TLR-4+ peripheral blood monocytes and cardiovascular events in patients with chronic kidney disease--a prospective follow-up study.
BACKGROUND
Atherosclerosis is an inflammatory process mediated by circulating immune cells, including monocytes. There is accumulating evidence for the involvement of Toll-like receptor 4 (TLR-4) as a mediator of atherogenesis.


METHODS
We evaluated the association between CD14+/TLR-4+ monocytes in peripheral blood (flow cytometry) and future cardiovascular events (CVE), e.g. myocardial infarction, percutaneous transluminal coronary angioplasty (including stenting), aortocoronary bypass, stroke and angiographically verified stenosis of peripheral arteries and cardiovascular (CV) death, in 191 patients with chronic kidney disease Stage V receiving hemodialysis therapy.


RESULTS
At baseline, CD14+/TLR-4+ monocytes correlated significantly with age (r = 0.2; P = 0.007), high-sensitivity C-reactive protein (r = 0.2; P = 0.008) and mean arterial pressure (r = -0.2; P = 0.02), but not with gender (P = 0.5), smoking (P = 0.6) and the presence of diabetes (P = 0.5). During a median follow-up period of 36 [1-54] months, 79 (41%) patients experienced a CVE. A total of 55 patients died during the follow-up period, 25 of those due to a confirmed CV cause. Log-rank test did not reveal statistical significance for TLR-4+ monocytes concerning incident CVE (P = 0.3), CV death (P = 0.85) and overall death (P = 0.8). In a multiple Cox-regression analysis, we identified age (P = 0.003) and smoking (P = 0.001) as the only independent variables associated with incident CVE.


CONCLUSIONS
Unexpectedly, we could not detect an association between CD14+/TLR-4+ monocytes and incident CVE as well as CV death in stable hemodialysis patients. Further studies have to clarify the potential role of this cell population for CV outcome in this population.
Division of Nephrology, Department of Internal Medicine, Hannover Medical School, Hannover, Germany.
Johan M
JM
Lorenzen
Sascha
S
David
Alena
A
Richter
Kirsten
K
de Groot
Jan T
JT
Kielstein
Hermann
H
Haller
Thomas
T
Thum
Danilo
D
Fliser
D000368:Aged; D002097:C-Reactive Protein / Q000378:metabolism; D002318:Cardiovascular Diseases / Q000175:diagnosis / Q000209:etiology / Q000378:metabolism*; D005260:Female; D005434:Flow Cytometry; D005500:Follow-Up Studies; D005919:Glomerular Filtration Rate; D006801:Humans; D007676:Kidney Failure, Chronic / Q000150:complications / Q000378:metabolism*; D007677:Kidney Function Tests; D007963:Leukocytes, Mononuclear / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D009000:Monocytes / Q000378:metabolism*; D011379:Prognosis; D011446:Prospective Studies; D006435:Renal Dialysis; D012307:Risk Factors; D015996:Survival Rate; D051197:Toll-Like Receptor 4 / Q000378:metabolism*
C495345:TLR4 protein, human; D051197:Toll-Like Receptor 4; D002097:C-Reactive Protein