{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T23:53:01Z","timestamp":1792799581714,"version":"4.5.0"},"reference-count":48,"publisher":"Oxford University Press (OUP)","issue":"10","license":[{"start":{"date-parts":[[2018,11,1]],"date-time":"2018-11-01T00:00:00Z","timestamp":1541030400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81370011"],"award-info":[{"award-number":["81370011"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Xijing Hospital Foundation","award":["XJZT11Z01"],"award-info":[{"award-number":["XJZT11Z01"]}],"id":[{"id":"https:\/\/ror.org\/05cqe9350","id-type":"ROR","asserted-by":"crossref"}]},{"name":"National Key Technology Research and Development Program of the Ministry of Science and Technology of China","award":["2012BA111B02"],"award-info":[{"award-number":["2012BA111B02"]}],"id":[{"id":"https:\/\/ror.org\/02kv4zf79","id-type":"ROR","asserted-by":"crossref"}]},{"name":"Changjiang Scholars and Innovative Research Team in University of China","award":["IRT-14R08"],"award-info":[{"award-number":["IRT-14R08"]}]},{"name":"NIH\/NHLBI","award":["1 K23 HL128882-01A1"],"award-info":[{"award-number":["1 K23 HL128882-01A1"]}]},{"DOI":"10.13039\/100000002","name":"NIH","doi-asserted-by":"publisher","award":["R37 DK39773"],"award-info":[{"award-number":["R37 DK39773"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"NIH","doi-asserted-by":"publisher","award":["R01 DK072381"],"award-info":[{"award-number":["R01 DK072381"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100005294","name":"Massachusetts General Hospital","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100005294","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2018,11,15]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Rationale<\/jats:title>\n                    <jats:p>No medical intervention has been identified that decreases acute kidney injury and improves renal outcome at 1 year after cardiac surgery.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objectives<\/jats:title>\n                    <jats:p>To determine whether administration of nitric oxide reduces the incidence of postoperative acute kidney injury and improves long-term kidney outcomes after multiple cardiac valve replacement requiring prolonged cardiopulmonary bypass.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Two hundred and forty-four patients undergoing elective, multiple valve replacement surgery, mostly due to rheumatic fever, were randomized to receive either nitric oxide (treatment) or nitrogen (control). Nitric oxide and nitrogen were administered via the gas exchanger during cardiopulmonary bypass and by inhalation for 24 hours postoperatively.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Measurements and Main Results<\/jats:title>\n                    <jats:p>The primary outcome was as follows: oxidation of ferrous plasma oxyhemoglobin to ferric methemoglobin was associated with reduced postoperative acute kidney injury from 64% (control group) to 50% (nitric oxide group) (relative risk [RR], 0.78; 95% confidence interval [CI], 0.62\u20130.97; P\u2009=\u20090.014). Secondary outcomes were as follows: at 90 days, transition to stage 3 chronic kidney disease was reduced from 33% in the control group to 21% in the treatment group (RR, 0.64; 95% CI, 0.41\u20130.99; P\u2009=\u20090.024) and at 1 year, from 31% to 18% (RR, 0.59; 95% CI, 0.36\u20130.96; P\u2009=\u20090.017). Nitric oxide treatment reduced the overall major adverse kidney events at 30 days (RR, 0.40; 95% CI, 0.18\u20130.92; P\u2009=\u20090.016), 90 days (RR, 0.40; 95% CI, 0.17\u20130.92; P\u2009=\u20090.015), and 1 year (RR, 0.47; 95% CI, 0.20\u20131.10; P\u2009=\u20090.041).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>In patients undergoing multiple valve replacement and prolonged cardiopulmonary bypass, administration of nitric oxide decreased the incidence of acute kidney injury, transition to stage 3 chronic kidney disease, and major adverse kidney events at 30 days, 90 days, and 1 year.<\/jats:p>\n                    <jats:p>Clinical trial registered with ClinicalTrials.gov (NCT01802619).<\/jats:p>\n                  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