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.

Structural and functional differences in gut microbiome composition in patients undergoing haemodialysis or peritoneal dialysis

“…Recently it has been shown that patients undergoing HD have a 2.4 fold higher risk of death compared to PD patients in a large propensity matched study, that could not be attributed to initial use of central venous catheters or lack of pre-dialysis care 19 . HD patients have also been shown particularly prone to endotoxemia and subsequent innate immune dysfunction and innate immune function seems to improve after kidney transplantation 20 . These findings raise the hypothesis that the gut microbiome as major contributor to bacterial translocation and inflammation might be involved in these differences.…”

The Role of Intestinal C‐type Regenerating Islet Derived‐3 Lectins for Nonalcoholic Steatohepatitis

“…Plasma LPS levels were measured using a reporter cell line (hkb-htlr4; Invivogen, San Diego, CA). (25) LPS results were confirmed in FFD-fed animals (data not shown), using a commercially available enzyme-linked immunosorbent assay (CEB526Ge; Cloud-Clone Corp., Katy, TX).…”

“…Aspartate aminotransferase (AST) was measured from plasma obtained from the inferior vena cava, using a kinetic assay (TR70121; Thermo Fisher Scientific). Plasma LPS levels were measured using a reporter cell line (hkb‐htlr4; Invivogen, San Diego, CA) . LPS results were confirmed in FFD‐fed animals (data not shown), using a commercially available enzyme‐linked immunosorbent assay (CEB526Ge; Cloud‐Clone Corp., Katy, TX).…”

Disease severity and proton pump inhibitor use impact strongest on faecal microbiome composition in liver cirrhosis

“…Albumin, bilirubin, hemoglobin, uric acid, creatinine, prothrombin time and CRP were measured in the routine labouratory. LPS was detected in serum with an adapted protocol using HEK‐Blue hTLR4 reporter cells (Invivogen, Toulouse, France) as published previously . All other assays were handled according to manufacturers’ instructions.…”

“…LPS was detected in serum with an adapted protocol using HEK-Blue hTLR4 reporter cells (Invivogen, Toulouse, France) as published previously. 38 All other assays were handled according to manufacturers' instructions. Enzyme linked immunosorbent assay were used to measure calprotectin, zonulin and serum DAO (Immundiagnostic AG, Bensheim, Germany), as well as LBP and sCD14 (Hycult biotechnology, Uden, the Netherlands).…”