Calcium-channel blockers and the progression of renal disease.

Effective blood pressure (BP) reduction is now generally recognized as a clinically proven strategy to retard the seemingly inexorable downhill progression of patients with diabetic and nondiabetic chronic renal disease. Although calcium-channel blockers (CCBs) are effective antihypertensive agents, the available experimental and clinical data are quite contradictory as to whether BP reduction achieved with CCBs provides the expected renoprotection. Blockade of the "L" type, voltage-gated Ca channels that mediate the BP reduction also concurrently impairs renal autoregulatory responses of the preglomerular vasculature. Because these renal autoregulatory resistance changes provide the primary protection against the transmission of systemic hypertension to the renal microvasculature, the adverse effects of CCBs on renal autoregulation counteract the beneficial effects on BP reduction. The degree of renoprotection achieved, therefore, depends on the balance between these two opposing effects. The data also indicate that there are probably important and clinically relevant differences between the classes of CCBs, with the dihydropyridine (DHP) CCBs most likely to have consistent deleterious effects on renal autoregulation. However, the available data also indicate that the adverse effects of DHP CCBs are not likely to be observed if BP is lowered well into the normotensive range, possibly through the use of combination therapies. Even when used as adjunctive therapy, close monitoring may be advisable to ensure BP normalization and the absence of any untoward effects on proteinuria and renal function.