The Relationship of Diabetic Retinopathy to Preclinical Diabetic Glomerulopathy Lesions in Type 1 Diabetic Patients The Renin-Angiotensin System Study Ronald Klein 1 , Bernard Zinman 2 , Robert Gardiner 3 , Samy Suissa 4 , Sandra M. Donnelly 5 , Alan R. Sinaiko 6 , Michael S. Kramer 7 , Paul Goodyer 8 , Scot E. Moss 1 , Trudy Strand 6 and Michael Mauer 6 1 Department of Ophthalmology and Visual Sciences, University of Wisconsin Medical School, Madison, Wisconsin 2 Division of Medicine, University of Toronto, Toronto, Ontario, Canada 3 Division of Medicine, McGill University, Montreal, Quebec, Canada 4 Departments of Epidemiology and Biostatistics and Medicine, McGill University, Montreal, Quebec, Canada 5 Department of Medicine, Samuel Lunenfeld Research Institute, Mount Sinai Hospital, University of Toronto, Toronto, Ontario, Canada 6 Department of Pediatrics, University of Minnesota, Minneapolis, Minnesota 7 Departments of Pediatrics and Epidemiology and Biostatistics, McGill University, Montreal, Quebec, Canada 8 Department of Pediatrics, McGill University, Montreal, Quebec, Canada Address correspondence to Ronald Klein, MD, MPH, Department of Ophthalmology and Visual Sciences, University of Wisconsin-Madison, 610 North Walnut St., 460 WARF Madison, WI 53726. E-mail: kleinr{at}epi.ophth.wisc.edu Abstract Few epidemiological data exist regarding the correlation of anatomic measures of diabetic retinopathy and nephropathy, especially early in the disease processes. The aim of this study was to examine the association of severity of diabetic retinopathy with histological measures of diabetic nephropathy in normoalbuminuric patients with type 1 diabetes. The study included participants ( n = 285) in the Renin-Angiotensin System Study (RASS; a multicenter diabetic nephropathy primary prevention trial) who were aged ≥16 years and had 2–20 years of type 1 diabetes with normal baseline renal function measures. Albumin excretion rate (AER), blood pressure, serum creatinine, and glomerular filtration rate (GFR) were measured using standardized protocols. Diabetic retinopathy was determined by masked grading of 30° color stereoscopic fundus photographs of seven standard fields using the Early Treatment Diabetic Retinopathy Study (ETDRS) severity scale. Baseline renal structural parameters, e.g., fraction of the glomerulus occupied by the mesangium or mesangial fractional volume Vv(Mes/glom) and glomerular basement membrane width, were assessed by masked electron microscopic morphometric analyses of research percutaneous renal biopsies. No retinopathy was present in 36%, mild nonproliferative diabetic retinopathy in 53%, moderate to severe nonproliferative diabetic retinopathy in 9%, and proliferative diabetic retinopathy in 2% of the cohort. Retinopathy was not related to AER, blood pressure, serum creatinine, or GFR. All renal anatomical end points were associated with increasing severity of diabetic retinopathy, while controlling for other risk factors. These data demonstrate a significant association between diabetic retinopathy and preclinical morphologic changes of diabetic nephropathy in type 1 diabetic patients. AER, albumin excretion rate ETDRS, Early Treatment Diabetic Retinopathy Study GBM, glomerular basement membrane GFR, glomerular filtration rate RASS, Renin-Angiotensin System Study Sv(PGBM), surface density of peripheral glomerular capillary GBM Vv(MC/glom), fractional volume of the glomerulus occupied by mesangial cells Footnotes R.K. has received honoraria for serving on the steering committee for the DIRECT Program from Astra-Zeneca. R.G. holds stock in and has received consulting fees from Merck. S.M.D. has received consulting fees from Merck. Accepted October 19, 2004. Received July 30, 2004. DIABETES