#2477 Longitudinal serum bicarbonate and mortality risk in older patients with advanced chronic kidney disease: analyses from the EQUAL cohort
Authors: Lombardi Gianmarco , Chesnaye Nicholas , Caskey Fergus , Dekker Friedo W , Evans Marie , Torino Claudia , Szymczak Maciej , Wanner Christoph , Gambaro Giovanni , Stel Vianda , Jager Kitty J , Ferraro Pietro Manuel 
Published: May 2024

Abstract

Background and Aims
Serum bicarbonate (SBC) disorders have been consistently linked to mortality in chronic kidney disease (CKD) patients. Low SBC levels have been extensively associated with increased mortality in CKD patients, possibly due to the detrimental effects of acidosis on various organs and systems. Likewise, several studies have identified high levels of SBC as a risk factor for mortality in the CKD population. To date, most studies have focused on the association between SBC levels and patient survival during the pre-kidney replacement therapy (KRT) period or the period after KRT initiation, considered separately. None have explored this association across the continuum of CKD (e.g., from pre-KRT to post-KRT start), which is relevant since metabolic acidosis is expected to be managed through dialysis in the KRT population, and thus its clinical outcomes might change after KRT initiation. To provide new insights on this topic, we aimed to explore the relationship between SBC and mortality in advanced CKD during three distinct treatment periods: during the pre-KRT period, during the transition phase surrounding the start of KRT (transition-CKD), and during KRT.

Method
Using the European QUALity Study on treatment in advanced CKD (EQUAL) cohort, which includes patients aged ≥65 years and eGFR ≤20 ml/min per 1.73 m2 from six European countries, we explored the association between longitudinal SBC and all-cause mortality in three separate CKD populations: pre-KRT, transition-CKD and in the KRT populations, using multivariable time-dependent Cox regression models. The cumulative time-averaged, the cumulative exposure of SBC, and the slope of the SBC trajectory during the pre-KRT phase were calculated and evaluated for association with all-cause mortality in the transition-CKD population. Subgroup analysis were used to evaluate the effect modification by pre-specified variables on the relationship between SBC and mortality.

Results
We included 1485 patients with a median follow-up of 2.9 (IQR 2.7) years, during which 529 (35.6%) patients died. A U-shaped relationship between SBC levels and all-cause mortality was observed in the pre-KRT population (p = 0.03; Fig.). Low cumulative exposure, defined as the area under the SBC trajectory before KRT initiation, was associated with increased mortality risk after transitioning to KRT (p = 0.01). Similarly, in the KRT population, low SBC levels showed a trend towards increased mortality risk (p = 0.13). We observed effect modification on the relationship between SBC and mortality by subjective global assessment category (p-value for interaction = 0.02) and KRT initiation (p-value for interaction = 0.02).

Conclusion
Our study has provided important insights into the relationship between SBC and mortality in advanced CKD patients. A U-shaped relationship describes the association between SBC and mortality in the advanced CKD pre-KRT population, whereas in patients that initiate KRT only low SBC levels are associated with an increased mortality risk. Our findings suggest that the relationship between SBC and mortality varies across different stages of CKD and that this relationship is modified by KRT initiation. From this point of view, it would be appropriate to consider a personalized management of acid-base balance disorders based on a comprehensive evaluation of the clinical status of the patient.