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Sex-Related Disparities in CKD Progression.

ABSTRACT: BACKGROUND:In the United States, incidence of ESRD is 1.5 times higher in men than in women, despite men's lower prevalence of CKD. Prior studies, limited by inclusion of small percentages of minorities and other factors, suggested that men have more rapid CKD progression, but this finding has been inconsistent. METHODS:In our prospective investigation of sex differences in CKD progression, we used data from 3939 adults (1778 women and 2161 men) enrolled in the Chronic Renal Insufficiency Cohort Study, a large, diverse CKD cohort. We evaluated associations between sex (women versus men) and outcomes, specifically incident ESRD (defined as undergoing dialysis or a kidney transplant), 50% eGFR decline from baseline, incident CKD stage 5 (eGFR<15 ml/min per 1.73 m2), eGFR slope, and all-cause death. RESULTS:Participants' mean age was 58 years at study entry; 42% were non-Hispanic black, and 13% were Hispanic. During median follow-up of 6.9 years, 844 individuals developed ESRD, and 853 died. In multivariable regression models, compared with men, women had significantly lower risk of ESRD, 50% eGFR decline, progression to CKD stage 5, and death. The mean unadjusted eGFR slope was -1.09 ml/min per 1.73 m2 per year in women and -1.43 ml/min per 1.73 m2 per year in men, but this difference was not significant after multivariable adjustment. CONCLUSIONS:In this CKD cohort, women had lower risk of CKD progression and death compared with men. Additional investigation is needed to identify biologic and psychosocial factors underlying these sex-related differences.

SUBMITTER: Ricardo AC

PROVIDER: S-EPMC6317604 | biostudies-literature | 2019 Jan

REPOSITORIES: biostudies-literature

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Project description:Rationale & objectiveEquations for estimated glomerular filtration rate (eGFR) that incorporate a term for race assign a higher value to Black individuals compared to non-Black individuals for the same sex, age, and serum creatinine concentration. This difference may contribute to racial disparities in kidney transplant access. We sought to (1) compare time from meeting a transplant eligibility threshold of eGFR ≤20 mL/min/1.73 m2 to kidney failure with replacement therapy (KFRT) among Black, Hispanic, and White patients, and (2) assess the impact of incorporation of race into eGFR expressions on establishment of waitlist eligibility and time from eligibility to KFRT.Study designRetrospective cohort.Setting & participantsUsing the OptumLabs Data Warehouse, we assembled a cohort of 40,042 White, 8,519 Black, and 3,569 Hispanic patients having at least one eGFR value between 20 and 60 mL/min/1.73 m2 within the preceding 2 years and an incident outpatient eGFR of ≤20 mL/min/1.73 m2 between 2008-2018, using the CKD-EPI creatinine equation that includes a term for race coded as Black or non-Black. We then reassembled a Black patient cohort based on incident eGFR ≤20 mL/min/1.73 m2 (n = 11,269) estimated using the same CKD-EPI equation but coding Black patients as non-Black.ExposureRace/ethnicity.OutcomeTime to KFRT.Analytical approachUnadjusted and adjusted Fine-Gray models; linear regression to compute eGFR slopes.ResultsBy 3 years, the cumulative incidence of KFRT was 20.5% among White patients, 40.9% among Hispanic patients, 36% among Black patients whose GFR was estimated using a race term coded as Black, and 28.7% among Black patients whose GFR was estimated using a race term coded as non-Black. In fully adjusted analyses including 11,269 Black patients with an eGFR ≤20 mL/min/1.73 m2 based on coding them as non-Black, KFRT risk remained greater among Black (HR, 1.28 [95% CI, 1.15-1.43]) and Hispanic (HR, 1.66 [95% CI, 1.18-2.31]) patients than among White patients. Based on slopes of eGFR decline, coding Black patients as non-Black would allow earlier waitlist activation by an estimated median of 0.5 [interquartile range, 0.27-1.23] years.LimitationsInability to exclude individuals who would not be kidney transplant candidates if comprehensively evaluated.ConclusionsA uniform eGFR threshold provides less opportunity for being placed on the transplant waitlist among Black and Hispanic patients. For many Black patients, estimation of GFR as if their race category were non-Black would allow substantially earlier waitlisting but would not eliminate their shorter time to KFRT and reduced opportunity for preemptive transplantation compared with White patients.

Project description:BackgroundAlzheimer's disease (AD) is the most common cause of dementia in the elderly and the sixth leading cause of death in the United States. AD is mainly considered a complex disorder with polygenic inheritance. Despite discovering many susceptibility loci, a major proportion of AD genetic variance remains to be explained.MethodsWe investigated the genetic architecture of AD in four publicly available independent datasets through genome-wide association, transcriptome-wide association, and gene-based and pathway-based analyses. To explore differences in the genetic basis of AD between males and females, analyses were performed on three samples in each dataset: males and females combined, only males, or only females.ResultsOur genome-wide association analyses corroborated the associations of several previously detected AD loci and revealed novel significant associations of 35 single-nucleotide polymorphisms (SNPs) outside the chromosome 19q13 region at the suggestive significance level of p < 5E-06. These SNPs were mapped to 21 genes in 19 chromosomal regions. Of these, 17 genes were not associated with AD at genome-wide or suggestive levels of associations by previous genome-wide association studies. Also, the chromosomal regions corresponding to 8 genes did not contain any previously detected AD-associated SNPs with p < 5E-06. Our transcriptome-wide association and gene-based analyses revealed that 26 genes located in 20 chromosomal regions outside chromosome 19q13 had evidence of potential associations with AD at a false discovery rate of 0.05. Of these, 13 genes/regions did not contain any previously AD-associated SNPs at genome-wide or suggestive levels of associations. Most of the newly detected AD-associated SNPs and genes were sex specific, indicating sex disparities in the genetic basis of AD. Also, 7 of 26 pathways that showed evidence of associations with AD in our pathway-bases analyses were significant only in females.ConclusionsOur findings, particularly the newly discovered sex-specific genetic contributors, provide novel insight into the genetic architecture of AD and can advance our understanding of its pathogenesis.

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Sex-Related Disparities in CKD Progression.

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