Randomised controlled trial of enalapril and beta blockers in non-diabetic chronic renal failure.

Objective--To compare the ability of angiotensin converting enzyme inhibitors and [beta] blockers to slow the development of end stage renal failure in nondiabetic patients with chronic renal failure.

Design--Open randomised multicentre trial with three year follow up.

Setting--Outpatient department of six French hospitals.

Patients--100 hypertensive patients with chronic renal failure (initial serum creatinine 200-400 [micro]mol/l). 52 randomised to enalapril and 48 to [beta] blockers (conventional treatment).

Interventions--Enalapril or [beta] blocker was combined with frusemide and, if necessary, a calcium blocker or centrally acting drug in patients whose diastolic pressure remained above 90 mm Hg.

Results--17 patients receiving conventional treatment and 10 receiving enalapril developed end stage renal failure. The cumulative renal survival rate was significantly better in the enalapril group than in the conventional group (P<0.05). The slope of the reciprocal serum creatinine concentration was steeper in the conventionally treated patients (-6.89x[10.sup.-5]l/[micro]mol/month) than in the enalapril group (-4.17x[10.sup.-5]l/[micro]mol/month; P<0.05). No difference in blood pressure was found between groups.

Conclusion--In hypertensive patients with chronic renal failure enalapril slows progression towards end stage renal failure compared with [beta] blockers. This effect was probably not mediated through controlling blood pressure.

Introduction

Chronic renal diseases are characterised by a continual deterioration eventually leading to end stage renal failure and expensive renal replacement therapy. Renal function deteriorates independently of the initial cause of the renal disease, suggesting that there is a final common pathway.(1) Although the mechanisms underlying progression remain ill defined, experimental data on ratss with diabetes mellitus or reduced renal mass have suggested a role for alterations in glomerular haemodynamics(1) or for maladaptive glomerular hypertrophy,(2) which eventually leads to glomerular sclerosis and further deterioration of renal function. In these models antihypertensive treatment gave some protection against renal lesions, and thus indirectly slowed progression of renal damage. Angiotensin converting inhibitors were claimed to be better than conventional drugs,(3)(4) although this has been challenged.(5)

The clinical consequences of these experimental findings have so far been tested mainly in insulin dependent diabetic nephropathy, where the rate of progression is relatively rapid and uniform. Prospective studies have clearly shown the benefits of antihypertensive drugs,(6) and recently angiotensin converting enzyme inhibitors were found to give more protection than a conventional treatment including [beta] blockers.(7)

Few studies have looked at patients with chronic renal failure due to other renal diseases. These nephropathies are heterogeneous, with differing rates of progression of renal failure and more diverse mechanisms than those in the experimental renal ablation model and diabetic nephropathy. We conducted a randomised three year trial to compare the effects of two antihypertensive regimens on renal function in patients with various chronic renal diseases.

Patients and methods

We recruited patients aged 18 to 70 years with chronic renal failure as defined by a serum creatinine concentration of 200-400 [micro]mol/l. Patients were entered into a one month run in period, in which no antihypertensive drugs were taken, to assess blood pressure. Hypertension was defined as diastolic blood pressure above 90 mm Hg when not taking antihypertensive drugs.

We excluded patients with the nephrotic syndrome (serum albumin concentration <30 g/l); systemic diseases including diabetes; malignant hypertension; renovascular hypertension; evolving obstructive nephropathy; and serious …