Glomerular function in relation to circulating adhesion molecules and inflammation markers in a general population

Abstract

Background: Inflammation is a hallmark of chronic kidney disease (CKD) and stimulates glomerular expression of vascular adhesion molecules (VCAMs). We investigated in a general population whether estimated glomerular filtration rate (eGFR) is associated with circulating adhesion molecules, inflammation markers or both.

Methods: We measured serum levels of five adhesion molecules [VCAM-1, intracellular adhesion molecule-1 (ICAM-1), P-selectin, E-selectin and monocyte chemoattractant protein-1 (MCP-1)] and seven inflammation markers [C-reactive protein (CRP), neutrophil gelatinase-associated lipocalin (NGAL), tumour necrosis factor receptor 1 (TNF-R1), TNF-α, interleukin 6 (IL-6), IL-8 and vascular endothelial growth factor] in 1338 randomly recruited people (50.8% women, mean age 51.7 years, eGFR 79.9 mL/min/1.73 m2).

Results: In multivariable-adjusted analyses, eGFR decreased (P ≤ 0.004) with higher VCAM-1 (association size expressed in mL/min/1.73 m2 for a doubling of the marker, -2.99), MCP-1 (-1.19), NGAL (-1.19), TNF receptor 1 (-2.78), TNF-α (-2.28) and IL-6 (-0.94). The odds ratios of having eGFR <60 versus ≥60 mL/min/1.73 m2 (n = 138 versus 1200) were significant (P ≤ 0.001) for VCAM-1 (1.77), MCP-1 (1.32), NGAL (1.26), TNF-R1 (1.49), TNF-α (1.45) and IL-6 (1.20). Compared with 24-h albuminuria, VCAM-1 increased (P <0.0001) the area under the curve from 0.57 to 0.65, MCP-1 to 0.67 and TNF-R1 to 0.79, but TNF-R1 outperformed both adhesion molecules (P < 0.0001).

Conclusions: In a general population, eGFR is inversely associated with circulating adhesion molecules VCAM-1 and MCP-1 and several inflammation markers, but inflammation markers, in particular TNF-R1 and TNF-α, identify patients with eGFR <60 mL/min/1.73 m2 more accurately.

FIGURE 1

Flowchart of participants included in the cross-sectional and longitudinal analyses.

FIGURE 2

–Log10(P) probability plot of the multivariable-adjusted associations of eGFR (continuous or categorical) with the baseline biomarkers. In categorical analyses, eGFR <60 and ≥60 mL/min/1.73 m² were contrasted. All analyses were adjusted for mean arterial pressure, waist:hip ratio, smoking, plasma glucose, γ-glutamyltransferase, total:HDL cholesterol ratio, 24-h microalbuminuria and use of diuretics, inhibitors of the renin–angiotensin system (β-blockers, ACE inhibitors and angiotensin type 1 receptor blockers), vasodilators (calcium channel blockers and α-blockers), lipid-lowering drugs and biomarker at baseline. The longitudinal analyses were additionally adjusted for follow-up duration.

FIGURE 3

AUC for the adhesion molecules and inflammation markers in the discrimination between eGFR Stage ≥3 versus Stage ≤2 in the baseline study. Vertical bars denote the 95% CI. The shaded area represents the 95% CI of the AUC for 24-h microalbumiuria. AUCs for the biomarkers were ordered by magnitude.

FIGURE 4

ROC curves for prediction of eGFR decline from ≥60 to <60 mL/min/1.73 m². Blue, green, red and black lines identify 24-h microalbuminuria and circulating VCAM-1, MCP-1 and TNF-R1 at baseline, respectively.