The impact of intravenous ferric carboxymaltose on renal function: an analysis of the<scp>FAIR‐HF</scp>study

Ponikowski, Piotr; Filippatos, Gerasimos; Colet, Josep Comín; Willenheimer, Ronnie; Dickstein, Kenneth; Lüscher, Thomas F.; Gaudesius, Giedrius; Rothe, B.; Mori, Claudio; Greenlaw, Nicola; Ford, Ian; Macdougall, Iain C.; Anker, Stefan D.

doi:10.1002/ejhf.229

Cited by 100 publications

(67 citation statements)

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“…Administration of iron to iron-deficient cardiorenal syndrome patients has recently been shown to improve their renal function. 28 Comparison of oral versus intravenous iron administration across the spectrum of CKD aetiologies currently favours the intravenous route in terms of iron repletion efficacy and reduction in reliance on ESAs, with a good reported safety profile. 29,30 Clinical guidelines suggest haemoglobin levels should not be maintained above 11.5 g/dL by ESA therapy, and that selection of the route of iron administration should be based on severity of the anaemia and iron deficiency, prior response or intolerance to treatments, availability of venous access, cost implications and current ESA use.…”

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confidence: 99%

Drug therapies to delay the progression of chronic kidney disease

2015

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Chronic kidney disease (CKD) is associated with significant morbidity and mortality, impacted not alone by progression to end-stage kidney disease, but also by the high associated incidence of cardiovascular events and related mortality. Despite our current understanding of the pathogenesis of CKD and the treatments available, the reported incidence of CKD continues to rise worldwide, and is often referred to as the silent public healthcare epidemic. The significant cost to patient wellbeing and to the economy of managing the later stages of CKD have prompted efforts to develop interventions to delay the development and progression of this syndrome. In this article, we review established and novel agents that may aid in delaying the progression of CKD and improve patient outcomes. KEYWORDS: Chronic kidney disease, progression, drug therapy IntroductionChronic kidney disease (CKD), as defined by proteinuria or a reduced glomerular filtration rate (GFR) below 90 mL/min/1.73 m 2 persisting for greater than 3 months, is reported to affect 13% of US adults.1 There is a significantly higher prevalence in the elderly and those with hypertension or diabetes, and with these comorbidities increasing in prevalence and the population ageing, CKD is projected to affect up to 16% of adults by 2030.2,3 Even in its early stages, CKD is associated with accelerated cardiovascular disease and increased mortality, with an exponential increase in attributable risk as GFR declines to end-stage kidney disease (ESKD). 4,5 The mortality rate in ESKD patients maintained on dialysis is striking, with a life expectancy less than one-third that of their counterparts without ESKD, and a 5-year survival rate on dialysis of only 40%. 6 There is also a substantial healthcare cost associated with provision of ESKD care, currently estimated at $33 billion annually in the US, ABSTRACT equating to 6.3% of the Medicare Budget. 6 Hence, there may be significant healthcare and economic benefits to be garnered from halting or delaying CKD progression. In this article, we discuss recent evidence for established and emerging therapies that may alter the progression of CKD. Non disease-specific drug therapies Sodium bicarbonateCKD is associated with a metabolic acidosis, particularly at lower levels of GFR <25 mL/min/1.73 m 2 , which is predominantly attributed to reduced hydrogen ion excretion as titratable acids or ammonium in the urine. Chronic metabolic acidosis exacerbates CKD-related mineral bone disease, leads to muscle atrophy, and is associated with other complications such as abnormal albumin synthesis, thyroid dysfunction and insulin resistance. 7,8 Observational data demonstrate a strong risk of progression of CKD in those with a lower serum bicarbonate level, as well as an increased mortality risk. 9,10 Possible mechanisms for the deleterious effect of acidosis on GFR may be the inadvertent pro-fibrotic effects of inducing regulatory mechanisms in the kidney, such as increased renal ammonium production, endothelin-A receptor activation and pr...

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confidence: 99%

Drug therapies to delay the progression of chronic kidney disease

2015

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“…Twenty-four weeks from commencing treatment with iron or placebo, the symptoms, functional capacity and quality of life were significantly better among patients receiving iron repletion than in the placebo-treated patients; rates of adverse events did not differ between the groups. The effects of iron supplementation were observed regardless of the presence of anemia, and iron treatment was associated with a modest but significant improvement in renal function (difference in estimated glomerular filtration rate 2.98 ml/ min/1.73 m 2 at week 24) [33] . The Ferric Carboxymaltose Evaluation on Performance in Patients with Iron Deficiency in Combination with Chronic Heart Failure (CONFIRM-HF) trial is another recently published RCT that examined the effects of iron treatment for approximately 1 year in 304 ambulatory symptomatic heart failure patients who had nearly identical iron profiles as those of the subjects in the FAIR-HF trial [34] .…”

Section: Iron and Cardiovascular Riskmentioning

confidence: 97%

How to Supplement Iron in Patients with Renal Anemia

Tanaka

2015

Nephron

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Iron deficiency is a major cause of hyporesponsiveness to erythropoiesis-stimulating agents (ESAs) and is often observed in chronic kidney disease (CKD) patients with anemia. With iron supplementation, ESA doses can be decreased, resulting in lower treatment costs and possibly lower cardiovascular risks that are associated with high-dose ESA therapy. The 2012 Kidney Disease: Improving Global Outcomes Guideline specified ferritin ≤500 ng/ml and transferrin saturation (TSAT) ≤30% as thresholds of iron parameters for CKD patients. However, long-term safety (in terms of mortality, cardiovascular/infection risk and tissue deposition) of high-dose intravenous iron supplementation with such high target levels of ferritin/TSAT has not been confirmed. Recently, there has been increase in the use of intravenous iron and average ferritin levels in dialysis patients in the United States. Clinical trials conducted so far have been underpowered to conclusively establish the long-term safety of intravenous iron supplementation. Results from observational studies are conflicting, and many experimental studies have even shown negative effects of intravenous iron. Clearly, randomized clinical trials are urgently needed, studying various doses of intravenous iron, with sufficient patient numbers and longer observation periods, to investigate mortality, cardiovascular effects and infection risks of this treatment. Until the long-term safety of iron supplementation at high doses is established, a more prudent decision on iron supplementation with lower target levels of ferritin/TSAT seems reasonable, in light of the decades of experience with ESA that has shown that definitive clinical outcomes have been dissociated from surrogate outcomes (especially hemoglobin concentration).

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“…33 A later analysis of these same patients showed that renal function was enhanced with iron as well. 34 Despite these persuasive findings, routine screening for iron deficiency did not become a standard practice in most HF programs. Accordingly, the Ferric Carboxymaltose Evaluation on Performance in Patients With Iron Deficiency in Combination With Chronic Heart Failure (CONFIRM-HF) trial was undertaken to address the sustainability of iron's beneficial effects.…”

Section: Iron Therapymentioning

confidence: 99%