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Nonproteinuric Diabetes-Associated Nephropathy in the Cohen Rat Model of Type 2 Diabetes

¹ Laboratory for Molecular Medicine and Israeli Rat Genome Center, Department of Nephrology and Hypertension, Faculty of Health Sciences, Barzilai Medical Center Campus of the Ben-Gurion University, Ashkelon, Israel
² Department of Ophthalmology, Sourasky Medical Center, Tel-Aviv, Israel
³ Department of Pathology, Barzilai Medical Center Campus of the Ben-Gurion University, Ashkelon, Israel
⁴ Department of Pathology, Sapir Medical Center, Kefar Saba, Israel
⁵ Goldschleger Eye Institute, Sheba Medical Center, Tel Hashomer, Israel
⁶ Soroka Medical Center, Faculty of Health Sciences, Ben-Gurion University, Beer Sheba, Israel
⁷ Hadassah Diabetes Research Center, Hadassah University Hospital, Jerusalem, Israel

The Cohen diabetic rat is an experimental model reminiscent of human type 2 diabetes. The aim of this study was to characterize the development of end-organ damage in this model. Cohen diabetic sensitive (CDs) and Cohen diabetic resistant (CDr) rats were fed regular diet or a diabetogenic diet. Glucose tolerance, renal function, and renal and retinal histology were studied at set intervals. CDs fed diabetogenic diet were the only strain that expressed the diabetic metabolic phenotype. In this strain, urinary protein excretion did not increase with the development of diabetes, but plasma urea and creatinine levels increased and creatinine clearance decreased. Light microscopy revealed in CDs enlarged glomeruli with increased mesangial matrix and thickening of the glomerular capillary wall; electron microscopy demonstrated thickened basement membrane and mesangial abundance. There was increased staining for type IV collagen in glomeruli and interstitium of CDs. The retinas of diabetic CDs demonstrated pathology consistent with nonproliferative diabetic retinopathy. The histological findings in the kidneys, the absence of proteinuria, the impairment in glomerular filtration, and the development of retinopathy in CDs are consistent with diabetes-associated nephropathy that is similar to a nonalbuminuric type of nephropathy associated with type 2 diabetes in humans.

Abbreviations: OGTT, oral glucose tolerance test; PAS, para-amino-salicylate

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