BACKGROUND: Monitoring of side effects of long-term HIV treatment has become increasingly important. Tenofovir disoproxil fumarate (TDF), a first-line treatment option, is associated with kidney tubular dysfunction (KTD). Our objective was to further investigate the prevalence and risk factors of KTD, in particular its association with TDF plasma concentration in HIV-infected patients treated with TDF for at least one year. METHODS: An observational cross-sectional single-centre study was conducted. KTD was defined as the presence of at least two of the following criteria: urinary α1-microglobulin/creatinine ratio >15 mg/10 mmol; fractional excretion (FE) of phosphate >20% in the presence of hypophosphataemia; FE of uric acid >10% in the presence of hypouricaemia and glucosuria. Multivariate logistic regression was used to study which variable was associated with KTD. RESULTS: A total of 161 HIV patients were included. Abnormalities in tubular function were observed in 101 patients (62.7%), while 17 patients (10.6%) fulfilled the definition of KTD. Urinary α1-microglobulin/creatinine ratio was the most sensitive parameter to detect KTD. Multivariate logistic regression showed TDF plasma concentration to be the only variable associated with KTD. Post hoc analysis showed a stronger association between the product of TDF plasma concentration and TDF exposure and KTD. CONCLUSIONS: Parameters of KTD are frequently observed in patients on long-term TDF-containing combination antiretroviral therapy. KTD is associated with higher TDF plasma concentrations. A stronger association between the product of TDF plasma concentration and TDF exposure and KTD could suggest cumulative toxicity. A causative role for elevated TDF plasma concentration in development of KTD cannot be demonstrated in this cross-sectional analysis. Longitudinal research is needed to investigate the development and clinical relevance of KTD.
BACKGROUND: Monitoring of side effects of long-term HIV treatment has become increasingly important. Tenofovir disoproxil fumarate (TDF), a first-line treatment option, is associated with kidney tubular dysfunction (KTD). Our objective was to further investigate the prevalence and risk factors of KTD, in particular its association with TDF plasma concentration in HIV-infectedpatients treated with TDF for at least one year. METHODS: An observational cross-sectional single-centre study was conducted. KTD was defined as the presence of at least two of the following criteria: urinary α1-microglobulin/creatinine ratio >15 mg/10 mmol; fractional excretion (FE) of phosphate >20% in the presence of hypophosphataemia; FE of uric acid >10% in the presence of hypouricaemia and glucosuria. Multivariate logistic regression was used to study which variable was associated with KTD. RESULTS: A total of 161 HIVpatients were included. Abnormalities in tubular function were observed in 101 patients (62.7%), while 17 patients (10.6%) fulfilled the definition of KTD. Urinary α1-microglobulin/creatinine ratio was the most sensitive parameter to detect KTD. Multivariate logistic regression showed TDF plasma concentration to be the only variable associated with KTD. Post hoc analysis showed a stronger association between the product of TDF plasma concentration and TDF exposure and KTD. CONCLUSIONS: Parameters of KTD are frequently observed in patients on long-term TDF-containing combination antiretroviral therapy. KTD is associated with higher TDF plasma concentrations. A stronger association between the product of TDF plasma concentration and TDF exposure and KTD could suggest cumulative toxicity. A causative role for elevated TDF plasma concentration in development of KTD cannot be demonstrated in this cross-sectional analysis. Longitudinal research is needed to investigate the development and clinical relevance of KTD.
Authors: Monica Gandhi; David V Glidden; Kenneth Mayer; Mauro Schechter; Susan Buchbinder; Beatriz Grinsztejn; Sybil Hosek; Martin Casapia; Juan Guanira; Linda-Gail Bekker; Alexander Louie; Howard Horng; Leslie Z Benet; Albert Liu; Robert M Grant Journal: Lancet HIV Date: 2016-08-31 Impact factor: 12.767
Authors: S M Baxi; R M Greenblatt; P Bacchetti; M Cohen; J A DeHovitz; K Anastos; S J Gange; M A Young; B E Aouizerat Journal: Pharmacogenomics J Date: 2017-05-02 Impact factor: 3.550
Authors: A Calcagno; J Cusato; L Marinaro; L Trentini; C Alcantarini; M Mussa; M Simiele; A D'Avolio; G Di Perri; S Bonora Journal: Pharmacogenomics J Date: 2015-10-06 Impact factor: 3.550
Authors: Lisa Hamzah; Amanda Samarawickrama; Lucy Campbell; Matthew Pope; Keith Burling; Martin Fisher; Yvonne Gilleece; Karen Walker-Bone; Frank A Post Journal: AIDS Date: 2015-09-10 Impact factor: 4.177
Authors: Sana Waheed; Doaa Attia; Michelle M Estrella; Yousuf Zafar; Mohamed G Atta; Gregory M Lucas; Derek M Fine Journal: Clin Kidney J Date: 2015-06-03