Soluble Urokinase Receptors in Focal Segmental Glomerulosclerosis: A Review on the Scientific Point of View

Table 1

Studies on suPAR in FSGS.

Pathogenic role of suPAR in FSGS	References	Nonpathogenic role of suPAR in FSGS	References
In vitro study
suPAR activated β3 integrin in a similar manner to membrane-bound uPAR in podocytes	[9]	Not repeated by others
Podocyte β3 integrin activation by suPAR was blocked by a blocking antibody specific to uPAR	[9]	Activated podocyte β3 integrin by plasma from patients with recurrent FSGS could be also reversed by blocking TNF-α	[101]
In vivo mice study
High-dose recombinant mouse suPAR induced podocyte integrin β3 activation, proteinuria, and foot process effacement in a uPAR-knockout () mice	[9]	Neither single-dose nor prolonged administration of recombinant suPAR induced albuminuria or podocyte foot process effacement despite massive suPAR deposits in the glomeruli in wild-type C57BL/6J and 129S2/SvPas mice	[68]
Proteinuria developed after LPS-induced suPAR production in a hybrid-transplant mice in which a kidney from uPAR-knockout () mice was transplanted in a wild-type mouse	[9]	Coadministration of either monomeric or chimeric suPAR produced no additional effect; LPS-induced podocyte effacement and proteinuria in C57BL/6J mice	[68]
Injection of a suPAR-producing plasmid in their skin led to increased serum suPAR concentrations and FSGS-like lesions with proteinuria in genetically engineered wild-type	[9]	Injection of Fc-chimeric suPAR to wild-type mice or continuous expression of suPAR from the liver in new transgenic mice did not induce proteinuria	[23]
Human study
suPAR is increased in FSGS compared to other glomerulopathies and healthy subjects	[9–12]	suPAR is not increased in FSGS compared to other glomerulopathies	[14–21]
suPAR is more increased in recurrent FSGS after KT than in nonrecurrent FSGS	[9]	Not studied in other groups
Pretransplant serum suPAR predicted recurrence of FSGS after KT	[9, 66]	Pretransplant serum suPAR did not predict recurrence of FSGS after KT	[18, 69]
		Rather, urine suPAR predicted recurrence of FSGS after KT	[22]
Increasing serum suPAR levels after KT predicted recurrence of FSGS	[9]	Serum suPAR levels did not increase at the time of FSGS recurrence after KT	[20]
Serum suPAR levels decreased after plasmapheresis or at remission of FSGS	[9, 10, 12, 65, 66]	Serum suPAR levels were similar regardless of FSGS recurrence after KT or between nephrotic state and remission of FSGS	[15, 18, 70]

uPAR, urokinase-type plasminogen activator receptor; suPAR, soluble urokinase-type plasminogen activator receptor; FSGS, focal segmental glomerulosclerosis; KT, kidney transplantation; TNF, tumor necrosis factor; LPS, lipopolysaccharide.