#2866 The CompAct-HD trial reports a persistent inflammatory profile in patients undergoing haemodialysis, acutely exacerbated with each treatment
Authors: Ilyas Duha , Blackburn Elizabeth , Herbert Andy , Ebah Leonard , Mackie Jennifer , Lindsay Thomas , Mitra Sandip 
Published: May 2024

Abstract

Background and Aims
Inflammation induced by haemodialysis (HD) treatment has been recognised for several decades. Despite significant advances in technology, there is evidence that incompatibility between the dialyser, a foreign surface, and the patients’ blood, results in activation of the immune system. With each session, blood-membrane interaction leads to a repetitive activation of the innate complement system and a subsequent inflammatory response. It is now widely acknowledged that the consequences of long-term inflammation include fibrosis and accelerated cardiovascular disease, a common cause of mortality in patients with renal failure.
The aim of the CompAct-HD trial is to characterize complement activation and biomarker response to blood-membrane-circuit interaction during HD.

Method
For a single session, six timed intradialytic blood samples were collected from HD patients during standard treatment with ultrapure water and high flux “biocompatible” membranes. Complement activity potential was determined from timepoint 1 and inflammatory biomarkers from timepoints 2 to 6. Single time point samples were also collected from 7 healthy donors.
Highly multiplexed assays enabled to determine 30 biomarkers of inflammation, including cytokines, chemokines, growth factors and complement proteins, from a single blood sample.
Data analysis was performed using Microsoft® Excel Version 16.80 and GraphPad Prism 10.1.0.

Results
354 patients were recruited from 8 dialysis units across Greater Manchester, UK. An interim analysis was performed on 150 HD patients receiving standard care as well as 7 healthy donors.
Dialysis appears to generate an acute inflammatory response, that is, within 15 minutes of commencing treatment which does not appear to resolve by the end of the session.
This heightened inflammatory state was observed in HD patients in comparison to healthy donors (Fig. 1) with most pronounced changes seen in cytokines IL-1β, IL-10, IL-12p40 and TNF-α during dialysis. Established markers such as IL-6 also showed a 6-fold increase at the 75th percentile. Similarly, an exaggerated intradialytic response was observed in complement proteins, including the terminal complement complex (TCC) C5b-9 and anaphylatoxin C5a with spikes of up to 7-fold and 10-fold respectively (Fig. 2).
A session of HD was shown to cause a relative increase in complement proteins and inflammatory biomarkers. The magnitude of response seen in patients was variable (Fig. 3) with the greatest rise seen in the top quartile (above the Q3 boundary).

Conclusion
Our findings evidence a sharp inflammatory response to modern day HD treatment across a large cohort of dialysis patients. When compared to healthy donors, we observed heightened levels of inflammation in dialysis patients that is further exacerbated with each treatment session.
This study shows that HD has a significant role to play in the chronic inflammatory state of patients with end stage renal failure. Furthermore, here we describe potential targets, in both cytokine and complement proteins, which could be the key to downregulation of inflammation. Using targeted therapeutics, we have an opportunity to deliver a more biocompatible treatment, improving patient outcomes.