role of calcium channel blockers in the treatment of diabetic nephropathy

Diabetic nephropathy [DNP] is a chronic renal disease [CRD] and a major cause of illness and premature death in people with diabetes mellitus [DM]. It 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. This article reviews the current development in DNP and the therapeutic challenge with particular reference to the role of calcium channel blockers. Moreover, renal ischaemia hastens the progression of DNP. Diltiazem and amlodipine have a tendency to reverse the changed parameters toward normal values but do not affect the biochemical parameters. Generally speaking, diltiazem is better than amlodipine in reversing biochemical and histopathological changes produced by DNP, and captopril reverses most of the changed parameters with the exception of the histopathological changes. These agents have nephroprotective properties and delay the progression of DNP

mechanism of action of calcium channel blockers in the treatment of diabetic nephropathy

Three types of calcium channels have been identified voltage-sensitive, receptor operated [cardiac muscle and vascular smooth muscle] and stretch operated [in some blood vessels] channels. Using electrophysiological and pharmacological techniques, three different types of voltage-gated calcium channels have been identified, namely, L-type [for long lasting, large channels], T-type [for transient, tiny channels] and N-type [for neuronal, neither L nor T]. Many compounds are known to have a calcium channel inhibitory effect. Calcium antagonists, based on the specificity of inhibition of the slow calcium current, can be classified into three groups: Group A: for 90 to 100 percent inhibition of calcium influx without change in the sodium current [verapamil, diltiazem and the dihydropyridines]; Group B: for 50 to 70 percent inhibition of calcium influx current without change in the sodium current [bepridil, cinnarizine and prenylamine] and Group C: for agents exhibiting some inhibition of calcium influx [phenytoin, indomethacin and propranolol]. There is now increasing evidence that, certain calcium channel blockers especially the dihydropyridines are more strongly associated with vasodilation of afferent arterioles than of efferent arterioles and also with increase intraglomerular pressure and albuminuria. Thus they have a beneficial effect in terms of reducing proteinuria and slowing the progression of diabetic renal failure