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NDT Advance Access published online on February 19, 2004

Nephrology Dialysis Transplantation, doi:10.1093/ndt/gfh107
© 2004 by European Renal Association - European Dialysis and Transplant Association
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Received September 8, 2003
Accepted December 12, 2003


Original Article

Long-term renal changes in the Goto-Kakizaki rat, a model of lean type 2 diabetes

Bieke F. Schrijvers 1*, An S. De Vriese 2, Johan Van de Voorde 3, Ruth Rasch 4, Norbert H. Lameire 5, Allan Flyvbjerg 6

1 Medical Research Laboratories, Institute of Experimental Clinical Research, Aarhus University Hospital, Aarhus, Denmark; Renal Unit, Department of Internal Medicine, Gent University Hospital, Gent, Belgium
2 Renal Unit, Department of Internal Medicine, Gent University Hospital; Renal Unit, Department of Internal Medicine, AZ Sint-Jan AV, Brugge, Belgium
3 Department of Physiology and Physiopathology, Gent University, Gent, Belgium
4 Department of Cell Biology, Institute of Anatomy, Aarhus University, Aarhus, Denmark
5 Renal Unit, Department of Internal Medicine, Gent University Hospital, Gent, Belgium
6 Medical Research Laboratories, Institute of Experimental Clinical Research, Aarhus University Hospital, Aarhus, Denmark

* To whom correspondence should be addressed. E-mail: Bieke.Schrijvers{at}UGent.be.



  Abstract

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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