IN the NEWS: Is this the end of suPAR?

Clinical and experimental evidence suggests the pathogenic role of circulating permeability factors, including soluble urokinase plasminogen activating receptor (suPAR). Serum suPAR levels were found to be elevated in Caucasian adults with primary FSGS and in two cohorts of children with FSGS from Europe and the United States. 

          This new study in KI March 2014 issue from India looked at the role of suPAR in all children with nephrotic syndrome. Compared to controls, suPAR levels were highest in FSGS and then other nephrotic syndromes from MCD and other congenital diseases. Interestingly, the study failed to show that this circulating factor that was really hallmark of FSGS diagnosis was specific for FSGS. Rather, it might be a biomarker for nephrotic syndrome in general.  Interestingly, levels of suPAR significantly correlated inversely with eGFR and CRP.

          So what this study is telling us is that suPAR gets elevated with downtrending GFR- perhaps it’s just a renal clearance marker. In addition, suPAR has been found to be elevated in sepsis, malaria and chronic infections such as Hepatitis and HIV. So it’s unclear if suPAR really is a marker of podocyte injury but rather a marker of generalized inflammation. 

          So, suPAR doesn’t answer our question for FSGS permeability factor anymore.  This study really highlighted the non specificity of suPAR for FSGS and even perhaps podocyte injury.

          

IN THE NEWS: SuPAR and FSGS more data revealed

A study done recently looked at suPAR levels in adults and pediatric patients with FSGS of two cohorts - the FSGS CT and PodoNet Cohort.  Compared to controls, they were elevated in 83% and 55% in two respective cohorts. Interestingly, MMF treated was associated with lower levels as compared to cyclosporine. In addition, it appears that the ones that had lower levels had more likely chance of remission. 

Why did one group of cohorts have a higher suPAR relationship compared to other? The mean serum creatinine was significantly higher in patients enrolled in the FSGS CT cohort than the PodoNet cohort and the authors suggest that this might be the reason for the difference. The entire article is an interesting read. 

The take home points are:

1. The circulating suPAR levels were markedly elevated in the majority of patients with primary FSGS in two distinct cohorts including children and adults
2. When evaluated with CRP levels, it was not due to inflammation that the suPAR was elevated. 
3. MMF therapy was associated with a lower serum level of suPAR; 
4. A decline in suPAR levels that was sustained over the course of 26 weeks of treatment was associated with decreased in proteinuria and remission
5. Serum suPAR levels were higher in familial cases including those with a defined podocin mutation.
6. Female patients had higher suPAR levels in both cohorts- unclear why.

Anti suPAR drugs should be great agents if this association continues to hold with FSGS??

Check out the full article in JASN

Journal Club: SuPAR and FSGS

Journal Club:SuPAR and FSGS

View more presentations from Nephrology, NSLIJ

IN THE NEWS: SuPAR circulating Factor for FSGS

Finally, the circulating factor in FSGS has been likely identified. Take a look at the most recent Nature paper by Wei et al. Some summary points:

1. Serum soluble urokinase receptor (suPAR) is elevated in 2/3 of the patients with FSGS
2. It is not elevated in other proteinuric glomerular diseases
3. Higher concentrations before transplantation- might suggest risk of recucurrence
4. Mouse models showed that elevated suPAR caused FSGS like pathology ( foot process effacement)
5. SuPAR decreased with plasmapheresis.

What is suPAR:- it is normal to have some amount of it as it is responsible for neutrophil trafficking.
Interestingly, it is elevated in HIV and some cancers- hmmm? perhaps a factor in HIV associated FSGS as well?
Can this be used as a marker? Perhaps- and even as a predictor of recurrence?
Can galactose bind to this circulating factor? Perhaps?...
What about the other 1/3 of FSGS?

Check out the ref at:
http://www.ncbi.nlm.nih.gov/pubmed/21804539