Immune deficiency is one of the numerous consequences of chronic renal failure. We can hypothesize that an abnormal natural killer (NK) cell response is present in patients with end-stage renal disease (ESRD). To characterize the immune defect in ESRD patients, we performed a NK cell subset analysis in 66 patients with ESRD treated by hemodialysis or peritoneal dialysis. Compared with healthy blood donors, patients undergoing chronic dialysis showed a profound decrease in NKG2D(+) cells within both CD8(+) T cell (58 vs. 67%, p = 0.03) and NK cell (39 vs. 56%, p = 0.002) populations. We further studied NK cell subsets in 55 hemodialysis patients and 17 patients treated by peritoneal dialysis. As compared to healthy donors, all these patients had significantly decreased NKG2D-positive NK cells. Patients using PMMA membranes (BK-F) or Helixone-FX membranes had a smaller decrease in NKG2D-positive NK cells when compared to patients treated with Nephral membranes. The expression of MICA on the cell surface of monocytes, which is a marker of inflammation induced by cellular stress, was also lower in patients using BK-F membranes. In conclusion, these data suggest that a subpopulation of NK cells is decreased in patients with ESRD. This decrease is associated with high circulating levels of the HLA-related molecule MICA. The dialysis membrane can influence the modulation of both the phenotype of NK cells and MICA overexpression.

Keywords:
MICA, Natural killer cell, NKG2D, Oxidative stress, Polymethylmethacrylate, Uremia
1.
Carrero JJ, Stenvinkel P: Inflammation in end-stage renal disease - what have we learned in 10 years? Semin Dial 2010;23:498-509.
2.
Kaysen GA: Inflammation: cause of vascular disease and malnutrition in dialysis patients. Semin Nephrol 2004;24:431-436.
3.
Maisonneuve P, Agodoa L, Gellert R, Stewart JH, Buccianti G, Lowenfelds AB, Wolfe RA, Jones E, Disney AP, Briggs D, et al: Cancer in patients on dialysis for end-stage renal disease: an international collaborative study. Lancet 1999;354:90-91.
4.
Knerr K, Füth R, Hemsen P, Mohne W, Heinig A, Keophas W, Scherbaum WA, Martin S: Chronic inflammation and hemodialysis reduce immune competence of peripheral blood leucocytes in end-stage renal failure patients. Cytokine 2005;30:132-138.
5.
Yoon JW, Pahl MV, Vaziri ND: Spontaneous leucocyte activation and oxygen-free radical generation in end-stage renal disease. Kidney Int 2007;71:167-172.
6.
Massry S, Smogorzewski M: Dysfunction of polymorphonuclear leukocytes in uremia: role of parathyroid hormone. Kidney Int 2001;78:S195-S196.
7.
Chatenoud L, Dugas B, Beaurain G, Touam M, Drueke T, Vasquez A, Galanaud B, Bach JF, Delfraissy JF: Presence of preactivated T cells in hemodialyzed patients: their possible role in altered immunity. Proc Natl Acad Sci USA 1996;83:7457-7461.
8.
Meier P, Golshayan D, Blanc E, Pascual M, Burnier M: Oxidized LDL modulates apoptosis of regulatory T cells in patients with ESRD. J Am Soc Nephrol 2009;20:1368-1384.
9.
Pahl MV, Gollapudi S, Sepassi L, Gollapudi P, Elahimehr R, Vaziri ND: Effects of end-stage renal disease on B-lymphocyte sub-populations, IL-7, BAFF and BAFF receptor expression. Nephrol Dial Transplant 2010;25:205-212.
10.
Deenitchina SS, Ando T, Okuda S, Kinukawa N, Hirakata H, Nagashima A, Fujishima M: Cellular immunity in hemodialysis patients: a quantitative analysis of immune cell subsets by flow cytometry. Am J Nephrol 1995;15:57-65.
11.
Vaziri ND, Pahl MV, Crum A, Norris K: Effect of uremia on structure and function of immune system. J Ren Nutrition 2012;22:149-156.
12.
Trinchieri G: Biology of natural killer cells. Adv Immunol 1989;47:187-201.
13.
Lanier LL: Up on the tightrope natural killer cell activation and inhibition. Nat Immunol 2008;9:495-502.
14.
Champsaur M, Lanier LL: Effect of NKG2D ligand expression on host immune responses. Immunol Rev 2010;235:267-285.
15.
Xia M, Guerra N, Sukhova GK, Yang K, Miller CK, Shi GP, Raulet DH, Xiong N: Immune activation resulting from NKG2D/ligand interaction promotes atherosclerosis. Circulation 2011;124:2933-2943.
16.
Cooper MA, Fehniger TA, Caligiuri MA: The biology of human natural killer-cell subsets. Trends Immunol 2001;22:633-640.
17.
Caligiuri MA: Human natural killer cells. Blood 2008;112:461-469.
18.
Moretta A, Bottino C, Mingari MC, Biassoni R, Moretta L: What is a natural killer cell? Nat Immunol 2002;3:6-8.
19.
Norman PJ, Parham P: Complex interactions: the immunogenetics of human leukocyte antigen and killer cell immunoglobulin-like receptors. Semin Hematol 2005;42:65-75.
20.
Lanier LL: NK cell recognition. Annu Rev Immunol 2005;23:225-274.
21.
Zafirova B, Wensveen FM, Gulin M, Polic B: Regulation of immune cell function and differentiation by the NKG2D receptor. Cell Mol Life Sci 2011;68:3519-3529.
22.
Nausch N, Cerwenka A: NKG2D in tumor immunity. Oncogene 2008;27:5944-5958.
23.
Wu J: An activating immunoreceptor complex formed by NKG2D and DAP10. Science 1999;285:730-732.
24.
Horng T, Bezbradica JS, Medzhitov R: NKG2D signaling is coupled to the interleukin 15 receptor signaling pathway. Nat Immunol 2007;8:1345-1352.
25.
Zwimmer NW, Dole K, Stastny N: Differential surface expression of MICA by endothelial cells, fibroblasts, keratinocytes, and monocytes. Hum Immunol 1999;60:323-330.
26.
Tieng V, Le Bouguenec C, Du Merle L, Bertheau P, Desreumaux P, Janin A, Charron D, Toubert A: Binding of Escherichia coli adhesin AfaE to CD55 triggers cell-surface expression of the MHC class I-related molecule MICA. Proc Natl Acad Sci USA 2002;99:2977-2982.
27.
Salih HR, Rammensee HG, Steinle A: Cutting edge: down-regulation of MICA on human tumors by proteolytic shedding. J Immunol 2002;169:4098-4102.
28.
Vacher-Coponat H, Brunet C, Lyonnet L, Bonnet E, Loundou A, Sampol J, Moal V, Dussol B, Brunet P, Berland Y, Dignat-George F, Paul P: Natural killer cell alterations correlate with loss of renal function and dialysis duration in uraemic patients. Nephrol Dial Transplant 2008;23:1406-1414.
29.
Peraldi MN, Berrou J, Dulphy N, Seidowsky A, Haas P, Boissel N, Metivier F, Randoux C, Kossari N, Guérin A, Geffroy S, Delavaud G, Marin-Esteban V, Glotz D, Charron D, Toubert A: Oxidative stress mediates a reduced expression of the activating receptor NKG2D in NK cells from end-stage renal disease patients. J Immunol 2009;182:1696-1705.
© 2013 S. Karger AG, Basel
2013
Copyright / Drug Dosage / Disclaimer
Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.
You do not currently have access to this content.