Primary focal and segmental glomerulosclerosis and soluble factor urokinase-type plasminogen activator receptor

Abstract

Primary focal and segmental glomerulosclerosis (FSGS) may be due to genetic or acquired etiologies and is a common cause of nephrotic syndrome with high morbidity that often leads to end-stage renal failure. The different available therapeutic approaches are unsuccessful, in part due to partially deciphered heterogeneous and complex pathophysiological mechanisms. Moreover, the term FSGS, even in its primary form, comprises a histological description shared by a number of different causes with completely different molecular pathways of disease. This review focuses on the latest developments regarding the pathophysiology of primary acquired FSGS caused by soluble factor urokinase type plasminogen activator receptor, a circulating permeability factor involved in proteinuria and edema formation, and describes recent advances with potential success in therapy.

Keywords: Primary acquired focal and segmental glomerulosclerosis, Soluble factor urokinase type plasminogen activator receptor, Proteinuria, Podocyte, Plasmin

Core tip: Primary acquired focal and segmental glomerulosclerosis is a frequent cause of nephrotic syndrome with no specific treatment. New discoveries in its pathophysiolohy have revealed that a podocyte permeability factor named soluble urokinase plasminogen activator receptor (suPAR) may be involved in the development of proteinuria and edema formation. This effect is supposed to be achieved by its interaction with podocyte integrins and subsequent cell contraction. Moreover, suPAR also activates water and sodium retention in this disease. Interestingly, plasmin mediates both effects. Amiloride is postulated to interfere with suPAR proteinuric actions.