Blog entry by Meguid El Nahas

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J Am Heart Assoc. 2015 Apr 20;4(4). pii: e001599. doi: 10.1161/JAHA.114.001599.

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.



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.


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.


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.


The Nephrology community has been led to beleive with weak evidence that increased serum bicarbonate levels slows CKD progression (1-3). Whilst little doubt exists in Nephrologists' mind that metabolic acidosis in CKD is harmful, increased emphasis has been over the last 5 years on aiming for higher than normal serum bicarbonate levels to slow CKD progression and delay ESRD (1-3).

Now data published this month from a CRIC cohort seems to confirm that impression with patients with CKD and serum bicarbonate levels >26mmol/l have a significant decrease incidence of adverse renal events including ESRD compared to those with sBic <22mmol/l. However, the same cohort study shows an alarming increase in congestive heart failure and death rate in those whose serum bicarbonate levels exceeds 26mmol/l...!!!!

Previous NHANES III observations suggested that low serum Bicarbonate levels <22mmol/l are associated with increased mortality in CKD patients (3).

So it seems to me that optimal serum bicarbonate levels in patients with CKD may be between 24-26mmol/l, thus aiming at minimising CKD progression whilst avoiding metabolic alkalosis and its negative effects on the myocardium resulting in congestive heart failure and death. In other words, keeping serum bicarbonate levels within the middle of the normal range (24-26mmol/l) may prove that moderation is the best option for CKD patients!


1. de Brito-Ashurst I, Varagunam M, Raftery MJ, Yaqoob MM. Bicarbonate
supplementation slows progression of CKD and improves nutritional status. J
Am Soc Nephrol. 2009;20:2075–2084.
2. Raphael KL, Wei G, Baird BC, Greene T, Beddhu S. Higher serum bicarbonate levels within the normal range are associated with better survival and renal outcomes in African Americans. Kidney Int. 2011;79:356–362.

3. Raphael KL, Zhang Y, Wei G, Greene T, Cheung AK, Beddhu S. Serum bicarbonate and mortality in adults in NHANES III. Nephrol Dial Transplant. 2013;28:1207–1213.



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