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Association of APOL1 Genotype with Renal Histology among Black HIV-Positive Patients Undergoing Kidney Biopsy.

ABSTRACT: Prior studies have shown that the APOL1 risk alleles are associated with a greater risk of HIV-associated nephropathy and FSGS among blacks who are HIV positive. We sought to determine whether the APOL1 high-risk genotype incrementally improved the prediction of these underlying lesions beyond conventional clinical factors.In a cross-sectional study, we analyzed data from 203 blacks who are HIV positive, underwent kidney biopsies between 1996 and 2011, and were genotyped for the APOL1 G1 and G2 alleles. Predictive logistic regression models with conventional clinical factors were compared with those that also included APOL1 genotype using receiver-operating curves and bootstrapping analyses with crossvalidation.The addition of APOL1 genotype to HIV-related risk factors for kidney disease in a predictive model improved the prediction of non-HIV-associated nephropathy FSGS, specifically, increasing the c statistic from 0.65 to 0.74 (P=0.04). Although two risk alleles were significantly associated with higher odds of HIV-associated nephropathy, APOL1 genotype did not add incrementally to the prediction of this specific histopathology.APOL1 genotype may provide additional diagnostic information to traditional clinical variables in predicting underlying FSGS spectrum lesions in blacks who are HIV positive. In contrast, although APOL1 risk genotype predicts HIV-associated nephropathy, it lacked a high c statistic sufficient for discrimination to eliminate the role of kidney biopsy in the clinical care of blacks who are HIV positive with nephrotic proteinuria or unexplained kidney disease.

SUBMITTER: Atta MG

PROVIDER: S-EPMC4741048 | biostudies-literature | 2016 Feb

REPOSITORIES: biostudies-literature

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Association of APOL1 Genotype with Renal Histology among Black HIV-Positive Patients Undergoing Kidney Biopsy.

Atta Mohamed G MG Estrella Michelle M MM Skorecki Karl L KL Kopp Jeffrey B JB Winkler Cheryl A CA Wasser Walter G WG Shemer Revital R Racusen Lorraine C LC Kuperman Michael M Foy Matthew C MC Lucas Gregory M GM Fine Derek M DM

Clinical journal of the American Society of Nephrology : CJASN 20151214 2

<h4>Background and objectives</h4>Prior studies have shown that the APOL1 risk alleles are associated with a greater risk of HIV-associated nephropathy and FSGS among blacks who are HIV positive. We sought to determine whether the APOL1 high-risk genotype incrementally improved the prediction of these underlying lesions beyond conventional clinical factors.<h4>Design, setting, participants, & measurements</h4>In a cross-sectional study, we analyzed data from 203 blacks who are HIV positive, unde ...[more]

PMID: 26668025

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Project description:APOL1 genotype is associated with advanced kidney disease in African Americans, but the pathogenic mechanisms are unclear. Here, associations of APOL1 genotype with urine biomarkers of glomerular and tubular injury and kidney function decline were evaluated.Observational study.431 human immunodeficiency virus (HIV)-infected African American women enrolled in Women's Interagency HIV Study (WIHS).APOL1 genotype.Albumin-creatinine ratio (ACR), 4 tubular injury biomarkers (interleukin 18 [IL-18], kidney injury molecule 1 [KIM-1], neutrophil gelatinase-associated lipocalin [NGAL], and ?1-microglobulin [A1M]), and kidney function estimated using the CKD-EPI cystatin C equation.Participants were genotyped for APOL1 single-nucleotide polymorphisms rs73885319 (G1 allele) and rs71785313 (G2 allele). Urine biomarkers were measured using stored samples from 1999-2000. Cystatin C was measured using serum collected at baseline and 4- and 8-year follow-ups.At baseline, ACRs were higher among 47 women with 2 APOL1 risk alleles versus 384 women with 0/1 risk allele (median, 24 vs 11mg/g; P<0.001). Compared with women with 0/1 risk allele, women with 2 risk alleles had 104% higher ACRs (95% CI, 29-223mg/g) and 2-fold greater risk of ACR>30 (95% CI, 1.17-3.44) mg/g after multivariable adjustment. APOL1 genotype showed little association with urine IL-18:Cr ratio, KIM-1:Cr ratio, and NGAL:Cr ratio (estimates of -5% [95% CI, -24% to 18%], -20% [95% CI, -36% to -1%], and 10% [95% CI, -26% to 64%], respectively) or detectable urine A1M (prevalence ratio, 1.13; 95% CI, 0.65-1.97) in adjusted analyses. Compared with women with 0/1 allele, women with 2 risk alleles had faster eGFR decline, by 1.2 (95% CI, 0.2 to 2.2) mL/min/1.73m(2) per year, and 1.7- and 3.4-fold greater rates of incident chronic kidney disease (95% CI, 1.1 to 2.5) and 10% annual eGFR decline (95% CI, 1.7 to 6.7), respectively, with minimal attenuation after adjustment for glomerular and tubular injury biomarker levels.Results may not be generalizable to men.Among HIV-infected African American women, APOL1-associated kidney injury appears to localize to the glomerulus, rather than the tubules.

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Association of APOL1 Genotype with Renal Histology among Black HIV-Positive Patients Undergoing Kidney Biopsy.

Publications

Association of APOL1 Genotype with Renal Histology among Black HIV-Positive Patients Undergoing Kidney Biopsy.

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