title: Daily variability in mineral metabolites in CKD and effects of dietary calcium and calcitriol.
abstract: OBJECTIVE
  Primary prevention of disordered mineral metabolism in CKD necessitates knowledge of its early pathophysiology. This study evaluated daily fluctuations in mineral metabolites in patients with CKD stages 3 and 4 before and after short-term calcitriol treatment and tested the effects of dietary calcium and calcitriol supplementation on these parameters in the dynamic postprandial setting.
  
  
  METHODS
  Twelve CKD patients received calcitriol (0.25 μg daily for 1 week) with hourly assessments of mineral metabolites made throughout the day and in the context of standardized meals before and after treatment. Calcium content (250 versus 500 mg) in the breakfasts constituted the dietary calcium intervention. Twelve healthy volunteers were used as controls.
  
  
  RESULTS
  At baseline, compared with controls, fasting CKD subjects had higher parathyroid hormone and fibroblast growth factor 23 levels and greater fractional excretion of phosphate. After breakfast, urinary calcium excretion increased and parathyroid hormone levels dipped transiently in both groups, but they rose soon thereafter, reaching higher peaks in CKD. Calcitriol decreased fasting parathyroid hormone levels, and when combined with dietary calcium load, it normalized the postprandial parathyroid and calcemic responses. Daily variability in mineral metabolites was preserved in CKD before and after calcitriol. Fibroblast growth factor 23 levels increased after calcitriol, although the response was heterogeneous.
  
  
  CONCLUSIONS
  Short-term treatment with calcitriol and dietary calcium supplementation normalizes the parathyroid and calcemic postprandial responses in patients with CKD, in whom the diurnal rhythms of mineral metabolites are preserved. Future studies should investigate the variable fibroblast growth factor 23 response to calcitriol in CKD.
authors.affiliation: Division of Nephrology and Hypertension, Department of Medicine, University of Miami Miller School of Medicine, Miami, Florida 33136, USA. tisakova@med.miami.edu
authors.forename: Tamara
authors.initials: T
authors.lastname: Isakova
authors.forename: Huiliang
authors.initials: H
authors.lastname: Xie
authors.forename: Allison
authors.initials: A
authors.lastname: Barchi-Chung
authors.forename: Kelsey
authors.initials: K
authors.lastname: Smith
authors.forename: Nicole
authors.initials: N
authors.lastname: Sowden
authors.forename: Michael
authors.initials: M
authors.lastname: Epstein
authors.forename: Gina
authors.initials: G
authors.lastname: Collerone
authors.forename: Leigh
authors.initials: L
authors.lastname: Keating
authors.forename: Harald
authors.initials: H
authors.lastname: Jüppner
authors.forename: Myles
authors.initials: M
authors.lastname: Wolf
mesh_terms: D000368:Aged; D002117:Calcitriol / Q000494:pharmacology* / Q000627:therapeutic use; D002118:Calcium / Q000032:analysis / Q000097:blood / Q000494:pharmacology* / Q000652:urine; D002940:Circadian Rhythm; D019587:Dietary Supplements; D005243:Feces / Q000737:chemistry; D005260:Female; D000089703:Fibroblast Growth Factor-23; D005346:Fibroblast Growth Factors / Q000097:blood / Q000187:drug effects; D006801:Humans; D008297:Male; D008875:Middle Aged; D010281:Parathyroid Hormone / Q000097:blood; D010710:Phosphates / Q000032:analysis / Q000097:blood / Q000652:urine; D019518:Postprandial Period; D051436:Renal Insufficiency, Chronic / Q000097:blood* / Q000188:drug therapy / Q000652:urine; D013997:Time Factors; D014815:Vitamins / Q000494:pharmacology* / Q000627:therapeutic use
chemical_list: D010281:Parathyroid Hormone; D010710:Phosphates; D014815:Vitamins; D005346:Fibroblast Growth Factors; D000089703:Fibroblast Growth Factor-23; D002117:Calcitriol; D002118:Calcium