Metabolic Acidosis Is Associated With an Accelerated Decline of Allograft Function in Pediatric Kidney Transplantation

Abstract

Introduction: We investigated the relationship between metabolic acidosis over time and allograft outcome in pediatric kidney transplantation (KTx).

Methods: This registry study collected data up to 10 years posttransplant. Survival analysis for a composite end point of graft loss or estimated glomerular filtration rate (eGFR) ≤ 30 ml/min per 1.73 m² or ≥50% decline from eGFR at month 3 posttransplant was performed. The association of serum bicarbonate concentration (HCO₃ ^-) < 22 mmol/l (metabolic acidosis) and HCO₃ ^- < 18 mmol/l (severe metabolic acidosis) with allograft outcome was investigated using stratified Cox models and marginal structural models. Secondary analyses included the identification of risk factors for metabolic acidosis and the relationship between alkali supplementation and allograft outcome.

Results: We report on 1911 patients, of whom 347 reached the composite end point. The prevalence of metabolic acidosis over time ranged from 20.4% to 38.9%. In the adjusted Cox models, metabolic acidosis (hazard ratio [HR], 2.00; 95% confidence interval [CI], 1.54-2.60) and severe metabolic acidosis (HR, 2.49; 95% CI, 1.56-3.99) were associated with allograft dysfunction. Marginal structural models showed similar results (HR, 1.75; 95% CI, 1.32-2.31 and HR, 2.09; 95% CI, 1.23-3.55, respectively). Older age was associated with a lower risk of metabolic acidosis (odds ratio [OR] 0.93/yr older; 95% CI, 0.91-0.96) and severe metabolic acidosis (OR, 0.89; 95% CI, 0.84-0.95). Patients with uncontrolled metabolic acidosis had the worst outcome compared to those without metabolic acidosis and without alkali (HR, 3.70; 95% CI, 2.54-5.40).

Conclusion: The degree of metabolic acidosis is associated with allograft dysfunction.

Keywords: acidosis; pediatric; transplantation.

Graphical abstract

Figure 1

(a) Proportion of patients with severe metabolic acidosis (HCO3⁻ ≤ 18 mmol/l, yellow bars), mild-to-moderate metabolic acidosis (HCO3⁻, 18.1–21.9 mmol/l, light green bars) and no metabolic acidosis (HCO3⁻ ≥22 mmol/l, dark green bars). (b) As above, with additional breakdown of mild-to-moderate metabolic acidosis into subgroups (HCO3⁻, 18.1–19 mmol/l; HCO3⁻, 19.1–21 mmol/l; and HCO3⁻, 21.1–21.9 mmol/l). HCO3⁻, serum bicarbonate concentration.

Figure 2

(a) Association between the cumulative incidence of time to composite end point and time-varying severe metabolic acidosis (red line), mild-to-moderate metabolic acidosis (blue line), and no acidosis (green line). (b) Association between the degree of time-varying metabolic acidosis and time to composite end point. Number at risk in Figure 2a and b corresponds to the number of patients with available HCO₃⁻ at a given time point. CI, confidence interval; HCO3⁻, serum bicarbonate concentration; HR, hazard ratio.

Figure 3

Association between the cumulative incidence of time to composite end point and the combination of time-varying HCO₃⁻ and alkali supplementation at the previous time point. Number at risk corresponds to the number of patients with available HCO₃⁻ at a given time point and information on alkali supplementation at the previous time point. CI, confidence interval; HCO3⁻, serum bicarbonate concentration; HR, hazard ratio.