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Abstract: FR-PO919

Metabolic Acidosis and CKD Progression

Session Information

Category: CKD (Non-Dialysis)

  • 2301 CKD (Non-Dialysis): Epidemiology, Risk Factors, and Prevention

Authors

  • Zoccali, Carmine, Renal Research Institute, New York, United States
  • D'Arrigo, Graziella, IFC-CNR, Reggio Calabria, Italy, Italy
  • Gori, Mercedes, IFC-CNR, Reggio Calabria, Italy, Italy
  • Tripepi, Giovanni, IFC-CNR, Reggio Calabria, Italy, Italy
  • Mallamaci, Francesca, IFC-CNR, Reggio Calabria, Italy

Group or Team Name

  • On Behalf of MAURO Study Group.
Background

An inverse relationship between venous bicarbonate and CKD progression has been reported in several observational studies, but only sparse longitudinal observations testing this relationship exist. Bicarbonate supplementation trials have been conflictual, with limited power and a high risk of bias. Longitudinal studies may provide circumstantial new evidence for implicating metabolic acidosis in the risk of adverse kidney outcomes.

Methods

We performed a longitudinal study in 528 patients with at least 3 longitudinal measurements of bicarbonate over 32 months (IQR: 30-36). The association between bicarbonate trajectories over time and the incidence of renal events (>30% eGFR reduction, dialysis or transplantation) were investigated by a two stages analysis: 1) in the first stage, we identified distinctive group-based bicarbonate trajectories analysis (GBTM); 2) in the second stage we assessed the association between bicarbonate trajectories groups and the risk of renal events by Cox model.

Results

Overall, 126 patients had renal events. Four trajectories of bicarbonate were identified and labelled as low trajectory [bicarbonate: 19.07± 2.5 mEq/L], moderate [21.2± 2.3 mEq/L], moderate-high [25.1± 2.2 mEq/L] and high [27.9± 2.8 mEq/L]. In crude and adjusted analyses (age, gender, systolic BP, haemoglobin, albumin, phosphate, PTH, 24h proteinuria, and eGFR), the hazard rate (HR) of renal events decreased in a dose-dependent fashion from the lowest bicarbonate trajectory (reference category, HR 1) [moderate (HR:0.82, 95%CI 0.50-1.35, p=0.443), high moderate (HR:0.59, 95%CI 0.34-1.00, p=0.050), and high bicarbonate category (HR: 0.37, 95%CI 0.15-0.95, p=0.039), p for trend p=0.010]. (P for trend=0.005). Thus, for patients in the high bicarbonate category (27.9± 2.8 mEq/L ), there is an 63% risk reduction for a renal composite endpoint.

Conclusion

In a longitudinal analysis of a cohort of CKD patients, high bicarbonate levels are associated with a substantially reduced risk of renal events. These findings represent a strong call for well-designed, adequately powered randomised trials testing the effect of bicarbonate supplements or pharmacologic interventions that increase serum bicarbonate on renal outcomes. Given the substantial risk reduction in patients in the highest bicarbonate trajectory, these trials are an absolute clinical research priority.