Abstract: SA-PO105
A Mouse Model of Moderate Diabetic Nephropathy on a Metabolic Syndrome Background
Session Information
- Diabetic Kidney Disease: Basic - III
October 27, 2018 | Location: Exhibit Hall, San Diego Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Diabetic Kidney Disease
- 601 Diabetic Kidney Disease: Basic
Authors
- van Koppen, Arianne, TNO, Leiden, Netherlands
- De Ruiter, Christa, TNO, Leiden, Netherlands
- Attema, Joline, TNO, Leiden, Netherlands
- Stokman, Geurt, TNO, Leiden, Netherlands
- Stoop, Reinout, TNO, Leiden, Netherlands
Background
Mouse models of diabetic nephropathy (DN) which not only recapitulate the early phases of the disease but also progress to a more advanced phase are urgently needed. We aim to develop a translational DN mouse model on metabolic syndrome background by incorporating the three main features of DN viz hyperglycemia, hyperlipidemia and hypertension.
Methods
Male KKAy mice were uninefrectomized and received high fat (45%) diet alone (HFD) or with prohypertensive (HFD+hyp) for 14 wk. At regular intervals, systolic blood pressure (SBP), 24h diuresis and plasma was collected. At sacrifice, GFR (inulin clearance) was determined, and renal injury was scored using histology. Age-matched chow-fed animals were controls.
Results
Mice fed with HFD developed hyperglycemia and hyperlipidemia. The prohypertensive group developed hypertension. GFR was significantly reduced in the HFD+hyp group compared to controls (2.5µl/min/g BW vs 4.6µl/min/g BW). Renal injury score showed glomerular hypertrophy, mesangium expansion, glomerulosclerosis, hyalinosis, micro-aneurisms and tubulo-interstitial fibrosis.
Conclusion
Combining three key features of DN in one mouse model induces moderate DN with a decline in GFR and morphological features resembling the human situation. We are currently forming a consortium to identify the temporal dynamics of key processes involved in disease development and progression.
Funding
- Government Support - Non-U.S.