The Role of Peritoneal Interleukin-6 in Predicting Patient Survival on Peritoneal Dialysis

Systemic inflammation predicts cardiovascular events and mortality in patients on peritoneal dialysis (PD). Peritoneal inflammation potentially causes adverse outcomes by increasing peritoneal solute transfer rates (PSTRs); however, the extent to which it contributes to systemic inflammation is uncertain. We sought to quantify the longitudinal interrelationship between peritoneal and systemic inflammation, to understand whether peritoneal or systemic inflammation should be targeted to reduce mortality.

We used patients recruited to the GLOBAL Fluid Study (GFS) within 90 days of starting PD, with ≥ 3 longitudinal paired dialysate and plasma samples. These were assayed for dialysate and plasma interleukin (IL)-6 levels by electrochemiluminescence (Meso-Scale Discovery, Gaithersburg, MD). Linear mixed models and univariate or bivariate joint longitudinal survival modelling were used.

Two hundred seventeen patients with 1273 measurements were included. Dialysate IL-6 levels increased with time (1.14 pg/ml/yr on PD, 95% confidence interval [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/yr 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 area under the curve (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).

Although 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 antiinflammatory interventions to improve patient survival should target systemic rather than peritoneal inflammation.