Cyclosporin induced glomerulosclerosis in developing kidney

Aim: to study glomerular changes in developing kidney by administering therapeutic doses of csa to pregnant albino mice throughout gestation. methods: twelve pregnant mice were divided into two groups,a and b,having six animals each. cyclosporin (sandimmun,novartis,switzerland) was freshly prepared in normal saline dailyhaving a concentration of 1mg/ml and administered subcutaneously by a single dose of 50 mg/kg in the morning to experimental group b during pregnancy from day 0 to day 18. the control group a was treated with the comparable volume of normal saline given subcutaneously for 18 days during gestation. the pregnant mice were sacrificed at the end of experimental period. the fetal kidneys were dissected,fixed in 10% formalin and the sections were stained with hematoxylin and eosin (h &e) for general histological study and periodic acid schiff (pas) for the demonstration of basement membranes. these sections were evaluated for glomerular changes using calcineurin inhibitor toxicity score. results: our work clearly illustrated statistically significant glomerular changes including thickening of the glomerular basement membrane,retraction of tuft of glomerular capillaries,increased urinary space,mesangial matrix expansion and capillary collapse. these glomerular lesions were more indicative of glomerulosclerosis suggestive of possible damage to the glomeruli. the score for glomerulosclerosis was high (1.68±0.47) in experimental group as compared to (0.43± 0.50; p < 0.000) in control group. conclusion: the current study investigated the effects of csa given to mice during intrauterine life in therapeutic doses. the work clearly illustrated harmful effects of the drug leading to statistically significant glomerular changes suggestive of fetal nephrotoxicity and may eventually lead to renal failure. it might produce comparable effects in human conceptuses after intake of csa by pregnant mothers.