Effect of antihypertensive treatment on progression of renal insufficiency in non-diabetics patients. (Espiral trial)

Abstract

A three year randomized, multicenter, prospective, open trial, will be developed with the aim of studying the influence of antihypertensive therapy on chronic renal failure progression in non-diabetics patients. The study will compare the effects of an angiotensin converting enzyme inhibitor, fosinopril, with a slow release calcium antagonist, nifedipine slow release. Two hundred and fifty patients, with progressively fallug renal function, shom by an increase of serum creatinine (SCr) of at least 25 % in the 2 years preceding entry to the study, and SCr levels between 1.5 and 4.0 mg/dl, will be included. The primary end point of the trial will be the rate of change of SCr (mg/dl/month) and of the reciprocal of serum creatinine concentration (1/SCr) over time. The secondary end point will be the percentage of patients with a doubling of SCr, progreswith to dialytic therapy, or deah during the study. Patients with nephrotic syndrome (serum albumin concentration < 3 g %), systemic disease (including diabetes), severe cardiac or hepatic dysfunction, malignant or renovascular hypertension, obstructive nephropathy, initial serum potassium concentration > 5.8 mmol/l and initial serum total cholesterol level ³ 270 mg/dl, will be excluded. After a «wash out» period of four weeks, patients with arterial blood pressure ³ 140/90 will be assigned either to fosinopril (10-30 mg/day) or nifedipine slow release (30-60 mg/day). In case of insufficient blood pressure control, furosemide (20- 100 mg/d) will be added as a first step and then atenolol (25-100 mg/d) and/or doxazosine (1-12 mg/d) in order to maintain arterial blood pressure control under 140/90. All patients will receive a diet with 4-5 g/day salt content and a protein content of 0.8-1 g/kg body weight. At the begining of the study, at 2, 4 and 8 weeks, and every 4 months, the following parameters will be measured: supine blood pressure after 5 minutes rest, body weight, SCr, 1/SCr, serum albumin, electrolytes and lipid pattern; urinary protein and urea concentrations and creatinine clearange. The relation between the progression chronic renal failure and ambulatory blood presure during 24 hours will be studied in some patients.