{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T16:17:32Z","timestamp":1792685852379,"version":"4.5.0"},"reference-count":51,"publisher":"Elsevier BV","issue":"10","license":[{"start":{"date-parts":[[2021,10,1]],"date-time":"2021-10-01T00:00:00Z","timestamp":1633046400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2021,10,1]],"date-time":"2021-10-01T00:00:00Z","timestamp":1633046400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"},{"start":{"date-parts":[[2021,7,12]],"date-time":"2021-07-12T00:00:00Z","timestamp":1626048000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["kireports.org","elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["Kidney International Reports"],"published-print":{"date-parts":[[2021,10]]},"DOI":"10.1016\/j.ekir.2021.07.006","type":"journal-article","created":{"date-parts":[[2021,7,23]],"date-time":"2021-07-23T08:46:21Z","timestamp":1627029981000},"page":"2575-2584","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":40,"title":["Safety and Efficacy of GFB-887, a TRPC5 Channel Inhibitor, in Patients With Focal Segmental Glomerulosclerosis, Treatment-Resistant Minimal Change Disease, or Diabetic Nephropathy: TRACTION-2 Trial Design"],"prefix":"10.1016","volume":"6","author":[{"given":"Liron","family":"Walsh","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John F.","family":"Reilly","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Caitlin","family":"Cornwall","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gregory A.","family":"Gaich","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Debbie S.","family":"Gipson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3126-3730","authenticated-orcid":false,"given":"Hiddo J.L.","family":"Heerspink","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leslie","family":"Johnson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Howard","family":"Trachtman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2235-0103","authenticated-orcid":false,"given":"Katherine R.","family":"Tuttle","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Youssef M.K.","family":"Farag","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Krishna","family":"Padmanabhan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xin-Ru","family":"Pan-Zhou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James R.","family":"Woodworth","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Frank S.","family":"Czerwiec","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"key":"10.1016\/j.ekir.2021.07.006_bib1","doi-asserted-by":"crossref","first-page":"172","DOI":"10.1053\/snep.2003.50025","article-title":"Trends in the epidemiology of focal segmental glomerulosclerosis","volume":"23","author":"Kitiyakara","year":"2003","journal-title":"Semin Nephrol"},{"key":"10.1016\/j.ekir.2021.07.006_bib2","doi-asserted-by":"crossref","first-page":"414","DOI":"10.1093\/ndt\/gfq665","article-title":"The incidence of primary glomerulonephritis worldwide: a systematic review of the literature","volume":"26","author":"McGrogan","year":"2011","journal-title":"Nephrol Dial Transplant"},{"key":"10.1016\/j.ekir.2021.07.006_bib3","doi-asserted-by":"crossref","first-page":"702","DOI":"10.1681\/ASN.2012070734","article-title":"The treatment of minimal change disease in adults","volume":"24","author":"Hogan","year":"2013","journal-title":"J\u00a0Am Soc Nephrol"},{"key":"10.1016\/j.ekir.2021.07.006_bib4","series-title":"Comprehensive Clinical Nephrology","first-page":"218","article-title":"Minimal change nephrotic syndrome","author":"Mason","year":"2010"},{"key":"10.1016\/j.ekir.2021.07.006_bib5","doi-asserted-by":"crossref","first-page":"2032","DOI":"10.2215\/CJN.11491116","article-title":"Diabetic kidney disease: challenges, progress, and possibilities","volume":"12","author":"Alicic","year":"2017","journal-title":"Clin J Am Soc Nephrol"},{"key":"10.1016\/j.ekir.2021.07.006_bib6","series-title":"2019 USRDS Annual Data Report: Epidemiology of kidney disease in the United States","year":"2019"},{"key":"10.1016\/j.ekir.2021.07.006_bib7","doi-asserted-by":"crossref","first-page":"28","DOI":"10.1007\/s00467-006-0310-4","article-title":"Therapeutic approach to FSGS in children","volume":"22","author":"Gipson","year":"2007","journal-title":"Pediatr Nephrol"},{"key":"10.1016\/j.ekir.2021.07.006_bib8","doi-asserted-by":"crossref","first-page":"678","DOI":"10.1038\/ki.2010.485","article-title":"Clinical trials treating focal segmental glomerulosclerosis should measure patient quality of life","volume":"79","author":"Gipson","year":"2011","journal-title":"Kidney Int"},{"key":"10.1016\/j.ekir.2021.07.006_bib9","doi-asserted-by":"crossref","first-page":"97","DOI":"10.2147\/IJNRD.S126844","article-title":"Optimal management of primary focal segmental glomerulosclerosis in adults","volume":"10","author":"Beaudreuil","year":"2017","journal-title":"Int J Nephrol Renovasc Dis"},{"key":"10.1016\/j.ekir.2021.07.006_bib10","doi-asserted-by":"crossref","first-page":"195","DOI":"10.1007\/978-981-13-8871-2_10","article-title":"Role of podocyte injury in glomerulosclerosis","volume":"1165","author":"Lu","year":"2019","journal-title":"Adv Exp Med Biol"},{"key":"10.1016\/j.ekir.2021.07.006_bib11","doi-asserted-by":"crossref","first-page":"625","DOI":"10.1038\/s41581-020-0319-0","article-title":"Precision medicine in kidney disease: the patient\u2019s view","volume":"16","author":"Brown","year":"2020","journal-title":"Nat Rev Nephrol"},{"key":"10.1016\/j.ekir.2021.07.006_bib12","doi-asserted-by":"crossref","first-page":"734","DOI":"10.1016\/j.kint.2016.02.009","article-title":"Precision medicine comes of age in nephrology: identification of novel biomarkers and therapeutic targets for chronic kidney disease","volume":"89","author":"Wyatt","year":"2016","journal-title":"Kidney Int"},{"issue":"suppl 3","key":"10.1016\/j.ekir.2021.07.006_bib13","doi-asserted-by":"crossref","first-page":"14","DOI":"10.1111\/dom.13417","article-title":"New clinical trial designs for establishing drug efficacy and safety in a precision medicine era","volume":"20","author":"Heerspink","year":"2018","journal-title":"Diabetes Obes Metab"},{"issue":"suppl 4","key":"10.1016\/j.ekir.2021.07.006_bib14","doi-asserted-by":"crossref","first-page":"iv105","DOI":"10.1093\/ndt\/gfv210","article-title":"Drugs meeting the molecular basis of diabetic kidney disease: bridging from molecular mechanism to personalized medicine","volume":"30","author":"Heerspink","year":"2015","journal-title":"Nephrol Dial Transplant"},{"key":"10.1016\/j.ekir.2021.07.006_bib15","doi-asserted-by":"crossref","first-page":"1332","DOI":"10.1126\/science.aal4178","article-title":"A\u00a0small-molecule inhibitor of TRPC5 ion channels suppresses progressive kidney disease in animal models","volume":"358","author":"Zhou","year":"2017","journal-title":"Science"},{"key":"10.1016\/j.ekir.2021.07.006_bib16","doi-asserted-by":"crossref","first-page":"349","DOI":"10.1016\/j.kint.2017.03.010","article-title":"Rac1 activation in podocytes induces the spectrum of nephrotic syndrome","volume":"92","author":"Robins","year":"2017","journal-title":"Kidney Int"},{"key":"10.1016\/j.ekir.2021.07.006_bib17","doi-asserted-by":"crossref","first-page":"709","DOI":"10.1038\/ncb1150","article-title":"Rapid vesicular translocation and insertion of TRP channels","volume":"6","author":"Bezzerides","year":"2004","journal-title":"Nat Cell Biol"},{"key":"10.1016\/j.ekir.2021.07.006_bib18","doi-asserted-by":"crossref","first-page":"ra77","DOI":"10.1126\/scisignal.2001200","article-title":"Antagonistic regulation of actin dynamics and cell motility by TRPC5 and TRPC6 channels","volume":"3","author":"Tian","year":"2010","journal-title":"Sci Signal"},{"key":"10.1016\/j.ekir.2021.07.006_bib19","doi-asserted-by":"crossref","first-page":"98","DOI":"10.3389\/fmed.2018.00098","article-title":"Molecular mechanisms of proteinuria in focal segmental glomerulosclerosis","volume":"5","author":"Wen","year":"2018","journal-title":"Front Med (Lausanne)"},{"key":"10.1016\/j.ekir.2021.07.006_bib20","doi-asserted-by":"crossref","first-page":"4127","DOI":"10.1172\/JCI46458","article-title":"Arhgap24 inactivates Rac1 in mouse podocytes, and a mutant form is associated with familial focal segmental glomerulosclerosis","volume":"121","author":"Akilesh","year":"2011","journal-title":"J\u00a0Clin Invest"},{"key":"10.1016\/j.ekir.2021.07.006_bib21","doi-asserted-by":"crossref","first-page":"1969","DOI":"10.1681\/ASN.2011040370","article-title":"Balancing calcium signals through TRPC5 and TRPC6 in podocytes","volume":"22","author":"Greka","year":"2011","journal-title":"J\u00a0Am Soc Nephrol"},{"key":"10.1016\/j.ekir.2021.07.006_bib22","doi-asserted-by":"crossref","first-page":"3243","DOI":"10.1172\/JCI69134","article-title":"ARHGDIA mutations cause nephrotic syndrome via defective RHO GTPase signaling","volume":"123","author":"Gee","year":"2013","journal-title":"J\u00a0Clin Invest"},{"key":"10.1016\/j.ekir.2021.07.006_bib23","doi-asserted-by":"crossref","first-page":"607","DOI":"10.1681\/ASN.20203110S1607d","article-title":"Urinary Rac1, a novel predictive biomarker, is elevated in FSGS and diabetic nephropathy patients and reduced by TRPC5 inhibition with GFB-887 in a rat FSGS model (PO1965)","volume":"31","author":"Dagon","year":"2020","journal-title":"J\u00a0Am Soc Nephrol"},{"key":"10.1016\/j.ekir.2021.07.006_bib24","doi-asserted-by":"crossref","first-page":"342","DOI":"10.1038\/s41419-018-0353-z","article-title":"Podocyte-specific Rac1 deficiency ameliorates podocyte damage and proteinuria in STZ-induced diabetic nephropathy in mice","volume":"9","author":"Lv","year":"2018","journal-title":"Cell Death Dis"},{"key":"10.1016\/j.ekir.2021.07.006_bib25","doi-asserted-by":"crossref","first-page":"1579","DOI":"10.1021\/acsmedchemlett.9b00430","article-title":"Discovery of a potent and selective TRPC5 inhibitor, efficacious in a focal segmental glomerulosclerosis model","volume":"10","author":"Yu","year":"2019","journal-title":"ACS Med Chem Lett"},{"key":"10.1016\/j.ekir.2021.07.006_bib26","doi-asserted-by":"crossref","first-page":"5298","DOI":"10.1172\/JCI71165","article-title":"Inhibition of the TRPC5 ion channel protects the kidney filter","volume":"123","author":"Schaldecker","year":"2013","journal-title":"J\u00a0Clin Invest"},{"key":"10.1016\/j.ekir.2021.07.006_bib27","doi-asserted-by":"crossref","first-page":"761","DOI":"10.1016\/j.cell.2009.03.039","article-title":"Essential role for TRPC5 in amygdala function and fear-related behavior","volume":"137","author":"Riccio","year":"2009","journal-title":"Cell"},{"key":"10.1016\/j.ekir.2021.07.006_bib28","first-page":"398","article-title":"GFB-887, a small molecule inhibitor of TRPC5, attenuates proteinuria in animal models of FSGS, minimal change disease and diabetic nephropathy (TH-PO1063)","volume":"30","author":"Reilly","year":"2019","journal-title":"J\u00a0Am Soc Nephrol"},{"key":"10.1016\/j.ekir.2021.07.006_bib29","first-page":"30.891440","article-title":"A\u00a0translational kidney organoid system bolsters human relevance of clinical development candidate","volume":"12","author":"Westerling-Bui","year":"2019","journal-title":"bioRxiv"},{"key":"10.1016\/j.ekir.2021.07.006_bib30","first-page":"817","article-title":"Small molecule inhibition of TRPC5 protects against podocyte injury and proteinuria in FSGS (SA-PO317)","volume":"29","author":"Westerling-Bui","year":"2018","journal-title":"J\u00a0Am Soc Nephrol"},{"key":"10.1016\/j.ekir.2021.07.006_bib31","doi-asserted-by":"crossref","first-page":"586","DOI":"10.1681\/ASN.20203110S1586b","article-title":"GFB-887, a TRPC5 inhibitor, is safe and well tolerated and engages the TRPC5 target leading to reductions in urinary Rac1 in healthy subjects (PO1886)","volume":"31","author":"Walsh","year":"2020","journal-title":"J\u00a0Am Soc Nephrol"},{"key":"10.1016\/j.ekir.2021.07.006_bib32","series-title":"Adaptive designs for clinical trials of drugs and biologics guidance for industry","year":"2019"},{"key":"10.1016\/j.ekir.2021.07.006_bib33","doi-asserted-by":"crossref","first-page":"931","DOI":"10.1038\/nm.1857","article-title":"The actin cytoskeleton of kidney podocytes is a direct target of the antiproteinuric effect of cyclosporine A","volume":"14","author":"Faul","year":"2008","journal-title":"Nat Med"},{"key":"10.1016\/j.ekir.2021.07.006_bib34","doi-asserted-by":"crossref","first-page":"414","DOI":"10.2215\/CJN.04780517","article-title":"An outcomes-based definition of proteinuria remission in focal segmental glomerulosclerosis","volume":"13","author":"Troost","year":"2018","journal-title":"Clin J Am Soc Nephrol"},{"key":"10.1016\/j.ekir.2021.07.006_bib35","first-page":"380","article-title":"FSGS minimal change disease patient-reported outcome (PRO) measure development (TH-PO1000)","volume":"30","author":"Carlozzi","year":"2019","journal-title":"J\u00a0Am Soc Nephrol"},{"key":"10.1016\/j.ekir.2021.07.006_bib36","doi-asserted-by":"crossref","first-page":"84","DOI":"10.1186\/s12955-016-0483-x","article-title":"Standardizing disease-specific quality of life measures across multiple chronic conditions: development and initial evaluation of the QOL Disease Impact Scale (QDIS\u00ae)","volume":"14","author":"Ware","year":"2016","journal-title":"Health Qual Life Outcomes"},{"key":"10.1016\/j.ekir.2021.07.006_bib37","first-page":"43","article-title":"Improving single-item generic health survey measures","volume":"26","author":"Ware","year":"2017","journal-title":"Qual Life Res"},{"key":"10.1016\/j.ekir.2021.07.006_bib38","series-title":"U.S. Dept. of Health, Education, and Welfare, publication no. 76-338","author":"Guy","year":"1976"},{"key":"10.1016\/j.ekir.2021.07.006_bib39","first-page":"393","article-title":"Development of a clinician-reported outcome measure for edema assessment (TH-PO1047)","volume":"30","author":"Carlozzi","year":"2019","journal-title":"J\u00a0Am Soc Nephrol"},{"key":"10.1016\/j.ekir.2021.07.006_bib40","doi-asserted-by":"crossref","first-page":"2220","DOI":"10.1046\/j.1523-1755.1999.00778.x","article-title":"A\u00a0randomized trial of\u00a0cyclosporine in patients with steroid-resistant focal\u00a0segmental glomerulosclerosis. North America Nephrotic Syndrome Study Group","volume":"56","author":"Cattran","year":"1999","journal-title":"Kidney Int"},{"key":"10.1016\/j.ekir.2021.07.006_bib41","doi-asserted-by":"crossref","first-page":"868","DOI":"10.1038\/ki.2011.195","article-title":"Clinical trial of focal segmental glomerulosclerosis in children and young adults","volume":"80","author":"Gipson","year":"2011","journal-title":"Kidney Int"},{"key":"10.1016\/j.ekir.2021.07.006_bib42","doi-asserted-by":"crossref","first-page":"2019","DOI":"10.1111\/dom.13312","article-title":"Determining the optimal dose of atrasentan by evaluating the exposure-response relationships of albuminuria and bodyweight","volume":"20","author":"Koomen","year":"2018","journal-title":"Diabetes Obes Metab"},{"key":"10.1016\/j.ekir.2021.07.006_bib43","doi-asserted-by":"crossref","first-page":"2304","DOI":"10.2337\/dc10-0833","article-title":"Impact of baseline renal function on the efficacy and safety of aliskiren added to losartan in patients with type 2 diabetes and nephropathy","volume":"33","author":"Persson","year":"2010","journal-title":"Diabetes Care"},{"key":"10.1016\/j.ekir.2021.07.006_bib44","doi-asserted-by":"crossref","first-page":"2260","DOI":"10.1093\/ndt\/gft227","article-title":"Effects of paricalcitol on calcium and phosphate metabolism and markers of bone health in patients with diabetic nephropathy: results of the VITAL study","volume":"28","author":"Coyne","year":"2013","journal-title":"Nephrol Dial Transplant"},{"key":"10.1016\/j.ekir.2021.07.006_bib45","doi-asserted-by":"crossref","first-page":"56","DOI":"10.1681\/ASN.V7156","article-title":"A\u00a0randomized double-blind placebo-controlled trial of cyclosporine in steroid-resistant idiopathic focal segmental glomerulosclerosis in children","volume":"7","author":"Lieberman","year":"1996","journal-title":"J\u00a0Am Soc Nephrol"},{"key":"10.1016\/j.ekir.2021.07.006_bib46","doi-asserted-by":"crossref","first-page":"e21","DOI":"10.1053\/j.ajkd.2017.02.003","article-title":"AJKD atlas of renal pathology: calcineurin inhibitor nephrotoxicity","volume":"69","author":"Lusco","year":"2017","journal-title":"Am J Kidney Dis"},{"key":"10.1016\/j.ekir.2021.07.006_bib47","doi-asserted-by":"crossref","first-page":"685","DOI":"10.1081\/JDI-100101956","article-title":"The treatment of primary focal segmental glomerulosclerosis","volume":"22","author":"Korbet","year":"2000","journal-title":"Ren Fail"},{"key":"10.1016\/j.ekir.2021.07.006_bib48","doi-asserted-by":"crossref","first-page":"2398","DOI":"10.1056\/NEJMra1106556","article-title":"Focal segmental glomerulosclerosis","volume":"365","author":"D'Agati","year":"2011","journal-title":"N\u00a0Engl J Med"},{"key":"10.1016\/j.ekir.2021.07.006_bib49","doi-asserted-by":"crossref","first-page":"445","DOI":"10.2215\/CJN.03531006","article-title":"Adult minimal-change disease: clinical characteristics, treatment, and outcomes","volume":"2","author":"Waldman","year":"2007","journal-title":"Clin J Am Soc Nephrol"},{"key":"10.1016\/j.ekir.2021.07.006_bib50","doi-asserted-by":"crossref","first-page":"532","DOI":"10.1053\/j.ajkd.2017.04.023","article-title":"Development of focal segmental glomerulosclerosis patient-reported outcome measures: symptom diary and symptom impact questionnaire","volume":"70","author":"Mathias","year":"2017","journal-title":"Am J Kidney Dis"},{"key":"10.1016\/j.ekir.2021.07.006_bib51","doi-asserted-by":"crossref","first-page":"1369","DOI":"10.1111\/dom.13245","article-title":"Rationale and protocol of the Study Of diabetic Nephropathy with AtRasentan (SONAR) trial: a clinical trial design novel to diabetic nephropathy","volume":"20","author":"Heerspink","year":"2018","journal-title":"Diabetes Obes Metab"}],"container-title":["Kidney International Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S2468024921013000?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S2468024921013000?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2025,11,11]],"date-time":"2025-11-11T03:37:37Z","timestamp":1762832257000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S2468024921013000"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,10]]},"references-count":51,"journal-issue":{"issue":"10","published-print":{"date-parts":[[2021,10]]}},"alternative-id":["S2468024921013000"],"URL":"https:\/\/doi.org\/10.1016\/j.ekir.2021.07.006","relation":{},"ISSN":["2468-0249"],"issn-type":[{"value":"2468-0249","type":"print"}],"subject":[],"published":{"date-parts":[[2021,10]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Safety and Efficacy of GFB-887, a TRPC5 Channel Inhibitor, in Patients With Focal Segmental Glomerulosclerosis, Treatment-Resistant Minimal Change Disease, or Diabetic Nephropathy: TRACTION-2 Trial Design","name":"articletitle","label":"Article Title"},{"value":"Kidney International Reports","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.ekir.2021.07.006","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2021 Published by Elsevier, Inc., on behalf of the International Society of Nephrology.","name":"copyright","label":"Copyright"}]}}