Association of Middle Molecules Clearance With HDF Volume

Association of Middle Molecules Clearance and Clinical Parameters With Haemodiafiltration Convection Volume

HDF is a dialysis technique which involves diffusion and convection. HDF with high convection volume has consistently shown to improve survival in dialysis patients in number of robust RCTs. The precise reason of this survival benefit remains unclear.

The investigators hypothesize that this survival benefit with high volume HDF is related to enhanced middle molecule clearance and hemodynamic stability. However, this relationship has not been studied so far.

This observational study is aimed to understand the relationship between HDF convection volume with middle molecules (Beta 2-Microglobulin) clearance during HDF.

Exploring the relationship of HDF volume with middle molecules clearance has significant clinical ramifications. Only a minority of patients are able to achieve target convection volume. Understanding these relationships can rationalize the HDF prescription from convection volume-based prescription to β2-Microglobulin clearance-based prescription which may be applicable to wider range of patients.

The relationship between pre-dialysis β2-Microglobulin levels and RKF offers the prospect of dispensing with pre- and post-dialysis urea and creatinine measurements and interdialytic urine collections, currently necessary for estimating RKF, thus simplifying its estimation.

β2-Microglobulin reduction ratio and its component pre and post-dialysis β2-Microglobulin levels could therefore provide a composite estimate of small and middle molecule clearance and RKF.

Study Overview

• Status: Recruiting
• Conditions: End Stage Renal Disease

Detailed Description

People with severe kidney failure need treatment by dialysis or transplantation to stay alive. In the UK there are 25,000 people receiving treatment with haemodialysis (HD). Conventional haemodialysis works on the principle of diffusion for removal of toxins. Haemodiafiltration (HDF) is a technique of dialysis which implies the principle of convection in addition to diffusion. Large clinical trials comparing haemodiafiltration with conventional haemodialysis have reported better survival in patients having haemodiafiltration with large convection volume. The mechanism of survival benefit with high convection volume remains unclear.

The investigators hypothesize that the benefit of high convection volume haemodiafiltration is due to enhanced removal of large sized toxins called 'middle molecules'. Additionally, it may also be due to better blood pressure control and less inflammation when dialysing using this technique. The literature so far has been inconsistent to confirm this. Understanding the relationship of haemodiafiltration convection volume with middle molecules removal and clinical parameters is crucial for adoption of this mode of treatment. Additionally, it can potentially transform the presently imperfect dialysis prescription based on small molecule removal to clinically relevant middle molecules removal.

In this single centre cross sectional study, the investigators aim to recruit 400 adult participants who have been on haemodiafiltration for at least 3 months. Once consented, the participants will be observed in a single routine dialysis sessions (study visit) to record all the standard care clinical parameters and dialysis related information including dialysis convection volume from haemodiafiltration. Participants will also have routine blood tests at the start and end of the observed dialysis session and additional blood tests to measure the removal of middle molecules at the same time. The relationship of these observed clinical and measured toxins removal parameters with convection volume will be determined from the collected data.

• Study Type: Observational
• Enrollment (Estimated): 400

Contacts and Locations

• Study Contact: Name: Usama A Butt, MBBS,MRCP; Phone Number: +441438284340; Email: usama.butt1@nhs.net

Study Locations

• United Kingdom
  • Hertfordshire
    • Stevenage, Hertfordshire, United Kingdom, SG1 4AB
      • Recruiting
      • East and North Hertfordshire NHS Trust
      • Contact: Usama A Butt, MBBS,MRCP; Phone Number: +441438 284340; Email: usama.butt1@nhs.net
      • Principal Investigator: Usama A Butt, MBBS,MRCP

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

End stage renal failure patient having renal replacement therapy in the form of Haemodiafiltration.

Description

Inclusion Criteria:

• Age 18 years or above.
• Ability to give informed consent.
• End stage renal failure treated by dialysis for at least 3 months.
• Established on hemodiafiltration for >4 weeks.
• Prognosis more than 6 months as assessed by PI

Exclusion Criteria:

• Age less than 18 years.
• Inability to give informed consent.
• Prognosis less than 6 months as assessed by PI

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort
HDF patients; ESRF patients who are receiving renal replacement therapy in the form of HDF

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
The relationship between HDF convection volume and β2 Microglobulin reduction ratio during a HDF session.	18 months
The relationship between HDF convection volume and serum pre dialysis β2 Microglobulin concentration (measured in mg/L).	18 months

Secondary Outcome Measures

Outcome Measure	Time Frame
The relationship of HDF convection volume with average intradialytic blood pressure (mmHg).	18 months
The relationship of HDF convection volume with average intradialytic core body temperature (degrees centigrade)	18 months
The relationship of HDF convection volume with CRP (mg/L).	18 months

Collaborators and Investigators

• Sponsor: East and North Hertfordshire NHS Trust
• Investigators: Principal Investigator: Usama A Butt, MBBS, MRCP, East and North Hertfordshire NHS Trust

Study record dates

Study Major Dates

• Study Start (Actual): January 19, 2024
• Primary Completion (Estimated): July 1, 2025
• Study Completion (Estimated): July 1, 2025

Study Registration Dates

• First Submitted: February 16, 2024
• First Submitted That Met QC Criteria: July 17, 2024
• First Posted (Actual): July 23, 2024

Study Record Updates

• Last Update Posted (Actual): July 23, 2024
• Last Update Submitted That Met QC Criteria: July 17, 2024
• Last Verified: July 1, 2024

More Information

Terms related to this study

• Keywords: HDF; Middle molecules; beta 2 microglobulin; Middle Molecules clearance in HDF; HDF convection volume
• Additional Relevant MeSH Terms: Pathologic Processes; Kidney Diseases; Urologic Diseases; Disease Attributes; Renal Insufficiency; Renal Insufficiency, Chronic; Chronic Disease; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Kidney Failure, Chronic
• Other Study ID Numbers: RD2023-68

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No