**7. Systematic reviews and meta-analyses on HDF**

patients undergoing stepped pharmacological therapy had superior renal function compared with that in patients receiving UF. A similar amount of weight loss was noted in both groups of patients. In addition, UF was found to be associated with a higher rate of adverse events. For patients with CHF, UF is usually reserved for cases of renal failure or unresponsiveness to pharmacological therapy. To study the safety and effectiveness of UF in patients hospitalized with decompensated CHF, investigators conducted the relief for acutely fluidoverloaded patients with decompensated congestive heart failure (RAPID-CHF) trial. This study, the first randomized controlled trial to compare UF with medical therapy, comprised 40 subjects [61]. A single 8-h course of UF with peripherally inserted catheters, along with supportive care and treatment, was compared with supportive care only. Patients who received UF had a greater volume of fluid removal (median 4650 vs. 2838 mL, *p* = 0.001) and improved signs and symptoms of congestion. Treatment with UF was well tolerated by the patients and did not result in any major adverse effects such as hemodynamic and renal complications. Thus, as can be deduced from the study, early treatment with UF for patients with CHF is a feasible treatment option that is well tolerated and can result in significant weight

Another study supporting the findings of the RAPID-CHF trial was the ultrafiltration versus intravenous diuretics for patients hospitalized for acute decompensated heart failure (UN‐ LOAD) trial [62]. The purpose of this randomized controlled trial was to study the safety and effectiveness of early treatment with primary UF in patients with ADHF. The study comprised 200 subjects with two or more signs of hypervolemia. At 48 h after the onset of treatment, weight reduction (5.0 ± 3.1 vs. 3.1 ± 3.5 kg, *p* = 0.001) and net fluid loss (4.6 vs. 3.3 L. *p* = 0.001) were higher in patients who were receiving UF. Furthermore, compared with the patients who were receiving diuretic therapy, the UF group showed lower rates of rehospitalization (0.22 ± 0.54 vs. 0.46 ± 0.76) with fewer days of in-hospital stay (1.4 ± 4.2 days vs. 3.8 ± 8.5 days) and fewer unscheduled medical visits (21% vs. 44%) within 90 days of hospital discharge. Through‐ out the study, changes in serum creatinine levels were similar in both groups. Episodes of hypotension during the first 48 h after hospitalization were similar (4% vs. 3%) in both groups. Thus, the UNLOAD trial demonstrated that, in patients with ADHF, UF is a safe treatment choice that produces higher weight and fluid loss compared with treatment with intravenous diuretics. In addition, UF also reduces a 90-day resource utilization in patients with ADHF. UF may thus prove to be an effective alternative to high doses of diuretic therapy in patients

Another small study designed for patients with ADHF investigated the effects of UF and standard intravenous diuretic (furosemide) therapy on the GFR and renal plasma flow [63]. The study comprised 19 patients who were randomized to receive UF (*n* = 9) or intravenous diuretics (*n* = 10). After treatment, no significant difference was seen in the GFR, renal plasma flow, and filtration fraction in the two groups. The difference in the net 48-h fluid removal between the two groups was also found to be insignificant. However, urine output during the

The results of these randomized trials demonstrate that UF is associated with no major safety concerns, and compared with diuretics, it improves total fluid volume removal with decreased

first 48 h was significantly higher in the furosemide group than in the UF group.

with ADHF, particularly in the presence of renal insufficiency.

loss and fluid removal.

66 Advances in Hemodiafiltration

Recently, several meta-analyses have been performed to compare UF with diuretics for treating volume overload in patients with ADHF. The first meta-analysis comprised nine studies involving 613 patients [22]. The mean weight loss in patients receiving UF therapy was 1.78 kg (95% CI −2.65 to −0.91 kg, *p* < 0.001). This loss was more than for those treated with standard diuretic therapy. However, between the two groups, there was little difference in postintervention creatinine levels (mean change = −0.25 mg/dL, 95% CI −0.56 to 0.06 mg/dL, *p* = 0.112). In addition, the results showed that, compared with patients treated with standard diuretics, in those treated with UF, the risk of all-cause mortality persisted (pooled risk ratio = 1.00, 95% CI 0.64–1.56, *p* = 0.993).


**Figure 2.** Forest plot of: a) Changes in weight loss at 48 h post therapy, b) all-cause mortality, c) all-cause rehospitaliza‐ tion. Reprinted from Cheng et al. [21], copyright with permission from International Heart Journal.

The second meta-analysis comprised seven RCTs with a total of 569 participants who met the eligibility criteria [21]. This analysis demonstrated that after 48 h of treatment, significantly higher amounts of weight loss and fluid removal were observed in the UF group compared with the diuretic group. Serum creatinine levels and changes in creatinine were found to be similar. There was no difference in all-cause mortality and all-cause rehospitalizations. In addition to these results, the authors noted that there were only minor differences between the UF and control groups in the incidence of adverse events, such as infections, anemia, hemor‐ rhage, progressive HF, and other cardiac disorders (**Figure 2**).
