{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,2]],"date-time":"2026-11-02T21:58:01Z","timestamp":1793656681102,"version":"4.5.1"},"reference-count":32,"publisher":"Oxford University Press (OUP)","issue":"6","license":[{"start":{"date-parts":[[2024,12,4]],"date-time":"2024-12-04T00:00:00Z","timestamp":1733270400000},"content-version":"vor","delay-in-days":1,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/100004326","name":"Bayer AG","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100004326","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2025,5,30]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n               <jats:sec>\n                  <jats:title>Background and hypothesis<\/jats:title>\n                  <jats:p>In chronic kidney disease (CKD) the nitric oxide (NO)\u2212soluble guanylate cyclase (sGC)\u2212cyclic guanosine monophosphate (cGMP) pathway is impaired. Runcaciguat, an sGC activator, activates heme-free sGC, restoring cGMP production. This phase 2a trial studied the efficacy, safety, and tolerability of runcaciguat in CKD patients with or without sodium-glucose co-transporter-2 inhibitor (SGLT2i).<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>Patients with CKD and established atherosclerotic cardiovascular disease or heart failure, plus type 2 diabetes (T2D) and\/or hypertension, were enrolled. All were receiving stable maximum tolerated renin\u2212angiotensin system inhibitors with or without SGLT2i. They were randomized 3:1 to runcaciguat once daily, titrated weekly (30\u2013120\u00a0mg if tolerated), or placebo for 8 weeks. The primary efficacy endpoint was urine albumin-to-creatinine ratio (UACR) (average of post-randomization Days 22, 29, and 57\u00a0vs baseline). CONCORD was separately powered for CKD and T2D with stable SGLT2i comedication, CKD and T2D without SGLT2i, and non-diabetic CKD.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>Of 243 patients randomized, 229 were included in the full analysis set (FAS) and 170 in the per-protocol set (PPS). In the PPS, UACR decreased by \u221245.2% versus placebo with runcaciguat in patients with CKD without SGLT2i (P\u00a0&amp;lt;\u00a00.001) and by \u221248.1% versus placebo in patients with CKD taking SGLT2i (P\u00a0=\u00a00.02) In the FAS, the relative reductions were \u221246.9% (P\u00a0&amp;lt;\u00a00.001) and \u221244.8% (P\u00a0=\u00a00.01), respectively. No significant difference was observed between patients with or without SGLT2i. In non-diabetic CKD, UACR was reduced versus baseline with runcaciguat, but the change was not statistically significant (P\u00a0=\u00a00.10). Serious treatment-emergent adverse events were reported in 7% of patients receiving runcaciguat and 8% receiving placebo.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusion<\/jats:title>\n                  <jats:p>Runcaciguat improved albuminuria in patients with CKD, irrespective of concomitant SGLT2i. Runcaciguat was well tolerated. sGC activation may represent a novel kidney-protective treatment in CKD patients (funded by Bayer AG; ClinicalTrials.gov number, NCT04507061).<\/jats:p>\n               <\/jats:sec>","DOI":"10.1093\/ndt\/gfae261","type":"journal-article","created":{"date-parts":[[2024,12,10]],"date-time":"2024-12-10T18:01:57Z","timestamp":1733853717000},"page":"1147-1160","source":"Crossref","is-referenced-by-count":23,"title":["The soluble guanylate cyclase activator runcaciguat significantly improves albuminuria in patients with chronic kidney disease: a randomized placebo-controlled clinical trial"],"prefix":"10.1093","volume":"40","author":[{"given":"Ron T","family":"Gansevoort","sequence":"first","affiliation":[{"name":"University Medical Center Groningen Department of Nephrology, , Groningen ,","place":["The Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David 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,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mario","family":"Berger","sequence":"additional","affiliation":[{"name":"Bayer AG Department of Reasearch & Develoment, , Berlin ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefan","family":"Klein","sequence":"additional","affiliation":[{"name":"Bayer AG Department of Reasearch & Develoment, , Berlin ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Frauke","family":"Friedrichs","sequence":"additional","affiliation":[{"name":"Bayer AG Department of Reasearch & Develoment, , Berlin ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karen","family":"Paraschin","sequence":"additional","affiliation":[{"name":"Bayer AG Department of Reasearch & Develoment, , Berlin ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roland 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