Red blood cell calcium homeostasis in patients with end-stage renal disease

U. Gafter, T. Malachi, H. Barak, M. Djaldetti, J. Levi

Research output: Contribution to journalArticlepeer-review

Abstract

Low cell calcium level is essential for preservation of red blood cell (RBC) membrane deformability and survival. RBCs from patients with end-stage renal disease (ESRD) demonstrate reduction in membrane deformability, possibly as a result of increased RBC cellular calcium level. To evaluate calcium homeostasis in RBCs from patients with ESRD, we measured cell calcium level, basal and 'calmodulin'-stimulated calcium-stimulated Mg-dependent ATPase (CaATPase) activity, and calcium 45 efflux were measured before and after hemodialysis. The in vitro effect of uremic plasma and of urea on CaATPase activity of nromal RBCs was tested, and 45Ca influx into RBCs of patients undergoing hemodialysis also was determined. A morphologic evaluation of red cells from patients with ESRD was performed with a scanning electron microscope. RBC calcium level in patients (mean ± SEM 21.2 ± 2.8 μmol/L of cells; n = 28) was higher than in controls (4.9 ± 0.3 μmol/L of cells; n = 24; p < 0.001). Hemodialysis had no effect on cell calcium level. Both basal and 'calmodulin'-stimulated RBC CaATPase activities in patients with ESRD (n = 9) were reduced by approximately 50% (p < 0.01), but after hemodialysis, enzyme activity returned to normal. 45Ca efflux from calcium-loaded cells, which was 2574.0 ± 217.0 μmol/L of cells per 0.5 hours before hemodialysis, increased to 3140.7 ± 206.8 μmol/L of cells per 0.5 hours after hemodialysis (p < 0.005). In vitro incubation of normal RBCs with uremic plasma depressed CaATPase activity, but incubation with urea had no effect. RBCs of patients with ESRD revealed increased 45Ca influx, 7.63 ± 1.15 μmol/L of cells per hour versus 4.61 ± 0.39 μmol/L of cells per hour (p < 0.025). RBCs of patients revealed a high incidence of spherocytosis and echynocytosis, which correlated with a high cell calcium level (r = 0.894, p<0.01). These results indicate that RBC calcium level is elevated in patients with ESRD and suggest that a dialyzable uremic factor inhibits RBC CaATPase activity and thereby calcium efflux, which may account for the elevated cell calcium level. The increased calcium influx further increases cellular calcium level. These abnormalities are associated with spherocytosis and echynocytosis and may contribute to the shortened survival of RBCs in uremia.

Original languageEnglish
Pages (from-to)222-231
Number of pages10
JournalJournal of Laboratory and Clinical Medicine
Volume114
Issue number3
StatePublished - 1989
Externally publishedYes

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