High urinary ferritin reflects myoglobin iron evacuation in DMD patients

Abstract Duchenne muscular dystrophy(DMD) is an X-linked disease caused by mutations in the dystrophingene leading to the absence of the normal dystrophinprotein. The efforts of many laboratories brought new treatments of DMD to the reality, but ongoing and forthcoming clinical trials suffer from absence of valuable biomarkers permitting to follow the outcome of the treatment day by day and to adjust the treatment if needed. In the present study the levels of 128 urinary proteins including growth factors, cytokines and chemokines were compared in urine of DMD patients and age related control subjects by antibody array approach. Surprisingly, statistically significant difference was observed only for urinary ferritinwhose level was 50 times higher in young DMD patients. To explain the observed high urinary ferritincontent we analysed the levels of iron, iron containing proteins and proteins involved in regulation of iron metabolism in serum and urine of DMD patients and their age-matched healthy controls. Obtained data strongly suggest that elevated level of urinary ferritinis functionally linked to the renal management of myoglobin iron derived from leaky muscles of DMD patients. This first observation of the high level of ferritinin urine of DMD patients permits to consider this protein as a new urinary biomarker in muscular dystrophiesand sheds light on the mechanisms of iron metabolism and kidney functioning in DMD.