As has been mentioned in previous post, the identification of the anti-PLA2R antibody has the potential to revolutionize the diagnosis of membranous GN and is already being used clinically on a small scale. It is found in 70% of patients with idiopathic MN and could replace a renal biopsy in some cases.
Last week, a paper was published in Nature Medicine that may be equally revolutionary. For a long time it has been suspected that a there is a circulating factor that is responsible for at least some cases of primary FSGS. This is suggested by the fact that recurrent FSGS after transplantation can be treated with plasmapheresis. However, up to now, this factor has remained elusive.
In 2008, a paper was published reporting that induction of the urokinase receptor in the podocytes of mice led to foot process effacement and proteinuria. The authors postulated that a circulating, soluble form of this receptor (suPAR), that is normally present in low concentration in the serum, could be responsible for some cases of recurrent FSGS.
They took 78 patients with FSGS and measured their levels of suPAR, comparing them to normal controls and patients with other glomerular diseases including MN, MCD and pre-eclampsia. Elevated suPAR levels were noted in the patients with FSGS and the highest levels were seen in the pre-transplant sera of patients who went on to develop recurrent FSGS after transplantation. Using 3000 pg/ml as a cut-off, 2/3 of the patients with FSGS had an elevated serum suPAR compared to no healthy controls, and no patients with MCD or pre-eclampsia. 4/11 patients with MN had suPAR levels in this range although the mean level was far lower. suPAR levels were also seen to fall significantly following plasmapheresis. Using 3 different models, they then showed that increased levels of suPAR caused foot process effacement and proteinuria in mice.
It is thought that suPAR mediates its effect by depositing in the glomeruli and activating podocyte β3 integrin. This appears to be enough to initiate foot process effacement. Measuring suPAR levels may be a means of guiding therapy for recurrent FSGS and could provide a new target for treatments in the future.