The Novel Phosphate and Bile Acid Sequestrant Polymer SAR442357 Delays Disease Progression in a Rat Model of Diabetic Nephropathy.

The Journal of Pharmacology and Experimental Therapeutics
Tamara R CastañedaThomas Hübschle

Abstract

As a gut-restricted, nonabsorbed therapy, polymeric bile acid sequestrants (BAS) play an important role in managing hyperlipidemia and hyperglycemia. Similarly, nonabsorbable sequestrants of dietary phosphate have been used for the management of hyperphosphatemia in end-stage renal disease. To evaluate the potential utility of such polymer sequestrants to treat type 2 diabetes (T2D) and its associated renal and cardiovascular complications, we synthesized a novel polymeric sequestrant, SAR442357, possessing optimized bile acid (BA) and phosphate sequestration characteristics. Long-term treatment of T2D obese cZucker fatty/Spontaneously hypertensive heart failure F1 hybrid (ZSF1) with SAR442357 resulted in enhanced sequestration of BAs and phosphate in the gut, improved glycemic control, lowering of serum cholesterol, and attenuation of diabetic kidney disease (DKD) progression. In comparison, colesevelam, a BAS with poor phosphate binding properties, did not prevent DKD progression, whereas losartan, an angiotensin II receptor blocker that is widely used to treat DKD, showed no effect on hyperglycemia. Analysis of hepatic gene expression levels of the animals treated with SAR442357 revealed upregulation of genes responsible for...Continue Reading

References

Apr 8, 1998·American Journal of Kidney Diseases : the Official Journal of the National Kidney Foundation·G A BlockF K Port
May 18, 2000·The New England Journal of Medicine·W G GoodmanI B Salusky
Sep 22, 2001·The New England Journal of Medicine·B M BrennerUNKNOWN RENAAL Study Investigators
Jun 26, 2002·Kidney International·Glenn M ChertowUNKNOWN Treat to Goal Working Group
Jul 12, 2002·Kidney International·William BraunlinS Randall Holmes-Farley
Jun 15, 2004·Journal of Pharmaceutical and Biomedical Analysis·Ronald A SwearingenEugene F Barry
Jul 31, 2004·Journal of the American Society of Nephrology : JASN·Geoffrey A BlockGlenn M Chertow
Jul 31, 2004·Nephrology, Dialysis, Transplantation : Official Publication of the European Dialysis and Transplant Association - European Renal Association·Jürgen Floege, Markus Ketteler
Sep 18, 2004·Circulation Research·Sharon M Moe, Neal X Chen
May 4, 2005·Cardiovascular Drug Reviews·Karen L Steinmetz, Kristine S Schonder
Jun 3, 2005·Nephrology, Dialysis, Transplantation : Official Publication of the European Dialysis and Transplant Association - European Renal Association·Hans-Gernot AsmusJürgen Bommer
Mar 8, 2006·Clinical Chemistry and Laboratory Medicine : CCLM·Marc ContiSylvain Loric
Apr 25, 2006·Biostatistics·W Evan JohnsonAriel Rabinovic
Jul 10, 2007·Experimental Gerontology·Aarthi RamanDale A Schoeller
Aug 31, 2007·American Journal of Physiology. Renal Physiology·Karen A GriffinAnil K Bidani
Dec 7, 2007·Clinical Journal of the American Society of Nephrology : CJASN·Kayser CaglarPeter Stenvinkel
May 2, 2008·Kidney International·Keith A HruskaRaymond Pratt
Sep 9, 2008·Diabetic Medicine : a Journal of the British Diabetic Association·R Bilous
Sep 12, 2008·The New England Journal of Medicine·Rury R HolmanH Andrew W Neil
Apr 24, 2009·The American Journal of Clinical Nutrition·Rajni SinghConnie M Weaver
Dec 1, 2009·Kidney International. Supplement·Phyllis P SunBertrand L Jaber
Dec 10, 2009·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·Hilde HerremaFolkert Kuipers
Jun 10, 2010·Laboratory Investigation; a Journal of Technical Methods and Pathology·Johanna H M StroeveFolkert Kuipers
Jul 17, 2010·Endocrine Practice : Official Journal of the American College of Endocrinology and the American Association of Clinical Endocrinologists·Julio RosenstockMichael R Jones
May 6, 2011·Diabetes Care·Yehuda Handelsman
May 4, 2011·World Journal of Diabetes·Kohzo TakebayashiToshihiko Inukai
Jun 18, 2011·The Journal of Endocrinology·Victor P BilanStevan P Tofovic
Jul 26, 2011·Clinical Journal of the American Society of Nephrology : CJASN·Juan F Navarro-GonzálezJavier García-Pérez
Sep 7, 2011·Nature Reviews. Nephrology·Alastair J HutchisonPaul E C Brenchley
Dec 6, 2011·American Journal of Kidney Diseases : the Official Journal of the National Kidney Foundation·Mahmut Ilker YilmazCarmine Zoccali
Jan 14, 2012·Clinical Journal of the American Society of Nephrology : CJASN·Biagio Di IorioUNKNOWN INDEPENDENT Study Investigators
Jan 28, 2012·American Journal of Physiology. Gastrointestinal and Liver Physiology·Quan ShangGuorong Xu
Mar 31, 2012·Clinical Journal of the American Society of Nephrology : CJASN·Helen VlassaraGary E Striker
May 18, 2012·Bioinformatics·Jun HuKejun Liu
Jun 21, 2012·Fundamental & Clinical Pharmacology·Ahmed A MouradMohamed A El-Moselhy
Jun 29, 2012·Kidney International·Nicholas J A WebbChun Lam
Dec 22, 2012·American Journal of Physiology. Gastrointestinal and Liver Physiology·Matthew J PotthoffShawn C Burgess
May 21, 2013·American Journal of Kidney Diseases : the Official Journal of the National Kidney Foundation·Biagio Di IorioUNKNOWN INDEPENDENT Study Investigators
Feb 4, 2014·Genome Biology·Charity W LawGordon K Smyth

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