Background: A recent cross-sectional study demonstrated that convective-controlled double high-flux hemodiafiltration (CC-HDF) could yield equivalent removal of small and middle molecule uremic toxins to on-line hemodiafiltration (OL-HDF). Methods: The present study was conducted to compare the 1-year efficacy between CC-HDF (n = 10) and OL-HDF (n = 16) in chronic hemodialysis patients undergoing thrice weekly high-flux hemodialysis for at least 6 months. Results: When compared with baseline (high-flux hemodialysis), 1-year treatment with both HDF modes had comparable efficacy in significantly lowering serum pre-dialysis β2-microglobulin (β2m) levels (p < 0.05) and significantly enhancing greater urea reduction ratio (p < 0.05). Both HDF modes could comparably maintain the hematology profile, calcium-phosphorus metabolism, and nutritional status according to the K-DOQI guidelines. Conclusion: CC-HDF can provide equivalent 1-year efficacy to OL-HDF and would be an effective alternative mode to OL-HDF.

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