Atherosclerotic cardiovascular disease (CVD), malnutrition, and inflammation are common clinical features of chronic renal failure and are associated with increased mortality. Elevated levels of C-reactive protein (CRP) and cytokines are commonly observed in dialysis patients and have been shown to predict mortality. Serum hyaluronan previously has been used as a marker of an inflammatory reaction, irrespective of its cause. We have determined serum levels of albumin and hyaluronan, as well as the prevalence of malnutrition (subjective global assessment, 2 to 4), inflammation (CRP >/= 10 mg/L), and overt CVD in a cohort of 97 predialysis patients (52 +/- 13 years). Moreover, we determined the outcome of these patients 29 +/- 11 months after the basal measurement of hyaluronan. Serum levels of hyaluronan (median) were markedly elevated in predialysis patients with signs of malnutrition (127.1 v 50.5 ng/mL; P < 0.0001), inflammation (130.1 v 55.0 ng/mL; P < 0.0001) and CVD (118.8 v 56.0 ng/mL; P < 0.001). The levels of log hyaluronan correlated significantly to log CRP (R = 0.35; P < 0.001), serum albumin (R = -0.40; P < 0.0001), CVD (R = 0.36; P < 0.001), and age (R = 0.40; P < 0.0001), respectively. Survival analysis by the Cox regression model showed that elevated hyaluronan levels were, independent of CVD, CRP, and age, significantly related to an increased mortality rate. The current study showed that markedly elevated serum hyaluronan levels are found in predialysis patients with malnutrition, inflammation, and CVD and that serum hyaluronan is a risk predictor of poor survival in dialysis.