title: Mode of renal replacement therapy determines endotoxemia and neutrophil dysfunction in chronic kidney disease.
abstract: Bacterial infection and sepsis are common complications of chronic kidney disease (CKD). A vicious cycle of increased gut permeability, endotoxemia, inadequate activation of the innate immune system and resulting innate immune dysfunction is hypothesized. We assessed endotoxemia, neutrophil function and its relation to oxidative stress, inflammation and gut permeability in patients with CKD grade 3-5 without renal replacement therapy (CKD group, n = 57), patients with CKD stage 5 undergoing haemodialysis (HD, n = 32) or peritoneal dialysis (PD, n = 28) and patients after kidney transplantation (KT, n = 67) in a cross-sectional observational study. In HD patients, endotoxin serum levels were elevated and neutrophil phagocytic capacity was decreased compared to all other groups. Patients on HD had a significantly higher mortality, due to infections during follow up, compared to PD (p = 0.022). Oxidative stress, neutrophil energy charge, systemic inflammation and gut permeability could not completely explain these differences. Our findings suggest that dialysis modality and not renal function per se determine the development of neutrophil dysfunction and endotoxemia in CKD-patients. HD patients are particularly prone to neutrophil dysfunction and endotoxemia whereas neutrophil function seems to improve after KT. Multi-target approaches are therefore warranted to improve neutrophil function and potentially reduce the rate of infections with patients undergoing haemodialysis.
authors.affiliation: Department of Internal Medicine, Division of Gastroenterology and Hepatology, Medical University of Graz, Graz, Austria.
authors.forename: Sandra
authors.initials: S
authors.lastname: Lemesch
authors.affiliation: Department of Internal Medicine, Clinical Division of Nephrology, Medical University of Graz, Graz, Austria.
authors.forename: Werner
authors.initials: W
authors.lastname: Ribitsch
authors.affiliation: Department of Internal Medicine, Clinical Division of Nephrology, Medical University of Graz, Graz, Austria.|Intensive Care Unit, Department of Internal Medicine, Medical University of Graz, Graz, Austria.
authors.forename: Gernot
authors.initials: G
authors.lastname: Schilcher
authors.affiliation: Department of Internal Medicine, Division of Gastroenterology and Hepatology, Medical University of Graz, Graz, Austria.
authors.forename: Walter
authors.initials: W
authors.lastname: Spindelböck
authors.affiliation: Department of Internal Medicine, Clinical Division of Nephrology, Medical University of Graz, Graz, Austria.
authors.forename: Hildegard
authors.initials: H
authors.lastname: Hafner-Gießauf
authors.affiliation: Institute of Experimental and Clinical Pharmacology, Medical University of Graz, Graz, Austria.
authors.forename: Gunther
authors.initials: G
authors.lastname: Marsche
authors.affiliation: Institute of Experimental and Clinical Pharmacology, Medical University of Graz, Graz, Austria.
authors.forename: Lisa
authors.initials: L
authors.lastname: Pasterk
authors.affiliation: Institute of Physiological Chemistry, Center of Physiological Medicine, Medical University of Graz, Graz, Austria.
authors.forename: Doris
authors.initials: D
authors.lastname: Payerl
authors.affiliation: Department of Surgery, Division of Transplantation Surgery, Medical University of Graz, Graz, Austria.
authors.forename: Bianca
authors.initials: B
authors.lastname: Schmerböck
authors.affiliation: Department of Internal Medicine, Division of Gastroenterology and Hepatology, Medical University of Graz, Graz, Austria.
authors.forename: Monika
authors.initials: M
authors.lastname: Tawdrous
authors.affiliation: Department of Internal Medicine, Clinical Division of Nephrology, Medical University of Graz, Graz, Austria.
authors.forename: Alexander R
authors.initials: AR
authors.lastname: Rosenkranz
authors.affiliation: Department of Surgery, Division of Transplantation Surgery, Medical University of Graz, Graz, Austria.
authors.forename: Philipp
authors.initials: P
authors.lastname: Stiegler
authors.affiliation: Institute of Physiological Chemistry, Center of Physiological Medicine, Medical University of Graz, Graz, Austria.
authors.forename: Gerd
authors.initials: G
authors.lastname: Kager
authors.affiliation: Institute of Physiological Chemistry, Center of Physiological Medicine, Medical University of Graz, Graz, Austria.
authors.forename: Seth
authors.initials: S
authors.lastname: Hallström
authors.affiliation: Institute of Physiological Chemistry, Center of Physiological Medicine, Medical University of Graz, Graz, Austria.
authors.forename: Karl
authors.initials: K
authors.lastname: Oettl
authors.affiliation: Core Facility Computational Bioanalytics, Center for Medical Research, Medical University of Graz, Graz, Austria.
authors.forename: Katharina
authors.initials: K
authors.lastname: Eberhard
authors.affiliation: Department of Internal Medicine, Division of Gastroenterology and Hepatology, Medical University of Graz, Graz, Austria.
authors.forename: Angela
authors.initials: A
authors.lastname: Horvath
authors.affiliation: Department of Surgery, Division of Transplantation Surgery, Medical University of Graz, Graz, Austria.
authors.forename: Bettina
authors.initials: B
authors.lastname: Leber
authors.affiliation: Department of Internal Medicine, Division of Gastroenterology and Hepatology, Medical University of Graz, Graz, Austria.
authors.forename: Vanessa
authors.initials: V
authors.lastname: Stadlbauer
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001424:Bacterial Infections / Q000097:blood* / Q000209:etiology / Q000401:mortality / Q000628:therapy; D003430:Cross-Sectional Studies; D019446:Endotoxemia / Q000097:blood* / Q000209:etiology / Q000401:mortality / Q000473:pathology; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009504:Neutrophils / Q000378:metabolism* / Q000473:pathology; D018384:Oxidative Stress; D051436:Renal Insufficiency, Chronic / Q000097:blood* / Q000401:mortality / Q000628:therapy*; D017582:Renal Replacement Therapy