Seek: pharmacological action of glucocorticoid on proteinuria

Abstract

Idiopathic nephrotic syndrome is one of the major renal diseases that require aggressive therapy. Over the past 60 years,glucocorticoid has been employed as a first line agent to treat idiopathic nephrotic syndrome; however, the mechanism of its pharmacological action in the improvement of heavy proteinuria still remains unclear. Previously, we revealed that the human glomerulus expressed glucocorticoid receptor that was translocated from the cytoplasm to the nucleus after the binding to the dexamethasone. We also proved that the human glomerulus expressed glucocorticoid inactivating enzyme that indeed possessed the enzyme activity in podocytes. Based on these findings, we provided the novel concept suggesting the direct action of the glucocorticoid on the injured podocytes. Then, we subsequently revealed that the energy imbalance in podocytes underlay the pathomechanism of the proteinuria in the nephrotic syndrome, which was identified to be a target site of the immunosuppressants including glucocorticoid. In the near future, the compounds that could exert the effect on the energy pathway would be expected to be candidates for novel therapeutic agent to overcome glucocorticoid dependence and resistance.