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FGF23 and the PTH response to paricalcitol in chronic kidney disease
Author(s) -
D'Arrigo Graziella,
Pizzini Patrizia,
Cutrupi Sebastiano,
Tripepi Rocco,
Tripepi Giovanni,
Mallamaci Francesca,
Zoccali Carmine
Publication year - 2020
Publication title -
european journal of clinical investigation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.164
H-Index - 107
eISSN - 1365-2362
pISSN - 0014-2972
DOI - 10.1111/eci.13196
Subject(s) - paricalcitol , medicine , endocrinology , parathyroid hormone , vitamin d and neurology , kidney disease , calcitriol receptor , placebo , secondary hyperparathyroidism , calcium , urology , pathology , alternative medicine
Background The parathyroid glands are endowed both with receptors responsive to FGF23 and to 1,25 vitamin D. Vitamin D receptor (VDR) activation, besides lowering PTH, also raises serum FGF23. FGF23 has been implicated in parathyroid resistance to VDR activation but the issue has never been investigated in predialysis CKD patients. Methods In the Paricalcitol and Endothelial Functio in Chronic Kidney Disease (PENNY) study (NCT01680198), a 12‐week randomized trial in stage G3‐4 CKD patients (placebo n = 44 and paricalcitol n = 44), we measured PTH and the active form of FGF23 with no missing value across the trial. Results At baseline, serum FGF23 and PTH were inter‐related ( r = .54, P < .01). Paricalcitol reduced serum PTH (−75.1 pg/mL, 95% CI: −90.4 to −59.8; P < .001) and increased FGF23 (+107 pg/mL, 95% CI: 44‐170 pg/mL, P = .001). Changes in the Ca × P product in response to paricalcitol were closely related to simultaneous FGF23 changes in an analysis adjusted for changes in serum calcium and phosphate ( P < .001). Of note, baseline FGF23, appropriately adjusted for baseline PTH, was unrelated with the PTH response to paricalcitol ( r = −.06, P = .72). Placebo did not change neither PTH nor FGF23. Conclusion Serum FGF23 and PTH are inter‐related and changes in the Ca × P product induced by paricalcitol per se correlate with the FGF23 response to this drug. Independently of serum FGF23, the parathyroid glands of patients with moderate to severe CKD maintain an intact ability to respond to VDR activation.