High-volume online haemodiafiltration improves erythropoiesis-stimulating agent (ESA) resistance in comparison with low-flux bicarbonate dialysis: results of the REDERT study.
BACKGROUND
In haemodialysis (HD) patients, anaemia is associated with reduced survival. Despite treatment with erythropoiesis-stimulating agents (ESAs), a large number of patients with chronic kidney disease show resistance to this therapy and require much higher than usual doses of ESAs in order to maintain the recommended haemoglobin (Hb) target, and recent studies suggest that hepcidin (HEP) may mediate the ESA resistance index (ERI). High-volume online haemodiafiltration (HV-OL-HDF) has been shown to improve anaemia and to reduce the need for ESAs in HD patients; this effect is associated with a reduced inflammatory state in these patients. The aim of the REDERT study (role of haemodiafiltration on ERI) was to investigate the effect of different dialysis techniques on ERI and HEP levels in chronic dialysis patients.


METHODS
A single cross-over, randomized, multicentre study (A-B or B-A) was designed. Forty stable HD patients from seven different dialysis units (male 65%, mean age 67.6 ± 14.7 years and mean dialytic age 48 ± 10 months) were enrolled. Patients were randomized to the standard bicarbonate dialysis (BHD) with low-flux polysulfone (PS) membrane group or to the HV-OL-HDF group with high-flux PS membranes and exchange volume of >20 L/session. After 6 months, patients were shifted to the other dialytic group for a further 6 months. Clinical data, Hb, ESA doses and iron metabolism were recorded every month. HEP, beta2-microglobulin (b2MG) and C-reactive protein (CRP) were determined every 3 months, and ERI was calculated monthly as the weekly ESA dose per kilogram of body weight divided by Hb level. Data were analysed using paired-samples t-test, Wilcoxon signed-rank test and Spearman's correlation coefficient.


RESULTS
Dialysis efficiency for small molecules assessed as Kt/V was significantly increased in HV-OL-HDF from 1.47 ± 0.24 to 1.49 ± 0.16; P < 0.01. A significant reduction of b2MG was obtained in HV-OL-HDF from month 3 whereas CRP values were not significantly changed during the study period either in BHD or HV-OL-HDF.ERI was significantly reduced in HV-OL-HDF at month 3 and 6 (from 9.1 ± 6.4 UI/weekly/Kg/Hb to 6.7 ± 5.3 UI/weekly/Kg/Hb; P < 0.05) due to a higher ESA consumption in BHD in spite of similar Hb levels. HEP levels were reduced in HV-OL-HDF with respect to BHD after 3 and 6 months. Iron consumption was not significantly different during BHD or HV-OL-HDF treatment as well as transferrin, ferritin and TSAT levels. A significant positive linear correlation between HEP and ERI (r(2) = 0.258, P < 0.001) was observed.


CONCLUSIONS
In a uraemic patient population with low-grade inflammation treated with HV-OL-HDF, we observed a significant reduction of ERI values as well as HEP levels. The positive correlation between these two parameters supports a role for HEP in the development of ERI in the dialytic population. Moreover, the lower b2MG and the higher Kt/V achieved in HV-OL-HDF confirms the better depurative effect of this technique in comparison with BHD with respect to middle molecules and small-molecular-weight molecules.
Nephrology and Dialysis, Versilia Hospital, Lido di Camaiore, Italy.
Vincenzo
V
Panichi
Nephrology and Dialysis, Versilia Hospital, Lido di Camaiore, Italy.
Alessia
A
Scatena
Nephrology and Dialysis, Lucca Hospital, Lucca, Italy.
Alberto
A
Rosati
Nephrology and Dialysis, Lucca Hospital, Lucca, Italy.
Riccardo
R
Giusti
Nephrology and Dialysis, Firenze OSMA, Firenze, Italy.
Giuseppe
G
Ferro
Nephrology and Dialysis, Lucca Hospital, Lucca, Italy.
Erasmo
E
Malagnino
Nephrology and Dialysis, Pistoia Hospital, Pistoia, Italy.
Alessandro
A
Capitanini
Nephrology and Dialysis, Pistoia Hospital, Pistoia, Italy.
Adriano
A
Piluso
Nephrology and Dialysis, Grosseto Hospital, Grosseto, Italy.
Paolo
P
Conti
Nephrology and Dialysis, Grosseto Hospital, Grosseto, Italy.
Giada
G
Bernabini
Nephrology and Dialysis, Versilia Hospital, Lido di Camaiore, Italy.
Massimiliano
M
Migliori
Nephrology and Dialysis, Firenze OSMA, Firenze, Italy.
David
D
Caiani
Fresenius Medical Care GmbH, Deutschland, Bad Homburg, Germany.
Ciro
C
Tetta
Nephrology and Dialysis, Carrara Hospital, Massa Carrara, Italy.
Aldo
A
Casani
Nephrology and Dialysis, Carrara Hospital, Massa Carrara, Italy.
Giancarlo
G
Betti
Nephrology and Dialysis, Firenze OSMA, Firenze, Italy.
Francesco
F
Pizzarelli
D000368:Aged; D000740:Anemia / Q000188:drug therapy*; D001639:Bicarbonates / Q000627:therapeutic use*; D002097:C-Reactive Protein / Q000378:metabolism; D018592:Cross-Over Studies; D004351:Drug Resistance; D004920:Erythropoiesis / Q000187:drug effects; D005260:Female; D006397:Hematinics / Q000494:pharmacology*; D017583:Hemodiafiltration / Q000379:methods*; D015312:Hemodialysis Solutions / Q000627:therapeutic use*; D006454:Hemoglobins / Q000378:metabolism; D064451:Hepcidins / Q000378:metabolism; D006801:Humans; D007249:Inflammation / Q000188:drug therapy; D007501:Iron / Q000378:metabolism; D008297:Male; D009862:Online Systems; D011446:Prospective Studies; D014511:Uremia / Q000188:drug therapy
D001639:Bicarbonates; D006397:Hematinics; D015312:Hemodialysis Solutions; D006454:Hemoglobins; D064451:Hepcidins; D002097:C-Reactive Protein; D007501:Iron
C-reactive protein; ESA resistance; chronic inflammation; hepcidin; online haemodiafiltration