Intracellular calcium homeostasis in patients with early stages of chronic kidney disease: effects of vitamin D3 supplementation.
BACKGROUND
Chronic renal failure has been referred to as a state of cellular calcium toxicity. The aim of this study was to investigate the status of free cytosolic calcium ([Ca(2+)](i)), intracellular calcium reserves and the capacitative calcium entry in peripheral blood mononuclear cells (PBMCs) of early-stage chronic kidney disease (CKD) patients, and to determine the effect of vitamin D(3) supplementation on these parameters.


METHODS
The study involved 44 patients with CKD stages 2-3; 27 of them were treated with cholecalciferol (5000 IU/week) for 12 months. [Ca(2+)](i) was measured using Fluo-3 AM fluorimetry. Intracellular calcium reserves were emptied by the application of thapsigargin (Tg), a specific inhibitor of endoplasmic reticulum Ca(2+)-ATPase. 2-Aminoethyl-diphenyl borate (2APB) was used to examine the capacitative calcium entry.


RESULTS
[Ca(2+)](i) of CKD patients was substantially higher in comparison with healthy subjects: 123 (115-127) versus 102 (98-103) nmol/l, P < 0.001. The calcium concentration of Tg-sensitive stores and the capacitative calcium entry were also significantly increased in CKD patients. After the 12-month vitamin D(3) supplementation, there was a marked decrease in [Ca(2+)](i) [105 (103-112) nmol/l, P < 0.001 versus baseline], independently of the increase in 25(OH)D(3) or the decrease in PTH levels. No significant changes in intracellular calcium reserves and the capacitative calcium entry were found.


CONCLUSIONS
Our results demonstrate that (1) [Ca(2+)](i), intracellular calcium stores and the capacitative calcium entry were significantly increased already in early stages of CKD; (2) long-term vitamin D(3) supplementation normalized [Ca(2+)](i) without any effect on intracellular calcium reserves or the capacitative calcium entry.
Lajdova
Ingrid
I
1Department of Clinical and Experimental Pharmacotherapy, Slovak Medical University, Bratislava, Slovak Republic. ingrid.lajdova@szu.sk
Spustova
Viera
V
Oksa
Adrian
A
Chorvatova
Alzbeta
A
Chorvat
Dusan
D
Dzurik
Rastislav
R
D000328:Adult; D000368:Aged; D002118:Calcium / Q000378:metabolism*; D002762:Cholecalciferol / Q000008:administration & dosage*; D002908:Chronic Disease; D019587:Dietary Supplements; D006706:Homeostasis; D006801:Humans; D007674:Kidney Diseases / Q000378:metabolism*; D008875:Middle Aged; D018048:Receptors, Purinergic P2 / Q000502:physiology; D058486:Receptors, Purinergic P2X7
C546468:P2RX7 protein, human; D018048:Receptors, Purinergic P2; D058486:Receptors, Purinergic P2X7; D002762:Cholecalciferol; D002118:Calcium