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Aspects of Immune Dysfunction in End-stage Renal Disease

Sawako Kato^*,, Michal Chmielewski^*,, Hirokazu Honda, Roberto Pecoits-Filho^||, Seiichi Matsuo, Yukio Yuzawa, Anders Tranaeus^*, Peter Stenvinkel^*, and Bengt Lindholm^*

^* Divisions of Renal Medicine and Baxter Novum, Department of Clinical Science, Intervention and Technology, Karolinska Institutet, Stockholm, Sweden; Division of Clinical Immunology, Department of Internal Medicine, Nagoya University Graduate School of Medicine, Nagoya, Japan; Department of Nephrology, Transplantology and Internal Medicine, Medical University of Gdansk, Gdansk, Poland; Department of Nephrology, Showa University School of Medicine, Tokyo, Japan; ^|| Centro de Ciencias Biologicas e da Saude, Pontificia Universidade Catolica do Parana, Curitiba, Brazil

Correspondence: Dr. Bengt Lindholm, Divisions of Renal Medicine and Baxter Novum, K-56 Karolinska University Hospital Huddinge, 141 86, Stockholm, Sweden. Phone: +46858582601; Fax: +46858583925; E-mail: bengt.lindholm{at}ki.se

End-stage renal disease (ESRD) is associated with significantly increased morbidity and mortality resulting from cardiovascular disease (CVD) and infections, accounting for 50% and 20%, respectively, of the total mortality in ESRD patients. It is possible that these two complications are linked to alterations in the immune system in ESRD, as uremia is associated with a state of immune dysfunction characterized by immunodepression that contributes to the high prevalence of infections among these patients, as well as by immunoactivation resulting in inflammation that may contribute to CVD. This review describes disorders of the innate and adaptive immune systems in ESRD, underlining the specific role of ESRD-associated disturbances of Toll-like receptors. Finally, based on the emerging links between the alterations of immune system, CVD, and infections in ESRD patients, it emphasizes the potential role of the immune dysfunction in ESRD as an underlying cause for the high mortality in this patient population and the need for more studies in this area.