The effects of an ACE inhibitor and a calcium antagonist on the progression of renal disease: the Nephros Study

Background. The renoprotective effect of ACE inhibition in chronic renal disease is well established but the studies on effects of calcium antagonists on progression of renal disease and on proteinuria have given varying results. Methods. We conducted an open long-term randomized prospective multi-centre study comparing the combination of ramipril (R) and felodipine ER (F) with either drug alone in non-diabetic renal disease. Included were patients with uncontrolled hypertension (diastolic blood pressure (DBP)) greater than or equal to 95 mmHg on treatment with a diuretic and a beta-blocker. Fifty-one patients received the combination of R and F. 54 patients R, and 53 patients F. The treatment goal was a DBP <90 mmHg and a similar BP reduction in the three groups. Mean doses at the last visit were 5 + 5, 10 and 9 mg, respectively, after a mean treatment time of nearly 2 years. The progression of renal impairment was Studied by serial measurements of serum creatinine. iohexol clearance, and albuminuria. Results. The reduction in supine systolic (S) BP and DBP expressed as median values were -19.0 -14.5, -14.3 -15.0 and -13.5 -13.3 mmHg in the R + F. R, and F groups, respectively. There was no significant difference between the groups. When correction for the acute drug effect was performed the R + F group had a slower progression rate of the renal disease (loss of glomerular filtration rate (GFR) ml/min/year) compared with the F group (P < 0.05) but not to the R group (P > 0.20). There was a rise in albuminuria after 2 years in the F group (P < 0.05), but no significant change was found in the other groups. Conclusions. In patients with non-diabetic renal disease the combination of an ACE inhibitor and a calcium antagonist in reduced doses used in addition to baseline therapy with beta-blockers and diuretics, tended to cause a better BP reduction as each drug per se. The R + F treatment also caused a slower progression of the renal disease compared with F alone. The combination treatment seems to afford better BP control and appears to be a favourable therapeutic option in patients with renal disease and hypertension.