*Purpose: Primary focal segmental glomerulosclerosis (FSGS) is a glomerular disease that frequently recurs after kidney transplantation. Several circulating factors have been proposed to cause recurrence of FSGS in the allograft, but pathophysiology remains largely unclear and treatment options are limited. Clinical predictors have not been validated since cohorts are small due to low incidence and large registries suffer from misclassification of disease and missing data.

*Methods: We established The Post-TrANsplant GlOmerular Disease (TANGO) study to comprehensively analyze the recurrence of glomerular diseases post-transplant in a large, international cohort of kidney transplant recipients. All consecutive subjects with biopsy-proven, primary FSGS who received a kidney transplant between 2005-2015 were retrospectively identified in 15 TANGO-study centers in Europe (n=5), United States (n=6) and Brazil (n=4). Detailed serial patient information was collected at the time of transplant and every year after transplant. Serum of samples from FSGS patients are currently being collected.

*Results: 552 kidney transplant recipients have been recruited to the study so far, of which 106 patients had the diagnosis of primary FSGS after stringent exclusion of all patients with possible secondary causes of FSGS. The incidence of recurrence was 30% (95% CI: 0.21-0.39). Contrary to previous studies, Cox regression analyses showed an increased risk of recurrence with age of primary diagnosis (aHR 1.04 per year, p=0.005, 95% CI 1.01-1.08). Recipients of grafts from living donors had an aHR of FSGS recurrence of 2.56 compared to deceased donor recipients (p=0.026, 95% CI: 1.12-5.88). Pre-transplant plasmapheresis had no effect on recurrence rate. However, in patients with a recurrence, pre-transplant plasmapheresis increased the chance of achieving complete remission with post-transplant treatment (aOR: 3.99, p=0.014, 95% CI: 0.81-7.17). Within patients with recurrent FSGS, only 7 (15%) and 16 (33%) patients achieved complete or partial remission after treatment, respectively. There was no difference in the remission rates across different treatment strategies, including high dose steroids, plasmapheresis/IVIG and/or rituximab. 16 (33%) of patients with FSGS recurrence experienced graft failure within 23 (1-56) months of recurrence.

*Conclusions: Our international multicenter cohort of kidney transplant recipients with primary FSGS allowed us to identify risk factors for recurrence and predictors of response to therapy. Complete remission was only achieved in 15% of patients independent of applied treatment strategies. Further studies to refine our understanding of the natural history of this severe condition and to explore the underlying mechanism with biobanked samples will be crucial to tackling this clinical challenge.

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