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Letters to the Editor |
Institute of Laboratory Medicine, Department of Clinical Chemistry, and Transfusion Medicine, and, Institute of Clinical Neuroscience, Department of Experimental Neuroscience, Sahlgrenska University Hospital, Göteborg University, Göteborg, Sweden
Address for correspondence: Center for Neurologic Diseases, Brigham and Women’s Hospital, Harvard Medical School, Harvard Institutes of Medicine, HIM-610, 77 Avenue Louis Pasteur, Boston, MA 02115. Fax 617-525-5305; e-mail hzetterberg{at}rics.bwh.harvard.edu.
To the Editor:
Patients suffering from chronic renal dysfunction are monitored by measurement of biochemical markers such as serum total alkaline phosphatase (ALP) to detect increased bone remodeling before the development of advanced renal osteodystrophy. There are at least five different isoforms/isoenzymes of ALP: hepatic, skeletal, intestinal, placental, and tumor-associated (1). These can be separated by electrophoresis and differ in their resistance to heat inactivation, with placental and tumor-associated ALP being the most resistant. Approximately 95% of the total ALP activity in serum is derived from bone and liver sources; these isoforms occur in an 
1:1 ratio in healthy adults (2).
Bone remodeling leads to release of skeletal ALP from osteoblasts and, hence, to increased total ALP activity in serum (1). However, one report has indicated that peritoneal dialysis per se may stimulate the intestine to secrete more intestinal ALP and intestinal variant ALP, leading to increased ALP activity in serum (3). I wish to report on two patients who were on long-term peritoneal dialysis and had moderately increased serum total ALP activity (2.4 and 4.4 µkat/L, respectively; cutoff value <1.8 µkat/L) without any biochemical signs of liver disease. Serum agarose gel electrophoresis followed by incubation of the gel with a chromogenic ALP substrate revealed a dominant band with electrophoretic mobility identical to that of intestinal ALP (Fig. 1
). The band was unaltered by ficin-induced immunoglobulin fragmentation and disappeared after heat inactivation, excluding that it might represent immunoglobulin-bound macro-ALP or placental or tumor-associated ALP.
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The two cases support the possibility of an association between peritoneal dialysis and increased serum concentrations of intestinal ALP and caution against interpreting increased total ALP activity in peritoneal dialysis patients as a sign of increased bone remodeling before further investigation by electrophoresis and/or determination of "bone-specific" ALP, for which immunochemical methods are available. It should in this context be noted that macro-ALP interferes with immunochemical tests for skeletal ALP (4). Thus, the presence of macro-ALP should be excluded by electrophoresis or an equivalent method in patients with increased serum concentrations of skeletal ALP.
The molecular mechanism behind the increase in intestinal ALP in peritoneal dialysis is unknown. There may be a direct association between increased production of intestinal ALP and the peritoneal dialysis technique, but because the presence of intestinal ALP has also been reported in hemodialysis patients and in patients with advanced liver cirrhosis, there may be other explanations as well. For example, competition for clearance by the asialoglycoprotein receptor of the liver between asialylated intestinal ALP and asialoglycoproteins can lead to increased serum concentrations of intestinal ALP (5). Whether this is the case in peritoneal dialysis patients remains to be investigated.
References
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