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Ca(2+)-Mg (2+)-dependent ATP-ase activity in hemodialyzed children. Effect of a hemodialysis session
Dorota Polak-Jonkisz1, Leszek Purzyc, Danuta Zwolińska
1Department of Pediatric Nephrology, Wrocław Medical University, Wrocław, Poland. dpjonkisz@nefped.am.wroc.pl
Insights
Children with chronic kidney disease (CKD) undergoing hemodialysis (HD) show disturbed calcium metabolism in red blood cells (RBCs). Hemodialysis temporarily improves calcium levels and related enzyme activities, but deficits persist compared to healthy individuals.
Area of Science:
- Nephrology
- Biochemistry
- Cell Biology
Background:
- Chronic kidney disease (CKD) is associated with elevated intracellular erythrocyte calcium (Ca(i)2+).
- Disturbed calcium metabolism in CKD is linked to reduced activity of Ca(2+)-Mg(2+)-dependent ATP-ase (PMCA) and its modulators: calmodulin (CALM), calpain (CANP), and calpastatin (CAST).
Purpose of the Study:
- To investigate the activity of PMCA, CALM, and the CANP-CAST system in the red blood cells (RBCs) of children on maintenance hemodialysis (HD).
- To assess the impact of a single HD session on these calcium-related parameters.
Main Methods:
- Analysis of CALM, Ca(i)2+ levels, basal PMCA (bPMCA), PMCA, CANP, and CAST activities in RBCs.
- Comparison between 18 hemodialyzed children and 30 healthy controls.
- Measurements taken before HD, after HD, and before the subsequent HD session.
Main Results:
- Children on HD exhibited higher Ca(i)2+ and CAST activity, and lower bPMCA, PMCA, CANP activities, and CALM levels compared to controls.
- A single HD session reduced Ca(i)2+ and CAST activity, while increasing PMCA, bPMCA, CANP, and CALM, though levels remained below those of healthy children.
- Pre-HD values before consecutive sessions were similar, indicating transient effects.
Conclusions:
- Severe disturbances in Ca(i)2+ homeostasis exist in children undergoing HD.
- Reduced PMCA activity, CALM deficiency, and CANP-CAST system alterations contribute to these disturbances.
- Hemodialysis offers a transient improvement in calcium homeostasis, highlighting the need for further therapeutic strategies.
Abstract:
In the course of chronic kidney disease (CKD) the intracellular erythrocyte calcium (Ca (i) (2+) ) level increases along with the progression of the disease. The decreased activity of Ca(2+)-Mg(2+)-dependent ATP-ase (PMCA) and its endogenous modulators calmodulin (CALM), calpain (CANP), and calpastatin (CAST) are all responsible for disturbed calcium metabolism. The aim of the study was to analyze the activity of PMCA, CALM, and the CANP-CAST system in the red blood cells (RBCs) of hemodialyzed (HD) children and to estimate the impact of a single HD session on the aforementioned disturbances. Eighteen patients on maintenance HD and 30 healthy subjects were included in the study. CALM, Ca (i) (2+) levels and basal PMCA (bPMCA), PMCA, CANP, and CAST activities were determined in RBCs before HD, after HD, and before the next HD session. Prior to the HD session, the level of Ca (i) (2+) and the CAST activity were significantly higher, whereas bPMCA, PMCA, and CANP activities and the CALM level were significantly lower than in controls. After the HD session, the Ca (i) (2+) concentration and the CAST activity significantly decreased compared with the basal values, whereas the other parameters significantly increased, although they did not reach the levels of healthy children. The values observed prior to both HD sessions were similar. Ca (i) (2+) homeostasis is severely disturbed in HD children, which may be caused by the reduction in the PMCA activity, CALM deficiency, and CANP-CAST system disturbances. A single HD session improved these disturbances but the effect is transient.
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