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


Journal

Journal of nephrology
ISSN: 1724-6059
Titre abrégé: J Nephrol
Pays: Italy
ID NLM: 9012268

Informations de publication

Date de publication:
Oct 2020
Historique:
received: 18 10 2019
accepted: 31 01 2020
pubmed: 10 2 2020
medline: 19 8 2021
entrez: 10 2 2020
Statut: ppublish

Résumé

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. 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. 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. 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.

Sections du résumé

BACKGROUND 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 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 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 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.

Identifiants

pubmed: 32036610
doi: 10.1007/s40620-020-00709-0
pii: 10.1007/s40620-020-00709-0
doi:

Substances chimiques

Hematinics 0
Hemoglobins 0

Types de publication

Journal Article Randomized Controlled Trial

Langues

eng

Sous-ensembles de citation

IM

Pagination

1037-1048

Références

Locatelli F, Covic A, Eckardt KU, Wiecek A, Vanholder R, on behalf of the ERA-EDTA ERBP Advisory Board. Anemia management in patients with chronic kidney disease: a position statement by the Anemia Working Group of European. Renal Best Practice (ERBP). Nephrol Dial Transplant 2009; 24: 348–354.
McFarlane PA, Pisoni RL, Eichleay MA, Wald R, Port FK, Mendelssohn D (2010) International trends in erythropoietin use and hemoglobin levels in hemodialysis patients. Kidney Int 78(2):215–223
doi: 10.1038/ki.2010.108
MacDougall IC, Cooper AC (2002) Erythropoietin resistance: the role of inflammation and pro-inflammatory cytokines. Nephrol Dial Transpl 17(Suppl 11):39–43
doi: 10.1093/ndt/17.suppl_11.39
Alves MT, Vilaca SS, Carvalho M, Fernandes AP, Dusse LM, Gomes KB (2015) Resistance of dialyzed patients to erythropoietin. Rev Bras Hematol Hemoter 37:190–197
doi: 10.1016/j.bjhh.2015.02.001
Solomon SD, Uno H, Lewis EF, Eckardt KU, Lin J, Burdmann EA et al (2010) Erythropoietic response and outcomes in kidney disease and type 2 diabetes. N Engl J Med 363:1146–1155
doi: 10.1056/NEJMoa1005109
Rene E, Lazrak HH, Laurin LP, Elftouh N, Vallee M, Lafrance JP (2017) Association of erythropoiesis-stimulating agents and the incidence risk of cancer diagnosis among chronic dialysis patients: a nested case-control study. Nephrol Dial Transpl 32(6):1047–1052
Luo J, Jensen DE, Maroni BJ, Brunelli SM (2016) Spectrum and burden of erythropoiesis-stimulating agent hyporesponsiveness among contemporary hemodialysis Patients. Am J Kidney Dis 68(5):763–771
doi: 10.1053/j.ajkd.2016.05.031
Perez-Garcia R, Varas J, Cives A, Martin-Malo A, Aljama P, Ramos R et al (2018) Increased mortality in hemodialysis patients administered high doses of erythropoiesis-stimulating agents: a propensity score-matched analysis. Nephrol Dial Transpl 33:690–699
doi: 10.1093/ndt/gfx269
Marcelli D, Bayh I, Merello JI, Ponce P, Heaton A, Kircelli F et al (2016) Dynamics of the erythropoiesis stimulating agent resistance index in incident hemodiafiltration and high-flux hemodialysis patients. Kidney Int 90(1):192–202
doi: 10.1016/j.kint.2016.03.009
Panichi V, Scatena A, Rosati A, Giusti R, Ferro G, Malagnino E et al (2015) High-volume online hemodiafiltration improves erythropoiesis-stimulating agent (ESA) resistance in comparison with low-flux bicarbonate dialysis: results of the REDERT study. Nephrol Dial Transpl 30:682–689
doi: 10.1093/ndt/gfu345
Pedrini LA, De Cristofaro V, Comelli M, Casino FG, Prencipe M, Baroni A et al (2011) Long-term effects of high-efficiency on-line hemodiafiltration on uraemic toxicity A multicentre prospective randomized study. Nephrol Dial Transplant 26(8):2617–2624
doi: 10.1093/ndt/gfq761
Vaslaki L, Major L, Berta K, Karatson A, Misz M, Pethoe F et al (2006) On-line hemodiafiltration versus hemodialysis: stable haematocrit with less erythropoietin and improvement of other relevant blood parameters. Blood Purif 24:163–173
doi: 10.1159/000090117
Tessitore N, Poli A, Bedogna V et al (2018) A single dialysis session of hemodiafiltration with sorbent-regenerated endogenous ultrafiltrate reinfusion (HFR) removes hepcidin more efficiently than bicarbonate hemodialysis: a new approach to containing hepcidin burden in dialysis patients? J Nephrol 31:297–306
doi: 10.1007/s40620-017-0383-0
Locatelli F, Altieri P, Andrulli S, Sau G, Bolasco P, Pedrini LA et al (2012) Predictors of hemoglobin levels and resistance to erythropoiesis-stimulating agents in patients treated with low-flux hemodialysis, haemofiltration and hemodiafiltration: results of a multicentre randomized and controlled trial. Nephrol Dial Transpl 27:3594–3600
doi: 10.1093/ndt/gfs117
Oates T, Pinney JH, Davenport A (2011) Hemodiafiltration versus high-flux hemodialysis: effects on phosphate control and erythropoietin response. Am J Nephrol 33:70–75
doi: 10.1159/000322834
van der Weerd NC, Den Hoedt CH, Blankestijn PJ, Bots ML, van der Dorpel MA, Levesque R et al (2014) Resistance to erythropoiesis stimulating agents in patients treated with online hemodiafiltration and ultrapure low-flux hemodialysis: results from a randomized controlled trial (CONTRAST). PLoS ONE 9:e94434
doi: 10.1371/journal.pone.0094434
Maduell F, Moreso F, Pons M, Ramos R, Mora-Macia J, Carreras J et al (2013) High-efficiency postdilution online hemodiafiltration reduces all-cause mortality in hemodialysis patients. J Am Soc Nephrol 24:487–497
doi: 10.1681/ASN.2012080875
Pedrini LA, Zawada AM, Winter AC, Pham J, Klein G, Wolf M et al (2019) Effects of high-volume online mixed-hemodiafiltration on anemia management in dialysis patients. PLoS ONE. https://doi.org/10.1371/journal.pone.0212795
doi: 10.1371/journal.pone.0212795 pubmed: 30794672 pmcid: 6386285
Pedrini LA, Cozzi G, Faranna P, Mercieri A, Ruggiero P, Zerbi S et al (2006) Transmembrane pressure modulation in high-volume mixed hemodiafiltration to optimize efficiency and minimize protein loss. Kidney Int 69(3):573–579
doi: 10.1038/sj.ki.5000110
Pedrini LA, Wiesen G (2011) Overcoming the limitations of post-dilution on-line hemodiafiltration: mixed dilution hemodiafiltration. Contrib Nephrol 175:129–140
doi: 10.1159/000333629
Shirazian S, Rios-Rojas L, Drakakis J, Dikkala S, Dutka P, Duey M et al (2012) The effect of hemodialysis ultrafiltration on changes in whole blood viscosity. Hemodial Int 16(3):342–350
doi: 10.1111/j.1542-4758.2012.00671.x
Bergstrom J, Wehle B (1987) No change in corrected β2-microglobulin concentration after cuprophane hemodialysis. Lancet 1:628–629
doi: 10.1016/S0140-6736(87)90266-2
Daugirdas JT (1995) Simplified equations for monitoring Kt/V, PCRn, eKt/V, and ePCRn. Adv Ren Ther 2:295–304
doi: 10.1016/S1073-4449(12)80028-8
Marcelli D, Kirchgessner J, Amato C, Steil H, Mitteregger A, Moscardo V et al (2001) EuCliD (European Clinical Database): a database comparing different realities. J Nephrol 14:S94–S100
pubmed: 11798154
Fleiss JL (1986) The cross-over study. In: Wiley, ed. The design and analysis of clinical experiments. New York, 263–281
The R Developement Core Team. R version 1.7.1. https://www.R-project.org . 2003. Vienna, Austria. Accessed 11 Dec 2019
Maduell F, del Pozo C, Garcia H, Sanchez L, Hdez-Jaras J, Albero MD et al (1999) Change from conventional hemodiafiltration to on-line hemodiafiltration. Nephrol Dial Transpl 14(5):1202–1207
doi: 10.1093/ndt/14.5.1202
Stefansson BV, Abramson M, Nilsson U, Haraldsson B (2012) Hemodiafiltration improves plasma 25-hepcidin levels: a prospective, randomized, blinded, cross-over study comparing hemodialysis and hemodiafiltration. Nephron Extra 2(1):55–65
doi: 10.1159/000336482
Georgatzakou HT, Antonelou MH, Papassideri IS, Kriebardis AG (2016) Red blood cell abnormalities and the pathogenesis of anemia in end stage renal disease. Proteomics Clin Appl 10:778–790
doi: 10.1002/prca.201500127
Antonelou MH, Kriebardis AG, Velentzas AD, Kokkalis AC, Georgakopoulou SC, Papassideri IS (2011) Oxidative stress-associated shape transformation and membrane proteome remodeling in erythrocytes of end stage renal disease patients on hemodialysis. J Proteomics 74:2441–2452
doi: 10.1016/j.jprot.2011.04.009
Bonomini M, Ballone E, Di Stante S, Bucciarelli T, Dottori S, Arduino A, Urbani A, Sirolli V (2004) Removal of uremic plasma factor(s) using different dialysis modalities reduces phosphatidylserine exposure in red blood cells. Nephrol Dial Transpl 19:68–74
doi: 10.1093/ndt/gfg532
Bonomini V, Arduino A, Sirolli V, Di Pietro N, Pandolfi A (2017) Erythtocyte abnormalities and their possible role in cardiovascular complications of uremia. G Ital Nephrol. 34:1–15
Polaschegg HD (2009) Red blood cell damage from extracorporeal circulation in hemodialysis. Semin Dial 22:524–531
doi: 10.1111/j.1525-139X.2009.00616.x
Watanabe N, Shimada T, Hakozaki M, Hara R (2018) Visualization of erythrocyte deformation induced by supraphysiological shear stress. Int J Artif Organs 41:838–844
doi: 10.1177/0391398818793387
Horobin JT, Sabapathy S, Simmonds MJ (2017) Repetitive supra-physiological shear stress impairs red blood cell deformability and induces hemolysis. Artif Organs 41(11):1017–1025
doi: 10.1111/aor.12890
Yen JH, Chen SF, Chern MK, Lu PC (2014) The effect of turbulent viscous shear stress on red blood cell hemolysis. Int J Artif Organs 17(2):178–185
doi: 10.1007/s10047-014-0755-3
Simmonds MJ, Meiselman HJ (2016) Prediction of the level and duration of shear stress exposure that induces subhemolytic damage to erythrocytes. Biorheology 53(5–6):237–249
pubmed: 28222499
McNamee AP, Tansley GD, Sabapathy S, Simmonds MJ (2016) Biphasic impairment of erythrocyte deformability in response to repeated, short duration exposures of supraphysiological, subhaemolytic shear stress. Biorheology 53(3–4):137–149
doi: 10.3233/BIR-15108
Jones SA (1995) A relationship between Reynolds stresses and viscous dissipation: implications to red cell damage. Ann Biomed Eng 23(1):21–28
doi: 10.1007/BF02368297
Pedrini LA, De Cristofaro V, Pagliari B, Samà F (2000) Mixed pre- and postdilution on-line hemodiafiltration: efficiency and safety compared with the traditional infusion modes. Kidney Int 58:2155–2165
doi: 10.1111/j.1523-1755.2000.00389.x
Olia S, Maul T, Antaki J, Kameneva M (2016) Mechanical blood trauma in assisted circulation: sublethal RBC damage preceding hemolysis. Int J Artif Organs 39(4):150–159
doi: 10.5301/ijao.5000478
Cozette P, Gaillard S, Rose E, Carnielo M (1979) Rheological effects of normovolemic hemodilution. Ann Anesthesiol Fr 20(9):775–783
pubmed: 45288
Masakane I, Kikuchi K, Kawanishi I (2017) Evidence for the clinical advantages of predilution on-line hemodiafiltration. Contrib Nephrol 189:17–23
doi: 10.1159/000450635

Auteurs

Luciano A Pedrini (LA)

Nephrology and Dialysis Unit, NephroCare, ASST Bergamo-Est, Bolognini Hospital, Seriate, Italy. Luciano.pedrini@fmc-ag.com.

Mario Comelli (M)

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

Pio Ruggiero (P)

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

Annalisa Feliciani (A)

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

Vania Manfrini (V)

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

Giorgio Cozzi (G)

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

Angelo Castellano (A)

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

Mauro Pezzotta (M)

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

Guido Gatti (G)

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

Marta Arazzi (M)

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

Laura Auriemma (L)

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

Attilio di Benedetto (A)

Medical Coordination NephroCare, Naples, Italy.

Stefano Stuard (S)

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

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