Impaired lymphocyte calcium metabolism in endstage renal disease: Enhancedinflux, decreased efflux, and reduced response to mitogen

Lymphocytes from patients with end-stage renal disease (ESRD) exhibit eleva ted cytosolic calcium concentration ((Ca2+)i), but the mechanisms responsib le 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 me asure calcium influx and efflux in lymphocytes from patients with ESRD; (2) to measure the effect of the calcium regulator parathyroid hormone (PTH) o n lymphocyte (Ca2+)i; (3) to measure cytosolic calcium signal in patients' lymphocytes after mitogenic stimulation. The three study groups were as fol lows: healthy subjects (control), patients with chronic renal failure (CRF) before the beginning of regular dialysis treatment, and patients undergoin g regular hemodialysis (HD) treatment. Peripheral blood lymphocytes were te sted in vitro for (Ca2+)i, Ca2+ influx, and membrane calcium-adenosine trip hosphatase (CaATPase) activity. Cytosolic Ca2+ signals were traced after st imulations by PTH and by phytohemagglutinin (PHA), Baseline (Ca2+)i was sig nificantly elevated in both ESRD groups. Ca2+ influx was enhanced and CaATP ase 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 signific antly smaller than that in the control group, These findings suggest that t he high (Ca2+)i found in lymphocytes from patients with ESRD is the result of enhanced Ca2+ influx concomitant with reduced Ca2+ extrusion, as reflect ed by reduced CaATPase activity. The patients' elevated serum PTH levels ma y have contributed to the high (Ca2+)i. The impaired cytosolic [Ca2+)i resp onse to PHA may explain in part the suppressed lymphocyte proliferative res ponse to PHA in patients with ESRD.