The role of hypercytokinemia in the pathophysiology of tumor lysis syndrome (TLS) and the treatment with continuous hemodiafiltration using a polymethylmethacrylate membrane hemofilter (PMMA-CHDF)

Objective: To examine the role of hypercytokinemia in the pathophysiology of tumor lysis syndrome (TLS) and the efficacy of continuous hemodiafiltration in the treatment of TLS. Design and setting: Retrospective observational study in a general intensive care unit of a university hospital. Patients: Four patients with hematological disorder developing TLS after the treatment of anti-tumor chemotherapy. Interventions: Continuous hemodiafiltration using a polymethylmethacrylate membrane hemofilter (PMMA-CHDF) was performed at the onset of TLS. Blood samples were collected daily after ICU admission, and clinical parameters and blood levels of cytokines were evaluated. Measurements and results: All four patients underwent induction anti-tumor chemotherapy, during which they developed hyperuricemia, hyperkalemia, and acute renal failure. Two of them also developed multiple organ failure. Serum levels of tumor necrosis factor (TNF) -alpha, interleukin-6 (IL-6), and IL-10 prior to the initiation of PMMA-CHDF were 102 +/- 85 pg/mL, 1097 +/- 546 pg/mL, and 98 83 pg/mL, respectively (mean +/- SD). After three days of PMMA-CHDF treatment, corresponding blood levels were 37 +/- 55 pg/mL, 326 +/- 511 pg/mL, and 9 +/- 8 pg/mL, respectively. Thus, all cytokine levels were significantly decreased by three days of PMMA-CHDF treatment (p < 0.05, paired t-test). Following three days of PMMA-CHDF treatment, blood urea nitrogen (BUN) and serum creatinine (Cre.) were significantly decreased (pre/post BUN 42.3 +/- 15.4/16.5 +/- 8.4 mg/dL, p < 0.05, pre/post Cre. 2.7 +/- 1.2/1.2 +/- 0.6 mg/dL, mean +/- SD, p < 0.05). Furthermore, the clinical condition of each patient was improved after the treatment of PMMA-CHDF, and all of four patients were survived. Conclusion: Hypercytokinemia plays a pivotal role in the pathophysiology of TLS and PMMA-CHDF may bean effective therapeutic modality for TLS patients not only as renal replacement therapy but also as a cytokine modulator. (C) 2008 Elsevier Ltd. All rights reserved.