RENAL-FUNCTION AND REQUIREMENT FOR DIALYSIS IN CHRONIC NEPHROPATHY PATIENTS ON LONG-TERM RAMIPRIL - REIN FOLLOW-UP TRIAL

Background The Ramipril Efficacy In Nephropathy (REIN) study found tha t in patients with chronic nephropathies and proteinuria of 3 g or mor e per 24 h, ramipril safely reduced the rate of decline of the glomeru lar filtration rate (GFR) and halved the combined risk of doubling of serum creatinine or end-stage renal failure (ESRF), as compared with p lacebo plus conventional antihypertensive drugs at the same level of b lood pressure control. At the end of the core study patients continued on or shifted to ramipril and were formally enrolled into the REIN fo llow-up study. Methods 97 patients entered the follow-up study. Patien ts originally randomised to ramipril continued with the same daily dos e (n=51), whereas those originally on placebo plus conventional antihy pertensive drugs switched to ramipril after the first visit of the fol low-up study (n=46). Ramipril (1.25 to 5.00 mg/day) and conventional a ntihypertensive therapy were targeted at achieving diastolic blood pre ssure under 90 mm Hg. The main efficacy variables were GFR decline and ESRF (need for dialysis). Analysis was by intention to treat. Finding s During the follow-up study the mean rate of GFR decline per month de creased from 0.44 (SD 0.54) mL/min per 1.73 m(2) in the core study to 0.10 (0.50) mL/min per 1.73 m(2) in patients originally randomised to ramipril (p=0.017), and from 0.81 (1.12) to 0.14 (0.87) mL/min per 1.7 3 m(2) in those originally randomised to placebo plus conventional ant ihypertensive therapy (p=0.017). At the final visit, mean absolute GFR values were 12 mL/min per 1.73 m(2) higher (33% better) in patients r andomised to ramipril than in those assigned placebo (n=26 and 17, res pectively: 35.5 [19.0] vs 23.8 [9.4] mL/min per 1.73 m(2), p=0.01). 19 of the patients originally on ramipril versus 35 switched from placeb o to ramipril progressed to ESRF (p=0.027) during the whole observatio n period; of these, six (8%) versus 14 (16%) reached that endpoint dur ing the follow-up study; and the risk ratios were 1.86 (95% Cl 1.07-3. 26) over the whole observation period and 2.95 (1.13-7.68) during foll ow-up. Beyond follow-up at month 36, the incidence of ESRF was zero in patients originally randomised to ramipril but 30% in patients on pla cebo plus conventional antihypertensive therapy. Interpretation In pat ients with chronic nephropathy and high risk of rapid progression to E SRF, ramipril reversed the tendency of GFR to decline with time. Moreo ver, a treatment period of sufficient duration (greater than or equal to 36 months) eliminated the need for dialysis. Even patients previous ly treated with antihypertensive drugs other than angiotensin-converti ng-enzyme inhibitors benefited shifting to ramipril.