Abstract
BackgroundTreatment with tenofovir is sometimes associated with renal dysfunction. Limited information is available on this side effect in patients with small body weight, although the use of tenofovir will spread rapidly in Asia and Africa, where patients are likely to be of smaller body weight.MethodsIn a single-center cohort, Japanese patients with HIV infection who started tenofovir-containing antiretroviral therapy were retrospectively analyzed. The incidence of tenofovir-associated renal dysfunction, defined as more than 25% decrement of estimated glomerular filtration rate (eGFR) from the baseline, was determined. The effects of small body weight and body mass index (BMI) on tenofovir-associated renal dysfunction, respectively, were estimated in univariate and multivariate Cox hazards models as the primary exposure. Other possible risk factors were evaluated by univariate analysis and those found significant were entered into the multivariate analysis.ResultsThe median weight of 495 patients was 63 kg. Tenofovir-related renal dysfunction occurred in 97 (19.6%) patients (incidence: 10.5 per 100 person-years). Univariate analysis showed that the incidence of tenofovir-related renal dysfunction was significantly associated with smaller body weight and BMI, respectively (per 5 kg decrement, HR = 1.23; 95% CI, 1.10–1.37; p<0.001)(per 1 kg/m2 decrement, HR = 1.14; 95% CI, 1.05–1.23; p = 0.001). Old age, high baseline eGFR, low serum creatinine, low CD4 count, high HIV viral load, concurrent nephrotoxic drugs, hepatitis C infection, and current smoking were also associated with tenofovir-related renal dysfunction. Multivariate analysis identified small body weight as a significant risk (adjusted HR = 1.13; 95% CI, 1.01–1.27; p = 0.039), while small BMI had marginal significance (adjusted HR = 1.07; 95% CI 1.00–1.16; p = 0.058).ConclusionThe incidence of tenofovir-associated renal dysfunction in Japanese patients was high. Small body weight was identified as an independent risk factor for tenofovir-associated renal dysfunction. Close monitoring of renal function is advocated for patients with small body weight treated with tenofovir.
Highlights
Tenofovir disoproxil fumarate (TDF) is one of the most widely used nucleotide reverse transcriptase inhibitors (NRTI) for patients with HIV infection, with proven efficacy and safety [1,2,3,4,5,6]
TDF is known to cause renal proximal tubular dysfunction, and several case reports have been published with TDF-related Fanconi syndrome, diabetes insipidus, and acute tubular necrosis, which sometimes lead to acute renal failure [7,8,9,10]
A recently published meta-analysis has reported that the use of TDF is associated with a statistically significant but only modest renal dysfunction, and recommended that TDF use should not be restricted even when regular monitoring of renal function and serum phosphate levels is impractical [15]
Summary
Tenofovir disoproxil fumarate (TDF) is one of the most widely used nucleotide reverse transcriptase inhibitors (NRTI) for patients with HIV infection, with proven efficacy and safety [1,2,3,4,5,6]. TDF is known to cause renal proximal tubular dysfunction, and several case reports have been published with TDF-related Fanconi syndrome, diabetes insipidus, and acute tubular necrosis, which sometimes lead to acute renal failure [7,8,9,10]. A recently published meta-analysis has reported that the use of TDF is associated with a statistically significant but only modest renal dysfunction, and recommended that TDF use should not be restricted even when regular monitoring of renal function and serum phosphate levels is impractical [15]. Limited information is available on this side effect in patients with small body weight, the use of tenofovir will spread rapidly in Asia and Africa, where patients are likely to be of smaller body weight
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