Search

The progression of diabetic nephropathy can be positively influenced by maintaining a low blood pressure level. This has been shown in studies with conventional antihypertensive treatment as well as with ACE inhibitors. Whether the latter group of drugs is more effective remains to be proven and was the aim of our study. In a prospective randomized study we compared the effects of ACE inhibition and beta-blockade on retarding progression of renal function in IDDM patients with an early stage of overt diabetic nephropathy. Twenty-nine patients were studied for 2 years, 15 were randomized for treatment with captopril and 14 for atenolol. Every 6 weeks blood pressure and urinary albumin and total protein excretion were measured. GFR was measured every 6 months as 51Cr-EDTA clearance. Baseline values for blood pressure, renal function and albuminuria were identical in the two groups. The effect of both drugs on blood pressure was not significantly different. In the captopril-treated patients MAP before and after 2 years was 110 +/- 3 (SEM) and 100 +/- 2 mm Hg, respectively and in the atenolol-treated patients 105 +/- 2 vs 101 +/- 2 mm Hg. Both drugs reduced albuminuria and total proteinuria to the same extent. With captopril albuminuria decreased from 1549 (989-2399) to 851 (537-1380) mg/24 h and proteinuria from 2.5 (1.6-3.8) to 1.2 (0.8-1.8) g/24 h. With atenolol albuminuria decreased from 933 (603-1445) to 676 (437-1047) mg/24 h and proteinuria from 1.5 (1.0-2.4) to 0.9 (0.6-1.5) g/24 h.(ABSTRACT TRUNCATED AT 250 WORDS)

Angiotensin-converting enzyme (ACE) inhibitors decrease albuminuria in patients with diabetic nephropathy. To study the change in albuminuria in relation to changes in systemic and renal hemodynamics, nine normotensive patients with type 1 (insulin-dependent) diabetes mellitus and persistent proteinuria were given a single oral dose of 25 mg of the ACE inhibitor captopril. Blood pressure, glomerular filtration rate (GFR), effective renal plasma flow (ERPF), and albumin excretion rate (AER) were measured in two periods of 40 minutes before and in four periods of 40 minutes after administration of captopril. A constant water diuresis was maintained. Blood pressure did not decrease significantly (130/79 +/- 4/3 v 124/74 +/- 4/3 mm Hg; mean +/- SEM), median AER decreased from 403 (interquartile range [IQR], 812) micrograms/min to 333 (707) micrograms/min (P < 0.01). GFR did not change (123 +/- 13 v 117 +/- 14 mL/min), but ERPF increased significantly from 609 +/- 56 to 714 +/- 55 mL/min (P < 0.01). Consequently, the filtration fraction (FF; quotient of GFR and ERPF) decreased from 0.20 +/- 0.014 to 0.17 +/- 0.014 (P < 0.01). A strong correlation was found between the decrease of AER and the decrease of FF (rs = 0.75; P < 0.02). No correlation was found between the decrease in AER and changes in GFR or blood pressure. In the normotensive patient with diabetic nephropathy, captopril causes an acute reduction of AER, which is probably mediated by a lowering of the intraglomerular pressure.

In a double-blind, randomized, cross-over study in 23 diabetic patients, insulin treated (N = 11) or noninsulin treated (N = 12), with mild to moderate hypertension, the hypotensive effects of captopril and atenolol were compared. Five patients had overt diabetic nephropathy. All patients received 50 mg twice daily of either drug. Treatment periods lasted 6 weeks and were preceded and separated by a placebo period. Two patients dropped out, one because of intermittent claudication during atenolol, one with cardiac arrhythmia during placebo. Blood pressure was reduced from 165 +/- 5/96 +/- 1 to 154 +/- 5/89 +/- 2 mmHg (mean +/- SEM: P less than 0.01) during captopril and from 171 +/- 5/98 +/- 1 to 159 +/- 6/89 +/- 2 mmHg (P less than 0.01) during atenolol. These antihypertensive effects are not significantly different. There was a wide inter- and intraindividual variation in hypotensive response to both drugs, which may have important consequences for treatment strategies. No consistent differences between insulin and noninsulin treated patients were seen. Parameters of glycemic control did not change during any therapy, neither in insulin treated nor in non-insulin treated patients. Albuminuria and renal function did not change. During captopril treatment one patient complained of a non-productive cough. Two patients experienced a severe hypoglycemic reaction during atenolol. No other major side-effects were seen. In conclusion, this study showed equal hypotensive effectivity of 100 mg captopril and 100 mg atenolol daily in hypertensive diabetics, without evident effect on glycemic control.