Effect Of L-Carnitine On Urinary IL-18 And GFR In Patient Receiving Cisplatin-Based Regimen

Abstract

Background: Nephrotoxicity is a major dose-limiting side effect facing cisplatin-based chemotherapy of a wide variety of cancers. Acute kidney injury occurs after cisplatin chemotherapy in approximately 30% of patients where severe and lifelong nephrotoxicity can result regardless of the use of powerful hydration with normal saline.In spite of scientific efforts to find relatively less toxic but equally effective substitutes, cisplatin continues to be widely involved in chemotherapy as first line antitumor agent. Apoptosis and necrosis, due to DNA damage response pathways, oxidative stress in association with severe inflammatory response and caspase activation, are the major sources of acute kidney injury due to cisplatin. L-carnitine with their antioxidant, anti-inflammatory and to some extent antiapoptotic effects may have ameliorative effect on nephrotoxicity.Aim: To assess the effects of L-carnitine in protection from cisplatin–induced nephrotoxicity in cancer patients.Patients and methods:28 patients were participated in the study and successfully completed their treatment cycles. They were randomized into two groups (N=14 in each). In group I, patients received six cycles of cisplatin based regimen with 21 days-intervals. In group II, patients received L-carnitine(500 mg oral tablet twice daily) plus cisplatin based regimen. GFR (Modification of Diet in renal Diseases formula) was measured at base line and 21 days after 1, 2, 4 and 6 cycles but IL-18 was measured at base line and 1 day after 1, 2, 4 and 6 cycles of cisplatin based regimen. Results:In patients of group I, cisplatin-based regimen caused significant (P<0.05) increment in serum creatinine and urea levels, highly significant (P<0.01) increment in serum urinary IL-18 levels, and significant (P<0.05) decrement in GFR in comparison to base line levels. Conclusions:Each of L-carnitine significantly ameliorated nephrotoxicity in patients that received cisplatin.