Topic Discussion: Serology based treatment of Membranous GN

Gone are the days of a kidney biopsy for Membranous GN… Can that happen?   Given the advent of PLAR2 antibody titers availability clinically, can we embark on a serological based approach to diagnosing and treatment of PLAR2 associated Membranous GN.  Here is a proposal from Glassock, Fervenza, Sethi  in JASN( Not evidence based at this point but pathophysiology and common sense based)

I think figures 4,5,6 summarize the entire paper nicely and are good flow charts for clinical use.

1.       Start with measurement of PLAR2 levels and screening for secondary causes.

2.       If PLAR2 is positive and no secondary cause, you have diagnosed PLAR2 associated membranous GN( perhaps no biopsy necessary—my editorial comment)

3.       If PLAR2 is negative, a kidney biopsy is mandatory ( if no contraindications and there should be PLAR2 antigen staining done on it)

4.       If PLAR2 antigen is positive on the biopsy—it’s likely a PLAR2 associated membranous GN and perhaps in immunological remission as PLAR2 antibodies were negative.  If the PLAR2 antigen in kidney is negative,   measurement of THDS7A antibody in serum and it’s antigen staining in the kidney should be performed. If that is positive, you have diagnosed THDS7A associated membranous GN and that has a strong association with cancer and hence  aggressive screening for cancer needs to be done.  IF it is PLAR2 antigen and THDS7A antigen negative but IgG subclass 3 positive, secondary causes need to be considered as this is secondary membranous GN.

5.       Once diagnosed with PLAR2 + membranous GN,  and the titer is in the high range( highest range in the respective lab), and any level of proteinuria,  the titer should be repeated twice a month and if it continues to rise, start cytotoxic agents.  If moderate PLAR2 or low and has nephrotic  or non nephrotic syndrome, again follow the titers and if rising, start treatment.  If titers are down trending or proteinuria is improving, no treatment necessary. There is going to be immunological remission before the proteinuria and clinical remission

6.       If PLAR2 AB response is rapid and >90% reduction in <6 months, consider stopping treatment

7.       If PLAR2 AB is 50% in 6 months or no response, consider changing treatment options

8.       If the response is slow (50-90%) at 6 months, continue treatment for longer time frame.