Drug-induced acute kidney injury: diverse mechanisms of tubular injury

Abstract

Purpose of review: Medications are a relatively common cause of acute kidney injury (AKI), especially in hospitalized patients who are exposed to numerous agents. Drug-related acute tubular/tubulointerstitial injury is the most common cause of AKI associated with these agents. Toxic effects of drugs and their renal handling often lead to various forms of AKI.

Recent findings: The inherent nephrotoxicity of drugs and their transport and metabolism by the kidneys play an important role in the occurrence of acute tubular injury. Apical transport of the aminoglycosides by endocytosis and apical pinocytosis of filtered hydroxyethyl starch into cells lead to acute tubular dysfunction. Transport of tenofovir and cisplatin by organic anion and cation transporters in the basolateral surface of the proximal tubule, respectively, are associated with intracellular drug accumulation and injury. Intratubular deposition of drug crystals with associated AKI occurs with several drugs, in particular the anticancer agent methotrexate. A potentially new mechanism of drug-induced AKI was described with vancomycin - acute vancomycin-related cast nephropathy. Immune-mediated acute tubulointerstitial injury is another cause of drug-induced AKI, as seen with immune checkpoint inhibitors.

Summary: Drugs lead to AKI through mechanisms that involve their inherent toxicity as well as their transport and handling by the kidneys.