Developing a novel therapy for rhabdomyolysis

A project led by Michael Hutchens, M.D., will establish causes of kidney failure due to muscle destruction. It is common to observe kidney failure after injuries that occur during armed conflicts or earthquakes. This research is funded by a $3 million grant by the Department of Defense.

Hutchens’ lab will collaborate with Martin Schreiber, M.D., and his team in the Department of Surgery. This three-year grant will investigate the therapeutic benefits of cilastatin administration to prevent renal failure in a disaster and combat-relevant large animal injury model.

Destruction of skeletal muscle (rhabdomyolysis) by crush, burn, or blast injury causes kidney failure, a frequent cause of death in earthquakes and armed conflict. However, the only therapies (intravenous fluids and dialysis) are challenging in these circumstances.

Rhabdomyolysis causes kidney failure because the muscle protein myoglobin, which is released into circulation, is directly toxic in the kidney. Like citizens of Troy welcoming hidden Greek soldiers, kidney cells take up myoglobin through a gateway protein, called megalin, only to find themselves being destroyed from within.

Hutchens’ lab recently found that removing megalin almost completely ameliorates rhabdomyolysis-induced kidney disease and that blocking megalin with an already FDA-approved inhibitor, cilastatin, is also effective.

This research program is designed to lay critical groundwork for clinical trials and the rapid adoption of a potentially lifesaving, inexpensive therapy. This funding will start in January 2020.