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Parathyroid hormone and its fragments in children with chronic renal failure

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Abstract

Parathyroid hormone (PTH) immunoradiometric assays (IRMA) exhibit cross-reactivity between 1-84 PTH and long carboxyl-terminal-PTH (C-PTH) molecules. C-PTH antagonizes the biological actions of 1-84 PTH and circulates in excess in chronic renal failure (CRF), partially explaining why supra-physiological PTH levels are recommended to maintain bone turnover. Furthermore, the ratio 1-84 PTH/C-PTH may be related to bone turnover. This study characterizes the 1-84 PTH/C-PTH ratio in children with varying severity of CRF and levels of PTH. Two hundred and forty-one children with CRF, managed with the aim of preventing the development of hyperparathyroidism, had PTH measured by ‘intact’ IRMA and a new more specific Cyclase-Activating-PTH (CAP) IRMA. C-PTH levels were calculated by subtracting CAP-IRMA from ‘intact’ IRMA. Fifty-three controls with normal renal function were also recruited. Mean ‘intact’ IRMA correlated with CAP-IRMA (r=0.98), but was higher (P<0.001). The mean 1-84 PTH/C-PTH ratio was lower than controls in dialysis patients (P=0.022) and those with a glomerular filtration rate <30 ml/min per m2 (P=0.033). This ratio was comparable to controls when the PTH level was normal, but was lower with PTH levels outside the normal range (P<0.01). These data suggest that CAP-IRMA gives a more accurate assessment of actual PTH levels than ‘intact’ IRMA in CRF. Maintenance of normal PTH levels throughout the course of CRF permits the maintenance of a normal 1-84 PTH/C-PTH ratio, the clinical significance of which requires further investigation in children.

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Acknowledgements

This work was supported by grants from the National Kidney Research Fund (R 18/2/2001), Renal Care and Research Association, and the Special Trustees of Great Ormond Street Hospital. Scantibodies Laboratory performed all the PTH assays. The work was presented at the 36th annual meeting of the ESPN (2002), Pediatr Nephrol 17:C27-C148. The authors would like to thank Dr. A. Rosenberg for his comments on this manuscript.

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Authors and Affiliations

  1. Department of Nephro-Urology, Institute of Child Health and Great Ormond Street Hospital for Children NHS Trust, London, UK

    Simon Waller & Lesley Rees

  2. Pediatric Epidemiology and Biostatistics Unit, Institute of Child Health and Great Ormond Street Hospital for Children NHS Trust, London, UK

    Deborah Ridout

  3. Department of Chemical Pathology, Great Ormond Street Hospital for Children NHS Trust, London, UK

    Anthony Reynolds

  4. Scantibodies Laboratories, Santee, California, USA

    Tom Cantor & Ping Gao

  5. Department of Nephro-Urology, Institute of Child Health, 30 Guilford Street, London WC1N 1EH, UK

    Simon Waller

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  1. Simon Waller
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Correspondence to Simon Waller.

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Waller, S., Reynolds, A., Ridout, D. et al. Parathyroid hormone and its fragments in children with chronic renal failure. Pediatr Nephrol 18, 1242–1248 (2003). https://doi.org/10.1007/s00467-003-1267-1

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