Systemic and intraperitoneal interleukin-6 system during the first year of peritoneal dialysis.
OBJECTIVE
To 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).


METHODS
Longitudinal study in retrospectively selected patients.


METHODS
Peritoneal dialysis (PD) unit of a university-based hospital.


METHODS
31 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.


RESULTS
D/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 > or = 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 > or = 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.


CONCLUSIONS
These 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.
Division of Renal Medicine and Baxter Novum, Karolinska Institutet, K-56, Huddinge University Hospital, 141 86 Stockholm, Sweden. roberto.pecoits-filho@klinvet.ki.se
Roberto
R
Pecoits-Filho
Maria João
MJ
Carvalho
Peter
P
Stenvinkel
Bengt
B
Lindholm
Olof
O
Heimbürger
D001692:Biological Transport; D015415:Biomarkers / Q000378:metabolism; D015314:Dialysis Solutions / Q000737:chemistry* / Q000493:pharmacokinetics*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D015850:Interleukin-6 / Q000378:metabolism*; D007676:Kidney Failure, Chronic / Q000378:metabolism / Q000628:therapy*; D008297:Male; D008875:Middle Aged; D010529:Peritoneal Cavity; D010530:Peritoneal Dialysis; D010537:Peritoneum / Q000378:metabolism*; D012189:Retrospective Studies; D013997:Time Factors; D016896:Treatment Outcome
D015415:Biomarkers; D015314:Dialysis Solutions; D015850:Interleukin-6