Systemic and Intraperitoneal Interleukin-6 System during the First Year of Peritoneal Dialysis

Abstract

ObjectiveTo investigate if intraperitoneal and systemic interleukin-6 (IL-6) and soluble IL-6 receptor (sIL-6R) are related to each other and to peritoneal solute transport rate (PSTR).DesignLongitudinal study in retrospectively selected patients.SettingPeritoneal dialysis (PD) unit of a university-based hospital.Patients and Methods31 PD patients on treatment with conventional glucose-based solutions participated in a longitudinal study. IL-6 and sIL-6R were measured in plasma and overnight effluent, both at baseline and after 12 ± 2 months on PD. C-reactive protein (CRP) and serum albumin were used as surrogate markers of inflammation. PSTR of small solutes was evaluated using the dialysate-to-plasma ratio (D/P) of creatinine after a 4-hour dwell; PSTR of large solutes was evaluated using the 24-hour D/P ratio of albumin.ResultsD/P creat increased over time (0.67 ± 0.15 vs 0.80 ± 0.11, p < 0.0001) and correlated to D/P albumin only at the baseline evaluation. Patients with plasma IL-6 ≥median had higher ( p < 0.005) D/P creat at baseline [0.74 (0.62 – 0.87)] compared to patients with IL-6 < median [0.57 (0.47 – 0.66)]. Dialysate IL-6 at baseline was also higher ( p < 0.05) in patients with plasma IL-6 ≥median [24.7 (16.5 – 38.5) pg/mL] compared to patients with IL-6 < median [14.1 (10 – 25.7) pg/mL]. Neither CRP nor albumin changed over time on PD, although they were closely linked to plasma IL-6 levels. A strong positive correlation was found between D/P creat and dialysate IL-6 (rho = 0.77, p < 0.0001) at baseline, but not at 1 year. In contrast, there was a significant correlation between D/P creat and dialysate sIL-6R (rho = 0.39, p < 0.05) at 1 year, but not at baseline. At 1 year, 17 patients with increasing PSTR had higher increases in dialysate IL-6 (28 ± 26 vs –21 ± 78 pg/mL, p < 0.05) and levels of dialysate sIL-6R (693 ± 392 vs 394 ± 274 pg/mL, p = 0.05) compared to patients with stable PSTR ( n = 11). Patients who had peritonitis presented higher baseline serum IL-6 concentration (6.8 ± 1.0 pg/mL) compared with patients without peritonitis (4.0 ± 0.6 pg/mL, p < 0.05). Finally, both at baseline and after 1 year, there were significant correlations between plasma and dialysate IL-6 (rho = 0.46, p < 0.05, and rho = 0.40, p < 0.05) respectively.ConclusionsThese findings indicate that, ( 1 ) intraperitoneal and systemic inflammation increase in PD patients during the first year of therapy; ( 2 ) intraperitoneal and systemic inflammation may be interrelated and the IL-6 system may be the link; ( 3 ) the IL-6 system (both intraperitoneal and systemic) is associated with PSTR, particularly in the early phase of PD treatment, in which small and large solute transport are linked. Signs of a transition between acute and chronic inflammation were observed in the follow-up evaluation. Inflammation may, at least in part, be responsible for the development of a high PSTR, and this could be one reason for the high mortality in patients with high PSTR.