NDT Advance Access originally published online on June 16, 2009
Nephrology Dialysis Transplantation 2009 24(11):3376-3381; doi:10.1093/ndt/gfp292
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Intracellular calcium homeostasis in patients with early stagesof chronic kidney disease: effects of vitamin D3 supplementation
1 Department of Clinical and Experimental Pharmacotherapy, Slovak Medical University, Bratislava, Slovak Republic 2 Research Centre, Centre Hospitalier Universitaire, CHU Sainte-Justine, University of Montreal 3 Department of Pediatrics, University of Montreal, Montreal, Quebec, Canada 4 Department of Biophotonics, International Laser Centre, Bratislava, Slovak Republic
Correspondence and offprint requests to: Ingrid Lajdova; E-mail: ingrid.lajdova{at}szu.sk
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Abstract |
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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 ([Ca2+]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 D3 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. [Ca2+]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 Ca2+-ATPase. 2-Aminoethyl-diphenyl borate (2APB) was used to examine the capacitative calcium entry.
Results. [Ca2+]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 D3 supplementation, there was a marked decrease in [Ca2+]i [105 (103–112) nmol/l, P < 0.001 versus baseline], independently of the increase in 25(OH)D3 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) [Ca2+]i, intracellular calcium stores and the capacitative calcium entry were significantly increased already in early stages of CKD; (2) long-term vitamin D3 supplementation normalized [Ca2+]i without any effect on intracellular calcium reserves or the capacitative calcium entry.
Keywords: chronic kidney disease; fluorescence; intracellular calcium; vitamin D3
Received for publication: 8. 1.09
Accepted in revised form: 26. 5.09