Positive Iron Balance in Chronic Kidney Disease: How Much is Too Much and How to Tell?

Abstract

Background: Regulation of body iron occurs at cellular, tissue, and systemic levels. In healthy individuals, iron absorption and losses are minimal, creating a virtually closed system. In the setting of chronic kidney disease and hemodialysis (HD), increased iron losses, reduced iron absorption, and limited iron availability lead to iron deficiency. Intravenous (IV) iron therapy is frequently prescribed to replace lost iron, but determining an individual’s iron balance and stores can be challenging and imprecise, contributing to uncertainty about the long-term safety of IV iron therapy. Summary: Patients on HD receiving judicious doses of IV iron are likely to be in a state of positive iron balance, yet this does not appear to confer an overt risk for clinically relevant iron toxicity. The concomitant use of iron with erythropoiesis-stimulating agents, the use of maintenance iron dosing regimens, and the reticuloendothelial distribution of hepatic iron deposition likely minimize the potential for iron toxicity in patients on HD. Key Messages: Because no single diagnostic test can, at present, accurately assess iron status and risk for toxicity, clinicians need to take an integrative approach to avoid iron doses that impose excessive exposure while ensuring sufficient replenishment of iron stores capable of overcoming hepcidin blockade and allowing for effective erythropoiesis.

Histological Scores Validate the Accuracy of Hepatic Iron Load Measured by Signal Intensity Ratio and R2* Relaxometry MRI in Dialysis Patients

“…Our study has some limitations. The first relates to the small sample size analysed here-this issue is intrinsically linked to the context of ESKD associated with frailty and increased haemorrhagic risk, limiting liver biopsy to mandatory cases explaining the previous suggestion of Rostoker, Vaziri and Fishbane in 2016 [4] and more recently in 2018 by a panel of experts (from a conference devoted to positive iron balance in ESKD [44]) on the value of gathering a collection of liver biopsies from dialysis patients. This situation has some analogy with the anatomic demonstration of accuracy of R2* MRI for the diagnosis of ferric cardiomyopathy performed in a small panel of thalassaemic patients (n = 12) either during heart transplantation or at autopsy [45].…”

Randomized Trial Comparing Proactive, High-Dose versus Reactive, Low-Dose Intravenous Iron Supplementation in Hemodialysis (PIVOTAL): Study Design and Baseline Data

“…If monthly testing demonstrated (1) ferritin > 200 µg/L and TSAT > 20%, (2) ferritin > 700 µg/L, or (3) TSAT ≥40%, iron was not administered that month. Provided that TSAT was < 40%, patients with ferritin < 100 µg/L received iron sucrose 200 mg during the first 2 dialysis sessions of the week; if ferritin was 100-200 µg/L, it was administered only during the first dialysis session of the week.…”

“…Since the introduction of erythropoiesis-stimulating agents (ESAs) for the management of anemia in chronic kidney disease, intravenous (IV) iron has been widely used, particularly in hemodialysis (HD) patients where the average daily losses of iron typically exceed the oral absorption of iron [1,2]. However, the maintenance IV iron regimen varies widely from one country to another, and indeed among dialysis centers in the same country.…”

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

“…Pancreatic involvement was evaluated in the 8 most motivated patients and was present in 3 cases (37%). The presence of iron deposits in the pancreas (in a third of investigated patients) mean these patients fulfill the criteria recently proposed as radiological surrogates of iron toxicity in dialysis patients (eg, visceral iron deposits external to the liver, in the heart and/or pancreas) by a panel of specialists at an international advisory board meeting, sponsored by Vifor Fresenius Medical Care Renal Pharma, a pharmaceutical firm which manufactures several iron replacement therapies . Iron deposits in the pancreas predict iron cardiomyopathy in thalassemia and act as an early warning system for cardiac iron‐loading in thalassemic patients; moreover, pancreatic iron deposits are also predictive for diabetes mellitus in various iron overload disorders .…”

“…Hepatic siderosis was present in 90% of patients and spleen involvement in 95%. 63 Iron deposits in the pancreas predict iron cardiomyopathy in thalassemia and act as an early warning system for cardiac iron-loading in thalassemic patients; 64 moreover, pancreatic iron deposits are also predictive for diabetes mellitus in various iron overload disorders. [64][65][66] None of the 21 dialysis patients had an abnormal cardiac R2*/T2* but the small number of patients studied makes it difficult to draw definitive conclusions about the risk of cardiac iron deposits in this high-ferritin subset of dialysis patients.…”