RENAL PROTECTION IN DIABETES - AN EMERGING ROLE FOR CALCIUM-ANTAGONISTS

Background The combination of diabetes and hypertension increases the chances of progressive renal disorder and, ultimately renal failure. R oughly 40% of all diabetics, whether insulin-dependent or not, develop diabetic nephropathy. Diabetic nephropathy is the single most importa nt cause of end-stage renal disease in the Western world and accounts for more than a quarter of all end-stage renal diseases. Diabetic neph ropathy is a major cause of increased morbidity and mortality in diabe tic patients. Increased arterial blood pressure is an early and common phenomenon in incipient and overt diabetic nephropathy. The relations hip between arterial blood pressure and diabetic nephropathy is a comp lex one, with diabetic nephropathy increasing blood pressure and blood pressure accelerating the course of nephropathy. Overview Calcium ant agonists antagonize preglomerular vasoconstriction. Additional putativ e mechanisms include the ability to retard renal growth and possibly t o attenuate mesangial entrapment of macromolecules, and to attenuate t he mitogenic effect of diverse growth factors. Calcium antagonists (ex cept the original short-acting dihydropyridine drugs) reduce microalbu minuria and preserve kidney function in diabetic patients with incipie nt diabetic nephropathy. There are still no long-term trials using the new long-acting dihydropyridine calcium antagonists to treat patients with incipient nephropathy. A recent, 1-year, randomized, double-blin d study in hypertensive insulin-dependent diabetic patients with diabe tic nephropathy showed a better attenuation of the rate of decline in glomerular filtration in patients treated with nisoldipine (long-actin g dihydropyridine) than with an angiotensin converting enzyme (ACE) in hibitor. The mean 24-h arterial blood pressure during this study was a lmost identical in both treatment groups, at 103 (SD 9) and 101 (SD 11 ) mmHg, respectively. Furthermore, a recent 5-year randomized open stu dy in hypertensive non-insulin-dependent patients with diabetic nephro pathy has revealed the same beneficial effect of a calcium antagonist and of ACE inhibition on the progression of nephropathy. In a third gr oup treated with sympatholytic drugs, creatinine levels doubled in mor e than 50% of the subjects compared to less than 10% in the two other groups mentioned above. However, long-term studies are needed to conso lidate these findings and expand them to insulin-dependent diabetic pa tients with diabetic kidney disease.