Unveiling a new era with liquid chromatography coupled with mass spectrometry to enhance parathyroid hormone measurement in patients with chronic kidney disease.
[en] Precise determination of circulating parathyroid hormone (PTH) concentration is crucial to diagnose and manage various disease conditions, including the chronic kidney disease-mineral and bone disorder. However, the lack of standardization in PTH assays is challenging for clinicians, potentially leading to medical errors because the different assays do not provide equivalent results and use different reference ranges. Here, we aimed to evaluate the impact of recalibrating PTH immunoassays by means of a recently developed LC-MS/MS method as the reference. Utilizing a large panel of pooled plasma samples with PTH concentrations determined by the LC-MS/MS method calibrated with the World Health Organization (WHO) 95/646 International Standard, five PTH immunoassays were recalibrated. The robustness of this standardization was evaluated over time using different sets of samples. The recalibration successfully reduced inter-assay variability with harmonization of PTH measurements across different assays. By recalibrating the assays based on the WHO 95/646 International Standard, we demonstrated the feasibility for standardizing PTH measurement results and adopting common reference ranges for PTH assays, facilitating a more consistent interpretation of PTH values. The recalibration process aligns PTH results obtained from various immunoassays with the LC-MS/MS method, providing more consistent and reliable measurements. Thus, establishing true standardization across all PTH assays is crucial to ensure consistent interpretation and clinical decision-making.
Disciplines :
Laboratory medicine & medical technology Urology & nephrology
Author, co-author :
Cavalier, Etienne ; Centre Hospitalier Universitaire de Liège - CHU > > Service de chimie clinique
Farre Segura, Jordi ; Université de Liège - ULiège > Département de pharmacie > Chimie médicale
LUKAS, Pierre ; Centre Hospitalier Universitaire de Liège - CHU > > Service de chimie clinique
GENDEBIEN, Anne-Sophie ; Centre Hospitalier Universitaire de Liège - CHU > > Service de chimie clinique
Peeters, Stéphanie ; Centre Hospitalier Universitaire de Liège - CHU > > Service de chimie clinique
Massonnet, Philippe ; Centre Hospitalier Universitaire de Liège - CHU > > Service de chimie clinique
Le Goff, Caroline ; Centre Hospitalier Universitaire de Liège - CHU > > Service de chimie clinique
Bouquegneau, Antoine ; Centre Hospitalier Universitaire de Liège - CHU > > Service de néphrologie
Souberbielle, Jean-Claude; Service des explorations fonctionnelles, Hôpital Necker-Enfants malades, AP-HP Paris, France
Delatour, Vincent; Department of Biomedical and Organic Chemistry, Laboratoire National de Métrologie et d'Essais (LNE), Paris, France
Delanaye, Pierre ; Centre Hospitalier Universitaire de Liège - CHU > > Service de néphrologie
Language :
English
Title :
Unveiling a new era with liquid chromatography coupled with mass spectrometry to enhance parathyroid hormone measurement in patients with chronic kidney disease.
Kidney Disease: Improving Global Outcomes (KDIGO) CKD-MBD Update Work Group. KDIGO 2017 Clinical Practice Guideline Update for the Diagnosis, Evaluation, Prevention, and Treatment of Chronic Kidney Disease-Mineral and Bone Disorder (CKD-MBD). Kidney Int Suppl (2011) 7 (2017), 1–59.
Cavalier, E., Vasikaran, S., Bhattoa, H.P., et al. The path to the standardization of PTH: is this a realistic possibility? A position paper of the IFCC C-BM. Clin Chim Acta 515 (2021), 44–51.
Sturgeon, C.M., Sprague, S., Almond, A., et al. Perspective and priorities for improvement of parathyroid hormone (PTH) measurement—a view from the IFCC Working Group for PTH. Clin Chim Acta 467 (2017), 42–47.
Souberbielle, J.-C., Boutten, A., Carlier, M.-C., et al. Inter-method variability in PTH measurement: implication for the care of CKD patients. Kidney Int 70 (2006), 345–350.
Gardella, T.J., Axelrod, D., Rubin, D., et al. Mutational analysis of the receptor-activating region of human parathyroid hormone. J Biol Chem 266 (1991), 13141–13146.
Segre, G.V., Perkins, A.S., Witters, L., Potts, J.T., Metabolism of parathyroid hormone by isolated rat Kupffer cells and hepatocytes. J Clin Invest 67 (1981), 449–457.
Hanley, D.A., Ayer, L.M., Calcium-dependent release of carboxyl-terminal fragments of parathyroid hormone by hyperplastic human parathyroid tissue in vitro. J Clin Endocrinol Metab 63 (1986), 1075–1079.
Mayer, G.P., Keaton, J.A., Hurst, J.G., Habener, J.F., Effects of plasma calcium concentration on the relative proportion of hormone and carboxyl fragments in parathyroid venous blood. Endocrinology 104 (1979), 1778–1784.
Yamashita, H., Gao, P., Cantor, T., et al. Large carboxy-terminal parathyroid hormone (PTH) fragment with a relatively longer half-life than 1-84 PTH is secreted directly from the parathyroid gland in humans. Eur J Endocrinol 149 (2003), 301–306.
Yamashita, H., Cantor, T., Uchino, S., et al. Sequential changes in plasma intact and whole parathyroid hormone levels during parathyroidectomy for secondary hyperparathyroidism. World J Surg 29 (2005), 169–173.
D'amour, P., Lazure, C., Labelle, F., Metabolism of radioiodinated carboxy-terminal fragments of bovine parathyroid hormone in normal and anephric rats. Endocrinology 117 (1985), 127–134.
D'Amour, P., Circulating PTH molecular forms: what we know and what we don't. Kidney Int 70:suppl 102 (2006), S29–S33.
Kritmetapak, K., Losbanos, L.A., Hines, J.M., et al. Chemical characterization and quantification of circulating intact PTH and PTH fragments by high-resolution mass spectrometry in chronic renal failure. Clin Chem 67 (2021), 843–853.
Lepage, R., Roy, L., Brossard, J.H., et al. A non-(1-84) circulating parathyroid hormone (PTH) fragment interferes significantly with intact PTH commercial assay measurements in uremic samples. Clin Chem 44 (1998), 805–809.
John, M.R., Goodman, W.G., Ping, G., et al. A novel immunoradiometric assay detects full-length human PTH but not amino-terminally truncated fragments: implications for PTH measurements in renal failure. J Clin Endocrinol Metab 84 (1999), 4287–4290.
Gao, P., Scheibel, S., D'Amour, P., et al. Development of a novel immunoradiometric assay exclusively for biologically active whole parathyroid hormone 1-84: implications for improvement of accurate assessment of parathyroid function. J Bone Miner Res 16 (2001), 605–614.
Farré-Segura, J., Le Goff, C., Lukas, P., et al. Validation of an LC-MS/MS method using solid-phase extraction for the quantification of 1-84 parathyroid hormone: toward a candidate reference measurement procedure. Clin Chem 3 (2022), 1399–1409.
Kidney Disease: Improving Global Outcomes (KDIGO) CKD-MBD Work Group. KDIGO clinical practice guideline for the diagnosis, evaluation, prevention, and treatment of chronic kidney disease-mineral bone disorder (CKD-MBD). Kidney Int 76:suppl 113 (2009), S1–S130.
National Kidney Foundation. K/DOQI clinical practice guidelines for bone metabolism and disease in chronic kidney disease. Am J Kidney Dis 42:4 suppl 3 (2003), S1–S201.
Cavalier, E., Delanaye, P., Vranken, L., et al. Interpretation of serum PTH concentrations with different kits in dialysis patients according to the KDIGO guidelines: importance of the reference (normal) values. Nephrol Dial Transplant 27 (2011), 1950–1956.
Souberbielle, J.-C., Brazier, F., Piketty, M.-L., et al. How the reference values for serum parathyroid hormone concentration are (or should be) established?. J Endocrinal Invest 40 (2016), 241–256.
Cavalier, E., Lukas, P., Bekaert, A.-C., et al. Analytical and clinical evaluation of the new Fujirebio Lumipulse®G non-competitive assay for 25(OH)-vitamin D and three immunoassays for 25(OH)D in healthy subjects, osteoporotic patients, third trimester pregnant women, healthy African subjects, hemodialyzed and intensive care patients. Clin Chem Lab Med 54 (2016), 1347–1355.
Yalla, N., Bobba, G., Guo, G., et al. Parathyroid hormone reference ranges in healthy individuals classified by vitamin D status. J Endocrinol Invest 42 (2019), 1353–1360.
Delgado, J.A., Bauça, J.M., Pastor, M.I., Barceló, A., Use of data mining in the establishment of age-adjusted reference intervals for parathyroid hormone. Clin Chim Acta 508 (2020), 217–220.
Hocher, B., Zeng, S., Clear the fog around parathyroid hormone assays: what do iPTH assays really measure?. Clin J Am Soc Nephrol 13 (2018), 524–526.
Hocher, B., Armbruster, F.P., Stoeva, S., et al. Measuring parathyroid hormone (PTH) in patients with oxidative stress—do we need a fourth generation parathyroid hormone assay?. PLoS One, 7, 2012, e40242.
Zhang, C.X., Weber, B.V., Thammavong, J., et al. Identification of carboxyl-terminal peptide fragments of parathyroid hormone in human plasma at low-picomolar levels by mass spectrometry. Anal Chem 78 (2006), 1636–1643.
Lopez, M.F., Rezai, T., Sarracino, D.A., et al. Selected reaction monitoring-mass spectrometric immunoassay responsive to parathyroid hormone and related variants. Clin Chem 56 (2010), 281–290.
Souberbielle, J.-C.P., Roth, H., Fouque, D.P., Parathyroid hormone measurement in CKD. Kidney Int 77 (2010), 93–100.
Cavalier, E., Daly, A.F., Betea, D., et al. The ratio of parathyroid hormone as measured by third- and second-generation assays as a marker for parathyroid carcinoma. J Clin Endocrinol Metab 95 (2010), 3745–3749.
Cavalier, E., Schleck, M.-L., Souberbielle, J.-C., Spurious intraoperative PTH results observed with 2nd, but not with 3rd generation PTH assays. Clin Chim Acta 477 (2018), 72–73.
Nguyen-Yamamoto, L., Rousseau, L., Brossard, J.H., et al. Origin of parathyroid hormone (PTH) fragments detected by intact-PTH assays. Eur J Endocrinol 147 (2002), 123–131.
Komaba, H., Takeda, Y., Shin, J., et al. Reversed whole PTH/intact PTH ratio as an indicator of marked parathyroid enlargement: five case studies and a literature review. NDT Plus, 1(suppl 3), 2008, iii54–iii58.