Circulating endotoxemia: a novel factor in systemic inflammation and cardiovascular disease in chronic kidney disease.
OBJECTIVE
Translocated endotoxin derived from intestinal bacteria has a wide range of adverse effects on cardiovascular (CV) structure and function, driving systemic inflammation, atherosclerosis and oxidative stress. This study's aim was to investigate endotoxemia across the spectrum of chronic kidney disease (CKD).


METHODS
Circulating endotoxin was measured in 249 patients comprising CKD stage 3 to 5 and a comparator cohort of hypertensive patients without significant renal impairment. Patients underwent extended CV assessment, including pulse wave velocity and vascular calcification. Hemodialysis (HD) patients also received detailed echocardiographic-based intradialytic assessments. Patients were followed up for 1 year to assess survival.


RESULTS
Circulating endotoxemia was most notable in those with the highest CV disease burden (increasing with CKD stage), and a sharp increase was observed after initiation of HD. In HD patients, predialysis endotoxin correlated with dialysis-induced hemodynamic stress (ultrafiltration volume, relative hypotension), myocardial stunning, serum cardiac troponin T, and high-sensitivity C-reactive protein. Endotoxemia was associated with risk of mortality.


CONCLUSIONS
CKD patients are characteristically exposed to significant endotoxemia. In particular, HD-induced systemic circulatory stress and recurrent regional ischemia may lead to increased endotoxin translocation from the gut. Resultant endotoxemia is associated with systemic inflammation, markers of malnutrition, cardiac injury, and reduced survival. This represents a crucial missing link in understanding the pathophysiology of the grossly elevated CV disease risk in CKD patients, highlighting the potential toxicity of conventional HD and providing a novel set of potential therapeutic strategies to reduce CV mortality in CKD patients.
McIntyre
Christopher W
CW
Department of Renal Medicine, Royal Derby Hospital, Uttoxeter Road, Derby, DE22 3NE, United Kingdom. chris.mcintyre@nottingham.ac.uk
Harrison
Laura E A
LE
Eldehni
M Tarek
MT
Jefferies
Helen J
HJ
Szeto
Cheuk-Chun
CC
John
Stephen G
SG
Sigrist
Mhairi K
MK
Burton
James O
JO
Hothi
Daljit
D
Korsheed
Shvan
S
Owen
Paul J
PJ
Lai
Ka-Bik
KB
Li
Philip K T
PK
D000328:Adult; D000368:Aged; D002318:Cardiovascular Diseases / Q000209:etiology*; D002908:Chronic Disease; D003430:Cross-Sectional Studies; D019446:Endotoxemia / Q000150:complications*; D005260:Female; D006801:Humans; D007249:Inflammation / Q000209:etiology*; D007674:Kidney Diseases / Q000150:complications*; D016014:Linear Models; D008297:Male; D008875:Middle Aged; D006435:Renal Dialysis