Statins Against Drug-Induced Nephrotoxicity

Abstract

Drug-induced nephrotoxicity (DIN) accounts for up to 60% of hospital acquired acute kidney injury with considerable morbidity and mortality. Several efforts have been made to reduce drug-induced nephrotoxicity; however, DIN remains a matter of concern. Statins with their antioxidant, anti-inflammatory and anti-apoptotic effects may have the potential to protect kidney against DIN. The present review evaluated all of the available in vitro and in vivo studies that examined the use of statins as renoprotective agents against nephrotoxic drugs. Materials for this review were obtained by searching Medline, PubMed, Scopus, Cochrane central register of controlled trials, and Cochrane database of systematic reviews. Key words used as search terms included “statin”, “3-hydroxy-3-methylglutaryl-coenzyme A reductase inhibitors, “HMG-CoA reductase inhibitors”, “nephroprotective”, “renoprotective”, “drug-induced renal diseases”, “drug-induced nephrotoxicity”, “drug-induced renal toxicity”, “drug-induced nephropathy”, “drug-induced renal side effects”, and “contrast-induced nephropathy”. This search was performed without time limitation. Only English language articles were included in this review. This review concluded that chronic statin user may be less prone to contrast-induced nephropathy (CIN) compared with statin non-users. Short-term high dose statin administration may also reduce the incidence of CIN in statin naïve patients. This renoprotective effect of statins against CIN is seen in low risk patients with normal kidney function or mild kidney dysfunction, but probably not in patients with moderate to severe renal dysfunction. Based on available animal data, statins may protect kidney against gentamicin-, cisplatin- and cyclosporine-induced nephrotoxicity, however, theses animal results have not yet been confirmed by human data. This article is open to POST-PUBLICATION REVIEW. Registered readers (see “For Readers”) may comment by clicking on ABSTRACT on the issue’s contents page.

Renoprotective approaches and strategies in acute kidney injury

“…Several mechanisms have been suggested to contribute to the renoprotective effects of statins in AKI. Statins with their antioxidant, anti-inflammatory and anti-apoptotic effects may protect kidney against gentamicin-, cisplatin- and cyclosporine-induced nephrotoxicity, beyond their lipid-lowering capacity (Dashti-Khavidaki et al, 2013; Kostapanos et al, 2009). They may also block the activation of mitogen-activated protein kinase (MAPK) and the redox-sensitive NF-kB and activator protein-1 (AP-1) (Gueler et al, 2002).…”

Effects of atorvastatin on biomarkers of acute kidney injury in amikacin recipients: A pilot, randomized, placebo-controlled, clinical trial

“…By inhibiting HMG-CoA reductase activity and consequently, decrease in the intracellular isoprenoid pyrophosphates, atorvastatin may limit renal cells accumulation of AG and following their cytotoxicity. [17]…”

“…Inhibition of drug accumulation in the proximal tubular cells, anti-inflammatory and antithrombotic effects, upregulation of endothelial NOS, activation of the antioxidant defense enzymes, inhibition of MAPK and NF-κβ signaling pathways, reducing ischemia and angiotensin II-induced AKI, downregulation of angiotensin receptors, and decrease in endothelin synthesis are the main proposed pathways. [17]…”

Imaging patients with renal impairment

“…Other useful strategies to prevent CIN include volume expansion and selection of a low or isoosmolar iodinated contrast agents [38]. More recent studies have suggested that the administration of statins may have nephroprotective effects in patient undergoing coronary angiography [43].…”