Volume 3 Issue 6
June 2018  
Article of Interest 
Schievink B et al. Early renin-angiotensin system intervention is more beneficial than late intervention in delaying ESRD in patients with type 2 diabetes. Diabetes, Obesity, and Metabolism. 2015.  ( Click to Access)

Context and Study Objective
Professional guidelines uniformly recommend angiotensin converting enzyme inhibitor (ACEi) or angiotensin receptor blocker (ARB) therapy for hypertensives with diabetes, particularly those with chronic kidney disease (CKD). However, certain patient populations are more likely to suffer complications such as kidney injury from these agents than to realize their nephroprotective effects. In this paper, Schievink endeavored to determine how many years end-stage renal disease (ESRD) would be delayed in hypertensive type 2 diabetics with renal dysfunction through the use of ACEi or ARBs.

Design, Setting, and Participants
Data from key trials (BENEDICT, IRMA-2, RENAALIDNT) quantifying the effect of ACEi/ARB therapy on diabetic nephropathy among type 2 diabetics with hypertension was extracted. After constructing a model of CKD progression from this information, time from disease onset to the need for dialysis or renal transplant was estimated among participants randomized to an ACEi/ARB or placebo. Renal insufficiency was graded as early  (glomerular filtration rate [GFR] >60mL/min/m2 and urinary albumin/creatinine <30 mg/g), moderate (GFR 30-60mL/min/m2 or urinary albumin/creatinine 30-300 mg/g), or advanced (GFR <30mL/min/m2 or urinary albumin/creatinine >300 mg/g).
-The CKD model generated was validated via internal and external data sets. 
-Characteristics of the aforementioned studies: 5025 subjects were followed for up to 3.7 years. Mean-age 60, men 60%,  African-American participation rate not specified. Bood Pressure (BP) upon entry 154/86 and termination 141/80 mm Hg. Cohort creatinine ranged from 0.9-2.4 mg/dL, GFR from 20-80 mL/min/m2,  HbA1c from 5.8-8.5%, albuminuria from 5-5200mg/g. 
-Figure:  With ACEi treatment from early CKD onwards, a 60 year old prolongs the onset of dialysis by 4 years; o nce advanced disease manifests, time to ESRD is delayed by  1.5 years. 
Clinical Perspective 
-This study depicts the natural history of diabetic (type 2) nephropathy reminding us that the progression from mild CKD to ESRD is a  decades-long process  even in the absence of an ACEi or  ARB
-Thus, one need not uniformly prescribe an ACEi for the indication of diabetic nephropathy if the patient's life expectancy is shorter than the predicted time to end-stage renal disease (e.g. the elderly with mild renal dysfunction). By administering ACEi/ARB on a case-by-case basis, acute kidney injury and other complications related to combined ACEi and diuretic therapy can be averted. 
-Given the high prevalence of diabetic renal insufficiency, why do more patients not require dialysis? Over the course of the study, 12% required dialysis but another 12% expired, commonly from a cardiovascular (CV) event. BP and lipid management are therefore imperative in this population. 
-Because of this CV burden, some believe that ACEi therapy is indicated for its cardio-protective effects in this group. However, I do not feel the evidence cited (HOPE trial) is sufficient to merit this broad recommendation.
-Study Limitations: Type 1 diabetics were not considered; declines in renal function are more gradual in the present era in which glycemic and BP targets are lower than those cited.   
-Disclosures: I have no conflicts to declare. 
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Creator & Author: Hillel Sternlicht, MD            
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