title: Serum Bicarbonate and Kidney Disease Progression and Cardiovascular Outcome in Patients With Diabetic Nephropathy: A Post Hoc Analysis of the RENAAL (Reduction of End Points in Non-Insulin-Dependent Diabetes With the Angiotensin II Antagonist Losartan) Study and IDNT (Irbesartan Diabetic Nephropathy Trial).
abstract: BACKGROUND
  Low serum bicarbonate level has been reported to be an independent predictor of kidney function decline and mortality in patients with chronic kidney disease. Mechanisms underlying low serum bicarbonate levels may differ in patients with and without diabetes. We aimed to specifically investigate the association of serum bicarbonate level with kidney disease progression and cardiovascular outcome in a cohort of patients with type 2 diabetes and nephropathy.
  
  
  METHODS
  Post hoc analysis of 2 multicenter randomized controlled trials.
  
  
  METHODS
  2,628 adults with type 2 diabetes and nephropathy.
  
  
  METHODS
  Serum bicarbonate level.
  
  
  RESULTS
  Incidence of: (1) end-stage renal disease (ESRD), (2) ESRD or doubling of serum creatinine level, (3) all-cause mortality, (4) cardiovascular events (fatal/nonfatal stroke/myocardial infarction), and (5) heart failure.
  
  
  METHODS
  Serum bicarbonate was measured at baseline as total carbon dioxide. Associations of baseline serum bicarbonate level with end points were investigated using Cox regression models. Serum bicarbonate levels were studied as a continuous variable and stratified in quartiles. Follow-up was 2.8±1.0 (SD) years.
  
  
  RESULTS
  Cox regression analyses showed that serum bicarbonate level had inverse associations with incident ESRD (HR, 0.91; 95% CI, 0.89-0.93; P<0.001) and incidence of the combined end point of ESRD or serum creatinine doubling (HR, 0.94; 95% CI, 0.92-0.96; P<0.001). These associations were independent of age, sex, and cardiovascular risk factors, but disappeared after adjustment for baseline estimated glomerular filtration rate (all P>0.05). Analysis of bicarbonate quartiles showed similar results for the quartile with the lowest bicarbonate (≤21 mEq/L) versus the quartile with normal bicarbonate levels (24-26 mEq/L). There was no association of bicarbonate level with cardiovascular events and heart failure.
  
  
  CONCLUSIONS
  Post hoc analysis and single measurement of serum bicarbonate.
  
  
  CONCLUSIONS
  In this cohort of patients with type 2 diabetes with nephropathy, serum bicarbonate level associations with kidney disease end points were not retained after adjustment for estimated glomerular filtration rate, which is in contrast to results of earlier studies in nondiabetic populations.
authors.affiliation: Department of Nephrology, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands.
authors.forename: Elise
authors.initials: E
authors.lastname: Schutte
authors.affiliation: Department of Clinical Pharmacy and Pharmacology, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands.
authors.forename: Hiddo J
authors.initials: HJ
authors.lastname: Lambers Heerspink
authors.affiliation: Department of Endocrinology, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands.
authors.forename: Helen L
authors.initials: HL
authors.lastname: Lutgers
authors.affiliation: Department of Nephrology, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands.
authors.forename: Stephan J L
authors.initials: SJ
authors.lastname: Bakker
authors.affiliation: Department of Health Sciences, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands.
authors.forename: Priya
authors.initials: P
authors.lastname: Vart
authors.affiliation: Department of Endocrinology, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands.
authors.forename: Bruce H R
authors.initials: BH
authors.lastname: Wolffenbuttel
authors.affiliation: Division of Nephrology and Hypertension, Henry Ford Hospital, Detroit, MI.
authors.forename: Kausik
authors.initials: K
authors.lastname: Umanath
authors.affiliation: Division of Nephrology, Vanderbilt University, Nashville, TN.
authors.forename: Julia B
authors.initials: JB
authors.lastname: Lewis
authors.affiliation: Department of Clinical Pharmacy and Pharmacology, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands.
authors.forename: Dick
authors.initials: D
authors.lastname: de Zeeuw
authors.affiliation: Department of Nephrology, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands. Electronic address: r.t.gansevoort@umcg.nl.
authors.forename: Ron T
authors.initials: RT
authors.lastname: Gansevoort
mesh_terms: D000328:Adult; D000368:Aged; D047228:Angiotensin II Type 1 Receptor Blockers / Q000627:therapeutic use*; D001639:Bicarbonates / Q000097:blood; D001713:Biphenyl Compounds / Q000627:therapeutic use; D003924:Diabetes Mellitus, Type 2 / Q000097:blood; D003925:Diabetic Angiopathies / Q000453:epidemiology; D003928:Diabetic Nephropathies / Q000097:blood* / Q000188:drug therapy; D018450:Disease Progression; D005260:Female; D006801:Humans; D000077405:Irbesartan; D007676:Kidney Failure, Chronic / Q000097:blood; D019808:Losartan / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D051436:Renal Insufficiency, Chronic / Q000097:blood*; D012307:Risk Factors; D013777:Tetrazoles / Q000627:therapeutic use
chemical_list: D047228:Angiotensin II Type 1 Receptor Blockers; D001639:Bicarbonates; D001713:Biphenyl Compounds; D013777:Tetrazoles; D000077405:Irbesartan; D019808:Losartan
keywords: Diabetes mellitus; cardiovascular disease; diabetic nephropathy; end-stage renal disease (ESRD); kidney disease progression; metabolic acidosis; mortality; risk predictor; serum bicarbonate; type 2 diabetes