1. The Relationship of Diabetic Retinopathy to Preclinical Diabetic Glomerulopathy Lesions in Type 1 Diabetic Patients The Renin-Angiotensin System study(RASS) The American Diabetes Association DIABETES, VOL 54, FEBRUARY 2005

2. Background Epidemiological studies : association diabetic retinopathy and nephropathy Diabetic retinopathy more common than diabetic nephropathy : 90% vs 25~40 % of pts. with ≥ 20 years of type 1 diabetes Direct exam. of anatomical retinal change, whereas nephropathy defined by functional abnormalities. Only a few studies : relationship between the anatomical lesions of retinopathy and nephropathy To describe association of severity of retinopathy with histological measures of nephropathy

3. Research design and methods RASS is parallel, double-blind, placebo-controlled, multicenter, primary prevention clinical trial of diabetic nephropathy conducted conducted at three clinical centers in Minneapolis, Minnesota, and Montreal and Toronto, Canada. 285 pts. Subjects were aged ≥16 years with 2-20 years of type 1 diabetes and onset before their 45th birthday. Normotensive Normoalbuminuric (albumin excretion rate [AER] <20 µg/min on at least two of three timed overnight urine collections) Normal or increased glomerular filtration rate (GFR; ≥90 ml. Min -1. 1.73 m -2 )

4. Research design and methods Baseline examination Blood pressure Height and weight 30° color stereoscopic fundus photographs taken of the seven standard fields, as defined in the Early Treatment Diabetic Retinopathy Study (ETDRS) protocol : modified Airlie House classification scheme and the ETDRS retinopathy severity scale GFR HbA 1C Renal biopsy

5. Research design and methods Retinopathy level None Early nonproliferative diabetic retinopathy Moderate to severe nonproliferative diabetic retinopathy Proliferative diabetic retinopathy Renal anatomical end points GBM width Mesangial fractional volume/glomerulus ; Vv (Mes/glom) Mesangial matrix fraction volume /glomerulus ; Vv(MM/glom) Mesangial cell fractional volume ; Vv(MC/glom) Peripheral GBM surface density/glomerulus Glomerulopathy index = GBM width/10 + [Vv(MM/ glom) × 100]

6. Result

7. No diabetic retinopathy 35 % Mild nonproliferative diabetic retinopathy 54 % Moderate to severe nonproliferative diabetic retinopathy 9 % Proliferative diabetic retinopathy 2 %

13. Discussion Previous studies conducted in patient with severe diabetic retinopathy. The few subjects without clinical nephropathy or with minimal microalbuminuria → marked discordance → more robust sample and selection of individuals with no clinical nephropathy Stronger association when renal structural measures used as continuous rather than dichotomous variables ; wide normal ranges for renal structural measures GBM width increases appear linear with duration. ; little increase in mesangial fractional volume in the first 10~15 years

14. Conclusion Cross-sectional associations of retinopathy severity with renal anatomic measures in type 1 diabetic normotensive patients with preclinical nephropathy Longitudinal study of the RASS cohort