Effect of nutritional calcium and phosphate loading on calciprotein particle kinetics in adults with normal and impaired kidney function
Open accessAbstract
Plasma approaches metastability with respect to its calcium and phosphate content, with only minor perturbations in ionic activity needed to sustain crystal growth once nucleated. Physiologically, calcium and phosphate are intermittently absorbed from the diet each day, yet plasma concentrations of these ions deviate minimally post-prandially. This implies the existence of a blood-borne mineral buffer system to sequester calcium phosphates and minimise the risk of deposition in the soft tissues. Calciprotein particles (CPP), endogenous mineral-protein colloids containing the plasma protein fetuin-A, may fulfill this function but definitive evidence linking dietary mineral loading with their formation is lacking. Here we demonstrate that CPP are formed as a normal physiological response to feeding in healthy adults and that this occurs despite minimal change in conventional serum mineral markers. Further, in individuals with Chronic Kidney Disease (CKD), in whom mineral handling is impaired, we show that both fasting and post-prandial levels of CPP precursors are markedly augmented and strongly inversely correlated with kidney function. This study highlights the important, but often neglected, contribution of colloidal biochemistry to mineral homeostasis and provides novel insight into the dysregulation of mineral metabolism in CKD.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
Fetuin-A is an inhibitor of calcium phosphate precipitation in the blood and has been shown not to be regulated in the post-prandial response of healthy volunteers.
“Fetuin-A is an inhibitor of calcium phosphate precipitation in the blood [54] and has been shown to be not regulated in the post-prandial response of healthy volunteers [53].”
From Controlled dietary phosphate loading in healthy young men elevates plasma phosphate and FGF23 levels (2025) · cites this paper as [53]
The citation [53] attaches to the post-prandial claim. The Discussion (page unavailable) says fetuin-A appeared stable in healthy controls, but also reports increases at 30 and 60 minutes in an uncorrected analysis and cautions that the study may have been underpowered to detect an effect. The source therefore does not establish that fetuin-A is not regulated after a meal. (LLM, conf=0.87)
Experimental — accuracy not yet measured
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
Estimation of Relationships for Limited Dependent Variables
Tobin, J. (1958) · Econometrica · doi:10.2307/1907382 · Cited by 6,996 · see citing works
Schäfer, C., Heiss, A., Schwarz, A., et al. (2003) · Journal of Clinical Investigation · doi:10.1172/jci17202 · Cited by 919 · see citing works
Structural Basis of Calcification Inhibition by α2-HS Glycoprotein/Fetuin-A
Heiss, A., DuChesne, A., Denecke, B., et al. (2003) · Journal of Biological Chemistry · doi:10.1074/jbc.m210868200 · Cited by 472 · see citing works
Selecting a sample size for studies with repeated measures
Guo, Y. M., Logan, H. L., Glueck, D. H., & Muller, K. E. (2013) · BMC Medical Research Methodology · doi:10.1186/1471-2288-13-100 · Cited by 379 · see citing works
Chen, J., Budoff, M. J., Reilly, M. P., Yang, W. P., Rosas, S. E., Rahman, M., Zhang, X., Roy, J. A., Lustigova, E., Nessel, L. C., et al. (2017) · JAMA Cardiology · doi:10.1001/jamacardio.2017.0363 · Cited by 367 · see citing works
Schinke, T., Amendt, C., Trindl, A., et al. (1996) · Journal of Biological Chemistry · doi:10.1074/jbc.271.34.20789 · Cited by 358 · see citing works
Nanoparticle-Based Test Measures Overall Propensity for Calcification in Serum
Pasch, A., Farese, S., Gräber, S., Wald, J., Richtering, W. H., Floege, J., & Jahnen‐Dechent, W. (2012) · Journal of the American Society of Nephrology · doi:10.1681/asn.2012030240 · Cited by 341 · see citing works
Self-citationLebreton, J. P., Joisel, F., Raoult, J. P., et al. (1979) · Journal of Clinical Investigation · doi:10.1172/jci109551 · Cited by 334 · see citing works
Sprague, S. M., Bellorín-Font, E., Jorgetti, V., Carvalho, A. B., Malluche, H. H., Ferreira, A., D’Haese, P. C., Drüeke, T. B., Du, H., Manley, T., et al. (2015) · American Journal of Kidney Diseases · doi:10.1053/j.ajkd.2015.06.023 · Cited by 318 · see citing works
Serum Calcification Propensity Predicts All-Cause Mortality in Predialysis CKD
Smith, E. R., Ford, M. L., Tomlinson, L. A., Bodenham, E., McMahon, L. P., Farese, S., Rajkumar, C., Holt, S. G., & Pasch, A. (2013) · Journal of the American Society of Nephrology · doi:10.1681/asn.2013060635 · Cited by 247 · see citing works
Self-citationAghagolzadeh, P., Bachtler, M., Bijarnia, R. K., et al. (2016) · Atherosclerosis · doi:10.1016/j.atherosclerosis.2016.05.044 · Cited by 239 · see citing works
Fetuin-Mineral Complex Reflects Extraosseous Calcification Stress in CKD
Hamano, T., Matsui, I., Mikami, S., Tomida, K., Fujii, N., Imai, E., Rakugi, H., & Isaka, Y. (2010) · Journal of the American Society of Nephrology · doi:10.1681/asn.2009090944 · Cited by 223 · see citing works
Smith, E. R., Ford, M. L., Tomlinson, L. A., Rajkumar, C., McMahon, L. P., & Holt, S. G. (2011) · Nephrology Dialysis Transplantation · doi:10.1093/ndt/gfr609 · Cited by 215 · see citing works
Self-citationA materials science vision of extracellular matrix mineralization
Reznikov, N., Steele, J. A. M., Fratzl, P., & Stevens, M. M. (2016) · Nature Reviews Materials · doi:10.1038/natrevmats.2016.41 · Cited by 200 · see citing works
Clearance of Fetuin-A–Containing Calciprotein Particles Is Mediated by Scavenger Receptor-A
Herrmann, M., Schäfer, C., Heiss, A., Gräber, S., Kinkeldey, A., Büscher, A., Schmitt, M. M. N., Bornemann, J., Nimmerjahn, F., i, M. H., et al. (2012) · Circulation Research · doi:10.1161/circresaha.111.261479 · Cited by 179 · see citing works
Jahnen‐Dechent, W., Schäfer, C., Ketteler, M., & McKee, M. D. (2007) · Journal of Molecular Medicine · doi:10.1007/s00109-007-0294-y · Cited by 173 · see citing works
Postprandial Mineral Metabolism and Secondary Hyperparathyroidism in Early CKD
Isakova, T., Gutiérrez, O. M., Shah, A., et al. (2008) · Journal of the American Society of Nephrology · doi:10.1681/asn.2007060673 · Cited by 160 · see citing works
Pasch, A., Block, G. A., Bachtler, M., Smith, E. R., Jahnen‐Dechent, W., Arampatzis, S., Chertow, G. M., Parfrey, P. S., Ma, X., & Floege, J. (2016) · Clinical Journal of the American Society of Nephrology · doi:10.2215/cjn.04720416 · Cited by 158 · see citing works
Self-citationHeiss, A., Pipich, V., Jahnen‐Dechent, W., & Schwahn, D. (2010) · Biophysical Journal · doi:10.1016/j.bpj.2010.10.030 · Cited by 127 · see citing works
Miura, Y., Iwazu, Y., Shiizaki, K., et al. (2018) · Scientific Reports · doi:10.1038/s41598-018-19677-4 · Cited by 127 · see citing works
The Human Response to Acute Enteral and Parenteral Phosphate Loads
Scanni, R., vonRotz, M., Jehle, S., Hulter, H. N., & Krapf, R. (2014) · Journal of the American Society of Nephrology · doi:10.1681/asn.2013101076 · Cited by 118 · see citing works
Niv, Y., & FRASER, G. M. (2002) · Journal of Clinical Gastroenterology · doi:10.1097/00004836-200207000-00003 · Cited by 115 · see citing works
Kestenbaum, B. R., Adeney, K. L., de Boer, I. H., Ix, J. H., Shlipak, M. G., & Siscovick, D. S. (2009) · Kidney International · doi:10.1038/ki.2009.298 · Cited by 113 · see citing works
A phosphate-centric paradigm for pathophysiology and therapy of chronic kidney disease
Kuro‐o, M. (2013) · Kidney International Supplements · doi:10.1038/kisup.2013.88 · Cited by 106 · see citing works
Calciprotein particles regulate fibroblast growth factor-23 expression in osteoblasts
Akiyama, K., Miura, Y., Hayashi, H., et al. (2019) · Kidney International · doi:10.1016/j.kint.2019.10.019 · Cited by 106 · see citing works
Bundy, J. D., Cai, X., Scialla, J. J., Dobre, M. A., Chen, J., Hsu, C., Leonard, M. B., Go, A. S., Rao, P. S., Lash, J. P., et al. (2019) · American Journal of Kidney Diseases · doi:10.1053/j.ajkd.2019.01.024 · Cited by 105 · see citing works
Self-citationKoppert, S., Büscher, A., Babler, A., Ghallab, A., Buhl, E. M., Latz, E., Hengstler, J., Smith, E. R., & Jahnen-Dechent, W. (2018) · Frontiers in Immunology · doi:10.3389/fimmu.2018.01991 · Cited by 103 · see citing works
Self-citationSmith, E. R., Cai, M. M., McMahon, L. P., et al. (2012) · Nephrology · doi:10.1111/nep.12021 · Cited by 89 · see citing works
Self-citationA novel fluorescent probe-based flow cytometric assay for mineral-containing nanoparticles in serum
Smith, E. R., Hewitson, T. D., Cai, M. M., Aghagolzadeh, P., Bachtler, M., Pasch, A., & Holt, S. G. (2017) · Scientific Reports · doi:10.1038/s41598-017-05474-y · Cited by 81 · see citing works
Self-citationLiu, C., Cripe, T. P., & Kim, M. (2010) · Molecular Therapy · doi:10.1038/mt.2010.127 · Cited by 76 · see citing works
Eelderink, C., Velde‐Keyzer, C. A. T., Frenay, A.-R. S., Vermeulen, E. A., Bachtler, M., Aghagolzadeh, P., van Dijk, P. R., Gansevoort, R. T., Vervloet, M. G., Hillebrands, J., et al. (2020) · Arteriosclerosis Thrombosis and Vascular Biology · doi:10.1161/atvbaha.120.314187 · Cited by 71 · see citing works
Self-citationMineralisation of soft and hard tissues and the stability of biofluids
Holt, C., Lenton, S., Nylander, T., Sørensen, E. S., & Teixeira, S. C. M. (2013) · Journal of Structural Biology · doi:10.1016/j.jsb.2013.11.009 · Cited by 69 · see citing works
Serum Calcification Propensity and Clinical Events in CKD
Bundy, J. D., Cai, X., Mehta, R. C., Scialla, J. J., de Boer, I. H., Hsu, C., Go, A. S., Dobre, M. A., Chen, J., Rao, P. S., et al. (2019) · Clinical Journal of the American Society of Nephrology · doi:10.2215/cjn.04710419 · Cited by 68 · see citing works
Self-citationJahnen‐Dechent, W., Büscher, A., Köppert, S., Heiss, A., Kuro‐o, M., & Smith, E. R. (2020) · Journal of Structural Biology · doi:10.1016/j.jsb.2020.107577 · Cited by 66 · see citing works
Self-citationThe role of fetuin-A in mineral trafficking and deposition
Cai, M. M., Smith, E. R., & Holt, S. G. (2015) · BoneKEy Reports · doi:10.1038/bonekey.2015.39 · Cited by 65 · see citing works
Self-citationAcute Adaption to Oral or Intravenous Phosphate Requires Parathyroid Hormone
Thomas, L., Bettoni, C., Knöpfel, T., Hernando, N., Biber, J., & Wagner, C. A. (2016) · Journal of the American Society of Nephrology · doi:10.1681/asn.2016010082 · Cited by 59 · see citing works
Biochemical transformation of calciprotein particles in uraemia
Smith, E. R., Hewitson, T. D., Hanssen, E. G., & Holt, S. G. (2018) · Bone · doi:10.1016/j.bone.2018.02.023 · Cited by 59 · see citing works
Self-citationKöppert, S., Ghallab, A., Peglow, S., Winkler, C. F., Gräber, S., Büscher, A., Hengstler, J. G., & Jahnen‐Dechent, W. (2021) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2021.633925 · Cited by 57 · see citing works
Herrmann, M., Babler, A., Moshkova, I., Gremse, F., Kiessling, F. M., Kusebauch, U., Nelea, V., Kramann, R., Moritz, R. L., McKee, M. D., et al. (2020) · PLoS ONE · doi:10.1371/journal.pone.0228503 · Cited by 52 · see citing works
Pasch, A., Jahnen‐Dechent, W., & Smith, E. R. (2018) · International Journal of Nephrology · doi:10.1155/2018/9182078 · Cited by 51 · see citing works
Self-citationIntestinal phosphate absorption in a model of chronic renal failure
Marks, J., Churchill, L. J., Srai, S. K., Biber, J., Murer, H., Jaeger, P., Debnam, E. S., & Unwin, R. J. (2007) · Kidney International · doi:10.1038/sj.ki.5002292 · Cited by 50 · see citing works
Chen, W., Anokhina, V. S., Dieudonné, G., et al. (2018) · Nephrology Dialysis Transplantation · doi:10.1093/ndt/gfy117 · Cited by 48 · see citing works
Bressendorff, I. O., Hansen, D., Pasch, A., et al. (2019) · Nephrology Dialysis Transplantation · doi:10.1093/ndt/gfz234 · Cited by 44 · see citing works
Self-citationCalciprotein particles: mineral behaving badly?
Smith, E. R., Hewitson, T. D., & Jahnen‐Dechent, W. (2020) · Current Opinion in Nephrology & Hypertension · doi:10.1097/mnh.0000000000000609 · Cited by 42 · see citing works
Self-citationNakazato, J., Hoshide, S., Wake, M., Miura, Y., Kuro‐o, M., & Kario, K. (2019) · Journal of Cardiology · doi:10.1016/j.jjcc.2019.04.008 · Cited by 39 · see citing works
Vascular Calcification in Uremia: New-Age Concepts about an Old-Age Problem
Smith, E. R. (2015) · Methods in molecular biology · doi:10.1007/978-1-4939-3353-2_13 · Cited by 38 · see citing works
Self-citationDiagnostic Tests for Vascular Calcification
Smith, E. R., Hewitson, T. D., & Holt, S. G. (2019) · Advances in Chronic Kidney Disease · doi:10.1053/j.ackd.2019.07.001 · Cited by 38 · see citing works
Self-citationNature’s remedy to phosphate woes: calciprotein particles regulate systemic mineral metabolism
Jahnen‐Dechent, W., & Smith, E. R. (2020) · Kidney International · doi:10.1016/j.kint.2019.12.018 · Cited by 35 · see citing works
Self-citationChen, W., Fitzpatrick, J., Trujillo, J. M. M., Sozio, S. M., Jaar, B. G., Estrella, M. M., Serrano, J., Anokhina, V. S., Miller, B. L., Melamed, M. L., et al. (2020) · American Journal of Kidney Diseases · doi:10.1053/j.ajkd.2020.05.031 · Cited by 34 · see citing works
ter Meulen, K. J., Dekker, M. J. E., Pasch, A., et al. (2019) · PLoS ONE · doi:10.1371/journal.pone.0225824 · Cited by 32 · see citing works
Self-citationShishkova, D. K., Velikanova, E. A., Sinitsky, M. Y., et al. (2019) · International Journal of Molecular Sciences · doi:10.3390/ijms20225728 · Cited by 31 · see citing works
Stremke, E. R., Wiese, G. N., Moe, S. M., Wastney, M. E., Moorthi, R. N., & Gallant, K. M. H. (2021) · Journal of the American Society of Nephrology · doi:10.1681/asn.2020091340 · Cited by 31 · see citing works
Yamada, H., Kuro‐o, M., Ishikawa, S., Funazaki, S., Kusaka, I., Kakei, M., & Hara, K. (2017) · Nephrology · doi:10.1111/nep.12994 · Cited by 27 · see citing works
The Role of Secondary Calciprotein Particles in the Mineralisation Paradox of Chronic Kidney Disease
Cai, M. M., Smith, E. R., Tan, S., Hewitson, T. D., & Holt, S. G. (2017) · Calcified Tissue International · doi:10.1007/s00223-017-0313-0 · Cited by 27 · see citing works
Self-citationGatate, Y., Nakano, S., Mizuno, Y., et al. (2020) · Atherosclerosis · doi:10.1016/j.atherosclerosis.2020.03.016 · Cited by 27 · see citing works
Thiem, U., Soellradl, I., Robl, B., Wątorek, E., Blum, S., Dumfarth, A., Marculescu, R., Pasch, A., Haller, M. C., & Cejka, D. (2020) · Clinical Kidney Journal · doi:10.1093/ckj/sfaa154 · Cited by 24 · see citing works
Self-citationSmith, E. R., Pan, F. F. M., Hewitson, T. D., et al. (2020) · Kidney International Reports · doi:10.1016/j.ekir.2020.06.014 · Cited by 23 · see citing works
Self-citationRuderman, I., Smith, E. R., Toussaint, N. D., et al. (2018) · BMC Nephrology · doi:10.1186/s12882-018-0910-9 · Cited by 22 · see citing works
Self-citationVorland, C. J., Biruete, A., Lachcik, P. J., et al. (2019) · Journal of Bone and Mineral Research · doi:10.1002/jbmr.3894 · Cited by 21 · see citing works
Volk, C., Schmidt, B., Brandsch, C., Kurze, T., Schlegelmilch, U., Grosse, I., Ulrich, C., Girndt, M., & Stangl, G. I. (2022) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/clinem/dgab635 · Cited by 21 · see citing works
The effect of lanthanum carbonate on calciprotein particles in hemodialysis patients
Nakamura, K., Nagata, Y., Hiroyoshi, T., et al. (2019) · Clinical and Experimental Nephrology · doi:10.1007/s10157-019-01832-4 · Cited by 20 · see citing works
Tiong, M. K. D., Krishnasamy, R., Smith, E. R., Hutchison, C. A., Ryan, E., Pascoe, E. M., Hawley, C. M., Hewitson, T. D., Jardine, M., Roberts, M. A., et al. (2021) · Hemodialysis International · doi:10.1111/hdi.12924 · Cited by 20 · see citing works
Self-citationImpaired Phosphate Tolerance Revealed With an Acute Oral Challenge
Turner, M. E., White, C. A., Hopman, W. M., Ward, E., Jeronimo, P. S., Adams, M. A., & Holden, R. M. (2017) · Journal of Bone and Mineral Research · doi:10.1002/jbmr.3294 · Cited by 19 · see citing works
The Isolation and Quantitation of Fetuin-A-Containing Calciprotein Particles from Biological Fluids
Smith, E. R. (2015) · Methods in molecular biology · doi:10.1007/978-1-4939-3353-2_15 · Cited by 13 · see citing works
Self-citationAcute Tissue Mineral Deposition in Response to a Phosphate Pulse in Experimental CKD
Zelt, J. G. E., Svajger, B. A., Quinn, K. L., Turner, M. E., Laverty, K. J., Shum, B., Holden, R. M., & Adams, M. A. (2018) · Journal of Bone and Mineral Research · doi:10.1002/jbmr.3572 · Cited by 13 · see citing works
Intestinal phosphorus absorption: recent findings in translational and clinical research
Gallant, K. M. H., & Vorland, C. J. (2021) · Current Opinion in Nephrology & Hypertension · doi:10.1097/mnh.0000000000000719 · Cited by 13 · see citing works
Calcium and Magnesium Phosphates: Normal and Pathological Mineralization
Magalhães, M. C. F., Marques, P. A. A. P., & Correia, R. N. (2006) · doi:10.1002/0470092122.ch3 · Cited by 12 · see citing works
Uedono, H., Mori, K., Ochi, A., Nakatani, S., Miki, Y., Tsuda, A., Morioka, T., Nagata, Y., Imanishi, Y., Shoji, T., et al. (2021) · Scientific Reports · doi:10.1038/s41598-021-86881-0 · Cited by 10 · see citing works
Reduction of Calciprotein Particles in Adults Receiving Infliximab for Chronic Inflammatory Disease
Tiong, M. K. D., Smith, E. R., Toussaint, N. D., Al‐Khayyat, H. F., & Holt, S. G. (2021) · JBMR Plus · doi:10.1002/jbm4.10497 · Cited by 8 · see citing works
Self-citationCalciprotein particles: A mineral biomarker in need of better measurement
Smith, E. R. (2020) · Atherosclerosis · doi:10.1016/j.atherosclerosis.2020.04.017 · Cited by 7 · see citing works
Self-citation
Flagged first, then by citations
Research works printed but not linked: 1
- [1]Magalhães, M. C. F., Marques, P. A. A. P. & Correia, R. N. Biomineralization—Medical Aspects of Solubility (eds. Königsberger, E. & Königsberger, L.). 71–123. (Wiley, 2006).
Cited by
Sorted by citations
Controlled dietary phosphate loading in healthy young men elevates plasma phosphate and FGF23 levels
Gerber, J. S., Arroyo, E. M. P., Pastor, J., Correia, M., Rudloff, S., Moe, O. W., Egli-Spichtig, D., Mohebbi, N., & Wagner, C. A. (2025) · Pflügers Archiv - European Journal of Physiology · doi:10.1007/s00424-024-03046-4 · Cited by 15 · see citing works
- Authors
- Tiong, M. K., Cai, M. M. X., Toussaint, N. D., Tan, S.-J., Pasch, A., & Smith, E. R.
- Affiliations
- The Royal Melbourne Hospital (AU)
- Johannes Kepler University of Linz (AT)
- Corresponding author
- Tiong, Mark K.
- Smith, Edward R.
- ORCID
- Venue
- Scientific Reports
- Published
- 2022-05-05
- Volume
- 12
- Issue
- 1
- Pages
- 7358-7358
- ISSN
- 2045-2322 (ISSN-L)
- PMC
- PMC9072391
- OpenAlex
- W4229043273
- Cited by
- 38
- References
- 70
- Citations by year
- 2026: 7 · 2025: 5 · 2024: 14 · 2023: 6 · 2022: 6
- FWCI
- 4.92
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- Scientific Reports (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
- Minerva Access (University of Melbourne) (submittedVersion, cc-by)
- Funders
- Royal Melbourne Hospital Research Funding Program Grant in Aid (Grant number 2018.036)
- Topics
- Health Sciences › Medicine › Nephrology › Parathyroid Disorders and Treatments
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Alkaline Phosphatase Research Studies
- Health Sciences › Medicine › Hematology › Iron Metabolism and Disorders
- Keywords
- calciprotein particles, fetuin-A, dietary calcium, dietary phosphorus, chronic kidney disease, mineral homeostasis, renal function, calcium phosphate deposition
- MeSH terms
- Adult, Calcium, Calcium, Dietary, Female, Humans, Kidney, Kinetics, Male, Minerals, Phosphates, Biomarkers, Renal Insufficiency, Chronic
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
