title: A potential kidney-bone axis involved in the rapid minute-to-minute regulation of plasma Ca2+.
abstract: BACKGROUND
  Understanding the regulation of mineral homeostasis and function of the skeleton as buffer for Calcium and Phosphate has regained new interest with introduction of the syndrome "Chronic Kidney Disease-Mineral and Bone Disorder"(CKD-MBD). The very rapid minute-to-minute regulation of plasma-Ca(2+) (p-Ca(2+)) takes place via an exchange mechanism of Ca(2+) between plasma and bone. A labile Ca storage pool exists on bone surfaces storing excess or supplying Ca when blood Ca is lowered. Aim was to examine minute-to-minute regulation of p-Ca(2+) in the very early phase of acute uremia, as induced by total bilateral nephrectomy and to study the effect of absence of kidneys on the rapid recovery of p-Ca(2+) from a brief induction of acute hypocalcemia.
  
  
  METHODS
  The rapid regulation of p-Ca(2+) was examined in sham-operated rats, acute nephrectomized rats (NX), acute thyroparathyrectomized(TPTX) rats and NX-TPTX rats.
  
  
  RESULTS
  The results clearly showed that p-Ca(2+) falls rapidly and significantly very early after acute NX, from 1.23 ± 0.02 to 1.06 ± 0.04 mM (p < 0.001). Further hypocalcemia was induced by a 30 min iv infusion of EGTA. Control groups had saline. After discontinuing EGTA a rapid increase in p-Ca(2+) took place, but with a lower level in NX rats (p < 0.05). NX-TPTX model excluded potential effect of accumulation of Calcitonin and C-terminal PTH, both having potential hypocalcemic actions. Acute TPTX resulted in hypercalcemia, 1.44 ± 0.02 mM and less in NX-TPTX rats,1.41 ± 0.02 mM (p < 0.05). Recovery of p-Ca(2+) from hypocalcemia resulted in lower levels in NX-TPTX than in TPTX rats, 1.20 ± 0.02 vs.1.30 ± 0.02 (p < 0.05) demonstrating that absence of kidneys significantly affected the rapid regulation of p-Ca(2+) independent of PTH, C-PTH and CT.
  
  
  CONCLUSIONS
  P-Ca(2+) on a minute-to-minute basis is influenced by presence of kidneys. Hypocalcemia developed rapidly in acute uremia. Levels of p-Ca(2+), obtained during recovery from hypocalcemia resulted in lower levels in acutely nephrectomized rats. This indicates that kidneys are of significant importance for the 'set-point' of p-Ca(2+) on bone surface, independently of PTH and calcitonin. Our results point toward existence of an as yet unknown factor/mechanism, which mediates the axis between kidney and bone, and which is involved in the very rapid regulation of p-Ca(2+).
authors.affiliation: Nephrological Department B, Herlev Hospital, DK 2730, Copenhagen, Denmark. a.nordholm@gmail.com.
authors.forename: Anders
authors.initials: A
authors.lastname: Nordholm
authors.affiliation: Nephrological Department B, Herlev Hospital, DK 2730, Copenhagen, Denmark. maria.lerche.mace@regionh.dk.
authors.forename: Maria L
authors.initials: ML
authors.lastname: Mace
authors.affiliation: Nephrological Department P, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark. eva.gravesen@regionh.dk.
authors.forename: Eva
authors.initials: E
authors.lastname: Gravesen
authors.affiliation: Nephrological Department P, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark. olgaard@rh.dk.
authors.forename: Klaus
authors.initials: K
authors.lastname: Olgaard
authors.affiliation: Nephrological Department B, Herlev Hospital, DK 2730, Copenhagen, Denmark. Ewa.Lewin@regionh.dk.|Nephrological Department P, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark. Ewa.Lewin@regionh.dk.
authors.forename: Ewa
authors.initials: E
authors.lastname: Lewin
mesh_terms: D000818:Animals; D015519:Bone Density / Q000502:physiology; D001842:Bone and Bones / Q000378:metabolism*; D002118:Calcium / Q000378:metabolism*; D004195:Disease Models, Animal; D018450:Disease Progression; D006706:Homeostasis / Q000502:physiology; D006934:Hypercalcemia / Q000097:blood* / Q000175:diagnosis; D006996:Hypocalcemia / Q000097:blood* / Q000175:diagnosis; D008297:Male; D009392:Nephrectomy / Q000379:methods; D016105:Parathyroidectomy / Q000379:methods; D011897:Random Allocation; D051381:Rats; D017208:Rats, Wistar; D012016:Reference Values; D013965:Thyroidectomy / Q000379:methods; D013997:Time Factors; D014511:Uremia / Q000209:etiology / Q000503:physiopathology*
chemical_list: D002118:Calcium