Risk of Acute Kidney Injury Associated With Nephrotoxic Burden in Hospitalized Patients: A Scoping Review

Limited evidence exists synthesizing the risk of acute kidney injury (AKI) associated with the concomitant administration of multiple nephrotoxic drugs, and even less examining the concept of nephrotoxic burden. The objective of this scoping review was to (1) identify definitions of nephrotoxic burden; (2) methods used to quantify (use of calculations) nephrotoxic burden; and (3) determine the association between nephrotoxic burden and AKI risk. Additionally, we assessed studies reporting the risk of AKI with the concurrent use of three or more nephrotoxic drugs. Following PRISMA guidelines, a comprehensive literature search was conducted. Observational studies in hospitalized patients were included if they assessed nephrotoxic burden or the risk of AKI with concurrent nephrotoxic drug use. Sixteen studies met the inclusion criteria. Four studies assessed nephrotoxic burden, two of which defined and quantified it, and two additional studies adopted those definitions to evaluate associations with AKI. All four reported a significant relationship between increased nephrotoxic burden and AKI risk. Twelve studies evaluated the likelihood of AKI with concurrent administration of three or more nephrotoxic drugs, with reported odds ratios ranging from 1.15 to 3.18 per additional drug. The deleterious effects of concomitant exposure to three or more nephrotoxins on the kidney are evident, stressing a need to take conscious action from a clinician and institutional perspective in the attempt to prevent AKI. Future research should incorporate drug-specific weighting and consistent reporting standards to improve nephrotoxic burden assessment and guide clinical decision-making to reduce AKI.