Inflammation and all-cause mortality in patients undergoing peritoneal dialysis

OBJECTIVE
This study aimed to evaluate inflammatory biomarkers in patients undergoing peritoneal dialysis and investigate their association with all-cause mortality or transfer to hemodialysis.


METHODS
This prospective cohort study included 43 patients undergoing peritoneal dialysis. Plasma levels of cytokines were measured using flow cytometry and capture enzyme-linked immunosorbent assay. Biomarkers were categorized based on their respective median values. Survival analysis was conducted using the Kaplan-Meier estimator, considering two outcomes: all-cause mortality and transfer to hemodialysis.


RESULTS
After adjusting for confounding factors, plasma levels above the median of the levels of CCL2 and plasma, as well as below the median of TNF-α, and the median of dialysate IL-17 levels, were associated with an increased risk of experiencing the specified outcomes after approximately 16 months of follow-up.


CONCLUSION
These findings suggest that inflammatory biomarkers may be a valuable tool for predicting all-cause mortality and transfer to hemodialysis in patients undergoing peritoneal dialysis.

Table 1S shows the survival estimates of the 43 patients on PD, their respective standard errors and 95%CI, obtained by the Kaplan Meier estimator.The table 2S presents the results of the hypothesis test for Pearson's correlation coefficient between Schoenfeld residuals and time.P-values greater than 5%, both in the global test and in the test for each covariate, indicate that there is no violation of the proportional hazards' assumption.This fact is corroborated by the observation of the graphs in figure 1S, in which there is no evidence of trends and it is noted that the residuals are randomly distributed around zero.The Martingale and Deviance residuals graphs (Figure 2S) constructed to assess the general quality of the fitted model indicate the model's suitability, as the residuals are randomly distributed around zero.Thus, the estimates of the final adjusted model are presented in table 2S, as well as the respective risk ratios.It is possible to conclude that with each occurrence of peritonitis, the risk of death or transfer to HD increases about 2 times.Patients with plasma levels of TNF-a below the median have a 3.29-fold greater risk of death or transfer to HD than patients with TNF-a levels above the median.The table 3S presents the results of the hypothesis test for Pearson's correlation coefficient between Schoenfeld residuals and time.P-values greater than 5%, both in the global test and in the test for each covariate, indicate that there is no violation of the proportional hazards' assumption.This fact is corroborated by the observation of the graphs in figure 3S, in which there is no evidence of trends and it is noted that the residuals are randomly distributed around zero.Thus, the estimates of the final adjusted model are presented in table 4S, as well as the respective risk ratios.It is possible to conclude that with each occurrence of peritonitis, the risk of death or transfer to HD increases about 2 times.DP timing does not accelerate or decelerate risk, although it is influential.Patients with plasma CCL2 levels above the median are 4 times more likely to die or transfer to HD than patients with CCL2 levels below the median.The table 5S presents the results of the hypothesis test for Pearson's correlation coefficient between Schoenfeld residuals and time.P-values greater than 5%, both in the global test and in the test for each covariate, indicate that there is no violation of the proportional hazards' assumption.This fact is corroborated by the observation of the graphs in figure 5S, in which there is no evidence of trends and it is noted that the residuals are randomly distributed around zero.Thus, the estimates of the final adjusted model are presented in table 5S, as well as the respective risk ratios.It is possible to conclude that with each occurrence of peritonitis, the risk of death or transfer to HD increases about 2 times.Patients with IL-17 dialysate levels below the median are almost 7 times more likely to die or transfer to HD than patients with IL-17 levels above the median.

Figure 1S .
Figure 1S.Plots of Schoenfeld residuals as a function of time for the adjusted Cox model considering the plasma TNF-α cytokine level

Figure 3S .
Figure 3S.Graphs of Schoenfeld residuals as a function of time for the adjusted Cox model

Figure 4S .
Figure 4S.Martingale and Deviance residues from the Cox model adjusted considering the plasma cytokine CCL2 level

Figure 5S .
Figure 5S.Plots of Schoenfeld residuals as a function of time for the adjusted Cox model considering the level of the cytokine IL-17 in the dialysate

Table 1S .
Survival estimates by Kaplan Meier SD: standard deviation; LL: lower limit; UL: upper limit.

Table 2S .
Results of the hypothesis test for Pearson's correlation coefficient between Schoenfeld residuals, considering the plasma TNF-a cytokine level and time

Table 3S .
Results of the hypothesis test for Pearson's correlation coefficient between Schoenfeld residuals, considering the plasma cytokine CCL2 level and time

Table 4S .
Estimates obtained for the parameters of the adjusted Cox model, and 95%CI, considering the competitive risks of death and transfer to hemodialysis and the cytokine IL-17 categorized by the median in the dialysate * Significant at 5%.PD: peritoneal dialysis; HD: hemodialysis; IL-17: interleukin-17.

Table 5S .
Results of the hypothesis test for Pearson's correlation coefficient between Schoenfeld residuals considering the level of the cytokine IL-17 in the dialysate and time PD: peritoneal dialysis; HD: hemodialysis; IL-17: interleukin-17.