Impact of serum and dialysates obtained from chronic hemodialysis patients maintained on high cut-off membranes on inflammation profile in human THP-1 monocytes.
Patients with chronic kidney disease maintained on intermittent hemodialysis suffer from systemic chronic inflammation which is causally associated with high mortality. Inflammation mediators of 15-45 kDa range cannot be effectively removed by conventional dialysis membranes. In this study, we tested the influence of serum and dialysates obtained from patients maintained on High cut-off or High flux membranes on the inflammation profile of THP-1 monocytes.



THP-1 monocytes were treated with serum or dialysates obtained from patients maintained on High cut-off and High flux membranes within a randomized crossover pilot trial. Serum-treated cells were subjected to qPCR analyses with TaqMan probes specific for IL6, TNFa, osteopontin and osteocalcin, and transcriptional screening with Inflammatory Array. Apoptosis assay was performed flow cytometrically with 7-AAD and Annexin V staining.



Treatment of the cells with High cut-off serum led to significant reduction of TNFa and IL-6 expression as well as inflammation-related osteopontin and osteocalcin as compared to High flux membrane treatment. As a complementary finding, treatment with High cut-off dialysates induced a pro-apoptotic phenotype in the cells as demonstrated by a significantly increased percentage of 7-AAD and Annexin V positivity. Global screening of serum-treated cells revealed noticeably decreased inflammation profile under High cut-off serum as compared to High flux treatment.



Taken together, these data demonstrate that High cut-off -membranes eliminate a spectrum of mediators from serum into the dialysate that possess proinflammatory properties and may impair cellular viability.
Department of Internal Medicine II, Martin-Luther-University Halle, Germany.
Bogusz
B
Trojanowicz
Department of Internal Medicine II, Martin-Luther-University Halle, Germany.
Christof
C
Ulrich
Department of Internal Medicine II, Martin-Luther-University Halle, Germany.
Roman
R
Fiedler
Department of Research and Development, Gambro Dialysatoren GmbH, Hechingen, Germany.
Markus
M
Storr
Department of Research and Development, Gambro Dialysatoren GmbH, Hechingen, Germany.
Torsten
T
Boehler
Institute for Clinical Epidemiology and Applied Biostatistics, University of Tübingen, Germany.
Peter
P
Martus
NMI Technology Transfer GmbH, Reutlingen, Germany.
Michael
M
Pawlak
Food Chemistry, Institute for Chemistry, Martin-Luther-University Halle, Germany.
Marcus A
MA
Glomb
Food Chemistry, Institute for Chemistry, Martin-Luther-University Halle, Germany.
Christian
C
Henning
NMI Technology Transfer GmbH, Reutlingen, Germany.
Markus
M
Templin
Department of Research and Development, Gambro Dialysatoren GmbH, Hechingen, Germany.
Kristin
K
Werner
Department of Nephrology and Internal Intensive Care Medicine, Charité-Universitaetsmedizin Berlin, Campus Virchow Clinic, Berlin, Germany.
Daniel
D
Zickler
Department of Nephrology and Internal Intensive Care Medicine, Charité-Universitaetsmedizin Berlin, Campus Virchow Clinic, Berlin, Germany.
Kevin
K
Willy
Department of Nephrology and Internal Intensive Care Medicine, Charité-Universitaetsmedizin Berlin, Campus Virchow Clinic, Berlin, Germany.
Ralf
R
Schindler
Department of Internal Medicine II, Martin-Luther-University Halle, Germany.
Matthias
M
Girndt
D000368:Aged; D018592:Cross-Over Studies; D015314:Dialysis Solutions / Q000378:metabolism*; D006801:Humans; D018836:Inflammation Mediators / Q000097:blood*; D009000:Monocytes / Q000378:metabolism*; D006435:Renal Dialysis / Q000009:adverse effects; D000074084:THP-1 Cells / Q000378:metabolism*
D015314:Dialysis Solutions; D018836:Inflammation Mediators
High cut-off; THP-1 monocytes; hemodialysis; inflammation