Can Dialysis Modality Influence Quality of Life in Chronic Hemodialysis Patients? Low-Flux Hemodialysis versus High-Flux Hemodiafiltration: A Cross-Over Study

Abstract

Background: Hemodiafiltration with online preparation of the substitution [online high-flux hemodiafiltration (OHDF)] and hemodiafiltration with prepared bags of substitution (HDF) are important, recently widely used renal replacement therapies in patients with end-stage renal disease. However, there is little information on the comparative impacts of these modalities versus conventional low-flux hemodialysis (HD) on the quality of life (QoL) of HD patients. This study investigates the effect of dialysis modality on QoL in chronic HD patients. Methods: In this prospective, randomized, cross-over, open label study, 24 patients were enrolled. Their age were 62 ± 13.34 years (mean ± SD), with the duration of dialysis of 31 ± 23.28 months (mean ± SD). Five of the patients were women. QoL was measured by the Short-Form Health Survey with 36 questions (SF-36) and subscale scores were calculated. Each patient received HD, OHDF, and HDF for 3 months, with the dialysis modality subsequently being altered. They completed the questionnaire of QoL at the end of each period. Results: There were statistical significant differences in QoL for the total SF-36 [36.1 (26.7–45.7) and 40.7 (30.2–62.8)], for classic low-flux HD and high-flux hemodiafiltration, for bodily pain [45 (26.9–66.9) and 55 (35.6–87.5)], and for role limitations due to emotional functioning [0 (0–33.3) and 33.3 (0–100)], respectively. The scores did not differ significantly between the two types of hemodiafiltration. Conclusions: Our study indicates that QoL differs significantly among patients receiving low-flux HD and high-flux hemodiafiltration, on total SF-36, bodily pain, and role limitations due to emotional functioning. Convective modalities may offer better QoL than diffusive HD.

• hemodialysis
• hemodiafiltration
• online hemodiafiltration
• quality of life

INTRODUCTION

Several epidemiological studies performed in recent decades based on large databases suggest that convective treatments may be superior at reducing morbidity and mortality in dialysis patients. But despite the ongoing technical improvements in dialysis, the annual mortality rate of patients with end-stage renal disease (ESRD) with thrice-weekly regular hemodialysis (HD) remains high (10–22%).^1,2 Hemodiafiltration has the advantage of clearing middle- and large-sized substances by convection while simultaneously clearing small-sized substances by diffusion. Many studies have compared the effects of this modality on cardiovascular outcomes and mortality.³ Others try to correlate inflammation, oxidative stress, and endothelial dysfunction relative to HD. However, a few studies have focused on the QoL of these patients. The differences in health-related QoL among patients undergoing either classic HD or convective dialysis modalities remain controversial.

QoL is an important factor affecting the outcome of patients with end-stage renal failure. Chronic kidney disease and renal replacement therapies (RRTs) can cause significant changes in patients’ lives and can substantially reduce QoL compared with a general population.⁴ QoL can be worse in these patients than in patients with cancer⁵ and is worse in patients beginning HD therapy than in those receiving established long-term HD.⁶ HD can provoke negative influence on QoL, because these patients have to deal with the symptoms; follow a special diet program; and reconsider their personal, social, and professional objectives.⁷ All of these factors have led to an increasing interest in health-related QoL as an important measure in the evaluation of the various RRTs. Moreover, it has been proposed that QoL in patients on RRTs can predict their future morbidity and mortality.^8–10 The Short-Form Health Survey with 36 questions (SF-36) is a well-documented scoring system that has been widely used and validated as a QoL assessment tool for patients receiving dialysis. This instrument has been shown to be valid, sensitive to treatment changes, and accepted by ESRD patients.¹¹

The aim of this study was to compare the possible effects of diffusive and convective HD therapies on QoL among patients on maintenance HD.

PATIENTS AND METHODS

Protocol

In this prospective, randomized, cross-over, open label study, 24 patients were randomized into two groups in order to perform three dialysis modalities: low-flux HD; online high-flux hemodiafiltration (OHDF); and high-flux hemodiafiltration with prepared bags of substitution (HDF). Inclusion criteria were having a stable health condition, undergoing low-flux HD for at least 3 months, and age >18 years.

In order to facilitate comparisons, the patients were randomized into two groups and consecutively received all the three studied methods according to the following protocol: the first group of 12 patients (Group A) was transferred from HD to OHDF to HD to HDF, while a second group of 12 patients (Group B) was transferred from OHDF to HD to HDF to HD (Figure 1).

Figure 1.  Study design.

Each dialysis modality was applied for 3 months.

Patients

Twenty-four patients were randomized in this study with mean ages of 62 ± 13.34 years and the mean duration of dialysis was 31 ± 23.28 months. Five of the patients were women.

Demographic data (including gender and age) and clinical parameters were collected for all of the patients. Clinical information comprises the number of hypotensive episodes during dialysis sessions, erythropoietin (EPO) use, hemoglobin, serum levels of ferritin, albumin, high-sensitivity C-reactive protein (CRP), calcium, phosphorus, parathyroid hormone, and β₂ microglobulin. Blood samples were drawn just before the start of the second dialysis session of the week, after every trimester of the study, and just before the first dialysis session of the new modality. A second-generation Daugirdas formula was used to calculate Kt/V.¹²

The causes of chronic renal failure were diabetic nephropathy in two patients, chronic glomerulonephritis in five patients, hypertension in six patients, chronic pyelonephritis in four patients, and unknown in the remaining seven patients.

All of the patients enrolled in the study were anuric and had either a native arteriovenous fistula or a synthetic graft for their dialysis. They received 4-h dialysis treatments with bicarbonate-containing solutions, thrice weekly. The sodium, potassium, calcium, and bicarbonate concentrations of the dialysate were the same for each patient and remained unchanged throughout the study period. All of the patients were dialyzed with a polysulfone dialyzer membrane; blood flow rates ranged from 250 to 350 mL/min and the dialysate flow rate was set between 500 and 700 mL/min. The hemodiafiltration was postdilution, and the volume of substitution fluid was 3.75–5 L/h for OHDF and 10 L/session for HDF.

This prospective study was approved by the University Hospital Ethics Committee. A written informed consent was obtained from each patient.

SF-36 QoL Scoring System

QoL was assessed using the SF-36 adapted for the Greek population. This version has been found to be valid and reliable.¹³ Patients completed the SF-36 questionnaire [International Quality Of Life Assessment Project (IQOLA) SF-36v1 Standard, Greece (Greek)] after every trimester of the study, just before the first dialysis session of the new modality, following the instructions we provided.

The SF-36 short-form questionnaire was developed in the Medical Outcome Study¹⁴ in the United States, and it measures eight dimensions: (1) physical functioning (PF, 10 items), which describes the ability to cope with the physical needs of life, such as walking and flexibility; (2) role limitations due to physical functioning (RP, four items), which evaluate limitations of physical activities; (3) bodily pain (BP, two items) describes the amount of pain that the patient has experienced during the previous 4 weeks and its effects on the activities performed; (4) general health perceptions (GH, five items), which evaluate the patient’s self-perceived general health; (5) vitality (VT, four items), which evaluates pep, energy, and fatigue; (6) social functioning (SF, two items), which describes the time spent with family, friends, and social life during the previous 4 weeks; (7) role limitations due to emotional functioning (RE, three items), which prescribe the effects of emotional feelings on working and other activities; and (8) mental health (MH, five items), which evaluates the existence of feelings such as depression or anxiety. The questionnaire contains a final item to describe changes in the reported health. These eight scales can be summarized into two general scales: physical component scale (PCS) and mental component scale (MCS).¹⁵

Items in each scale are added together to form subscale scores, which are transformed to a scale from 0 to 100. Higher scores indicate better QoL.

Statistics

Demographic and clinical data are described as mean ± SD values for continuous variables. SF-36 scores as non-normally distributed variables were described with medians and interquartile ranges (IQRs). Differences in the other parameters and SF-36 scores between the groups were analyzed using independent samples Student’s t-test for normally distributed variables and Mann–Whitney test for non-normally distributed variables. Statistical analysis was performed using SPSS version 12.0 for Windows (SPSS Inc., Chicago, IL, USA).

A p-value of 0.05 or less was considered to indicate statistical significance.

RESULTS

The patients in the two groups did not differ in age, duration of HD, gender, or the primary cause of ESRD (Table 1). The laboratory data of the patients are listed in Tables 2 and 3. The only laboratory parameters that differed significantly between the modalities were the serum levels of phosphorus (6.01 mg/dL ± 1.27 for HD vs. 5.49 mg/dL ± 1.23 for OHDF and 5.36 mg/dL ± 1.11 for HDF) and β₂ microglobulin (47.36 mg/L ± 12.21 for HD vs. 32.66 mg/L ± 7.71 for OHDF and 31.08 mg/L ± 7.66 for HDF). The number of hypotensive episodes during sessions; the EPO use; the plasma levels of hemoglobin; and serum levels of ferritin, albumin, high-sensitivity CRP, calcium, and parathyroid hormone did not statistically significantly differ. The patients had better regulation of phosphorus levels and β₂ microglobulin due to their convective clearance.

Table 1.  Baseline demographic characteristics of patients.

Baseline demographic characteristics	Group A	Group B	p-Value
Age (years)	61.79 ± 13.94	62.14 ± 1.33	1.00
Duration of dialysis (months)	2.53 ± 1.71	3.67 ± 2.78	0.378
Gender M/F	10/2	9/3	0.615
Diabetes mellitus Y/N	0/12	1/11	0.307

Note: Bold p-values are considered to be statistically significant, p < 0.05.

Table 2.  Comparison of clinical data in patients receiving diffusive (HD) versus convective (OHDF + HDF) dialysis therapies.

Parameters	HD (n = 48)	OHDF + HDF (n = 48)	p-Value
Kt/V	1.42 ± 0.17	1.45 ± 0.16	0.33
Hypotension n/session	3.96 ± 4.68	4.02 ± 4.89	0.91
Hemoglobin (g/dL)	12.13 ± 0.82	12.19 ± 0.71	0.62
EPO (IU/week)	6659.7 ± 4054.3	6493.3 ± 4081.8	0.74
Ca (mg/dL)	9.29 ± 0.58	9.35 ± 0.52	0.48
P (mg/dL)	6.01 ± 1.27	5.42 ± 1.19	0.02
Ferritin (μg/L)	361.2 ± 264.56	408.4 ± 447.79	0.89
CRP (mg/dL)	0.86 ± 0.91	0.84 ± 0.94	0.83
Albumin (g/dL)	4.20 ± 0.28	4.20 ± 0.33	0.72
PTH (pg/mL)	297.88 ± 282.4	294.34 ± 280.69	0.99
β2 Microglobulin (mg/dL)	47.36 ± 12.21	31.87 ± 7.64	<0.01

Notes: Bold p-values are considered to be statistically significant, p < 0.05. CRP, C-reactive protein; PTH, parathyroid hormone.

Table 3.  Comparison of clinical data in patients receiving convective dialysis therapies, OHDF versus HDF.

Parameters	OHDF (n = 24)	HDF (n = 24)	p-Value
Kt/V	1.45 ± 0.16	1.45 ± 0.15	0.89
Hypotension n/session	5.21 ± 6.17	2.83 ± 2.81	0.43
Hemoglobin (g/dL)	12.36 ± 0.66	12.01 ± 0.74	0.13
EPO (IU/week)	6527.8 ± 4175.9	6458.9 ± 4075.1	0.97
Ca (mg/dL)	9.32 ± 0.59	9.37 ± 45	0.67
P (mg/dL)	5.49 ± 1.23	5.36 ± 1.11	0.75
Ferritin (μg/L)	444.9 ± 590.2	371.9 ± 242.1	0.59
CRP (mg/dL)	0.72 ± 0.74	0.96 ± 1.11	0.47
Albumin (g/dL)	4.23 ± 0.18	4.17 ± 0.27	0.67
PTH (pg/mL)	316.07 ± 299.66	273.61 ± 266.70	0.73
β2 Microglobulin (mg/dL)	32.66 ± 7.71	31.08 ± 7.66	0.635

Notes: Bold p-values are considered to be statistically significant, p < 0.05. CRP, C-reactive protein; PTH, parathyroid hormone.

We compared SF-36 scores among patients receiving different dialysis modalities. Of the 24 patients enrolled in this study, two did not complete the SF-36 questionnaires. The total SF-36 score differed significantly between HD and hemodiafiltration (OHDF and HDF): 36.1(26.7–45.7) versus 40.7(30.2–62.8), p = 0.029; for bodily pain: 45(26.9–66.9) versus 55(35.6–87.5), p = 0.025; and for role limitations due to emotional functioning: 0(0–33.3) versus 33.3(0–100), p = 0.019. However, there were no statistical differences between the two types of hemodiafiltration. These results are presented in Tables 4 and 5.

Table 4.  Comparison of QoL scores in patients receiving diffusive (HD) versus convective (OHDF + HDF) dialysis therapies.

SF-36	HD^a (n = 44)	HDF–OHDF^a (n = 44)	p-Value
SF-36 total	36.1 (26.7–45.7)	40.7 (30.2–62.8)	0.029
Physical functioning (PF) (10)	45 (21.3–55)	45 (25–65)	0.355
Role limitations—physical RP (4)	0 (0–25)	0 (0–43.7)	0.344
Bodily pain (BP) (2)	45 (26.9–66.9)	55 (35.6–87.5)	0.025
General health (5)	27.5 (25–43.75)	30 (25–55)	0.146
Emotional well-being (5)	52 (32–67)	56 (36–72)	0.320
Role limitations—emotional (3)	0 (0–33.3)	33.3 (0–100)	0.019
Social function (2)	50 (15.6–62.5)	50 (28.1–75)	0.116
Energy/fatigue (4)	40 (25–53.7)	42.5 (30–60)	0.147
SF-12 Physical Health Composite	31.6 (25.6–34.9)	34.8 (27.3–39.8)	0.048
SF-12 Mental Composite	39.5 (31.4–44.1)	41.9 (32.1–53.5)	0.087

Notes: Bold p-values are considered to be statistically significant, p < 0.05.

^aData are reported as median (IQR).

Table 5.  Comparison of QoL scores in patients receiving convective dialysis therapies, OHDF versus HDF.

SF-36	OHDF^a (n = 22)	HDF^a (n = 22)	p-Value
SF-36 total	36.6 (24.6–61.7)	43.2 (32.3–65.2)	0.573
Physical functioning (PF) (10)	45 (22.5–61.2)	47.5 (25–65)	0.742
Role limitations—physical RP (4)	0 (0–31.2)	0 (0–50)	0.924
Bodily pain (BP) (2)	50 (30.6–85)	60 (45–88.1)	0.442
General health (5)	30 (25–55)	32.5 (25–55)	0.953
Emotional well-being (5)	54 (32–72)	60 (36–72)	0.769
Role limitations—emotional (3)	33.3 (0–100)	33.3 (0–100)	0.663
Social function (2)	56.2 (25–78.1)	50 (34.4–78.1)	0.915
Energy/fatigue (4)	40 (25–56.2)	47.5 (33.7–61.2)	0.383
SF-12 Physical Health Composite	33.8 (26.8–38.7)	34.8 (29.9–40.6)	0.557
SF-12 Mental Composite	40.3 (31.6–53.8)	42.5 (32.7–53.9)	0.707

Notes: Bold p-values are considered to be statistically significant, p < 0.05.

^aData are reported as median (IQR).

DISCUSSION

This study compares QoL between patients undergoing different dialysis modalities: conventional low-flux HD, OHDF, and high-flux hemodiafiltration with prepared bags of substitution. A total of 24 patients were enrolled in this cross-over study with each patient receiving all the three HD methods in sequence, so that each patient can compare with himself/herself and with the other patients in order to facilitate comparisons. Low-flux HD can be considered as a treatment (washout phase).

The results of this prospective, randomized, cross-over study indicate a better QoL during hemodiafiltration rather than in diffusive HD. Although it is quite difficult to recognize the precise underlying cause of this beneficial feature, it might be influenced by the higher clearances of middle molecules, β₂ microglobulin, and phosphorus. Interestingly, numerous middle molecules seem to affect several pathophysiological pathways that may offer the basis for the different therapeutic outcomes among diffusive and convective dialysis modalities.¹⁶ There was neither any statistically significant difference in cardiovascular stability (similar number of hypotensive episodes) nor in patients’ anemia correction (hemoglobin levels were the same with the same dose of EPO) (Table 2). Possibly the short duration of each dialysis modality prevented the probability of finding changes. Equally, the longer duration of hemodiafiltration could more clearly reveal the improvements in QoL.

Hemodiafiltration is a newer dialysis method that fulfills the major requirements of dialysis and provides improved extracorporeal blood purification by combining efficient clearance of small solutes by diffusion (HD) with the convective removal of medium-sized and large-sized molecules (hemofiltration). Hemodiafiltration thus enlarges the spectrum of uremic toxins that are cleared. Online hemodiafiltration offers the capability of producing safe, pyrogene-free, and low-cost substitution using bicarbonate as a buffer, providing a practical and cost-effective way to perform the method.

QoL is an important factor that predicts morbidity and mortality.¹⁷ Many methods to assess QoL are reported in the literature, but the SF-36 is a relatively easy, self-reported, multidimensional, and generic instrument that has been widely used.¹⁸ SF-36 contains 36 items from the total of 149 items from the begging questionnaire developed in the Medical Outcome Study in the United States. The questionnaire SF-36 is a health-related QoL measure that was designed for self-administration by many populations, including dialysis patients.¹¹ The SF-36 has been translated into many languages (including Greek) according to the documented procedures of the IQOLA¹¹ working group and in compliance with the international guidelines for the translation of questionnaires.¹⁹ The Greek version of SF-36 has been found to be valid and reliable for HD patients.¹³

Many large studies have demonstrated that QoL is a consistent and powerful predictor of death and hospitalization in HD patients.²⁰ The Dialysis Outcomes and Practice Patterns Study showed that the PCS score of the SF-36 predicts mortality better than the serum albumin levels.²¹

A few studies have compared the effects of dialysis method on QoL. Ward et al.¹⁸ used the Kidney Disease Questionnaire (a validated tool for QoL assessment in renal patients) and it revealed no significant differences between HDF and HD in all dimensions. The hemodialysis study (HEMO) found no differences between patients treated with low-flux HD and high-flux HD,²² but when the dialysis dose was increased there was a slight improvement in QoL. Altieri²³ found that QoL differed among patients receiving HD and hemofiltration due to general improvement in physical well-being; this result was also found by Beerenhout et al.²⁴ Knezevic et al.²⁵ showed that patients on HDF have better QoL compared with patients on HD. Additionally, comparisons of HD with hemodiafiltration have produced conflicting results: three studies suggested an improvement in QoL^25–27 but another three studies found no such differences.^2,18,28

QoL measurements are based on a patient’s subjective sense of well-being and are commonly used as an important clinical measure for assessing the benefit of medical treatments for these patients.

The dialysis modality can influence patient’s lifestyle. In such patients, physical symptoms (e.g., fatigue and loss of energy) and limitations of social life are the main factors affecting QoL, probably due to the long duration of the sessions and the high burden of the comorbidity and complications of ESRD. Measuring the health-related QoL is becoming more important not only as an outcome measure in chronic disease but also as an adjustment factor in economic evaluations, especially given that current dialysis modalities are already among the most expensive therapies.²⁹

Conclusively, this study found statistically significant differences in QoL among patients receiving low-flux HD versus high-flux hemodiafiltration in terms of scores for the total SF-36, for bodily pain, and for role limitations due to emotional functioning. Since it is crucial to maximize the QoL in patients on maintenance HD, these results suggest that convective modalities may be more beneficial than diffusive HD in offering a better QoL. Prospective, large, long-term evaluation studies may confirm these findings.

Declaration of interest: The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper.