APOL1 renal risk alleles are associated with chronic kidney disease (CKD) in adults, with the strongest effect being for HIV-associated nephropathy. Their role in youth with perinatal HIV-1 infection (PHIV) has not been studied. In a nested case–control study of 451 PHIV participants in the Pediatric HIV/AIDS Cohort Study, we found a 3.5-fold increased odds of CKD in those carrying high-risk APOL1 genotypes using a recessive model [95% confidence interval (CI): 1.2 to 10.0]. We report an unadjusted incidence of 1.2 CKD cases/100 person-years (95% CI: 0.5 to 2.5) in PHIV youth carrying APOL1 high-risk genotypes, with important implications for sub-Saharan Africa.
*Division of Pediatric Infectious Disease, Department of Pediatrics, Bronx-Lebanon Hospital Center, Albert Einstein College of Medicine, Bronx, NY;
†Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA;
‡Basic Science Laboratory, Center for Cancer Research, National Cancer Institute, Leidos Biomedical Inc. Frederick National Laboratory, Frederick, MD;
§Department of Pediatrics, University of California San Diego (UCSD), La Jolla, CA;
‖Rady Children's Hospital, San Diego, CA;
¶Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD;
#Department of Pediatrics, Miller School of Medicine, University of Miami, Miami, FL;
**Department of Pediatrics, Tulane University School of Medicine, New Orleans, LA; and
††National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD.
Correspondence to: Murli U. Purswani, MD, Division of Pediatric Infectious Disease, Bronx-Lebanon Hospital Center, 1685 Morris Avenue, Suite 1G, Bronx, NY 10457 (e-mail: email@example.com).
The Pediatric HIV/AIDS Cohort Study (PHACS) was supported by the Eunice Kennedy Shriver National Institute of Child Health and Human Development with co-funding from the National Institute on Drug Abuse, the National Institute of Allergy and Infectious Diseases, the Office of AIDS Research, the National Institute of Mental Health, the National Institute of Neurological Disorders and Stroke, the National Institute on Deafness and Other Communication Disorders, the National Heart Lung and Blood Institute, the National Institute of Dental and Craniofacial Research, and the National Institute on Alcohol Abuse and Alcoholism, through cooperative agreements with the Harvard T.H. Chan School of Public Health (HD052102) (Principal Investigator: George Seage; Project Director: Julie Alperen) and the Tulane University School of Medicine (HD052104) (Principal Investigator: Russell Van Dyke; Co-Principal Investigator: Kenneth Rich; Project Director: Patrick Davis). This work was also supported in part by the Intramural Research Programs of the National Institute of Diabetes and Digestive and Kidney Diseases and the National Cancer Institute, the National Institute of Neurological Disorders and Stroke (5 R01NS077874), and the National Cancer Institute (under contract HSN26120080001E). Data management services were provided by Frontier Science and Technology Research Foundation (Principal Investigator: Suzanne Siminski), and regulatory services and logistical support were provided by Westat, Inc. (Principal Investigator: Julie Davidson).
Presented in part as a poster at the Annual Conference on Retroviruses and Opportunistic Infections, February 20–23, 2015, Seattle, WA; a poster at the Annual meeting of the Pediatric Academic Societies, May 5, 2013, Washington, DC; and as a platform presentation at the Annual meeting of the Eastern Society for Pediatric Research, March 23, 2013, Philadelphia, PA.
The authors have no conflicts of interest to disclose.
All authors meet authorship criteria. B.K. and K.P. had full access to all the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis. Conception and design of the study: J.B.K., M.U.P., and K.P. Acquisition of data, analysis, and interpretation of data: All authors. Drafting of manuscript: M.U.P., J.B.K., K.P., and C.A.W. Critical revision of manuscript: All authors. Final approval of submitted version: All authors. Statistical analysis: B.K. and K.P. Administrative, technical, or material support: All authors. Supervision of the study: M.U.P., J.B.K., and K.P.
The conclusions and opinions expressed in this article are those of the authors and do not necessarily reflect those of the National Institutes of Health or US Department of Health and Human Services, nor does mention of trade names, commercial products, or organizations imply endorsement by the US Government.
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Received December 15, 2015
Accepted March 07, 2016