Associations between circulating inflammatory markers and residual renal function in CRF patients.
BACKGROUND
Circulating levels of cytokines and other inflammation markers are markedly elevated in patients with chronic renal failure. This could be caused by increased generation, decreased removal, or both. However, it is not well established to what extent renal function per se contributes to the uremic proinflammatory milieu. The aim of the present study is to analyze the relationship between inflammation and glomerular filtration rate (GFR) in 176 patients (age, 52 +/- 1 years; GFR, 6.5 +/- 0.1 mL/min) close to the initiation of renal replacement therapy.


METHODS
Circulating levels of high-sensitivity C-reactive protein (hsCRP), tumor necrosis factor-alpha (TNF-alpha), interleukin-6 (IL-6), hyaluronan, and neopterin were measured after an overnight fast. Patients subsequently were subdivided into two groups according to median GFR (6.5 mL/min).


RESULTS
Despite the narrow range of GFR (1.8 to 16.5 mL/min), hsCRP, hyaluronan, and neopterin levels were significantly greater in the subgroup with lower GFRs, and significant negative correlations were noted between GFR and IL-6 (rho = -0.18; P < 0.05), hyaluronan (rho = -0.25; P < 0.001), and neopterin (rho = -0.32; P < 0.0005). In multivariate analysis, although age and GFR were associated with inflammation, cardiovascular disease and diabetes mellitus were not.


CONCLUSIONS
These results show that a low GFR per se is associated with an inflammatory state, suggesting impaired renal elimination of proinflammatory cytokines, increased generation of cytokines in uremia, or an adverse effect of inflammation on renal function.
Pecoits-Filho
Roberto
R
Division of Renal Medicine, Department of Clinical Science, Karolinska Institutet, Huddinge University Hospital, Stockholm, Sweden.
Heimbürger
Olof
O
Bárány
Peter
P
Suliman
Mohamed
M
Fehrman-Ekholm
Ingela
I
Lindholm
Bengt
B
Stenvinkel
Peter
P
D015415:Biomarkers; D002097:C-Reactive Protein / Q000032:analysis; D002318:Cardiovascular Diseases / Q000150:complications; D016207:Cytokines / Q000097:blood*; D048909:Diabetes Complications; D005260:Female; D005919:Glomerular Filtration Rate; D006801:Humans; D006820:Hyaluronic Acid / Q000097:blood; D007249:Inflammation / Q000097:blood*; D018836:Inflammation Mediators / Q000097:blood*; D015850:Interleukin-6 / Q000097:blood; D007668:Kidney / Q000503:physiopathology*; D007676:Kidney Failure, Chronic / Q000097:blood* / Q000150:complications / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D019798:Neopterin / Q000097:blood; D012709:Serum Albumin / Q000032:analysis; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis
D015415:Biomarkers; D016207:Cytokines; D018836:Inflammation Mediators; D015850:Interleukin-6; D012709:Serum Albumin; D014409:Tumor Necrosis Factor-alpha; D019798:Neopterin; D006820:Hyaluronic Acid; D002097:C-Reactive Protein