NDT Advance Access first published online on October 23, 2009
This version published online on November 6, 2009
Nephrology Dialysis Transplantation, doi:10.1093/ndt/gfp436
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The endogenous modulators of Ca2+–Mg2+-dependent ATPase in children with chronic kidney disease (CKD)
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1
ska1
1 Department of Pediatric Nephrology, Wroclaw Medical University, Poland 2 Department of Medical Biochemistry, Wroclaw Medical University, Poland 3 Department of Pathophysiology, Wroclaw Medical University, Poland
Correspondence and offprint requests to: Dorota Polak-Jonkisz; E-mail: dpjonkisz{at}nefped.am.wroc.pl
| Abstract |
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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 Ca2+–Mg2+-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 (Cai2+), activity of Ca2+–Mg2+-transporting ATPase (PMCA), basal PMCA (bPMCA), calmodulin (CALM), CANP, CAST.
Results. In all groups, Cai2+ 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 Cai2+ 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.
Keywords: Ca2+–Mg2+-transporting ATPase; children; chronic kidney disease; cytosolic calcium; erythrocytes
The original version was incorrect. The author names have been corrected as they were initially transposed.
Received for publication: 5. 5.09
Accepted in revised form: 4. 8.09