Dataset Information

Association of RAC1 Gene Polymorphisms with Primary End-Stage Renal Disease in Chinese Renal Recipients.

ABSTRACT: BACKGROUND/OBJECTIVE:RAC1 gene could influence susceptibility to renal failure by altering the activity and expression of Rac1, which is a member of the Rho family of small GTP-binding proteins. In clinical practice, renal transplantation provides the optimal treatment for people with end-stage renal disease (ESRD). The objective of this present study was to determine whether the RAC1 gene polymorphisms were associated with primary ESRD susceptibility in Chinese renal recipients. METHODS:Six single nucleotide polymorphisms (SNPs) of RAC1 gene, including rs836488 T>C, rs702482 A>T, rs10951982 G>A, rs702483 A>G, rs6954996 G>A, and rs9374 G>A, were genotyped in 300 renal transplant recipients (cases) and 998 healthy Chinese subjects (controls) by using TaqMan SNP genotyping assay. Allele, genotype, and haplotype frequencies of the six SNPs were compared between cases and controls. Odds ratios (OR) and 95% confidence intervals (CI) were calculated in logistic regression models to evaluate the associations of the six SNPs with ESRD risk. RESULTS:The genotype distributions for the six SNPs in controls were consistent with Hardy-Weinberg equilibrium (P > 0.05). Association analysis revealed that three SNPs were significantly associated with ESRD risk. Positive associations with ESRD risk were found for the rs836488, rs702482, and rs702483 in the co-dominant model (minor allele homozygotes versus major allele homozygotes); specifically, the frequencies of the minor allele homozygotes and the minor allele for the three SNPs were higher in the cases than in the controls. In addition, these three SNPs also had associations with increased ESRD risk under the additive model (P < 0.05), and positive associations were also found for the rs836488 in the dominant model (P < 0.05) and for the rs702483 in the recessive model (P < 0.05). All these associations were independent of confounding factors. The other three SNPs (rs10951982, rs6954996, and rs9374), in all comparison models, were not associated with ESRD risk (P > 0.05). In haplotype analysis, carriers with "C-T-G-G-G-G" haplotype had a significantly higher risk of ESRD compared with the most common haplotype "T-A-G-A-G-G" (P = 0.011, OR = 1.46, 95% CI = 1.09-1.94). CONCLUSION:This study suggested that polymorphisms of RAC1 gene might influence the susceptibility to ESRD in Chinese Han population. Further studies are necessary to confirm our findings.

SUBMITTER: Liu Y

PROVIDER: S-EPMC4739498 | biostudies-literature | 2016

REPOSITORIES: biostudies-literature

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Association of RAC1 Gene Polymorphisms with Primary End-Stage Renal Disease in Chinese Renal Recipients.

Liu Yani Y Zhou Jiali J Luo Xiaomei X Yang Chunxiao C Zhang Yu Y Shi Shaojun S

PloS one 20160203 2

<h4>Background/objective</h4>RAC1 gene could influence susceptibility to renal failure by altering the activity and expression of Rac1, which is a member of the Rho family of small GTP-binding proteins. In clinical practice, renal transplantation provides the optimal treatment for people with end-stage renal disease (ESRD). The objective of this present study was to determine whether the RAC1 gene polymorphisms were associated with primary ESRD susceptibility in Chinese renal recipients.<h4>Meth ...[more]

PMID: 26841219

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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.

Project description:BackgroundPrevious studies have demonstrated that early pre-end-stage renal disease (ESRD) nephrology care could improve postdialysis prognosis. However, less is known about the specific types of interventions responsible for the improved outcomes. We hypothesized that more frequent predialysis laboratory testing is associated with better postdialysis outcomes in incident ESRD patients.MethodsIn all, 23?089 patients with available outpatient laboratory tests performed during the 2-year predialysis (i.e. prelude) period were identified from a total of 52?172 American veterans with chronic kidney disease (CKD) transitioning to dialysis between October 2007 and September 2011. The associations between the frequency of combined laboratory tests, including serum creatinine, serum potassium and hemoglobin (test trio), with postdialysis mortality and hospitalization were examined in multivariable adjusted Cox and logistic regression models.ResultsWhen entering the 2-year prelude period, the mean age (Standard Deviation) of the patients was 66.2 (SD 11.3)?years and the mean estimated glomerular filtration rate was 46.8 (SD 23.9)?mL/min/1.73 m2. In all, 14% of patients had the test trio performed less than twice in 24?months and 8.9% had the trio measured more often than every other month. Over a 2.5-year median postdialysis follow-up period, 15?303 (66.3%) patients died (mortality rate 260/1000 patient-years). The adjusted hazard ratio of all-cause mortality and adjusted odds ratio of the composite of hospitalization or death associated with lab testing done >12/24?months compared with 2-?4/24 months were 0.68 [95% confidence interval (CI) 0.65-0.73] and 0.70 (95% CI 0.62-0.79), respectively.ConclusionsMore frequent laboratory testing in patients with advanced CKD is associated with better clinical outcomes after dialysis. Further examination in clinical trials is needed before the implementation of more frequent laboratory testing in clinical practice.

Project description:ImportanceHypertension is a leading risk factor of cardiovascular morbidity and mortality. The role of nonmalignant hypertension as the sole initiating factor of end-stage renal disease (ESRD) in non-African American populations has recently been questioned.ObjectiveTo investigate the association between hypertension and future ESRD in otherwise healthy adolescents.Design, setting, and participantsThis retrospective cohort study examined the data of 16- to 19-year-old healthy candidates for military service in the Israel Defense Forces between January 1, 1967, and December 31, 2013. Data were obtained from the central conscription registry of the Israel Defense Forces and the ESRD registry of the Israel Ministry of Health. Participants underwent a comprehensive medical assessment prior to their military service. Individuals with evidence of renal damage or kidney-related risk factors were excluded. The data analysis was conducted from February 12, 2017, to October 16, 2018.Main outcomes and measuresEnd-stage renal disease as recorded by the Israeli ESRD registry, including hemodialysis, peritoneal dialysis, renal transplant diagnosed between January 1, 1990, and December 31, 2014.ResultsThe cohort included 2 658 238 adolescents (1 596 709 [60.1%] male with a mean [SD] age of 17.4 [0.5] years), of whom 7997 (0.3%) had an established hypertension diagnosis. Half of the individuals in the hypertensive group were overweight (1559 [20.1%]) or obese (2243 [28.9%]), and most (7235 [90.5%]) were male. During a median follow-up of 19.6 years (52 287 945 person-years), 2189 individuals developed ESRD, with an incidence rate of 3.9 per 100 000 person-years. Adolescent hypertension was found to be associated with future ESRD (crude hazard ratio [HR], 5.07; 95% CI, 3.73-6.88). In a multivariable model adjusted for sex, age, years of education, body mass index, and other sociodemographic variables, the HR was 1.98 (95% CI, 1.42-2.77). When excluding participants with severe hypertension, the association with ESRD remained statistically significant (HR, 1.93; 95% CI, 1.37-2.70). In the subanalysis of nonoverweight adolescents, the association between hypertension and ESRD was statistically significant as well (HR, 2.11; 95% CI, 1.05-4.24).Conclusions and relevanceHypertension appears to be associated with a doubling of the risk of future ESRD in an otherwise healthy adolescent population.

Project description:ImportanceMedicare beneficiaries with end-stage renal disease (ESRD) are a medically complex group accounting for less than 1% of the Medicare population but more than 7% of Medicare fee-for-service payments.ObjectiveTo evaluate the association of the Comprehensive End-Stage Renal Disease Care (CEC) model with Medicare payments, health care use, and quality of care.Design, setting, and participantsIn this economic evaluation, a difference-in-differences design estimated the change in outcomes for 73 094 Medicare fee-for-service beneficiaries aligned to CEC dialysis facilities between the baseline (from January 2014 to March 2015) and intervention periods (from October 2015 to December 2017) relative to 60 464 beneficiaries at matched dialysis facilities. In the CEC model, dialysis facilities, nephrologists, and other providers partner to form ESRD Seamless Care Organizations (ESCOs), specialty-oriented accountable care organizations that coordinate care for beneficiaries with ESRD. ESCOs with expenditures below a benchmark set by the Centers for Medicare & Medicaid Services are eligible to share in savings if they meet quality thresholds. A total of 685 dialysis facilities affiliated with 37 ESCOs participated in the CEC model as of January 2017. Thirteen ESCOs joined the CEC model on October 1, 2015 (wave 1), and 24 ESCOs joined on January 1, 2017 (wave 2). Patients with ESRD who were aligned with CEC dialysis facilities were compared with patients at matched dialysis facilities.Main outcomes and measuresMedicare total and service-specific payments per beneficiary per month; hospitalizations, readmissions, and emergency department visits; and select quality measures.ResultsRelative to the comparison group (n = 60 464; 55% men; mean [SD] age, 63.5 [14.4] years), total Medicare payments for CEC beneficiaries (n = 73 094; 56% men; mean [SD] age, 63.0 [14.4] years) decreased by $114 in payments per beneficiary per month (95% CI, -$202 to -$26; P = .01), associated primarily with decreases in payments for hospitalizations and readmissions. Payment reductions were offset by shared savings payments to ESCOs, resulting in net losses of $78 in payments per beneficiary per month (95% CI, -$8 to $164; P = .07). Relative to the comparison group, CEC beneficiaries had 5.01 fewer hospitalizations per 1000 beneficiaries per month (95% CI, -8.45 to -1.56; P = .004), as well as fewer catheter placements (CEC beneficiaries with catheter as vascular access for periods longer than 90 days decreased by 0.78 percentage points [95% CI, -1.36 to -0.19; P = .01]) and fewer hospitalizations for ESRD complications (CEC beneficiaries were 0.11 percentage points less likely [95% CI, -0.20 to -0.02; P = .01] to be hospitalized in a given month). Total dialysis sessions and payments increased, suggesting improved adherence to dialysis treatments.Conclusions and relevanceEarly findings from the CEC model demonstrate that a specialty accountable care organization model focused on a particular population was associated with reduced payments and improved quality of care. Future research can assess the longer-term outcomes of the CEC model and its applicability to populations with other complex chronic conditions.

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Dataset Information

Association of RAC1 Gene Polymorphisms with Primary End-Stage Renal Disease in Chinese Renal Recipients.

Publications

Association of RAC1 Gene Polymorphisms with Primary End-Stage Renal Disease in Chinese Renal Recipients.

Similar Datasets

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