Preservation of renal function: the spectrum of effects by calcium-channel blockers

The vast majority of animal data derived from models of either remnant kidney or diabetes demonstrate that dihydropyridine (nifedipine-like) calcium-channel blockers (DHPCCBs) effectively reduce arterial pressure but do not significantly affect proteinuria nor prevent development of glomerular scarring. Conversely, the non-DHPCCBs such as diltiazem and verapamil blunt both the rise in proteinuria as well as mesangial matrix expansion and subsequent glomerular scarring in diabetes. Additionally, the non-DHPCCBs markedly attenuate development of glomerular scarring in the remnant kidney model. The primary reasons for these differences between subclasses of CCBs relates to a lack of the following attributes by DHPCCBs: (1) they fail to reduce glomerular membrane permeability which is increased in these models; (2) they fail to affect the synthesis of certain key matrix proteins that perpetuate development of glomerular scarring (this effect may be due to the differential expression of calcium channels within the glomerular mesangium); and (3) the DHPCCBs totally abolish renal autoregulation in these models, an effect not observed with non-DHPCCBs. Taken together with long-term (> 3 year) clinical studies, primarily in diabetic nephropathy, it is clear that the non-DHPCCBs seem to offer protection to the kidney not available with DHPCCBs alone, unless systolic arterial pressure is reduced to levels of < or = 110 mmHg.