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Kidney Week

Abstract: SA-PO592

The CompAct-HD Trial Reports an Acute Complement Activity-Associated Inflammatory Response Within 15 Minutes of Starting Hemodialysis

Session Information

Category: Dialysis

  • 801 Dialysis: Hemodialysis and Frequent Dialysis

Authors

  • Herbert, Andy, Invizius Ltd, Motherwell, North Lanarkshire, United Kingdom
  • Ilyas, Duha, Manchester Foundation Trust, Manchester, Greater Manchester, United Kingdom
  • Blackburn, Elizabeth A., Invizius Ltd, Motherwell, North Lanarkshire, United Kingdom
  • Ebah, Leonard, Manchester Foundation Trust, Manchester, Greater Manchester, United Kingdom
  • Mackie, Jennifer, Invizius Ltd, Motherwell, North Lanarkshire, United Kingdom
  • Mitra, Sandip, Manchester Foundation Trust, Manchester, Greater Manchester, United Kingdom
Background

It is well established that kidney patients experience aberrant complement pathway activation. A heightened inflammatory state is thought to contribute to excess cardiac deaths and cardiovascular events in those undergoing hemodialysis (HD). The aim of the CompAct-HD trial is to characterize complement activation and biomarker response to blood-membrane-circuit interaction during HD.

Methods

Six timed intradialytic blood samples were collected in 300 HD patients during a standard treatment with ultrapure water and high flux membranes. Complement activity potential was determined from timepoint 1 and inflammatory biomarkers from timepoints 2 to 6. Highly multiplexed assays enabled us to determine 60 biomarkers of complement activation and inflammation from a single blood sample.

Results

The 6 blood samples for each patient revealed changes in inflammatory biomarkers within 15 minutes (T3, sCD40L, panel A) of starting dialysis. There was a wide range in the magnitude of this response between individuals. Most biomarker levels increased, peaking during the first hour of dialysis and then fell; not always to the level at the start of dialysis. Interrogating the data for sCD40L to remove patients with Alternative Pathway activity in the first and second quartile showed that patients with complement activity above the median experienced a larger median inflammatory response at all time points (panel B).

Conclusion

Patients with an elevated complement activation potential experienced an exaggerated acute intradialytic inflammatory response within 15 mins of HD treatment, which did not always resolve to baseline by the end of the dialysis session.

Funding

  • Commercial Support – Invizius Ltd