Before the introduction of erythropoiesis-stimulating agents (ESAs) in 1989, repeated transfusions given to patients with end-stage renal disease caused iron overload, and the need for supplemental iron was rare. However, with the widespread introduction of ESAs, it was recognized that supplemental iron was necessary to optimize hemoglobin response and allow reduction of the ESA dose for economic reasons and recent concerns about ESA safety. Iron supplementation was also found to be more efficacious via intravenous compared to oral administration, and the use of intravenous iron has escalated in recent years. The safety of various iron compounds has been of theoretical concern due to their potential to induce iron overload, oxidative stress, hypersensitivity reactions, and a permissive environment for infectious processes. Therefore, an expert group was convened to assess the benefits and risks of parenteral iron, and to provide strategies for its optimal use while mitigating the risk for acute reactions and other adverse effects.

Anaemia is a commonly diagnosed complication among patients suffering with chronic kidney disease. If left untreated, it may affect patient quality of life. There are several causes for anaemia in this patient population. As the kidney function deteriorates, together with medications and dietary restrictions, patients may develop iron deficiency, resulting in reduction of iron supply to the bone marrow (which is the body organ responsible for the production of different blood elements). Chronic kidney disease patients may not be able to utilise their own body’s iron stores effectively and hence, many patients, particularly those receiving haemodialysis, may require additional iron treatment, usually provided by infusion.With further weakening of kidney function, patients with chronic kidney disease may need additional treatment with a substance called erythropoietin which drives the bone marrow to produce its own blood. This substance, which is naturally produced by the kidneys, becomes relatively deficient in patients with chronic kidney disease. Any patients will eventually require treatment with erythropoietin or similar products that are given by injection.Over the last few years, several iron and erythropoietin products have been licensed for treating anaemia in chronic kidney disease patients. In addition, several publications discussed the benefits of each treatment and possible risks associated with long term treatment. The current guidelines provide advice to health care professionals on how to screen chronic kidney disease patients for anaemia, which patients to investigate for other causes of anaemia, when and how to treat patients with different medications, how to ensure safe prescribing of treatment and how to diagnose and manage complications associated with anaemia and the drugs used for its treatment.

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Abstract. Resistance to recombinant human erythropoietin occurs in a small but important proportion of hemodialysis patients. This may be due to increased immune activation because pro-inflammatory cytokines inhibit erythropoiesis in vitro. Using FACScan flow cytometry, the proportion of PMA/ ionomycin-stimulated T cells expressing cytokines ex vivo was compared in 18 poor responders to erythropoietin, 14 good responders to erythropoietin, and 14 normal controls. CD4 ϩ T cells from poor responders expressed more interferon-␥ (IFN-␥; 19 Ϯ 6%) compared with good responders (11 Ϯ 6%, P Ͻ 0.001) and controls (12 Ϯ 6%, P Ͻ 0.01). Similarly, CD4 ϩ T cells from poor responders expressed more tumor necrosis factor-␣ (TNF-␣; poor responders: 51 Ϯ 19% versus good responders: 27 Ϯ 15% [P Ͻ 0.01] and controls: 30 Ϯ 19% [P Ͻ 0.01]). CD4 ϩ expression of IL-10 was also enhanced (poor responders: 1.6 Ϯ 1.1% versus good responders: 0.7 Ϯ 0.6% [P Ͻ 0.05] and controls: 0.5 Ϯ 0.2% [P Ͻ 0.01]).Likewise, CD4 ϩ expression of interleukin-13 (IL-13) was increased (poor responders: 4.4 Ϯ 4.2% versus good responders: 1.6 Ϯ 1.7% [P Ͻ 0.05] and controls: 1.6 Ϯ 1.5% [P Ͻ 0.05]). CD8 ϩ T cells from poor responders also showed enhanced expression of cytokines. For IFN-␥, poor responder expression was 48 Ϯ 20% compared with 31 Ϯ 17% (P Ͻ 0.05) for good responders and 23 Ϯ 15% (P Ͻ 0.01) for controls. TNF-␣ expression for poor responders was 41 Ϯ 21% versus 25 Ϯ 14% for good responders (P Ͻ 0.05) and 21 Ϯ 15% for controls (P Ͻ 0.01). IL-10 expression for poor responders was 2.0 Ϯ 1.2% (good responders: 0.7 Ϯ 0.6% [P Ͻ 0.01]; controls: 0.5 Ϯ 0.2% [P Ͻ 0.001]). These data indicate that T cells from poor responders are in an enhanced activation state possibly as a result of chronic inflammation. In the absence of any other cause (such as iron deficiency), the overproduction of cytokines may account for hyporesponsiveness to erythropoietic therapy in patients with renal failure.

Abstract. It was hypothesized that pentoxifylline might improve the response to recombinant human erythropoietin (rhEpo) in anemic renal failure patients. Sixteen patients with ESRD and rh-Epo-resistant anemia, defined by a hemoglobin of Ͻ10.7 g/dl for 6 mo before treatment and a rh-Epo dose of Ն12,000 IU/wk, were recruited. They were treated with oral pentoxifylline 400 mg o.d. for 4 mo. Ex vivo T cell generation of tumor necrosis factor alpha (TNF-␣) and interferon gamma (IFN-␥) from the patients was assessed before treatment and 6 to 8 wk after therapy. A total of 12 of 16 patients completed the study. Before therapy, the 12 patients' mean hemoglobin concentration was 9.5 Ϯ 0.9 g/dl. After 4 mo of pentoxifylline treatment, the mean hemoglobin concentration increased to 11.7 Ϯ 1.0 g/dl (P ϭ 0.0001). Baseline ex vivo T cell expression of TNF-␣ decreased from 58% Ϯ 11% to 31% Ϯ 23% (P ϭ 0.0007) after therapy. Likewise, IFN-␥ expression decreased from 31% Ϯ 10% to 13% Ϯ 10% (P ϭ 0