{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,20]],"date-time":"2026-10-20T11:39:31Z","timestamp":1792496371719,"version":"4.5.0"},"reference-count":19,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"4","license":[{"start":{"date-parts":[[2025,12,22]],"date-time":"2025-12-22T00:00:00Z","timestamp":1766361600000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100031531","name":"Travere Therapeutics, Inc.","doi-asserted-by":"crossref","id":[{"id":"10.13039\/100031531","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["lww.com","ovid.com"],"crossmark-restriction":true},"short-container-title":["CJASN"],"published-print":{"date-parts":[[2026,4]]},"abstract":"\n Key Points<\/jats:title>\n \n \n \n This analysis explored the association between complete remission of proteinuria and kidney function decline during sparsentan or irbesartan treatment.<\/jats:p>\n <\/jats:list-item>\n \n Patients achieving complete remission of proteinuria experienced better eGFR preservation and fewer kidney failure events.<\/jats:p>\n <\/jats:list-item>\n \n These data support Kidney Disease Improving Global Outcomes guideline recommendations to maintain proteinuria levels in IgA nephropathy ideally below 0.3 g\/d.<\/jats:p>\n <\/jats:list-item>\n <\/jats:list>\n <\/jats:p>\n <\/jats:sec>\n \n Background<\/jats:title>\n \n In the phase 3, randomized, double-blind PROTECT (NCT03762850) trial, sparsentan, a single-molecule dual endothelin angiotensin receptor antagonist, reduced proteinuria and preserved kidney function compared with maximum labeled dose irbesartan in adults with IgA nephropathy. In this\n post hoc<\/jats:italic>\n analysis of PROTECT, we assessed the association between complete remission of proteinuria (CR) and preservation of kidney function.\n <\/jats:p>\n <\/jats:sec>\n \n Methods<\/jats:title>\n This analysis compared kidney function in patients who achieved CR (urine protein excretion <0.3 g\/d) by week 36 (CR36) or at any time up to week 110 (CR110) versus those who did not (non-CR), regardless of original treatment allocation. End points assessed by CR status were change in proteinuria, eGFR, and BP, rate of eGFR decline, a composite kidney end point, and safety.<\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n \n Of 404 patients who were randomized and received study drug, 43 (11%) achieved CR36 and 85 (21%) achieved CR110. CR patients demonstrated greater and more rapid reductions in proteinuria compared with non-CR patients. CR110 patients had a smaller absolute change in eGFR versus non-CR patients (\u22124.0 versus \u22128.6 ml\/min per 1.73 m\n 2<\/jats:sup>\n ) and a slower rate of eGFR decline (day 1\u2013week 110; \u22120.7 versus \u22124.2 ml\/min per 1.73 m\n 2<\/jats:sup>\n per year). Fewer CR110 patients (1%) reached the composite kidney end point versus non-CR patients (14%). CR110 patients were more likely to experience treatment-emergent adverse events associated with hypotension (hypotension, orthostatic hypotension, or BP systolic decreased) and less likely to experience treatment-emergent adverse events of hypertension than non-CR patients. More non-CR patients versus CR110 patients discontinued treatment due to AEs (11% versus 4%, respectively) or patient decision (8% versus 2%, respectively).\n <\/jats:p>\n <\/jats:sec>\n \n Conclusions<\/jats:title>\n Participants in PROTECT who achieved CR36 or CR110 showed greater eGFR preservation, fewer kidney failure events, and similar safety profiles compared to non-CR participants. These data reinforce recommendations to maintain proteinuria levels ideally <0.3 g\/d and underscore its relationship with kidney function preservation.<\/jats:p>\n <\/jats:sec>\n \n Clinical Trial registry name and registration number:<\/jats:title>\n ClinicalTrials.gov, NCT03762850.<\/jats:p>\n <\/jats:sec>","DOI":"10.2215\/cjn.0000000961","type":"journal-article","created":{"date-parts":[[2025,12,22]],"date-time":"2025-12-22T17:00:34Z","timestamp":1766422834000},"page":"578-592","update-policy":"https:\/\/doi.org\/10.1097\/lww.0000000000001000","source":"Crossref","is-referenced-by-count":8,"title":["Association between Complete Proteinuria Remission and Kidney Function in the Phase 3 PROTECT Trial of Sparsentan in IgA Nephropathy"],"prefix":"10.2215","volume":"21","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3126-3730","authenticated-orcid":false,"given":"Hiddo J.L.","family":"Heerspink","sequence":"first","affiliation":[{"name":"Department of Clinical Pharmacy and Pharmacology, University of Groningen, University Medical Center, Groningen, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5639-0210","authenticated-orcid":false,"given":"Brad H.","family":"Rovin","sequence":"additional","affiliation":[{"name":"University Wexner Medical Center, Columbus, Ohio"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-7814-5324","authenticated-orcid":false,"given":"Radko","family":"Komers","sequence":"additional","affiliation":[{"name":"Travere Therapeutics, Inc., San Diego, California"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7950-7685","authenticated-orcid":false,"given":"Bruce","family":"Hendry","sequence":"additional","affiliation":[{"name":"Travere Therapeutics, Inc., San Diego, California"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-5279-1416","authenticated-orcid":false,"given":"Alex","family":"Mercer","sequence":"additional","affiliation":[{"name":"JAMCO Pharma Consulting, Stockholm, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3841-0414","authenticated-orcid":false,"given":"Priscila","family":"Preciado","sequence":"additional","affiliation":[{"name":"Travere Therapeutics, Inc., San Diego, California"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Edward","family":"Murphy","sequence":"additional","affiliation":[{"name":"Travere Therapeutics, Inc., San Diego, California"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6982-0689","authenticated-orcid":false,"given":"Vladimir","family":"Tesar","sequence":"additional","affiliation":[{"name":"General University Hospital, Charles University, 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