Transforming growth factor beta1 and additional renoprotective effect of combination ACE inhibitor and angiotensin II receptor blocker in hypertensive subjects with minor renal abnormalities: a 24-week randomized controlled trial

Objective: To verify the benefit of Renin-Angiotensin-system blockade in hypertension, the effects of 24 weeks losartan and ramipril treatment, both alone and in combination, on urinary albumin excretion (UAE) and circulating transforming growth factor β1 (TGF β1) have been evaluated in hypertensive subjects with minor renal abnormalities. Design and Methods: Fifty one patients with stage 1 essential hypertension and with UAE > 20 mg/24h but with maintened renal function have been included. After four weeks run in with placebo administration, a randomized double-blind, three arm double dummy trial was used. All the hypertensives (HT) were randomly allocated to three treatment arms (17 pts for each group) and they were single matched for age, gender, BMI, systolic and diastolic blood pressure. Active treatment consisted of losartan (50 mg/daily), ramipril (5 mg/daily), and combined (losartan 50 mg plus ramipril 5 mg/daily) for 24 weeks. Hydrochlorothiazide 12.5 mg/daily was added in HT patients with uncontrolled blood pressure (≥140/90 mmHg) during the active treatment period. In all patients UAE, by immunonephelometric assay, circulating TGFβ1 by a solid phase specific sandwich ELISA technique, BUN, creatinine and clearance and potassium by routine laboratory methods were determined after placebo treatment and 24 weeks follow-up. Results: The three treatment groups were comparable for gender, age, BMI, blood pressure, UAE and renal function measurements. During the active treatment period it has been necessary to add hydrochlorothiazide in five patients, respectively two of losartan and ramipril groups and one of combined group. At the end of treatment, a significant (p<0.05) reduction in systolic, diastolic and mean blood pressure, UAE and TGFβ1 levels were observed in all the groups. No change in renal function measurements were also observed. The absolute and percent reduction in UAE and TGFβ1 were significantly higher in combined group than losartan or ramipril group. No significant change in absolute and percent reduction of systolic, diastolic and mean blood pressure were found. All treatment regimens were well tolerated with few and transient side effects. Conclusion: These data indicate an additional renoprotective effect of dual blockade of Renin-Angiotensin-System (RAS) in hypertensive patients with minor renal abnormalities. In addition the contemporaneus and marked decrease in TGFβ1 and UAE levels in hypertensives treated with combined therapy might indicate the presence of subset of subjects who may particular benefit from complete RAS blockade.