Impact of renin angiotensin system blockade on night to day blood pressure ratio in diabetic nephropathy

Abstract

Sir, Elevated systemic blood pressure is a risk factor for progression of diabetic nephropathy. Ambulatory blood pressure measurements offer additional risk stratification compared to office blood pressure in patients with hypertension [1]. In addition, an abnormal diurnal blood pressure pattern characterized by an elevated night to day ratio is found more commonly in diabetic patients and, as reviewed by Miller et al. [2], is associated with poor renal outcome. The renin angiotensin system (RAS) is involved in both initiation and progression of diabetic nephropathy and blocking this system with ACE-inhibitors (ACE-I) and/or angiotensin II receptor blockers (ARBs) improves kidney survival and prognosis. Miller et al. [2] reported that treatment with enalapril (0.1 mg/kg BID) corrects the abnormally high night to day blood pressure ratio found in 10 uncomplicated adolescents, and this could contribute to the beneficial renoprotective effects of RAS blockade. In this letter, we further investigate whether RAS blockade corrects an abnormal 24 h blood pressure pattern by presenting data on the short-term effects of single and dual blockade of the RAS on a 24 h blood pressure profile and a night to day blood pressure ratio in type 1 diabetic patients with diabetic nephropathy. Our data are a post-hoc analysis of three earlier studies [3–5]. As described previously [3], we performed a randomized, double blind, cross-over trial, in which 18 patients received 8 weeks of placebo, benazepril 20 mg once daily, valsartan 80 mg once daily and a combination of benazepril 20 mg and valsartan 80 mg once daily in random order [3]. The main findings were: (1) mono-therapy with ACE-I or ARBs treatment was equally effective with regard to antialbuminuric and antihypertensive effects; (2) dual blockade of the RAS caused a further reduction in albuminuria of 43% and 7/6 mmHg in 24 h blood pressure compared with both mono-therapies; (3) night to day ratio of 24 h blood pressure on each treatment is shown in Table 1. A post-hoc power calculation estimated a power in each study of � 0.80 to detect a difference of 0.05 in night to day ratio with a significance level of 0.05. In agreement, when looking at the fraction of patients with night to day blood pressure ratio above the median on placebo treatment (>0.91), we found no changes in the night to day ratio on RAS blockade. Furthermore, in two other studies demonstrating that dual blockade of the RAS