Vitamin nephrotoxicity

The answer is c. (Hardman, p 15.33.) Enthusiastic over medication with vitamin D may lead to a toxic syndrome called hy/jervitamijmsis D. The initial symptoms can include weakness, nausea, weight loss, anemia, and mild acidosis. As the excessive doses are continued, signs of nephrotoxicity are manifested, such as polyuria, polydipsia, azotemia, and eventually nephrocalcinosis. In adults, osteoporosis can occur. Also, there is CNS impairment, which can result in mental retardation and convulsions. 

These drugs (e.g., cephaloridine) may be nephrotoxic causing proximal tubular necrosis. Cephaloridine is actively taken up from blood into proximal tubular cells by OAT 1. The drug therefore accumulates in the kidney. Metabolic activation via cytochrome P-450 may be involved. GSH is oxidized, and as NADPH is also depleted, the GSSG cannot be reduced back to GSH. As vitamin E-depleted animals are more susceptible, it has been suggested that lipid peroxidation may be involved. Damage to mitochondria also occurs. 

C. Wang, A. K. Salahudeen, Lipid Peroxidation Accompanies Cyclosporine Nephrotoxicity Effects of Vitamin E, Kidney Int 47 (1995) 927-34. 

Interventions to ameliorate the nephrotoxicity observed with vancomycin have largely been confined to the laboratory and have focused on attenuating oxidative stress. Oxidative stress has been postulated as the primary mechanism in the pathogenesis of vancomycin-induced nephrotoxicity [200]. A study by Ocak et al tested a diverse group of antioxidants that included caffeic acid phenethyl ester (CAPE), vitamin C, vitamin E and N-acetylcysteine [198]. Each of these agents were... 

Ocak S, Gorur S, Flakverdi S, Celik S, Erdogan 5, Protective effects of caffeic acid phenethyl ester, vitamin C, vitamin E and N-ace-tylcysteine on vancomycin- induced nephrotoxicity in rats, Basic Clin Pharmacol Toxicol, 2007,100 328-333. 

Other mechanisms and mediators have been implicated in the genesis and prevention of chronic CSA nephrotoxicity. Reactive oxygen species, besides their functional effects on renal function, are also mediators of tissue injury favoring fibrosis. Use of the antioxidant vitamin E inhibited increases in TGF-beta and osteopontin mRNA and development of renal fibrosis in CSA-treated rats [184]. Mazzali et al showed that hyperuricemia exacerbates experimental chronic CSA nephrotoxicity, apparently due to activation of the RAS and inhibition of renal NO production [520]. The complement system was studied in a mouse model of chronic CSA nephrotoxicify, and the authors found an increased expression of C3, C4d and membrane... 

Parra T, de Arriba G, Conejo JR, Cantero M, Arribas i, Rodriguez-Puyol D, Rodriguez-Puyol M, Carballo F. Cyclosporine increases local glomerular synthesis of reactive oxygen species in rats effect of vitamin Eon cyclosporine nephrotoxicity.Transplantation 1998 66 1325-1329. 

Wang C, Salahudeen AK. Lipid peroxidation accompanies cyclosporine nephrotoxicity effects of vitamin E. Kidney Int 1995 47 927-934. 

Jenkins JK, Huang H, Ndebele K, Salahudeen AK. Vitamin E inhibits renai mRNA expression of COX ii, HO i, TGFbeta, and oste-opontin in the rat modei ofcyciosporine nephrotoxicity.Transpiantation 2001 71 331-334. 

Zai F, Mostafavi-Pour Z, Vessai M. Comparison of the effects of vitamin E and/or quercetin in attenuating chronic cyciosporine A-induced nephrotoxicity in maie rats. Ciin Exp Pharmacoi Physioi 2007 34 720-724. (Erratum in Ciin Exp Pharmacoi Physioi 2007 34 953. 

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