The role of the calcium-sensing receptor (CaSR) in chronic kidney disease

Bone ◽  
2012 ◽  
Vol 51 (6) ◽  
pp. S24
Author(s):  
T.B. Drüeke
Keyword(s):  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
Calcium Sensing Receptor ◽  
Calcium Sensing

scholarly journals Effect of MgCl2 and GdCl3 on ORAI1 Expression and Store-Operated Ca2+ Entry in Megakaryocytes

2021 ◽  
Vol 22 (7) ◽  
pp. 3292
Author(s):  
Kuo Zhou ◽  
Xuexue Zhu ◽  
Ke Ma ◽  
Jibin Liu ◽  
Bernd Nürnberg ◽  
...  
Keyword(s):  
Chronic Kidney Disease ◽  
Transcription Factor ◽  
Smooth Muscle ◽  
Kidney Disease ◽  
Protein Abundance ◽  
Rt Pcr ◽  
Calcium Sensing Receptor ◽  
Transcript Levels ◽  
Calcium Sensing ◽  
Store Depletion

In chronic kidney disease, hyperphosphatemia upregulates the Ca2+ channel ORAI and its activating Ca2+ sensor STIM in megakaryocytes and platelets. ORAI1 and STIM1 accomplish store-operated Ca2+ entry (SOCE) and play a key role in platelet activation. Signaling linking phosphate to upregulation of ORAI1 and STIM1 includes transcription factor NFAT5 and serum and glucocorticoid-inducible kinase SGK1. In vascular smooth muscle cells, the effect of hyperphosphatemia on ORAI1/STIM1 expression and SOCE is suppressed by Mg2+ and the calcium-sensing receptor (CaSR) agonist Gd3+. The present study explored whether sustained exposure to Mg2+ or Gd3+ interferes with the phosphate-induced upregulation of NFAT5, SGK1, ORAI1,2,3, STIM1,2 and SOCE in megakaryocytes. To this end, human megakaryocytic Meg-01 cells were treated with 2 mM ß-glycerophosphate for 24 h in the absence and presence of either 1.5 mM MgCl2 or 50 µM GdCl3. Transcript levels were estimated utilizing q-RT-PCR, protein abundance by Western blotting, cytosolic Ca2+ concentration ([Ca2+]i) by Fura-2 fluorescence and SOCE from the increase in [Ca2+]i following re-addition of extracellular Ca2+ after store depletion with thapsigargin (1 µM). As a result, Mg2+ and Gd3+ upregulated CaSR and blunted or virtually abolished the phosphate-induced upregulation of NFAT5, SGK1, ORAI1,2,3, STIM1,2 and SOCE in megakaryocytes. In conclusion, Mg2+ and the CaSR agonist Gd3+ interfere with phosphate-induced dysregulation of [Ca2+]i in megakaryocytes.

scholarly journals Effect of paricalcitol and cinacalcet on serum phosphate, FGF-23, and bone in rats with chronic kidney disease

2010 ◽  
Vol 298 (6) ◽  
pp. F1315-F1322 ◽  
Author(s):  
Jane L. Finch ◽  
Masanori Tokumoto ◽  
Hironori Nakamura ◽  
Wei Yao ◽  
Mohammad Shahnazari ◽  
...  
Keyword(s):  
Chronic Kidney Disease ◽  
Parathyroid Hormone ◽  
Kidney Disease ◽  
Bone Volume ◽  
Serum Phosphate ◽  
Dialysis Patients ◽  
Calcium Sensing Receptor ◽  
Calcium Sensing ◽  
Osteoid Surface ◽  
Fgf 23

Calcimimetics activate the calcium-sensing receptor (CaR) and reduce parathyroid hormone (PTH) by increasing the sensitivity of the parathyroid CaR to ambient calcium. The calcimimetic, cinacalcet, is effective in treating secondary hyperparathyroidism in dialysis patients [chronic kidney disease (CKD 5)], but little is known about its effects on stage 3–4 CKD patients. We compared cinacalcet and paricalcitol in uremic rats with creatinine clearances “equivalent” to patients with CKD 3–4. Uremia was induced in anesthetized rats using the 5/6th nephrectomy model. Groups were 1) uremic control, 2) uremic + cinacalcet (U+Cin; 15 mg·kg−1·day−1 po for 6 wk), 3) uremic + paricalcitol (U+Par; 0.16 μg/kg, 3 × wk, ip for 6 wk), and 4) normal. Unlike U+Par animals, cinacalcet promoted hypocalcemia and marked hyperphosphatemia. The Ca × P in U+Cin rats was twice that of U+Par rats. Both compounds suppressed PTH. Serum 1,25-(OH)2D3 was decreased in both U+Par and U+Cin rats. Serum FGF-23 was increased in U+Par but not in U+Cin, where it tended to decrease. Analysis of tibiae showed that U+Cin, but not U+Par, rats had reduced bone volume. U+Cin rats had similar bone formation and reduced osteoid surface, but higher bone resorption. Hypocalcemia, hyperphosphatemia, low 1,25-(OH)2D3, and cinacalcet itself may play a role in the detrimental effects on bone seen in U+Cin rats. This requires further investigation. In conclusion, due to its effects on bone and to the hypocalcemia and severe hyperphosphatemia it induces, we believe that cinacalcet should not be used in patients with CKD without further detailed studies.

Potential effect of pharmaceutical care to improve outcomes in patients with chronic kidney disease-mineral bone disorder in Sulaimani dialysis centers

2020 ◽  
pp. 82-94
Keyword(s):  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
Pharmaceutical Care ◽  
Biochemical Parameters ◽  
Positive Impact ◽  
Potential Effect ◽  
Care Group ◽  
Mineral Bone Disorder ◽  
Bone Disorder

Objective: the present study was aimed to evaluate the role of pharmaceutical services in improving the outcome of mineral bone disorder in patients with advanced chronic kidney disease. Methodology: One hundred and twenty patients with chronic kidney disease-mineral bone disorder (CKD-MBD) screened for eligibility, seventy-six patients enrolled in the study and randomly allocated into two groups: pharmaceutical care and usual care, both groups interviewed by the pharmacist using specific questionnaire for assessing the quality of life (QoL). All the drug related problems (DRPs) including drug-drug interactions (DDIs) were recorded by the pharmacist. Blood samples were collected and utilized for analyzing the levels of vitamin D, phosphorous, calcium, albumin and parathyroid hormone at baseline and three months after. The pharmaceutical care group received all the educations about their medications and how to minimize DRPs; improve the QoL. Additionally, the pharmaceutical intervention included correcting the biochemical parameters. Results: Pharmaceutical care significantly improved patients QoL and minimized DRPs and DDIs. It was also effective in improving the biochemical parameters. Conclusion: Pharmaceutical care has a positive impact on improving the outcome of patients with CKD-MBD through attenuating DRPs, improving the biochemical parameters and the QoL.

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