Serum Ferritin Variations and Mortality in Incident Hemodialysis Patients

Abstract

Background: Higher serum ferritin levels may be influenced by iron use and inflammation, and are associated with higher mortality in hemodialysis (HD) patients. We hypothesized that a major rise in serum ferritin is associated with a higher risk of mortality, irrespective of baseline serum ferritin in incident HD patients. Methods: In a cohort of 93,979 incident HD patients between 2007 and 2011, we examined the association of change in serum ferritin from the baseline patient quarter (first 91 days from dialysis start) to the subsequent quarter with mortality. Multivariable adjustments were done for case-mix and markers of the malnutrition, and inflammation complex and intravenous iron dose. Change in serum ferritin was stratified into 5 groups: <-400, -400 to <-100, -100 to <100, 100 to <400, and ≥400 ng/mL/quarter. Results: The median change in serum ferritin was 89 ng/mL/quarter (interquartile range -55 to 266 ng/mL/quarter). Compared to stable serum ferritin (-100 to <100 ng/mL/quarter), a major rise (≥400 ng/mL/quarter) was associated with higher all-cause mortality (hazard ratio [95% CI] 1.07 [0.99-1.15], 1.17 [1.09-1.24], 1.26 [1.12-1.41], and 1.49 [1.27-1.76] according to baseline serum ferritin: <200, 200 to <500, 500 to <800, and ≥800 ng/mL in adjusted models, respectively. The mortality risk associated with a rise in serum ferritin was robust, irrespective of intravenous iron use. Conclusions: During the first 6-months after HD initiation, a major rise in serum ferritin in those with a baseline ferritin ≥200 ng/mL and even a slight rise in serum ferritin in those with a baseline ferritin ≥800 ng/mL are associated with higher mortality.

Ten-Year Survival of End-Stage Renal Disease Patients Treated with High-Efficiency Online Hemodiafiltration: A Cohort Study of a Center in South East Asia

“…The high-efficiency OL-HDF might already place β 2 M into the lowest level due to the fact that the patients got the maximal survival benefit from effective large molecular toxin clearance. Interestingly, some previous studies also showed the mortality risk of high ferritin in HD patients as in the present study [19-21]. The adverse effects of high iron in the body have been established.…”

Optimal Serum Ferritin Levels for Iron Deficiency Anemia during Oral Iron Therapy (OIT) in Japanese Hemodialysis Patients with Minor Inflammation and Benefit of Intravenous Iron Therapy for OIT-Nonresponders

“…International guidelines for the management of IDA recommend that IV iron should be discontinued when serum ferritin is >1123.5–2696.4 pmol/L [ 3 , 29 ]. However, high levels of CRP [ 6 , 30 ] and serum ferritin of >179.8–1797.6 pmol/L were associated with worse outcome in HD patients [ 14 , 31 , 32 , 33 , 34 ]. In addition, serum ferritin levels of >1123.5–1797.6 pmol/L were associated with high mortality in HD patients in Europe, the U.S. [ 34 , 35 ] and Taiwan [ 31 ].…”

“…However, high levels of CRP [ 6 , 30 ] and serum ferritin of >179.8–1797.6 pmol/L were associated with worse outcome in HD patients [ 14 , 31 , 32 , 33 , 34 ]. In addition, serum ferritin levels of >1123.5–1797.6 pmol/L were associated with high mortality in HD patients in Europe, the U.S. [ 34 , 35 ] and Taiwan [ 31 ]. In these studies [ 31 , 34 , 35 ], the levels of CRP were high in the majority of the HD patients.…”

Impact of Inflammation on Ferritin, Hepcidin and the Management of Iron Deficiency Anemia in Chronic Kidney Disease

“…Thus, inflammation significantly affects upper serum ferritin targets to avoid iron overload for the management of IDA in CKD patients. In support of this hypothesis, in the setting of concomitant inflammation, serum ferritin levels of ≥500–800 ng/mL are found to be predictive of high mortality in HD patients of Europe [ 9 , 101 ] and Taiwan [ 92 ] and USA [ 95 ]. High CRP levels alone may predict high mortality in HD patients [ 62 , 102 ].…”

“…It is controversial whether iron overload is associated with a risk of infection or infection-related mortality [ 91 ]. High serum ferritin has been shown to be an independent risk factor of infection-related mortality in HD patients [ 7 , 92 , 93 , 94 , 95 ]. Bolus dosing of ferric gluconate could increase a risk of infection-related mortality and hospitalization in HD patients with catheter [ 96 ].…”