Early Changes in Monocyte Adhesion Molecule Expression and Tumor Necrosis Factor-α Levels in Chronic Kidney Disease - A 5-Year Prospective Study.
Despite the absence of clinical symptoms, patients with chronic kidney disease (CKD) exhibit elevated levels of pro-inflammatory markers. To investigate whether it is possible to detect inflammatory activity and altered monocyte function at an early stage of renal disease, we studied patients with CKD stages 2-3 over 5 years.



The expression of adhesion molecules on monocytes at resting state and after stimulation with formyl-methionyl-leucyl-phenylalanine (fMLP), as well as oxidative metabolism capacity was measured with flow cytometry in 108 CKD patients and healthy controls. Soluble markers of inflammation, such as cytokines, were analyzed using the Milliplex technique.



Patients showed significantly lower CD11b expression after stimulation during the 3rd (p = 0.002) and the 5th year (p < 0.001), together with a lower oxidative burst in response to fMLP over time (p = 0.02). The expression of CD62L on resting monocytes was lower during the 3rd (p = 0.001) and the 5th (p = 0.001) year in patients. Levels of tumor necrosis factor-α and RANTES were significantly increased (p = 0.001, p = 0.006) and interleukin-12 levels were also higher in CKD patients during the 5th year (p = 0.007).



Monocytes in CKD stages 2-3 show emerging functional abrasions, with altered adhesion molecule expression and impaired fMLP response. These findings suggest that a transformation of monocyte function occurs at an early phase of renal impairment and may together with increased plasma levels of pro-inflammatory cytokines contribute to the higher vulnerability of CKD patients to comorbidities, such as infections and cardiovascular disease.
Department of Nephrology, Karolinska Institutet, and Karolinska University Hospital, Stockholm, Sweden.
Carin
C
Wallquist
Ladan
L
Mansouri
Mattias
M
Norrbäck
Britta
B
Hylander
Stefan H
SH
Jacobson
Joachim
J
Lundahl
D000328:Adult; D039481:CD11b Antigen / Q000097:blood*; D016022:Case-Control Studies; D002478:Cells, Cultured; D018946:Chemokine CCL5 / Q000097:blood; D005260:Female; D006801:Humans; D018664:Interleukin-12 / Q000097:blood; D019041:L-Selectin / Q000097:blood*; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D009000:Monocytes / Q000187:drug effects / Q000378:metabolism* / Q000502:physiology; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000494:pharmacology; D011446:Prospective Studies; D051436:Renal Insufficiency, Chronic / Q000097:blood*; D016897:Respiratory Burst / Q000187:drug effects; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000097:blood*
D039481:CD11b Antigen; D018946:Chemokine CCL5; D014409:Tumor Necrosis Factor-alpha; D019041:L-Selectin; D018664:Interleukin-12; D009240:N-Formylmethionine Leucyl-Phenylalanine