Iron Supplementation and Mortality in Incident Dialysis Patients: An Observational Study

Zitt, Emanuel; Sturm, Gisela; Kronenberg, Florian; Neyer, Ulrich; Knoll, Florian; Lhotta, Karl; Weiss, Günter

doi:10.1371/journal.pone.0114144

Cited by 36 publications

(36 citation statements)

References 56 publications

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“…In another observational study, ferritin <800 ng/mL in incident dialysis patients was associated with lower mortality risk after iron supplementation [16]. Recently published guidelines recommended considering iron administration in dialysis patients with ferritin ≤500 ng/mL for safety [4, 20].…”

Section: Discussionmentioning

confidence: 99%

“…Higher ferritin levels ≥800 ng/mL may be detrimental to patient survival and has been found to be associated with higher mortality risk in dialysis patients after adjustment for iron supplementation, safety of iron administration, malnutrition, or inflammation [16–18]. However, no study has investigated the relationship of abrupt changes in ferritin with mortality in incident HD patients.…”

Section: Introductionmentioning

confidence: 99%

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Serum Ferritin Variations and Mortality in Incident Hemodialysis Patients

et al. 2017

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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.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Serum Ferritin Variations and Mortality in Incident Hemodialysis Patients

et al. 2017

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“…In contrast, intravenous (i.v.) iron preparations allow effective administration of high iron doses [4], which are generally considered to be well tolerated [5, 6]. …”

Section: Introductionmentioning

confidence: 99%

Impact of individual intravenous iron preparations on the differentiation of monocytes towards macrophages and dendritic cells

Fell¹,

Seiler-Mußler²,

Sellier³

et al. 2016

Nephrol. Dial. Transplant.

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BackgroundTreatment of iron deficiency with intravenous (i.v.) iron is a first-line strategy to improve anaemia of chronic kidney disease. Previous in vitro experiments demonstrated that different i.v. iron preparations inhibit differentiation of haematopoietic stem cells to monocytes, but their effect on monocyte differentiation to macrophages and mature dendritic cells (mDCs) has not been assessed. We investigated substance-specific effects of iron sucrose (IS), sodium ferric gluconate (SFG), ferric carboxymaltose (FCM) and iron isomaltoside 1000 (IIM) on monocytic differentiation to M1/M2 macrophages and mDCs.MethodsVia flow cytometry and microRNA (miRNA) expression analysis, we morphologically and functionally characterized monocyte differentiation to M1/M2 macrophages and mDCs after monocyte stimulation with IS, SFG, FCM and IIM (0.133, 0.266 and 0.533 mg/mL, respectively). To assess potential clinical implications, we compared monocytic phagocytosis capacity in dialysis patients who received either 500 mg IS or IIM.ResultsPhenotypically, IS and SFG dysregulated the expression of macrophage (e.g. CD40, CD163) and mDC (e.g. CD1c, CD141) surface markers. Functionally, IS and SFG impaired macrophage phagocytosis capacity. Phenotypic and functional alterations were less pronounced with FCM, and virtually absent with IIM. In miRNA expression analysis of mDCs, IS dysregulated miRNAs such as miR-146b-5p and miR-155-5p, which are linked to Toll-like receptor and mitogen-activated protein kinase signalling pathways. In vivo, IS reduced monocytic phagocytosis capacity within 1 h after infusion, while IIM did not.ConclusionsThis study demonstrates that less stable i.v. iron preparations specifically affect monocyte differentiation towards macrophages and mDCs.

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“…The followup period was adequate for analyzing the effects of the treatment on anemia parameters, but it was not valid for evaluating the long-term outcomes associated with each formulation. Further to above specified potential iron accumulation in tissues such as liver, heart and kidney, high doses of ESAs [43,44] and/or IV iron [45,46] have been linked to increased mortality in HD patients. In this study the use of iron sucrose similar is associated with higher ESA doses and higher IV iron doses, than with the IV iron original formulation.…”

Section: Discussionmentioning

confidence: 99%