Effect of angiotensin converting enzyme inhibitor or beta blocker on glomerular structural changes in young microalbuminuric patients with Type I (insulin-dependent) diabetes mellitus

Abstract

Long-term treatment with angiotensin converting enzyme inhibitors (ACEI) has a beneficial effect on the progression of microalbuminuria in patients with Type I (insulin-dependent) diabetes mellitus [1,2]. In addition, some clinical studies but not all [3±5] have suggested a superior effect of ACE-inhibitors over beta-blockers on the progressive decline in glomerular filtration rate (GFR) in Type I diabetic patients with nephropathy.Microalbuminuria predicts overt diabetic renal disease [6]. Still around 30 % of patients with low- Diabetologia (1999) Abstract Aims/hypothesis. To investigate the influence of angiotensin converting enzyme inhibitors and beta blockers on the progression of early diabetic glomerulopathy.Methods. Thirteen patients with Type I (insulin-dependent) diabetes mellitus (mean age 18.8 years) with microalbuminuria 31 (19±160) mg/min were randomised to treatment with enalapril (group 1, n = 7) or metoprolol (group 2, n = 6). Renal biopsies were taken before and after 38 (36±48) months of treatment. Albumin excretion rate, blood pressure and HbA 1 c were measured every third month. A reference group without antihypertensive treatment (group 3, n = 9), with similar age, diabetes duration and degree of microalbuminuria as group 1 and 2, had baseline and follow-up renal biopsies taken previously with an interval of 26±34 months, analysed at the same laboratory. Glomerular structures were measured by stereological methods.

The kidney in diabetes: dynamic pathways of injury and repair. The Camillo Golgi Lecture 2007

“…Indeed, there was no change over this time interval in any structural parameter in the enalapril, nifedipine or placebo groups. Another study compared renal structure before and after 38 months of treatment with enalapril or metoprolol in 13 type 1 diabetic patients with microalbuminuria [62], reporting no change over time in either group. In 19 type 2 diabetic patients, 2 years of treatment with perindopril prevented the progression of interstitial fibrosis compared with controls [63], without affecting glomerular structure.…”

“…Thus, as clearly demonstrated by the studies performed to date [61][62][63], clinical trials using renal structure as an endpoint, especially in the early stages of DN, require large numbers and, most importantly, a long follow-up duration (likely 7-10 years). This would require the cooperation of industries and national funding agencies, along with strong commitment from the investigators and patients.…”

Prevention and Regression of Chronic Kidney Disease and Hypertension

“…In the study on type 1 diabetic patients with microalbuminuria, treatment with enalapril, perindopril, or metoprolol resulted in a decrease in glomerular basement membrane thickness after 3-4 years of follow-up (Nankervis et al, 1998) (Rudberg et al, 1999). Other studies have suggested that glomerular volumes may be reduced by RAS inhibition, however the contribution of changes in blood pressure is unclear (Perrin et al, 2008).…”

Review: Early renal involvement in Type 1 diabetes mellitus — Part 2: ACE inhibitor intervention in Type 1 diabetes with low grade microalbuminuria

“…26 Thirteen patients with Type 1 diabetes mellitus and microalbuminuria were treated with either enalapril or metoprolol. Renal biopsies were taken before and after 38 months of treatment.…”

“…44 In a number of clinical trials encompassing microalbuminuric Type 1 diabetic patients, antihypertensive treatment in particular with ACE inhibitors (ACE-I), has been shown to reduce albuminuria. 45,46 Importantly, data suggesting positive effects on harder endpoints such as GFR 25 and glomerulopathy 26 are now emerging. At present, the consensus calls for antihypertensive treatment in most patients with microalbuminuria, regardless of BP.…”