Effect of Some Calcium Channel Blockers in Experimentally Induced Diabetic Nephropathy in Rats

Diabetic nephropathy (DNP) is considered a CRD (Chronic Renal Disease); it is a major cause of illness and premature death in people with DM. The present study was designed to illustrate the role of CCBs (amlodipine and diltiazem) in prevention and treatment of DNP in rats. Eighty male albino rats weighing (130-180gm) were used in this study. These animals were subdivided into five equal groups. Insulinopenic diabetes was induced by STZ, two weeks later, 30 minutes of complete ischemia was induced in the left kidney to induce diabetic nephropathy then treatment was started for 12 weeks. At the end of experiment urine samples and blood samples were taken for biochemical analysis and kidneys were taken for histopathological evaluation. Combination of renal ischemia with DM produced a significant increase in rat weight, rat kidney weight, BUN (Blood Urea Nitrogen) level, K/B (Kidney/Body weight) ratio, random blood glucose, 24 hrs urine proteins, and 24 hrs urine volumes and creatinine clearance. Treatment with diltiazem or amlodipine significantly lowered elevated SBP and elevated 24 hrs urine volumes. Furthermore, treatment with captopril produced a highly significant lowering of elevated SBP and elevated serum creatinine; and a significant reduction in elevated K/B ratio and proteinuria. Light microscopic examination of diabetic kidneys revealed glomerulopathy characterized by thickening of the glomerular basement membrane, mesangial matrix expansion, arteriolar hyalinosis and large proteinaceous deposits occluding some capillary loops and hyaline droplets within the glomeruli. Moreover, examination of kidneys of ischemic animals by light microscope revealed focal tubular necrosis at multiple points along the nephron, interstitial edema and accumulation of leucocytes within dilated vasa recta.