title: Association of APOL1 Genotype with Renal Histology among Black HIV-Positive Patients Undergoing Kidney Biopsy.
abstract: OBJECTIVE
  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.
  
  
  METHODS
  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.
authors.affiliation: Departments of Medicine and matta1@jhmi.edu.
authors.forename: Mohamed G
authors.initials: MG
authors.lastname: Atta
authors.affiliation: Departments of Medicine and.
authors.forename: Michelle M
authors.initials: MM
authors.lastname: Estrella
authors.affiliation: Rappaport Faculty of Medicine and Research Institute, Technion-Israel Institute of Technology, Haifa, Israel; Department of Medicine, Rambam Health Care Campus, Haifa, Israel;
authors.forename: Karl L
authors.initials: KL
authors.lastname: Skorecki
authors.affiliation: Kidney Disease Section, Kidney Diseases Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland;
authors.forename: Jeffrey B
authors.initials: JB
authors.lastname: Kopp
authors.affiliation: Basic Research Laboratory, Center for Cancer Research, National Cancer Institute Frederick, Leidos Biomedical Research, Inc., Frederick National Laboratory, Frederick, Maryland;
authors.forename: Cheryl A
authors.initials: CA
authors.lastname: Winkler
authors.affiliation: Department of Medicine, Rambam Health Care Campus, Haifa, Israel;
authors.forename: Walter G
authors.initials: WG
authors.lastname: Wasser
authors.affiliation: Rappaport Faculty of Medicine and Research Institute, Technion-Israel Institute of Technology, Haifa, Israel; Department of Medicine, Rambam Health Care Campus, Haifa, Israel;
authors.forename: Revital
authors.initials: R
authors.lastname: Shemer
authors.affiliation: Pathology, Johns Hopkins University School of Medicine, Baltimore, Maryland;
authors.forename: Lorraine C
authors.initials: LC
authors.lastname: Racusen
authors.affiliation: Department of Pathology, Baylor University Medical Center, Dallas, Texas; and.
authors.forename: Michael
authors.initials: M
authors.lastname: Kuperman
authors.affiliation: Division of Internal Medicine, Louisiana State University Health Science Center, Baton Rouge, Louisiana.
authors.forename: Matthew C
authors.initials: MC
authors.lastname: Foy
authors.affiliation: Departments of Medicine and.
authors.forename: Gregory M
authors.initials: GM
authors.lastname: Lucas
authors.affiliation: Departments of Medicine and.
authors.forename: Derek M
authors.initials: DM
authors.lastname: Fine
mesh_terms: D016263:AIDS-Associated Nephropathy / Q000175:diagnosis / Q000208:ethnology / Q000235:genetics*; D000328:Adult; D001741:Black or African American / Q000235:genetics*; D000075944:Apolipoprotein L1; D001053:Apolipoproteins / Q000235:genetics*; D001706:Biopsy; D016009:Chi-Square Distribution; D003430:Cross-Sectional Studies; D005260:Female; D020022:Genetic Predisposition to Disease; D005923:Glomerulosclerosis, Focal Segmental / Q000175:diagnosis / Q000208:ethnology / Q000235:genetics*; D015658:HIV Infections / Q000175:diagnosis / Q000208:ethnology / Q000235:genetics*; D006801:Humans; D007668:Kidney / Q000473:pathology*; D008075:Lipoproteins, HDL / Q000235:genetics*; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D016017:Odds Ratio; D010641:Phenotype; D011237:Predictive Value of Tests; D012189:Retrospective Studies; D018570:Risk Assessment; D012307:Risk Factors
chemical_list: C108666:APOL1 protein, human; D000075944:Apolipoprotein L1; D001053:Apolipoproteins; D008075:Lipoproteins, HDL
keywords: AIDS-associated nephropathy; APOL1; African Americans; HIV; alleles; biopsy; genotype; glomerulosclerosis, focal segmental; humans; kidney diseases