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

Abstract

BackgroundSerum ferritin concentration >100 ng/mL was associated with a higher risk of death in hemodialysis patients in Japan, whereas such an association was less clear in hemodialysis patients in Western countries. Since Japanese dialysis patients are generally less inflamed than those in Western countries, inflammation may modify the association between serum ferritin and the adverse outcomes.MethodsWe performed an observational cohort study using data from 2606 Japanese hemodialysis patients who participated in the Dialysis Outcomes and Practice Patterns Study (DOPPS) III (2005–2008) or DOPPS IV (2009–2012). The predictor was serum ferritin category (<50, 50–99.9, 100–199.9, and ≥200 ng/mL), and the primary and secondary outcomes were all-cause mortality and cardiovascular hospitalization, respectively. C-reactive protein (CRP, cut-off by 0.3 mg/dL) and serum albumin (cut-off by 3.8 g/dL) were stratification factors related to systemic inflammation.ResultsAfter adjustment for relevant confounding factors, a U-shaped association was observed between serum ferritin and all-cause mortality in the group with low CRP levels, whereas such relationship was not significant in the high CRP counterparts. In contrast, we found a linear association between serum ferritin and cardiovascular hospitalization in the low CRP and high CRP groups commonly. Similar results were obtained when the total cohort was stratified by serum albumin.ConclusionsSerum ferritin showed different patterns of association with all-cause mortality in hemodialysis patients with versus without inflammation, whereas its association with cardiovascular hospitalization was similar regardless of inflammatory conditions.

Elevated Serum Ferritin Levels Are Predictive of Renal Function Recovery among Patients with Acute Kidney Injury

“…While both inflammation and anemia management practices influenced ferritin levels, the relationship between high ferritin and mortality was attenuated more by adjustment for markers of inflammation than by hemoglobin levels, intravenous iron, and erythropoiesisstimulating agents doses. The recent paper also encourages the view that the association between serum ferritin and allcause mortality in HD patients is modified by inflammation (Shoji et al 2017).…”

Iron status in the elderly: A review of recent evidence

“…In a study of 2,606 (mean age 64 years) patients on hemodialysis without inflammation, Shoji et al (2017) reported that both low and high ferritin levels were significantly associated with all-cause mortality (Cox proportional hazard ratios: 1.79 and 1.55 respectively). Similarly, Park et al (2015) in a prospective cohort study of 946 (mean age 60 years, range 49-70, 61% males) patients found that serum ferritin levels at the start of hemodialysis were independently associated with all-cause mortality risk, infection related and cardiovascular mortality risk (p=0.003, HR1.5, 95% CI 1.156-2.069; p=0.032, HR1.9, 95%CI 1.056-3.476 and p=0.033 HR1.6, 95%CI 1.040-2.474 respectively).…”

“…This shift is more pronounced in older women rather than men and, at least in part, is attributed to their ceased reproductive function (no iron losses related to menstruation or pregnancy). Furthermore, elevated iron stores have been linked to exercise in the aged population (Jehn, 2004;Li et al, 2013Li et al, , 2014Shoji et al, 2017).…”

The Role of Iron in the Pathogenesis of Atherosclerosis

“…Not only iron overload but also iron deficiency and chronic anemia are associated with increased cardiovascular risk, which suggests that the relationship between iron and CVD is not linear but rather U-shaped (Shoji et al 2016). In one prospective cohort of the ARIC Study, the presence of anemia (defined as a hemoglobin concentration <130 g/l in men and <120 g/l in women) was independently associated with increased risk of CVD (HR 1.41 [95 % CI: 1.01, 1.95]) (Sarnak et al 2002).…”