HDF promise for the future

2705 2. Kontoghiorghes GJ. Deferasirox: uncertain future following renal failure fatalities, agranulocytosis and other toxicities. Reply Sir, We would like to thank Dr Hirschberg and colleagues for their interest in our report, which was aimed to raise awareness of the rare but repeatedly described untoward effects of deferoxamine on renal function. Moreover, we aimed to propose a mechanism by which these untoward effects on renal function could be mediated [2]. In the discussion we stated that a different drug, deferasirox, has 'been repeatedly shown to cause acute renal failure' quoting a recent paper by Kontoghiorghes [3]. Dr Hirschberg and colleagues, who, as members of the renal safety board for deferasirox, had detailed knowledge of the post-marketing surveillance data, are 'very sceptical' that deferasiox was responsible for these cases of acute renal failure. We can only refer to data available in the public domain. According to the FDA website, there had been 115 reports of suspected adverse drug reactions in the association with the use of deferasirox Sixteen unduplicated reports described renal adverse events. Seven patients improved after discontinuation of deferasirox. Seven patients had 'acute renal failure' with an onset between 5 and 58 days after initiation of the therapy. Dr Hirschberg and colleagues state that 'the term acute renal failure was inappropriately used in many cases to describe a relatively minor increase in serum creatinine (<2× upper limit of normal) that developed over the course of several weeks'. Unfortunately, there had been no uniformly accepted definition of acute renal failure [4]. However , in a variety of settings, there is accumulating evidence that small increments in serum creatinine are associated with adverse outcomes [4]. Therefore, the term acute kidney injury (increase of creatinine >25 µmol/l over 48 h), which is often superimposed on pre-existing CKD, was recently introduced. This definition will increase the clinical awareness and the detection of injury to the kidney and should, in our view, also be used in the setting of pharma-covigilance. Aside from the FDA information, Vichinsky et al. [5] showed in 132 adult and paediatric patients that deferasirox administration was accompanied in a mild and stable increase of serum creatinine in 36.4% of the patients. Of the 63 patients in that study that received deferoxamine, 22.2% experienced such an increase of serum creatinine. In contrast to deferoxamine, where the mean change in creati-nine was 3.06 µmol/l, the mean increase in the deferasirox-treated group was …