Renal Protection in Diabetes-An Emerging Role for Calcium Antagonists

Abstract

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.

Protection from vascular risk in diabetic hypertension

“…Calcium-channel blockers may be superior to ACE inhibitors as direct vasodilators to provide the more strict blood pressure control needed to delay progression of nephropathy in patients with complicated DM. In fact, with the exception of the short-acting dihydropyridine agents, a recent analysis shows that most calcium-channel blockers reduce or stabilize glomerular filtration rate in DM [36].…”

Long-term effects of angiotensin-converting enzyme inhibition and metabolic control in hypertensive type 2 diabetic patients

“…pril in patients with nondiabetic proteinuria Ͼ3 g/day [33]. Despite these encouraging results, in view of the There is a high prevalence of hypertension, ranging from 30 to 90%, depending on definitions, in type 2 metabolic milieu and multiple medical problems in the majority of type 2 diabetic patients, findings from other diabetes [29,30]. Despite the magnitude of this health problem, there are only a few long-term studies, lasting patient groups may not necessarily be applicable to the majority of hypertensive type 2 diabetic patients.…”

Calcium-channel blockers and the progression of renal disease

“…With smaller BP reductions, proteinuria is either unchanged or has been observed to increase. Although it has been suggested that a lack of consistent beneficial effects on proteinuria may not necessarily indicate a lack of effectiveness for long-term preservation of renal function [44], such interpretations are contrary to the known natural history of treated or untreated proteinuric renal disease [3,5,18•].…”