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Mixed hemodiafiltration reduces erythropoiesis stimulating agents requirement in dialysis patients: a prospective randomized study

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Abstract

Background

Improved responsiveness to erythropoiesis stimulating agents (ESAs) in patients on on-line post-dilution hemodiafiltration (Post-HDF) compared with conventional hemodialysis (HD) was reported by some authors but challenged by others. This prospective, cross-over randomized study tested the hypothesis that an alternative infusion modality of HDF, mixed-dilution HDF (Mixed HDF), could further reduce ESAs requirement in dialysis patients compared to the traditional Post-HDF.

Methods

One-hundred-twenty prevalent patients from 6 Dialysis Centers were randomly assigned to two six-months treatment sequences: A–B and B–A (A, Mixed HDF; B, Post-HDF). Primary outcome was comparative evaluation of ESA (darbepoetin alfa) requirement and ESA resistance. Treatments efficiency, iron and vitamins status, inflammation and nutrition parameters were monitored.

Results

In sequence A, darbepoetin requirement decreased during Mixed HDF from 29.5 to 23.7 µg/month and increased significantly during Post-HDF (32.3 µg/month at 6th month) while, in sequence B, it increased during Post-HDF from 38.2 to 43.7 µg/month and decreased during Mixed HDF (23.9 µg/month at 6th month). Overall, EPO doses at 6 months on Mixed and Post-HDF were 23.8 and 38.4 µg/month, respectively, P < 0.01. A multiple linear model confirmed that Mixed HDF vs Post-HDF reduced significantly ESA requirement and ESA resistance (P < 0.0001), by a mean of 29% (CI 23–35%) in the last three months of the observation periods.

Conclusions

Mixed HDF decreased darbepoetin-alfa requirement in dialysis patients. This might help preventing the untoward side effects of high ESA doses, besides having a remarkable economic impact. Additional evidence is needed to confirm this potential benefit of Mixed-HDF.

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Acknowledgements

The authors thank all physicians and nurses working at the 6 NephroCare Dialysis Centers participating in this study for their efforts in handling the EuCliD data, which made this project possible. Centers participating in this study were: Nephrology and Dialysis Unit NephroCare, Bolognini Hospital, Seriate, and Dialysis Centers of “S.Isidoro” Hospital, Trescore Balneario, “Briolini” Hospital, Gazzaniga, “Faccanoni” Hospital, Sarnico, “Locatelli” Hospital, Piario, “Capitanio e Gerosa Hospital”, Lovere. All the Hospitals belong to the Azienda Socio-Sanitaria Territoriale Bergamo-Est, Italy, and Dialysis Centers operate within a public–private participation with NephroCare S.p.a., Italy.

Funding

We did not receive any financial support for this study.

Author information

Authors and Affiliations

  1. Nephrology and Dialysis Unit, NephroCare, ASST Bergamo-Est, Bolognini Hospital, Seriate, Italy

    Luciano A. Pedrini, Pio Ruggiero, Annalisa Feliciani, Vania Manfrini, Giorgio Cozzi, Angelo Castellano, Mauro Pezzotta, Guido Gatti & Marta Arazzi

  2. Department of Brain and Behavioural Sciences, University of Pavia, Pavia, Italy

    Mario Comelli

  3. Biochemistry Unit, ASST Bergamo-Est, Bolognini Hospital, Seriate, Italy

    Laura Auriemma

  4. Medical Coordination NephroCare, Naples, Italy

    Attilio di Benedetto

  5. Fresenius Medical Care, Clinical and Therapeutical Governance, Bad Homburg, Germany

    Stefano Stuard

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  1. Luciano A. Pedrini
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Contributions

Study conception and design: LAP, AF, SS. Analysis and interpretation of data: LAP, PR, MC, LA. Data acquisition: VM, AC, MP, GG, GC, MA. Writing of manuscript draft: LAP, MC. Providing intellectual content of critical importance to the work: all authors. All authors take responsibility for the integrity and accuracy of the work. All authors read and approved the final manuscript.

Corresponding author

Correspondence to Luciano A. Pedrini.

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Conflict of interest

LAP has a consultancy agreement with NephroCare, Italy, as Medical Director of the Unit of Nephrology and Dialysis of the Bolognini Hospital, Seriate, managed by NephroCare in the frame of a public–private participation with the Azienda Socio Sanitaria territoriale (ASST) Bergamo-Est, Italy. ADB, AF, VM, AC,MP, GG, MA are Nephrologists employees of NephroCare, Italy. SS is employee of Fresenius Medical Care, Germany. LAP is the patent holder “'The present invention refers to a method for blood purification by means of hemodialysis and/or hemofiltration, wherein to the blood in the extra-corporeal circuit of the hemodialysis and/or hemofiltration device a substitution solution is added upstream as well as downstream of the hemodialyser and/or hemofilter.” Documented at the following link: https://patents.google.com/patent/US6821441B2/en?inventor=luciano+pedrini&assignee=Fresenius+Medical+Care+Deutschland+Gmbh.

Ethical statement

The study was conducted in accordance with the basic principles of the Declaration of Helsinki and the rules of Good Clinical Practice and the protocol was approved by the local Ethic Committee.

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Pedrini, L.A., Comelli, M., Ruggiero, P. et al. Mixed hemodiafiltration reduces erythropoiesis stimulating agents requirement in dialysis patients: a prospective randomized study. J Nephrol 33, 1037–1048 (2020). https://doi.org/10.1007/s40620-020-00709-0

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  • DOI: https://doi.org/10.1007/s40620-020-00709-0

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