The role of soluble urokinase-type Plasminogen Activator Receptor (suPAR) in Chronic Kidney Disease

Abstract

Kidney disease affects 800 million children and adults worldwide, and the numbers keep increasing. A better understanding of the pathogenesis in kidney diseases, especially on a biomolecular level, is much needed to identify novel biomarkers and therapeutic targets for kidney diseases. The glomerular filtration barrier comprises endothelial cells, the glomerular basement membrane, and podocytes. The podocyte has a central role in part of the glomerular filtration barrier. The normal functioning of podocytes is particularly important in preventing the heavy proteinuria seen in nephrotic syndrome or diabetic nephropathy, or in the disease process of focal segmental glomerulosclerosis. The podocyte is injured by circulating factors, which finally results in deranged podocyte motility. Soluble urokinase-type plasminogen activator receptor (suPAR) is a circulating form of glycosyl-phosphatidylinositol uPAR domain membrane protein and is known to play a role in the pathogenesis in kidney diseases, specifically focal segmental glomerulosclerosis and diabetic nephropathy. suPAR binds to αvβ3 integrin on podocyte foot processes and causes podocyte structure disorganization leading to glomerular filtration disruption and hence proteinuria. suPAR is also a potential biomarker to predict the incidence of CKD.

The Unique Difference Between Serum Level of Soluble Urokinase Plasminogen Activator Receptor (suPAR) in Steroid-Resistant Nephrotic Syndrome Children Treated with an Alkylating Agent and Calcineurin Inhibitors

“…Persistent proteinuria was due to podocyte effacement, injury, or collapse which led to glomerular sclerosis, fibrosis, and the progressive deterioration of the kidney (17,57,73,74). Also, patients diagnosed with FSGS, MPGN, and Mes-GN have a greater tendency for developing hypertension, compared to MCD patients, except for when there is a state of steroid toxicity (68,(75)(76)(77).…”

“…Soluble urokinase plasminogen activator receptor is the circulating form of glycosylphosphatidylinositolanchored three-domain membrane protein expressed in various cells, including the immunologically active and endothelial types and podocytes (11)(12)(13)(14)(15). Furthermore, suPAR is a 20 -55 kD protein, while circulating uPAR is a membrane-bound receptor for UPA and urokinase (3,(11)(12)(13)(14)(15)(16)(17). So far, only three known isoforms on humans and mice have been identified, including 1, 2, and 3.…”