Iatrogenic iron overload and its potential consequences in patients on hemodialysis

Rostoker, Guy; Vaziri, Nosratola D.

doi:10.1016/j.lpm.2017.10.014

Cited by 27 publications

(35 citation statements)

References 85 publications

(250 reference statements)

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“…Iron metabolism differs markedly between patients undergoing peritoneal dialysis (PD) and hemodialysis (HD). Peritoneal dialysis has fewer sources of iron deficiency, including blood loss directly related to the hemodialysis technique and occult gastrointestinal tract bleeding aggravated by anticoagulation of hemodialysis circuits . This lower need for iron store replenishment explains the more conservative strategy advocated for PD patients in current guidelines, with a ferritin target of >100 μg/L and oral iron for first‐line therapy .…”

Section: Iron Products As Second‐line Treatment In Peritoneal Dialmentioning

confidence: 99%

“…Partial correction of anemia with routine use of recombinant erythropoiesis‐stimulating agents (ESA) over the past three decades has deeply improved quality of life in most end‐stage renal disease (ESRD) patients, reducing the need for blood transfusions and anemia‐related morbidities . ESA use frequently leads to functional iron deficiency (termed iron‐restricted anemia), due to massive transfer of stored iron to erythroid progenitor cells and inadequate iron mobilization from repleted stores (related to high levels of hepcidin), together with true iron deficiency due to blood loss related to the hemodialysis procedure, uremic enteropathy and blood sampling . True iron deficiency is thus a major clinical concern, giving rise to ESA resistance, impaired cellular function and aggravated cardiac insufficiency which is frequently encountered in this setting …”

Section: Introduction and General Remarksmentioning

confidence: 99%

“…Intravenous (IV) iron is typically administered during dialysis sessions, with almost all ESA‐treated hemodialysis patients receiving parenteral iron to restore the body iron pool before and during ESA therapy. Iron therapy is considered, with ESA, as the mainstay of anemia treatment in ESRD . Iron metabolism is a closed system, critically regulated by hepcidin without any excretory mechanisms for excess iron.…”

Section: Introduction and General Remarksmentioning

confidence: 99%

“…Iron metabolism is a closed system, critically regulated by hepcidin without any excretory mechanisms for excess iron. As a result, iron levels in ESRD patients chronically treated with IV iron products may exceed their ongoing blood losses, exposing them to an increased risk of positive iron balance . These twin risks of iron deficiency and iron overload must be closely monitored .…”

Section: Introduction and General Remarksmentioning

confidence: 99%

“…By activating macrophages, elevated hepcidin can cause atherosclerotic plaque instability and increase the risk of ischemic cardiovascular complications . High hepcidin‐25 levels were recently linked to cardiovascular events in dialysis patients, pointing to its role as a mediator of cardiovascular morbidity encountered in patients with iatrogenic iron overload . This detrimental effect induced by liver iron overload may explain the results of the 3 long‐term epidemiological studies (including the DOPPS study of 32 435 hemodialysis patients followed for a median of 1.7 years in 12 industrialized countries) demonstrating the association of excessive IV iron doses with increased risk of cardiovascular morbidity and mortality among hemodialysis patients …”

Section: Introduction and General Remarksmentioning

confidence: 99%

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When should iron supplementation in dialysis patients be avoided, minimized or withdrawn?

Rostoker

2018

Seminars in Dialysis

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Parenteral iron is used to restore the body's iron pool before and during erythropoiesis-stimulating agent (ESA) therapy; together these agents form the backbone of anemia management in end-stage renal disease (ESRD) patients undergoing hemodialysis. ESRD patients receiving chronic intravenous iron products, which exceed their blood loss are exposed to an increased risk of positive iron balance. Measurement of the liver iron concentration (LIC) reflects total body iron stores in patients with secondary hemosiderosis and genetic hemochromatosis. Recent studies of LIC in hemodialysis patients, measured by quantitative MRI and magnetic susceptometry, have demonstrated a high risk of iron overload in dialysis patients treated with IV iron products at doses advocated by current anemia management guidelines for dialysis patients. Liver iron overload causes increased production of hepcidin and elevated plasma levels, which can activate macrophages of atherosclerotic plaques. This mechanism may explain the results of 3 long-term epidemiological studies which showed the association of excessive IV iron doses with increased risk of cardiovascular morbidity and mortality among hemodialysis patients. A more physiological approach of iron therapy in ESRD is needed. Peritoneal dialysis patients, hemodialysis patients infected with hepatitis C virus, and hemodialysis patients with ferritin above 1000 μg/L without a concomitant inflammatory state, all require specific and cautious iron management. Two recent studies have shown that most hemodialysis patients will benefit from lower maintenance IV iron dosages; their results are applicable to American hemodialysis patients. Novel pharmacometric and economic approaches to iron therapy and anemia management are emerging which are designed to lessen the potential side effects of excessive IV iron while maintaining hemoglobin stability without an increase in ESA dosing.

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Section: Iron Products As Second‐line Treatment In Peritoneal Dialmentioning

confidence: 99%

Section: Introduction and General Remarksmentioning

confidence: 99%

Section: Introduction and General Remarksmentioning

confidence: 99%

Section: Introduction and General Remarksmentioning

confidence: 99%

Section: Introduction and General Remarksmentioning

confidence: 99%

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When should iron supplementation in dialysis patients be avoided, minimized or withdrawn?

Rostoker

2018

Seminars in Dialysis

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Prevalence of iron overload in patients with chronic kidney disease on peritoneal dialysis: A scoping review

Nashwan,

Abuawwad,

Jaradat

et al. 2024

Health Science Reports

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Background and AimsChronic kidney disease (CKD) patients undergoing peritoneal dialysis (PD) are susceptible to complications, including iron overload, which can significantly impact their prognosis and overall health. This scoping review aimed to study the prevalence and implications of iron overload in CKD patients undergoing PD.MethodsA comprehensive search was conducted across five databases, leading to the selection of 18 papers for in‐depth analysis. These studies collectively involved 381 PD patients, 60.3% were males.ResultsNo consensus was reached regarding the exact diagnostic cutoff for iron overload. The investigations revealed four main aspects: (1) Seven papers identified various factors contributing to iron overload, emphasizing the role of different iron supplements and magnetic resonance imaging's capability to diagnose iron accumulation in organs; (2) Iron overload in young patients was found to hinder growth; (3) Six studies highlighted the adverse effects of iron overload, with cardiac issues being the most significant; (4) Three studies demonstrated the efficacy of iron‐chelating agents, Deferoxamine and Deferasirox, in treating iron overload patients undergoing PD. Overall, the estimated prevalence of liver iron overload in CKD patients on PD ranges from approximately 10% to 28.6%, which is far lower than the prevalence of 75% elegantly shown in HD patients.ConclusionWhile iron overload was a significant concern for CKD patients undergoing PD in the past, it is less common in the current era due to advancements in treatments, such as erythropoiesis‐stimulating agents. Treatment with specific chelation agents has proven beneficial, but there is also a risk of adverse effects, necessitating meticulous monitoring and timely intervention.

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Pharmacokinetics and Safety of Intravenous Ferric Pyrophosphate Citrate: Equivalence to Administration via Dialysate

Marbury

Heuveln

Horst

et al. 2022

The Journal of Clinical Pharma

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Ferric pyrophosphate citrate (FPC) is indicated to maintain hemoglobin in patients with stage 5 hemodialysis-dependent chronic kidney disease on chronic hemodialysis by addition to the dialysate. An intravenous (IV) FPC presentation containing 6.75 mg of iron in 4.5 mL was developed. The objective was to establish the equivalence of iron delivery via dialysate and IV infusion using a pharmacokinetic approach. An open-label, randomized, multiple-period, single-dose, crossover study was conducted in 27 patients with CKD-5HD. Each patient received (1) a basal iron profile over 12 hours, (2) FPC 6.75 mg Fe IV predialyzer, (3) FPC 6.75 mg Fe IV postdialyzer, and (4) FPC 2 μM (110 μg Fe/L of hemodialysate). Serum and plasma iron was analyzed for total Fe and transferrin bound iron (TBI). Equivalence was determined by comparing maximum observed concentration and area under the concentration-time curve from time 0 to the last observation of 110 μg Fe/L of hemodialysate (reference) and test treatments Fe predialyzer and postdialyzer iron profiles. The main outcome measure was the measurement of bioequivalence between the reference and test treatments. Bioequivalence parameters showed that infusion of FPC iron IV, predialyzer and postdialyzer delivered equivalent iron as via hemodialysate. The increment in serum total Fe from predialysis to postdialysis was the same as observed in the long-term clinical studies of FPC. FPC IV was well tolerated. IV infusion of 6.75 mg iron as FPC during 3 hours of HD delivers an equivalent amount of iron as when Triferic is delivered via hemodialysate. The IV presentation of FPC extends the ability to provide FPC iron to all patients receiving hemodialysis or hemodiafiltration.

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Iatrogenic iron overload and its potential consequences in patients on hemodialysis

Cited by 27 publications

References 85 publications

When should iron supplementation in dialysis patients be avoided, minimized or withdrawn?

When should iron supplementation in dialysis patients be avoided, minimized or withdrawn?

Prevalence of iron overload in patients with chronic kidney disease on peritoneal dialysis: A scoping review

Pharmacokinetics and Safety of Intravenous Ferric Pyrophosphate Citrate: Equivalence to Administration via Dialysate

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