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: Anders Nordholm, Maria L Mace, Eva Gravesen, Klaus Olgaard, Ewa Lewin
• Journal: BMC nephrology (BMC Nephrol) Vol. 16 Pg. 29 (Mar 15 2015) ISSN: 1471-2369 [Electronic] England
• PMID: 25885328 (Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Calcium

Topics

• Animals
• Bone Density (physiology)
• Bone and Bones (metabolism)
• Calcium (metabolism)
• Disease Models, Animal
• Disease Progression
• Homeostasis (physiology)
• Hypercalcemia (blood, diagnosis)
• Hypocalcemia (blood, diagnosis)
• Male
• Nephrectomy (methods)
• Parathyroidectomy (methods)
• Random Allocation
• Rats
• Rats, Wistar
• Reference Values
• Thyroidectomy (methods)
• Time Factors
• Uremia (etiology, physiopathology)