Nephrol Dial Transplant (2003) 18: 1592-1600
© 2003 European Renal Association-European Dialysis and Transplant Association
Mononuclear leukocyte apoptosis in haemodialysis patients: the role of cell thiols and vitamin E
1 Department of Internal Medicine, Section of Applied and Clinical Biochemistry, University of Perugia, 2 ‘G. Fornaini’ Institute of Biological Chemistry, University of Urbino, 3 Department of Biology, University of Rome ‘Tor Vergata’, 4 Nephrology and Dialysis Unit, ‘R. Silvestrini’ Hospital, Perugia and 5 Department of Nephrology, San Bortolo Hospital, Vicenza, Italy
Correspondence and offprint requests to: Francesco Galli, PhD, Department of Internal Medicine, Section of Applied and Clinical Biochemistry, University of Perugia, Via del Giochetto, 06126 Perugia, Italy. Email: f.galli{at}unipg.it The authors wish it to be known that, in their opinion, the first two authors contributed equally to this work
Background. An increased apoptotic rate of peripheral blood mononuclear leukocytes (PBMLs) in haemodialysis (HD) patients has been reported in several studies, but its underlying mechanisms remain poorly understood. Oxidant stress is a well known cause of cell damage, and several lines of evidence suggest that it might influence the induction and signalling steps of mononuclear cell apoptosis through different mechanisms so as to provoke disturbances of the intracellular pool of thiols (SHi). In this study, we investigated the in vitro apoptotic rate and SHi of PBMLs in end-stage renal disease (ESRD) patients on HD or peritoneal dialysis (PD).
Methods. Apoptosis and SHi were evaluated in vitro in PBMLs obtained from 40 ESRD patients (HD, n = 30 and PD, n = 10) and 10 healthy controls. A subgroup of HD patients was also studied before and after 1 month of treatment with a vitamin E-coated dialyser (CL-E). Cell thiols and viability were also assessed in the monocyte-like cell line U937 and PBMLs after incubation in the presence of uraemic plasma with or without supplementation of the antioxidants vitamin E (70 µM) or N-acetyl-cysteine (NAC) (0.5 mM).
Results. After 24 h in culture, the PBMLs of HD patients, but not those of CAPD patients, showed an apoptotic rate twice that of healthy controls and a 40% decrease of SHi levels (P < 0.01 in both). A negative correlation between the apoptotic rate and SHi was observed in both patients and controls (r = 0.648, P < 0.001). Plasma and ultrafiltrate samples from HD patients contained solutes (mainly in the low–middle molecular weight range) able to trigger apoptosis and oxidative stress in U937 cells. The treatment of HD patients with CL-E, as well as the in vitro supplementation of U937 cells with vitamin E or NAC during the exposure to uraemic plasma, decreased the rate of apoptosis and partially restored SHi.
Conclusions. This study showed an association between an increased apoptotic rate and decreased SHi in PBML of HD patients, but not of CAPD patients. These changes are partially due to different pro-apoptogens that accumulate in the plasma and are at least partially prevented by exogenous antioxidants able to restore SHi, such as vitamin E or thiol suppliers.
Keywords: apoptosis; haemodialysis; mononuclear leukocytes; oxidant stress; thiols; vitamin E
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