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.
abstract: BACKGROUND
  Serum bicarbonate varies over time in chronic kidney disease (CKD) patients, and this variability may portend poor cardiovascular outcomes. The aim of this study was to conduct a time-updated longitudinal analysis to evaluate the association of serum bicarbonate with long-term clinical outcomes: heart failure, atherosclerotic events, renal events (halving of estimated glomerular filtration rate [eGFR] or end-stage renal disease), and mortality.
  
  
  RESULTS
  Serum bicarbonate was measured annually, in 3586 participants with CKD, enrolled in the Chronic Renal Insufficiency Cohort (CRIC) study. Marginal structural models were created to allow for integration of all available bicarbonate measurements and proper adjustment for time-dependent confounding. During the 6 years follow-up, 512 participants developed congestive heart failure (26/1000 person-years) and 749 developed renal events (37/1000 person-years). The risk of heart failure and death was significantly higher for participants who maintained serum bicarbonate >26 mmol/L for the entire duration of follow-up (hazard ratio [HR] 1.66; 95% confidence interval [CI], 1.23 to 2.23, and HR 1.36, 95% CI 1.02 to 1.82, respectively) compared with participants who kept their bicarbonate 22 to 26 mmol/L, after adjusting for demographics, co-morbidities, medications including diuretics, eGFR, and proteinuria. Participants who maintained serum bicarbonate <22 mmol/L had almost a 2-fold increased risk of renal disease progression (HR 1.97; 95% CI, 1.50 to 2.57) compared with participants with bicarbonate 22 to 26 mmol/L.
  
  
  CONCLUSIONS
  In this large CKD cohort, persistent serum bicarbonate >26 mmol/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 CKD to prevent adverse clinical outcomes.
authors.affiliation: Division of Nephrology and Hypertension, Case Western Reserve University, University Hospital Case Medical Center, Cleveland, OH (M.D., T.H., M.R.).
authors.forename: Mirela
authors.initials: M
authors.lastname: Dobre
authors.affiliation: Center for Clinical Epidemiology and Biostatistics, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA (W.Y., Q.P., H.F.).
authors.forename: Wei
authors.initials: W
authors.lastname: Yang
authors.affiliation: Center for Clinical Epidemiology and Biostatistics, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA (W.Y., Q.P., H.F.).
authors.forename: Qiang
authors.initials: Q
authors.lastname: Pan
authors.affiliation: Department of Medicine, Johns Hopkins University, Baltimore, MD (L.A., B.G.J.) Department of Epidemiology, Johns Hopkins University, Baltimore, MD (L.A., B.G.J.) Department of Welch Center for Prevention, Epidemiology and Clinical Research, Johns Hopkins University, Baltimore, MD (L.A., B.G.J.).
authors.forename: Lawrence
authors.initials: L
authors.lastname: Appel
authors.affiliation: St. John Hospital and Medical Center Detroit, MI (K.B.).
authors.forename: Keith
authors.initials: K
authors.lastname: Bellovich
authors.affiliation: Section of Nephrology and Hypertension, Department of Medicine, Tulane University School of Medicine, New Orleans, LA (J.C., H.).
authors.forename: Jing
authors.initials: J
authors.lastname: Chen
authors.affiliation: Center for Clinical Epidemiology and Biostatistics, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA (W.Y., Q.P., H.F.).
authors.forename: Harold
authors.initials: H
authors.lastname: Feldman
authors.affiliation: Jesse Brown VAMC and University of Illinois Hospital and Health Sciences System, Chicago, IL (M.J.F.).
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Fischer
authors.affiliation: Section of Nephrology and Hypertension, Department of Medicine, Tulane University School of Medicine, New Orleans, LA (J.C., H.).
authors.forename: L L
authors.initials: LL
authors.lastname: Ham
authors.affiliation: Division of Nephrology and Hypertension, Case Western Reserve University, University Hospital Case Medical Center, Cleveland, OH (M.D., T.H., M.R.).
authors.forename: Thomas
authors.initials: T
authors.lastname: Hostetter
authors.affiliation: Department of Medicine, Johns Hopkins University, Baltimore, MD (L.A., B.G.J.) Department of Epidemiology, Johns Hopkins University, Baltimore, MD (L.A., B.G.J.) Department of Welch Center for Prevention, Epidemiology and Clinical Research, Johns Hopkins University, Baltimore, MD (L.A., B.G.J.).
authors.forename: Bernard G
authors.initials: BG
authors.lastname: Jaar
authors.affiliation: Renal, Electrolyte and Hypertension Division, Department of Medicine, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA (R.R.K.).
authors.forename: Radhakrishna R
authors.initials: RR
authors.lastname: Kallem
authors.affiliation: Joslin Diabetes Center and Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA (S.E.R.).
authors.forename: Sylvia E
authors.initials: SE
authors.lastname: Rosas
authors.affiliation: Duke University School of Medicine, Durham, NC (J.J.S.).
authors.forename: Julia J
authors.initials: JJ
authors.lastname: Scialla
authors.affiliation: Division of Nephrology and Hypertension, Northwestern University Feinberg School of Medicine, Chicago, IL (M.W.).
authors.forename: Myles
authors.initials: M
authors.lastname: Wolf
authors.affiliation: Division of Nephrology and Hypertension, Case Western Reserve University, University Hospital Case Medical Center, Cleveland, OH (M.D., T.H., M.R.) Louis Stokes Cleveland VA Medical Center, Cleveland, OH (M.R.).
authors.forename: Mahboob
authors.initials: M
authors.lastname: Rahman
mesh_terms: D001639:Bicarbonates / Q000097:blood*; D018450:Disease Progression; D004232:Diuretics / Q000627:therapeutic use; D005260:Female; D005919:Glomerular Filtration Rate; D006333:Heart Failure / Q000097:blood / Q000209:etiology*; D006801:Humans; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D051436:Renal Insufficiency, Chronic / Q000097:blood / Q000150:complications* / Q000188:drug therapy; D012307:Risk Factors
chemical_list: D001639:Bicarbonates; D004232:Diuretics
keywords: CKD; heart failure; serum bicarbonate