Urinary proteomics and molecular determinants of chronic kidney disease: possible link to proteases.

Chronic kidney disease (CKD) is the gradual decrease in renal function. Currently available biomarkers are effective only in detecting late stage CKD. Biomarkers of early stage CKD and prognostic biomarkers are required. We review the major findings in urinary proteomics in CKD during the last five years. Significant progress has been made and today urinary proteomics is applied in large randomized trials, and in patient management. Many of the biomarkers indicate altered protease activity. We therefore also review the literature on proteases associated with renal function loss. We anticipate in silico prediction tools of protease activity and additional system biology studies may contribute to biomarker discovery and elucidate the role of proteases in CKD development and progression. These approaches will enable the deciphering of the molecular pathophysiology of CKD, and hence definition of the most appropriate therapeutic targets in the future. Together with stable biomarker panels available today, this will significantly improve patient management.