Antihypertensive therapy and progression of diabetic renal disease.
A number of changes in intrarenal hemodynamics and morphology are characteristic of diabetic nephropathy. These changes include: increases in intraglomerular pressure and volume, glomerular capillary permeability to macromolecules, and mesangial matrix expansion. Most antihypertensive drugs attenuate some of the increases in these parameters. Certain antihypertensive agents, however, have effects on all these parameters. Studies in animal models of diabetes demonstrate that the angiotensin-converting enzyme (ACE) inhibitors reduce both intraglomerular volume and pressure, mesangial matrix expansion, and albuminuria. The calcium antagonists TA-3090 (diltiazem-like) and verapamil recently have been shown to have most of these effects. Conversely, the dihydropyridine calcium antagonists (nifedipine, felodipine, nitrendipine) do not attenuate increases in most of these parameters. In several clinical studies, nifedipine either did not affect or increased urinary albumin excretion in diabetic patients with renal insufficiency. Moreover, in animal models of diabetes, most dihydropyridine compounds do not prevent progression of glomerulosclerosis in spite of blood pressure control. Although the majority of clinical studies support the concept that reduction of arterial pressure preserves renal function, recent long-term clinical studies show that ACE inhibitors and heart-rate-lowering calcium antagonists (diltiazem, verapamil) attenuate progression of diabetes to a greater extent than most other agents do.
Hoelscher
D
D
Department of Preventive Medicine, Rush Presbyterian/St. Luke's Medical Center, Chicago, Illinois.
Bakris
G
G
D000419:Albuminuria / Q000517:prevention & control; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000627:therapeutic use; D000818:Animals; D000959:Antihypertensive Agents / Q000627:therapeutic use*; D003928:Diabetic Nephropathies / Q000503:physiopathology*; D006439:Hemodynamics; D006801:Humans; D007668:Kidney / Q000503:physiopathology
D000806:Angiotensin-Converting Enzyme Inhibitors; D000959:Antihypertensive Agents