Metabolic Acidosis and Long-Term Clinical Outcomes in Kidney Transplant Recipients

Abstract

Metabolic acidosis (MA), indicated by low serum total CO₂ (TCO₂) concentration, is a risk factor for mortality and progressive renal dysfunction in CKD. However, the long-term effects of MA on kidney transplant recipients (KTRs) are unclear. We conducted a multicenter retrospective cohort study of 2318 adult KTRs, from January 1, 1997 to March 31, 2015, to evaluate the prevalence of MA and the relationships between TCO₂ concentration and clinical outcomes. The prevalence of low TCO₂ concentration (<22 mmol/L) began to increase in KTRs with eGFR<60 ml/min per 1.73 m² and ranged from approximately 30% to 70% in KTRs with eGFR<30 ml/min per 1.73 m² Multivariable Cox proportional hazards models revealed that low TCO₂ concentration 3 months after transplant associated with increased risk of graft loss (hazard ratio [HR], 1.74%; 95% confidence interval [95% CI], 1.26 to 2.42) and death-censored graft failure (DCGF) (HR, 1.66; 95% CI, 1.14 to 2.42). Cox regression models using time-varying TCO₂ concentration additionally demonstrated significant associations between low TCO₂ concentration and graft loss (HR, 3.48; 95% CI, 2.47 to 4.90), mortality (HR, 3.16; 95% CI, 1.77 to 5.62), and DCGF (HR, 3.17; 95% CI, 2.12 to 4.73). Marginal structural Cox models adjusted for time-varying eGFR further verified significant hazards of low TCO₂ concentration for graft loss, mortality, and DCGF. In conclusion, MA was frequent in KTRs despite relatively preserved renal function and may be a significant risk factor for graft failure and patient mortality, even after adjusting for eGFR.

Keywords: acidosis; chronic graft deterioration; glomerular filtration rate; kidney transplantation; mortality; transplant recipients.