Acute kidney injury caused by tenofovir disoproxil fumarate and diclofenac co-administration

作者：Bickel M^*; Khaykin P; Stephan C; Schmidt K; Buettner M; Amann K; Lutz T; Gute P; Haberl A; Geiger H; Brodt H R; Jung O

来源：HIV Medicine, 2013, 14(10): 633-638.

DOI：10.1111/hiv.12072

• acute kidney injury
• drug-drug interaction
• Fanconi syndrome
• HIV
• nonsteroidal anti-inflammatory drugs
• tenofovir

ObjectivesThe 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. %26lt;br%26gt;MethodsA 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. %26lt;br%26gt;ResultsAmong 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). %26lt;br%26gt;ConclusionsDrug-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.

• 出版日期2013-11