Enhanced neutrophil apoptosis accompanying myeloperoxidase release during hemodialysis

Abstract

Biocompatibility of hemodialysis (HD) systems have been considerably improved. However, mortality and morbidity rates of patients have remained high, raising questions regarding the biocompatibility of current systems. In the present study, 70 patients on regular HD (51 males; mean age, 63 years; median duration of HD, 18 months) with high-performance membrane (polysulfone, 77%; polymethylmethacrylate, 23%) at Tohoku University Hospital were examined. Blood samples before and after HD, were subjected to measure apoptosis cells of white blood cells, plasma levels of the following molecules: myeloperoxidase (MPO), pentraxin 3 (PTX3), angiogenin, complements, and 17 cytokines. The main findings were as follows: significant decreases in leukocyte counts by dialysis, significant increases in apoptosis-positive leukocytes by dialysis (neutrophils and monocytes), and significant decrease in plasma angiogenin accompanying increase in plasma MPO and PTX3 levels, with no or only marginal changes in plasma pro-inflammatory cytokine levels and complement products by dialysis. The findings underlined the unsolved issue of bio-incompatibility of HD systems, and suggest the possible pathology of neutrophil apoptosis accompanying MPO release for the development of microinflammation in patients on HD.

Immune System Dysfunction and Inflammation in Hemodialysis Patients: Two Sides of the Same Coin

“…Fukushi examined peripheral leukocytes and neutrophils counts in HD patients treated with polysulfone membranes, revealing a decrease in neutrophils number at the end of the HD session and a significant increase in apoptosis-positive cells among neutrophils and monocytes, but not among lymphocytes. The activation of the complement system and the increased apoptotic cell levels mainly caused this transient leukopenia [53].…”

Inflammation and Cardiovascular Disease Associated With Hemodialysis for End-Stage Renal Disease

“…Anti-myeloperoxidase antibodies (MPO), a type of anti-neutrophil cytoplasmic antibody (ANCA), are a functional marker and activation marker of neutrophils, and changes in their levels and activity are representative of the functional and active status of neutrophilic polymorphonuclear leukocytes (PMN). The excessive apoptosis of neutrophils due to increased MPO release is thought to be the pathological mechanism underlying the development of microinflammation in HD patients ( Fukushi et al, 2020 ), leading to an increased risk of infection and mortality from infection in patients starting HD. This mechanism also confirms the conclusion that plasma MPO is an independent risk factor for all-cause mortality in HD patients, as suggested by two clinical studies in recent years ( Nakayama et al, 2018 ; Kim et al, 2020 ).…”

The Pathogenesis of End-Stage Renal Disease from the Standpoint of the Theory of General Pathological Processes of Inflammation

“…This variant of programmed necrosis of neutrophils and other phagocytes is designated as NETosis. In particular, during a hemodialysis session, neutrophil NETosis is accompanied by the release of myeloperoxidase, elastase, and other phlogogenic factors into the bloodstream [ 223 , 224 ]. Furthermore, in ESRD, intravascular eosinophil activation is observed, as evidenced by a rise in blood eosinophilic cationic protein (ECP), a factor in tissue change [ 192 , 225 ].…”