Erythropoietin-stimulating agent (ESA) hyporesponsiveness is aggravated by chronic inflammation in maintenance hemodialysis (MHD) patients. Dyslipidemia is prevalent in MHD patients. Statin therapy has been demonstrated to not only be effective in lowering lipid levels, but also numerous pleiotropic effects including anti-inflammatory, anti-fibrotic and endothelial function improvement. Recently, a retrospective study has shown that statin therapy decreases ESA requirements in MHD patients. We conducted a prospective study to analyze the effect of statin therapy on ESA hyporesponsiveness, and especially emphasized its anti-inflammatory benefits in MHD patients. This prospective study enrolled 30 patients with baseline cholesterol >220 mg/dl. Low-dose atorvastatin (10 mg/day) was prescribed for 12 weeks. We prospectively recorded patients’ biochemistry and hematological profiles, ESA prescription and some inflammatory markers at baseline, 4 weeks and 12 weeks. Statistically significant changes were noted after 4 and 12 weeks of statin therapy for cholesterol (272.5 ± 41.1 to 184.4 ± 37.6 and 196.4 ± 40.2 mg/dl, p < 0.05) and ESA hyporesponsiveness, which demonstrated as erythropoietin to hematocrit ratio (EHR) (129.3 ± 58.2 to 122.3 ± 53.5 and 121.0 ± 53.3 EPO U/Hct/week, p < 0.05). Mean values for proinflammatory cytokines included interleukin-6 and tumor necrotic factor-α levels decreased by 30.8 and 10.6%, respectively. Thus, these data suggest that statin therapy may improve ESA hyporesponsiveness in dialysis patients. This improvement in ESA hyporesponsiveness is associated with the effects of statins on inflammation.

Background/Aims: This study investigated changes of interleukin-18 (IL-18) levels before and after dialysis, and the possible association with other pro-inflammatory cytokines, such as interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α). Methods: Plasma IL-18 of healthy controls, and pre- and post-dialysis of uremic patients undergoing hemodialysis (HD) were evaluated by ELISA methodology. Results: Plasma IL-18 levels were significantly increased in patients with maintenance HD (p <0.001) compared to its level in normal subjects. When compared to pre-dialysis levels, a significant increase in plasma IL-18 was measured at the end of HD (p = 0.032). There was a significant correlation among plasma IL-18, IL-6 and TNF-α levels in HD patients. Conclusion: Plasma IL-18 concentration was significantly higher in HD patients and was significantly elevated by cellulose-based HD processes. Pre-activation of immunologically active cells may contribute to the association between pre-dialysis IL-18 and post-dialysis IL-6 and TNF-α levels.