Abstract: SA-PO113
Unilateral Nephrectomy and Salt Loading Differentially Alter Glomerular Filtration Rate in the Hypertensive, Obese, Type 2 Diabetic SDT Fatty Rat Model of Diabetic Nephropathy
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
- Briand, Francois, Physiogenex SAS, Labege, France
- Yamaguchi, Fuminari, Scohia Pharma Inc., Fujisawa, Japan
- Katayama, Yuko, Scohia Pharma, Inc., Fujisawa, KANAGAWA, Japan
- Suzuki, Tomohisa, Scohia Pharma, Inc., Fujisawa, Kanagawa, Japan
- Shinohara, Masami, CLEA Japan, Inc., Meguro, Japan
Background
Evaluation of drugs targeting diabetic nephropathy (DN) requires diabetic animal models developing renal complications and alteration of glomerular filtration rate (GFR) in a short period of time. These models should exhibit hyperfiltration followed by a >50% GFR decline. The hypertensive, obese, Spontaneously Diabetic Torii (SDT) fatty rat develops kidney lesions and may serve as a relevant model for DN. To promote alteration of GFR, we here evaluated the effects of unilateral nephrectomy (Unx) and salt loading in SDT fatty rats.
Methods
10-week old, male SDT fatty rats were included into 4 treatment groups (n=7/group): 1) normal water without Unx, 2) 0.3% salt water with Unx, 3) 0.6% salt water without Unx or 4) 0.8% salt water without Unx. Biochemical parameters and GFR were then followed for 13 weeks.
Results
Compared to SDT fatty rats under normal water without Unx, salt supplementation and Unx slightly attenuated the diabetic phenotype, with lower hyperglycemia (~400mg/dL vs. ~600mg/dL). However, it also resulted in a progressive induction of dyslipidemia, leading to a strong hypertriglyceridemia (~2000mg/dL vs. ~500mg/dL in rats under normal water without Unx) and hypercholesterolemia (~450mg/dL vs. ~150mg/dL) at 13 weeks. Under normal water without Unx, SDT fatty rats showed a gradual increase in hyperfiltration over 13 weeks with GFR raising from 13 +/- 2 to 22 +/- 5 mL/min/kg. This gradual increase was abolished by 0.6% salt without Unx, with stable GFR values over 13 weeks. However, 0.8% salt without Unx induced a progressive decline in GFR (36% lower at 13 weeks vs. baseline). In sharp contrast, 0.3% salt with Unx resulted in a rapid GFR decline from 2 weeks to 13 weeks (63% lower than baseline).
Conclusion
In the SDT fatty rat, Unx and salt loading have limited effect on diabetic state while they favor induction of dyslipidemia and differentially alter GFR. Depending on the experimental setting, this rat model should be helpful to evaluate the effects of drugs on hyperfiltration and GFR decline for the treatment of DN.
Funding
- Commercial Support – SCOHIA PHARMA Inc.