Renal and Retinal Effects of Enalapril and Losartan in Type 1 Diabetes
By M. Mauer, B. Zinman, R. Gardiner, S. Suissa, A. Sinaiko, T. Strand, K. Drummond, S. Donnelly, P. Goodyer, M. Gubler and 1 more. New England Journal of Medicine, 2009
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Background Nephropathy and retinopathy remain important complications of type 1 diabetes. It is unclear whether early administration of drugs that block the renin-angiotensin system slows their progression. Methods The Renin Angiotensin System Study [RASS] was a multicenter controlled trial in 285 normoalbuminuric, normotensive type 1 diabetic patients who were randomized to losartan (100mg daily), enalapril (20mg daily) or placebo and followed for 5 years. The primary endpoint was change in glomerular mesangial fractional volume in kidney biopsies. The retinopathy endpoint was a 2-step or greater progression in retinopathy severity scale. Intention-to-treat data analyses used linear and logistic regression models. Results Ninety and 82% of patients had complete renal biopsy and retinopathy data, respectively. Change in mesangial fractional volume per glomerulus over 5 years in placebo (0.016 units) was not significantly different from enalapril (p=0.38) or losartan (p=0.26), nor were there significant changes in other biopsy assessed renal structural variables. Five-year cumulative microalbuminuria incidence was higher for losartan than placebo (14% vs. 4%; logrank p=0.015) but not for enalapril (6% vs. 4%; logrank p=0.96). Two-step or more retinopathy progression incidence was reduced by 65% in the enalapril (O.R. 0.35; 95% C.I., 0.14–0.85) and 70% in the losartan group (O.R. 0.30; 95% C.I., 0.12–0.73) independent of changes in blood pressure. There were three biopsy-related serious adverse events that completely resolved. Chronic cough occurred in 12 enalapril, 6 losartan and 4 placebo patients. Conclusions Early renin-angiotensin system blockade did not modify nephropathy progression in type 1 diabetic patients, but had important effects in slowing retinopathy.
Subfields: Nephrology, Ophthalmology
View Paper: https://www.semanticscholar.org/paper/296941038b5b2943e46024dd57c0664eeca76e39
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Citations in the corpus
- Standards of Medical Care in Diabetes—2013 (2012, background): “ARBs do not prevent onset of albuminuria in normotensive patients with type 1 or type 2 diabetes (342,343); however, ARBs have been shown to reduce the rate of progression from micro- to macroalbuminuria as well as ESRD in patients with type 2 diabetes (344–346).”
- Standards of Medical Care in Diabetes—2014 (2013, background): “ARBs do not prevent onset of elevated albuminuria in normotensive patients with type 1 or type 2 diabetes (418,419); however, ARBs have been shown to reduce the progression rate of albumin levels from 30 to 299 mg/24 h to levels $300 mg/24 h as well as ESRD in patients with type 2 diabetes (420–422)”
- Diabetes and Hypertension: A Position Statement by the American Diabetes Association (2017, background): “In two trials of patients without albuminuria or hypertension, one including peoplewith type 1 diabetes (132) and the other type 2 diabetes (133), RAS inhibitors did not prevent the development of diabetic glomerulopathy assessed by kidney biopsy.”
- Renal Hemodynamic Effect of Sodium-Glucose Cotransporter 2 Inhibition in Patients With Type 1 Diabetes Mellitus (2014, result): “44 However, in contrast with RAAS inhibitors, which do not improve renal outcomes in normoalbuminuric patients with T1D and normal renal function, 45 our results suggest that SGlT2 inhibition reduces hyperfiltration, 4 which has been implicated in the initiation and progression of diabetic…”
- Standards of Medical Care in Diabetes—2012 (2011, background): “ARBs donot preventmicroalbuminuria in normotensive patients with type 1 or type 2 diabetes (301,302); however, ARBs have been shown to reduce the rate of progression from micro- to macroalbuminuria as well as ESRD in patients with type 2 diabetes (303–305).”
- Mechanisms of diabetic complications. (2013, result): “However, the role of specific interruption of the RAAS in the prevention and management of early diabetic nephropathy remains controversial, with recent relatively disappointing results in this context (46, 377).”
- KDOQI Clinical Practice Guideline for Diabetes and CKD: 2012 Update. (2012, background): “0% to prevent or delay progression of the microvascular complications of diabetes, including DKD. (1A) 2.2: We recommend not treating to an HbA 1c target of 7.0% in patients at risk of hypoglycemia.”
- Inflammation in Diabetic Retinopathy (2011, positive): “…can be reduced by aggressive intervention to control hyperglycemia (Diabetes Control and Complications Trial Research Group, 1993; UK Prospective Diabetes Study Group, 1998), blood pressure, and lipids (Chaturvedi et al., 1998; Mauer et al., 2009; UK Prospective Diabetes Study Group, 1998).”