Modulation of the Association of Hypobicarbonatemia and Incident Kidney Failure With Replacement Therapy by Venous PH: A Cohort Study

Rationale & Objective: Studies showing an association between lower bicarbonate levels and worse kidney disease prognosis have not accounted for the influence of pH. It remains unknown whether this association is consistent across a wide range of blood pH values. This study sought to assess how pH modifies the relationship between hypobicarbonatemia and incident kidney failure requiring kidney replacement therapy (KFRT).

Study Design: Retrospective cohort study.

Setting & Participants: 1,058 Japanese patients with estimated glomerular filtration rates<60mL/min/1.73m.

Exposure: Baseline venous bicarbonate levels and venous pH.

Outcome: KFRT defined as initiation of kidney replacement therapy (hemodialysis, peritoneal dialysis, and kidney transplantation).

Analytical Approach: Cox proportional hazards model assessing the interaction between baseline bicarbonate levels and venous pH on incident KFRT.

Results: In the lowest bicarbonate quartile (≤21.5 mEq/L), 59% of patients had acidemia (pH<7.32), whereas 38% had venous pH within the normal range and 3% had alkalemia (pH>7.42). During a median follow-up of 3.0 years, 374 patients developed KFRT. Venous pH modified the association between bicarbonate level and rate of KFRT (P for interaction=0.04). After adjustment for potential confounders, including capacity for respiratory compensation, the lowest (vs the highest) bicarbonate quartile was associated with a 2.29-fold (95% CI, 1.10-4.77; P=0.03) higher rate of KFRT among patients with acidemia (pH<7.32). In contrast, among patients without acidemia (pH≥7.32), no significant association was found between bicarbonate level and KFRT. In an exploratory analysis, patients with higher respiratory compensation capacity had a lower rate of KFRT (HR per 0.1 increase in respiratory compensation capacity, 0.90; 95% CI, 0.87-0.94; P<0.001).

Limitations: Observational study design; blood gas measurements were performed in a select patient population.

Conclusions: Venous pH modified the association of hypobicarbonatemia with progression of chronic kidney disease to KFRT. Measurement of venous pH may be valuable for identifying patients with chronic kidney disease and hypobicarbonatemia and may inform treatment.