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Genetic contribution and associated pathophysiology in end-stage renal disease.

ABSTRACT: End-stage renal disease (ESRD) or chronic kidney disease (CKD) is the terminal state of the kidney when its function has been permanently and irreversibly damaged. A wide variety of etiologies and pathological processes culminate in ESRD, and both environmental and genetic factors contribute to its development and progression. Various reports suggest that susceptibility to develop ESRD has a significant genetic component. These studies include familial aggregation studies, comparisons of incidence rates between different racial or ethnic populations, and segregation analysis. Genetic approaches have been used to identify genes that contribute to genetic susceptibility. Many studies have now been carried out assessing the contribution of specific "candidate genes", which correlate with different functions that are involved in the renal pathogenesis. Independent studies for specific associated genes have frequently provided contradictory results. This may be due, in part, to the modest contribution to genetic susceptibility which these genes impart. With the availability of different genomewide association studies, chromosomal regions harboring novel, previously unrecognized, genes that may contribute to renal diseases have been recently reported. We have focused on different genetic studies conducted on ESRD and have discussed the strength and weaknesses of these studies. The nonmuscle myosin heavy chain 9 gene (MYH9) and renin-angiotensin system (RAS) have been discussed in detail.

SUBMITTER: Agrawal S

PROVIDER: S-EPMC3681165 | biostudies-literature | 2010

REPOSITORIES: biostudies-literature

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Genetic contribution and associated pathophysiology in end-stage renal disease.

Agrawal Suraksha S Agarwal Ss S Naik Sita S

The application of clinical genetics 20100805

End-stage renal disease (ESRD) or chronic kidney disease (CKD) is the terminal state of the kidney when its function has been permanently and irreversibly damaged. A wide variety of etiologies and pathological processes culminate in ESRD, and both environmental and genetic factors contribute to its development and progression. Various reports suggest that susceptibility to develop ESRD has a significant genetic component. These studies include familial aggregation studies, comparisons of inciden ...[more]

PMID: 23776353

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Project description:OBJECTIVE:Hyperphosphatemia is common in end-stage renal disease and associates with mortality. Phosphate binders reduce serum phosphorus levels; however, adherence is often poor. This pilot study aims to assess patients' self-motivation to adhere to phosphate binders, its association with phosphorus control, and potential differences by race. DESIGN AND METHODS:Cross sectional design. Subjects were enrolled from one academic medical center dialysis practice from July to November 2012. Self-motivation to adhere to phosphate binders was assessed with the autonomous regulation (AR) scale (range: 1-7) and self-reported medication adherence with the Morisky Medication Adherence Scale. Linear regression models adjusting for age, sex, health literacy, and medication adherence were applied to determine associations with serum phosphorus level, including any evidence of interaction by race. RESULTS:Among 100 participants, mean age was 51 years (±15 years), 53% were male, 72% were non-white, 89% received hemodialysis, and mean serum phosphorus level was 5.7 ± 1.6 mg/dL. More than half (57%) reported the maximum AR score (7). Higher AR scores were noted in those reporting better health overall (P = .001) and those with higher health literacy (P = .01). AR score correlated with better medication adherence (r = 0.22; P = .02), and medication adherence was negatively associated with serum phosphorus (r = -0.40; P < .001). In subgroup analysis among non-whites, higher AR scores correlated with lower serum phosphorus (high vs lower AR score: 5.55 [1.5] vs 6.96 [2.2]; P = .01). Associations between AR score (? 95% confidence interval: -0.37 [-0.73 to -0.01]; P = .04), medication adherence (? 95% confidence interval: -0.25 [-0.42 to -0.07]; P = .01), and serum phosphorus persisted in adjusted analyses. CONCLUSIONS:Self-motivation was associated with phosphate binder adherence and phosphorus control, and this differed by race. Additional research is needed to determine if personalized, culturally sensitive strategies to understand and overcome motivational barriers may optimize mineral bone health in end-stage renal disease.

Project description:Purpose of reviewGenetic testing can improve diagnostic precision in some patients with end-stage renal disease (ESRD) providing the potential for targeted therapy and improved patient outcomes. We sought to describe the genetic architecture of ESRD and Canadian data sources available for further genetic investigation into ESRD.Sources of informationWe performed PubMed searches of English, peer-reviewed articles using keywords "chronic kidney disease," "ESRD," "genetics," "sequencing," and "administrative databases," and searched for nephrology-related Mendelian diseases on the Online Mendelian Inheritance in Man database.MethodsIn this narrative review, we discuss our evolving understanding of the genetic architecture of kidney disease and ESRD, the risks and benefits of using genetic data to help diagnose and manage patients with ESRD, existing public Canadian biobanks and databases, and a vision for future genetic studies of ESRD in Canada.Key findingsESRD has a polygenic architecture including rare Mendelian mutations and common small effect genetic polymorphism contributors. Genetic testing will improve diagnostic accuracy and contribute to a precision medicine approach in nephrology. However, the risk and benefits of genetic testing needs to be considered from an individual and societal perspective, and further research is required. Merging existing health data, linking biobanks and administrative databases, and forming Canadian collaborations hold great potential for genetic research into ESRD. Large sample sizes are necessary to perform the suitably powered investigations required to bring this vision to reality.LimitationsThis is a narrative review of the literature discussing future directions and opportunities. It reflects the views and academic biases of the authors.ImplicationsNational collaborations will be required to obtain sample sizes required for impactful, robust research. Merging established datasets may be one approach to obtain adequate samples. Patient education and engagement will improve the value of knowledge gained.

Project description:OBJECTIVE:Serum albumin is a marker of malnutrition and inflammation and has been demonstrated as a strong predictor of mortality in chronic kidney disease (CKD) and end-stage renal disease (ESRD) patients. Yet, whether serum albumin levels in late-stage CKD are associated with adverse outcomes after the transition to ESRD is unknown. We hypothesize that lower levels and a decline in serum albumin in late-stage CKD are associated with higher risk of mortality and hospitalization rates 1 year after transition to ESRD. DESIGN AND METHODS:This retrospective cohort study included 29,124 US veterans with advanced CKD transitioning to ESRD between 2007 and 2015. We evaluated the association of pre-ESRD (91 days before transition) serum albumin with 12-month post-ESRD all-cause, cardiovascular, and infection-related mortalities and hospitalization rates as well as the association of 1-year pre-ESRD albumin slope and 12-month post-ESRD mortality using hierarchical multivariable adjustments. RESULTS:There was a negative linear association between serum albumin and all-cause mortality, such that risk doubled (hazard ratio [HR]: 2.07, 95% confidence interval [CI]: 1.87, 2.28) for patients with the lowest serum albumin <2.8 g/dL (ref: ?4.0 g/dL) after full adjustment. A consistent relationship was observed between serum albumin and cardiovascular and infection-related mortality, and hospitalization outcomes. An increase in serum albumin of >0.25 g/dL/year was associated with reduced mortality risk (HR: 0.76, 95% CI: 0.63, 0.91) compared with a slight decline in albumin (ref: >-0.25 to 0 g/dL/year), whereas a decline more than 0.5 g/dL/year was associated with a 55% higher risk in mortality (HR: 1.55, 95% CI: 1.43, 1.68) in fully adjusted models. CONCLUSIONS:Lower pre-ESRD serum albumin was associated with higher post-ESRD all-cause, cardiovascular, and infection-related mortalities and hospitalization rates. Declining serum albumin levels in the pre-ESRD period were also associated with worse 12-month post-ESRD mortality.

Dataset Information

Genetic contribution and associated pathophysiology in end-stage renal disease.

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Genetic contribution and associated pathophysiology in end-stage renal disease.

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