Dataset Information

Sickle Cell Trait and Kidney Disease in People of African Ancestry With HIV.

ABSTRACT:

Introduction

Sickle cell trait (SCT) has been associated with chronic kidney disease (CKD) in African Americans, although evidence for its impact in Africans and people with HIV is currently lacking. We conducted a cross-sectional study investigating the association between SCT and kidney disease in people of African ancestry with HIV in the UK.

Methods

The primary outcome was estimated glomerular filtration rate (eGFR) <60 ml/min per 1.73 m². Secondary outcomes were eGFR <90 ml/min per 1.73 m², end-stage kidney disease (ESKD; eGFR <15 ml/min per 1.73 m², chronic dialysis, or having received a kidney transplant), proteinuria (protein-to-creatinine ratio >50 mg/mmol), and albuminuria (albumin-to-creatinine ratio >3 mg/mmol). Multivariable logistic regression was used to estimate the associations between SCT and kidney disease outcomes.

Results

A total of 2895 participants (mean age 48.1 [SD 10.3], 57.2% female) were included, of whom 335 (11.6%) had SCT and 352 (12.2%) had eGFR <60 ml/min per 1.73 m². After adjusting for demographic, HIV, and kidney risk factors including APOL1 high-risk genotype status, individuals with SCT were more likely to have eGFR <60 ml/min per 1.73 m² (odds ratio 1.62 [95% CI 1.14-2.32]), eGFR <90 ml/min per 1.73 m² (1.50 [1.14-1.97]), and albuminuria (1.50 [1.09-2.05]). Stratified by APOL1 status, significant associations between SCT and GFR <60 ml/min per 1.73 m², eGFR <90 ml/min per 1.73 m², proteinuria, and albuminuria were observed for those with APOL1 low-risk genotypes.

Conclusion

Our results extend previously reported associations between SCT and kidney disease to people with HIV. In people of African ancestry with HIV, these associations were largely restricted to those with APOL1 low-risk genotypes.

SUBMITTER: Hung RKY

PROVIDER: S-EPMC8897676 | biostudies-literature | 2022 Mar

REPOSITORIES: biostudies-literature

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Publications

Sickle Cell Trait and Kidney Disease in People of African Ancestry With HIV.

Hung Rachel K Y RKY Binns-Roemer Elizabeth E Booth John W JW Hilton Rachel R Fox Julie J Burns Fiona F Harber Mark M Ustianowski Andrew A Hamzah Lisa L Burns James E JE Clarke Amanda A Price David A DA Kegg Stephen S Onyango Denis D Santana-Suarez Beatriz B Campbell Lucy L Bramham Kate K Sharpe Claire C CC Sabin Caroline A CA Winkler Cheryl A CA Post Frank A FA

Kidney international reports 20211213 3

<h4>Introduction</h4>Sickle cell trait (SCT) has been associated with chronic kidney disease (CKD) in African Americans, although evidence for its impact in Africans and people with HIV is currently lacking. We conducted a cross-sectional study investigating the association between SCT and kidney disease in people of African ancestry with HIV in the UK.<h4>Methods</h4>The primary outcome was estimated glomerular filtration rate (eGFR) <60 ml/min per 1.73 m<sup>2</sup>. Secondary outcomes were eG ...[more]

PMID: 35257059

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Project description:ImportanceThe association between sickle cell trait (SCT) and chronic kidney disease (CKD) is uncertain.ObjectiveTo describe the relationship between SCT and CKD and albuminuria in self-identified African Americans.Design, setting, and participantsUsing 5 large, prospective, US population-based studies (the Atherosclerosis Risk in Communities Study [ARIC, 1987-2013; n = 3402], Jackson Heart Study [JHS, 2000-2012; n = 2105], Coronary Artery Risk Development in Young Adults [CARDIA, 1985-2006; n = 848], Multi-Ethnic Study of Atherosclerosis [MESA, 2000-2012; n = 1620], and Women's Health Initiative [WHI, 1993-2012; n = 8000]), we evaluated 15,975 self-identified African Americans (1248 participants with SCT [SCT carriers] and 14,727 participants without SCT [noncarriers]).Main outcomes and measuresPrimary outcomes were CKD (defined as an estimated glomerular filtration rate [eGFR] of <60 mL/min/1.73 m2 at baseline or follow-up), incident CKD, albuminuria (defined as a spot urine albumin:creatinine ratio of >30 mg/g or albumin excretion rate >30 mg/24 hours), and decline in eGFR (defined as a decrease of >3 mL/min/1.73 m2 per year). Effect sizes were calculated separately for each cohort and were subsequently meta-analyzed using a random-effects model.ResultsA total of 2233 individuals (239 of 1247 SCT carriers [19.2%] vs 1994 of 14,722 noncarriers [13.5%]) had CKD, 1298 (140 of 675 SCT carriers [20.7%] vs 1158 of 8481 noncarriers [13.7%]) experienced incident CKD, 1719 (150 of 665 SCT carriers [22.6%] vs 1569 of 8249 noncarriers [19.0%]) experienced decline in eGFR, and 1322 (154 of 485 SCT carriers [31.8%] vs 1168 of 5947 noncarriers [19.6%]) had albuminuria during the study period. Individuals with SCT had an increased risk of CKD (odds ratio [OR], 1.57 [95% CI, 1.34-1.84]; absolute risk difference [ARD], 7.6% [95% CI, 4.7%-10.8%]), incident CKD (OR, 1.79 [95% CI, 1.45-2.20]; ARD, 8.5% [95% CI, 5.1%-12.3%]), and decline in eGFR (OR, 1.32 [95% CI, 1.07-1.61]; ARD, 6.1% [95% CI, 1.4%-13.0%]) compared with noncarriers. Sickle cell trait was also associated with albuminuria (OR, 1.86 [95% CI, 1.49-2.31]; ARD, 12.6% [95% CI, 7.7%-17.7%]).Conclusions and relevanceAmong African Americans in these cohorts, the presence of SCT was associated with an increased risk of CKD, decline in eGFR, and albuminuria, compared with noncarriers. These findings suggest that SCT may be associated with the higher risk of kidney disease in African Americans.

Project description:BackgroundChronic kidney disease (CKD) is a leading cause of morbidity and mortality globally. The risk of CKD is increased in people of African ancestry and with Human Immunodeficiency Virus (HIV) infection.MethodsWe conducted a cross-sectional study investigating the relationship between region of ancestry (East, Central, South or West Africa) and kidney disease in people of sub-Saharan African ancestry with HIV in the UK between May 2018 and February 2020. The primary outcome was renal impairment (estimated glomerular filtration rate [eGFR] of <60 mL/min/1.73 m2). Secondary outcomes were stage 5 CKD (eGFR <15 ml/min/1.73 m2, on dialysis for over 3 months or who had received a kidney transplant), proteinuria (urine protein/creatinine ratio >50 mg/mmol), and biopsy-confirmed HIV-associated nephropathy (HIVAN), focal segmental glomerulosclerosis (FSGS) or arterionephrosclerosis. Multivariable robust Poisson regression estimated the effect of region of African ancestry on kidney disease outcomes.FindingsOf the 2468 participants (mean age 48.1 [SD 9.8] years, 62% female), 193 had renal impairment, 87 stage 5 CKD, 126 proteinuria, and 43 HIVAN/FSGS or arterionephrosclerosis. After adjusting for demographic characteristics, HIV and several CKD risk factors and with East African ancestry as referent, West African ancestry was associated with renal impairment (prevalence ratio [PR] 2.06 [95% CI 1.40-3.04]) and stage 5 CKD (PR 2.23 [1.23-4.04]), but not with proteinuria (PR 1.27 [0.78-2.05]). West African ancestry (as compared to East/South African ancestry) was also strongly associated with a diagnosis of HIVAN/FSGS or arterionephrosclerosis on kidney biopsy (PR 6.44 [2.42-17.14]).InterpretationOur results indicate that people of West African ancestry with HIV are at increased risk of kidney disease. Although we cannot rule out the possibility of residual confounding, geographical region of origin appears to be a strong independent risk factor for CKD as the association did not appear to be explained by several demographic, HIV or renal risk factors.

Project description:Background and objectivesSickle cell trait and sickle cell disease are associated with faster GFR decline compared with normal hemoglobin phenotypes. We sought to compare the AKI risk in sickle cell trait/disease to normal hemoglobin phenotypes and investigate the association between AKI and GFR decline in sickle cell trait/disease.Design, setting, participants, & measurementsThis multicenter observational study used registry data (January 2005-June 2018) of adult Black patients with sickle cell trait/disease (exposures) and normal hemoglobin phenotype (reference) ascertained by hemoglobin electrophoresis. Outcomes of interest (incident AKI [1.5 times baseline serum creatinine or higher], incident severe AKI [doubling of baseline serum creatinine or higher], and incident sustained AKI [AKI persisting for ≥72 hours]) were adjudicated by chart review and evaluated by Cox regression. The association between AKI and GFR decline (linear mixed models) was also investigated.ResultsWe identified 8968 reference patients, 1279 patients with sickle cell trait, and 254 patients with sickle cell disease with a median follow-up of 7.6 years and mean baseline serum creatinine of 0.8 mg/dl. We observed 796 AKI events, 452 sustained AKI events, and 466 severe AKI events. Compared with people with a normal hemoglobin phenotype, sickle cell trait was associated with higher risk for sustained AKI (adjusted hazard ratio, 1.64; 95% confidence interval, 1.27 to 2.11), but not AKI (adjusted hazard ratio, 1.11; 95% confidence interval, 0.91 to 1.36) or severe AKI (adjusted hazard ratio, 1.26; 95% confidence interval, 0.96 to 1.64). Sickle cell disease was associated with AKI (adjusted hazard ratio, 2.85; 95% confidence interval, 2.13 to 3.81), severe AKI (adjusted hazard ratio, 2.38; 95% confidence interval, 1.65 to 3.42), and sustained AKI (adjusted hazard ratio, 2.50; 95% confidence interval, 1.68 to 3.71). Post-AKI GFR decline was significantly faster in sickle cell trait (0.37 ml/min per 1.73 m2 per year faster, P<0.01) and disease (1.69 ml/min per 1.73 m2 per year faster, P<0.01) compared with the reference.ConclusionsSickle cell trait and disease are associated with higher risk of AKI, which is associated with accelerated decline in eGFR.

Dataset Information

Sickle Cell Trait and Kidney Disease in People of African Ancestry With HIV.

Introduction

Methods

Results

Conclusion

Publications

Sickle Cell Trait and Kidney Disease in People of African Ancestry With HIV.

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