Expanded Hemodialysis Versus Online Hemodiafiltration

Hemodialysis-Induced Symptom Clinical Trial

Official title:

Expanded Hemodialysis Versus Online Hemodiafiltration: a Pilot Study on Intradialytic Hemodynamics and Fluid Status

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03274518
• Other study ID #: 16928
• Status: Completed
• Phase: N/A
• Start date: November 13, 2017
• Est. completion date: March 11, 2019

Study information

• Verified date: September 2019
• Source: University of Sao Paulo
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 16
• Est. completion date: March 11, 2019
• Est. primary completion date: October 18, 2018
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 65 Years

Eligibility

Inclusion Criteria:

• Adult patients who are on maintenance hemodialysis at Hospital das Clínicas and agree to participate in the study by signing the informed consent form.

Exclusion Criteria:

• Patients who cannot understand or who refuse to sign the informed consent form; Patients who are currently on daily hemodialysis or online hemodiafiltration.

Related Conditions & MeSH terms

• Dialysis Hypotension
• Dialysis Related Complication
• Hemodialysis-Induced Symptom
• Hypotension

Intervention

Device:
• Expanded Hemodialysis
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
• 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.

Locations

Country	Name	City	State
Brazil	Hospital das Clínicas	São Paulo

Sponsors (1)

Lead Sponsor	Collaborator
University of Sao Paulo

Country where clinical trial is conducted

Brazil, 

References & Publications (9)

Álvares VRC, Ramos CD, Pereira BJ, Pinto AL, Moysés RMA, Gualano B, Elias RM. Pneumatic Compression, But Not Exercise, Can Avoid Intradialytic Hypotension: A Randomized Trial. Am J Nephrol. 2017;45(5):409-416. doi: 10.1159/000471513. Epub 2017 Apr 14. — View Citation

Argilés A, Ficheux A, Thomas M, Bosc JY, Kerr PG, Lorho R, Flavier JL, Stec F, Adelé C, Leblanc M, Garred LJ, Canaud B, Mion H, Mion CM. Precise quantification of dialysis using continuous sampling of spent dialysate and total dialysate volume measurement — View Citation

Cheng YL, Shek CC, Wong AK, Wong FK, Chau KF, Li CS. A partial dialysate collection method. Int J Artif Organs. 1997 Jan;20(1):14-7. — View Citation

Cheng YL, Shek CC, Wong FK, Choi KS, Chau KF, Ing TS, Li CS. Determination of the solute removal index for urea by using a partial spent dialysate collection method. Am J Kidney Dis. 1998 Jun;31(6):986-90. Erratum in: Am J Kidney Dis 1998 Oct;32(4):704. — View Citation

Jimenez ZN, Silva BC, Reis LD, Castro MC, Ramos CD, Costa-Hong V, Bortolotto LA, Consolim-Colombo F, Dominguez WV, Oliveira IB, Moysés RM, Elias RM. High Dialysate Calcium Concentration May Cause More Sympathetic Stimulus During Hemodialysis. Kidney Blood — View Citation

Karohl C, de Paiva Paschoal J, de Castro MC, Elias RM, Abensur H, Romão JE Jr, Passlick-Deetjen J, Jorgetti V, Moysés RM. Effects of bone remodelling on calcium mass transfer during haemodialysis. Nephrol Dial Transplant. 2010 Apr;25(4):1244-51. doi: 10.1 — View Citation

Oliveira CM, Kubrusly M, Mota RS, Silva CA, Choukroun G, Oliveira VN. The phase angle and mass body cell as markers of nutritional status in hemodialysis patients. J Ren Nutr. 2010 Sep;20(5):314-20. doi: 10.1053/j.jrn.2010.01.008. Epub 2010 Mar 19. — View Citation

Silva BC, Freitas GR, Silva VB, Abensur H, Luders C, Pereira BJ, de Oliveira RB, Castro MC, Moysés RM, Elias RM. Hemodynamic behavior during hemodialysis: effects of dialysate concentrations of bicarbonate and potassium. Kidney Blood Press Res. 2014;39(5) — View Citation

Silva BC, Moysés RM, Silva VB, Freitas GR, Elias RM. Parathyroidectomized patients have impaired capacity of peripheral vascular constriction during hemodialysis. Hemodial Int. 2016 Jan;20(1):50-5. doi: 10.1111/hdi.12309. Epub 2015 Apr 28. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Fluid Status	noninvasive assessment of extracellular and total body water	One month after starting protocol
Primary	Medium Molecule Clearance	Beta-2-Microglobulin clearance	One month after starting protocol
Primary	Medium Molecule Removal	Beta-2-Microglobulin extraction	One month after starting protocol
Secondary	Intradialytic Hemodynamics	noninvasive cardiac output assessment	Cardiac output (liters per minute) one month after starting protocol