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Published on: September 1, 2015
The endogenous modulators of Ca2+-Mg2+-dependent ATPase in children with chronic kidney disease (CKD)
Dorota Polak-Jonkisz1, Leszek Purzyc, Krystyna Laszki-Szczachor
1Department of Pediatric Nephrology, Wroclaw Medical University, Poland.
Insights
Children with chronic kidney disease (CKD) show increased erythrocyte calcium levels due to decreased Ca(2+)-Mg(2+)-dependent ATPase (PMCA) activity, calmodulin deficiency, and a dysregulated calpain-calpastatin (CANP-CAST) system.
Area of Science:
- Pediatric Nephrology
- Cellular Physiology
- Biochemistry
Background:
- Chronic kidney disease (CKD) disrupts calcium homeostasis, leading to elevated intracellular calcium in erythrocytes.
- Maintaining calcium gradients requires complex cellular regulation, which is compromised in CKD.
Purpose of the Study:
- To evaluate the activity of the Ca(2+)-Mg(2+)-dependent ATPase (PMCA), calmodulin, and the calpain-calpastatin (CANP-CAST) system in erythrocytes of children with CKD stages II-IV.
- To understand the role of these systems in erythrocyte calcium dysregulation in pediatric CKD.
Main Methods:
- Studied 36 children with CKD (stages II-IV) and 30 healthy controls.
- Measured serum intact parathormone, total calcium, and creatinine.
- Assessed red blood cell free cytosolic calcium (Ca(i)(2+)), PMCA and basal PMCA (bPMCA) activity, calmodulin (CALM), CANP, and CAST concentrations.
Main Results:
- Erythrocyte Ca(i)(2+) concentrations were significantly higher in all CKD groups compared to controls.
- PMCA and bPMCA activities were lower in CKD patients.
- Calmodulin concentrations were decreased, while CANP-CAST system activity showed complex alterations across CKD stages.
Conclusions:
- Intracellular calcium homeostasis is disturbed in pediatric CKD, worsening renal function.
- Decreased PMCA activity, calmodulin deficiency, and dysregulated CANP-CAST system contribute to elevated erythrocyte calcium.
- The findings highlight multifactorial mechanisms underlying calcium dysregulation in pediatric CKD.
Background:
Calcium homeostasis is disturbed in many ways in the course of chronic kidney disease (CKD). The concentration of free cytoplasmic calcium in erythrocytes is increased. Maintenance of a high concentration gradient (between the cystoplasmic and extracellular space) is possible only due to a finely tuned cooperation between many regulating systems in the cytoplasmic membranes and cell organelles. The aim of our study was to evaluate the activity of Ca(2+)-Mg(2+)-dependent ATPase (PMCA), calmodulin and calpain-calpastatin (CANP-CAST) system in erythrocytes of CKD children treated conservatively in the stages II-IV.
Methods:
A total of 36 patients with CKD were enrolled in the study. Group A contained patients with CKD stage II; group B with CKD stage III; and group C with CKD stage IV. The control group D consisted of 30 healthy subjects. In the serum, we determined the following: intact parathormon, total calcium, creatinine; in the red blood cells: free cytosolic calcium concentration (Ca(i)(2+)), activity of Ca(2+)-Mg(2+)-transporting ATPase (PMCA), basal PMCA (bPMCA), calmodulin (CALM), CANP, CAST.
Results:
In all groups, Ca(i)(2+) concentrations were significantly higher, whereas PMCA and bPMCA activity were lower than in the controls. CANP concentrations in group A were elevated compared to the controls, whereas in groups B and C they were significantly lower. In group C, the mean CAST activity reached the highest values. CALM concentrations were decreased versus controls in all groups of patients.
Conclusions:
The intracellular Ca(i)(2+) homeostasis is disturbed in children with CKD and aggravates the deterioration of renal function as well. The reasons for the progressing increase of erythrocyte calcium concentration are multifactorial. Undoubtedly, the decreased PMCA activity, the calmodulin deficiency and the dysregulated CANP-CAST system are responsible for that phenomenon. The impact of many other biological modulators, creating a network defending the cell against the calcium accumulation, cannot be excluded.
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