TOPLINE:

Total alkaline phosphatase (ALP) levels increased progressively across chronic kidney disease (CKD) stages, driven by an increase in liver, bone, and intestinal fractions. Liver ALP was linked to inflammation and independently predicted the risk for 5-year mortality in patients undergoing haemodialysis.

METHODOLOGY:

• Researchers examined serum activity levels of ALP fractions across CKD stages, their clinical and biochemical determinants, and their association with mortality in 523 patients with CKD across all stages (G1-5 and those undergoing dialysis) and 21 healthy control individuals.
• The mean age of participants was 62 years, and 58% were men.
• Patients were categorised by CKD stage on the basis of the estimated glomerular filtration rate: G1-2 (> 60 mL/min/1.73 m²; n = 90), G3 (30-60 mL/min/1.73 m²; n = 100), G4-5 (< 30 mL/min/1.73 m²; n = 139), and G5D (those undergoing dialysis; n = 194).
• Serum samples were collected and analysed for total ALP activity and its liver, bone, and intestinal fractions, along with various biochemical markers.
• All-cause mortality was assessed over a 5-year follow-up period.

TAKEAWAY:

• Serum total ALP and its liver, bone, and intestinal fractions increased significantly with advancing CKD stage (P < .001 for all); in patients with kidney failure, liver ALP levels were more than twice as high as those in healthy control individuals.
• Total ALP was independently associated with parathyroid hormone (PTH) and C-reactive protein (CRP) across all stages of CKD. Lower 25-hydroxyvitamin D was also identified as an independent determinant of elevated total ALP in patients with CKD stages G1-5.
• Liver ALP was independently associated with CRP in patients with CKD stages G1-5 and in those undergoing dialysis (P < .001 for both), and bone ALP was independently associated with PTH in both groups (P < .001 for both).
• In the haemodialysis subgroup (n = 82), higher total ALP and liver ALP were independently associated with an increased risk for 5-year mortality (adjusted hazard ratio, 2.63 and 2.17, respectively; P < .001 for both).

IN PRACTICE:

"Clinicians adopting this strategy [using total ALP as a screening marker for bone turnover in patients with CKD stages G4 and 5] should be aware of the potential bias by inflammation in addition to liver dysfunction per se when considering total ALP as a proxy for bone ALP," the authors wrote.

"High total ALP may signal increased mortality risk not only through disturbances in mineral metabolism, but also through an underlying inflammatory state, with liver ALP emerging as a key fraction in this pathway," they added.

SOURCE:

This study was led by Dieter Smout, Katholieke Universiteit Leuven, Leuven, Belgium. It was published online on March 11, 2026, in Clinical Kidney Journal.

LIMITATIONS:

The cross-sectional design of the study prevented causal inference. Blood samples were not strictly fasting, which may have led to an overestimation of intestinal ALP. Additionally, liver function tests such as transaminases and gamma-glutamyl transferase were available only for a subset of patients.

DISCLOSURES:

Some authors reported receiving a fellowship or grant support from sources including the Research Foundation Flanders and KU Leuven. Some reported receiving lecture fees or travel support, serving as employees or consultants, and holding other ties with various pharmaceutical companies and organisations.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.