Focal segmental glomerulosclerosis (FSGS) is a histologically-defined lesion that results from many etiologies such as drugs, infections, and genetic mutations. It can also occur secondary to other renal lesions, and in many cases the causes is unknown and referred to as primary or idiopathic. FSGS manifests predominantly with significant proteinuria on presentation, and is a leading cause of primary proteinuric kidney disease.

Recurrence of FSGS post-transplantation is variable and unpredictable. Many factors are associated with higher risk of recurrence, such as younger age of onset of FSGS, rapid worsening of initial disease, low body mass index, and a previous history of recurrence. Early recurrence after transplantation in patients with primary FSGS is usually detected through screening for proteinuria from day one post-transplantation. Some groups have even recommended that patients with significant proteinuria undergo native nephrectomy prior to transplantation in order to ensure an accurate quantification of proteinuria post-transplant.

FSGS recurrence after kidney transplantation is a major risk factor for graft loss. The current prophylactic measures to prevent recurrence of primary FSGS are very limited. While some transplant centers use plasmapheresis or rituximab, neither have been clearly shown to significantly reduce the rates of recurrence. A recent study reported that idiopathic FSGS recurs after the first transplant in one third of cases and is associated with a five-fold higher risk of graft loss.

In a recent AJKD article, Hamroun et al reported a case of successful kidney graft reuse in an adult recipient, 8 months after post-transplant FSGS recurrence, which was resistant to all available therapeutics at that time. Prior to this report, there were two case reports of kidney transplant transfer after early primary FSGS recurrence; in both cases transplant nephrectomy and kidney graft reuse occurred very early, within the first month post-transplantation. It has been hypothesized that late nephrectomy and re-use in post-transplant FSGS recurrence is possible, however there were no prior reports of such cases.

The authors describe a 23-year-old patient with kidney failure due to primary FSGS who received a deceased donor kidney transplant. Thymoglobulin was used for induction, and maintenance triple immunosuppression included tacrolimus. Graft function was immediate. On the third post-operative day, nephrotic range proteinuria was detected. A renal allograft biopsy was performed on post-operative day ten, which confirmed primary FSGS recurrence. The recurrence was managed with corticosteroids, plasma exchange, and more immunosuppression. Three months later, the proteinuria persisted with a deteriorating renal function. A second renal allograft biopsy was done at six months post-transplant and demonstrated worsening FSGS lesions.

The patient requested a transplant nephrectomy due to non-resolving nephrotic syndrome, which was done eight months after transplantation. The kidney was then retransplanted in the second recipient, a 78-year-old man with no history of FSGS. The patient demonstrated immediate allograft function, and the allograft remained stable with non-significant proteinuria one-year post-transplantation.

Figure 1 from Hamroun et al, AJKD © National Kidney Foundation

Figure 2 from Hamroun et al, AJKD © National Kidney Foundation

The pathogenesis of primary FSGS is incompletely understood. This case, along with other reported cases of allograft nephrectomy and retransplantation in recurrent FSGS, supports the mechanism of a circulating factor as the cause of primary FSGS, as evidenced by the rapid recovery of renal allograft function after retransplantation and the improvement of the histopathologic findings. The timing of renal allograft nephrectomy for reuse is important and ideally should be done prior to extensive scarring of the graft.  The histopathological findings in this case demonstrated partial recovery of the podocyte lesion, which may also imply that the podocyte injury before scar formation can be a reversible lesion.

This case report supports the hypothesis that late nephrectomy and re-use in FSGS recurrence is possible. This practice is of significance in times when the supply of renal transplant organs does not meet the demand.

– Post prepared by Mohamed M. Ibrahim @DrMoIbrahim, nephrology transplant fellow at Washington University in St. Louis, and Andrew Malone @AndrewFMalone, AJKDBlog Contributor. 

To view Hamroun et al, please visit AJKD.org.

Title: Successful Reuse of Kidney Graft After Early Recurrence of Primary Focal and Segmental Glomerulosclerosis
Authors: Aghilès Hamroun, Jean-Baptiste Gibier, Mehdi Maanaoui, Arnaud Lionet, Viviane Gnemmi, Sébastien Bouyé, Jean-Christophe Fantoni, Benoît Averland, Corinne Antoine, Rémi Lenain, Marc Hazzan, and François Provôt
DOI: 10.1053/j.ajkd.2021.03.028