Inflammation and Progression of CKD: The CRIC Study

Background and objectives CKD is a global public health problem with significant mortality and morbidity. Design, setting, participants, & measurements We examined the multivariable association of plasma levels of IL-1, IL-1 receptor antagonist, IL-6, TNF-alpha, TGF-beta, high-sensitivity-C-reactive protein, fibrinogen, and serum albumin with progression of CKD in 3430 Chronic Renal Insufficiency Cohort study participants. Results Over a median follow-up time of 6.3 years, 899 participants reached the composite end point of >= 50% decline in eGFR from baseline or onset of ESRD. Elevated plasma levels of fibrinogen, IL-6, and TNF-alpha and lower serum albumin were associated with a greater decline in eGFR over time. After adjusting for demographics, BP, laboratory variables, medication use, and baseline eGFR, hazard ratios for the composite outcome were greater for the patients in the highest quartile of fibrinogen (hazard ratio, 2.05; 95% confidence interval, 1.64 to 2.55; P<0.001), IL-6 (hazard ratio, 1.44; 95% confidence interval, 1.17 to 1.77; P<0.01), and TNF-alpha (hazard ratio, 1.94; 95% confidence interval, 1.52 to 2.47; P<0.001) compared with those in the respective lowest quartiles. The hazard ratio was 3.48 (95% confidence interval, 2.88 to 4.21; P<0.001) for patients in the lowest serum albumin quartile relative to those in the highest quartile. When also adjusted for albuminuria, the associations of fibrinogen (hazard ratio, 1.49; 95% confidence interval, 1.20 to 1.86; P<0.001), serum albumin (hazard ratio, 1.52; 95% confidence interval, 1.24 to 1.87; P<0.001), and TNF-alpha (hazard ratio, 1.42; 95% confidence interval, 1.11 to 1.81; P<0.001) with outcome were attenuated but remained significant. Conclusions Elevated plasma levels of fibrinogen and TNF-alpha and decreased serum albumin are associated with rapid loss of kidney function in patients with CKD.