{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T09:45:12Z","timestamp":1791279912741,"version":"4.1.0"},"reference-count":37,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"4","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["JAHA"],"published-print":{"date-parts":[[2015,4,22]]},"abstract":"\n Background<\/jats:title>\n \n Serum bicarbonate varies over time in chronic kidney disease (\n CKD<\/jats:styled-content>\n ) patients, and this variability may portend poor cardiovascular outcomes. The aim of this study was to conduct a time\u2010updated longitudinal analysis to evaluate the association of serum bicarbonate with long\u2010term clinical outcomes: heart failure, atherosclerotic events, renal events (halving of estimated glomerular filtration rate [\n eGFR<\/jats:styled-content>\n ] or end\u2010stage renal disease), and mortality.\n <\/jats:p>\n <\/jats:sec>\n \n Methods and Results<\/jats:title>\n \n Serum bicarbonate was measured annually, in 3586 participants with\n CKD<\/jats:styled-content>\n , enrolled in the Chronic Renal Insufficiency Cohort (\n CRIC<\/jats:styled-content>\n ) study. Marginal structural models were created to allow for integration of all available bicarbonate measurements and proper adjustment for time\u2010dependent confounding. During the 6\u00a0years follow\u2010up, 512 participants developed congestive heart failure (26\/1000\u00a0person\u2010years) and 749 developed renal events (37\/1000\u00a0person\u2010years). The risk of heart failure and death was significantly higher for participants who maintained serum bicarbonate >26\u00a0mmol\/L for the entire duration of follow\u2010up (hazard ratio [\n HR<\/jats:styled-content>\n ] 1.66; 95% confidence interval [\n CI<\/jats:styled-content>\n ], 1.23 to 2.23, and\n HR<\/jats:styled-content>\n 1.36, 95%\n CI<\/jats:styled-content>\n 1.02 to 1.82, respectively) compared with participants who kept their bicarbonate 22 to 26 mmol\/L, after adjusting for demographics, co\u2010morbidities, medications including diuretics,\n eGFR,<\/jats:styled-content>\n and proteinuria. Participants who maintained serum bicarbonate <22\u00a0mmol\/L had almost a 2\u2010fold increased risk of renal disease progression (\n HR<\/jats:styled-content>\n 1.97; 95%\n CI<\/jats:styled-content>\n , 1.50 to 2.57) compared with participants with bicarbonate 22 to 26 mmol\/L.\n <\/jats:p>\n <\/jats:sec>\n \n Conclusion<\/jats:title>\n \n In this large\n CKD<\/jats:styled-content>\n cohort, persistent serum bicarbonate >26\u00a0mmol\/L was associated with increased risk of heart failure events and mortality. Further studies are needed to determine the optimal range of serum bicarbonate in\n CKD<\/jats:styled-content>\n to prevent adverse clinical outcomes.\n <\/jats:p>\n <\/jats:sec>","DOI":"10.1161\/jaha.114.001599","type":"journal-article","created":{"date-parts":[[2015,4,21]],"date-time":"2015-04-21T01:32:48Z","timestamp":1429579968000},"update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":80,"title":["Persistent High Serum Bicarbonate and the Risk of Heart Failure in Patients With Chronic Kidney Disease (CKD): A Report From the Chronic Renal Insufficiency Cohort (CRIC) Study"],"prefix":"10.1161","volume":"4","author":[{"given":"Mirela","family":"Dobre","sequence":"first","affiliation":[{"name":"Division of Nephrology and Hypertension, Case Western Reserve University, University Hospital Case Medical Center, Cleveland, OH"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei","family":"Yang","sequence":"additional","affiliation":[{"name":"Center for Clinical Epidemiology and Biostatistics, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qiang","family":"Pan","sequence":"additional","affiliation":[{"name":"Center for Clinical Epidemiology and Biostatistics, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lawrence","family":"Appel","sequence":"additional","affiliation":[{"name":"Department of Medicine, Johns Hopkins University, Baltimore, MD"},{"name":"Department of Epidemiology, Johns Hopkins University, Baltimore, MD"},{"name":"Department of Welch Center for Prevention, Epidemiology and Clinical Research, Johns Hopkins University, Baltimore, MD"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Keith","family":"Bellovich","sequence":"additional","affiliation":[{"name":"St. John Hospital and Medical Center Detroit, MI"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jing","family":"Chen","sequence":"additional","affiliation":[{"name":"Section of Nephrology and Hypertension, Department of Medicine, Tulane University School of Medicine, New Orleans, LA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Harold","family":"Feldman","sequence":"additional","affiliation":[{"name":"Center for Clinical Epidemiology and Biostatistics, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael J.","family":"Fischer","sequence":"additional","affiliation":[{"name":"Jesse Brown VAMC and University of Illinois Hospital and Health Sciences System, Chicago, IL"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"L. L.","family":"Ham","sequence":"additional","affiliation":[{"name":"Section of Nephrology and Hypertension, Department of Medicine, Tulane University School of Medicine, New Orleans, LA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas","family":"Hostetter","sequence":"additional","affiliation":[{"name":"Division of Nephrology and Hypertension, Case Western Reserve University, University Hospital Case Medical Center, Cleveland, OH"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bernard G.","family":"Jaar","sequence":"additional","affiliation":[{"name":"Department of Medicine, Johns Hopkins University, Baltimore, MD"},{"name":"Department of Epidemiology, Johns Hopkins University, Baltimore, MD"},{"name":"Department of Welch Center for Prevention, Epidemiology and Clinical Research, Johns Hopkins University, Baltimore, MD"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Radhakrishna R.","family":"Kallem","sequence":"additional","affiliation":[{"name":"Renal, Electrolyte and Hypertension Division, Department of Medicine, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sylvia E.","family":"Rosas","sequence":"additional","affiliation":[{"name":"Joslin Diabetes Center and Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julia J.","family":"Scialla","sequence":"additional","affiliation":[{"name":"Duke University School of Medicine, Durham, NC"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Myles","family":"Wolf","sequence":"additional","affiliation":[{"name":"Division of Nephrology and Hypertension, Northwestern University Feinberg School of Medicine, Chicago, IL"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mahboob","family":"Rahman","sequence":"additional","affiliation":[{"name":"Division of Nephrology and Hypertension, Case Western Reserve University, University Hospital Case Medical Center, Cleveland, OH"},{"name":"Louis Stokes Cleveland VA Medical Center, Cleveland, OH"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"name":"and the CRIC Study 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