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PubMed · 12041521

Renal osteodystrophy.

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Wilfred C G Peh. 2002. Renal osteodystrophy.. https://pubmed.ncbi.nlm.nih.gov/12041521/

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Parathyroid hormone (PTH), PTH-derived peptides, and new PTH assays in renal osteodystrophy.

Parathyroid hormone (PTH), PTH-derived peptides, and new PTH assays in renal osteodystrophy. Reliable measurements of parathyroid hormone (PTH) concentrations in serum or plasma are critical for the appropriate diagnosis and management of patients with renal osteodystrophy. With the introduction of second generation immunometric assays for PTH, it is now possible to measure exclusively full-length, biologically active PTH(1-84). In contrast, first generation immunometric assays that have been used widely for many years detect not only PTH(1-84), but also other large amino-terminally-truncated, PTH-derived peptides. This development will require a careful re-evaluation of PTH measurements, as determined by either first or second generation immunometric assays, and their relationship to bone histology and bone remodeling rates in patients with end-stage renal disease (ESRD). Such information is essential for proper clinical management, but only limited bone biopsy data are available to guide the interpretation of PTH results using second generation PTH assays. The different performance characteristics of first and second generation immunometric PTH assays also makes it possible to quantify the plasma levels of amino-terminally-truncated, PTH-derived peptides, which may accumulate disproportionately in patients with ESRD. Recent experimental evidence indicates that one or more of these peptides can modify bone cell activity and skeletal remodeling, possibly by interacting with a PTH receptor distinct from the type I PTH receptor that binds to the amino-terminal portion of PTH and mediates the classical biological actions of the hormone. The putative C-PTH receptor interacts with mid- and/or carboxyterminal regions of PTH and other amino-terminally-truncated PTH-derived peptides; signaling through it may contribute to the skeletal resistance to PTH that characterizes ESRD. The current review discusses certain aspects of the molecular structure of PTH and its interaction with various receptors, briefly comments about selected components of PTH secretion, highlights recent technical advances in PTH assays, and summarizes the effects of various PTH-derived peptides on bone cells and on skeletal metabolism.

Chronic Kidney Disease-Mineral and Bone Disorder↗

Influence of PTH assay methodology on differential diagnosis of renal bone disease.

BACKGROUND: Determination of plasma parathyroid hormone (PTH) is routinely performed to diagnose and monitor renal bone disease. Recently, a new PTH assay ('whole PTH') using an antibody directed specifically against PTH(1-4) has been introduced. It was the aim of the current study to evaluate whole PTH and parameters derived from whole PTH in renal bone disease. METHODS: The following measurements were carried out in blood samples from 141 unselected haemodialysis patients: three intact PTH assays (Nichols, Roche Elecsys), Scantibodies total); whole PTH (Scantibodies); bone-specific alkaline phosphatase (bAP); tartrate-resistant acid-phosphatase 5b (TRAP 5b); osteocalcin, 25-hydroxyvitamin D. Parameters derived from whole PTH were: (i) non-PTH(1-84), difference between intact PTH (Scantibodies assay) and whole PTH; (ii) whole PTH/non-PTH(1-84) ratio. RESULTS: The values generated by the intact PTH assays were comparable. The mean whole PTH concentration was lower than mean intact PTH concentrations (16.9+/-18.1 vs 26.4+/-30.5 pmol/l, Nichols, P<0.05). The correlation coefficients between all four PTH assays were comparable and were very high (r>0.96, ns). The rank order of values generated by the whole PTH assay was statistically not significantly different from the rank order generated by the Nichols intact PTH assay. The median non-PTH(1-84) concentration was 5.2 pmol/l (range 0-49.4). All PTH assays correlated highly significantly with non-PTH(1-84) (correlation coefficients 0.83-0.92). Corrected serum calcium was also associated with non-PTH(1-84) but the correlation was weaker (r=0.28). Regression analysis indicated that the non-PTH(1-84) concentration could be predicted by 76.6-84.6% by the prevailing intact PTH concentrations. Other parameters contributed only marginally to prediction of non-PTH(1-84). In the entire patient group, there was no statistically significant correlation between the whole PTH/non-PTH(1-84) ratio and any of the PTH assays or biochemical bone markers. Eight of 141 patients had a whole PTH/non-PTH(1-84) ratio <1. TRAP 5b, bAP and osteocalcin had high correlations with intact PTH assays and the whole PTH assay (correlation coefficients 0.51-0.56, no significant difference). None of the PTH assays was superior to any other PTH assay in predicting serum concentrations of the bone markers. Therapy with active vitamin D metabolites (n=70) did not alter the results of our analyses. CONCLUSIONS: With respect to information about bone turnover we were not able to find differences between whole PTH and intact PTH assays. Our data also suggest that whole PTH and intact PTH assays give similar information. (i) The correlation between all PTH assays was very high. (ii) The rank order between whole PTH and Nichols intact PTH assays was comparable. (iii) The association between intact PTH assays and non-PTH(1-84) was very high. Albeit non-PTH(1-84) was mostly determined by the prevailing intact PTH concentration, diagnostic information on parathyroid activity provided by whole PTH or intact PTH, respectively, may differ in individual patients. How often this would happen cannot be answered with the currently available data. Unequivocal structural identification of the non-PTH(1-84) fraction would facilitate the answer to that question. The use of the whole PTH/non-PTH(1-84) ratio as a biochemical bone marker in renal bone disease requires further investigation.

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[Intraoperative parathyroid hormone monitoring in neck exploration for renal hyperparathyroidism?].

INTRODUCTION: In operations for renal hyperparathyroidism the value of intraoperative parathormone monitoring was investigated. PATIENTS AND METHODS: Intraoperative intact parathyroid hormone levels were determined (PTH Quick assay) in 40 patients undergoing first cervical exploration and in two patients with graft-dependent recurrence of renal hyperparathyroidism. RESULTS: In 33 patients, total parathyroidectomy with autotransplantation was carried out. The median parathormone levels decreased from 652 pg/ml to 120 pg/ml (19% of initial level) 5 min after total parathyroidectomy. In seven patients, fewer than 4 parathyroid glands each were identified during cervical exploration and "total parathyroidectomy (?)" without autotransplantation was performed. Intraoperatively median parathormone level decreased from 1193 pg/ml to 116 pg/ml (10% of initial level). In one of these seven patients, hyperparathyroidism persisted due to an ectopic fourth gland within the carotid sheath. In two of these patients, hypoparathyroidism occurred and a delayed autotransplantation of cryopreserved parathyroid tissue was carried out. On the first day after total parathyroidectomy with autotransplantation and "total parathyroidectomy (?)", median levels of intact parathyroid hormone were 1.9 pg/ml and 82.5 pg/ml, respectively. CONCLUSION: Intraoperative monitoring is not useful in first cervical exploration for renal hyperparathyroidism because it cannot predict complete resection of parathyroid tissue. The parathormone level on the first postoperative day allows precise evaluation of the efficacy of the surgical procedure.

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