Elastase, α1-Proteinase Inhibitor, and Interleukin-8 in Children and Young Adults with End-Stage Kidney Disease Undergoing Continuous Ambulatory Peritoneal Dialysis

Abstract

Peritoneal dialysis is one of the main modality of treatment in end-stage kidney diseases (ESKD) in children. In our previous work in chronic kidney disease patients, in pre-dialyzed period and on hemodialysis, the neutrophils were highly activated. The aim of this study was to assess an inflammatory condition and neutrophil activation in ESKD patients undergoing continuous ambulatory peritoneal dialysis (CAPD). Thirteen CAPD patients without infection, both sexes, aged 2.5–24 years, and group of healthy subjects (C) were studied. For comparative purposes the conservatively treated (CT) group of ESKD patients was included. Neutrophil elastase in complex with α1-proteinase inhibitor (NE-α1PI; ELISA), α1-proteinase inhibitor (α1PI; radial immunodiffusion) and interleukin-8 (IL-8; ELISA) were measured in the blood samples from CAPD, CT, and C group and in the peritoneal dialysate fluid (PDF) samples of patients on CAPD. A significantly increased plasma NE-α1PI levels (median 176.5 μg/L, range 85.2–373.2 μg/L; p < 0.00005), serum IL-8 (median 18.6 pg/mL, range 15.73–35.28 pg/mL; p < 0.05), and slightly decreased serum α1PI (median 1,540 mg/L, range 1,270–1,955; p ≤ 0.05) compared to the control groups were found. There were no significant differences of analyzed parameters between CAPD and CT patients. The concentration ratio of NE-α1PI, α1PI and IL-8 in blood/PDF was 29.97, 8.24, and 4.48, respectively. There were significantly positive correlations between serum and PDF concentration of α1PI and IL-8 (r = 0.613, p < 0.05; r = 0.59; p < 0.005, respectively). The results of our study demonstrate that neutrophils are highly activated in non-infected CAPD patients. The pivotal marker of this activation is NE-α1PI. It may contribute to chronic inflammation and tissues injury.

Low serum levels of vitamin D are associated with anxiety in children and adolescents with dialysis

“…A growing body of evidence suggests the involvement of cytokines in the process of anxiety by modulating the metabolism of neurotransmitters such as dopamine and serotonin 20 – 23 . Up-regulation of inflammatory cytokines and neutrophil activation has been found in non-infected pediatric patients with dialysis 24 , 25 . Therefore, these results suggest that vitamin D might play an important role in anxiety among children and adolescents receiving dialysis.…”

Neutrophil Elastase Inhibitors and Chronic Kidney Disease

“…Anemia is a common complication in CKD patients that results from a reduced production of erythropoietin by the failing kidneys and may contribute to enhance inflammation. Neutrophil elastase inhibitors, as therapeutic agents, can be used to inhibit these proteases released by the activated neutrophils at renal inflammatory sites, preventing worsening of renal damage and, thus, the development of CKD and the associated complications (Figure 3 ) 10 , 11 , 123 - 125 .…”

“…The NE-α1-PI was positively correlated with α1-PI and seems to be a better predictor of the inflammatory state in CKD patients than α1-PI and IL-8 125 . NE-α1PI and IL-8 levels were also raised in non-infected children and young adults with CKD on continuous ambulatory peritoneal dialysis (CAPD), and the interaction between NE, α1-PI and IL-8 seems to enable the recruitment of inflammatory cells and tissue damage 10 .…”

“…Inflammation, dyslipidemia, as well as disturbances in erythropoiesis, iron metabolism, endothelial function and in nutritional status, are common features in ESRD patients 5 . The chronic inflammation in patients with ESRD under hemodialysis has been associated with an imbalance between oxidant and anti-oxidant mechanisms, neutrophil activation with release of reactive oxygen species (ROS) and release of granule content, namely, neutrophil serine proteases (NSPs), such as neutrophil elastase (NE); and to activation of inflammatory cells through stimulation of cytokines by the released inflammatory products 6 - 10 . The inflammatory process and the development of oxidative stress are two main factors for worsening of anemia and to increase the risk for cardiovascular events 11 - 13 .…”

Polysulfone Membranes Doped with Human Neutrophil Elastase Inhibitors: Assessment of Bioactivity and Biocompatibility

“…Thus, elastase may contribute to perpetuating the inflammatory state in patients with CKD and favor the development of other inflammatory conditions. [ 4 , 7 , 8 , 9 , 10 , 11 , 12 ]. High levels of elastase have been associated with CV diseases [ 4 , 7 , 8 , 9 , 10 ] and with chronic obstructive pulmonary disease, acute lung injury, cystic fibrosis, and ulcerative colitis [ 8 , 9 , 13 ].…”