Tenofovir (TDF) is a preferred NRTI in the current DHHS guidelines, however use is usually restricted to those with creatinine clearance (CrCl) greater than 60 ml/min due to concerns of renal failure and/or Fanconi's syndrome. Today at the 17th International AIDS Conference in Mexico City, Castellano et al of Duke University presented results from an observational study of 1574 patients attending the Duke HIV clinic between 2001 and 2007.
Out of the 1574 patients in the study, 744 received TDF for at least three months. Of these, 35 met clinical criteria of significant nephrotoxicity (7.55%) whereas in the 191 TDF non-exposed patients, eight met criteria for significant nephrotoxicity ((4.2%), P=0.052). Patients were diagnosed with acute renal dysfunction using The Acute Dialysis Quality Initiative's (ADQI) RIFLE criteria of a 50% reduction in GFR and/or a reduction in CrCl greater than or equal to 25ml/min.
A case-control design was used to investigate associations between clinical variables and the development of renal dysfunction. Variables studied included ARV history, pre-existing renal disease, CD4+ peak and nadir, HIV-1 RNA, presence of hypertension, diabetes mellitus, chronic pain (a marker for NSAID use), hepatitis B/C, obesity, smoking, malignancy, heart failure, and use of nephrotoxic drugs.
Significant predictors of nephrotoxicity in patients treated with TDF included concurrent use of nephrotoxic agents, medical co-morbidities, hypertension, chronic pain, concurrent and previous protease inhibitor use, receiving Medicaid/Medicare benefits, and lower nadir CD4+ counts. A diminished risk was noted in patients with concurrent use of NNRTIs (OR 0.29 [0.14, 0.599]).
While 25/25 (100%) of TDF recipients with both hypertension and nephrotoxic drug-use experienced nephrotoxicity, when both factors were absent, only 1/39 (3%) experienced nephrotoxicity.
This study suggests that clinical factors can be used to predict the risk of nephrotoxicity associated with use of TDF.
Reference:
Castellano C, et al. Clinical predictors of Tenofovir associated nephrotoxicity in HIV-1- infected patients. 17th International AIDS Conference; August 3-8, 2008; Mexico City, Mexico. Abstract WEAB0104.
08/06/08
Tenofovir and Nephrotoxicity
Source: Reporting from Mexico City for PRN News: Anita Radix MD, MPH and Rona Vail MD