BACKGROUND: Although controlling hyperglycemia and proteinuria is currently the main focus of diabetic kidney disease management, some existing drugs and other new compounds are being evaluated for their ability to interrupt the disease process. Specifically, drugs that interfere with the formation and action of advanced glycation end products and reduce or inhibit fibrosis of the glomerular structures in the presence of hyperglycemia are just 2 examples. OBJECTIVE: The aim is to provide an in-depth review of drugs currently being investigated to treat diabetic kidney disease (DKD) through novel mechanisms of action that interrupt the pathologic process. METHODS: A literature search was performed of the search engines PubMed (www.pubmed.gov) and ClinicalTrials.gov (www.clinicaltrials.gov), initially using the broad search terms diabetic nephropathy, diabetic kidney disease, and advanced glycation end products. Limits were set to include only English-language articles and studies performed in human subjects from January 2000. Previous review articles on this subject captured through the initial search also served as a basis for identifying drugs that had been under evaluation. Once a list of drugs and compounds was established, each agent was used as an independent search term through the same search engines listed to capture any new and/or ongoing studies for inclusion in this review. Any trials in DKD patients collected through this process were evaluated in this review including Phase I, II, and III studies. RESULTS: Fifteen drugs were identified, and 24 studies were reviewed. Ten drugs have evidence of beneficial effects in treating DKD patients as reported by improvements in glomerular filtration rate, albumin-to-creatinine ratio, proteinuria, or serum creatinine concentrations. Five drugs demonstrated no significant benefit or side-effect profiles that would prohibit their routine use. CONCLUSIONS: Pirfenidone, doxycycline, bardoxolone, pentoxifylline, ruboxistaurin, pyridoxamine, paricalcitol, FG-3019, AST-120, and allopurinol have shown beneficial effects in treating patients with DKD through modification of the pathologic mechanisms by which hyperglycemia alters the structure and function of the glomerulus. Further evaluation using well-controlled trials in larger patient populations are needed to confirm these benefits.
BACKGROUND: Although controlling hyperglycemia and proteinuria is currently the main focus of diabetic kidney disease management, some existing drugs and other new compounds are being evaluated for their ability to interrupt the disease process. Specifically, drugs that interfere with the formation and action of advanced glycation end products and reduce or inhibit fibrosis of the glomerular structures in the presence of hyperglycemia are just 2 examples. OBJECTIVE: The aim is to provide an in-depth review of drugs currently being investigated to treat diabetic kidney disease (DKD) through novel mechanisms of action that interrupt the pathologic process. METHODS: A literature search was performed of the search engines PubMed (www.pubmed.gov) and ClinicalTrials.gov (www.clinicaltrials.gov), initially using the broad search terms diabetic nephropathy, diabetic kidney disease, and advanced glycation end products. Limits were set to include only English-language articles and studies performed in human subjects from January 2000. Previous review articles on this subject captured through the initial search also served as a basis for identifying drugs that had been under evaluation. Once a list of drugs and compounds was established, each agent was used as an independent search term through the same search engines listed to capture any new and/or ongoing studies for inclusion in this review. Any trials in DKD patients collected through this process were evaluated in this review including Phase I, II, and III studies. RESULTS: Fifteen drugs were identified, and 24 studies were reviewed. Ten drugs have evidence of beneficial effects in treating DKD patients as reported by improvements in glomerular filtration rate, albumin-to-creatinine ratio, proteinuria, or serum creatinine concentrations. Five drugs demonstrated no significant benefit or side-effect profiles that would prohibit their routine use. CONCLUSIONS:Pirfenidone, doxycycline, bardoxolone, pentoxifylline, ruboxistaurin, pyridoxamine, paricalcitol, FG-3019, AST-120, and allopurinol have shown beneficial effects in treating patients with DKD through modification of the pathologic mechanisms by which hyperglycemia alters the structure and function of the glomerulus. Further evaluation using well-controlled trials in larger patient populations are needed to confirm these benefits.
Authors: A Cayir; R A Ugan; A Albayrak; D Kose; E Akpinar; Y Cayir; H T Atmaca; Z Bayraktutan; M Kara Journal: J Endocrinol Invest Date: 2015-04-07 Impact factor: 4.256
Authors: Pengfei Liu; Wang Tian; Shasha Tao; Joseph Tillotson; E M Kithsiri Wijeratne; A A Leslie Gunatilaka; Donna D Zhang; Eli Chapman Journal: Cell Chem Biol Date: 2019-08-08 Impact factor: 8.116
Authors: Laura A Maile; Walker H Busby; Katherine A Gollahon; William Flowers; Nikol Garbacik; Stefani Garbacik; Kara Stewart; Timothy Nichols; Dwight Bellinger; Amit Patel; Paul Dunbar; Matt Medlin; David Clemmons Journal: Endocrinology Date: 2014-08-29 Impact factor: 4.736
Authors: Laura A Maile; Katherine Gollahon; Christine Wai; Paul Dunbar; Walker Busby; David Clemmons Journal: J Diabetes Res Date: 2014-10-20 Impact factor: 4.011