Association between Albuminuria, Kidney Function, and Inflammatory Biomarker Profile in CKD in CRIC

Background and objectives Increased risk of mortality in patients with CKD has been attributed to inflammation. However, the association between kidney function, albuminuria, and biomarkers of inflammation has not been examined in a large cohort of CKD patients. Design, setting, participants, & measurements This study measured the plasma levels of IL-1 beta, IL-1 receptor antagonist (IL-1RA), IL-6, TNF-alpha, TGF-beta, high-sensitivity C-reactive protein (hs-CRP), fibrinogen, and serum albumin in 3939 participants enrolled in the Chronic Renal Insufficiency Cohort study between June 2003 and September 2008. An inflammation score was established based on plasma levels of IL-1 beta, IL-6, TNF-alpha, hs-CRP, and fibrinogen. Estimated GFR (eGFR) and serum cystatin C were used as measures of kidney function. Albuminuria was quantitated by urine albumin to creatinine ratio (UACR). Results Plasma levels of IL-1 beta, IL-IRA, IL-6, TNF-alpha, hs-CRP, and fibrinogen were higher among participants with lower levels of eGFR. Inflammation score was higher among those with lower eGFR and higher UACR. In regression analysis adjusted for multiple covariates, eGFR, cystatin C, and UACR were strongly associated with fibrinogen, serum albumin, IL-6, and TNF-alpha. Each unit increase in eGFR, cystatin C, and UACR was associated with a -1.2% (95% confidence interval, -1.4, -1), 64.9% (56.8, 73.3) and 0.6% (0.4, 0.8) change in IL-6, respectively (P<0.001). Conclusions Biomarkers of inflammation were inversely associated with measures of kidney function and positively with albuminuria. Clin J Am Soc Nephrol 7: 1938-1946, 2012. doi: 10.2215/CJN.03500412