The high-energy diet/streptozotocin treated munich wistar fromter rats: a new experimental model of diabetes induction in established kidney disease

Objective: Chronic kidney disease (CKD) is especially prevalent in patients with diabetes mellitus (DM). We aim to induce diabetes in the Munich Wistar Frömter (MWF) rat, a genetic model of established CKD. Design and method: 16-week-old male MWF rats (n = 10 rats/group) were fed standard chow (MWF) or a high fat/high-sucrose diet for 6 weeks together with streptozotocin administration (STZ; 15mg/Kg i.p.) at the start of dietary exposure (MWF-D). Results: Water intake, urine excretion, GTT and HOMA-IR index evidenced the development of diabetes in MWF-D rats. Albuminuria was higher in MWF with no further effect of diabetes. However, renal expression of Kim-1 and Ngal, markers of renal damage, AT1R, AT2R and Collagen 1A1 were significantly higher in MWF-D rats. Perirenal adipose tissue (PRAT) amount was significantly higher in MWF-D rats and exhibited an upregulation of TNF-alpha and profibrotic factors (TGF-beta and Collagen 1A1), together with a downregulation of IL-10. Although blood pressure was not further increased by the induction of diabetes, heart weight and left ventricular wall thickness were higher in MWF-D, coincident with a reduction in systolic volume, but without a change in the ejection fraction. Conclusions: We propose the MWF-D rat as an experimental model of NDKD and suggest a strong relation between alterations in PRAT and increased renal damage.