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.
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).
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.
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.