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. It is also 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, diabetic nephropathy increasing blood pressure and blood pressure accelerating the course of nephropathy. Calcium antagonists antagonize preglomerular vasoconstriction. Furthermore, additional putative mechanisms include the ability to retard renal growth and possibly to attenuate mesangial entrapment of macromolecules and to attenuate the mitogenic effects of diverse growth factors. Calcium antagonists (except the old short-acting dihydropyridine drugs) reduce microalbuminuria and preserve kidney function in diabetic patients with incipient diabetic nephropathy. Long-term trials using the new long-acting dihydropyridine calcium antagonists for the treatment of patients with incipient nephropathy are still lacking. A recent 1-year randomized double-blind study in hypertensive insulin-dependent diabetic patients with diabetic nephropathy showed a more beneficial effect on the decline rate in the glomerular filtration rate of nisoldipine (long-acting dihydropyridine) than angiotensin-converting-enzyme (ACE) inhibition. The mean arterial blood pressure during the study based on 24-hour recordings was nearly identical, 103 (SD 9) and 101 (SD 11) mm Hg in the two groups. Furthermore, a recent 5-year randomized open study in hypertensive noninsulin-dependent patients with diabetic nephropathy has revealed the same beneficial effect of a calcium antagonist and ACE inhibition on the progression of nephropathy. In a third group treated with sympatholytic drugs, more than 50% of the subjects had a doubling of their creatinine as 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.