PMID- 33615106
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20230919
IS  - 2473-4039 (Electronic)
IS  - 2473-4039 (Linking)
VI  - 5
IP  - 2
DP  - 2021 Feb
TI  - Renal Phosphate Handling: Independent Effects of Circulating FGF23, PTH, and 
      Calcium.
PG  - e10437
LID - 10.1002/jbm4.10437 [doi]
LID - e10437
AB  - Excess fibroblast growth factor 23 (FGF23), excess PTH, and an increase in 
      extracellular calcium cause hypophosphatemia by lowering the maximum renal 
      phosphate reabsorption threshold (TmP/GFR). We recently reported two cases of 
      X-linked hypophosphatemia (XLH) with severe tertiary hyperparathyroidism who had 
      normalization of TmP/GFR upon being rendered hypoparathyroid following total 
      parathyroidectomy, despite marked excess in both C-terminal FGF23 (cFGF23) and 
      intact FGF23 (iFGF23). We explored the effects of FGF23, PTH, and calcium on 
      TmP/GFR in a cross-sectional study (n = 74) across a spectrum of clinical cases 
      with abnormalities in TmP/GFR, PTH, and FGF23. This comprised three groups: 
      FGF23-dependent hypophosphatemia (n = 27), hypoparathyroidism (HOPT; n = 17), and 
      chronic kidney disease (n = 30). Measurements included TmP/GFR, cFGF23, PTH, 
      ionized calcium, vitamin D metabolites, and bone turnover markers. The combined 
      effect of cFGF23, PTH, and ionized calcium on TmP/GFR was modeled using 
      hierarchical multiple regression and was probed by moderation analysis with 
      PROCESS. Modeling analysis showed independent effects on TmP/GFR by cFGF23, PTH, 
      and ionized calcium in conjunction with a weak but significant effect of the 
      interaction term for PTH and FGF23; probing showed that the effect was most 
      prominent during PTH deficiency. Teriparatide 20 mug daily was self-administered 
      for 28 days by one case of X-linked hypophosphatemia with hypoparathyroidism 
      (XLH-HOPT) to assess the response of TmP/GFR, cFGF23, iFGF23, nephrogenous cyclic 
      adenosine monophosphate (NcAMP), vitamin D metabolites, and bone turnover 
      markers. After 28 days, TmP/GFR was lowered from 1.10 mmol/L to 0.48 mmol/L; this 
      was accompanied by increases in NcAMP, ionized calcium, and bone turnover 
      markers. In conclusion, the effect of FGF23 excess on TmP/GFR is altered by PTH 
      such that the effect is ameliorated by hypoparathyroidism and the effect is 
      augmented by hyperparathyroidism. (c) 2020 The Authors. JBMR Plus published by 
      Wiley Periodicals LLC. on behalf of American Society for Bone and Mineral 
      Research.
CI  - (c) 2020 The Authors. JBMR Plus published by Wiley Periodicals LLC. on behalf of 
      American Society for Bone and Mineral Research.
FAU - McKenna, Malachi J
AU  - McKenna MJ
AUID- ORCID: 0000-0002-6564-7011
AD  - UCD School of Medicine University College Dublin Dublin Ireland.
AD  - Department of Clinical Chemistry St. Vincent's University Hospital Dublin 
      Ireland.
AD  - Department of Endocrinology St. Vincent's University Hospital Dublin Ireland.
FAU - Crowley, Rachel K
AU  - Crowley RK
AD  - UCD School of Medicine University College Dublin Dublin Ireland.
AD  - Department of Clinical Chemistry St. Vincent's University Hospital Dublin 
      Ireland.
AD  - Department of Endocrinology St. Vincent's University Hospital Dublin Ireland.
FAU - Twomey, Patrick J
AU  - Twomey PJ
AD  - UCD School of Medicine University College Dublin Dublin Ireland.
AD  - Department of Clinical Chemistry St. Vincent's University Hospital Dublin 
      Ireland.
FAU - Kilbane, Mark T
AU  - Kilbane MT
AD  - UCD School of Medicine University College Dublin Dublin Ireland.
AD  - Department of Clinical Chemistry St. Vincent's University Hospital Dublin 
      Ireland.
LA  - eng
PT  - Journal Article
DEP - 20201209
PL  - England
TA  - JBMR Plus
JT  - JBMR plus
JID - 101707013
PMC - PMC7872336
OTO - NOTNLM
OT  - FIBROBLAST GROWTH FACTOR 23
OT  - HYPERPARATHYROIDISM
OT  - HYPOPARATHYROIDISM
OT  - PARATHYROID HORMONE
OT  - X-LINKED HYPOPHOSPHATEMIA
EDAT- 2021/02/23 06:00
MHDA- 2021/02/23 06:01
PMCR- 2020/12/09
CRDT- 2021/02/22 05:59
PHST- 2020/11/09 00:00 [received]
PHST- 2020/11/13 00:00 [accepted]
PHST- 2021/02/22 05:59 [entrez]
PHST- 2021/02/23 06:00 [pubmed]
PHST- 2021/02/23 06:01 [medline]
PHST- 2020/12/09 00:00 [pmc-release]
AID - JBM410437 [pii]
AID - 10.1002/jbm4.10437 [doi]
PST - epublish
SO  - JBMR Plus. 2020 Dec 9;5(2):e10437. doi: 10.1002/jbm4.10437. eCollection 2021 Feb.