Background:  To date, little is known about renal toxicity of tenofovir (TDF) in children. Progressive renal tubular dysfunction associated with long term use of TDF was shown in HIV-infected adults.  The aim of this study was to assess the long term renal safety of TDF in a cohort of pediatric patients.

Methods:  This was a single-site longitudinal observational study. We enrolled 27 vertically HIV-infected youths, aged 4.9 to 18.0 years with undetectable viral load receiving HAART containing lamivudine, stavudine (d4T) and a protease inhibitor (PI). At enrolment all cases replaced d4T with TDF and PI with efavirenz. Parameters of glomerular function (serum creatinine [SC], glomerular filtration rate [GFR], urinary protein/creatinine ratio [U_P/C]) and tubular function (serum phosphorus [SP], glucosuria, urinary alpha-1-microglobulin/creatinine ratio [U _{α1 M/C}], maximal tubular phosphate reabsorption [TmPO₄ /GFR] were assessed every 6 months through 60 months. Glomerular filtration rate (GFR) was computed in cases younger than 18 years by Schwartz equation suitable for enzymatic creatinine methods with calibration traceable to an isotope dilution mass spectroscopy reference-measurement procedure, and in cases older 18 yrs by Cockcroft-Gault equation. The outcome of GFR, SC, SP and TmPO₄ /GFR was evaluated using generalized estimating equations. Outcome variables were log-transformed and the follow-up time was used as equally-spaced time variable. Other predictors were gender and age at baseline.

Results:  The great majority (85%) of patients completed the follow-up. Of 293 expected determinations, we obtained 293 values for U _{α1 M/C} and glycosuria, 287 (98%) values for SC and GFR , 282 (96.2%) values for SP,  256 (87.3%) values for TmPO₄ /GFR 272 data for U_P/C (92.8%)_. Significant effects of time of follow- up were found for ln(GFR): +0.3 mL/m every 6 months of follow-up (P <0.05) but not for the other outcome variables. Increasing age was associated with increasing values of SC, SP, and TmPO₄ /GFR. No patient showed proteinuria (U_P/C≥0.2 mg/mg), nor glycosuria at baseline and during the study period. Mean U _{α1 M/C}  ratio remained unchanged through 60 months of follow-up. A GFR <60 mL/min was only once observed in a underweight girl (BMI 18 kg/m²) with GFR value at the lower normal limit at baseline and during the follow-up.

Conclusions:  Through 60 months, we found no evidence of impaired glomerular or tubular renal function in TDF treated HIV-infected youths