Introduction: in hemodialysis (HD) patients, poor health-related quality of life (HR-QoL) is prevalent and associated with adverse outcomes. HR-QoL is strictly linked to nutritional status of HD patients. Hemodiafiltration with endogenous reinfusion (HFR) is an alternative dialysis technique that combines diffusion, convection and absorption. It reduces burden of inflammation and malnutrition and this effect may cause beneficial effect on HR-QoL. However no data on HR-QoL in HFR is currently available.
Methods: we designed a cross-sectional multicentre study in order to compare the HR-QoL in patients treated with HFR versus Bicarbonate HD (BHD). We enrolled adult patients HFR treated for at least 6 months, with life expectancy greater than six months and without overt cognitive deficit. The recruited patients in HFR were matched for age, gender, dialytic vintage and performance in activities of daily living (Barthel index) with BHD treated patients. SF-36 questionnaire for the assessment of HR-QoL was administered.
Results: one hundred fourteen patients (57 HFR vs 57 BHD) were enrolled (age 65.4±13.5 years; dialysis vintage 5.4 (3.3-10.3) years; 53% males) from 18 dialysis non-profit centres in central and southern Italy. As result of matching, no difference in age, gender, dialytic age and Barthel index was found between HFR and BHD patients. In HFR patients we observed better values of physical component score (PCS) of SF-36 than BHD patients (P=0.048), whereas no significant difference emerged in the mental component score (P=0.698). In particular HFR patients were associated with higher Physical Functioning (P=0.045) and Role Physical (P=0.027).
Conclusions: HFR is associated with better physical component of HR-QoL than BHD, independently of age, gender, dialysis vintage and invalidity score. Whether these findings translate into a survival benefit must be investigated by longitudinal studies.
Despite the improvement in the treatment of complications and symptoms of End Stage Renal Disease (ESRD) observed in these last decades, patients on maintenance hemodialysis (HD) experience poor quality of life   (full text), associated with increased morbidity and mortality (full text)  (full text) .
Health Related-Quality of Life (HR-QoL) is directly dependent on functional status of patients, that is the ability of individual to perform daily activities, such as walking, dressing, bathing, etc. In fact, the initiation of dialysis is associated with a substantial and sustained decline in functional status. In particular, a survey performed in 3702 nursing home residents in the United States starting HD treatment, showed that after 12 months from the initiation of HD, 58% had died and 29% had a substantial decline in functional status; therefore pre-dialysis functional status was maintained in only a remarkable minority (13%) of patients  (full text). This decline in functional status in HD patients has a complex and multi-factorial pathogenesis: CKD-related factors, such as malnutrition, chronic inflammation, acidosis, anemia, bone demineralization, muscle hypotrophy, increased burden of co-morbidities (CV diseases, diabetes) as well as the side effects of treatment   (full text).
Hemodiafiltration (HDF), ameliorating the uremic symptoms, could potentially provide a beneficial effect on HR-QoL, however available data on the effect of different HD techniques on HR-QoL remain controversial   (full text)   (full text)   (full text).
Haemodiafiltration with endogenous reinfusion (HFR) is a dialysis technique, that combines three mechanisms, diffusion, convection and absorption. Some studies showed an improvement of nutritional and inflammatory status in patients treated by HFR  (full text)  (full text)   , as well as an amelioration of hemodynamic instability . The beneficial effect on the inflammatory status, on the oxidative stress and on the malnutrition in HD patients may be associated with an improvement of functional status and consequently of HR-QoL. However data on HR-QoL in HFR are not currently available.
Therefore, aim of this cross-sectional study is to evaluate HR-QoL in HFR patients as compared with those treated with standard Bicarbonate HD.
This is a cross-sectional study, which involved 18 centers in central and southern Italy (10 centers in Campania, 8 centers in Lazio).
All adult patients treated with HFR, from at least 6 months were included into the study and they were matched with patients in HD standard (1:1), by age, gender, dialysis age and disability score (Barthel index). Exclusion criteria were: treatment with other dialysis techniques, life expectancy lesser than six months, overt cognitive deficits.
In all selected patients,main demographic, clinical and therapy were collected and SF-36 questionnaire for the evaluation of HR-QoL were administered.
As shown in Table 1, the SF-36 questionnaire consists of 36 items that can be summarized in 8 scales, from which you get two summary scores: one for the component Physical (PCS, Physical Composite Score) and one for the mental component (MCS, Mental Composite Score) [REF?]. Each component consists of 4 domains, respectively Physical function (PF); Role-Physical (RP); Bodily Pain (BP) and General Health (GH) for PCS and Vitality (VT); Social Functioning (SF); Role Emotional (RE) and Mental Health (MH) for MCS.
HFR, depicted in Figure 1, is provided by means of double chamber filter (2.2 m2 of surface): first chamber consists of a high-flux membrane, which produces an ultrafiltrate (UF) that is “regenerated” through the passage in a styrenic cartridge, which adsorbs toxins and saves nutrients, such as amino-acids. Then, blood flows into the second chamber, consisting of low-flux polyphenylene membrane, where diffusion is performed.
BHD was performed by means of filters in polyphenylene, PMMA or polysulfone, blood flow at least 300 ml/min and dialysis flow at least 500 ml/min. The composition of the dialysate was the following: sodium: 140-143 mEq / L, potassium: 2-3 meq / L and calcium: 1.25-1.75 meq / L.
Continuous variables were reported as either mean and standard deviation (SD) or median and interquartile ranges (IQR) according to their distribution. The differences were assessed intergroup were analyzed using T-test for parametric variables or by Kruskall-Wallis for non parametric variables. Categorical variables were reported as percentages, and analyzed by chi-squared test. A two-tailed p value <0.05 was considered significant. Data were analyzed using STATA 11.
On the basis of the selection criteria 114 patients were enrolled (57 in HFR and 57 in BHD) from 18 participating centers.
In overall cohort, mean age was 65.4±13.5 years, 53% were males and dialytic vintage was in median 5.4 (IQR: 3.3-10.3) years. As result of matching, no difference emerged in terms of age, male gender, dialytic vintage and Barthel index in the two groups under study (Table 2)
As illustrated in Figure 2, in the group of patients treated by HFR, a better score of PCS was found (56±20) compared with BHD (48±23;P=0.048). In particular, in HFR we observed higher score in PF(61±26 versus 51±30, P=0.045) and in RP 66±47 versus 45±46, P=0.027), whereas in the remaining two items of PCS (BP nad GH) no significant difference was found in the two groups, respectively BP=63±25 and GH=40±17 in HFR and BP=58±31 (p=0.346) and GH 39±19 (p=0.676) in BHD.
As regard to the mental composite score of SF-36, no significant differences was found (57±21 in HFR vs 55±19 in BHD; P=0.698). In particular, in HFR we found VT=51±22, SF=64±25, RE=64±40 and MH=64±24. Similarly in BHD we registered the following scores: VT=48±21 (P=0.492 vs HFR), SF= 69±20 (P=0.290 vs HFR), RE: 60±43 (P=0.595 vs HFR) e MH: 60±22 (P=0.437 vs HFR).
In this study we report the findings of a cross-sectional analysis, comparing HR-QoL of ESRD patients treated by HFR as compared to those treated by BHD. Main result was that the patients treated by HFR showed higher score of physical component of SF-36 and particularly in the components of physical functioning and daily activities.
It is well recognized that HD per se associates with decline of functional status, independent of type of treatment (HD or HDF)  (full text). Novel finding of this study is that in ESRD patients matched by age, dialysis vintage and invalidity score, those treated by HFR reported a better ability to exert daily activities. This observation may be effect of the reduction of main uremic complications, such s as inflammation malnutrition and anemia, as previously reported in HFR-treated patients  (full text)  (full text)     ; however, this association remains matter of speculation because it was not assessed in this cross-sectional analysis.
Early studies have reported an higher score of PCS in HDF versus BHD patients   (full text) , but these findings were not confirmed in longitudinal studies. Indeed, the CONTRAST study, the longitudinal study evaluating HR-QoL after two years from initiation of dialysis, has not demonstrated an improvement of HR-QoL in HDF versus BHD  (full text).The cross-sectional design of our study does not allow to draw any causal conclusion on the observed findings. Therefore longitudinal studies designed ad hoc are needed to understand if these finding may turn into long term benefit on the HR-QoL as on the survival of these patients.
This cross-sectional analysis suggests that HFR is associated with higher score of SF-36 physical component, probably due to an improvement of oxidative stress and inflammatory status. This encouraging findings need to be validated by longitudinal studies in large cohorts.
 Evans RW, Manninen DL, Garrison LP Jr et al. The quality of life of patients with end-stage renal disease. The New England journal of medicine 1985 Feb 28;312(9):553-9
 Mittal SK, Ahern L, Flaster E et al. Self-assessed physical and mental function of haemodialysis patients. Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association – European Renal Association 2001 Jul;16(7):1387-94 (full text)
 Untas A, Thumma J, Rascle N et al. The associations of social support and other psychosocial factors with mortality and quality of life in the dialysis outcomes and practice patterns study. Clinical journal of the American Society of Nephrology : CJASN 2011 Jan;6(1):142-52 (full text)
 Kalantar-Zadeh K, Kopple JD, Block G et al. Association among SF36 quality of life measures and nutrition, hospitalization, and mortality in hemodialysis. Journal of the American Society of Nephrology : JASN 2001 Dec;12(12):2797-806 (full text)
 DeOreo PB Hemodialysis patient-assessed functional health status predicts continued survival, hospitalization, and dialysis-attendance compliance. American journal of kidney diseases : the official journal of the National Kidney Foundation 1997 Aug;30(2):204-12
 Kurella Tamura M, Covinsky KE, Chertow GM et al. Functional status of elderly adults before and after initiation of dialysis. The New England journal of medicine 2009 Oct 15;361(16):1539-47 (full text)
 Inouye SK, Peduzzi PN, Robison JT et al. Importance of functional measures in predicting mortality among older hospitalized patients. JAMA 1998 Apr 15;279(15):1187-93
 Cook WL, Jassal SV Functional dependencies among the elderly on hemodialysis. Kidney international 2008 Jun;73(11):1289-95 (full text)
 Moreno F, López Gomez JM, Sanz-Guajardo D et al. Quality of life in dialysis patients. A spanish multicentre study. Spanish Cooperative Renal Patients Quality of Life Study Group. Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association – European Renal Association 1996;11 Suppl 2:125-9
 Ward RA, Schmidt B, Hullin J et al. A comparison of on-line hemodiafiltration and high-flux hemodialysis: a prospective clinical study. Journal of the American Society of Nephrology : JASN 2000 Dec;11(12):2344-50 (full text)
 Lin CL, Huang CC, Chang CT et al. Clinical improvement by increased frequency of on-line hemodialfiltration. Renal failure 2001 Mar;23(2):193-206
 Canaud B, Bragg-Gresham JL, Marshall MR et al. Mortality risk for patients receiving hemodiafiltration versus hemodialysis: European results from the DOPPS. Kidney international 2006 Jun;69(11):2087-93 (full text)
 Schiffl H Prospective randomized cross-over long-term comparison of online haemodiafiltration and ultrapure high-flux haemodialysis. European journal of medical research 2007 Jan 31;12(1):26-33
 Mazairac AH, de Wit GA, Grooteman MP et al. Effect of hemodiafiltration on quality of life over time. Clinical journal of the American Society of Nephrology : CJASN 2013 Jan;8(1):82-9 (full text)
 Panichi V, Manca-Rizza G, Paoletti S et al. Effects on inflammatory and nutritional markers of haemodiafiltration with online regeneration of ultrafiltrate (HFR) vs online haemodiafiltration: a cross-over randomized multicentre trial. Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association – European Renal Association 2006 Mar;21(3):756-62 (full text)
 Calò LA, Naso A, Carraro G et al. Effect of haemodiafiltration with online regeneration of ultrafiltrate on oxidative stress in dialysis patients. Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association – European Renal Association 2007 May;22(5):1413-9 (full text)
 Borrelli S, Minutolo R, De Nicola L et al. Intradialytic changes of plasma amino acid levels: effect of hemodiafiltration with endogenous reinfusion versus acetate-free biofiltration. Blood purification 2010;30(3):166-71
 Borrelli S, Minutolo R, De Nicola L et al. Effect of hemodiafiltration with endogenous reinfusion on overt idiopathic chronic inflammation in maintenance hemodialysis patients: a multicenter longitudinal study. Hemodialysis international. International Symposium on Home Hemodialysis 2014 Oct;18(4):758-66
 Borrelli S, De Simone W, Zito B et al. [Hemodiafiltration with endogenous reinfusion in chronic inflammation: a possible therapeutic alternative?]. Giornale italiano di nefrologia : organo ufficiale della Societa italiana di nefrologia 2014 Jan-Feb;31(1)
 Bolasco PG, Ghezzi PM, Serra A et al. Hemodiafiltration with endogenous reinfusion with and without acetate-free dialysis solutions: effect on ESA requirement. Blood purification 2011;31(4):235-42
 Nacca R, Fini R, Vezza E et al. [HFR-AEQUILIBRIUM and intradialytic cardiovascular stability: results of the first multicenter study in Lazio]. Giornale italiano di nefrologia : organo ufficiale della Societa italiana di nefrologia 2013 Sep-Oct;30(5)