title: Tenofovir treatment duration predicts proteinuria in a multiethnic United States Cohort of children and adolescents with perinatal HIV-1 infection.
abstract: BACKGROUND
  Tenofovir is associated with renal proximal tubule injury. Such toxicity has not been extensively studied in HIV-1-infected children, in whom tenofovir is increasingly used.
  
  
  METHODS
  History, urine and blood were collected at regular intervals from 448 children and adolescents with perinatal HIV-1 infection followed in the Pediatric HIV/AIDS Cohort study. Relationships between tenofovir use and proteinuria and chronic kidney disease (CKD) outcomes were examined using multivariable logistic regression models. Proteinuria was defined as at least one urine protein/creatinine ratio (uPCR) ≥ 0.2, and CKD as ≥ 2 sequential uPCR ≥ 0.2 or estimated glomerular filtration rates <60 mL/min/1.73 m with no subsequent resolution, or a clinical diagnosis not contradicted by a normal uPCR. Subjects with ≥ 2 uPCR <0.2, and no abnormal uPCR and eGFR comprised the comparison group.
  
  
  RESULTS
  Subjects were 47% male, 72% black, 24% Hispanic, with entry mean age (± standard deviation) of 11.5 ± 2.5 years. Proteinuria prevalence at entry, and annually during 3 years, ranged from 10.3% to 13.7%. The cumulative prevalence of proteinuria was 22% (94/434, 95% confidence interval: 18%-26%) and CKD 4.5% (20/448, 95% confidence interval: 2.7%-6.8%). Duration of tenofovir use was an independent predictor of proteinuria, with >3 years of exposure having the highest risk compared with no exposure (odds ratio: 2.53, 95% confidence interval: 1.23-5.22, overall P = 0.01). Overall, duration of tenofovir use did not significantly predict the presence of CKD.
  
  
  CONCLUSIONS
  Rates of proteinuria and CKD were lower than those seen in the pre-highly active antiretroviral therapy era. However, prolonged exposure to tenofovir increases risk of renal injury.
authors.affiliation: Bronx-Lebanon Hospital Center, Albert Einstein College of Medicine, Bronx, NY 10457, USA. mpurswan@bronxleb.org
authors.forename: Murli
authors.initials: M
authors.lastname: Purswani
authors.forename: Kunjal
authors.initials: K
authors.lastname: Patel
authors.forename: Jeffrey B
authors.initials: JB
authors.lastname: Kopp
authors.forename: George R
authors.initials: GR
authors.lastname: Seage
authors.forename: Miriam C
authors.initials: MC
authors.lastname: Chernoff
authors.forename: Rohan
authors.initials: R
authors.lastname: Hazra
authors.forename: George K
authors.initials: GK
authors.lastname: Siberry
authors.forename: Lynne M
authors.initials: LM
authors.lastname: Mofenson
authors.forename: Gwendolyn B
authors.initials: GB
authors.lastname: Scott
authors.forename: Russell B
authors.initials: RB
authors.lastname: Van Dyke
mesh_terms: D000225:Adenine / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D000293:Adolescent; D001741:Black or African American; D019380:Anti-HIV Agents / Q000009:adverse effects* / Q000627:therapeutic use; D002648:Child; D015331:Cohort Studies; D005260:Female; D015658:HIV Infections / Q000188:drug therapy* / Q000208:ethnology / Q000652:urine*; D006630:Hispanic or Latino; D006801:Humans; D018445:Infectious Disease Transmission, Vertical; D008297:Male; D015999:Multivariate Analysis; D016017:Odds Ratio; D063065:Organophosphonates / Q000009:adverse effects* / Q000627:therapeutic use; D015995:Prevalence; D011446:Prospective Studies; D011507:Proteinuria / Q000139:chemically induced* / Q000821:virology*; D051436:Renal Insufficiency, Chronic / Q000139:chemically induced / Q000652:urine / Q000821:virology; D018709:Statistics, Nonparametric; D000068698:Tenofovir; D014481:United States
chemical_list: D019380:Anti-HIV Agents; D063065:Organophosphonates; D000068698:Tenofovir; D000225:Adenine