NDT Advance Access originally published online on February 19, 2004
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Nephrol Dial Transplant (2004) 19: 1092-1097
Nephrol Dial Transplant Vol. 19 No. 5 © ERA-EDTA 2004; all rights reserved
Original Article
Long-term renal changes in the Goto-Kakizaki rat, a model of lean type 2 diabetes
1Medical Research Laboratories, Institute of Experimental Clinical Research, Aarhus University Hospital, 2Department of Cell Biology, Institute of Anatomy, Aarhus University, Aarhus, Denmark, 3Renal Unit, Department of Internal Medicine, Gent University Hospital, 4Department of Physiology and Physiopathology, Gent University, Gent and 5Renal Unit, Department of Internal Medicine, AZ Sint-Jan AV, Brugge, Belgium
Correspondence and offprint requests to: Bieke Schrijvers, Renal Unit, Gent University Hospital, Gent, Belgium. Email: Bieke.Schrijvers{at}UGent.be
Background. Type 2 diabetes has become the single most frequent cause of end-stage renal disease. The Goto–Kakizaki rat is currently used as a model for lean type 2 diabetes, but its renal changes have not been fully characterized. We investigated long-term functional and structural renal changes in the Goto–Kakizaki rat to evaluate if this animal model resembles the changes observed in human diabetic kidney disease.
Methods. Urinary albumin excretion, creatinine clearance and blood pressure were measured at the age of 2, 8 and 14 months in 12 female Goto–Kakizaki rats and 10 female, non-diabetic Wistar rats. To study kidney morphology, kidney weight, glomerular volume, basement membrane thickness, mesangial fraction and total mesangial volume were determined at 14 months.
Results. Urinary albumin excretion rose progressively over time in both groups, but was significantly higher in Goto–Kakizaki rats than in Wistar rats. Creatinine clearance decreased over time in Goto–Kakizaki rats but not in Wistar rats. Blood pressure was in the normotensive range in all animals throughout the study. Kidney weight, glomerular volume, basement membrane thickness, mesangial fraction and total mesangial volume were significantly higher in Goto–Kakizaki rats than in Wistar rats. Body weight and blood glucose levels were higher, whereas serum insulin levels were not different or lower in Goto–Kakizaki rats compared with Wistar rats.
Conclusion. The Goto–Kakizaki rat is a lean, hyperglycaemic, euinsulinaemic, normotensive experimental model of type 2 diabetes with robust functional and structural renal changes.
Keywords: albuminuria; basement membrane thickness; glomerular volume; Goto–Kakizaki rat; kidney; mesangium
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