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

• Published in: American journal of kidney diseases Vol. 77; no. 1; pp. 35 - 43
• Main Authors: Kajimoto, Sachio, Sakaguchi, Yusuke, Asahina, Yuta, Kaimori, Jun-Ya, Isaka, Yoshitaka
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.01.2021
• Subjects: acid load; acid-base disturbance; Acid-Base Imbalance - blood; Acid-Base Imbalance - etiology; acidemia; alkali therapy; bicarbonate level; Bicarbonates - blood; blood gas analysis; chronic kidney disease (CKD); Disease Progression; Female; Glomerular Filtration Rate; Humans; Hydrogen-Ion Concentration; hypobicarbonatemia; Japan - epidemiology; kidney disease progression; kidney failure with replacement therapy (KFRT); Kidney Failure, Chronic - blood; Kidney Failure, Chronic - diagnosis; Kidney Failure, Chronic - therapy; Male; Metabolic acidosis; Middle Aged; Outcome and Process Assessment, Health Care; Prognosis; Renal Insufficiency - epidemiology; Renal Insufficiency - metabolism; Renal Insufficiency - physiopathology; renal replacement therapy (RRT); Renal Replacement Therapy - methods; Renal Replacement Therapy - statistics & numerical data; respiratory compensation; Water-Electrolyte Imbalance - blood; Water-Electrolyte Imbalance - etiology; Japan; acid load; kidney disease progression; acidemia; hypobicarbonatemia; renal replacement therapy (RRT); chronic kidney disease (CKD); blood gas analysis; pH; acid-base disturbance; bicarbonate level; kidney failure with replacement therapy (KFRT); respiratory compensation; alkali therapy; Metabolic acidosis
• ISSN: 0272-6386; 1523-6838
• DOI: 10.1053/j.ajkd.2020.06.019

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). Retrospective cohort study. 1,058 Japanese patients with estimated glomerular filtration rates<60mL/min/1.73m2. Baseline venous bicarbonate levels and venous pH. KFRT defined as initiation of kidney replacement therapy (hemodialysis, peritoneal dialysis, and kidney transplantation). Cox proportional hazards model assessing the interaction between baseline bicarbonate levels and venous pH on incident KFRT. 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). Observational study design; blood gas measurements were performed in a select patient population. 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.