Calcium-channel blockers for treatment of diabetic nephropathy

The use of calcium-channel blockers (CCBs) to reduce proteinuria associated with nephropathy in patients with diabetes mellitus is discussed. Metabolically induced damage to the nephrons in diabetic nephropathy decreases the filtration rate and increases the glomerular plasma flow rate and transcapillary hydraulic pressure. Microalbuminuria, which is predictive of nephropathy in patients with insulin-dependent diabetes mellitus, is associated with the development of clinical proteinuria and increased mortality. Micro-albuminuria should be evaluated periodically in diabetic patients, and antihypertensive therapy should be initiated when proteinuria is present or blood pressure control is needed. CCBs lower blood pressure because they prevent the action of angiotensin II by blocking the entry of calcium into renal vascular smooth muscle. Some CCBs, such as diltiazem and nicardipine, decrease glomerular pressure by increasing efferent arteriolar dilation. Others, such as nifedipine, may dilate both the afferent and efferent arterioles, thus causing increased excretion of protein. Studies in patients with diabetic nephropathy have shown that individual CCBs vary in their effects on proteinuria; this variation is attributable to their different sites of action and different effects on intrarenal activity. The choice of a CCB or an angiotensin-converting-enzyme inhibitor should be based on concomitant disease states and adverse-effect profiles. For control of hypertension in patients with diabetic nephropathy, diltiazem should be considered initially. Nicardipine is effective for short-term use but has not been tested in long-term studies; it should be considered a reasonable alternative.