Angiotensin converting enzyme inhibitors, calcium channel blockers, and their combination in the treatment of glomerular disease.
BACKGROUND
Glomerular diseases may progress to end-stage renal failure via the development of glomerulosclerosis. Systemic hypertension and intraglomerular hypertension are important, although not the only, determinants of this process. Proteinuria (albuminuria) is a surrogate marker for glomerular damage and renal prognosis.
In animal experiments and in controlled clinical studies, ACE inhibitors have proved to be effective in reducing proteinuria and in preventing glomerulosclerosis or progression to end-stage renal failure, possibly more than can be explained by their effects on blood pressure.
In contrast to the uniform efficacy of ACE inhibitors, the effect of calcium channel blockers is less uniform. It depends on the model of renal damage used, the extent of the fall in systemic blood pressure and the type of calcium channel blocker used. Nevertheless, clinical studies have shown a reduction in proteinuria and at least an attenuation of progression with the use of long-acting calcium channel blockers.
If angiotensin II influences the progression of renal failure, as is universally accepted, then the combination of an ACE inhibitor (reducing the generation of angiotensin II) and a calcium channel blocker (reducing target-organ responsiveness to angiotensin II) appears a promising one.
In animal experiments, co-administration of an ACE inhibitor and a calcium channel blocker caused a more marked reduction in glomerulosclerosis, and this was seen in the stroke-prone spontaneously hypertensive rat model even at non-antihypertensive doses. In human diabetic nephropathy at least, proteinuria (measured as a surrogate marker of the illness) was lowered more effectively by the combination of an ACE inhibitor and a calcium channel blocker than either drug used as monotherapy despite a similar fall in blood pressure.
Ritz
E
E
Department of Internal Medicine, Ruperto Carola University, Heidelberg, Germany.
Orth
S R
SR
Strzelczyk
P
P
D000806:Angiotensin-Converting Enzyme Inhibitors / Q000627:therapeutic use*; D000818:Animals; D002121:Calcium Channel Blockers / Q000627:therapeutic use*; D004359:Drug Therapy, Combination; D006801:Humans; D051381:Rats; D051437:Renal Insufficiency / Q000188:drug therapy*
D000806:Angiotensin-Converting Enzyme Inhibitors; D002121:Calcium Channel Blockers