Effect of chronic renal failure on bone turnover and bone alkaline phosphatase isoforms.
BACKGROUND
Biochemical markers of bone turnover are used to monitor metabolic bone disease associated with renal failure. We have applied a comprehensive panel of markers to patients with chronic renal failure (CRF), with particular focus on the isoforms of bone alkaline phosphatase (BALP).


METHODS
Twenty CRF patients undergoing hemodialysis (N = 9) and peritoneal dialysis (N = 11) were measured for serum parathyroid hormone (PTH), osteocalcin, total ALP, and four BALP isoforms (B/I, B1x, B1, and B2) by high-performance liquid chromatography. These BALP isoforms were also compared with BALP measured by three commercial immunoassays (Alkphase-B, Tandem-R Ostase, and Tandem-MP Ostase). Type I collagen turnover was assessed by serum samples using the type I procollagen intact amino- and carboxy-terminal propeptides (PINP and PICP) and two fragments (ICTP and CrossLaps) derived from the carboxy-terminal telopeptide of mature matrix collagen by different degradative pathways.


RESULTS
Mean levels of bone turnover markers were elevated in CRF, with marked increases in those markers, osteocalcin, ICTP, and CrossLaps, cleared by the kidney. Total ALP activities were increased corresponding to elevated B/I and B2 isoform levels. The B1 isoform level was not significantly different from healthy controls. B1x was detected in 60% of the patients but was not resolved in healthy individuals. Kendall's tau rank correlation showed that B1x correlated significantly (P < 0.05) with B1 (0.53) and PINP (0.55), and was the only marker to correlate with PTH (0.49). B1x was not significantly correlated with any of the commercial BALP immunoassays. Interestingly, the immunoassay calibrators contained high activities of the B/I peak (39 to 80%) compared with human serum (4%).


CONCLUSIONS
There are selective differences between the BALP isoforms in CRF compared with healthy adults. The commercial BALP immunoassays are comparable with each other but are unable to distinguish the BALP isoform-specific differences in CRF patients.
Magnusson
P
P
Bone and Mineral Metabolic Unit, Division of Clinical Chemistry, Department of Biomedicine and Surgery, Linköping University Hospital, Linköping, Sweden. per.magnusson@med.va.gov
Sharp
C A
CA
Magnusson
M
M
Risteli
J
J
Davie
M W
MW
Larsson
L
L
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000469:Alkaline Phosphatase / Q000378:metabolism*; D015415:Biomarkers / Q000097:blood; D016723:Bone Remodeling; D001842:Bone and Bones / Q000201:enzymology*; D002851:Chromatography, High Pressure Liquid; D003094:Collagen / Q000378:metabolism; D005260:Female; D006801:Humans; D007118:Immunoassay; D007527:Isoenzymes / Q000378:metabolism*; D007676:Kidney Failure, Chronic / Q000097:blood / Q000503:physiopathology*; D008297:Male; D008875:Middle Aged; D015675:Osteocalcin / Q000097:blood; D010281:Parathyroid Hormone / Q000097:blood; D011933:Reagent Kits, Diagnostic
D015415:Biomarkers; D007527:Isoenzymes; D010281:Parathyroid Hormone; D011933:Reagent Kits, Diagnostic; D015675:Osteocalcin; D003094:Collagen; D000469:Alkaline Phosphatase