The role of peritoneal IL-6 in predicting patient survival on PD

Elphick, Emma H., Zavvos, Vasileios, Belcher, John, Topley, Nicholas, Chess, James A., Holmes, Clifford J., Davies, Simon J., Fraser, Donald ORCID: https://orcid.org/0000-0003-0102-9342 and Lambie, Mark 2025. The role of peritoneal IL-6 in predicting patient survival on PD. Kidney International Reports 10.1016/j.ekir.2025.06.049

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Abstract

Background Systemic inflammation predicts cardiovascular events and mortality in peritoneal dialysis patients (PD). Peritoneal inflammation potentially causes adverse outcomes by increasing peritoneal solute transfer rates (PSTR), but the extent to which it contributes to systemic inflammation is uncertain. We sought to quantify the longitudinal inter-relationship between peritoneal and systemic inflammation, to understand whether peritoneal or systemic inflammation should be targeted to reduce mortality. Methods We used patients recruited to the GLOBAL Fluid Study within 90 days of starting PD, with three or more longitudinal paired dialysate and plasma samples. These were assayed for dialysate and plasma IL-6 levels by electrochemiluminescence (MSD). Linear mixed models and univariate/bivariate joint longitudinal survival modelling were used. Results 217 patients with 1273 measurements were included. Dialysate IL-6 levels increased with time (1.14pg/ml per year on PD, 95% CI 1.10-1.19), with an associated increase in PSTR (p=0.001). Plasma IL-6 levels increased over time (1.07 pg/ml per year on PD, 95% CI 1.04-1.10), with an associated increase in dialysate IL-6 (p<0.001) and reduction in residual kidney function (p=0.01). Dialysate IL-6 levels estimated at any given time point weakly predicted mortality (AUC 0.57) and did not improve the prediction of mortality by plasma IL-6 (combined dialysate/plasma IL-6 AUC 0.79, plasma IL-6 only AUC 0.81). Conclusion Whilst rising dialysate IL-6 levels may contribute to rising PSTR and increasing systemic inflammation independently of declining kidney function over time, it is plasma IL-6 that confers mortality risk. This suggests future anti-inflammatory interventions to improve patient survival should target systemic rather than peritoneal inflammation.

Item Type:	Article
Date Type:	Published Online
Status:	In Press
Schools:	Schools > Medicine
Additional Information:	License information from Publisher: LICENSE 1: URL: http://creativecommons.org/licenses/by-nc-nd/4.0/, Start Date: 2025-06-25
Publisher:	Elsevier
ISSN:	2468-0249
Date of First Compliant Deposit:	10 July 2025
Date of Acceptance:	24 June 2025
Last Modified:	10 Jul 2025 09:45
URI:	https://orca.cardiff.ac.uk/id/eprint/179690

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