The Effects of 24 Hour Continuous Deferoxamine Intensification on Serum Creatinine.

BACKGROUND: With new chelation regimes such as deferasirox, there has been interest in their effects on serum creatinine, as about one third of patients show a small non-progressive increase within a few weeks of starting treatment. A question arises as to whether creatinine increases occur with other modalities of chelation therapy. The effects of deferoxamine (DFO) on serum creatinine have not been widely studied, particularly when intensive chelation regimes are used with 24 hour (h) exposure. Intensified 24h DFO for patients with high risk iron overload has been in use for selected patients for over 20 years. However, whilst factors leading to retinal and ototoxicity are well described, effects on serum creatinine are largely confined to case reports. We postulated that small increments in serum creatinine might be an inevitable effect of treatment intensification. We therefore undertook retrospectively to examine the effects on serum creatinine in patients in whom standard DFO therapy (40mg/kg as 8–10h infusions 5 days/ week) was switched to an intensive DFO monotherapy regime with 24h/day therapy.

PATIENTS AND METHODS: We examined the records of 10 patients with transfusion dependent thalassaemia attending the haematology department at University College London Hospitals, between 1989 and 2008, who required an intensification of their DFO regime as a result of failure to control their iron burden with their existing regime. Nine out of the 10 patients required portacath insertion for their DFO to be delivered intravenously, the tenth patient was switched to subcutaneous DFO administered 24h/ day. The patient characteristics were as follows: 8 male and 2 female. Two had thalassaemia intermedia and the rest had thalassaemia major. Those with a portacath were commenced on warfarin as thromboprophylaxis for the portacath. Co-morbidities for the patients included splenectomy (2); diabetes (2); cardiac failure (3); arrhythmias (2). The mean dose of deferoxamine administered was 52mg/kg/24h (9 of the patients had doses between 35–60 mg/kg/24h and only 1 patient had a dose of 100 mg/kg/24h).

RESULTS: The results of the study revealed a mean ferritin of 6113.2μg/L ± 1681.3 and 3910.5μg/L ± 1438.4 pre and post intensification of DFO respectively. Of the 10 patients, 6 of them displayed an increase in creatinine of over 25% of their original level on standard DFO, the other 4 also had an increase albeit a more modest one. The increase in creatinine did not correlate with the dose of DFO given. The creatinine pre-intensification showed a mean of 62.3μmol/L ± 10.19 and post intensification showed 92.3μmol/L ± 11.17. This was a statistically significant difference with a p value of 0.0016 using a paired student t test. No patient went on to develop progressive renal dysfunction and creatinine returned to baseline in all patients when the regime returned to standard therapy.

CONCLUSIONS: We conclude that intensification of DFO using 24h chelation results in small increments in serum creatinine, even when doses are as low as 40–70mg/kg. The findings suggest that increments in creatinine with chelation therapy are more frequent than hitherto recognised and may be a general effect of continuous chelation therapy. These changes were reversible on returning to original intermittent DFO. While none of these patients developed permanent changes, we propose that patients who are commenced on DFO, especially at continuous intensified doses, should have their creatinine measured on a regular basis, and caution should be employed with those patients who have borderline high creatinine.