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African origins and chronic kidney disease susceptibility in the human immunodeficiency virus era.

ABSTRACT: Chronic kidney disease (CKD) is a major public health problem worldwide with the estimated incidence growing by approximately 6% annually. There are striking ethnic differences in the prevalence of CKD such that, in the United States, African Americans have the highest prevalence of CKD, four times the incidence of end stage renal disease when compared to Americans of European ancestry suggestive of genetic predisposition. Diabetes mellitus, hypertension and human immunodeficiency virus (HIV) infection are the major causes of CKD. HIV-associated nephropathy (HIVAN) is an irreversible form of CKD with considerable morbidity and mortality and is present predominantly in people of African ancestry. The APOL1 G1 and G2 alleles were more strongly associated with the risk for CKD than the previously examined MYH9 E1 risk haplotype in individuals of African ancestry. A strong association was reported in HIVAN, suggesting that 50% of African Americans with two APOL1 risk alleles, if untreated, would develop HIVAN. However these two variants are not enough to cause disease. The prevailing belief is that modifying factors or second hits (including genetic hits) underlie the pathogenesis of kidney disease. This work reviews the history of genetic susceptibility of CKD and outlines current theories regarding the role for APOL1 in CKD in the HIV era.

SUBMITTER: Kasembeli AN

PROVIDER: S-EPMC4419140 | biostudies-literature | 2015 May

REPOSITORIES: biostudies-literature

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African origins and chronic kidney disease susceptibility in the human immunodeficiency virus era.

Kasembeli Alex N AN Duarte Raquel R Ramsay Michèle M Naicker Saraladevi S

World journal of nephrology 20150501 2

Chronic kidney disease (CKD) is a major public health problem worldwide with the estimated incidence growing by approximately 6% annually. There are striking ethnic differences in the prevalence of CKD such that, in the United States, African Americans have the highest prevalence of CKD, four times the incidence of end stage renal disease when compared to Americans of European ancestry suggestive of genetic predisposition. Diabetes mellitus, hypertension and human immunodeficiency virus (HIV) in ...[more]

PMID: 25949944

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Project description:Background and objectivesHIV-infected patients are at risk for developing chronic kidney disease (CKD), defined by estimated glomerular filtration rate (eGFR) <60 ml/min/1.73m2. Our purpose was to understand the genesis of CKD in HIV patients from a large urban clinic in Houston, Texas, USA, and to characterize progression of CKD in the cohort.Design, setting, participants and measurementsA retrospective cohort study (2012-2016) was conducted in all HIV-infected patients seen in a federally qualified community health center in Houston, Texas. CKD prevalence and its association with HIV viral load and CD4 count were determined. The association of the change in eGFR over time and comorbidities was assessed using linear mixed models.ResultsOf 3714 HIV-infected patients analyzed, 153 (4.1%) had CKD. The prevalence of CKD in the different racial groups was 5.4% White, 4.0% African American, 2.8% Hispanic/Latino and 3.2% Asian. There was no difference in the rate of decline in kidney function in White vs. African American HIV infected patients with CKD. Compared with non-CKD patients, CKD patients were older, had lived longer with HIV infection, had lower CD4 cell counts, higher proportions of hypertension, hyperlipidemia, and cerebrovascular disease, and had significantly higher rates of eGFR deterioration represented by a median decrease of 26.5% from first to last follow-up eGFR (versus 0% change). Linear mixed modeling identified older age, male gender, White race, longer time with HIV infection, hypertension, history of kidney stones, cerebrovascular disease, autoimmune disease, increased potassium and total cholesterol levels, and being treated with combination ART as associated with a worsening eGFR over time.ConclusionThis study demonstrates a prevalence of CKD in HIV-infected patients of 4.1% and points to an important role for HIV medications and other common comorbidities in the genesis and progression of kidney disease. Importantly, CKD was not more prevalent in African Americans than in Whites, perhaps due to a low prevalence of IV drug abuse as inferred from the lower prevalence of HCV infection in this cohort.

Project description:Hepatitis C virus (HCV) and human immunodeficiency virus (HIV) are both associated with chronic kidney disease (CKD), a major complication after orthotopic liver transplantation (OLT). The aim of this study was to assess predictors of post-OLT CKD in HIV/HCV-coinfected recipients versus HIV-infected recipients without HCV (HIV/non-HCV recipients). Data from a National Institutes of Health study of 116 OLT recipients (35 HIV/non-HCV recipients and 81 HIV/HCV-coinfected recipients) from 2003 to 2010 (Solid Organ Transplantation in HIV: Multi-Site Study) were analyzed for the pretransplant CKD prevalence [estimated glomerular filtration rate (eGFR)?<?60 mL/minute for ?3 months] and the incidence of CKD up to 3 years posttransplant. Proportional hazards models were performed to assess predictors of posttransplant CKD. A contemporaneous cohort of HCV-monoinfected transplant recipients from the Scientific Registry of Transplant Recipients database was also analyzed. The median age at transplant was 48 years, the median serum creatinine level was 1.1 mg/dL, and the median eGFR was 77 mL/minute. Thirty-four patients were suspected to have pretransplant CKD; 20 of these patients (59%) had posttransplant CKD. Among the 82 patients without pretransplant CKD (26 HIV/non-HCV patients and 56 HIV/HCV-coinfected patients), the incidence of stage 3 CKD 3 years after OLT was 62% (55% of HIV/non-HCV patients and 65% of HIV/HCV-coinfected patients), and the incidence of stage 4/5 CKD was 8% (0% of HIV/non-HCV patients and 12% of HIV/HCV-coinfected patients). In a multivariate analysis, older age [[hazard ratio (HR)?=?1.05 per year, P?=?0.03] and the CD4 count (HR?=?0.90 per 50 cells/?L, P?=?0.01) were significant predictors of CKD. HCV coinfection was significantly associated with stage 4/5 CKD (HR?=?10.8, P?=?0.03) after adjustments for age. The cumulative incidence of stage 4/5 CKD was significantly higher for HIV/HCV-coinfected patients versus HIV/non-HCV transplant recipients and HCV-monoinfected transplant recipients (P?=?0.001). In conclusion, CKD occurs frequently in HIV-infected transplant recipients. Predictors of posttransplant CKD include older age and a lower posttransplant CD4 count. HCV coinfection is associated with a higher incidence of stage 4/5 CKD.

Project description:BackgroundRoutine primary care visits provide an educational opportunity for African-Americans with chronic kidney disease (CKD) and CKD risk factors such as hypertension. The nature of patient-physician discussions about CKD and their impact on CKD awareness in this population have not been well explored.ObjectiveTo characterize patient CKD awareness and discussions about CKD between patients and primary care physicians (PCPs).DesignMixed methods study.PatientsAfrican-American patients with uncontrolled hypertension (≥ 140/90 mmHg) and CKD (albuminuria or eGFR < 60 ml/min/1.73 m2) recruited from an urban primary care clinic.Main measuresWe assessed patient CKD awareness with questionnaires and audio-recorded patients-PCP discussions during a routine visit. We characterized discussions and used multivariate regression analysis to identify independent patient and visit predictors of CKD awareness or CKD discussions.ResultsAmong 48 African-American patients with uncontrolled hypertension and CKD, 29% were aware of their CKD. After adjustment, CKD awareness was associated with moderate-severe CKD (stages 3-4) (vs. mild CKD [stages 1-2]) (prevalence ratio [PR] 2.82; 95% CI 1.18-6.78) and inversely associated with diabetes (vs. without diabetes) (PR 0.28; 95% CI 0.10-0.75). CKD discussions occurred in 30 (63%) visits; most focused on laboratory assessment (n = 23, 77%) or risk factor management to delay CKD progression (n = 19, 63%). CKD discussions were associated with moderate-severe CKD (vs. mild CKD) (PR 1.57; 95% CI 1.04-2.36) and diabetes (vs. without diabetes) (PR 1.42; 95% CI 1.09-1.85), and inversely associated with uncontrolled hypertension (vs. controlled) (PR 0.58; 95% CI 0.92-0.89). In subgroup analysis, follow-up CKD awareness did not change by presence or absence of CKD discussion (10.5% vs. 7.7%, p = 0.8).ConclusionsIn patients at risk of CKD progression, few were aware of CKD, and CKD discussions were not associated with CKD awareness. More resources may be needed to enhance the clarity of clinical messages regarding CKD and its significance for patients' health.Trial registrationClinicalTrials.gov Identifier: NCT01902719.

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African origins and chronic kidney disease susceptibility in the human immunodeficiency virus era.

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African origins and chronic kidney disease susceptibility in the human immunodeficiency virus era.

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