Tenofovir treatment duration predicts proteinuria in a multiethnic united states cohort of children and adolescents with perinatal HIV-1 infection

Murli Purswani, Kunjal Patel, Jeffrey B. Kopp, George R. Seage, Miriam C. Chernoff, Rohan Hazra, George K. Siberry, Lynne M. Mofenson, Gwendolyn B. Scott, Russell B. Van Dyke

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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 <60mL/min/1.73 m2 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.

Original languageEnglish (US)
Pages (from-to)495-500
Number of pages6
JournalPediatric Infectious Disease Journal
Volume32
Issue number5
DOIs
StatePublished - 2013

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Tenofovir
Proteinuria
HIV Infections
HIV-1
Chronic Renal Insufficiency
Urine
Creatinine
Logistic Models
Therapeutics
Proximal Kidney Tubule
Highly Active Antiretroviral Therapy
Wounds and Injuries
Glomerular Filtration Rate
Acquired Immunodeficiency Syndrome
Proteins
Cohort Studies
History
Odds Ratio
HIV
Confidence Intervals

Keywords

  • Chronic kidney disease
  • Nephrotoxicity
  • Proteinuria
  • Proximal tubules
  • Tenofovir
  • Urine protein/creatinine ratio

ASJC Scopus subject areas

  • Pediatrics, Perinatology, and Child Health
  • Microbiology (medical)
  • Infectious Diseases

Cite this

Tenofovir treatment duration predicts proteinuria in a multiethnic united states cohort of children and adolescents with perinatal HIV-1 infection. / Purswani, Murli; Patel, Kunjal; Kopp, Jeffrey B.; Seage, George R.; Chernoff, Miriam C.; Hazra, Rohan; Siberry, George K.; Mofenson, Lynne M.; Scott, Gwendolyn B.; Van Dyke, Russell B.

In: Pediatric Infectious Disease Journal, Vol. 32, No. 5, 2013, p. 495-500.

Research output: Contribution to journalArticle

Purswani, Murli ; Patel, Kunjal ; Kopp, Jeffrey B. ; Seage, George R. ; Chernoff, Miriam C. ; Hazra, Rohan ; Siberry, George K. ; Mofenson, Lynne M. ; Scott, Gwendolyn B. ; Van Dyke, Russell B. / Tenofovir treatment duration predicts proteinuria in a multiethnic united states cohort of children and adolescents with perinatal HIV-1 infection. In: Pediatric Infectious Disease Journal. 2013 ; Vol. 32, No. 5. pp. 495-500.
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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 <60mL/min/1.73 m2 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.",
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author = "Murli Purswani and Kunjal Patel and Kopp, {Jeffrey B.} and Seage, {George R.} and Chernoff, {Miriam C.} and Rohan Hazra and Siberry, {George K.} and Mofenson, {Lynne M.} and Scott, {Gwendolyn B.} and {Van Dyke}, {Russell B.}",
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AU - Patel, Kunjal

AU - Kopp, Jeffrey B.

AU - Seage, George R.

AU - Chernoff, Miriam C.

AU - Hazra, Rohan

AU - Siberry, George K.

AU - Mofenson, Lynne M.

AU - Scott, Gwendolyn B.

AU - Van Dyke, Russell B.

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N2 - 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 <60mL/min/1.73 m2 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.

AB - 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 <60mL/min/1.73 m2 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.

KW - Chronic kidney disease

KW - Nephrotoxicity

KW - Proteinuria

KW - Proximal tubules

KW - Tenofovir

KW - Urine protein/creatinine ratio

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