Effects of dihydropyridine calcium channel blockers, angiotensin-converting enzyme inhibition, and blood pressure control on chronic, nondiabetic nephropathies. Gruppo Italiano di Studi Epidemiologici in Nefrologia (GISEN).
Dihydropyridine-type calcium channel blockers (dihydropyridine CCB) adversely affect renal function in diabetes. The effects of dihydropyridine CCB on 24-h urinary protein excretion rate and GFR decline (deltaGFR) were prospectively evaluated in 117 nondiabetic patients with chronic, proteinuric nephropathies enrolled in the Ramipril Efficacy in Nephropathy study and randomized to angiotensin-converting enzyme inhibition (ACEI) or placebo plus conventional antihypertensive therapy. Sixty-three percent of patients were treated with dihydropyridine CCB. During follow-up, CCB-treated compared with no CCB patients had higher proteinuria (mean+/-SEM: 4.8+/-0.2 g/24 h versus 4.2+/-0.2 g/24 h, respectively, P = 0.015) and mean arterial BP (MAP). The difference in proteinuria was significant in the placebo group (5.1+/-0.2 g/24 h versus 4.3+/-0.3 g/24 h, P = 0.02), but not in the ACEI group (4.4+/-0.2 g/24 h versus 4.1+/-0.2 g/24 h). Of note, CCB-treated patients had significantly less proteinuria (P = 0.028) in the ACEI group compared with placebo. CCB-treated versus no CCB patients had a faster deltaGFR in the overall study population and in the placebo group, but not in the Ramipril group. Proteinuria was comparable in CCBtreated and no CCB patients for MAP < or = 100 mmHg, but was higher in CCB-treated patients for MAP >100 mmHg. Similarly, proteinuria was comparable in the placebo and in the ACEI group for MAP < or = 100 mmHg, but was higher in the placebo group for MAP >100 mmHg. In CCB- and placebo-treated patients, a linear correlation (P = 0.006 for both groups) was found between proteinuria and MAP values. MAP, proteinuria, and deltaGFR in patients given nifedipine versus those given other dihydropyridine CCB were comparable. Thus, in nondiabetic proteinuric nephropathies, dihydropyridine CCB may have an adverse effect on renal protein handling that depends on the severity of hypertension and is minimized by ACEI therapy or tight BP control. ACE inhibitors may electively limit proteinuria in patients on dihydropyridine CCB treatment and/or with uncontrolled hypertension.
Ruggenenti
P
P
Mario Negri Institute for Pharmacological Research, Clinical Research Center for Rare Diseases "Aldo e Cele Daccò, Ranica, Italy.
Perna
A
A
Benini
R
R
Remuzzi
G
G
D000293:Adolescent; D000328:Adult; D000368:Aged; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000627:therapeutic use*; D000959:Antihypertensive Agents / Q000627:therapeutic use*; D001794:Blood Pressure / Q000187:drug effects; D002121:Calcium Channel Blockers / Q000627:therapeutic use*; D002908:Chronic Disease; D004095:Dihydropyridines / Q000627:therapeutic use*; D005260:Female; D005919:Glomerular Filtration Rate / Q000187:drug effects; D006801:Humans; D007674:Kidney Diseases / Q000188:drug therapy* / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies
D000806:Angiotensin-Converting Enzyme Inhibitors; D000959:Antihypertensive Agents; D002121:Calcium Channel Blockers; D004095:Dihydropyridines