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Impact of serum and dialysates obtained from chronic hemodialysis patients maintained on high cut-off membranes on inflammation profile in human THP-1 monocytes

Trojanowicz, B., Ulrich, C., Fiedler, R., Storr, M., Boehler, T., Martus, P., Pawlak, M., Glomb, M. A., Henning, C., Templin, M., Werner, K., Zickler, D., Willy, K., Schindler, R., Girndt, M. (2017).

Hemodial Int. 2017 Jul;21(3):348-358. doi: 10.1111/hdi.12494. Epub 2016 Sep 26.

INTRODUCTION: 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. METHODS: 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. FINDINGS: 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. DISCUSSION: 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.