Low Frequency of Renal Function Impairment During One-Year of Therapy with Tenofovir-Containing Regimens in the Real-World: A Case-Control Study

Abstract

Concern exists about the risk of nephrotoxicity using tenofovir (TDF) in HIV-infected patients. We performed a retrospective case-control study including 122 consecutive TDF-naive patients who started treatment with TDF-containing regimens and 194 patients receiving antiretroviral therapy with other antiretroviral drugs. During a 12-month observation period 5 (4.1%) patients in the TDF group versus 1 (0.5%) in the control group developed grade 1 or higher serum creatinine elevations (p = 0.018). Only 2 (1.6%) patients discontinued TDF treatment as a result of serum creatinine level elevations. In 4 of the 5 patients developing creatinine elevations TDF was combined with lopinavir-ritonavir. The use of TDF in clinical practice during a 12-month period is associated with low risk of mild renal failure. Further studies to assess long-term renal safety of this drug are needed.

In Vitro Cytotoxicity and Mitochondrial Toxicity of Tenofovir Alone and in Combination with Other Antiretrovirals in Human Renal Proximal Tubule Cells

“…Total RNA was obtained by an affinity column-based procedure (RNeasy; QIAGEN), and on-column DNA VOL. 50,2006 TENOFOVIR IN KIDNEY IN VITRO 3825 digestion was performed during RNA purification (RNase-free DNase set; QIAGEN) to avoid genomic DNA contamination. Quantification of the COII transcript mitochondrial DNA-encoded mRNA was performed by quantitative real-time PCR.…”

“…Controlled clinical studies in humans found TDF to be safe, with the incidence of TDF-associated renal impairment (elevated serum creatinine or hypophosphatemia) being 1 to 3% and with minimal differences from comparative non-TDF arms (22,23,29,30,34,50,62). However, several reports have reassessed the renal safety of TFV, and presently there is a progressively growing subset of TFV-treated patients presenting with acute renal failure, with Fanconi syndrome and/or nephrogenic diabetes insipidus, attributed to this drug (3, 10, 16, 18, 24-26, 32, 36-38, 40, 43, 46, 49, 51, 53, 55, 58-61, 66, 67).…”

Chronic Administration of Tenofovir to Rhesus Macaques from Infancy through Adulthood and Pregnancy: Summary of Pharmacokinetics and Biological and Virological Effects

“…Renal toxicity is usually manifested as renal insufficiency and proximal renal tubular dysfunction (PRTD). During clinical trials of TDF, the frequency of clinically significant renal changes was very low among populations with normal renal values at baseline (and not different from the frequencies seen with other highly active antiretroviral therapy regimens [24,27,37,49,53,69]); furthermore, renal toxicity has been observed infrequently through continued clinical monitoring as described in case reports and cohort study reports (8,21,22,27,35,37,44,47,48,53,70,71). Some reports on TDF-treated populations describe small reductions in creatinine clearance that remained within the normal range and were thus of uncertain clinical significance (22,24,25,37,40,70).…”

Monitoring of Renal Function among HIV-Infected Patients Receiving Tenofovir in a Resource-Limited Setting

“…Rates of TDF-associated nephrotoxicity in retrospective cohort studies have been reported in general at approximately 2%. 28,29 We found a higher incidence of TDF-associated renal function decline among Thai HIV-infection, which ranged from approximately 5% to 18%, depending on the criteria. This may be explained by a lower body weight, experience to ART, and use of protease inhibitor in our population enrolled in the cohort.…”