Journal Article

Dynamics of secretion and metabolism of PTH during hypo‐ and hypercalcaemia in the dog as determined by the ‘intact’ and ‘whole’ PTH assays

Jose C. Estepa, Ignacio Lopez, Arnold J. Felsenfeld, Ping Gao, Tom Cantor, Mariano Rodríguez and Escolastico Aguilera‐Tejero

in Nephrology Dialysis Transplantation

Published on behalf of European Renal Association - European Dialysis and Transplant Assoc

Volume 18, issue 6, pages 1101-1107
Published in print June 2003 | ISSN: 0931-0509
Published online June 2003 | e-ISSN: 1460-2385 | DOI: http://dx.doi.org/10.1093/ndt/gfg104
Dynamics of secretion and metabolism of PTH during hypo‐ and hypercalcaemia in the dog as determined by the ‘intact’ and ‘whole’ PTH assays

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Background. Recent evidence has shown that the assay for ‘intact’ parathyroid hormone (I‐PTH) not only reacts with 1–84 PTH but also with large non‐1–84 PTH fragments, most of which is probably 7–84 PTH. As a result, an assay specific for 1–84 PTH named ‘whole’ PTH (W‐PTH) has been developed. The present study was designed: (i) to determine whether the W‐PTH assay reliably measures PTH values in the dog; (ii) to evaluate differences between the W‐PTH and I‐PTH assays during hypo‐ and hypercalcaemia; and (iii) to assess the peripheral metabolism of W‐PTH and I‐PTH.

Methods. In normal dogs, hypocalcaemia was induced by EDTA infusion and was followed with a 90 min hypocalcaemic clamp. Hypercalcaemia was induced with a calcium infusion.

Results. I‐PTH and W‐PTH values increased from 36±8 and 13±3 pg/ml (P=0.01) at baseline to a maximum of 158±40 and 62±15 pg/ml (P=0.02 vs I‐PTH) during hypocalcaemia. The W‐PTH/I‐PTH ratio, 38±4% at baseline, did not change during the induction of hypocalcaemia, but sustained hypocalcaemia increased (P<0.05) this ratio. During hypercalcaemia, maximal suppression for I‐PTH was 2.0±0.5 and only 5.7±0.6 pg/ml for W‐PTH, due to a decreased sensitivity of the W‐PTH assay at values <5 pg/ml. The disappearance rate of PTH was determined in five additional dogs which underwent a parathyroidectomy (PTX). At 2.5 min after PTX, W‐PTH was metabolized more rapidly, with a value of 25±2% of the pre‐PTX value vs 30±3% for I‐PTH (P<0.05).

Conclusions. (i) The W‐PTH/I‐PTH ratio is less in the normal dog than in the normal human, suggesting that the percentage of non‐1–84 PTH measured with the I‐PTH assay is greater in normal dogs than in normal humans; (ii) the lack of change in the W‐PTH/I‐PTH ratio during acute hypocalcaemia is different from the situation observed in humans; and (iii) the dog appears to be a good model to study I‐PTH and W‐PTH assays during hypocalcaemia.

Keywords: calcium; hypercalcaemia; hypocalcaemia; intact PTH; parathyroid hormone; whole PTH

Journal Article.  4873 words.  Illustrated.

Subjects: Nephrology

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