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

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 MA, Henning C, Templin M, Werner K, Zickler D, Willy K, Schindler R, Girndt M
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.

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