Renal impairment in patients receiving a tenofovir-cART regimen: impact of tenofovir trough concentration

J Acquir Immune Defic Syndr. 2013 Apr 1;62(4):375-80. doi: 10.1097/QAI.0b013e31827ce4ee.

Abstract

Objective: Tenofovir disoproxil fumarate (TDF) is known to induce renal dysfunction in HIV-infected patients. The aim of this retrospective study was to evaluate the correlation between TDF trough concentration (Ctrough-TDF) and glomerular filtration rate (GFR) in a cohort of patients on antiretroviral therapy.

Methods: A total of 163 patients with at least one determination of Ctrough-TDF between 17-24 hours were retrospectively selected from a computerized database and distributed into 3 groups defined by TDF concentrations <40 (11.7%), between 40 and 90 (36.8%), and >90 (high-level group, 51.5%) ng/mL. GFR was measured by Cockcroft-Gault, Modification of Diet in Renal Disease, and Chronic Kidney Disease Epidemiology Collaboration formulae at the times of TDF initiation and Ctrough-TDF determination and after 12 months.

Results: At the time of Ctrough-TDF measurement, median duration of TDF-based therapy was 21.1 months. GFR was significantly decreased in high-level group (-8.5 mL/min; P < 0.001) whatever the method used. GFR decline was significantly associated with an older age. Gender-stratified analysis showed that the early impact of Ctrough-TDF >90 ng/mL was significant in women only. After 12 months, the decrease in GFR in patients with high Ctrough-TDF was observed in both men and women (-8.27; P = 0.003).

Conclusions: The high prevalence of elevated Ctrough-TDF and its correlation with an increased risk of renal impairment support the usefulness of therapeutic drug monitoring for TDF, particularly in women and older patients.

MeSH terms

  • Adenine / adverse effects
  • Adenine / analogs & derivatives*
  • Adenine / therapeutic use
  • Adult
  • Female
  • Glomerular Filtration Rate
  • Humans
  • Kidney / drug effects*
  • Kidney / physiopathology
  • Male
  • Middle Aged
  • Organophosphonates / adverse effects
  • Organophosphonates / therapeutic use*
  • Reverse Transcriptase Inhibitors / adverse effects
  • Reverse Transcriptase Inhibitors / therapeutic use*
  • Ruanda
  • Tenofovir

Substances

  • Organophosphonates
  • Reverse Transcriptase Inhibitors
  • Tenofovir
  • Adenine