Date Published: 
Thursday, 26 November, 2015

Commentary on the FAIR-HF article by Ponikowski et al., EJHF 2015

Provided by Ewa Jankowska, Wrocław Medical University, Poland

It is commonly acknowledged that there is a strong interplay between functioning of the kidneys and heart, which can lead to the development of the so-called cardio-renal syndrome. Moreover, in recent years, substantial pathophysiological evidence has been published showing that anaemia and iron deficiency (ID) may contribute to these mutual and complex associations.

Renal dysfunction constitutes a common and ominous co-morbidity among patients with heart failure (HF) (1,2). Impaired renal functioning itself negatively affects the prognosis in patients with HF, and importantly HF patients with advanced kidney disease are deprived of cetain life-saving HF therapies, because some are contraindicated when serum creatinine is substantially increased. Surprisingly, despite numerous attempts in recent decades to amend renal function in patients with HF, until now there has been no evidence supporting any therapy that could safely and effectively improve kindey function in patients with HF (in spite of mechanical haemodynamic support in advanced HF (3)).

The results of a study by Ponikowski et al., published recently in the European Journal of Heart Failure (4), seem to meet this clinical need. The authors analysed renal function among participants of the Ferinject® Assessment in Patients With Iron Deficiency and Chronic Heart Failure (FAIR-HF) study, a randomized, double-blind, placebo-controlled trial assessing the safety and efficacy of intravenous ferric carboxymaltose (FCM) in 459 iron deficient patients with symptomatic systolic HF. Estimated glomerular filtration rate (eGFR) was the primary index of renal function assessed at baseline and at 4, 12 and 24 weeks, and was estimated based on the Chronic Kidney Disease Epidemiology Collaboration (CKD–EPI) formula and the The Modification of Diet in Renal Disease (MDRD) formula. Follwingintravenous iron therapy, eGFR increased as early as 4 weeks after treatment and remained high until the end of 24-week follow-up. Notably, improvements in renal function were seen in all pre-specified clinical subgroups, regardless of baseline renal function, circulating ferritin, age, sex, body mass index, HF severity and aetiology, left-ventricular ejection fraction, or presence of anaemia or diabetes mellitus.

These findings are of particular importance for patients with HF considering the high prevalence of ID among this group. The study confirms that intravenous FCM therapy does not deteriorate (as a substantial group of experts would expect), but rather improves renal function in patients with systolic HF, including those with markedly impaired renal function, anaemia, diabetes and severe HF. It is also worth emphasising that in a subgroup of patients with HF and renal dysfunction, treatment with intravenous FCM resulted in a lower rate of cardiovascular hospitalisations compared with placebo.

The explanation of these results is not straightforward. Iron supplementation in iron deficient patients can be considered a metabolic treatment, leading to optimisation of iron status, which subsequently results in normalisation of energy metabolism (5–7). It is known that not only iron excess, but also ID results in mitochondrial dysfunction, oxidative stress and inefficient energy production (6–8). The kidneys and heart are both organs characterised by high energy demand, hence in these tissues the preservation of optimal intracellular iron is of particular importance (5,7,8). Undoubtedly, further pathological studies are needed in order to establish the mechanism of the favourable effects of intravenous iron therapy on renal function in iron deficient patients with HF.