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Novel Haplotype Indicator for End-Stage Renal Disease Progression among Saudi Patients.

ABSTRACT: Background:End-stage renal disease (ESRD) is the result of hypertensive nephrosclerosis and chronic glomerular diseases and is associated with high morbidity and mortality. There are strong heritable components in the manifestation of the disease with a genetic predisposition to renal disorders, including focal segmental glomerulosclerosis and arterionephrosclerosis. Recent studies in genetics have examined modifiable risk factors that contribute to renal disease, and this has provided a deep insight into progressive kidney disease. Single-nucleotide polymorphisms at the proximity of SHROOM3, CST3, SLC7A9, and MYH9 genes have been associated with an increased risk of developing CKD and ESRD. Methods:A total of 160 CKD patients and 189 control subjects of Saudi origin participated in the study. Eight polymorphisms (SHROOM3-rs9992101, rs17319721; SLC7A9-rs4805834; MYH9-rs4821480, rs4821481, rs2032487, rs3752462; CST3-rs13038305) were genotyped using TaqMan assay, and the haplotype analysis was done using the HaploView 4.2 software. Results:Haplotype analysis revealed a novel haplotype "E6"-GTTT to be associated significantly with an increased risk for ESRD (p=0.0001) and CKD (p=0.03). Conclusion:CKD is often silent until symptomatic uremia during the advanced stages of the disease. The newly identified haplotype will help recognize patients at risk for a rapid progression of CKD to ESRD. Accurate detection and mapping of the genetic variants facilitates improved risk stratification and development of improved and targeted therapeutic management for CKD.

SUBMITTER: Cyrus C

PROVIDER: S-EPMC6724424 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature

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Novel Haplotype Indicator for End-Stage Renal Disease Progression among Saudi Patients.

Cyrus Cyril C Chathoth Shahanas S Vatte Chittibabu C Alrubaish Nafie N Almuhanna Othman O Borgio J Francis JF Al-Mueilo Samir S Al Muhanna Fahd F Al Ali Amein K AK

International journal of nephrology 20190822

<h4>Background</h4>End-stage renal disease (ESRD) is the result of hypertensive nephrosclerosis and chronic glomerular diseases and is associated with high morbidity and mortality. There are strong heritable components in the manifestation of the disease with a genetic predisposition to renal disorders, including focal segmental glomerulosclerosis and arterionephrosclerosis. Recent studies in genetics have examined modifiable risk factors that contribute to renal disease, and this has provided a ...[more]

PMID: 31534799

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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

Novel Haplotype Indicator for End-Stage Renal Disease Progression among Saudi Patients.

Publications

Novel Haplotype Indicator for End-Stage Renal Disease Progression among Saudi Patients.

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