Circulating monocyte subpopulations with high expression of angiotensin-converting enzyme predict mortality in patients with end-stage renal disease.
BACKGROUND
Circulating monocytes can be divided into distinct populations according to their expression of surface markers CD14 and CD16. In patients with chronic kidney disease (CKD), the cell fraction expressing high levels of CD14 and CD16 is expanded and the numbers of these cells are predictive for cardiovascular disease. The present pilot study describes the predictive role of a combined biomarker consisting of high numbers of CD14(++)CD16(+) cells together with high expression of angiotensin-converting enzyme (ACE) on these cells for mortality in CKD Stage V(D) (dialysis) patients.


METHODS
In a prospective observational study, monocyte subpopulations were enumerated and ACE expression was quantified in 74 CKD patients by flow cytometry. Patients were assigned to one of four groups according to monocyte population numbers and ACE expression below and above the respective medians and observed for mortality and cardiovascular events for 46 months.


RESULTS
Patients stratified to the 'high CD14(++)CD16(+), high ACE' group (n = 22) had a dramatically enhanced mortality of 70% at 2 years compared to all other patient groups (mortality 14.8%, HR 4.86 [95% CI 2.17-10.86, P < 0.0001]). Atherosclerosis-associated events predominated among the causes of death.


CONCLUSIONS
This study describes a new combined biomarker of monocyte subpopulation numbers together with high expression of ACE that has a striking predictive value for mortality of CKD patients. Further research into the pathophysiologic background of this observation is warranted.
Ulrich
Christof
C
Department of Internal Medicine II, Martin Luther University of Halle-Wittenberg, Halle, Germany.
Heine
Gunnar H
GH
Seibert
Eric
E
Fliser
Danilo
D
Girndt
Matthias
M
D000368:Aged; D015415:Biomarkers / Q000097:blood; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D053208:Kaplan-Meier Estimate; D007676:Kidney Failure, Chronic / Q000097:blood* / Q000401:mortality*; D018950:Lipopolysaccharide Receptors / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D009000:Monocytes / Q000378:metabolism*; D007703:Peptidyl-Dipeptidase A / Q000097:blood*; D010865:Pilot Projects; D011237:Predictive Value of Tests; D011379:Prognosis; D011446:Prospective Studies; D017452:Receptors, IgG / Q000378:metabolism
D015415:Biomarkers; D018950:Lipopolysaccharide Receptors; D017452:Receptors, IgG; D007703:Peptidyl-Dipeptidase A