{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T16:30:03Z","timestamp":1790872203190,"version":"4.1.0"},"reference-count":46,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"1","funder":[{"name":"Cyclerion Therapeutics, Inc."}],"content-domain":{"domain":["lww.com","ovid.com"],"crossmark-restriction":true},"short-container-title":["CJASN"],"published-print":{"date-parts":[[2021,1]]},"abstract":"<jats:sec>\n                    <jats:title>Background and objectives<\/jats:title>\n                    <jats:p>Impaired nitric oxide signaling through soluble guanylate cyclase has been implicated in the pathophysiology of diabetic kidney disease. Praliciguat, a soluble guanylate cyclase stimulator that amplifies nitric oxide signaling, inhibited kidney inflammation and fibrosis in animal models.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Design, setting, participants, &amp; measurements<\/jats:title>\n                    <jats:p>\n                      In a phase 2 trial, 156 adults with type 2 diabetes, eGFR 30\u201375 ml\/min per 1.73 m\n                      <jats:sup>2<\/jats:sup>\n                      , and urine albumin-creatinine ratio 200\u20135000 mg\/g treated with renin-angiotensin system inhibitors were randomly allocated 1:1:1 to placebo, 20 mg praliciguat, or 40 mg praliciguat daily for 12 weeks. The primary efficacy and safety outcomes were change from baseline to weeks 8 and 12 in urine albumin-creatinine ratio and treatment-emergent adverse events, respectively. Other outcomes assessed were 24-hour ambulatory BP and metabolic parameters.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Of 156 participants randomized, 140 (90%) completed the study. The primary efficacy analysis demonstrated a mean change from baseline in urine albumin-creatinine ratio of \u221228% (90% confidence interval, \u221236 to \u221218) in the pooled praliciguat group and \u221215% (\u221228 to 0.4) in the placebo group (difference \u221215%; \u221231 to 4;\n                      <jats:italic toggle=\"yes\">P<\/jats:italic>\n                      =0.17). Between-group decreases from baseline to week 12 for praliciguat versus placebo were seen in mean 24-hour systolic BP (\u22124 mm Hg; \u22128 to \u22121), hemoglobin A1c (\u22120.3%; \u22120.5 to \u22120.03), and serum cholesterol (\u221210 mg\/dl; \u221219 to \u22121). The incidence of treatment-emergent adverse events was similar in the pooled praliciguat and placebo groups (42% and 44%, respectively). Serious adverse events, events leading to study drug discontinuation, and events potentially related to BP lowering were reported at higher frequency in the 40-mg group but were similar in 20-mg and placebo groups.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Praliciguat treatment for 12 weeks did not significantly reduce albuminuria compared with placebo in the primary efficacy analysis. Nonetheless, the observed changes in urine albumin-creatinine ratio, BP, and metabolic variables may support further investigation of praliciguat in diabetic kidney disease.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Clinical Trial registry name and registration number:<\/jats:title>\n                    <jats:p>A Study to Evaluate the Soluble Guanylate Cyclase (sGC) Stimulator IW-1973 in Diabetic Nephropathy\/Diabetic Kidney Disease as Measured by Albuminuria, NCT03217591<\/jats:p>\n                  <\/jats:sec>","DOI":"10.2215\/cjn.08410520","type":"journal-article","created":{"date-parts":[[2020,12,16]],"date-time":"2020-12-16T17:08:36Z","timestamp":1608138516000},"page":"59-69","update-policy":"https:\/\/doi.org\/10.1097\/lww.0000000000001000","source":"Crossref","is-referenced-by-count":43,"title":["Effects of the Soluble Guanylate Cyclase Stimulator Praliciguat in Diabetic Kidney Disease"],"prefix":"10.2215","volume":"16","clinical-trial-number":[{"clinical-trial-number":"nct03217591","registry":"10.18810\/clinical-trials-gov","type":"results"},{"clinical-trial-number":"nct03217591","registry":"10.18810\/clinical-trials-gov"}],"author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7095-9490","authenticated-orcid":false,"given":"John P.","family":"Hanrahan","sequence":"first","affiliation":[{"name":"Cyclerion Therapeutics, Inc., Cambridge, Massachusetts"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1571-7592","authenticated-orcid":false,"given":"Ian H.","family":"de Boer","sequence":"additional","affiliation":[{"name":"Department of Medicine, Kidney Research Institute, University of Washington, Seattle, Washington"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"George L.","family":"Bakris","sequence":"additional","affiliation":[{"name":"Department of Medicine, Comprehensive Hypertension Center, The University of Chicago Medicine, Chicago, Illinois"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Phebe J.","family":"Wilson","sequence":"additional","affiliation":[{"name":"Cyclerion Therapeutics, Inc., Cambridge, Massachusetts"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James D.","family":"Wakefield","sequence":"additional","affiliation":[{"name":"Cyclerion Therapeutics, Inc., Cambridge, Massachusetts"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jelena P.","family":"Seferovic","sequence":"additional","affiliation":[{"name":"Cyclerion Therapeutics, Inc., Cambridge, Massachusetts"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jennifer G.","family":"Chickering","sequence":"additional","affiliation":[{"name":"Cyclerion Therapeutics, Inc., Cambridge, Massachusetts"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yueh-tyng","family":"Chien","sequence":"additional","affiliation":[{"name":"Cyclerion Therapeutics, Inc., Cambridge, Massachusetts"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kenneth","family":"Carlson","sequence":"additional","affiliation":[{"name":"Cyclerion Therapeutics, Inc., Cambridge, Massachusetts"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael D.","family":"Cressman","sequence":"additional","affiliation":[{"name":"Cardiovascular\/Metabolic Unit, Covance Inc., Princeton, New Jersey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark G.","family":"Currie","sequence":"additional","affiliation":[{"name":"Cyclerion Therapeutics, Inc., Cambridge, Massachusetts"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"G. 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