Drug Class Combination-Associated Acute Kidney Injury

Ann Pharmacother. 2016 Nov;50(11):953-972. doi: 10.1177/1060028016657839. Epub 2016 Oct 1.


Objective: To evaluate the quality of available evidence of drug class combinations and their association with the development of acute kidney injury (AKI).

Data sources: A search of MEDLINE and Embase databases was completed using the following terms: "risk factor AND (acute kidney injury or acute kidney failure) AND (drug or medication)."

Study selection and data extraction: Inclusion criteria were the following: English language, full-text availability, and at least 1 drug-combination. Each citation was evaluated using the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) criteria. The literature was evaluated using the quality of evidence component of GRADE. No standardized definition of AKI was applied throughout..

Data synthesis: Out of 2139 total citations, 151 were assessed for full-text review, with 121 citations (6%) meeting inclusion criteria, producing76 unique drug class combinations. Overall, 56 combinations (73.7%) were considered very low quality; 12 (15.8%) were considered low quality. There were 8 (10.5%) of moderate quality, and no combination was considered high quality. 58 (76%) combinations that had a single citation,with a mean of 1.6 citations per drug class combination. The combination of nonsteroidal anti-inflammatory drugs (NSAIDs) and diuretics was reported in 10 citations, the largest number of citations.

Conclusions: Our study demonstrates a lack of well-designed studies addressing drug class combination-associated AKI. The combination of NSAIDs and diuretics with or without additional renin-angiotensin aldosterone agents had the strongest level of evidence. Despite limitations, the information included in this review may result in additional scrutiny about combining certain individual nephrotoxic drugs.

Keywords: adverse drug reactions; kidney failure; nephrology; nephrotoxicity; renal failure.

Publication types

  • Review

MeSH terms

  • Acute Kidney Injury / chemically induced*
  • Anti-Inflammatory Agents, Non-Steroidal / administration & dosage
  • Anti-Inflammatory Agents, Non-Steroidal / adverse effects*
  • Drug Therapy, Combination
  • Humans


  • Anti-Inflammatory Agents, Non-Steroidal