Endotoxemia in End‐Stage Kidney Disease

Abstract

Chronic unexplained inflammation remains a prevalent and clinically significant problem for patients with end-stage kidney disease (ESKD), especially in the dialysis population. The causes of persistent inflammation are likely to be multifactorial, but the underlying mechanisms remain to be elucidated. Endotoxins are reported to play a significant role in the pathogenesis of inflammation in patients with ESKD. However, blood endotoxin measurement with the Limulus amoebocyte lysate (LAL) assay is difficult with current detection systems. The reported degree and prevalence of endotoxemia varies in the literature. There are questions as to whether endotoxemia is truly present; whether the varied findings are due to methodological issues with the LAL assay and whether any endotoxemia that might be present plays a role in chronic inflammation frequently observed in ESKD patients. This review will discuss the challenges of accurate blood endotoxin detection, the potential source of blood endotoxins, and the significance of endotoxemia to patient with ESKD.

Cardiovascular Disease in Dialysis Patients

“…Endotoxaemia not only occurs in sepsis, but has also been identified in congestive heart failure and in ESKD [149][150][151]. Current endotoxin detection assays are however limited by their poor sensitivity and validation in ESKD [152]. Potential sources of endotoxaemia that are pertinent to the ESKD population include contaminated dialysate, dialysis catheters and circuitry (HD and PD), peritoneal membrane dysfunction, gastrointestinal bacterial translocation and periodontal disease [12,152].…”

“…Current endotoxin detection assays are however limited by their poor sensitivity and validation in ESKD [152]. Potential sources of endotoxaemia that are pertinent to the ESKD population include contaminated dialysate, dialysis catheters and circuitry (HD and PD), peritoneal membrane dysfunction, gastrointestinal bacterial translocation and periodontal disease [12,152]. Preventative strategies such as avoidance of temporary dialysis catheters and use of ultrapure water have been shown to reduce endotoxin levels [153,154].…”

The Effect of Intra-Dialytic Exercise on Inflammation and Blood Endotoxin Levels

“…Endotoxemia in dialysis patients is a frequently reported phenomenon and associated with inflammation [11]. However, blood endotoxin detection is difficult and all published studies in the dialysis population have utilized the limulus amebocyte lysate (LAL) assay [11], a biological assay based on the blood of the horseshoe crab [12].…”

“…Endotoxemia in dialysis patients is a frequently reported phenomenon and associated with inflammation [11]. However, blood endotoxin detection is difficult and all published studies in the dialysis population have utilized the limulus amebocyte lysate (LAL) assay [11], a biological assay based on the blood of the horseshoe crab [12]. This assay is not endotoxin-specific and can be activated by (1→3)-β-D glucan (BG), which are major carbohydrate constituents of cereal, yeast and fungal cell walls [13,] potentially leading to falsely elevated estimates of endotoxin levels.…”

“…It is therefore important to rule out BG interference when measuring blood endotoxin in HD patients using the LAL assay. With one notable exception [15], nearly all studies did not take measures to exclude false positive activation of the LAL assay by BG [11]. …”