Association of Pre-ESRD Serum Bicarbonate with Post-ESRD Mortality in Patients with Incident ESRD

Abstract

<b><i>Background:</i></b> Serum bicarbonate or total carbon dioxide (CO<sub>2</sub>) 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 CO<sub>2</sub> 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 CO<sub>2</sub> 6 months prior to ESRD transition were excluded, the study population includes 32,655 patients. Associations between CO<sub>2</sub> 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 CO<sub>2</sub> were 23 ± 4 mEq/L, and median (interquartile range) change in CO<sub>2</sub> were −1.8 [−3.4, −0.2] mEq/L/year. High (≥28 mEq/L) and low (<18 mEq/L) CO<sub>2</sub> 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 CO<sub>2</sub> 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 CO<sub>2</sub> >4 mEq/L/year. <b><i>Conclusion:</i></b> Both high and low pre-ESRD CO<sub>2</sub> levels (≥28 and <18 mEq/L) during 6 months prior to dialysis transition and rate of CO<sub>2</sub> decline >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 CO<sub>2</sub> in patients with advanced CKD stages transitioning to ESRD.

The AE4 transporter mediates kidney acid-base sensing

“…Failure to maintain systemic pH within limits compatible with normal cell and organ function causes disease and constitutes a major complication of other underlying diseases 2 . Acid-base disturbances are an independent risk factor for morbidity and mortality in the setting of various conditions 3 , 4 .…”