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The Relationship of Diabetic Retinopathy to Preclinical Diabetic Glomerulopathy Lesions in Type 1 Diabetic Patients

The Renin-Angiotensin System Study

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

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.

Abbreviations: 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

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