P0348THE DUAL ENDOTHELIN ETA AND ANGIOTENSIN AT1 RECEPTOR BLOCKER SPARSENTAN PROTECTS AGAINST THE DEVELOPMENT OF ALBUMINURIA AND GLOMERULOSCLEROSIS IN THE GDDY MOUSE MODEL OF IGA
| Autor: | Maiko Nakayama, Seiji Ueda, Celia Jenkinson, Yusuke Fukao, Radko Komers, Tomoyuki Otsuka, Yusuke Suzuki, Hitoshi Suzuki, Kai Liu, Hajime Nagasawa |
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| Rok vydání: | 2020 |
| Předmět: |
medicine.hormone
Transplantation medicine.medical_specialty Angiotensin II receptor type 1 business.industry Glomerulosclerosis Glomerulonephritis medicine.disease Endothelins Endocrinology Valsartan Nephrology Internal medicine Renin–angiotensin system medicine Albuminuria medicine.symptom business Endothelin receptor medicine.drug |
| Zdroj: | Nephrology Dialysis Transplantation. 35 |
| ISSN: | 1460-2385 0931-0509 |
| DOI: | 10.1093/ndt/gfaa142.p0348 |
| Popis: | Background and Aims gddY mice are an IgA nephropathy (IgAN)-prone mouse model that develops albuminuria by 8 weeks (wks) of age with glomerular IgA, IgG, and C3 deposits and progressive mesangioproliferative glomerulonephritis. A previous study in the ddY mouse model, the more genetically heterogeneous predecessor of gddY mice, using the endothelin type A receptor (ETAR) antagonist FR139317 resulted in amelioration of proteinuria and preservation of kidney function. Treatment of ddY mice with the angiotensin II type 1 receptor (AT1R) blocker valsartan resulted in significant protection from glomerulosclerosis (GS) without a significant prevention in proteinuria. Here we examined the effect of sparsentan (SP), a dual ETAR and AT1R blocker, currently in phase 3 trials for focal segmental glomerulosclerosis and IgAN, on the development of albuminuria and GS in gddY mice. Method gddY mice at 4 wks of age were fed with control (C) chow (n=5) or chow containing 900 ppm (n=10) or 1800 ppm (n=10) SP (approximately 180 and 360 mg/kg/day) for 8 wks. Albuminuria (U-Alb) was assessed at 4, 6, 8, and 12 wks of age and plasma levels of SP were determined at 8 am and 4 pm at wks 6, 8, and 12. Kidney biopsies were taken at the end of the study at 12 wks of age for processing and 30 glomeruli per animal were scored for the percentage of GS. Results gddY mice fed SP in the diet for 8 wks from 4 wks of age demonstrated significantly (*P Conclusion Eight weeks of treatment with SP attenuated increases in albuminuria and GS associated with the development of IgAN in gddY mice. If translated to the clinic, these data support SP as a new approach to the treatment of IgAN. |
| Databáze: | OpenAIRE |
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