Diagnostische Wertigkeit von beta-CrossLaps bei Hämodialysepatienten

In routine clinical practice, diagnosis and therapy of renal osteodystrophy in chronic haemodialysis patients are based on the laboratory control of calcium, phosphorus and intact parathyroid hormone. Bone biopsy as diagnostic gold standard is performed only in singular cases with coexisting pathological conditions. For the purpose of this thesis, the diagnostic properties of a new biomarker of bone resorption, ß-CrossLaps, were studied in chronic haemodialysis patients (n=123). ß-CrossLaps and its correlation with conventional markers of bone metabolism were monitored over a six month period. In addition, the influence of the haemodialysis procedure was analysed and short term interdialytic variability was monitored. ß-CrossLaps are degradation products of type I collagen, which represents the greatest amount of anorganic bone matrix. The antibody detects a cross-linked fragment of the C-terminal telopeptide after degradation by cathepsin K. These properties are specific for degradation products of bone collagen. In all haemodialysis patients, ß-CrossLaps are clearly elevated above the age- and sex-related normal values. This could be reproduced after the six month period (date I: 1.56 ± 0.11 ng/ml, date II: 1.60 ± 0.11 ng/ml). Significant positive correlations were found for intact parathyroid hormone (r=0.717), osteocalcin (r=0.746) and alkaline phosphatase (r=0.449). Individual variability in the six month period was mostly modest. However, the spectrum ranged from -83.7% to +66.8%. Correlation with the differences of the other bone markers again were positive significant (intact parathyroid hormone: r=0.467, osteocalcin: r=0.543, alkaline phosphatase: r=0.250). By haemodialysis, ß-CrossLaps are eliminated with an average reduction rate of 40%. Absolute and relative elimination is higher in high flux haemodialysis (reduction rate 49%, amount in dialysate 20.67 µg) as compared to low flux treatment (reduction rate 22%, amount in dialysate 10.66 µg). Short term variability between consecutive dialysis sessions is low and the length of the dialysis interval has no influence on predialytic ß-CrossLaps concentrations. In conclusion, ß-CrossLaps can be used as a biomarker in monitoring bone turnover in haemodialysis patients. Further studies and the comparison with histomorphometric data are needed to define its role in the diagnosis of renal osteodystrophy. The dialysis procedure has a clear impact on plasma concentrations of ß-CrossLaps. Therefore analysis of predialytic samples is advisable in order to get comparable results.