Changes in fat mass correlate with changes in soluble sCD163, a marker of mature macrophages, in patients with CKD.
BACKGROUND
Recently, adipose tissue was shown to contain macrophages capable of contributing to systemic inflammation and cardiovascular disease (CVD). Here, we investigate this putative relationship in patients with chronic kidney disease (CKD) by using the novel macrophage marker soluble (s)CD163.


METHODS
One hundred twenty patients with CKD stage 5 (mean glomerular filtration rate [GFR], 7 +/- 1 mL/min [0.12 +/- 0.02 mL/s; mean age, 53 +/- 1 years; 65% men), 38 patients with CKD stages 3 to 4 (mean GFR, 33 +/- 3 mL/min [0.55 +/- 0.05 mL/s]; mean age, 67 +/- 2 years; 68% men), and 28 healthy controls (mean GFR, 89 +/- 3 mL/min [1.48 +/- 0.05 mL/s]; mean age, 63 +/-2 years; 69% men) were characterized post hoc with a follow-up of up to 5 years (mean, 47 +/- 1 months). sCD163 levels, body composition (dual-energy x-ray absorptiometry), clinical parameters, and levels of circulating inflammatory markers (enzyme-linked immunosorbent assay) were assessed at baseline and, in a subset population, after 1 year of dialysis therapy (hemodialysis, n = 19; peritoneal dialysis, n = 30).


RESULTS
sCD163 level increased in patients with both severe (median, 4.3 mg/L; range, 1.3 to 23.4 mg/L) and moderate (median, 3.6 mg/L; range, 1.6 to 9.8 mg/L) CKD compared with controls (median, 2.6 mg/L; range, 0.8 to 7.6 mg/L; P < 0.001). Furthermore, sCD163 levels correlated with both truncal (rho = 0.17; P < 0.05) and total (rho = 0.17; P < 0.05) fat mass, as well as with all measured markers of inflammation and endothelial adhesion molecules. After 1 year, patients who increased body fat mass (average, 11% +/- 5% versus -5% +/- 5%; P < 0.05) also showed a significant increase in sCD163 levels (median, 2.2 versus -0.97 mg/L; P < 0.01). Finally, patients with sCD163 levels greater than 4.0 mg/L had a statistically significantly worse outcome than patients with sCD163 levels less than this value, even after adjustment for age, sex, and diabetes mellitus (chi-square = 19.98; P < 0.001). However, this effect was lost after adjustment for either inflammation or CVD.


CONCLUSIONS
We show that increasing fat mass is associated with increasing levels of sCD163, a circulating marker of macrophages also associated with inflammatory biomarkers. We thus hypothesize that adipose tissue macrophages may have a role in the proinflammatory state observed in patients with renal disease. Finally, we propose the term "uremic-metabolic syndrome" to describe this state of increased adipose tissue signaling in patients with uremia, a phenomenon that may share some characteristics with the metabolic syndrome of obesity.
Axelsson
Jonas
J
Division of Renal Medicine, Department of Molecular Medicine, Karolinska Institutet, Stockholm, Sweden. jonas.axelsson@ki.se
Møller
Holger Jon
HJ
Witasp
Anna
A
Qureshi
Abdul Rashid
AR
Carrero
Juan Jesus
JJ
Heimbürger
Olof
O
Bárány
Peter
P
Alvestrand
Anders
A
Lindholm
Bengt
B
Moestrup
Søren K
SK
Stenvinkel
Peter
P
D000273:Adipose Tissue / Q000502:physiology*; D015703:Antigens, CD / Q000097:blood*; D015214:Antigens, Differentiation, Myelomonocytic / Q000097:blood*; D001823:Body Composition; D016207:Cytokines / Q000097:blood; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006706:Homeostasis / Q000502:physiology; D006801:Humans; D007249:Inflammation / Q000097:blood; D007676:Kidney Failure, Chronic / Q000097:blood / Q000628:therapy; D008262:Macrophage Activation / Q000502:physiology; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D009752:Nutritional Status; D012372:ROC Curve; D011956:Receptors, Cell Surface / Q000097:blood*; D006435:Renal Dialysis; D051436:Renal Insufficiency, Chronic / Q000097:blood* / Q000628:therapy; D000098902:CD163 Antigen
D015703:Antigens, CD; D015214:Antigens, Differentiation, Myelomonocytic; D000098902:CD163 Antigen; D016207:Cytokines; D011956:Receptors, Cell Surface