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

HIV Med. 2013 Nov;14(10):633-8. doi: 10.1111/hiv.12072. Epub 2013 Aug 28.


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.

Keywords: Fanconi syndrome; HIV; acute kidney injury; drug−drug interaction; nonsteroidal anti-inflammatory drugs; tenofovir.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acute Kidney Injury / etiology*
  • Adenine / adverse effects
  • Adenine / analogs & derivatives*
  • Adenine / therapeutic use
  • Adult
  • Anti-Inflammatory Agents, Non-Steroidal / adverse effects
  • Anti-Inflammatory Agents, Non-Steroidal / therapeutic use
  • Diclofenac / adverse effects*
  • Diclofenac / therapeutic use
  • Drug Interactions
  • Fanconi Syndrome / etiology
  • Female
  • Germany
  • HIV Infections / complications
  • HIV Infections / drug therapy
  • Humans
  • Hypophosphatemia
  • Male
  • Middle Aged
  • Organophosphonates / adverse effects*
  • Organophosphonates / therapeutic use
  • Retrospective Studies
  • Tenofovir


  • Anti-Inflammatory Agents, Non-Steroidal
  • Organophosphonates
  • Diclofenac
  • Tenofovir
  • Adenine