Tartrat-resistente saure Phophatase (TRAP) Isoform 5b: ein neuer Serummarker der Knochenresorption bei Hämodialyse-Patienten

Die chronische, dialysepflichtige Niereninsuffizienz ist in den westlichen Industrie-ländern mitbedingt durch die ansteigende Zahl von Diabetikern eine zahlenmäßig zunehmende Erkrankung. In Deutschland liegt die Inzidenz der dialysepflichtigen Niereninsuffizienz bei 0,7/1000 Personen in der Bevölker...

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Bibliographic Details
Main Author: Bandorski, Martina
Contributors: Wahl, H.G. (PD Dr. Dr.) (Thesis advisor)
Format: Dissertation
Published: Philipps-Universität Marburg 2015
Online Access:PDF Full Text
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Table of Contents: The number of patients with renal end-stage disease is increasing in western countries, due to the increasing numbers of diabetics. In Germany, the incidence of patients with renal end-stage disease is 0.7/1000 persons, while the prevalence is 0.18/1000 persons. The numbers of patients with end-stage renal disease is also increasing elsewhere, such as in the United States of America. The increasing numbers of patients with renal end-stage disease has resulted in a concomitant increase in the prevalence of renal osteopathy, which starts in the early stages of renal failure, indicated by a low creatinine clearance of 50 ml/min. Metabolic bone diseases are predicted to be the seventh commonest chronic disease in the year 2030, and are thus classed as “major health problem” by the World Health Organisation. The diagnosis of renal osteopathy includes anamnesis, X-ray, and invasive procedures such as a bone biopsy. However, the early stages of renal osteopathy cannot always be detected. Laboratory investigations close this diagnostic gap. Correct interpretation of diagnostic parameters, including clinical chemistry, permit diagnosis of renal osteopathy prior to the emergence of morphological characteristics. A stable parameter for diagnosis of renal osteopathy is the 5b isoform of tartrate resistant acid phosphatase (TRAP). The TRAP 5b is secreted by osteoclasts as active enzyme into the blood circulation. Ae recent study analysed the activity of TRAP 5b in the serum of 161 patients. The immunoassay employed (from Medac, Hamburg) detects exclusively active enzymes. Secreted inactive molecules (such as those activated macrophages) and the TRAP 5a isoform (from Gaucher’s cells) are not detected by this immunoassay. The TRAP 5b is a specific marker of the grade of bone resorption at the time-point of determination of TRAP 5b concentration in serum. Other markers of bone resorption determined in the present study were alkaline phosphatase (AP) and intact parathyroid hormone (iPTH). Correlations between the values and clinical data including the age of patients and the duration of hemodialysis were performed. All parameters were evaluated again after six months. For a variety of reasons (transplantation, death, stationary treatment, change of center for dialysis, others) only 126 patients were included in the second analysis. Correlations with high statistical significance between the initial levels determined for AP and TRAP 5b were 0.406 (p<0.01) and between iPTH levels and TRAP 5b 0levels, .535 (p<0.01). Low correlations were found between the time of hemodialysis and TRAP 5b levels (0.264; p<0.01) and between the age of patients and TRAP 5b, where a reversed correlation of -0.273 (p<0.01) was noted. Correlations in 126 patients, investigated initially and after six months, between time of dialysis and TRAP 5b levels (0.298; p<0.01) and between the age of patients and TRAP 5b levels (-0.254; p<0.01) were similar to the values of the 161 patients investigated initially. Overall the correlations after six months were lower. During the six months, the concentration of TRAP 5b decreased from 5.78± 3.3 U/l to 5.19±2.89 U/l. The patients with decreased TRAP 5b levels exhibited a significant higher intake of phosphate binder Al(OH)3 (4.8 ±3.3 g/d versus 0.6 ±1.0 g/d) whereas the intake of calcitriol/-calcitriol was not different (0.160.54 g/week versus 0.451.14 g/week). The value of iPTH did change significantly during this time in both groups. The stability of TRAP 5b in serum was analysed in the present study as well. The results revealed high stability of TRAP 5b, with high intra-individual stability, and a variance of maximally 5% during storage of the samples at -20 C. The activity of TRAP 5 b was not influenced by the length of the time between the dialysis. The recent study revealed that TRAP 5b levels are elevated in the serum of patients with renal end-stage disease in contrast to healthy individuals, without significant differences between women and men. Under a treatment with antiresorptive drugs, the values of TRAP 5b are more sensitive than other parameters of bone resorption. Estimation of serum levels of TRAP 5b enables a non-invasive means of monitoring of renal osteopathy.