Genome-Wide Study Updates in the International Genetics and Translational Research in Transplantation Network (iGeneTRAiN)

The prevalence of end-stage renal disease (ESRD) and the number of kidney transplants performed continues to rise every year, straining the procurement of deceased and living kidney allografts and health systems. Genome-wide genotyping and sequencing of diseased populations have uncovered genetic contributors in substantial proportions of ESRD patients. A number of these discoveries are beginning to be utilized in risk stratification and clinical management of patients. Specifically, genetics can provide insight into the primary cause of chronic kidney disease (CKD), the risk of progression to ESRD, and post-transplant outcomes, including various forms of allograft rejection. The International Genetics &Translational Research in Transplantation Network (iGeneTRAiN), is a multi-site consortium that encompasses>45 genetic studies with genome-wide genotyping from over 51,000 transplant samples, including genome-wide data from>30 kidney transplant cohorts (n = 28,015). iGeneTRAiN is statistically powered to capture both rare and common genetic contributions to ESRD and post-transplant outcomes. The primary cause of ESRD is often difficult to ascertain, especially where formal biopsy diagnosis is not performed, and is unavailable in ∼2% to>20% of kidney transplant recipients in iGeneTRAiN studies. We overview our current copy number variant (CNV) screening approaches from genome-wide genotyping datasets in iGeneTRAiN, in attempts to discover and validate genetic c...
Source: Frontiers in Genetics - Category: Genetics & Stem Cells Source Type: research

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Contributors : Nissim Ben-Haim ; Tomer KaliskySeries Type : Expression profiling by high throughput sequencingOrganism : Homo sapiensEnd-stage renal disease is a worldwide epidemic requiring renal replacement therapy. Harvesting tissue from failing kidneys and autotransplantation of expanded committed progenitors giving rise to renal parenchyma could theoretically allow for the restoration of kidney function delaying or preventing the need for dialysis or a renal allograft. Here we utilized healthy and end-stage human adult kidneys to robustly expand proliferative kidney epithelial cells and establish 3D-kidney epithelial ...
Source: GEO: Gene Expression Omnibus - Category: Genetics & Stem Cells Tags: Expression profiling by high throughput sequencing Homo sapiens Source Type: research
Purpose of review Despite improvement in short-term renal allograft survival in recent years, renal transplant recipients (RTR) have poorer long-term allograft outcomes. Allograft function slowly declines with periods of stable function similar to natural progression of chronic kidney disease in nontransplant population. Nearly all RTR transitions to failing renal allograft (FRG) period and require transition to dialysis. Conservative chronic kidney disease management before transition to end-stage renal disease is an increasingly important topic; however, there is limited data in RTR regarding how to delay dialysis init...
Source: Current Opinion in Nephrology and Hypertension - Category: Urology & Nephrology Tags: NOVEL THERAPEUTIC APPROACHES IN NEPHROLOGY AND HYPERTENSION: Edited by Kamyar Kalantar-Zadeh and Ekamol Tantisattamo Source Type: research
Abstract This paper aims to identify the reasons for choosing or refusing kidney transplantation as renal replacement therapy among patients with Chronic Kidney Disease (CKD). Data were collected through interviews with CKD patients treated by dialysis. Health professionals were also interviewed. A thematic analysis was used to analyze the data. Results show that various reasons account for CKD patients' refusal to have a kidney transplant: the perception of kidney transplantation as a renal replacement therapy without positive outcome, refusal to have an allograft. There are also situations such as the lack of or...
Source: Nephrologie and Therapeutique - Category: Urology & Nephrology Authors: Tags: Nephrol Ther Source Type: research
Conclusion In this study, which included mainly patients with grade 1 ACLF at the time of LT, its presence had no impact on post-LT survival or on the occurrence of CKD or EAD.
Source: European Journal of Gastroenterology and Hepatology - Category: Gastroenterology Tags: Original Articles: Hepatology Source Type: research
Sonia Mehrotra, Raj Kumar Sharma, Manas R PatelIndian Journal of Nephrology 2019 29(4):242-247 Vitamin-D has immuno-modulatory properties besides its role in mineral and bone disorder (MBD) and could have a role in allograft outcome. Fifty-two chronic kidney disease patients on dialysis going for transplantation were prospectively studied before and after renal transplantation. FGF23, 25(OH) vitamin D, 1,25-Dihydroxyvitamin D, PTH, serum Ca, serum PO4, and e-GFR status were evaluated. Vitamin D deficiency was seen in 25.0% of recipients before transplant (26.09 ± 12.19 ng/mL) and in 48.1% at 6 months post-tra...
Source: Indian Journal of Nephrology - Category: Urology & Nephrology Authors: Source Type: research
Purpose of review The population of kidney transplant recipients with advanced chronic kidney disease is growing but their outcomes are poor and care is not standardized. There has been wide variety of research in recent years on different aspects of care in failing allografts, and these research findings may help the providers in optimizing care. The purpose of the review is to outline the challenges and opportunities in management of failing allograft, and provide tools for improvement. Recent findings This review summarizes the recent research in field of failing allograft including outcomes, immunosuppression, ris...
Source: Current Opinion in Organ Transplantation - Category: Surgery Tags: KIDNEY PANCREAS: Edited by Matthew Cooper Source Type: research
In this study, we pursued a candidate gene approach to measure WNT pathway genes in residual clinical FFPE biopsies with and without MVI. We focused on the WNT pathway because of previous translational studies that implicated this pathway in chronic renal allograft injury as well as vascular injury in native chronic kidney disease.
Source: GEO: Gene Expression Omnibus - Category: Genetics & Stem Cells Tags: Expression profiling by array Homo sapiens Source Type: research
Kidney transplantation (KT) is the treatment of choice for end stage kidney disease , offering the highest survival benefit amongst all the different renal replacement therapies1. Long term renal allograft and patient survival have shown substantial improvements over time: however, death with a functioning allograft remains the leading cause of late allograft loss with cardiovascular disease (CVD) related deaths representing a major cause of mortality2. While recipients of kidney transplants have lower risk for CVD when compared to the 10-20 fold increased risk in patients with dialysis, their risk of CVD is substantially ...
Source: Kidney International - Category: Urology & Nephrology Authors: Tags: Policy Forum Source Type: research
This study sought to evaluate the possible role of immunological tests. Four unrelated recipients and one living donor who have chronic kidney disease were evaluated for HLA-typing, PRA, CXM tests to conduct parathyroid allotransplantation. Parathyroid glands were obtained and resected from the donor, then cells were isolated and cryopreserved. Upon histologic examination, cells were cultivated and injected into muscle of four recipients. Recipient's were followed for parathormone and calcium levels for four years. PRA screening were monitored and de novo DSA was evaluated as well. In two of the recipients, allografts cont...
Source: Immunobiology - Category: Allergy & Immunology Authors: Tags: Immunobiology Source Type: research
Abstract BACKGROUND: In chronic kidney disease (CKD), intensive systolic blood pressure (SBP) control reduces mortality at a cost of greater acute kidney injury (AKI) risk. Kidney transplantation involves implantation of denervated kidneys and immunosuppressive medications that increase AKI risk. The optimal blood pressure (BP) target in kidney transplant recipients (KTRs) is uncertain. Prior observational studies from the Folic Acid for Vascular Outcome Reduction in Transplantation (FAVORIT) trial demonstrate associations of lower SBP levels and reduced mortality risk, but the relationship of BP with kidney allog...
Source: American Journal of Hypertension - Category: Cardiology Authors: Tags: Am J Hypertens Source Type: research
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