Update on the treatment of focal segmental glomerulosclerosis in renal transplantation

Abstract

Focal segmental glomerulosclerosis (FSGS) represents one of the most severe glomerular diseases, with frequent progression to end-stage renal disease and a high rate of recurrence in renal allografts (30%-50%). Recurrent FSGS portends a negative outcome, with the hazard ratio of graft failure being two-fold higher then that of other glomerulonephritis. Two patterns of clinical presentations are observed: Early recurrence, which is characterized by massive proteinuria within hours to days after implantation of the renal graft, and late recurrence, which occurs several months or years after the transplantation. Many clinical conditions have been recognized as risk factors for recurrence, including younger age, rapid progression of the disease to end-stage renal disease on native kidneys, and loss of previous renal allografts due to recurrence. However, much less is known about the incidence and risk factors of the so-called "de novo" type of FSGS, for which sufferers are transplanted patients without disease on native kidneys; but, rapid development of allograft failure is frequently observed. Management of both forms is challenging, and none of the approaches proposed to date have been demonstrated as consistently beneficial or effective. In the present review we report an update on the available therapeutic strategies for FSGS in renal transplantation within the context of a critical overview of the current literature.

Keywords: Focal segmental glomerulosclerosis; Kidney transplantation; Permeability factors; Plasma exchange; Rituximab.

Figure 1

Evolution of the therapeutic approaches for focal segmental glomerulosclerosis recurrence and related recent perspectives. The various treatments and their mechanisms are represented by the star shapes. CyA: Cyclosporine; PE: Plasma exchange; MMF: Mycophenolate mofetil; suPAR: Soluble form of the urokinase type plasminogen activator receptor; CYC: Cyclophosphamide; RTX: Rituximab^®; IA: Immuno-adsorption; Synpo: Synaptopodine; SMLPD-3b: Sphingomyelin-phosphodiesterase-acid-like-3b protein. Note: Steroids also regulate the podocyte activity of stabilizing the actin cytoskeleton, preserving glomerular permeselectivity, and directly reducing apoptosis via the PI3K/Akt signaling pathway.