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Abstract: TH-PO1080

Non-Skeletal, as Opposed to Skeletal, Alkaline Phosphatase Associates with Mortality in Patients with CKD Not Yet on Dialysis

Session Information

Category: CKD (Non-Dialysis)

  • 2302 CKD (Non-Dialysis): Clinical, Outcomes, and Trials


  • Smout, Dieter, Katholieke Universiteit Leuven, Leuven, Flanders, Belgium
  • Joergensen, Hanne Skou, Katholieke Universiteit Leuven, Leuven, Belgium
  • Meijers, Björn Ki, Katholieke Universiteit Leuven, Leuven, Flanders, Belgium
  • Dejongh, Sander, Katholieke Universiteit Leuven, Leuven, Flanders, Belgium
  • Cavalier, Etienne, Universite de Liege, Liege, Belgium
  • Haarhaus, Mathias, Karolinska Universitetssjukhuset, Stockholm, Sweden
  • Van Craenenbroeck, Amaryllis H., Katholieke Universiteit Leuven, Leuven, Flanders, Belgium
  • Evenepoel, Pieter, Katholieke Universiteit Leuven, Leuven, Flanders, Belgium

Group or Team Name

  • Nephrology and Renal Transplantation Research Group - KU Leuven.

High total alkaline phosphatase (ALP) levels associate with increased mortality in patients with chronic kidney disease (CKD). The underlying mechanisms remain poorly understood. Emphasis has been on the skeletal fraction and its link with accelerated vascular calcification, but intestinal and liver ALP may be implicated given their role in the detoxification of bacterial endotoxins. This study aimed to identify the ALP fraction driving the association with mortality in CKD.


Demographics, Framingham risk factors, total and bone-specific ALP, and parameters of inflammation (CRP) and metabolic endotoxemia (lipopolysaccharide binding protein (LBP)) were assessed in 432 patients with CKD grade 1-5. Non-skeletal ALP levels were estimated as residuals of linear regression (according to Filipowicz et al. CJASN 2013). Mortality data were censored at time of renal replacement therapy or loss of follow up.


Median age was 63 years, 54% were men, 19% had diabetes, and 31% had cardiovascular disease. During a median follow-up of 8.0 years, 131 patients died. High total and non-skeletal ALP were significant and independent predictors of increased all-cause mortality risk, while bone ALP was not predictive (Table). Total and non-skeletal ALP were independent determinants of elevated CRP (>10 mg/L) after adjusting for demographics and eGFR. Non-skeletal ALP was also independently associated with high LBP (Figure).


Non-skeletal ALP drives the association of total ALP with all-cause mortality in patients with CKD not yet on dialysis. We speculate that inflammation and metabolic endotoxemia are implicated in the poor outcomes seen with elevated total ALP.


  • Government Support – Non-U.S.