Pierre Delanaye1, François Paquot1, Antoine Bouquegneau1, Frank Blocki2, Jean-Marie Krzesinski1, Pieter Evenepoel3, Hans Pottel4, Etienne Cavalier5. 1. Department of Nephrology, Dialysis, Hypertension, Transplantation, University of Liège (ULg CHU), CHU Sart Tilman, Liège, Belgium. 2. Medical LIAISON Bone & Mineral, DiaSorin Inc, Stillwater, MN, USA. 3. Department of Nephrology and Renal Transplantation, University of Leuven, University Hospitals Leuven, Leuven, Belgium. 4. Department of Public Health and Primary Care at Kulak, University of Leuven, Kortrijk, Belgium. 5. Department of Clinical Chemistry, University of Liège, CHU Sart Tilman, Liège, Belgium.
Abstract
Background: Sclerostin, a 22-kDa protein secreted by osteocytes, acts as a potent inhibitor of osteoblast activity. In chronic kidney disease (CKD), sclerostin is a putative driver of the bone-vascular axis. However, large discrepancies between sclerostin assays have been described. Methods: We compared four different assays [Biomedica (BM), TecoMedical (TE), R&D (RD) and MesoScaleDiscovery (MSD)] in an analytical study and addressed the question whether bioassay choice affects the correlation between circulating sclerostin and clinical and biochemical determinants. Circulating sclerostin levels were determined in 39 prevalent dialysis patients and 82 non-dialysis patients referred for glomerular filtration rate measurement. Results: In the 82 non-dialysis patients, we observed large differences in median (interquartile range) sclerostin concentrations (in pg/mL): BM, 984 [interquartile range (IQR) 648]; TE, 629 (IQR 237); RD, 154 (IQR 84) and MSD, 36 (IQR 19). The concordance correlation coefficient between assays was poor (0.1-0.44). The same discrepancies were observed in dialysis patients. A significant negative rank correlation was found between glomerular filtration rate and sclerostin measured by BM and TE but not by MSD and RD. Associations between sclerostin and age, gender, weight or parathormone were also different according to the assay considered. Conclusions: Clinical inference relating sclerostin levels found in the general, CKD and dialysis populations is largely influenced by the assay used to measure this biomarker.
Background: Sclerostin, a 22-kDa protein secreted by osteocytes, acts as a potent inhibitor of osteoblast activity. In chronic kidney disease (CKD), sclerostin is a putative driver of the bone-vascular axis. However, large discrepancies between sclerostin assays have been described. Methods: We compared four different assays [Biomedica (BM), TecoMedical (TE), R&D (RD) and MesoScaleDiscovery (MSD)] in an analytical study and addressed the question whether bioassay choice affects the correlation between circulating sclerostin and clinical and biochemical determinants. Circulating sclerostin levels were determined in 39 prevalent dialysis patients and 82 non-dialysis patients referred for glomerular filtration rate measurement. Results: In the 82 non-dialysis patients, we observed large differences in median (interquartile range) sclerostin concentrations (in pg/mL): BM, 984 [interquartile range (IQR) 648]; TE, 629 (IQR 237); RD, 154 (IQR 84) and MSD, 36 (IQR 19). The concordance correlation coefficient between assays was poor (0.1-0.44). The same discrepancies were observed in dialysis patients. A significant negative rank correlation was found between glomerular filtration rate and sclerostin measured by BM and TE but not by MSD and RD. Associations between sclerostin and age, gender, weight or parathormone were also different according to the assay considered. Conclusions: Clinical inference relating sclerostin levels found in the general, CKD and dialysis populations is largely influenced by the assay used to measure this biomarker.
Authors: Gerhard Klingenschmid; Lena Tschiderer; Gottfried Himmler; Gregorio Rungger; Stefan Brugger; Peter Santer; Johann Willeit; Stefan Kiechl; Peter Willeit Journal: J Am Heart Assoc Date: 2020-03-15 Impact factor: 5.501