Intracellular calcium homeostasis in patients with early stagesof chronic kidney disease: effects of vitamin D3 supplementation

Lajdova, Ingrid; Spustová, Viera; Oksa, A; Chorvatova, Alzbeta; Chorvát, D.; Dzúrik, R

doi:10.1093/ndt/gfp292

Cited by 25 publications

(33 citation statements)

References 25 publications

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“…Many studies have evaluated vitamin D (either cholecalciferol or ergocalciferol) as a treatment for vitamin D insufficiency or SHPT in adults with predialysis CKD [25,26,27,28,29,30,31,32,33,34,35,36,37,38,39,40,41,42]. Most were open-label studies and some were conducted in patients exhibiting SHPT.…”

Section: Discussionmentioning

confidence: 99%

Modified-Release Calcifediol Effectively Controls Secondary Hyperparathyroidism Associated with Vitamin D Insufficiency in Chronic Kidney Disease

et al. 2014

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Background/Aims: Vitamin D insufficiency drives secondary hyperparathyroidism (SHPT) and is associated with increased cardiovascular mortality in patients with chronic kidney disease (CKD). SHPT is poorly addressed by current vitamin D repletion options. The present study evaluated a novel investigational vitamin D repletion therapy: a modified-release (MR) formulation of calcifediol designed to raise serum 25-hydroxyvitamin D in a gradual manner to minimize the induction of CYP24 and, thereby, improve the SHPT control. Methods: This randomized, double-blind, placebo-controlled trial evaluated MR calcifediol in CKD subjects (n = 78) with plasma intact parathyroid hormone (iPTH) >70 pg/ml and serum total 25-hydroxyvitamin D <30 ng/ml. Subjects received daily treatment for six weeks with oral MR calcifediol (30, 60 or 90 µg) or a placebo. Results: More than 90% of subjects treated with MR calcifediol achieved serum 25-hydroxyvitamin D levels ≥30 ng/ml versus 3% of subjects treated with placebo (p < 0.0001). Mean plasma iPTH decreased from baseline (140.3 pg/ml) by 20.9 ± 6.2% (SE), 32.8 ± 5.7 and 39.3 ± 4.3% in the 30, 60 and 90 µg dose groups, respectively, and increased 17.2 ± 7.8% in the pooled placebo group (p < 0.005). No clinically significant safety concerns arose during MR calcifediol treatment. Conclusion: Oral MR calcifediol appears safe and highly effective in treating SHPT associated with vitamin D insufficiency in CKD.

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Section: Discussionmentioning

confidence: 99%

Modified-Release Calcifediol Effectively Controls Secondary Hyperparathyroidism Associated with Vitamin D Insufficiency in Chronic Kidney Disease

et al. 2014

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“…In our previous studies, we demonstrated that calcitriol, an active metabolite of vitamin D, prevents Ca 2+ increase through P2X 7 channels and reduces the membrane permeability through P2X 7 pores [13] . Moreover, vitamin D 3 supplementation in early stages of CKD decreased [Ca 2+ ] i but did not affect intracellular calcium reserves and calcium entry through CRAC channels [10] . These findings point to the potential role of P2X 7 receptors in enhanced [Ca 2+ ] i in this disease.…”

Section: Discussionmentioning

confidence: 90%

“…[25,26] , by the enhanced calcium influx [9] and the increase in intracellular calcium reserves [10] . The main mechanism of the lymphocyte [Ca 2+ ] i increase involves CRAC channels.…”

Section: Discussionmentioning

confidence: 99%

“…We have previously reported that [Ca 2+ ] i , intracellular calcium reserves and Ca 2+ influx through the calcium release-activated calcium (CRAC) channels are increased in human PBMCs in early stages of CKD; thus, the balance between calcium entry and its extrusion or buffering within the cells is impaired. Vitamin D 3 treatment decreased elevated [Ca 2+ ] i in CKD patients, but did not affect intracellular calcium reserves or calcium entry through the CRAC channels [10] . This points to the potential role of purinergic P2X 7 receptors in these processes.…”

Section: Introductionmentioning

confidence: 86%

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Purinergic P2X<sub>7</sub> Receptors Participate in Disturbed Intracellular Calcium Homeostasis in Peripheral Blood Mononuclear Cells of Patients with Chronic Kidney Disease

Lajdova

Oksa²,

Chorvát³

et al. 2011

Kidney Blood Press Res

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Background: P2X₇ receptors intervene with lymphocyte activation and are responsible for multiple processes, including calcium influx. Here, we studied the participation of P2X₇ receptors in disturbed intracellular calcium homeostasis regulation in early-stage chronic kidney disease (CKD). Methods: The study involved 20 healthy volunteers and 20 CKD stage 2–3 patients. The free cytosolic calcium concentration ([Ca²⁺]_i) was measured using fluorimetry. The P2X₇ pore function was evaluated by the fluorescent dye ethidium bromide. Results: In peripheral blood mononuclear cells (PBMCs) of patients, [Ca²⁺]_i, intracellular calcium stores and the capacitative calcium entry were increased when compared with healthy subjects. The agonist of P2X₇ receptor BzATP caused a sustained increase in [Ca²⁺]_i in both groups, but the effect was smaller in patients. The antagonist at the P2X₇ receptor KN-62 reduced [Ca²⁺]_i in patients, but had no effect in healthy subjects. In patients, the permeability of ethidium bromide through P2X₇ pores, as well as through BzATP-activated and KN-62-inhibited pores, was distinct from permeability in healthy volunteers. Conclusions: These results demonstrate that the calcium signaling pathway in PBMCs of CKD patients is defective already in CKD stage 2–3, and the pore-forming P2X₇ receptors are involved in these pathophysiological processes.

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“…PBMC were isolated from heparinized blood of healthy volunteers by Ficoll gradient centrifugation, diluted 1:1 with RPMI-1640 medium, layered onto an equivalent volume of medium LSM-1077 and centrifuged at 700G for 20 min at 20°C, as previously reported [7]. The PBMC layer was washed in 40 ml RPMI, resuspended in 10 ml RPMI and 10% fetal bovine serum (FBS), centrifuged for 10 min at 300g and 22°C.…”

Section: Preparation Of Pbmcmentioning

confidence: 99%

Time-resolved fluorescence monitoring of cholesterol in peripheral blood mononuclear cells

Martinakova

Horilova

Lajdova

et al. 2014

19th Polish-Slovak-Czech Optical Conference on Wave and Quantum Aspects of Contemporary Optics

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Precise evaluation of intracellular cholesterol distribution is crucial for improving diagnostics of diseased states associated with cholesterol alteration. Time-resolved fluorescence techniques are tested for non-invasive investigation of cholesterol in living cells. Fluorescent probe NBD attached to cholesterol was employed to evaluate cholesterol distribution in peripheral blood mononuclear cells (PBMC) isolated from the human blood. Fluorescence Lifetime Imaging Microscopy (FLIM) was successfully applied to simultaneously monitor the spatial distribution and the timeresolved characteristics of the NBD-cholesterol fluorescence in PBMC. Gathered data are the first step in the development of a new perspective non-invasive diagnostic method for evaluation of cholesterol modifications in diseases associated with disorders of lipid metabolism.

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Intracellular calcium homeostasis in patients with early stagesof chronic kidney disease: effects of vitamin D3 supplementation

Cited by 25 publications

References 25 publications

Modified-Release Calcifediol Effectively Controls Secondary Hyperparathyroidism Associated with Vitamin D Insufficiency in Chronic Kidney Disease

Modified-Release Calcifediol Effectively Controls Secondary Hyperparathyroidism Associated with Vitamin D Insufficiency in Chronic Kidney Disease

Purinergic P2X<sub>7</sub> Receptors Participate in Disturbed Intracellular Calcium Homeostasis in Peripheral Blood Mononuclear Cells of Patients with Chronic Kidney Disease

Time-resolved fluorescence monitoring of cholesterol in peripheral blood mononuclear cells

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