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.
Abstract

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