Renal protection in diabetes: an emerging role for calcium antagonists

The combination of diabetes and hypertension increases the chances of progressive renal disorder and, ultimately, renal failure. Roughly 40% of all diabetics, whether insulin-dependent or not, develop diabetic nephropathy. Diabetic nephropathy is the single most important cause of end-stage renal disease in the Western world and accounts for more than a quarter of all end-stage renal diseases. Diabetic nephropathy is a major cause of increased morbidity and mortality in diabetic patients. Increased arterial blood pressure is an early and common phenomenon in incipient and overt diabetic nephropathy. The relationship between arterial blood pressure and diabetic nephropathy is a complex one, with diabetic nephropathy increasing blood pressure and blood pressure accelerating the course of nephropathy.

Calcium antagonists antagonize preglomerular vasoconstriction. Additional putative mechanisms include the ability to retard renal growth and possibly to attenuate mesangial entrapment of macromolecules, and to attenuate the mitogenic effect of diverse growth factors. Calcium antagonists (except the original short-acting dihydropyridine drugs) reduce microalbuminuria and preserve kidney function in diabetic patients with incipient 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-blind study in hypertensive insulin-dependent diabetic patients with diabetic nephropathy showed a better attenuation of the rate of decline in glomerular filtration in patients treated with nisoldipine (long-acting dihydropyridine) than with an angiotension converting enzyme (ACE) inhibitor. The mean 24-h arterial blood pressure during this study was almost identical in both treatment groups, at 103 (SD 9) and 101 (SD 11) mmHg, respectively. Furthermore, a recent 5-year randomized open study in hypertensive non-insulin-dependent patients with diabetic nephropathy has revealed the same beneficial effect of a calcium antagonist and of ACE inhibition on the progression of nephropathy. In a third group treated with sympatholytic drugs, creatinine levels doubled in more than 50% of the subjects compared to less than 10% in the two other groups mentioned above. However, long-term studies are needed to consolidate these findings and expand them to insulin-dependent diabetic patients with diabetic kidney disease.