Serum Ferritin Predicts Mortality Regardless of Inflammatory and Nutritional Status in Patients Starting Dialysis: A Prospective Cohort Study

Abstract

Background: The impact of serum ferritin on prognosis in patients starting hemodialysis (HD) is not fully elucidated. Methods: A prospective cohort of 946 incident HD patients from 26 dialysis centers in Korea was selected for this study. Patients were divided into tertiles according to natural logarithm (Ln) ferritin concentrations. Results: During a median follow-up of 39 months, 88 (9.3%) patients died. Multivariate Cox proportional hazard analysis demonstrated that Ln ferritin was independently associated with an increase in cardiovascular mortality risk (hazard ratio (HR) 1.604, 95% CI 1.040-2.474, p = 0.033), infection-related mortality risk (HR 1.916, 95% CI 1.056-3.476, p = 0.032), and all-cause mortality risk (HR 1.547, 95% CI 1.156-2.069, p = 0.003). Conclusion: Serum ferritin levels at the time of HD commencement were a significant independent risk factor for mortality regardless of systemic inflammation and nutritional status. Therefore, elevated serum ferritin levels could be an effective indicator for prognosis.

Both low and high serum ferritin levels predict mortality risk in hemodialysis patients without inflammation

“…They discussed that the increased mortality risk in those with high serum ferritin concentration was due mostly to the confounding effects by systemic inflammation and/or malnutrition. In contrast, a recent study by Park et al [7] showed that the groups with high serum ferritin level (>142.6 ng/mL) showed a higher all-cause mortality risk than those with lower serum ferritin levels, and that the association between serum ferritin and mortality risk was independent of systemic inflammation and nutritional status in incident hemodialysis patients by including CRP as one of the covariates in the Cox model. The median serum ferritin in the Korean hemodialysis cohort was 213 ng/mL, much lower than that in the US patients, but slightly higher than that of Japanese hemodialysis patients [5, 16].…”

“…The median serum ferritin in the Korean hemodialysis cohort was 213 ng/mL, much lower than that in the US patients, but slightly higher than that of Japanese hemodialysis patients [5, 16]. The study by Park et al [7] may be of clinical importance because the results suggest the possible direct effects of ferritin independent of inflammation. However, their study does not answer the question whether or not systemic inflammation affects the association between serum ferritin and mortality risk.…”

“…As discussed by Park et al [7], ferritin appears to reflect some systemic conditions, other than inflammation, that could result in increased mortality and other adverse outcomes. Serum ferritin was reported to be increased in the presence of renal cell carcinoma [17] and other malignancies [18].…”

“…On the other hand, it is known that there is considerable overlapping in the roles of inflammation, oxidative stress and PEW in prognosis of patients with CKD [14]. In addition, serum ferritin and CRP concentrations correlate with each other to a moderate extent [7]. Therefore, among subjects with signs of inflammation or at a higher grade of inflammation, it may be difficult to separate the roles of ferritin and inflammation in epidemiologic studies, as we report in this study.…”

“…Based on the facts that serum ferritin is lower in Japanese hemodialysis patients than those in other countries [6], that serum ferritin is increased in the presence of inflammation [7], and that the Japanese dialysis patients are generally less inflamed as shown by a lower C-reactive protein (CRP) level than those in the Western countries [8, 9], we hypothesized that the association between serum ferritin and the adverse outcomes could be modified by the presence of inflammation.…”