Oxidative modifications of urinary proteins increase kidney stone risk

Clinical and animal studies have demonstrated the increasing evidence of oxidative stress in kidney stone disease. Recent findings have shown that the interactions between calcium oxalate (CaOx) crystals and renal tubular cells can promote many cellular events such as cell proliferation, cell death, cellular injury, mitochondrial dysfunction and inflammatory cascade. All of these cellular events are associated with oxidative stress and overproduction of free radicals and reactive oxygen species (ROS) such as superoxide and hydrogen peroxide in renal tubular cells. However, almost all of these references have shown that oxidative stress occurs after the causative crystals have been deposited in the kidney or exposed to renal tubular cells, whereas its primary role as the etiology remained unclear. In this study, we examined effects of oxidative modifications of urinary proteins on CaOx stone formation processes. Urinary proteins were modified by performic oxidation and the presence of oxidatively modified urinary proteins was verified, quantified and characterized by Oxyblot assay and tandem mass spectrometry (nanoLC-ESI-LTQ-Orbitrap-MS/MS). Subsequently, activities of oxidatively modified urinary proteins on CaOx stone formation processes were examined.