Enalapril does not alter renal function in normotensive, normoalbuminuric, hyperfiltering Type 1 (insulin-dependent) diabetic children

Abstract

Summary. Using a prospective randomised double-blind crossover design, the effect of the angiotensin converting enzyme inhibitor enalapril compared to a placebo was studied in 18 normotensive, normoalbuminuric Type 1 (insulin-dependent) diabetic children. Each patient had a high normal or dearly elevated glomerular filtration rate (145 ml.min -1. 1.73 m 2 or higher) in the 6 months prior to the study. Enalapril, 0.5 mg.kg -1. day -1, was given for 4 weeks followed by placebo for 4 weeks, or vice versa. At the end of each period, glomerular filtration rate, renal plasma flow, blood pressure, plasma renin activity, and converting enzyme activity were determined. Enalapril caused significant reduction (p= < 0.001) in blood pressure and converting enzyme activity and a rise in plasma renin activity. A slight but not significant rise in glomerular filtration rate and renal plasma flow without change in filtration fraction was observed. These data suggest that the renin angiotensin system is not involved in the glomerular hyperfiltration of Type 1 diabetes, and can be interpreted as showing no evidence for the presence of intraglomerular hypertension in these patients.

The effects of candesartan on diabetes glomerulopathy: a double-blind, placebo-controlled trial

“…GFR tended to decline, but no significant difference was noted between groups. In MA type 1 diabetes patients treated with ACE-is or a betablocker during 3-5 years, GFR was not affected [20,25,26,31], although some observed an initial fall in GFR during the first 6 months of treatment [31]. The previously observed increase in severity of morphological changes between 10 and 16 years' duration in our NA/NT patients with diabetes [15] was not confirmed during the 5-year observation period of this study.…”

“…Although candesartan had no apparent effect on UAE, most of our patients had very low UAE at baseline and follow-up; the majority had no measurable UAE. In MA and proteinuric patients with diabetes, however, several authors have reported significant decline in UAE after treatment with ARBs and ACE-is [8,16,17,24,[26][27][28][29][30]. GFR tended to decline, but no significant difference was noted between groups.…”

“…We compared patients' renal function with that of healthy adolescents and young adults (presumptive kidney donors) who had been matched for age and gender on a group level and evaluated in our Pediatric Nephrology Unit at the Children's Hospital. Controls had a GFR of 114 (13) and 113 (14) ml/min per 1.73 m 2 , an ERPF of 626 (113) and 602 (106) ml/min per 1.73 m 2 and an FF of 18.8 (2.9)% and 19.2 (3)% at mean 25 (20)(21)(22)(23)(24)(25)(26)(27)(28)(29) years (46 controls) and 30 (29-31) (15 controls) years of age, respectively. Hyperfiltration was defined as GFR >2 standard deviations (SD) of controls.…”

Enalapril therapy in Type 1 (insulin-dependent) diabetic children

“…Dear Sir, While accepting the suggestion from Drummond et al [1] that an increase in glomerular filtration rate (GFR) is secondary to a rise in renal plasma flow, I am unsure that any other conclusions can be drawn from this study especially with reference to intervention for the prevention of long-term diabetic nephropathy. My concern centres around the selection of the subjects.…”

When to initiate ACEI/ARB therapy in patients with type 1 and 2 diabetes

“…Despite their small patient populations, these studies have often been characterized by careful clinical phenotyping (GFR by clearance methods) and even kidney biopsy. In addition to the above-mentioned study of Cook and colleagues [9], an 8-week cross-over study by Drummond and coworkers [42] of enalapril versus placebo in 18 normotensive, normoalbuminuric children with T1DM showed that the ACEI reduced blood pressure but had no short-term effect on the GFR or AER compared to placebo. A two-biopsy study by Rudberg and colleagues [43] compared 13 adolescent and young adult patients (mean age 18.8 years) with T1DM and microalbuminuria treated with either enalapril or metoprolol and also compared the outcomes with those of nine untreated T1DM control patients.…”