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Abstract: PO0482

High Serum Alkaline Phosphatase Predicts CKD Progression: Effect Modification by GFR

Session Information

Category: CKD (Non-Dialysis)

  • 2101 CKD (Non-Dialysis): Epidemiology, Risk Factors, and Prevention

Authors

  • Mallamaci, Francesca, Nephrology, Dialysis and Transplantation Unit, Reggio Calabria, Italy
  • D'Arrigo, Graziella, CNR-IFC, Reggio Calabria, Italy
  • Marino, Francesco, Nephrology, Dialysis and Transplantation Unit, Reggio Calabria, Italy
  • Caridi, Graziella, Nephrology, Dialysis and Transplantation Unit, Reggio Calabria, Italy
  • Parlongo, Giovanna, Nephrology, Dialysis and Transplantation Unit, Reggio Calabria, Italy
  • Leonardis, Daniela, CNR-IFC, Reggio Calabria, Italy
  • Pizzini, Patrizia, CNR-IFC, Reggio Calabria, Italy
  • Cutrupi, Sebastiano, CNR-IFC, Reggio Calabria, Italy
  • Pisano, Anna, CNR-IFC, Reggio Calabria, Italy
  • Tripepi, Giovanni, CNR-IFC, Reggio Calabria, Italy
  • Zoccali, Carmine, CNR-IFC, Reggio Calabria, Italy
Background

In the post-hoc analyses of SUSTAIN/ASSURE trials, Apabetalone, an epigenetic modulator which lowers alkaline phosphatase (AlkPhos), stabilized the GFR in patients with CV disease and GFR <60/ml/min/1.73m2. Analyzing the relationship between AlkPhos and renal outcomes in patients with CKD is useful to explore the biological hypothesis that AlkPhos is implicated in CKD progression.

Methods

We investigated the relationship between AlkPhos and the risk of a combined end-point (30% GFR loss or dialysis/renal transplantation) in 609 stage 3-5 CKD patients (mean GFR: 34.8±12.1ml/min/1.73 m2).

Results

Median AlkPhos was 91 IU/L and in the majority of patients had values below 147 IU/L (the upper limit of the normal range). Over a median follow up of 3 yrs, 200 patients had the combined end-point. In an unadjusted analysis, 1 ln increase in AlkPhos entailed a 49% risk excess for the renal end-point (HR:1.49, 95% CI 1.11-2.01,P=0.008). Adjusting for age, gender, smoking, diabetes, cholesterol, BMI, systolic BP, CV comorbidities, hemoglobin, albumin, phosphate, and hs-CRP, did not modify this association (HR:1.48, 95% CI 1.08-2.02, P=0.016). In a fully adjusted analysis testing the GFR as an effect modifier of the AlkPhos - combined renal end point link showed a GFR- AlkPhos interaction (Figure). Indeed, the risk for the combined end-point was gradually more pronounced at progressively more severe degrees of renal dysfunction (see Figure).

Conclusion

In stage 3-5 CKD patients, AlkPhos within the normal range is associated with the progression to ESRD and the GFR is an effect modifier of this relationship. These findings are compatible with the hypothesis that within the normal range of this biomarker, the risk for CKD progression by AlkPhos is amplified by CKD severity. These data are in keeping with post-hoc analyses of SUSTAIN/ASSURE trials and support the hypothesis that interventions lowering AlkPhos may mitigate CKD progression.

Funding

  • Government Support - Non-U.S.