Inflammation, kidney function and albuminuria in the Framingham Offspring cohort

Abstract

Background: Inflammation and chronic kidney disease (CKD) are both associated with cardiovascular disease (CVD). Whether inflammatory biomarkers are associated with kidney function and albuminuria after accounting for traditional CVD risk factors is not completely understood.

Methods: The sample comprised Framingham Offspring cohort participants (n = 3294, mean age 61, 53% women) who attended the seventh examination cycle (1998-2001). Inflammatory biomarkers [C-reactive protein (CRP), tumour necrosis factor (TNF)-alpha, interleukin-6, TNF receptor 2 (TNFR2), intercellular adhesion molecule-1 (ICAM-1), monocyte chemoattractant protein-1 (MCP-1), P-selectin, CD-40 ligand, osteoprotegerin, urinary isoprostanes, myeloperoxidase and fibrinogen] were measured on fasting blood samples. Serum creatinine-based estimated glomerular filtration rate (eGFR) and serum cystatin C concentration were used to assess kidney function. Urinary albumin-to-creatinine ratio (UACR) was used to assess albuminuria. Linear or logistic regression was used to test associations between biomarkers and kidney measures.

Results: Chronic kidney disease (CKD), defined as eGFR < 59/64 mL/min/1.73 m(2) in women/men, was present in 8.8% (n = 291) of participants. TNF-alpha, interleukin-6, TNFR2, MCP-1, osteoprotegerin, myeloperoxidase and fibrinogen were higher among individuals with CKD; all biomarkers except for urinary isoprostanes were elevated in higher cystatin C quartiles; and TNF-alpha, interleukin-6, TNFR2, ICAM-1 and osteoprotegerin were elevated in higher UACR quartiles-all assessed after multivariable adjustment. Almost 6% and 17% of variability in TNFR2 were explained by CKD status and higher cystatin C quartiles, respectively.

Conclusions: Biomarkers of inflammation are associated with kidney function and albuminuria. In particular, substantial variability in soluble TNFR2 is explained by CKD and cystatin C.

Fig. 1

(A) Age- and sex-adjusted mean standardized inflammatory marker levels by chronic kidney disease status. Bars represent standard errors. CRP, C-reactive protein; TNF, tumour necrosis factor; IL-6, interleukin-6; TNFR2, TNF receptor 2; ICAM1, intercellular adhesion molecule-1; MCP-1, monocyte chemoattractant protein-1; CD40p, CD40 ligand-plasma; OPG, osteoprotegerin; U-Iso, urinary isoprostanes; MPO, myeloperoxidase; Fib, fibrinogen. (B) Age- and sex-adjusted mean inflammatory marker levels by quartile of cystatin C. Bars represent standard errors. (C) Age- and sex-adjusted mean inflammatory marker levels by quartiles of urinary albumin excretion. Bars present standard errors.