AcCoA accumulation in mitochondria by stimulating reverse carnitine acetyltransferase reaction, which leads to insulin resistance in skeletal muscle. PMID:27895387

  18. Neurodevelopmental Status and Adaptive Behaviors in Preschool Children with Chronic Kidney Disease

    ERIC Educational Resources Information Center

    Duquette, Peter J.; Hooper, Stephen R.; Icard, Phil F.; Hower, Sarah J.; Mamak, Eva G.; Wetherington, Crista E.; Gipson, Debbie S.

    2009-01-01

    This study examines the early neurodevelopmental function of infants and preschool children who have chronic kidney disease (CKD). Fifteen patients with CKD are compared to a healthy control group using the "Mullen Scales of Early Learning" (MSEL) and the "Vineland Adaptive Behavior Scale" (VABS). Multivariate analysis reveals…

  19. Glycosaminoglycan Overproduction in the Aorta Increases Aortic Calcification in Murine Chronic Kidney Disease

    PubMed Central

    Purnomo, Eko; Emoto, Noriaki; Nugrahaningsih, Dwi Aris Agung; Nakayama, Kazuhiko; Yagi, Keiko; Heiden, Susi; Nadanaka, Satomi; Kitagawa, Hiroshi; Hirata, Ken‐ichi

    2013-01-01

    Background Vascular calcification accompanying chronic kidney disease increases the mortality and morbidity associated with cardiovascular disorders, but no effective therapy is available. We hypothesized that glycosaminoglycans may contribute to osteoblastic differentiation of vascular smooth muscle cells during vascular calcification. Methods and Results We used exostosin‐like glycosyltranferase 2–deficient (EXTL2 knockout) mice expressing high levels of glycosaminoglycans in several organs including the aorta. We performed 5/6 subtotal nephrectomy and fed the mice a high‐phosphate diet to induce chronic kidney disease. Overexpression of glycosaminoglycans in the aorta enhanced aortic calcification in chronic kidney disease in EXTL2 knockout mice. Ex vivo and in vitro, matrix mineralization in aortic rings and vascular smooth muscle cells of EXTL2 knockout mice was augmented. Furthermore, removal of glycosaminoglycans in EXTL2 knockout and wild‐type mice‐derived vascular smooth muscle cells effectively suppressed calcium deposition in a high‐phosphate environment. Conclusions These results illustrate an important role for glycosaminoglycans in the development of vascular calcification. Manipulation of glycosaminoglycan expression may have beneficial effects on the progression of vascular calcification in chronic kidney disease patients. PMID:23985378

  20. Mineralocorticoid receptor blockade—a novel approach to fight hyperkalaemia in chronic kidney disease

    PubMed Central

    Ritz, E.; Pitt, B.

    2013-01-01

    Hyperkalaemia continues to be a major hazard of mineralocorticoid receptor blockade in an effort to retard the progression of chronic kidney disease (CKD). In cardiac patients on mineralocorticoid receptor blockade, RLY-5016 which captures K+ in the colon has been effective in reducing the risk of hyperkalaemia. This compound might be useful in CKD as well. PMID:26120440

  1. New treatment for hepatitis C in chronic kidney disease, dialysis, and transplant.

    PubMed

    Fabrizi, Fabrizio; Martin, Paul; Messa, Piergiorgio

    2016-05-01

    The evidence that chronic hepatitis C plays a detrimental role in survival among patients on maintenance dialysis or renal transplant recipients promotes the antiviral treatment of hepatitis C virus (HCV) among chronic kidney disease patients. Also, it seems that HCV infection is associated with an increased risk of developing chronic kidney disease in the adult general population. Interferon-based regimens have provided limited efficacy and safety among chronic kidney disease patients, whereas the advent of the new direct-acting antivirals for the treatment of hepatitis C (launched over the past 5 years) has given the opportunity to reach sustained virologic response rates of 90% for many patient groups. Unfortunately, poor information exists regarding the antiviral treatment of hepatitis C in the chronic kidney disease population. The first published data on the treatment of hepatitis C among patients with chronic kidney disease (stage 4-5) and HCV genotype 1 regard the grazoprevir (NS3/4A protease inhibitor) and elbasvir (NS5A inhibitor) combination; excellent efficacy (sustained viral response, 94.3%; 115/122) and safety have been achieved. Preliminary evidence on the combined treatment of sofosbuvir (NS5B inhibitor) and simeprevir (NS3/4A inhibitor) has given a viral response of 89%, but the size of the study group (n = 38 patients with end-stage renal disease) was small. Some phase 2 and 3 clinical trials based on other antiviral combinations (3D regimen, sofosbuvir/ledipasvir, or other sofosbuvir-containing approaches) are ongoing. Thus, the antiviral regimens based on direct-acting antivirals promise to play a pivotal role in the eradication of hepatitis C among kidney disease patients. Direct-acting antivirals are very expensive; in an era of cost containment this is a crucial point either in developed and developing countries. Adverse drug reactions resulting from concomitantly administered medications are another ongoing concern for patients undergoing

  2. Donor-specific HLA antibodies in chronic renal allograft rejection: a prospective trial with a four-year follow-up.

    PubMed

    Lachmann, Nils; Terasaki, Paul I; Schönemann, Constanze

    2006-01-01

    A total of 1,043 serum samples of kidney allograft recipients with functioning grafts at a mean of 6 years after transplantation were tested once for HLA abs and monitored for graft and patient survival for 4 years after testing. All grafts were transplanted between 1984 and 2004 at the Charité hospital (Berlin, Germany). 1. To our knowledge this is the first study with more than 1,000 patients designed to elucidate the impact of DSA and NDSA on late renal graft outcome. True donor specificity of HLA abs in 30% of antibody positive patients was determined by using a single HLA antigen coated bead assay. 2. The long-term graft survival was adversely impacted by the presence of HLA abs directed against mismatched HLA antigens and to a lesser extent also by NDSA. This difference was shown to be leveled at late stages of graft damage, suggesting NDSA as a predictor of adsorbed DSA killing the graft. 3. The deleterious effect of preexisting and de novo formed HLA abs on long-term graft function was shown to be equal. Despite a negative crossmatch at the time of transplantation sensitized recipients and those who produced HLA abs de novo posttransplant showed the same increased risk of late graft failure. 4. Among patients with DSA and additional NDSA the majority of 74% of assigned potential HLA class I epitopes were shared among DSA and NDSA suggesting mismatched donor antigens as the cause of detected NDSA.

  3. Prevalence of Chronic Kidney Disease in Korea: the Korean National Health and Nutritional Examination Survey 2011-2013.

    PubMed

    Park, Ji In; Baek, Hyunjeong; Jung, Hae Hyuk

    2016-06-01

    Chronic kidney disease is a leading public health problem related to poor quality of life and premature death. As a resource for evidence-informed health policy-making, we evaluated the prevalence of chronic kidney disease using the data of non-institutionalized adults aged ≥ 20 years (n = 15,319) from the Korean National Health and Nutrition Examination Survey in 2011-2013. Chronic kidney disease was defined as a urine albumin-to-creatinine ratio ≥ 30 mg/g or an estimated glomerular filtration rate < 60 mL/min/1.73 m(2) using the Chronic Kidney Disease-Epidemiology Collaboration equation. The total prevalence estimate of chronic kidney disease for adults aged ≥ 20 years in Korea was 8.2%. By disease stage, the prevalence of chronic kidney disease was as follows: stage 1, 3.0%; stage 2, 2.7%; stage 3a, 1.9%; stage 3b, 0.4%; and stages 4-5, 0.2%. When grouped into three risk categories according to the 2012 Kidney Disease: Improving Global Outcomes guidelines, the proportions for the moderately increased risk, high risk, and very high risk categories were 6.5%, 1.2%, and 0.5%, respectively. Factors including older age, diabetes, hypertension, cardiovascular disease, body mass indexes of ≥ 25 kg/m(2) and < 18.5 kg/m(2), and rural residential area were independently associated with chronic kidney disease. Based on this comprehensive analysis, evidence-based screening strategies for chronic kidney disease in the Korean population should be developed to optimize prevention and early intervention of chronic kidney disease and its associated risk factors.

  4. Historical perspective of pregnancy in chronic kidney disease.

    PubMed

    Hou, Susan

    2007-04-01

    Preeclampsia was first recognized as a cause of proteinuria unique to pregnancy in 1843 and the risk of pregnancy in women with preexisting renal disease was noted in the 1930s. Since then, we have recognized that the majority of women with kidney disease who become pregnant have surviving infants. The exception is women on dialysis whose pregnancies result in only 50% to 75% of infant survival. All women with renal disease are at increased risk for hypertension during pregnancy, but the risk of more rapid than expected progression of renal disease generally occurs in women with serum creatinines greater than 1.4 mg/dL, with an even higher risk in women with serum creatinines greater than 2 mg/dL. Dialysis patients conceive infrequently and have a high frequency of fetal loss and neonatal death. Fertility is restored by renal transplant and guidelines are being developed regarding the ideal timing of pregnancy, the kidney function required for a safe pregnancy, and the use of immunosuppressive drugs in pregnancy.

  5. Acute kidney injury in patients with chronic liver disease

    PubMed Central

    Rognant, Nicolas

    2015-01-01

    Acute kidney injury (AKI) is a frequent clinical event in patients with liver disease, compounding their prognosis. Furthermore, it is likely that the occurrence of AKI has a detrimental impact on the subsequent renal function and the long-term survival of these patients. Recently, some authors advocated the use of new diagnostic criteria for detecting acute kidney injury in patients with cirrhosis. These criteria are based on the rapidity and extent of the creatinine increase comparing to the basal creatinine and also on the kinetics of diuresis decrease. Although their validity in this population requires further studies to be clearly established, these new criteria could have two advantages: (1) to allow earlier diagnosis of AKI and, thus, hepatorenal syndrome for which earlier intervention could improve patients’ survival; and (2) to promote more intensive monitoring of renal function in these patients with high risk of AKI. Finally, recent practice guidelines about the prevention and treatment of general AKI have been published which should be useful in optimising the management of AKI in cirrhotic patients. PMID:25954481

  6. Early-life course socioeconomic factors and chronic kidney disease.

    PubMed

    Brophy, Patrick D; Shoham, David A; Charlton, Jennifer R; Carmody, J Bryan; Reidy, Kimberly J; Harshman, Lyndsay; Segar, Jeffrey; Askenazi, David

    2015-01-01

    Kidney failure or ESRD affects approximately 650,000 Americans, whereas the number with earlier stages of CKD is much higher. Although CKD and ESRD are usually associated with adulthood, it is likely that the initial stages of CKD begin early in life. Many of these pathways are associated with low birth weight and disadvantaged socioeconomic status (SES) in childhood, translating childhood risk into later-life CKD and kidney failure. Social factors are thought to be fundamental causes of disease. Although the relationship between adult SES and CKD has been well established, the role of early childhood SES for CKD risk remains obscure. This review provides a rationale for examining the association between early-life SES and CKD. By collecting data on early-life SES and CKD, the interaction with other periods in the life course could also be studied, allowing for examination of whether SES trajectories (eg, poverty followed by affluence) or cumulative burden (eg, poverty at multiple time points) are more relevant to lifetime CKD risk.

  7. High prevalence of and potential mechanisms for chronic kidney disease in patients with acute intermittent porphyria.

    PubMed

    Pallet, Nicolas; Mami, Iadh; Schmitt, Caroline; Karim, Zoubida; François, Arnaud; Rabant, Marion; Nochy, Dominique; Gouya, Laurent; Deybach, Jean-Charles; Xu-Dubois, Yichum; Thervet, Eric; Puy, Hervé; Karras, Alexandre

    2015-08-01

    Acute intermittent porphyria (AIP) is a genetic disorder of the synthesis of heme caused by a deficiency in hydroxymethylbilane synthase (HMBS), leading to the overproduction of the porphyrin precursors δ-aminolevulinic acid and porphobilinogen. The aim of this study is to describe the clinical and biological characteristics, the renal pathology, and the cellular mechanisms of chronic kidney disease associated with AIP. A total of 415 patients with HMBS deficiency followed up in the French Porphyria Center were enrolled in 2003 in a population-based study. A follow-up study was conducted in 2013, assessing patients for clinical, biological, and histological parameters. In vitro models were used to determine whether porphyrin precursors promote tubular and endothelial cytotoxicity. Chronic kidney disease occurred in up to 59% of the symptomatic AIP patients, with a decline in the glomerular filtration rate of ~1 ml/min per 1.73 m(2) annually. Proteinuria was absent in the vast majority of the cases. The renal pathology was a chronic tubulointerstitial nephropathy, associated with a fibrous intimal hyperplasia and focal cortical atrophy. Our experimental data provide evidence that porphyrin precursors promote endoplasmic reticulum stress, apoptosis, and epithelial phenotypic changes in proximal tubular cells. In conclusion, the diagnosis of chronic kidney disease associated with AIP should be considered in cases of chronic tubulointerstitial nephropathy and/or focal cortical atrophy with severe proliferative arteriosclerosis.

  8. The Western-style diet: a major risk factor for impaired kidney function and chronic kidney disease.

    PubMed

    Odermatt, Alex

    2011-11-01

    The Western-style diet is characterized by its highly processed and refined foods and high contents of sugars, salt, and fat and protein from red meat. It has been recognized as the major contributor to metabolic disturbances and the development of obesity-related diseases including type 2 diabetes, hypertension, and cardiovascular disease. Also, the Western-style diet has been associated with an increased incidence of chronic kidney disease (CKD). A combination of dietary factors contributes to the impairment of renal vascularization, steatosis and inflammation, hypertension, and impaired renal hormonal regulation. This review addresses recent progress in the understanding of the association of the Western-style diet with the induction of dyslipidemia, oxidative stress, inflammation, and disturbances of corticosteroid regulation in the development of CKD. Future research needs to distinguish between acute and chronic effects of diets with high contents of sugars, salt, and fat and protein from red meat, and to uncover the contribution of each component. Improved therapeutic interventions should consider potentially altered drug metabolism and pharmacokinetics and be combined with lifestyle changes. A clinical assessment of the long-term risks of whole-body disturbances is strongly recommended to reduce metabolic complications and cardiovascular risk in kidney donors and patients with CKD.

  9. Risk of kidney cancer and chronic kidney disease in relation to hepatitis C virus infection: a nationwide register-based cohort study in Sweden

    PubMed Central

    Hofmann, Jonathan N; Törner, Anna; Chow, Wong-Ho; Ye, Weimin; Purdue, Mark P; Duberg, Ann-Sofi

    2011-01-01

    Chronic hepatitis C virus (HCV) infection is an established cause of liver cancer, and recent studies have suggested a link with kidney cancer. The aim of this study was to evaluate risk of kidney cancer in relation to HCV infection in a nationwide registry-based study of Swedish residents diagnosed with HCV between 1990 and 2006. A total of 43,000 patients with chronic HCV infection were included, and the mean follow-up time was 9.3 years. Observed kidney cancer incidence and mortality in the cohort were compared with expected values based on the age- and sex-adjusted rates in the general population. Risk of hospitalization for other chronic kidney disease was also evaluated using Cox proportional hazards regression. No association between HCV infection and risk of kidney cancer was observed [standardized incidence ratio with one-year lag = 1.2; 95% confidence interval (CI) 0.8–1.7]. Risk of hospitalization for non-cancer kidney disease was significantly elevated in the HCV cohort, with significantly stronger associations observed among women than among men [hazard ratio = 5.8 (95% CI 4.2–7.9) and 3.9 (95% CI 3.2–4.8) for women and men, respectively]. Results of this study do not support the hypothesis that chronic HCV infection confers an increased risk of kidney cancer. However, we did find an association between HCV infection and chronic kidney disease, particularly among women. Given inconsistent findings in the literature, it is premature to consider HCV infection to be a risk factor for kidney cancer. PMID:21386707

  10. A stepwise approach for effective management of chronic pain in autosomal-dominant polycystic kidney disease

    PubMed Central

    Casteleijn, Niek F.; Visser, Folkert W.; Drenth, Joost P.H.; Gevers, Tom J.G.; Groen, Gerbrand J.; Hogan, Marie C.; Gansevoort, Ron T.; Drenth, J.P.H.; de Fijter, J.W.; Gansevoort, R.T.; Peters, D.J.M.; Wetzels, J.; Zietse, R.

    2014-01-01

    Chronic pain, defined as pain existing for >4–6 weeks, affects >60% of patients with autosomal-dominant polycystic disease (ADPKD). It can have various causes, indirectly or directly related to the increase in kidney and liver volume in these patients. Chronic pain in ADPKD patients is often severe, impacting physical activity and social relationships, and frequently difficult to manage. This review provides an overview of pathophysiological mechanisms that can lead to pain and discusses the sensory innervation of the kidneys and the upper abdominal organs, including the liver. In addition, the results of a systematic literature search of ADPKD-specific treatment options are presented. Based on pathophysiological knowledge and evidence derived from the literature an argumentative stepwise approach for effective management of chronic pain in ADPKD is proposed. PMID:25165181

  11. A stepwise approach for effective management of chronic pain in autosomal-dominant polycystic kidney disease.

    PubMed

    Casteleijn, Niek F; Visser, Folkert W; Drenth, Joost P H; Gevers, Tom J G; Groen, Gerbrand J; Hogan, Marie C; Gansevoort, Ron T

    2014-09-01

    Chronic pain, defined as pain existing for >4-6 weeks, affects >60% of patients with autosomal-dominant polycystic disease (ADPKD). It can have various causes, indirectly or directly related to the increase in kidney and liver volume in these patients. Chronic pain in ADPKD patients is often severe, impacting physical activity and social relationships, and frequently difficult to manage. This review provides an overview of pathophysiological mechanisms that can lead to pain and discusses the sensory innervation of the kidneys and the upper abdominal organs, including the liver. In addition, the results of a systematic literature search of ADPKD-specific treatment options are presented. Based on pathophysiological knowledge and evidence derived from the literature an argumentative stepwise approach for effective management of chronic pain in ADPKD is proposed.

  12. A best practice position statement on pregnancy in chronic kidney disease: the Italian Study Group on Kidney and Pregnancy.

    PubMed

    Cabiddu, Gianfranca; Castellino, Santina; Gernone, Giuseppe; Santoro, Domenico; Moroni, Gabriella; Giannattasio, Michele; Gregorini, Gina; Giacchino, Franca; Attini, Rossella; Loi, Valentina; Limardo, Monica; Gammaro, Linda; Todros, Tullia; Piccoli, Giorgina Barbara

    2016-06-01

    Pregnancy is increasingly undertaken in patients with chronic kidney disease (CKD) and, conversely, CKD is increasingly diagnosed in pregnancy: up to 3 % of pregnancies are estimated to be complicated by CKD. The heterogeneity of CKD (accounting for stage, hypertension and proteinuria) and the rarity of several kidney diseases make risk assessment difficult and therapeutic strategies are often based upon scattered experiences and small series. In this setting, the aim of this position statement of the Kidney and Pregnancy Study Group of the Italian Society of Nephrology is to review the literature, and discuss the experience in the clinical management of CKD in pregnancy. CKD is associated with an increased risk for adverse pregnancy-related outcomes since its early stage, also in the absence of hypertension and proteinuria, thus supporting the need for a multidisciplinary follow-up in all CKD patients. CKD stage, hypertension and proteinuria are interrelated, but they are also independent risk factors for adverse pregnancy-related outcomes. Among the different kidney diseases, patients with glomerulonephritis and immunologic diseases are at higher risk of developing or increasing proteinuria and hypertension, a picture often difficult to differentiate from preeclampsia. The risk is higher in active immunologic diseases, and in those cases that are detected or flare up during pregnancy. Referral to tertiary care centres for multidisciplinary follow-up and tailored approaches are warranted. The risk of maternal death is, almost exclusively, reported in systemic lupus erythematosus and vasculitis, which share with diabetic nephropathy an increased risk for perinatal death of the babies. Conversely, patients with kidney malformation, autosomal-dominant polycystic kidney disease, stone disease, and previous upper urinary tract infections are at higher risk for urinary tract infections, in turn associated with prematurity. No risk for malformations other than those

  13. Liver and kidney lesions and associated enzyme changes induced in rabbits by chronic cyanide exposure.

    PubMed

    Okolie, N P; Osagie, A U

    1999-07-01

    The effect of prolonged chronic cyanide exposure on liver and kidney integrity, as well as some associated enzyme and metabolite changes, were investigated in New Zealand white rabbits (initial mean weight 1.52 kg) using a combination of colorimetric, spectrophotometric, enzymatic, gravimetric and histological procedures. Two groups of rabbits were fed for 40 weeks on either pure growers' mash or growers' mash containing 702 ppm inorganic cyanide. Results obtained indicate that the cyanide-fed rabbits had significantly decreased liver activities of alkaline phosphatase, glutamate pyruvate transaminase and sorbitol dehydrogenase relative to controls (P<0.05). On the other hand, there were significant increases (P<0.05) in the serum activities of these enzymes in the cyanide-treated group. Kidney alkaline phosphatase activity was significantly decreased (P<0.05), while serum urea and creatinine were significantly higher (P<0.05) in the cyanide group relative to controls. The cyanide treatment led to significant increases in both tissue and serum activities of lactate dehydrogenase. In addition, liver and kidney rhodanese activities were significantly raised in the cyanide-fed group. There were marked degenerative changes in the liver and kidney sections from the cyanide-treated rabbits. These results suggest that chronic cyanide exposure may be deleterious to liver and kidney functions.

  14. Chronic Kidney Disease, Obesity, and Hypertension: The Role of Leptin and Adiponectin

    PubMed Central

    Tesauro, M.; Mascali, A.; Franzese, O.; Cipriani, S.; Cardillo, C.; Di Daniele, N.

    2012-01-01

    Chronic kidney disease is a major public health problem and characterized by a progressive loss in renal function over a period of months or years as defined by structural or functional abnormalities of the kidney. Several elements contribute to determine a progression of the kidney injury, inducing a worsening of renal damage and accelerating the decline of renal function: obesity and hypertension are two known factors of kidney progression. Remarkable improvements have been recently achieved in the study of the endocrine features of the adipose tissue and have been able to produce hormone-like peptides named adipokines or adipocytokines. Among these adipocytokines, which represent a link between obesity, hypertension, and chronic nephropathy, leptins and adiponectin appear to play an important role. Leptin not only is a prohypertension element (renal progression factor) through the activation sympathetic nervous, but also is able to induce prosclerotic effects directly on the kidney. In contrast, a decline of adiponectin levels has been shown to be related to a picture of hypertension: an endothelial dysfunction has been described as the main pathogenic mechanism responsible for this phenomenon. PMID:23320148

  15. Association Between Retinopathy and Cardiovascular Disease in Patients with Chronic Kidney Disease (From the Chronic Renal Insufficiency Cohort [CRIC] Study)

    PubMed Central

    Grunwald, Juan E.; Ying, Gui-Shuang; Maguire, Maureen; Pistilli, Maxwell; Daniel, Ebenezer; Alexander, Judith; Whittock-Martin, Revell; Parker, Candace; Mohler, Emile; Chia-Mei Lo, Joan; Townsend, Raymond; Gadegbeku, Crystal Ann; Lash, James Phillip; Fink, Jeffrey Craig; Rahman, Mahboob; Feldman, Harold; Kusek, John Walter; Xie, Dawei; Coleman, Martha; Keane, Martin Gerard

    2012-01-01

    Patients with chronic kidney disease (CKD) experience co-morbid illneses including cardiovascular disease (CVD) and retinopathy. The purpose of this study was to assess the association between retinopathy and self reported CVD in a subgroup of the participants of the Chronic Renal Insufficiency Cohort (CRIC) study. In this observational, ancillary investigation, 2605 CRIC participants were invited to participate in this study, and non-mydriatic fundus photographs in both eyes were obtained in 1936 subjects. Photographs were reviewed in a masked fashion at a central photograph reading center. Presence and severity of retinopathy (diabetic, hypertensive or other) and vessel diameter caliber were assessed using standard protocols by trained graders masked to information about study participants. History of self-reported cardiovascular disease was obtained using a medical history questionnaire. Kidney function measurements, traditional and non-traditional risk factors for CVD were obtained from the CRIC study. Greater severity of retinopathy was associated with higher prevalence of any cardiovascular disease and this association persisted after adjustment for traditional risk factors for CVD. Presence of vascular abnormalities usually associated with hypertension was also associated with increased prevalence of CVD. We found a direct relationship between CVD prevalence and mean venular caliber. In conclusion, presence of retinopathy was associated with CVD, suggesting that retinovascular pathology may be indicative of macrovascular disease even after adjustment for renal dysfunction and traditional CVD risk factors. This would make assessment of retinal morphology a valuable tool in chronic kidney disease studies of CVD outcomes. PMID:22516527

  16. Developing educational material on chronic kidney disease using best practices in health literacy.

    PubMed

    Santos, Luanda Thaís Mendonça; Bastos, Marcus Gomes

    2017-03-01

    Based in the precepts of Health Literacy (HL), an educational booklet "Do you know the Chronic Kidney Disease?" was written. It was used as a basic text for development of a Brazilian instrument for Assessment of Health Literacy (Teste de Avaliação de Letramento em Saúde or TALES). The guideline used to create the TALES obeyed four steps: systematization of content; creation and drawing of images by an expert designer; submission to a Committee of Experts on nephrology and linguistics; and editing and printing of the content. The content covering six aspects of chronic kidney disease (definition, diagnosis, signs and symptoms, prevention, risk factors and treatment) was developed utilizing multimodality techniques such as: creation of personages; verbal and visual metaphors; metonymy; personifications; direct dialogue; and plain language avoided of technicalities. During the development of TALES, the booklet proved to be useful in translating complicated scientific concepts on kidney disease into meaningfuly health messages. In conclusion, besides of being used as basic text for the development of TALES, the booklet "Do you know chronic kidney disease?", based in best practices in HL, can assist health professionals in communicating to patients using consumer-friendly educational materials that might impact positive health-related behaviors and results.

  17. Understanding health decisions using critical realism: home-dialysis decision-making during chronic kidney disease.

    PubMed

    Harwood, Lori; Clark, Alexander M

    2012-03-01

    Understanding health decisions using critical realism: home-dialysis decision-making during chronic kidney disease This paper examines home-dialysis decision making in people with Chronic Kidney Disease (CKD) from the perspective of critical realism. CKD programmes focus on patient education for self-management to delay the progression of kidney disease and the preparation and support for renal replacement therapy e.g.) dialysis and transplantation. Home-dialysis has clear health, societal and economic benefits yet service usage is low despite efforts to realign resources and educate individuals. Current research on the determinants of modality selection is superficial and insufficient to capture the complexities embedded in the process of dialysis modality selection. Predictors of home-dialysis selection and the effect of chronic kidney disease educational programmes provide a limited explanation of this experience. A re-conceptualization of the problem is required in order to fully understand this process. The epistemology and ontology of critical realism guides our knowledge and methodology particularly suited for examination of these complexities. This approach examines the deeper mechanisms and wider determinants associated with modality decision making, specifically who chooses home dialysis and under what circumstances. Until more is known regarding dialysis modality decision making service usage of home dialysis will remain low as interventions will be based on inadequate epistemology.

  18. The UK model for system redesign and chronic kidney disease services.

    PubMed

    Stevens, Paul E; O'Donoghue, Donal J

    2009-09-01

    The British National Health Service is a closed managed care system. This single health care system for the United Kingdom is funded by the government and paid for by general taxation. All UK citizens are registered with primary care physicians who control access to secondary care services. As a managed care system it should be able to offer integrated care across the whole patient pathway. In reality there are professional, organizational, and institutional barriers to coordination and delivery of care in the NHS. Historically, the United Kingdom has been among the lowest health care spenders of organizations for economic cooperation in developed countries, in absolute terms as well as proportion of the gross domestic product. However, since a Government pledge to place quality at the heart of the NHS and a commitment in 2000 to increase spending on the NHS, the NHS budget has more than doubled-an unprecedented rate of growth, roughly by 7.5% annually in real terms. A quality and outcomes framework has been introduced into primary care to systematically incentivize process measures such as computerization and chronic disease management by establishing practice-based disease registers. The strategic planning for kidney services in England has been developed in this national environment complemented by local research findings and the wider international consensus that has emerged since the publication of the classification of chronic kidney disease in 2002. This program of work has resulted in a paradigm shift from kidney disease being viewed as a secondary care condition to being a primary care priority as part of vascular disease control and management. In the first 2 years of the initiative more than 40% of the expected chronic kidney disease stage 3 to 5 population have been registered in primary care. Kidney disease now is recognized as a public health problem in the United Kingdom, preventative strategies are being integrated into comprehensive vascular risk

  19. CE: Improving Outcomes for Patients with Chronic Kidney Disease: Part 2.

    PubMed

    Norton, Jenna M; Newman, Eileen P; Romancito, Gayle; Mahooty, Stephanie; Kuracina, Theresa; Narva, Andrew S

    2017-03-01

    : Coping with chronic kidney disease (CKD) is challenging for many people, since symptoms often don't appear until the disease is advanced and the patient is close to requiring dialysis. This two-part article aims to provide nurses with the basic information necessary to assess and manage patients with CKD. Part 1, which appeared last month, offered an overview of the disease, described identification and etiology, and discussed ways to slow disease progression. Part 2 addresses disease complications and treatment for kidney failure.

  20. Chronic kidney disease in an adolescent with hyperuricemia: familial juvenile hyperuricemic nephropathy.

    PubMed

    Alaygut, Demet; Torun-Bayram, Meral; Soylu, Alper; Kasap, Belde; Türkmen, Mehmet; Kavukçu, Salih

    2013-01-01

    Chronic kidney disease (CKD) is a life-long condition associated with substantial morbidity and premature death due to complications from a progressive decrease in kidney function. Especially in children, early diagnosis and detection of the etiologic factors are important to improve their health outcomes. Familial juvenile hyperuricemic nephropathy (FJHN) is a rare autosomal-dominant disorder characterized by hyperuricemia with renal uric acid under-excretion and CKD. Genetic studies have revealed mutations in the uromodulin (UMOD) gene. Highlighting the importance of CKD in children, a 14-year-old girl with the rare diagnosis of FJHN is reported herein.

  1. Strategies of the Brazilian chronic kidney disease prevention campaign (2003-2009).

    PubMed

    Mastroianni-Kirsztajn, Gianna; Bastos, Marcus G; Burdmann, Emmanuel A

    2011-01-01

    In Brazil, as in the rest of the world, the prevalence of chronic kidney disease (CKD) is increasing. In order to alert the population, health professionals and authorities to this risk, in 2003, the Brazilian Society of Nephrology launched a CKD prevention campaign called 'Previna-se'. In addition, since its onset, Brazil has participated in the World Kidney Day efforts and has developed several prevention strategies. Here, we summarize the main strategies adopted in this campaign (population screening, events and meetings, distribution of educational materials, routine report of estimated glomerular filtration rate) and our initial results, sharing practical experience that could be useful in other developing countries.

  2. [CKD-MBD (Chronic Kidney Disease-Mineral and Bone Disorder). Lanthanum carbonate and new phosphate binders in patients with chronic kidney disease].

    PubMed

    Negi, Shigeo; Shigematsu, Takashi

    2010-07-01

    Hyperphosphatemia is a serious complication which has been linked with an increased risk of cardiovascular mortality in patients with chronic kidney disease. Lanthanum carbonate is a novel non-calcium, non-aluminum phosphate-binding agent, and has approved for clinical use in patients on hemodialysis in Japan on March in 2009. Compared to calcium carbonate and sevelamer hydrochloride, lanthanum carbonate is a powerful phosphate binder. There is no evidence of bone toxicity and neurotoxicity of lanthanum carbonate previously reported for aluminium hydroxide. However, further studies are needed to address the longer term toxic effect on bone and other organs.

  3. Chronic kidney disease as a global public health problem: approaches and initiatives - a position statement from Kidney Disease Improving Global Outcomes.

    PubMed

    Levey, A S; Atkins, R; Coresh, J; Cohen, E P; Collins, A J; Eckardt, K-U; Nahas, M E; Jaber, B L; Jadoul, M; Levin, A; Powe, N R; Rossert, J; Wheeler, D C; Lameire, N; Eknoyan, G

    2007-08-01

    Chronic kidney disease (CKD) is increasingly recognized as a global public health problem. There is now convincing evidence that CKD can be detected using simple laboratory tests, and that treatment can prevent or delay complications of decreased kidney function, slow the progression of kidney disease, and reduce the risk of cardiovascular disease (CVD). Translating these advances to simple and applicable public health measures must be adopted as a goal worldwide. Understanding the relationship between CKD and other chronic diseases is important to developing a public health policy to improve outcomes. The 2004 Kidney Disease Improving Global Outcomes (KDIGO) Controversies Conference on 'Definition and Classification of Chronic Kidney Disease' represented an important endorsement of the Kidney Disease Outcome Quality Initiative definition and classification of CKD by the international community. The 2006 KDIGO Controversies Conference on CKD was convened to consider six major topics: (1) CKD classification, (2) CKD screening and surveillance, (3) public policy for CKD, (4) CVD and CVD risk factors as risk factors for development and progression of CKD, (5) association of CKD with chronic infections, and (6) association of CKD with cancer. This report contains the recommendations from the meeting. It has been reviewed by the conference participants and approved as position statement by the KDIGO Board of Directors. KDIGO will work in collaboration with international and national public health organizations to facilitate implementation of these recommendations.

  4. Chronic kidney disease in Latin America: time to improve screening and detection.

    PubMed

    Cusumano, Ana Maria; González Bedat, Maria Carlota

    2008-03-01

    Latin America is a conglomerate of adjacent countries that share a Latin extraction and language (Spanish or Portuguese) and exhibit extreme variations in socioeconomic status. End-stage renal disease prevalence and incidence rates have been growing steadily, probably as a result of the increase in life expectancy, aging of the population, a growing epidemic of type 2 diabetes, and a fast epidemiologic transition across the region. Chronic noncommunicable diseases impose an enormous cost, barely supported at present and unlikely afforded by Latin America in the future. National health surveys in Chile, Mexico, and Argentina showed a high prevalence of cardiovascular risk factors. A total of 21% of the Chilean population had a creatinine clearance <80 ml/min. Among the surveyed people, 8.6% of Argentines, 14.2% of Chileans, and 9.2% of Mexicans had proteinuria. There are ongoing national chronic kidney disease detection programs in Brazil, Cuba, Peru, Uruguay, and Venezuela; Argentina, Colombia, Bolivia, Dominican Republic, Guatemala, and Paraguay are still developing them. The prevalence of cardiovascular and renal risk factors is high in Latin America. Data about chronic kidney disease are scarce, but public health awareness is high, evidenced by ongoing or developing chronic kidney disease detection programs. High-risk patients (e.g., those with hypertension or diabetes, elderly) must be studied, using simple determinations such as creatinine and proteinuria. For these programs to succeed, lifestyle changes must be encouraged, and public awareness must be increased through teaching and media-oriented activities.

  5. Activating chronic kidney disease patients and family members through the Internet to promote integration of care

    PubMed Central

    Trisolini, Michael; Roussel, Amy; Zerhusen, Eileen; Schatell, Dorian; Harris, Shelly; Bandel, Karen; Salib, Philip; Klicko, Kristi

    2004-01-01

    Abstract Purpose To describe the potential role of the Internet as a vehicle for improving integration of care through activating chronic kidney disease patients and their family members. Also, to describe how that potential is being developed through a website sponsored by the Medicare program in the United States. Background The Internet is expanding at a rapid rate, and health-related websites are one of its most popular features. Efforts to promote integration of care have focused mainly on providers up to now, and more emphasis is needed on the potential roles of patients. Chronically ill patients have particular needs for improved education about their conditions and enhanced involvement in care planning and treatment decisions. Medicare developed the Dialysis Facility Compare website to serve those goals for people with chronic kidney disease. Methods We conducted qualitative research with 140 chronic kidney disease patients and family members, and 130 renal care professionals to evaluate and improve the Dialysis Facility Compare website. A series of 19 focus groups, 13 triads (small focus groups), and 56 individual interviews were conducted in four regions of the United States and by telephone. Results We found that the Dialysis Facility Compare website has the potential to improve integration of care for people with chronic kidney disease in at least three ways. First: by expanding the roles of patients as members of the multi-disciplinary team of caregivers treating their disease. Second: through better integration of the informal care provided in the home and community with the formal care provided by health professionals. Third: by improving coordination of between care provided in the pre-dialysis and dialysis phases of the disease. Discussion We developed recommendations for revising and enhancing the Dialysis Facility Compare website in a number of ways to better promote patient activation and integration of care. The unique features of the Internet

  6. Gender differences in adenine-induced chronic kidney disease and cardiovascular complications in rats.

    PubMed

    Diwan, Vishal; Small, David; Kauter, Kate; Gobe, Glenda C; Brown, Lindsay

    2014-12-01

    Gender contributes to differences in incidence and progression of chronic kidney disease (CKD) and associated cardiovascular disease. To induce kidney damage in male and female Wistar rats (n = 12/group), a 0.25% adenine diet for 16 wk was used. Kidney function (blood urea nitrogen, plasma creatinine, proteinuria) and structure (glomerular damage, tubulointerstitial atrophy, fibrosis, inflammation); cardiovascular function (blood pressure, ventricular stiffness, vascular responses, echocardiography) and structure (cardiac fibrosis); plasma testosterone and estrogen concentrations; and protein expression for oxidative stress [heme oxygenase-1, inflammation (TNF-α), fibrosis (transforming growth factor-β), ERK1/2, and estrogen receptor-α (ER-α)] were compared in males and females. Adenine-fed females had less decline in kidney function than adenine-fed males, although kidney atrophy, inflammation, and fibrosis were similar. Plasma estrogen concentrations increased and plasma testosterone concentrations decreased in adenine-fed males, with smaller changes in females. CKD-associated molecular changes in kidneys were more pronounced in males than females except for expression of ER-α in the kidney, which was completely suppressed in adenine-fed males but unchanged in adenine-fed females. Both genders showed increased blood pressure, ventricular stiffness, and cardiac fibrosis with the adenine diet. Cardiovascular changes with adenine were similar in males and females, except males developed concentric, and females eccentric cardiac hypertrophy. In hearts from adenine-fed male and female rats, expression of ER-α and activation of the ERK1/2 pathway were increased, in part explaining changes in cardiac hypertrophy. In summary, adenine-induced kidney damage may be increased in males due to the suppression of ER-α.

  7. [Tubulointerstitial rejection of renal allografts].

    PubMed

    Malušková, Jana; Honsová, Eva

    2015-01-01

    Tubulo-intersticial rejection represents T-cell mediated rejection of kidney allografts with the morphology of immune-mediated interstitial nephritis. Diagnosis is dependent on the histopathological evaluation of a graft biopsy sample. The key morphological features are interstitial inflammatory infiltrate and damage to tubular epithelial cell which in severe cases can result in the ruptures of the tubular basement membranes. The differential diagnosis of tubulo-interstitial rejection includes acute interstitial nephritis and viral inflammatory kidney diseases, mainly polyomavirus nephropathy.

  8. In chronic kidney disease staging the use of the chronicity criterion affects prognosis and the rate of progression.

    PubMed

    Eriksen, B O; Ingebretsen, O C

    2007-11-01

    The Kidney Disease Outcomes Quality Initiative definition and staging of chronic kidney disease (CKD) have been adopted by most nephrologists but include a criterion of chronicity that has not been investigated. This criterion specifies that renal structural damage and/or reduction in glomerular filtration rate (GFR) should be present for periods lasting longer than 3 months. We examined the effects of changing this criterion to 6, 9, or 12 months on the prognosis and the rate of progression in population-based cohorts with CKD stages 3 and 4. A 12-month chronicity criterion significantly reduced the number of CKD patients relative to the 3-month criterion for both stages 3 and 4. For both stages, there were statistically significant differences in 5-year mortality between the 6- and 9-month cohorts. For stage 4, the 5-year cumulative incidence of renal failure significantly increased from 6 to 9 months, and the rate of change in GFR significantly decreased between the same two cohorts. The 5-year cumulative incidence of improvement in GFR lasting 1 year or more was significantly higher for the 3-month cohort than for the 12-month cohort in the stage 3 group. Hence, we suggest that the chronicity criterion is an important determinant of the characteristics of the population of patients with CKD stages 3 and 4. This may have practical consequences in both research and clinical work.

  9. Elevated Endothelial Hypoxia-Inducible Factor-1α Contributes to Glomerular Injury and Promotes Hypertensive Chronic Kidney Disease.

    PubMed

    Luo, Renna; Zhang, Weiru; Zhao, Cheng; Zhang, Yujin; Wu, Hongyu; Jin, Jianping; Zhang, Wenzheng; Grenz, Almut; Eltzschig, Holger K; Tao, Lijian; Kellems, Rodney E; Xia, Yang

    2015-07-01

    Hypertensive chronic kidney disease is one of the most prevalent medical conditions with high morbidity and mortality in the United States and worldwide. However, early events initiating the progression to hypertensive chronic kidney disease are poorly understood. We hypothesized that elevated endothelial hypoxia-inducible factor-1α (HIF-1α) is a common early insult triggering initial glomerular injury leading to hypertensive chronic kidney disease. To test our hypothesis, we used an angiotensin II infusion model of hypertensive chronic kidney disease to determine the specific cell type and mechanisms responsible for elevation of HIF-1α and its role in the progression of hypertensive chronic kidney disease. Genetic studies coupled with reverse transcription polymerase chain reaction profiling revealed that elevated endothelial HIF-1α is essential to initiate glomerular injury and progression to renal fibrosis by the transcriptional activation of genes encoding multiple vasoactive proteins. Mechanistically, we found that endothelial HIF-1α gene expression was induced by angiotensin II in a nuclear factor-κB-dependent manner. Finally, we discovered reciprocal positive transcriptional regulation of endothelial Hif-1α and Nf-κb genes is a key driving force for their persistent activation and disease progression. Overall, our findings revealed that the stimulation of HIF-1α gene expression in endothelial cells is detrimental to induce kidney injury, hypertension, and disease progression. Our findings highlight early diagnostic opportunities and therapeutic approaches for hypertensive chronic kidney disease.

  10. Practical Approach to Detection and Management of Chronic Kidney Disease for the Primary Care Clinician.

    PubMed

    Vassalotti, Joseph A; Centor, Robert; Turner, Barbara J; Greer, Raquel C; Choi, Michael; Sequist, Thomas D

    2016-02-01

    A panel of internists and nephrologists developed this practical approach for the Kidney Disease Outcomes Quality Initiative to guide assessment and care of chronic kidney disease (CKD) by primary care clinicians. Chronic kidney disease is defined as a glomerular filtration rate (GFR) <60 mL/min/1.73 m(2) and/or markers of kidney damage for at least 3 months. In clinical practice the most common tests for CKD include GFR estimated from the serum creatinine concentration (eGFR) and albuminuria from the urinary albumin-to-creatinine ratio. Assessment of eGFR and albuminuria should be performed for persons with diabetes and/or hypertension but is not recommended for the general population. Management of CKD includes reducing the patient's risk of CKD progression and risk of associated complications, such as acute kidney injury and cardiovascular disease, anemia, and metabolic acidosis, as well as mineral and bone disorder. Prevention of CKD progression requires blood pressure <140/90 mm Hg, use of angiotensin-converting enzyme inhibitors or angiotensin receptor blockers for patients with albuminuria and hypertension, hemoglobin A1c ≤7% for patients with diabetes, and correction of CKD-associated metabolic acidosis. To reduce patient safety hazards from medications, the level of eGFR should be considered when prescribing, and nephrotoxins should be avoided, such as nonsteroidal anti-inflammatory drugs. The main reasons to refer to nephrology specialists are eGFR <30 mL/min/1.73 m(2), severe albuminuria, and acute kidney injury. The ultimate goal of CKD management is to prevent disease progression, minimize complications, and promote quality of life.

  11. Prevalence and incidence of chronic kidney disease stage G5 in Japan.

    PubMed

    Yamagata, Kunihiro; Yagisawa, Takashi; Nakai, Shigeru; Nakayama, Masaaki; Imai, Enyu; Hattori, Motoshi; Iseki, Kunitoshi; Akiba, Takashi

    2015-02-01

    The prevalence and incidence of end-stage kidney disease (ESKD) have continued to increase worldwide. Japan was known as having the highest prevalence of ESKD in the world; however, Taiwan took this place in 2001, with the USA still in third position. However, the prevalence data from Japan and Taiwan consisted of dialysis patients only. The prevalence and incidence of Kidney Transplantation (KT) in Japan were quite low, and the number of KT patients among those with ESKD was regarded as negligibly small. However, the number of KT recipients has increased recently. Furthermore, there are no reports about nationwide surveys on the prevalence and incidence of predialysis chronic kidney failure patients in Japan. This review describes our recent study on the estimated number of chronic kidney disease (CKD) stage G5 patients and the number of ESKD patients living in Japan, obtained via the cooperation of five related medical societies. From the results, as of Dec 31, 2007, 275,242 patients had received dialysis therapy and 10,013 patients had a functional transplanted kidney, and as of Dec 31, 2008, 286,406 patients had received dialysis therapy and 11,157 patients had a functional transplanted kidney. Consequently, there were 285,255 patients with CKD who reached ESKD and were living in Japan in 2008 and 297,563 in 2009. We also estimated that there were 67,000 predialysis CKD stage G5 patients in 2009, 37,365 patients introduced to dialysis therapy, and 101 patients who received pre-emptive renal transplantation in this year. In total, there were 37,466 patients who newly required renal replacement therapy (RRT) in 2009. Not only the average ages, but also the primary renal diseases of the new ESKD patients in each RRT modality were different.

  12. Baseline General Characteristics of the Korean Chronic Kidney Disease: Report from the KoreaN Cohort Study for Outcomes in Patients With Chronic Kidney Disease (KNOW-CKD)

    PubMed Central

    2017-01-01

    The KoreaN Cohort Study for Outcomes in Patients With Chronic Kidney Disease (KNOW-CKD) was developed to investigate various clinical courses and risk factors for progression of Korean chronic kidney disease (CKD). The KNOW-CKD study consists of nine clinical centers in Korea, and patients aged between 20 and 75 years with CKD from stage 1 to 5 (predialysis) were recruited. At baseline, blood and urine samples were obtained and demographic data including comorbidities, drugs, quality of life, and health behaviors were collected. Estimated glomerular filtration rate (eGFR) was calculated by 4-variable Modification of Diet in Renal Disease (MDRD) equation using isotope dilution mass spectrometry (IDMS)-calibrated serum creatinine measured at a central laboratory. As a dynamic cohort, a total of 2,341 patients were enrolled during the enrollment period from 2011 until 2015, among whom 2,238 subjects were finally analyzed for baseline profiles. The mean age of the cohort was 53.7 ± 12.2 year and 61.2% were men. Mean eGFR was 50.5 ± 30.3 mL/min/1.73 m2. The participants with lower eGFR had a tendency to be older, with more comorbidities, to have higher systolic blood pressure (BP) and pulse pressure, with lower income level and education attainment. The patients categorized as glomerulonephritis (GN) were 36.2% followed by diabetic nephropathy (DN, 23.2%), hypertensive nephropathy (HTN, 18.3%), polycystic kidney disease (PKD, 16.3%), and other unclassified disease (6.1%). The KNOW-CKD participants will be longitudinally followed for 10 years. The study will provide better understanding for physicians regarding clinical outcomes, especially renal and cardiovascular outcomes in CKD patients. PMID:28049232

  13. Baseline Cardiovascular Characteristics of Adult Patients with Chronic Kidney Disease from the KoreaN Cohort Study for Outcomes in Patients With Chronic Kidney Disease (KNOW-CKD)

    PubMed Central

    2017-01-01

    Cardiovascular disease (CVD) is the most common cause of death in patients with chronic kidney disease (CKD). We report the baseline cardiovascular characteristics of 2,238 participants by using the data of the KoreaN Cohort Study for Outcomes in Patients With Chronic Kidney Disease (KNOW-CKD) study. The cohort comprises 5 subcohorts according to the cause of CKD: glomerulonephritis (GN), diabetic nephropathy (DN), hypertensive nephropathy (HTN), polycystic kidney disease (PKD), and unclassified. The average estimated glomerular filtration rate (eGFR) was 50.5 ± 30.3 mL/min−1/1.73 m−2 and lowest in the DN subcohort. The overall prevalence of previous CVD was 14.4% in all patients, and was highest in the DN followed by that in the HTN subcohort. The DN subcohort had more adverse cardiovascular risk profiles (higher systolic blood pressure [SBP], and higher levels of cardiac troponin T, left ventricular mass index [LVMI], coronary calcium score, and brachial-ankle pulse wave velocity [baPWV]) than the other subcohorts. The HTN subcohort exhibited less severe cardiovascular risk profiles than the DN subcohort, but had more severe cardiovascular risk features than the GN and PKD subcohorts. All these cardiovascular risk profiles were inversely correlated with eGFR. In conclusion, this study shows that the KNOW-CKD cohort exhibits high cardiovascular burden, as other CKD cohorts in previous studies. Among the subcohorts, the DN subcohort had the highest risk for CVD. The ongoing long-term follow-up study up to 10 years will further delineate cardiovascular characteristics and outcomes of each subcohort exposed to different risk profiles. PMID:28049233

  14. Baseline Cardiovascular Characteristics of Adult Patients with Chronic Kidney Disease from the KoreaN Cohort Study for Outcomes in Patients With Chronic Kidney Disease (KNOW-CKD).

    PubMed

    Kim, Hyoungnae; Yoo, Tae Hyun; Choi, Kyu Hun; Oh, Kook Hwan; Lee, Joongyub; Kim, Soo Wan; Kim, Tae Hee; Sung, Suah; Han, Seung Hyeok

    2017-02-01

    Cardiovascular disease (CVD) is the most common cause of death in patients with chronic kidney disease (CKD). We report the baseline cardiovascular characteristics of 2,238 participants by using the data of the KoreaN Cohort Study for Outcomes in Patients With Chronic Kidney Disease (KNOW-CKD) study. The cohort comprises 5 subcohorts according to the cause of CKD: glomerulonephritis (GN), diabetic nephropathy (DN), hypertensive nephropathy (HTN), polycystic kidney disease (PKD), and unclassified. The average estimated glomerular filtration rate (eGFR) was 50.5 ± 30.3 mL/min⁻¹/1.73 m⁻² and lowest in the DN subcohort. The overall prevalence of previous CVD was 14.4% in all patients, and was highest in the DN followed by that in the HTN subcohort. The DN subcohort had more adverse cardiovascular risk profiles (higher systolic blood pressure [SBP], and higher levels of cardiac troponin T, left ventricular mass index [LVMI], coronary calcium score, and brachial-ankle pulse wave velocity [baPWV]) than the other subcohorts. The HTN subcohort exhibited less severe cardiovascular risk profiles than the DN subcohort, but had more severe cardiovascular risk features than the GN and PKD subcohorts. All these cardiovascular risk profiles were inversely correlated with eGFR. In conclusion, this study shows that the KNOW-CKD cohort exhibits high cardiovascular burden, as other CKD cohorts in previous studies. Among the subcohorts, the DN subcohort had the highest risk for CVD. The ongoing long-term follow-up study up to 10 years will further delineate cardiovascular characteristics and outcomes of each subcohort exposed to different risk profiles.

  15. Baseline General Characteristics of the Korean Chronic Kidney Disease: Report from the KoreaN Cohort Study for Outcomes in Patients With Chronic Kidney Disease (KNOW-CKD).

    PubMed

    Kang, Eunjeong; Han, Miyeun; Kim, Hyunsuk; Park, Sue Kyung; Lee, Joongyub; Hyun, Young Youl; Kim, Yong Soo; Chung, Wookyung; Kim, Hyo Jin; Oh, Yun Kyu; Ahn, Curie; Oh, Kook Hwan

    2017-02-01

    The KoreaN Cohort Study for Outcomes in Patients With Chronic Kidney Disease (KNOW-CKD) was developed to investigate various clinical courses and risk factors for progression of Korean chronic kidney disease (CKD). The KNOW-CKD study consists of nine clinical centers in Korea, and patients aged between 20 and 75 years with CKD from stage 1 to 5 (predialysis) were recruited. At baseline, blood and urine samples were obtained and demographic data including comorbidities, drugs, quality of life, and health behaviors were collected. Estimated glomerular filtration rate (eGFR) was calculated by 4-variable Modification of Diet in Renal Disease (MDRD) equation using isotope dilution mass spectrometry (IDMS)-calibrated serum creatinine measured at a central laboratory. As a dynamic cohort, a total of 2,341 patients were enrolled during the enrollment period from 2011 until 2015, among whom 2,238 subjects were finally analyzed for baseline profiles. The mean age of the cohort was 53.7 ± 12.2 year and 61.2% were men. Mean eGFR was 50.5 ± 30.3 mL/min/1.73 m². The participants with lower eGFR had a tendency to be older, with more comorbidities, to have higher systolic blood pressure (BP) and pulse pressure, with lower income level and education attainment. The patients categorized as glomerulonephritis (GN) were 36.2% followed by diabetic nephropathy (DN, 23.2%), hypertensive nephropathy (HTN, 18.3%), polycystic kidney disease (PKD, 16.3%), and other unclassified disease (6.1%). The KNOW-CKD participants will be longitudinally followed for 10 years. The study will provide better understanding for physicians regarding clinical outcomes, especially renal and cardiovascular outcomes in CKD patients.

  16. Clinical imaging of vascular disease in chronic kidney disease.

    PubMed

    Sag, Alan A; Covic, Adrian; London, Gerard; Vervloet, Marc; Goldsmith, David; Gorriz, Jose Luis; Kanbay, Mehmet

    2016-06-01

    Arterial wall calcification, once considered an incidental finding, is now known to be a consistent and strong predictor of cardiovascular events in patients with chronic renal insufficiency. It is also commonly encountered in radiologic examinations as an incidental finding. Forthcoming bench, translational, and clinical data seek to establish this and pre-calcification changes as surrogate imaging biomarkers for noninvasive prognostication and treatment follow-up. Emerging paradigms seek to establish vascular calcification as a surrogate marker of disease. Imaging of pre-calcification and decalcification events may prove more important than imaging of the calcification itself. Data-driven approaches to screening will be necessary to limit radiation exposure and prevent over-utilization of expensive imaging techniques.

  17. Social support of adults and elderly with chronic kidney disease on dialysis

    PubMed Central

    da Silva, Simone Márcia; Braido, Natalia Fernanda; Ottaviani, Ana Carolina; Gesualdo, Gabriela Dutra; Zazzetta, Marisa Silvana; Orlandi, Fabiana de Souza

    2016-01-01

    ABSTRACT Objective: to evaluate the instrumental and emotional social support of patients with chronic kidney disease on hemodialysis. Method: descriptive cross-sectional study. The sample was sized for convenience and included 103 participants under treatment in a Renal Replacement Therapy Unit. Data were collected through individual interviews, using the Social Support Scale. Results: the mean scores of the emotional and instrumental social support were 3.92 (± 0.78) and 3.81 (± 0.69) respectively, an indication of good support received. The most frequent sources of instrumental and emotional social support mentioned by participants were partners, spouse, companion or boyfriend and friends. Conclusion: patients with chronic kidney disease have high social support, both instrumental and emotional, and the main support comes from the family. PMID:27508920

  18. Chronic kidney disease of unknown aetiology and ground-water ionicity: study based on Sri Lanka.

    PubMed

    Dharma-Wardana, M W C; Amarasiri, Sarath L; Dharmawardene, Nande; Panabokke, C R

    2015-04-01

    High incidence of chronic kidney disease of unknown aetiology (CKDU) in Sri Lanka is shown to correlate with the presence of irrigation works and rivers that bring-in 'nonpoint source' fertilizer runoff from intensely agricultural regions. We review previous attempts to link CKDU with As, Cd and other standard toxins. Those studies (e.g. the WHO-sponsored study), while providing a wealth of data, are inconclusive in regard to aetiology. Here, we present new proposals based on increased ionicity of drinking water due to fertilizer runoff into the river system, redox processes in the soil and features of 'tank'-cascades and aquifers. The consequent chronic exposure to high ionicity in drinking water is proposed to debilitate the kidney via a Hofmeister-type (i.e. protein-denaturing) mechanism.

  19. Subfractions of high-density lipoprotein (HDL) and dysfunctional HDL in chronic kidney disease patients.

    PubMed

    Rysz-Górzyńska, Magdalena; Banach, Maciej

    2016-08-01

    A number of studies have shown that chronic kidney disease (CKD) is associated with increased risk for cardiovascular disease (CVD). Chronic kidney disease is characterized by significant disturbances in lipoprotein metabolism, including differences in quantitative and qualitative content of high-density lipoprotein (HDL) particles. Recent studies have revealed that serum HDL cholesterol levels do not predict CVD in CKD patients; thus CKD-induced modifications in high-density lipoprotein (HDL) may be responsible for the increase in CV risk in CKD patients. Various methods are available to separate several subclasses of HDL and confirm their atheroprotective properties. However, under pathological conditions associated with inflammation and oxidation, HDL can progressively lose normal biological activities and be converted into dysfunctional HDL. In this review, we highlight the current state of knowledge on subfractions of HDL and HDL dysfunction in CKD.

  20. Subfractions of high-density lipoprotein (HDL) and dysfunctional HDL in chronic kidney disease patients

    PubMed Central

    Banach, Maciej

    2016-01-01

    A number of studies have shown that chronic kidney disease (CKD) is associated with increased risk for cardiovascular disease (CVD). Chronic kidney disease is characterized by significant disturbances in lipoprotein metabolism, including differences in quantitative and qualitative content of high-density lipoprotein (HDL) particles. Recent studies have revealed that serum HDL cholesterol levels do not predict CVD in CKD patients; thus CKD-induced modifications in high-density lipoprotein (HDL) may be responsible for the increase in CV risk in CKD patients. Various methods are available to separate several subclasses of HDL and confirm their atheroprotective properties. However, under pathological conditions associated with inflammation and oxidation, HDL can progressively lose normal biological activities and be converted into dysfunctional HDL. In this review, we highlight the current state of knowledge on subfractions of HDL and HDL dysfunction in CKD. PMID:27478466

  1. Zinc deficiency in chronic kidney disease: is there a relationship with adipose tissue and atherosclerosis?

    PubMed

    Lobo, Julie Calixto; Torres, João Paulo Machado; Fouque, Denis; Mafra, Denise

    2010-06-01

    Cardiovascular complications caused by an accelerated atherosclerotic disease consist the major cause of morbidity and mortality in patients with chronic kidney disease (CKD). These patients present multiple atherosclerotic risk factors, considered traditional, as well as nontraditional risk factors such as inflammation and oxidative stress. These complications are also seen in obesity, in which endothelial dysfunction is one of the early stages of atherosclerosis. The impact of trace metal deficiencies on this process is not well studied in patients with CKD and in obese people, although the influence of trace elements depletion, particularly zinc (Zn), may have significant clinical implications. This brief review describes the functions of Zn as well as the respective role of this trace element in atherosclerosis processes, with a particular emphasis on obese patients with chronic kidney disease.

  2. The chronic kidney disease epidemic: a challenge for nephrology training programs.

    PubMed

    Kohan, Donald E; Rosenberg, Mark E

    2009-09-01

    A major challenge facing the nephrology community in the United States is the training of adequate numbers of nephrologists to meet patient care and research needs. There is particular cause for concern because of the increasing incidence and prevalence of patients with chronic kidney disease. Data on the clinical and research nephrology workforce are incomplete or absent. However, the number of such individuals likely is inadequate to meet current and projected needs. To solve these workforce shortages, significant issues with regard to clinical and research training need to be addressed. These include funding of fellowship training, increasing the pipeline of medical students and internal medicine residents, and enhancing interest in nephrology among international and particularly US medical graduates. This review discusses these challenges facing the renal community, with emphasis on the care, prevention, and treatment of chronic kidney disease, and identifies potential pathways to developing solutions.

  3. Applications of acoustic radiation force impulse quantification in chronic kidney disease: a review

    PubMed Central

    2016-01-01

    Acoustic radiation force impulse (ARFI) imaging is an emerging technique with great promise in the field of elastography. Previous studies have validated ARFI quantification as a method of estimating fibrosis in chronic liver disease. Similarly, fibrosis is the principal process underlying the progression of chronic kidney disease, which is the major cause of renal failure. However, the quantification of tissue stiffness using ARFI imaging is more complex in the kidney than in the liver. Moreover, not all previous studies are comparable because they employed different procedures. Therefore, subsequent studies are warranted, both in animal models and in clinical patients, in order to better understand the histopathological mechanisms associated with renal elasticity and to further improve this imaging method by developing a standardized guidelines for its implementation. PMID:27599890

  4. Human embryonic mesenchymal stem cell-derived conditioned medium rescues kidney function in rats with established chronic kidney disease.