Association of APOL1 genotype with renal histology among black HIV-positive patients undergoing kidney biopsy

Mohamed Atta, Michelle M. Estrella, Karl L. Skorecki, Jeffrey B. Kopp, Cheryl A. Winkler, Walter G. Wasser, Revital Shemer, Lorraine C Racusen, Michael Kuperman, Matthew C. Foy, Gregory M Lucas, Derek M Fine

Research output: Contribution to journalArticle

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 APOL1high–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.

Original languageEnglish (US)
Pages (from-to)262-270
Number of pages9
JournalClinical Journal of the American Society of Nephrology
Volume11
Issue number2
DOIs
StatePublished - Feb 5 2016

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Histology
AIDS-Associated Nephropathy
Genotype
HIV
Kidney
Biopsy
Alleles
Kidney Diseases
Logistic Models
Proteinuria
Cross-Sectional Studies

Keywords

  • African Americans
  • AIDS-associated nephropathy
  • Alleles
  • APOL1
  • Biopsy
  • Genotype
  • Glomerulosclerosis, focal segmental
  • HIV
  • Humans
  • Kidney diseases

ASJC Scopus subject areas

  • Nephrology
  • Transplantation
  • Epidemiology
  • Critical Care and Intensive Care Medicine

Cite this

Association of APOL1 genotype with renal histology among black HIV-positive patients undergoing kidney biopsy. / Atta, Mohamed; Estrella, Michelle M.; Skorecki, Karl L.; Kopp, Jeffrey B.; Winkler, Cheryl A.; Wasser, Walter G.; Shemer, Revital; Racusen, Lorraine C; Kuperman, Michael; Foy, Matthew C.; Lucas, Gregory M; Fine, Derek M.

In: Clinical Journal of the American Society of Nephrology, Vol. 11, No. 2, 05.02.2016, p. 262-270.

Research output: Contribution to journalArticle

Atta, Mohamed ; Estrella, Michelle M. ; Skorecki, Karl L. ; Kopp, Jeffrey B. ; Winkler, Cheryl A. ; Wasser, Walter G. ; Shemer, Revital ; Racusen, Lorraine C ; Kuperman, Michael ; Foy, Matthew C. ; Lucas, Gregory M ; Fine, Derek M. / Association of APOL1 genotype with renal histology among black HIV-positive patients undergoing kidney biopsy. In: Clinical Journal of the American Society of Nephrology. 2016 ; Vol. 11, No. 2. pp. 262-270.
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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 APOL1high–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.",
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AU - Atta, Mohamed

AU - Estrella, Michelle M.

AU - Skorecki, Karl L.

AU - Kopp, Jeffrey B.

AU - Winkler, Cheryl A.

AU - Wasser, Walter G.

AU - Shemer, Revital

AU - Racusen, Lorraine C

AU - Kuperman, Michael

AU - Foy, Matthew C.

AU - Lucas, Gregory M

AU - Fine, Derek M

PY - 2016/2/5

Y1 - 2016/2/5

N2 - 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 APOL1high–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.

AB - 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 APOL1high–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.

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KW - Alleles

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KW - Genotype

KW - Glomerulosclerosis, focal segmental

KW - HIV

KW - Humans

KW - Kidney diseases

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