Depressed Phagocytosis in Hemodialyzed Patients: In vivo and in vitro Mechanisms

Abstract

Infection is a frequent complication and the major cause of death among end-stage renal patients. Polymorphonuclear phagocytes (PMNL) are important in host defense mainly because of bacterial destruction by nicotinamide adenine dinucleotide phosphate (NADPH) oxidase-related free radical production following phagocytosis. In this study, hexose monophosphate pathway glycolytic activity, delivering energy to NADPH oxidase, is evaluated in vivo and in vitro, in healthy controls and in dialyzed renal failure patients. Our results show a marked parallel and correlated inhibition in the response to three stimuli for phagocytic activity (Siaphylococcus aureus, formyl-methionine-leucine-phenylalanine, phorbol myristic acid) in predialysis samples. These data point to a main suppression of metabolic pathways, possibly beyond protein kinase C. This response is further suppressed at the 15th minute of cuprophane dialysis, for all stimuli studied (-40 to -94%; p < 0.001) except PMA. PMNL response remains intact during dialysis with non-complement-activating dialyzers. In vitro experiments confirm decreased PMNL glycolytic activity after the suspension of cuprophane fragments in normal whole blood. We conclude that polymorphonuclear cell energy delivery to NADPH oxidase is impaired in patients with end-stage renal failure. The impaired response against various stimuli is different in predialysis blood samples compared to samples collected during cuprophane dialysis, and may be related to two different conditions. These events probably contribute to the acquired immune suppression of uremia and the high incidence of infection among dialysis patients.

Anti-<i>Toxoplasma gondii</i> Antibodies in Haemodialysis Patients

“…Uremic patients are affected with suppressed cellular and humoral immune responses (Vanholder et al, 1993;Stuart, 1976). It has been suggested that because of reduced circulating T-cells and increased suppressor cells, then haemodialysis can not return the impairment of the immune status in CRF (Glorieux et al, 2009).…”

Polymorphonuclear function in naturally occurring renal failure in dogs

“…It was proposed that haemodialysis per se may partly evoke disturbances in phagocytosis (Vanholder et al, 1993;Sardenberg et al, 2006). Nevertheless, there are some studies with non-haemodialysed uremic people, where the phagocytic function was impaired (Sharma et al, 2000).…”

“…This is well documented in men, where infections are still a major cause of morbidity and mortality in end-stage renal disease patients. There are many reports of neutrophil dysfunction and increased risk of infection in these patients (Vanholder and Ringoir, 1992;Vanholder et al, 1993;Sharma et al, 2000). The functional impairment described in uremic neutrophils is there-fore mainly a result of their reduced ability to kill microorganisms intracellularly and is believed to increase the susceptibility to infections (Anding et al, 2003).…”

Leukocyte Function in High-Flux Hemodialysis

“…In spite of the process in the last years to strive towards more biocompatible materials and methods, including highflux dialysis treatment, patients on hemodialysis still display a high morbidity and mortality in infections (Bloembergen & Port 1996;Powe et al 1999;Graff et al 2002). Neutrophil dysfunction in dialysis patients is manifested by reduced chemotaxis, adherence, respiratory burst and glucose consumption in response to an inflammatory stimulus (Vanholder et al 1993b;Vanholder et al 1993a). …”