Hemofiltration and Hemodiafiltration Reduce Intradialytic Hypotension in ESRD

Symptomatic intradialytic hypotension is a common complication of hemodialysis (HD). The application of convective therapies to the outpatient setting may improve outcomes, including intradialytic hypotension. In this multicenter, open-label, randomized controlled study, we randomly assigned 146 long-term dialysis patients to HD (n = 70), online predilution hemofiltration (HF; n = 36), or online predilution hemodiafiltration (HDF; n = 40). The primary end point was the frequency of intradialytic symptomatic hypotension (ISH). Compared with the run-in period, the frequency of sessions with ISH during the evaluation period increased for HD (7.1 to 7.9%) and decreased for both HF (9.8 to 8.0%) and HDF (10.6 to 5.2%) (P < 0.001). Mean predialysis systolic BP increased by 4.2 mmHg among those who were assigned to HDF compared with decreases of 0.6 and 1.8 mmHg among those who were assigned to HD and HF, respectively (P = 0.038). Multivariate logistic regression demonstrated significant risk reductions in ISH for both HF (odds ratio 0.69; 95% confidence interval 0.51 to 0.92) and HDF (odds ratio 0.46, 95% confidence interval 0.33 to 0.63). There was a trend toward higher dropout for those who were assigned to HF (P = 0.107). In conclusion, compared with conventional HD, convective therapies (HDF and HF) reduce ISH in long-term dialysis patients.Hemodialysis (HD) is not an effective treatment for long-term dialysis patients with stage 5 chronic kidney disease (CKD), and their comorbidities, including intradialytic symptomatic hypotension (ISH), are persistently very high,¹ possibly contributing to their high mortality rate.² Convective treatments (CTs)—increasing “middle molecule” removal and removing fluids by more physiologic convection—have been suggested for improving dialysis patient outcomes including the reduction of ISH.^3,4 Observational studies have consistently suggested that high-flux treatments for long-term dialysis patients with stage 5 CKD are associated with reduced morbidity and mortality.^5–8 The Hemodialysis (HEMO) Study,⁹ a landmark randomized, controlled trial designed to test the effect of membrane flux and dialysis dosage on mortality, showed that high-flux HD is associated with a nonsignificantly lower relative mortality risk of 8%, although a secondary analysis suggested a significant advantage of high-flux membranes in patient subgroups. More recently, the Membrane Permeability Outcome (MPO) study¹⁰ found that survival could be significantly improved by using high-flux as compared with low-flux membranes in high-risk patients identified by serum albumin of ≤4 g/dl as well as in patients with diabetes in a post hoc analysis. By extrapolating the experimental results of these multicenter studies, it can be hypothesized that the benefits could be even greater by further increasing convection in treating long-term dialysis patients with stage 5 CKD. The number of randomized, prospective trials that have compared CTs with standard HD is still very low, and no conclusive data are available concerning the effect of CTs in their various forms on morbidity and survival in long-term dialysis patients with stage 5 CKD.It is very interesting to observe that the concept of dialysis adequacy has now widened to include not only urea kinetics¹¹ but also middle and high molecule removal^12,13 and biocompatibility.¹⁴ Locatelli et al.,¹⁵ in a controlled randomized multicenter study involving 380 patients, compared four treatment dialysis modalities: Low-flux Cuprophan HD, low-flux polysulfone HD, high-flux polysulfone HD, and high-flux polysulfone hemodiafiltration (HDF). Although a reduction in predialysis β-2 microglobulin levels in high-flux HD and HDF compared with low-flux HD was found, no differences were reported in treatment tolerance; however, the number of symptomatic treatments were far fewer than expected, thus reducing the statistical power of the study. Canaud et al.¹⁶ analyzed the data from Dialysis Outcomes and Practice Patterns Study (DOPPS) and reported that survival was associated with the amount of convection.Two prospective clinical trials performed by the Sardinian Collaborative Group^3,4 compared the clinical effects of (bicarbonate) high-flux HD and predilution online (bicarbonate) HF in clinically stable patients, with different³ and similar⁴ equilibrated Kt/V (eKt/V) and treatment times. Polyamide membranes, ultrapure fluid with similar electrolyte composition, and the same dialysis machine were used in both studies. These studies showed fewer symptoms, including hypotension in HF as compared with HD also in clinically stable small-sized patient groups. A third prospective collaborative study performed by the same collaborative group comparing HF with HDF¹⁷ in a group of 39 stable patients, after a run-in treatment period of 6 months on low-flux HD, found that HF was more effective in reducing the frequency of hypotension. On the basis of the results of these Sardinian studies, we planned a prospective, multicenter randomized study to compare low-flux HD with online predilution HF and/or HDF to evaluate the sessions with ISH of two different types and dosages of convection in comparison with HD, as routinely performed by investigators in day-to-day clinical practice.