Drug-induced nephrotoxicity mechanism

In general, drug-induced nephrotoxicity is reversible but given the high morbidity and mortality associated with AKI and the frequent and necessary use of drugs in critically iU patients clinicians should be aware of the potential nephrotoxicities and mechanisms. Thus this review will discuss mechanisms of drug-induced AKI and preventive strategies. We wiU discuss broadly... 

Kandasamy K, Chuah JK, Su R, Huang P, Eng KG, Xiong S, Li Y, Chia CS, Loo LH, Zink D. 2015. Prediction of drug-induced nephrotoxicity and injury mechanisms with human induced plu-ripotent stem cell-derived cells and machine learning methods. Scientific Reports 5 12337. 

T. D. Nolin and J. Himmelfarb, Mechanisms of drug-induced nephrotoxicity, Handb. Exp. Pharmacol., 2010, 196, 111-130. 

There are several mechanisms by which drugs can lead to nephrotoxicity. Table 1 lists these mechanisms along with prototypical drugs that may induce nephrotoxicity. Understanding their mechanism of action will permit the optimal preventative measures. 

Perazella MA. 2003. Drug-induced renal failure update on new medications and unique mechanisms of nephrotoxicity. Am J Med Sd 325 349-362. 

The mechanism of BCNU-induced nephrotoxicity is most hkely based on a direct nephrotoxic effect but differs from that of streptozotocin manifested by proximal tubular dysfunction and acute renal failure that may abate when the drug is discontinued. 

There are numerous methods to determine the nephrotoxic potential of a chemical or to study the mechanism(s) by which a chemical induces nephrotoxicity. In humans, the concern is most often related to either drug-induced or occupationally associated nephrotoxicity. Evaluation of nephrotoxicity in humans is limited primarily to the measurement of urinary changes (e.g., volume, enzymes, protein, etc.), BUN or serum creatinine concentrations, creatinine clearance, or renal biopsy. The measurement of an increase in urinary N-acetyl-jS-D-glucosaminidase (NAG) or alanine aminopeptidase (AAP) levels,... 

Moreover, it has recently been postulated that dietary supplementation with food antioxidants may provide a safe and effective means of enhancing response to cancer chemotherapy (Conklin, 2000). Much more research is needed to validate this claim however, the stimulation of oxygen radical formation by antitumor drugs is a known cause of side effects of chemotherapy like cardio- or nephrotoxicity. The approved chemoprotectants used clinically to date are not neutral to the organism either. In contrast, certain antioxidative food components, in doses that are without adverse effects, could improve the quality of life of patients by ameliorating chemotherapy-induced side effects and also enhance activity of antitumor drugs by different mechanisms (e.g., inhibition of topoisomerase II). 

Specific drug-induced renal structural-functional alterations constitute the remainder of this discussion under the seven broad headings listed in Table 46-1. The general orientation of these topics is in order of decreasing clinical incidence. Pathophysiologic mechanisms of nephrotoxicity will be emphasized, in addition to clinical findings, prevention, and management. 

The immunosuppressive drug cyclosporine A (CSA) has revolutionized transplant medicine. However, CSA induced-nephrotoxicity still represents a major therapeutic challenge. Chronic CSA nephropathy is characterized by a decrease in glomerular filtration rate (GFR), tubular atrophy, interstitial fibrosis and progressive renal dysfunction. It is difficult to delineate the mechanisms of CSA toxicity from clinical data since the majority of clinical experiences with CSA have been in renal transplant recipients. Animal models of CSA nephropathy have brought some insights, how-... 

A broad range of experimental models has been developed for the study of mechanisms of chemically induced nephrotoxicity and the screening of potential new drugs for adverse... 

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