Supplementary Material for: Association of Pre-ESRD Serum Bicarbonate with Post-ESRD Mortality in Patients with Incident ESRD

<b><i>Background:</i></b> Serum bicarbonate or total carbon dioxide (CO₂) concentrations decline as chronic kidney disease (CKD) progresses and rise after dialysis initiation. While metabolic acidosis accelerates the progression of CKD and is associated with higher mortality among patients with end stage renal disease (ESRD), there are scarce data on the association of CO₂ concentrations before ESRD transition with post-ESRD mortality. <b><i>Methods:</i></b> A historical cohort from the Transition of Care in CKD (TC-CKD) study includes 85,505 veterans who transitioned to ESRD from October 1, 2007, through March 31, 2014. After 1,958 patients without follow-up data, 3 patients with missing date of birth, and 50,889 patients without CO₂ 6 months prior to ESRD transition were excluded, the study population includes 32,655 patients. Associations between CO₂ concentrations averaged over the last 6 months and its rate of decline during the 12 months prior to ESRD transition and post-ESRD all-cause, cardiovascular (CV), and non-CV mortality were examined by using hierarchical adjustment with Cox regression models. <b><i>Results:</i></b> The cohort was on average 68 ± 11 years old and included 29% Black veterans. Baseline concentrations of CO₂ were 23 ± 4 mEq/L, and median (interquartile range) change in CO₂ were −1.8 [−3.4, −0.2] mEq/L/year. High (≥28 mEq/L) and low (&lt;18 mEq/L) CO₂ concentrations showed higher adjusted mortality risk while there was no clear trend in the middle range. Consistent associations were observed irrespective of sodium bicarbonate use. There was also a U-shaped association between the change in CO₂ and all-cause, CV, and non-CV mortality with the lowest risk approximately at −2.0 and 0.0 mEq/L/year among sodium bicarbonate nonusers and users, respectively, and the highest mortality was among patients with decline in CO₂ &gt;4 mEq/L/year. <b><i>Conclusion:</i></b> Both high and low pre-ESRD CO₂ levels (≥28 and &lt;18 mEq/L) during 6 months prior to dialysis transition and rate of CO₂ decline &gt;4 mEq/L/year during 1 year before dialysis initiation were associated with greater post-ESRD all-cause, CV, and non-CV mortality. Further studies are needed to determine the optimal management of CO₂ in patients with advanced CKD stages transitioning to ESRD.