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

Clin J Am Soc Nephrol. 2016 Feb 5;11(2):262-70. doi: 10.2215/CJN.07490715. Epub 2015 Dec 14.

Abstract

Background and objectives: 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.

Design, setting, participants, & measurements: 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.

Results: 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.

Conclusions: 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.

Keywords: AIDS-associated nephropathy; APOL1; African Americans; HIV; alleles; biopsy; genotype; glomerulosclerosis, focal segmental; humans; kidney diseases.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, N.I.H., Intramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • AIDS-Associated Nephropathy / diagnosis
  • AIDS-Associated Nephropathy / ethnology
  • AIDS-Associated Nephropathy / genetics*
  • Adult
  • African Americans / genetics*
  • Apolipoprotein L1
  • Apolipoproteins / genetics*
  • Biopsy
  • Chi-Square Distribution
  • Cross-Sectional Studies
  • Female
  • Genetic Predisposition to Disease
  • Glomerulosclerosis, Focal Segmental / diagnosis
  • Glomerulosclerosis, Focal Segmental / ethnology
  • Glomerulosclerosis, Focal Segmental / genetics*
  • HIV Infections / diagnosis
  • HIV Infections / ethnology
  • HIV Infections / genetics*
  • Humans
  • Kidney / pathology*
  • Lipoproteins, HDL / genetics*
  • Logistic Models
  • Male
  • Middle Aged
  • Multivariate Analysis
  • Odds Ratio
  • Phenotype
  • Predictive Value of Tests
  • Retrospective Studies
  • Risk Assessment
  • Risk Factors

Substances

  • APOL1 protein, human
  • Apolipoprotein L1
  • Apolipoproteins
  • Lipoproteins, HDL