The Mechanism of Drug Nephrotoxicity and the Methods for Preventing Kidney Damage

Abstract

Acute kidney injury (AKI) is a global health challenge of vast proportions, as approx. 13.3% of people worldwide are affected annually. The pathophysiology of AKI is very complex, but its main causes are sepsis, ischemia, and nephrotoxicity. Nephrotoxicity is mainly associated with the use of drugs. Drug-induced AKI accounts for 19-26% of all hospitalized cases. Drug-induced nephrotoxicity develops according to one of the three mechanisms: (1) proximal tubular injury and acute tubular necrosis (ATN) (a dose-dependent mechanism), where the cause is related to apical contact with drugs or their metabolites, the transport of drugs and their metabolites from the apical surface, and the secretion of drugs from the basolateral surface into the tubular lumen; (2) tubular obstruction by crystals or casts containing drugs and their metabolites (a dose-dependent mechanism); (3) interstitial nephritis induced by drugs and their metabolites (a dose-independent mechanism). In this article, the mechanisms of the individual types of injury will be described. Specific groups of drugs will be linked to specific injuries. Additionally, the risk factors for the development of AKI and the methods for preventing and/or treating the condition will be discussed.

Keywords: acute kidney injury; acute tubular necrosis; casts nephropathy; interstitial nephritis; nephrotoxicity.

Figure 1

Schematic illustration of drug nephrotoxicity. AG+ aminoglycosides, PL- anionic phospholipids, MC megalin-cubilin, HES hydroxyethyl starch, TF tenofovir, CIS cisplatin, OATorganic anion transporter, OCT organic cation transporter, hMATE humanmultidrug, and toxin extrusion protein transporter, MRP multidrug resistance protein transporter, Pgp P-glucoprotein transporter, ROS reactive oxygen species, TGFβtransforming growth factor-beta, TNF-α transforming growth factor-beta.