Expanded Hemodialysis Versus Online Hemodiafiltration
Condition: Dialysis Related Complication; Dialysis Hypotension; Hemodialysis-Induced Symptom
MeSH terms: Hypotension
Study type: Interventional

Summary: 
      Conventional hemodialysis (HD) is essential for the treatment of end-stage renal disease
      (ESRD) patients, by reducing serum concentration of uremic toxins and correcting fluid
      overload.

      Nevertheless, HD removes almost exclusively low-range uremic toxins. Therefore, medium-range
      molecules, such as beta-2-microglobulin might accumulate in tissues, leading to many clinical
      complications, such as neuropathies, tendinopathies, anemia, bone mineral disease and reduced
      growth in children.

      Convective methods might reduce incidence of these complications, by removing molecules of
      medium-range molecular weight. Online hemodiafiltration (olHDF) is the most extensively used
      method in this regard. Nevertheless, there are some barriers to the wider introduction of
      this method in clinical practice, since specific machines are needed for this procedure, the
      costs with dialysis lines are higher and water consumption increases. More recently, the
      development of new membranes for hemodialysis allowed removal of medium- and high-range
      uremic toxins, with albumin retention. Thus, they allow removal of a broad range of uremic
      toxins, without changing dialysis machine or increasing water consumption. Such therapy is
      known as expanded hemodialysis (HDx).

      The aim of this present study is to compare the extraction of middle-size molecules, the
      hemodynamic behavior, fluid and nutritional status of patients submitted to olHDF or HDx, in
      a crossover study.
    

Detailed description: 
      Hypothesis

      Our hypothesis is that HDx is noninferior to olHDF in the following parameters:

        -  Hemodynamic stability

        -  Nutritional and fluid status

        -  Removal of beta-2 microglobulin

      Objectives To evaluate each patient, through a prospective, randomized and cross-over study,
      the intradialytic hemodynamic behavior, fluid and nutritional status assessed by electrical
      bioimpedance and B2M removal in two dialytic modalities: HDFol versus HDx.

      Concise methods

        1. Clinical and laboratorial data Clinical data will be collected from the institution's
           chart, recorded and filled with all necessary precautions to keep confidentiality of
           patient's information. They are: baseline renal disease, age, history of smoking,
           sedentary lifestyle, presence of comorbidities such as hypertension and diabetes
           mellitus, family history of cardiovascular disease, history of coronary and
           cerebrovascular disease and medications.

           Laboratory tests used to determine the biochemical, hematological and bone mineral
           profile characteristics will be obtained from routinely collected exams. Such exams are
           processed by the Central Laboratory of Hospital das Clínicas / FMUSP.

        2. Dialysis All dialysis procedures will be performed by the Dialog+ Admea™ machine (BBraun
           Melsungen AG, Germany).

           The olHDF will be prescribed as follows: blood flow 350 - 400 ml/min, dialysate flow 800
           ml/min, post-dilution flow (90-100 ml/min), with high-flux Xevonta™ (BBraun Melsungen
           AG, Germany) or CAHP/DICE™ (Baxter Healthcare Corporation, Germany) dialyzers, with
           surface area of 1.7-2.4 m². The duration of each session will be from 3,5h to 4h,
           depending on current dialysis prescription. Total substitution volume will be higher
           than 20 L per session.

           HDx will follow the same prescription of olHDF, regarding blood and dialysate flows and
           dialysis duration. There will be no substitution volume. Theranova™ dialyzers (Baxter
           Healthcare Corporation, Germany) will be used for each session.

           Before initiating protocol and during the washout period, patients will be submitted to
           high-flux HD, which is the standard treatment in our service.

        3. Hemodynamic monitoring Cardiac output index (CI), stroke volume (SV - integrated mean of
           the flow waveform between the current upstroke and the dichotic notch), peripheral
           arterial resistance (PAR - ratio of mean arterial pressure to stroke volume multiplied
           by heart rate) and blood pressure (BP) will be accessed by finger beat to-beat monitor
           Finometer™ (Finapress Medical Systems BV, Arnhem, The Netherlands), within 15 minutes
           after starting olHDF or HDx sessions (predialysis) and again, 15 minutes before its end
           (post-dialysis).

        4. Bioelectrical impedance Segmental tetrapolar bioelectrical impedance (BIS) will be
           performed in all patients while recumbent, before starting study protocol and before
           each phase of the study (HDx or olHDF), by the multifrequency InBody™ S10 (Biospace Co.,
           Ltd., Korea) device. It allows assessment of the following parameters regarding body
           fluids: total body water, total extracellular body water, lower limbs total water
           content, lower limbs extracellular water content. Additionally, α-angle, which is a
           marker of cellular integrity and nutritional status, will be noted.

        5. Blood and Effluent samples Blood samples will be collected pre-session, mid-session and
           post-dialysis sessions, both in the first and last dialysis sessions of each of the
           periods studied (HDFol or HDx). Pre-session blood samples will be collected immediately
           after arteriovenous fistula puncture and the middle and post-session samples will be
           collected from the arterial line, 2 minutes after reduction of blood flow to 50 ml/min
           and suspension of dialysate flow and/ or replacement.

      In addition, partial and homogeneous collection of the effluent will be performed by a
      drainage hose, with an infusion pump operating continuously at a rate of 1l/h. The whole
      effluent of dialysis session will be collected.
    

Intervention name(s): Expanded Hemodialysis; Online Hemodiafiltration
Intervention type(s): Device; Device
Intervention description(s): Intervention: Conversion from conventional HD to expanded hemodialysis por 1 month.
High cutoff with high retention onset dialyzers allow clearance of middle molecules, without reducing significantly serum concentration of albumin. It allows higher convective clearance in comparison to conventional hemodialysis, but it is unknown if such clearance is similar to online hemodiafiltration. Therefore, the aim of the present intervention is to compare this dialyzer with online hemodiafiltration; Intervention: Conversion from conventional HD to online Hemodiafiltration por 1 month.
Online hemodiafiltration has been associated with lower incidence of intradialytic hypotension in comparison to conventional hemodialysis.
Other intervention name(s): Theranova Dialyzer
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: Single (Investigator)
Primary purpose: Treatment
Keywords: Hemodialysis; Hemodiafiltration; fluid status; hemodynamics