Serum suPAR in patients with FSGS: trash or treasure?
- PDF / 484,889 Bytes
- 8 Pages / 595.276 x 790.866 pts Page_size
- 63 Downloads / 174 Views
REVIEW
Serum suPAR in patients with FSGS: trash or treasure? Rutger J. H. Maas & Jeroen K. J. Deegens & Jack F. M. Wetzels
Received: 17 December 2012 / Revised: 20 January 2013 / Accepted: 26 February 2013 / Published online: 21 March 2013 # IPNA 2013
Abstract The urokinase-type plasminogen activator receptor (uPAR) has important functions in cell migration. uPAR can be shed from the cell membrane resulting in soluble uPAR (suPAR). Further cleavage gives rise to shorter fragments with largely unknown functions. Recent studies have demonstrated that both overexpression of uPAR on podocytes and the administration of suPAR cause proteinuria in mice. The common pathogenic mechanism involves the activation of podocyte β3-integrin. Increased activation of β3-integrin is also observed in patients with focal and segmental glomerulosclerosis (FSGS). These observations form the basis for the hypothesis that suPAR may be the circulating factor causing FSGS. A recent study fosters this idea by demonstrating increased suPAR levels in the serum of patients with FSGS and reporting an association with recurrence after transplantation and response to plasmapheresis. However, this study was heavily biased, and subsequent studies have given conflicting results. Although the experimental work is very suggestive, at present there is no proof that any known human suPAR fragment causes FSGS in humans. We therefore suggest that the measurement of suPAR using currently available assays has absolutely no value at the present time in decision-making in routine clinical practice. Keywords Focal segmental glomerulosclerosis . Nephrotic syndrome . Transplantation . Recurrence . Urokinase receptor . Integrin
Introduction Focal and segmental glomerulosclerosis (FSGS) is a common histological finding in children and adults with nephrotic syndrome [1, 2]. Podocyte damage plays a pivotal role in the development of proteinuria [3]. Well-known causes of podocyte injury and FSGS include genetic mutations, viral infections and drugs [4]. However, in most patients with nephrotic syndrome and FSGS the underlying cause is unknown, a condition also defined as primary or idiopathic FSGS. It is now well-accepted that the pathogenesis of primary FSGS involves a circulating factor that disturbs podocyte function and increases glomerular permeability. This concept of a circulating permeability factor as a cause of primary FSGS is supported by experimental and clinical evidence (summarized in Table 1) [5–11]. Although the existence of a permeability factor is not disputed, the search for a causative permeability factor has thus far been unsuccessful. Wei et al. recently proposed soluble urokinase-type plasminogen activator receptor (suPAR) as a circulating factor causing FSGS [12]. In this review, we briefly summarize the structure and function of uPAR and the relevance of the cellular actions of both soluble and membrane-bound uPAR for the development of proteinuria. We discuss the evidence that suPAR is a cause of primary FSGS, and whether measurement of suPA
Data Loading...
