Emerging treatments
Novel therapies for CKD
Currently, there are many novel agents that are being investigated to slow progression of CKD. Most studies have focused on diabetic kidney disease; however, there are small clinical trials suggesting benefit of some agents in nondiabetic kidney disease. Antifibrotic agents such as tranilast have been shown to reduce the decline in kidney function and proteinuria; however, there has been concern for adverse hepatic and renal effects when used at higher doses in cardiology trials.[115]Vilayur E, Harris DC. Emerging therapies for chronic kidney disease: what is their role? Nat Rev Nephrol. 2009 Jul;5(7):375-83.
http://www.ncbi.nlm.nih.gov/pubmed/19455178?tool=bestpractice.com
Agents targeting glycosaminoglycan metabolism such as sulodexide, inhibitors of advanced glycation end products, and anti-inflammatory agents such as pentoxifylline have all demonstrated short-term effects in proteinuria reduction.[115]Vilayur E, Harris DC. Emerging therapies for chronic kidney disease: what is their role? Nat Rev Nephrol. 2009 Jul;5(7):375-83.
http://www.ncbi.nlm.nih.gov/pubmed/19455178?tool=bestpractice.com
[116]Li R, Xing J, Mu X, et al. Sulodexide therapy for the treatment of diabetic nephropathy, a meta-analysis and literature review. Drug Des Devel Ther. 2015 Dec 3;9:6275-83.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4671764/
http://www.ncbi.nlm.nih.gov/pubmed/26664049?tool=bestpractice.com
[117]Rhee SY, Kim YS. The role of advanced glycation end products in diabetic vascular complications. Diabetes Metab J. 2018 Jun;42(3):188-95.
https://e-dmj.org/DOIx.php?id=10.4093/dmj.2017.0105
http://www.ncbi.nlm.nih.gov/pubmed/29885110?tool=bestpractice.com
[118]Leporini C, Pisano A, Russo E, et al. Effect of pentoxifylline on renal outcomes in chronic kidney disease patients: a systematic review and meta-analysis. Pharmacol Res. 2016 May;107:315-32.
http://www.ncbi.nlm.nih.gov/pubmed/26995301?tool=bestpractice.com
How these agents will perform in large-scale randomized clinical trials remains to be seen. As of now, there are no novel approved therapies for the treatment of CKD.
Roxadustat
Roxadustat is an oral inhibitor of hypoxia-inducible factor (HIF) prolyl hydroxylase that stimulates erythropoiesis and regulates iron metabolism. It shows promise as an alternative to epoetin alfa as a therapy for anemia in patients with CKD. It is currently in phase III clinical trials.[119]Chen N, Hao C, Peng X, et al. Roxadustat for anemia in patients with kidney disease not receiving dialysis. N Engl J Med. 2019 Sep 12;381(11):1001-10.
https://www.nejm.org/doi/full/10.1056/NEJMoa1813599?url_ver=Z39.88-2003&rfr_id=ori%3Arid%3Acrossref.org&rfr_dat=cr_pub++0pubmed
http://www.ncbi.nlm.nih.gov/pubmed/31340089?tool=bestpractice.com
[120]Chen N, Hao C, Liu BC, et al. Roxadustat treatment for anemia in patients undergoing long-term dialysis. N Engl J Med. 2019 Sep 12;381(11):1011-22.
https://www.nejm.org/doi/full/10.1056/NEJMoa1901713?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub%20%200pubmed
http://www.ncbi.nlm.nih.gov/pubmed/31340116?tool=bestpractice.com
Veverimer
Veverimer is a nonabsorbed polymer which selectively binds and removes hydrochloric acid from the gastrointestinal lumen and is being investigated for the treatment of metabolic acidosis in patients with CKD. It has been shown to significantly increase serum bicarbonate concentration, with minimal adverse effects. The Food and Drug Administration is currently reviewing an application for approval.[121]Wesson DE, Mathur V, Tangri N, et al. Veverimer versus placebo in patients with metabolic acidosis associated with chronic kidney disease: a multicentre, randomised, double-blind, controlled, phase 3 trial. Lancet. 2019 Apr 6;393(10179):1417-27.
http://www.ncbi.nlm.nih.gov/pubmed/30857647?tool=bestpractice.com
[122]Wesson DE, Mathur V, Tangri N, et al. Long-term safety and efficacy of veverimer in patients with metabolic acidosis in chronic kidney disease: a multicentre, randomised, blinded, placebo-controlled, 40-week extension. Lancet. 2019 Aug 3;394(10196):396-406.
http://www.ncbi.nlm.nih.gov/pubmed/31248662?tool=bestpractice.com