Efficacy of Uremic Toxins Clearance With Expanded Hemodialysis
Efficacy of Uremic Toxins Clearance With Expanded Hemodialysis
The aim of this study is to quantify the B2-microglobulin reduction rate based on the type of
 extracorporeal therapy (ET) used: HDx (expanded hemodialysis), HDc (high-flux conventional
 hemodialysis), or HDF (hemodiafiltration).

 And to compare the magnitude of the B2-microglobulin reduction rate based on the type of
 extracorporeal therapy (ET) used: HDx, HDc, or HDF
A controlled, randomized, crossover clinical trial is planned to compare the magnitude of the
 B2-microglobulin reduction rate in three different extracorporeal therapies (ETs): HDc, HDx,
 and HDF.

 The selection of study subjects will be consecutive and for convenience

 This study will be divided into six periods: three treatment periods (one for each therapy to
 be compared) and three of "washout" periods (interspersed between the treatment periods). The
 treatment periods will last four weeks (12 ET sessions, three per week) and will be preceded
 by a one-week washout period (three ET sessions)

 After inclusion in the protocol, patients will be randomly assigned (with the help of a table
 of random numbers) to one of three ETs to be evaluated (HDc, HDx, or HDF). Afterwards, the
 first washout period will begin with high-flow conventional hemodialysis (HDc). At the end of
 the first washout period, the ET randomly assigned to one of three ETs to be evaluated (HDc,
 HDx, or HDF), following the sequence: Washout 1 -> Period 1 (HDC, HDx, or HDF) -> Washout 2
 -> Period 2, etc.

 For each period of ET, there will be two sampling times: baseline and final

 Blood samples will be obtained through the arterial port of the extracorporeal circuit, at
 the beginning and at the end of the ET session. The "slow flow" method will be used (UF: 0
 mL/min, Qd: 0 mL/min, and Qb: 100 mL/min, for 30 seconds, before extracting the sample from
 the arterial port) (24). Blood samples will be collected in dry tubes (without anticoagulant)
 and centrifuged for 10 minutes at 3,000 RPM. The supernatant will be divided into three
 aliquots and stored at -70°C for further processing.

 To calculate sample size, the formula for a noninferiority study was used (Pharmaceutical
 statistics. 2016;15(1):80-9), which is detailed below:

 n= ((r+1) (Z_(1-β)+Z_(1-α) )^2 σ^2)/(r((μ_A-μ_B )-d_NI )^2 )

 The terms above, are substituted with values obtained from the publication of Kirsch et al.
 (Nephrol Dial Transplant. 2017 Jan 1;32(1):165-172) as follows:

 Objective: Non-inferiority (Ho µA - µB ≤ -dNI vs. µA - µB > -dNI) Outcome: B2-microglobulin
 reduction rate. r: allocation ratio by group:1 beta: type II error (90% power):1.2816 alpha:
 type I error (level of significance 5%):1.960 (variance in the population):1.33 µA - µB
 (magnitude of the observed effect):80.6 - 78.5 = 2.1 dNI (non-inferiority limit): 3.5

 n= ((1+1) (1.2816+1.960)^2 〖(1.33)〗^2)/(1((2.1)-3.5)^2 )= 19, we estimate a 20 % loss in the
 follow-up , then we consider a sample size of n = 23 patients

 The nominal variables will be presented in frequencies and proportions. Continuous numerical
 variables will be analyzed using the Kolmogorov-Smirnov "Z" test to determine their
 distribution. The results will be shown as the means ± standard deviation in case of normal
 distribution and as a median with minimum and maximum limits for variables with non-normal
 distribution.

 The total serum concentration of the biochemical variables in general as well as the uremic
 toxins will be analyzed. Additionally, the reduction rate and purification of the uremic
 toxins will be analyzed.

 The analyses of the inter- and intra-group differences will be performed using the one-way
 multiple comparisons (ANOVA) method. Post hoc analysis using the Bonferroni method will be
 used in cases where the groups present a normal distribution; otherwise, the Kruskal-Wallis
 method will be used. A result with a p < 0.05 will be considered significant
Inclusion Criteria:

 -  Over 18 years

 -  Anuric patients (residual urinary volume ≤ 100 mL/24 h)

 -  Intermittent chronic hemodialysis (three sessions per week, of 3.5 to 4 hours each)

 -  Without modification of their prescription in the last three months

 -  Functional arteriovenous fistula, indwelling vascular access (Qb ≥ 300 mL/min), or
 both

 -  Letter of acceptance to enter the protocol and a signed informed consent.

 Exclusion Criteria:

 -  Under 18 years

 -  Active intake or intake in the last six months of immunosuppressants or systemic
 steroids

 -  Active autoimmune disease

 -  Evidence of active systemic infectious event at the time of inclusion or two weeks
 prior

 -  Diagnosis of neoplasia or active oncological disease

 -  Hypoalbuminemia (< 3.2 g/dL)

 -  Pregnancy or lactation

 -  Refusal to participate in the study