|Year : 2018 | Volume
| Issue : 1 | Page : 107-113
|Comparison of survival between dialysis patients with incident high-flux hemodialysis versus on-line hemodiafiltration: A single center experience in Saudi Arabia
Mohamed Said Abdelsalam1, Mohamed Rashwan2, Mohamed Mahdi Althaf2, Osman I Alfurayh2, Lutfi Alkorbi2, Ihab A Ibrahim3
1 Department of Medicine, Section of Nephrology, King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia; Department of Internal Medicine, Nephrology Unit, Faculty of Medicine, Alexandria University, Alexandria, Egypt
2 Department of Medicine, Section of Nephrology, King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia
3 Department of Kidney and Pancreas Transplantation, King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia; Division of Nephrology, Department of Internal Medicine, Cairo University School of Medicine, Cairo, Egypt
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|Date of Web Publication||15-Feb-2018|
| Abstract|| |
Conventional hemodialysis (HD) is the most common treatment modality used for renal replacement therapy. The concept of HD is based on the diffusion of solutes across a semipermeable membrane. Hemofiltration (HF) is based on convective transport of solutes; hemodiafiltration (HDF) is based on combined convective and diffusive therapies. Data about survival benefit of on-line HDF (OL-HDF) over high-flux HD (HF-HD) is conflicting. We conducted this study to investigate if there is a survival difference between the two treatment modalities. This study is a retrospective, single-center study in which 78 patients were screened; 18 were excluded and 60 patients were analyzed. The study patients were aged 47.5 ± 20.7 years, 33 patients (55%) were on HF-HD, and 27 patients (45%) were on OL-HDF. A total of 24 patients (40%) of both groups were diabetic and, the mean duration on dialysis was 43.5 ±21.3 months in the HF-HD group and 41.2 ± 22.0 months in the OL-HDF group. The mean substitution volume for OL-HDF was 22.3 ± 2.5 L. Survival was 73% [95%, confidence interval (CI) 60–84] in the HF-HD group and 65% (95%, CI 54–75) in the OL-HDF group by the end of the study period. The unadjusted hazard ratio (HR) with 95% CI comparing HF-HD to high-volume postdilution OL-HDF was 0.78 (0.10–5.6; P = 0.810). Kaplan–Meier analysis for patient survival over five years showed no significant difference between the two modalities. Prospective controlled trials with a larger number of patients will be needed to assess the long-term clinical outcome of postdilution OL-HDF over HF-HD.
|How to cite this article:|
Abdelsalam MS, Rashwan M, Althaf MM, Alfurayh OI, Alkorbi L, Ibrahim IA. Comparison of survival between dialysis patients with incident high-flux hemodialysis versus on-line hemodiafiltration: A single center experience in Saudi Arabia. Saudi J Kidney Dis Transpl 2018;29:107-13
|How to cite this URL:|
Abdelsalam MS, Rashwan M, Althaf MM, Alfurayh OI, Alkorbi L, Ibrahim IA. Comparison of survival between dialysis patients with incident high-flux hemodialysis versus on-line hemodiafiltration: A single center experience in Saudi Arabia. Saudi J Kidney Dis Transpl [serial online] 2018 [cited 2019 Nov 13];29:107-13. Available from: http://www.sjkdt.org/text.asp?2018/29/1/107/225191
| Introduction|| |
Hemodialysis (HD) has been used to treat patients with established end-stage renal disease (ESRD) since the 1950s. Conventional HD is the most common treatment modality used for renal replacement therapy. The concept of HD is based on diffusion of solutes across a semipermeable membrane and is effective in removing small solutes; however, it is ineffective in removal of larger solutes. High-flux dialyzers remove larger molecular weight uremic toxins. Hemofiltration is based on convective transport of solutes through the infusion of a large volume of ultrapure fluid to the patient (substitution volume) either pre-dialyzer or postdialyzer, associated with convection volume which is the sum of intradialytic weight loss in liters and substitution volume per dialysis session. Hemodiafiltration (HDF) is based on combined convective and diffusive therapies. Several studies have suggested that on-line HDF (OL-HDF) may improve clinical outcomes.,,
A prospective, observational study on 757 dialysis patients with a 30-month follow-up, the (RISCAVID study) showed the enhanced cumulative survival of patients receiving HDF in comparison to HD. Vilar et al reported in another retrospective analysis a survival benefit for HDF. Ok et al, in the Turkish study, which was an open-label, prospective, multicenter, randomized trial, showed that the composite of all-cause mortality and nonfatal cardiovascular event rate was not different in the OL-HDF and in the high-flux HD groups while in a post hoc analysis, OL-HDF treatment with substitution volumes over 17.4 L was associated with better cardiovascular and overall survival. On the other side, two prospective and randomized studies failed to demonstrate any survival benefit of OL-HDF over the high-flux HD modality.,
In the year 2011, there were over 12000 patients with ESRD on HD in Saudi Arabia with a steady increase of around 5%–7%/year according to the Saudi Center for Organ Transplantation (SCOT) data (www.scot.org). Majority of these patients are in their most socially productive years in the age category between 26 and 65 years in contrast to the growing trend of octogenarians initiating HD with ESRD in the United States. The King Faisal Specialist Hospital and Research Center (KFSHRC) is the only dialysis center in Saudi Arabia that provides OL-HDF modality for a large number of patients. Since data about survival advantage of OL-HDF over HD is conflicting,,,,,, we conducted this study to investigate if there is any difference in survival between the two treatment modalities.
| Materials and Methods|| |
A total of 78 patients were screened of whom, 18 patients were excluded from the study. Thus, 60 patients with established ESRD, initiated on conventional HD were either continued on HD or switched to postdilution OL-HDF within three months of initiation in the period from January 2010 to December 2014, were included in this study. Before 2010, all dialysis patients were maintained on HF-HD. Based on available data that OL-HDF may improve clinical outcomes, there was a gradual trend in our unit to shift patients (especially those with intradialytic hemodynamic instability, and those with larger body surface area) from HF-HD to OL-HDF.
The inclusion criteria for the study were as follows:
- Age equal to or >18 years
- ESRD defined as estimated glomerular filtration rate <10 mL/min
- Patients maintained on HF-HD, or OL-HDF three times per week.
The exclusion criteria were as follows:
- Patients, who did not complete a minimum of 24 months follow-up period for any reason; for example, underwent renal transplantation, transfer to another dialysis center, or death
- Presence of life-threatening comorbid conditions, namely advanced cardiac, pulmonary hepatic failure, or active malignancy
- Insufficient vascular access (blood flow rate lower than 300 mL/min)
- Pregnancy during the study.
This was a retrospective cohort study comparing survival of patients with the main predictor being dialysis modality, namely postdilution OL-HDF versus HF-HD in the renal dialysis unit of the KFSHRC, Riyadh, Saudi Arabia. Other predictors assessed were age, gender, the presence of hypertension, the presence of diabetes mellitus and Charlson comorbidity index (CCI). The primary end-point was all-cause mortality evaluated during a minimum of 24 months follow-up period since initiation of dialysis. The mean follow-up reached a maximum observation period of 60 months. During the study period, patients were censored by loss to follow-up, renal transplantation or transfer to another dialysis center. The study design and waiver of informed consent for data collection was approved by the KFSHRC, project number: 2131077.
All patients were initially started on HD modality; 33 patients continued on HF-HD while 27 patients were switched to OL-HDF. Both treatment modalities were carried out on Fresenius Medical Care (FMC) 5008 dialysis machines. Dialyzers used were FMC Helixone high-flux dialyzers of the FX-class®, made of polypropylene. OL-HDF was performed postdilution in the auto-substitution mode. Dialysate and substitution fluid were ultrapure (defined as <0.1 colony-forming units/mm, and <0.03 endotoxin units/mm) and generated in-house. The composition of the dialysate was same in the two groups as was the reinfusate in OL-HDF. Mineral components were sodium ranging from 135–140 mmol/L, potassium 1.0–3.0 mmol/L, calcium 1.25–1.5 mmol/L, magnesium 0.5 mmol/L, chloride 106–109 mmol/L, bicarbonate 30–38 mmol/L and glucose 1.1 mmo/L. The target hemoglobin was from 90–110 g/L. The average dialysis time was 240 minutes for each session, three times per week for both groups, and the prescribed Kt/v was 1.4 or greater.
| Statistical Analysis|| |
Kaplan–Meier analysis was used to assess patient survival among the two groups. Statistical significance between the plotted graphs was analyzed using Log-Rank test. Cox proportional hazards model was applied to assess covariates. The covariates were adjusted for age at dialysis initiation, gender, the presence of hypertension, the presence of diabetes mellitus and CCI. Independent-samples t-test was used to for comparison of the means of both groups. Hazard ratios (HRs) and the corresponding 95% confidence intervals (CI) are reported. All data were analyzed using Statistical Package for Social Sciences (SPSS) Version 17.0 (SPSS Inc., Chicago, IL, USA).
| Results|| |
A total of sixty patients met the inclusion criteria; 33 of them are female. There was no difference in baseline characteristics between patients in the two treatment groups [Table 1]. The mean age of all patients in the study was 47.5 ± 20.7 years. About 83% of patients had a history of hypertension while 40% were diabetic. 33 patients (55%) were on HF-HD while the remaining 27 (45%) were on OL-HDF. The mean duration on dialysis was 43.5 ± 21.3 months in the HF-HD group and 41.2 ± 22 months in the OL-HDF group. Regarding the vascular access, 38 patients had an arteriovenous fistula, 19 patients in each group; 12 patients had arteriovenous graft, eight in HF-HD, and four patients in the OL-HDF group; 10 patients had tunneled catheter, six in HF-HD and four in the OL-HDF group. The follow-up period was similar in the two groups. No difference was seen in mean serum albumin levels between the two groups at the end of the study [Table 2]. CCI was calculated for all patients; in the HF-HD group, the CCI score was 5.1 ± 3.6, and in the OL-HDF group, it was 5.07± 3.5 (P = 0.960) suggesting that there was no statistically significant difference in the degree of comorbidities between the two groups. The mean equilibrated Kt/v was higher in the OL-HDF group (1.89 ± 0.27) with statistical significance (P =0.002). All patients on OL-HDF had mean substitution volume of 22.3 ± 2.5 L. There were 15 deaths (25%); 10 (66%) were cardiovascular-related and five (33%) infection-related, with 5 years survival rate of 73% (95% CI 60–84) in the HF-HD group and 65% (95% CI 54–75) in the OL-HDF group by the end of the study. Kaplan–Meier analysis showed that there was no difference in survival rate between the two treatment modalities during the follow-up period. However, at the end of 48-month follow-up, there was better survival for patients on OL-HDF compared with HF-HD, but it was statistically insignificant [Figure 1], (P-value of 0.776 analyzed by Log-Rank test). The mortality risks adjusted for the covariates considered at the end of follow-up are shown in [Table 3]. Unadjusted HR with 95% CI comparing HF-HD to high-volume OL-HDF was 0.78 (0.10–5.6) (P = 0.810) which suggests lower mortality risk in HF-HD compared to OL-HDF, but it was statistically insignificant even after adjustment for covariates (gender CCI, diabetes mellitus, and hypertension; [Table 3]). Age at dialysis initiation was the only covariate that had significant HR for death regardless of dialysis modality, 1.05 (1.02–1.09) per year (P = 0.001).
|Table 1: Baseline characteristics for both groups based on treatment modalities.|
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|Figure 2: Kaplan-Meier analysis of patient survival time stratified by dialysis modality.|
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| Discussion|| |
The aim of this retrospective observational study was to investigate if there is a survival benefit for OL-HDF over HF-HD in a group of dialysis patients at the KFSHRC, Saudi Arabia. Several previous trials had been conducted to study how to reduce mortality in dialysis patients.
Locatelli et al randomly assigned incident patients to low-flux and high-flux (HD); they reported survival benefit only for patients with diabetes and those with hypoalbuminemia. Eknoyan et al reported in the hemodialysis (HEMO) study that there was no survival advantage, reduction in morbidity or maintenance of serum albumin levels using high-flux dialyzers and higher doses of dialysis over low-flux dialyzers and lower doses of dialysis. However, Cheung et al in a sub-group analysis revealed a reduction in all-cause mortality for patients using high-flux dialyzers with >3.7 years dialysis vintage.
In the current study, all patients on OL-HDF had high convection volume (>17 L); it has been shown by Canaud et al in the Dialysis Outcomes and Practice Patterns Study (DOPPS) that a higher substitution volume in OL-HDF was associated with 35% reduction in mortality over low-flux HD. In addition, there was better survival among HDF over combined group of high-flux (29%) and low-flux (71%) HD.
Our results showed that there is no impact of dialysis modality on serum albumin level-up to 60 months of follow-up in both groups, which might suggest that there is no nutritional benefit of HDF over high-flux HD. Contrary to our results, Velasco reported that HDF can be associated with improved nutritional state and favorable outcomes in inner-city British population.
Similar to our results, Schiffl reported in a small, single-center, crossover, randomized trial, no difference in mortality between patients on OL-HDF and high-flux HD. Furthermore, Grooteman et al in the Dutch Convective Transport Study, randomized 714 patients to low-flux HD or OL-HDF; at the end of the study (3 years) there was no mortality benefit for patients on OL-HDF. However, sub-group analysis suggested a benefit among patients on OL-HDF treated with over 21.95 L convective volume. Recently, Ok et al in the Turkish HDF study compared high-flux HD to OL-HDF in terms of all-cause mortality and nonfatal cardiovascular outcomes (mean follow-up of 22.7 ± 10.9 months); no difference was found between the two groups. However, the on-treatment analysis revealed that patients with an ultrafiltration volume >17.4 L had a decreased risk for all-cause mortality.
Contrary to our results, Vilar et al showed lower HR for death in the OL-HDF group compared with the HF-HD group in an epidemiological cohort study from the Balkan states. Furthermore, Imamovic et al compared incident patient survival of three modalities: HF-HD, low volume OL-HDF and high volume OL-HDF and they reported that only highvolume OL-HDF (substitution volume >20.4 L) was associated with improved survival compared to HF-HD. Finally, the Spanish ESHOL study,, compared high-flux HD (including 6.3% low-flux HD) to OL-HDF. Those assigned to OL-HDF had a 30% lower risk of all-cause mortality, a 33% lower risk of cardiovascular mortality and a 55% lower risk of infection-related mortality.
The study is limited by its retrospective deign, the potential for selection bias, and a small number of patients.
| Conclusion|| |
The results of this study showed that there is no significant difference between the two treatment modalities, HF-HD, and OL-HDF, in improving mortality. Future randomized clinical trials including larger number of patients studying the effect of dialysis modality on outcomes are needed.
Conflict of interest: None declared.
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Dr. Mohamed Said Abdelsalam
Department of Medicine, Section of Nephrology, MBC #46, King Faisal Specialist Hospital and Research Center, P. O. Box 3354, Riyadh 11211, Saudi Arabia
[Figure 1], [Figure 2]
[Table 1], [Table 2], [Table 3]
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