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- Title
Acute kidney injury caused by tenofovir disoproxil fumarate and diclofenac co-administration.
- Authors
Bickel, M; Khaykin, P; Stephan, C; Schmidt, K; Buettner, M; Amann, K; Lutz, T; Gute, P; Haberl, A; Geiger, H; Brodt, HR; Jung, O
- Abstract
Objectives The renal elimination of tenofovir ( TFV) may be subject to renal drug−drug interactions that may increase the risk of kidney injury. Case reports indicated that diclofenac might increase TFV-associated nephrotoxicity via a drug−drug interaction, leading to an increased intracellular TFV concentration in proximal tubular cells. Methods A retrospective analysis of data for all patients from the Frankfurt HIV Cohort ( FHC) who had diclofenac prescriptions between January 2008 and June 2012 was carried out. Results Among 89 patients with diclofenac use, 61 patients (68.5%) were treated with tenofovir disoproxil fumarate ( TDF) and 28 patients (31.5%) were treated with TDF-sparing combination antiretroviral therapy ( cART). Thirteen patients (14.6%) developed acute kidney injury ( AKI) shortly after initiating diclofenac treatment. AKI occurred exclusively in TDF-treated patients, although all had previously stable renal function. All cases were accompanied by new onset of at least two parameters indicating proximal tubular damage, such as normoglycaemic-glucosuria and hypophosphataemia. TFV-associated nephrotoxicity was demonstrated by renal biopsy in four cases. Additionally, 11.5% of patients on TDF treatment developed new-onset proximal tubular damage, while having a preserved glomerular filtration rate. In contrast, diclofenac did not affect renal function in patients with TDF-sparing cART, as only one case of isolated hypophataemia was observed in these patients. In univariate analysis, risk factors for AKI were TDF-containing cART ( P = 0.0076) and pre-existing hypophosphataemia ( P = 0.0086). Conclusions Drug−drug interaction caused by diclofenac could exacerbate TFV-associated nephrotoxicity. Diclofenac should be used with caution in patients on TDF therapy, especially in those with hypophosphataemia. Our findings need to be confirmed in larger studies.
- Subjects
COMBINATION drug therapy; DICLOFENAC; DRUG interactions; FISHER exact test; NEPHROTOXICOLOGY; STATISTICAL hypothesis testing; U-statistics; RETROSPECTIVE studies; TENOFOVIR; HYPOPHOSPHATEMIA; DISEASE complications
- Publication
HIV Medicine, 2013, Vol 14, Issue 10, p633
- ISSN
1464-2662
- Publication type
Article
- DOI
10.1111/hiv.12072