Bone Enzyme Linked to Greater Short-Term Mortality in Dialysis Patients

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High levels of bone alkaline phosphatase (BAP) are associated with increased short-term mortality among dialysis patients, a finding that underscores the important impact of bone turnover in this population, investigators reported.

In a study led by Christiane Drechsler, MD, of Leiden University Medical Center, Leiden, the Netherlands, dialysis patients in the highest tertile of BAP level had a 5.7 times increased risk of all-cause mortality within six months compared with those in the lowest tertile, after adjusting for numerous confounders.

“Longitudinal assessments of BAP may be useful for the treatment monitoring in clinical practice in dialysis patients,” the authors concluded in the Clinical Journal of the American Society of Nephrology (2011;6:1752-1759).

The researchers observed similar associations with cardiovascular and non-cardiovascular causes of death. Compared with subjects in the lowest tertile of BAP, those in the highest tertile had a fivefold and sixfold increased risk of death from cardiovascular and non-cardiovascular causes, respectively, in adjusted analyses.

Alkaline phosphatases are enzymes that remove phosphate from proteins and nucleotides and function optimally at alkaline pH, Dr. Drechsler's group explained. Clinical studies, they pointed out, have found these enzymes to be associated with coronary artery calcification and all-cause mortality in CKD patients and those on dialysis.

Dr. Drechsler and her colleagues prospectively studied 800 patients with end-stage renal disease (ESRD). All were participants in the Netherlands Cooperative Study on the Adequacy of Dialysis, an observational prospective follow-up study. Investigators measured BAP at 12 months after the start of dialysis (baseline) and divided patients into BAP tertiles, with the first, second, and third tertiles defined as BAP levels of 12 U/L or less, 12-18 U/L, and greater than 18 U/L, respectively.

Noting that BAP levels were determined only once after dialysis initiation, the authors observed that low BAP levels may indicate that “serious attention was paid to the development and correction of secondary hyperparathyroidism during predialysis care by the attending physicians. Low BAP may thus additionally represent a surrogate parameter of the general quality of care before and during ESRD.”

In their discussion of potential study limitations, the researchers noted that their study cohort consisted of stable ESRD patients, so they cannot extrapolate their findings to ESRD patients starting dialysis.

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