Research Viewpoints Recurrent Focal Segmental Glomerulosclerosis

Viewpoint On

Shoji J, Mii A, Terasaki M, Shimizu A: Update on Recurrent Focal Segmental Glomerulosclerosis in Kidney Transplantation. Nephron DOI 10.1159/000510748

Recurrent focal segmental glomerulosclerosis (FSGS) in a kidney allograft performed in a patient with kidney failure presumed to be due to primary (permeability factor-related) FSGS is a common occurrence (up to 70% of such patients experience a recurrence when secondary and genetic forms of FSGS have been excluded). Such recurrences are highly predictive of graft failure. Repeated recurrences occur in up to 90% of patients retransplanted after loss of the first graft to a recurrence of FSGS. Thus, this is a very serious problem needing a good solution involving a better identification of risk, a better monitoring of the recurrence itself, a better understanding of the mechanisms involved and, most of all, how to prevent recurrence or to treat it when it has developed.

Shoji and colleagues provide an excellent and up to date review of the permeability factors posited to be involved in recurrences of primary (permeability factor-related) FSGS. Clearly multiple clinical factors present in the patient with presumed primary FSGS prior to transplantation can help to roughly estimate the risk of a recurrence. The earliest lesion identifying a recurrence can be found on electron microscopy of post-transplant kidney biopsies, showing diffuse foot process effacement. Unfortunately, the “permeability factors” believed to be operating in recurrent primary FSGS are biochemically heterogeneous and likely cause podocyte injury by a variety of mechanisms.

While much progress has been made, the lack of consistent confirmatory studies has hampered the application of assays for these factors in clinical kidney transplantation. Perhaps a “panel” of assays will help to alleviate this deficiency. At this moment, testing for single factors may not be sufficient for evaluation of risk or for post-transplant monitoring, and none have reached any kind of regulatory approval. More work is clearly needed. Sadly, this otherwise excellent review did not analyze how the knowledge concerning permeability factors, as limited as it is, might be best applied to specific prevention and treatment stratagems, such as PLEX, immunoadsorption, anti-CD20 monoclonal antibodies, or lipid apheresis. Perhaps this will be the topic of a follow-up mini-review.