Department of Pediatric Nephrology, Wroclaw Medical University, Poland.
Nephrol Dial Transplant. 2010 Feb;25(2):438-44. doi: 10.1093/ndt/gfp436. Epub 2009 Oct 23.
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.
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.
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.
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.
慢性肾脏病（CKD）过程中会以多种方式扰乱钙稳态。红细胞细胞质中游离钙浓度增加。只有通过细胞质膜和细胞器中许多调节系统的精细协调，才能维持高浓度梯度（细胞浆和细胞外空间之间）。我们研究的目的是评估保守治疗的 CKD 儿童红细胞中 Ca(2+)-Mg(2+)-依赖性 ATP 酶（PMCA）、钙调蛋白和钙蛋白酶-钙蛋白酶抑制剂（CANP-CAST）系统的活性。
共纳入 36 例 CKD 患儿，A 组为 CKD Ⅱ期患儿，B 组为 CKD Ⅲ期患儿，C 组为 CKD Ⅳ期患儿，D 组为 30 例健康对照者。检测血清中完整甲状旁腺素、总钙、肌酐，红细胞中游离细胞内钙浓度（Ca(i)(2+)）、Ca(2+)-Mg(2+)-转运 ATP 酶（PMCA）活性、基础 PMCA（bPMCA）、钙调蛋白（CALM）、CANP、CAST。
所有组的 Ca(i)(2+)浓度均显著升高，而 PMCA 和 bPMCA 活性均低于对照组。A 组的 CANP 浓度与对照组相比升高，而 B 组和 C 组的 CANP 浓度显著降低。C 组的 CAST 平均活性达到最高值。与对照组相比，所有患者组的 CALM 浓度均降低。
CKD 儿童细胞内 Ca(i)(2+)稳态受到干扰，肾功能恶化进一步加重。红细胞钙浓度升高的原因是多因素的。毫无疑问，PMCA 活性降低、钙调蛋白缺乏和 CANP-CAST 系统失调是造成这种现象的原因。许多其他生物调节剂的影响，形成一个网络来保护细胞免受钙积累的影响，不能被排除。
