EFFECT OF CYCLOSPORINE A ON THE KIDNEY OF RABBIT: A LIGHT AND ULTRASTRUCTURAL STUDY

Background: Nephrotoxicity is a relatively common problem in patients immunosuppressed with cyclosporine A (CsA) with an incidence reaching up to thirty percent. The present work aimed to study the histological and ultrastructural effects of CsA on the kidney of rabbit. Materials and Methods: Two groups of Egyptian adult rabbits were used for this study (5 rabbits for each). One group was used as a control and the other group (experimental) was treated with CsA in a dose of 15 mg/kg of body weight for two weeks. The animals were anaesthetized; and kidney specimens were obtained, fixed and processed for light and electron microscopic examinations. Results: CsA had adverse effects on the kidney especially renal corpuscles, proximal convoluted tubules, distal convoluted tubules and afferent glomerular arterioles. The renal corpuscles were observed with shrunken glomeruli, widening of Bowman?s space and thickening of the Bowman?s capsule. Also, there was obvious increase in mesangial cell number and overall glomerular obliteration due to large lining endothelial cells and encroachment of the mesangial cell matrix onto the capillary lumen. The renal tubules showed vacuolization and PAS positive inclusion bodies. The cells showed disordered brush border of microvilli. Many fibrocytes appeared inbetween the tubules. Peritubular capillary congestion was observed with an increase in the surrounding connective tissue. Ultrastructurally, the proximal convoluted tubules showed thick basement membrane with loss of the basal infolding. The mitochondria appeared degenerated with damaged transverse cristae. Electron dense lysosomes were seen in the cytoplasm. In distal convoluted tubules, the cells showed degenerated mitochondria and pyknotic nuclei. The afferent glomerular arterioles appeared with hyperplasia of juxtaglomerular cells that contained massive renin granules. The lining endothelial cells appeared protruding their nuclei into the lumen due to contraction of the smooth muscles. Conclusions: It could be concluded that CsA had adverse structural changes on the kidney mainly on the nephron; renal corpuscles, proximal convoluted tubules, distal convoluted tubules and afferent glomerular arterioles. Defective renal function should always be a concern in the management of CsA treated patient.