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

Abstract

Metabolic acidosis (MA), indicated by low serum total CO (TCO) 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 TCO concentration and clinical outcomes. The prevalence of low TCO concentration (<22 mmol/L) began to increase in KTRs with eGFR<60 ml/min per 1.73 m and ranged from approximately 30% to 70% in KTRs with eGFR<30 ml/min per 1.73 m Multivariable Cox proportional hazards models revealed that low TCO 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 TCO concentration additionally demonstrated significant associations between low TCO 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 TCO 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.

Association of blood bicarbonate and pH with mineral metabolism disturbance and outcome after kidney transplantation

“…In summary, this large cohort study urges that we take into account both blood collection site and bicarbonate assessment method to delineate interventional studies targeting acidosis correction in KTRs. Our results also confirm the finding of Park et al that low bicarbonate levels represent a risk factor for renal allograft loss and therefore prompt interventional trials investigating the impact of alkalinizing therapies on KTR outcome. Finally, our study establishes a robust link between acid‐base status and mineral metabolism disturbances, suggesting that acidemia correction may further improve posttransplantation hyperparathyroidism, and subsequently bone health.…”

“…Of note, our study focused on gas panel‐derived plasma bicarbonate and not on total plasma CO 2 measured using a chemistry analyzer. Although the latter has been used more extensively to define metabolic acidosis in CKD patients, both parameters have been shown to associate with outcomes in large cohorts . Blood gas has been recently proposed as a confirmatory test to diagnose acid‐base disorders in patients with CKD, but both techniques have specific pitfalls and distinct normal ranges.…”

“…Reduction in blood bicarbonate is not uncommon in kidney transplant recipients (KTRs), especially in the first months following transplantation. Recently, a large monocentric observational study identified low serum total CO 2 as an independent factor for allograft loss . Total CO 2 reflects the amount of plasma CO 2 and HCO 3 − but does not provide direct information regarding acid‐base status.…”

“…Recently, a large monocentric observational study identified low serum total CO 2 as an independent factor for allograft loss. 6 Total CO 2 reflects the amount of plasma CO 2 and HCO 3 − but does not provide direct information regarding acid-base status. In fact, low total CO 2 levels may be associated with either acidemia in uncompensated metabolic acidosis, normal pH, or even elevated pH in uncompensated respiratory alkalosis.…”

Diagnosis and Treatment of Metabolic Acidosis in Patients with Chronic Kidney Disease – Position Statement of the Working Group of the Polish Society of Nephrology

“…In patients with CKD receiving peritoneal dialysis, metabolic acidosis occurs rarely [64]. In renal transplant patients, the results of the few available observational studies suggest that metabolic acidosis is a risk factor for adverse prognosis in terms of graft and patient survival [65,66]. So far, there have been no interventional studies on treatment of metabolic acidosis which include a sufficiently large group of patients undergoing renal replacement therapy.…”