Date Published: 
Thursday, 5 November, 2015

Commentary on the review by Charytan et al., JASN 2015

Iain Macdougall, King's College London, United Kingdom

David Charytan and other members of the Dialysis Advisory Group of the American Society of Nephrology have written a highly pertinent and timely review on the need for a robust evidence base for clinical practice in nephrology. In contrast to cardiology (and indeed most other hospital specialties!), nephrology lags behind, in terms of robust scientific evidence for much of its clinical practice, and this is the main focus of Charytan’s review. It discusses and highlights the complete lack of Grade A evidence supporting the use of many of the therapies for dialysis patients – including phosphate binders, which are almost universally prescribed for such patients. The main focus of the article, however, is on intravenous iron use in this patient population.

Although there is a plethora of publications on both i.v. iron use in haemodialysis patients, and on the possible harm that too liberal a use of iron in clinical practice might cause, much of what we need to know is not known. We certainly know that using i.v. iron reduces the dose requirements of erythropoiesis-stimulating agent (ESA) therapy, and this could potentially be beneficial, since there are concerns that high-dose ESA therapy could be harmful. There are also significant cost savings in countries where ESA therapy is expensive, in comparison with i.v. iron.

However, concerns about too liberal an approach with i.v. iron focus on its potential for exacerbating oxidative stress, cardiovascular harm and infections. There is no shortage of laboratory data to support these concerns, but observational data both support and refute them, and the bottom line is that no one knows the threshold of i.v. iron administration at which the risks outweigh the benefits. Charytan’s review discusses this in an erudite and cogent manner, and it is also the subject of a report from a 2014 Iron Controversies Conference hosted by KDIGO that is due for publication shortly in Kidney International. Charytan’s review also makes reference to the ongoing UK PIVOTAL study, which is aiming to recruit 2,080 haemodialysis patients across 55 centres and which has already attained over 66% of its target sample size. It is intended to include a minimum of 2 years’ follow-up of each patient, with a hard primary composite endpoint of death, heart attack, stroke, or hospitalisation for heart failure. The incidence of infections is an important secondary endpoint in this study.

Charytan’s review sets the scene very nicely. Thankfully, with PIVOTAL there is light at the end of the tunnel. But there is also a need for further robust scientific evidence in this important area of dialysis patient management.