Study of association between interleukin-17 and interferon-gamma and recombinant human erythropoietin dose in patients undergoing peritoneal dialysis.

BACKGROUND: A common complication in patients undergoing peritoneal dialysis (PD) is a chronic inflammatory state and anemia that can be treating by recombinant human erythropoietin (rHuEPO). Higher required dose of rHuEPO could be expected in patients with higher cytokine levels. Additionally, it is known that peritoneal inflammation can be correlated with systemic inflammation and this could contribute to the compromised rHuEPO required dose in anemic patients with end stage renal disease (ESRD). Thus, the current study aimed to evaluate the association between levels of systemic and local interferon (IFN)-γ, interleukin (IL)-17 and other cytokines and the dose of rHuEPO used by patients undergoing PD for the correction of anemia. METHODS: Thirty-one patients under PD using rHuEPO were evaluated in this cross-sectional study. Plasma and dialysate levels of IL-2, IL-4, IL-6, IL-10, IL-17, tumour necrosis factor (TNF)-α and IFN-γ were determined using the Cytometric Bead Array TM kit (CBA; BD Bioscences, San Jose, CA). The relation between the levels of each cytokine levels and the tertiles of rHuEPO were plotted on box-plot graphics and then the medians of interleukins levels were compared by median comparison test. The significance level adopted was 5% and the analysis was performed by the softwares STATA (version 12.0) and GraphPad Prism 3.0. RESULTS: The median of IL-17 and IFN-γ plasma levels were significant higher in the group with higher rHuEPO dosage. However, this association was not observed in the dialysate levels, as well as was not observed a relationship between the other plasma and dialysate cytokines evaluated in this study and the dose of rHuEPO. CONCLUSIONS: Our study found increased IL-17 and IFN-γ plasma, but no dialysate levels, in patients receiving higher doses of rHuEPO, suggesting may exist a relationship between systemic inflammation of ESRD, and the necessary levels of rHuEPO for the correction of anemia in these patients.

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.

CA-125 and CCL2 may indicate inflammation in peritoneal dialysis patients.

INTRODUCTION: Progressive structural changes in the peritoneal membrane occur over the course of treatment in peritoneal dialysis (PD), resulting in an increase in cytokines such as CCL2 and structural changes in peritoneal membrane triggering an increase in CA-125 in dialysate, which reflects a probable local inflammatory process, with possible loss of mesothelial cells. Thus, the current study aimed to evaluate the association between plasma and CCL2 and CA-125 dialysate levels in patients undergoing PD. METHODS: Cross-sectional study was conducted with 41 patients undergoing PD. The assessments of CA-125 and CCL2 levels were performed using a capture ELISA. Correlations were estimated using Spearman's correlation and the investigation of the association between the explanatory variables (CCL2) and response variable (CA-125) was done for crude ratio of arithmetic means and adjusted utilizing generalized linear models. RESULTS: A moderate positive correlation was observed between the levels of CA-125 and CCL2 in the dialysate (rho = 0.696). A statistically significant association was found between the levels in the CCL2 and CA-125 dialysate (RoM=1.31; CI = 1.20-1.43), which remained after adjustment for age (RoM = 1.31; CI=1.19-1.44) and for time in months of PD (RoM=1.34, CI=1.22-1.48). CONCLUSION: The association of CA-125 levels with CCL2 in the dialysate may indicate that the local inflammatory process leads to temporary or definitive changes in peritoneal membrane. A better understanding of this pathogenesis could contribute to the discovery of new inflammatory biomarkers.

CA-125 and CCL2 may indicate inflammation in peritoneal dialysis patients / CA-125 e CCL2 podem indicar inflamação em pacientes em diálise peritoneal

Abstract Introduction: Progressive structural changes in the peritoneal membrane occur over the course of treatment in peritoneal dialysis (PD), resulting in an increase in cytokines such as CCL2 and structural changes in peritoneal membrane triggering an increase in CA-125 in dialysate, which reflects a probable local inflammatory process, with possible loss of mesothelial cells. Thus, the current study aimed to evaluate the association between plasma and CCL2 and CA-125 dialysate levels in patients undergoing PD. Methods: Cross-sectional study was conducted with 41 patients undergoing PD. The assessments of CA-125 and CCL2 levels were performed using a capture ELISA. Correlations were estimated using Spearman's correlation and the investigation of the association between the explanatory variables (CCL2) and response variable (CA-125) was done for crude ratio of arithmetic means and adjusted utilizing generalized linear models. Results: A moderate positive correlation was observed between the levels of CA-125 and CCL2 in the dialysate (rho = 0.696). A statistically significant association was found between the levels in the CCL2 and CA-125 dialysate (RoM=1.31; CI = 1.20-1.43), which remained after adjustment for age (RoM = 1.31; CI=1.19-1.44) and for time in months of PD (RoM=1.34, CI=1.22-1.48). Conclusion: The association of CA-125 levels with CCL2 in the dialysate may indicate that the local inflammatory process leads to temporary or definitive changes in peritoneal membrane. A better understanding of this pathogenesis could contribute to the discovery of new inflammatory biomarkers.

Resumo Introdução: Alterações estruturais progressivas na membrana peritoneal ocorrem no decorrer do tratamento em diálise peritoneal (DP), resultando em um aumento de citocinas como CCL2 e alterações estruturais na membrana peritoneal desencadeando um aumento de CA-125 no dialisato, o que reflete um provável processo inflamatório local, com possível perda de células mesoteliais. Assim, o presente estudo teve como objetivo avaliar a associação entre CCL2 e CA-125 no plasma e no dialisato de pacientes submetidos à DP. Métodos: Foi realizado um estudo transversal com 41 pacientes submetidos à DP. As avaliações dos níveis de CA-125 e CCL2 foram realizadas utilizando ELISA de captura. As correlações foram estimadas usando a correlação de Spearman, e a investigação da associação entre as variáveis explicativas (CCL2) e a variável resposta (CA-125) foi feita pela razão bruta das médias aritméticas e ajustada utilizando modelos lineares generalizados. Resultados: Foi observada uma correlação positiva moderada entre os níveis de CA-125 e CCL2 no dialisato (rho = 0,696). Foi encontrada uma associação estatisticamente significativa entre os níveis no dialisato de CCL2 e CA-125 (RoM=1,31; IC = 1,20-1,43), que permaneceu após ajuste por idade (RoM = 1,31; IC=1,19-1,44) e pelo tempo de DP em meses (RoM=1,34, IC=1,22-1,48). Conclusão: A associação dos níveis de CA-125 com CCL2 no dialisato pode indicar que o processo inflamatório local leva a alterações temporárias ou definitivas na membrana peritoneal. Uma melhor compreensão desta patogênese pode contribuir para a descoberta de novos biomarcadores inflamatórios.

Peritoneal dialysis and inflammation.

Peritoneal dialysis (PD) is a kidney replacement therapy for end stage renal disease (ESRD) patients. Despite being a lifesaving treatment, the rate of mortality in patients under PD is elevated, mainly due to the chronic peritoneal dysfunction which is characterized by inflammation, peritoneal fibrosis and neoangiogenesis. The inflammatory process is trigged and modulated by the type of the peritoneal dialysis solutions (PDSs) used during PD. Currently, different PDSs are commercially available: (i) the conventional solutions; (ii) solutions of neutral pH containing low concentration of glucose degradation products (GDPs); (iii) solutions with icodextrin; and (iv) solutions containing taurine. Therefore, the aim of this review is to describe the different types of peritoneal dialysis solutions used during PD and their relationship with systemic and intraperitoneal inflammation. Some studies suggested that solutions of neutral pH containing low concentration of GDPs, icodextrin and taurine have better biocompatibility and lower influence on the inflammatory process compared to the conventional one. On the other hand, the studies, in general, were performed with a small population and for a short period of time. Therefore, further well-designed and -controlled clinical trials with larger number of individuals are required in order to better understand the role of different peritoneal dialysis solution types in the development of inflammation in patients with chronic peritoneal dialysis. Accordingly, studies that are more well-designed, well-controlled and with a larger number of patients are needed to explain and define the role of different types of PDS in the inflammation development in patients with chronic peritoneal dialysis.

Inflammation, neoangiogenesis and fibrosis in peritoneal dialysis.

Peritoneal dialysis (PD) is a form of renal replacement therapy used in patients with end stage renal disease (ESRD). It is based on using the peritoneum as a semipermeable membrane through which ultrafiltration (UF) and diffusion occur. Despite several benefits, PD has long-term complications, including inflammation, neoangiogenesis and fibrosis. Several inflammatory molecules can be found in the dialysate of PD patients including: interleukins (IL), tumor necrosis factor α (TNF-α) and C-reactive protein (CRP). Angiogenesis results in increased effective surface area exchange. Consequently, the glucose-driven osmotic pressure of the peritoneal dialysis fluid (PDF) is significantly reduced leading to UF failure (UFF). Several factors are implicated in the development of peritoneal fibrosis (PF) in PD patients. The most important factor is the conventional bio-incompatible PD solution, which contains high concentration of glucose and glucose degradation products (GDP). Although there are several studies elucidating the mechanisms leading to UFF in PD patients, more studies needed to be developed in this area and more research is required to find mechanisms to delay or to minimize the occurrence of many deleterious changes in peritoneal membrane (PM) during PD.