uPAR (CD87) as a biocompatibility marker of dialysis membrane.
OBJECTIVE
Hemodialysis (HD) therapy may lead to functional changes in patient leukocytes. For example, the upregulation of inflammatory cytokines, such as IL-1beta and TNFalpha, has been well characterized. However, these findings do not explain the entire response of leukocytes in HD. In this study, we carried out a comprehensive gene expression analysis in leukocytes treated with various dialysis membranes using DNA microarrays. The identified gene has the potential to be a new marker for testing dialysis membrane biocompatibility.


METHODS
Gene expression profiles were compared between a group of leukocytes treated with various dialysis membranes and an untreated group by using DNA microarray analysis. Expression was confirmed by quantitative RT-PCR. The expression of the gene product (leukocyte surface protein) was examined in 20 chronic HD patients by flow cytometry.


RESULTS
In addition to the inflammatory cytokines, the urokinase plasminogen activator receptor (uPAR or CD87) gene was induced in leukocytes treated with each dialysis membrane. The extent of induction depended on the membrane's material composition. The expression of the uPAR (CD87) protein on leukocytes was markedly increased in patients undergoing dialysis therapy. The magnitude of uPAR (CD87) protein expression was correlated with clinical findings, i.e., the degree of leukopenia and the expression of adhesion molecules.


CONCLUSIONS
The gene and protein expression of uPAR (CD87) depended on the dialysis membrane material and correlated closely with clinical findings. These results suggest that uPAR has the potential to serve as a marker not only for clinical use but also for the development of new dialysis membranes.
Sohka
Takayuki
T
Second Department, Central Technology Laboratory, Asahi Kasei Corporation, Fuji, Japan. souka.tb@om.asahi-kasei.co.jp
Ohno
Takeshi
T
Ichinose
Mayuri
M
Okonogi
Hideo
H
Kawaguchi
Yoshindo
Y
Hosoya
Tatsuo
T
Nakamura
Kazuyoshi
K
Kataoka
Eiko
E
Suzuki
Mari
M
Koremoto
Masahide
M
Sumita
Masaya
M
Shirai
Takasi
T
Kasai
Kenji
K
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001672:Biocompatible Materials; D015415:Biomarkers / Q000737:chemistry*; D005260:Female; D020869:Gene Expression Profiling; D006801:Humans; D008297:Male; D008567:Membranes, Artificial; D008875:Middle Aged; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods*; D011956:Receptors, Cell Surface / Q000737:chemistry / Q000235:genetics; D055293:Receptors, Urokinase Plasminogen Activator; D006435:Renal Dialysis / Q000379:methods*; D020133:Reverse Transcriptase Polymerase Chain Reaction
D001672:Biocompatible Materials; D015415:Biomarkers; D008567:Membranes, Artificial; C524898:PLAUR protein, human; D011956:Receptors, Cell Surface; D055293:Receptors, Urokinase Plasminogen Activator