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NDT Advance Access published online on August 3, 2004
Nephrology Dialysis Transplantation, doi:10.1093/ndt/gfh278
© 2004 by European Renal Association - European Dialysis and Transplant Association
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Received October 11, 2003
Accepted February 6, 2004

Original Article

Oxidative stress induced by iron released from transferrin in low pH peritoneal dialysis solution

Yasuyoshi Yamaji 1*, Yuichi Nakazato 2, Naoki Oshima 1, Matsuhiko Hayashi 2, Takao Saruta 2

1 Kidney Disease Center and Internal Medicine, Saitama Social Insurance Hospital, Saitama-City, Saitama, Japan
2 Department of Internal Medicine, School of Medicine, Keio University, Tokyo, Japan

* To whom correspondence should be addressed. E-mail: yamaji{at}1985.jukuin.keio.ac.jp.



  Abstract

Background. Transferrin binds extracellular iron and protects tissues from iron-induced oxidative stress. The binding of iron and transferrin is pH dependent and conventional peritoneal dialysis (PD) solutions have unphysiologically low pH values. Herein, we investigated whether conventional PD solution releases iron from transferrin and if the released iron causes oxidative stress.

Methods. Effects of PD solutions on iron binding to transferrin were examined with purified human transferrin and transferrin in dialysates drained from PD patients. Oxidative stress induced by iron released from transferrin was evaluated in terms of the formation of thiobarbituric acid reactive substance (TBARS) and protein carbonylation in the human red blood cell (RBC) membrane. The iron deposition in peritoneal tissue from PD patients was evaluated by Perls' staining with diaminobenzidine intensification.

Results. Low pH PD solution released iron from transferrin. This iron release occurred within 1 min. Iron release was not observed in neutralized PD solution. Iron released from transferrin in low pH PD solution increased TBARS formation and protein carbonylation in the human RBC membrane. Iron deposition, which is prominent in the fibrotic area facing the peritoneal cavity, was observed in the peritoneum of PD patients.

Conclusions. Iron released from transferrin in low pH PD solution can produce oxidative stress in the peritoneum of a PD patient. Neutralizing PD solution can avoid this problem. Iron deposition in the peritoneum may participate in the pathogenesis of peritoneal fibrosis in PD patients.

Keywords: dialysate; fibrosis; iron; oxidative stress; peritoneal dialysis; peritoneal function; pH.
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