Impaired lymphocyte calcium metabolism in end-stage renal disease: Enhanced influx, decreased efflux, and reduced response to mitogen

Y. Ori, A. Korzets, T. Malachi, U. Gafter, H. Breitbart

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24 Scopus citations

Abstract

Lymphocytes from patients with end-stage renal disease (ESRD) exhibit elevated cytosolic calcium concentration ((Ca2+)i), but the mechanisms responsible for this elevated (Ca2+)i have not been entirely elucidated. In addition, lymphocyte proliferative responses to mitogenic stimuli are suppressed in patients with ESRD. The objectives of the study were as follows: (1) to measure calcium influx and efflux in lymphocytes from patients with ESRD; (2) to measure the effect of the calcium regulator parathyroid hormone (PTH) on lymphocyte (Ca2+)i; (3) to measure cytosolic calcium signal in patients' lymphocytes after mitogenic stimulation. The three study groups were as follows: healthy subjects (control), patients with chronic renal failure (CRF) before the beginning of regular dialysis treatment, and patients undergoing regular hemodialysis (HD) treatment. Peripheral blood lymphocytes were tested in vitro for (Ca2+)i, Ca2+ influx, and membrane calcium-adenosine triphosphatase (CaATPase) activity. Cytosolic Ca2+ signals were traced after stimulations by PTH and by phytohemagglutinin (PHA). Baseline (Ca2+)i was significantly elevated in both ESRD groups. Ca2+ influx was enhanced and CaATPase activity was reduced in both ESRD groups. PTH caused a (Ca2+)i increase in normal cells in a dose-dependent manner. PHA caused a (Ca2+)i elevation, with a Ca2+ signal in both groups of patients with ESRD that was significantly smaller than that in the control group. These findings suggest that the high (Ca2+)i found in lymphocytes from patients with ESRD is the result of enhanced Ca2+ influx concomitant with reduced Ca2+ extrusion, as reflected by reduced CaATPase activity. The patients' elevated serum PTH levels may have contributed to the high (Ca2+)i. The impaired cytosolic (Ca2+)i response to PHA may explain in part the suppressed lymphocyte proliferative response to PHA in patients with ESRD.

Original languageEnglish
Pages (from-to)391-400
Number of pages10
JournalJournal of Laboratory and Clinical Medicine
Volume133
Issue number4
DOIs
StatePublished - Apr 1999

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