Introduction: Primary FSGS recurs in up to 60% of first transplants, significantly impacting allograft longevity and patient quality of life. We sought to evaluate pathological features in the first biopsy documenting recurrence that may be associated with clinical outcome in a cohort of patients with FSGS.
Methods: This is a retrospective multicenter cohort study of children with FSGS from Italy and the United States. Children (< 18 years old) with any form of FSGS were included in the cohort. Clinical, pathological, and immunogenetic data was collected by chart review. Data analysis was performed using Stata v18. Statistical significance was set at a p-value < 0.05. Cox proportional hazards models were used to estimate hazards.
Results: The cohort included 105 patients of whom 38 (36.2%) experienced FSGS recurrence at a median of 4 [IQR 2, 8] days after transplant, of whom 33/38 had a biopsy (86.8%). Biopsy occurred a median 81 [IQR 11, 342] days after transplant. At the time of biopsy, patients had median urine protein to creatinine ratio 4.0 [IQR 0.94, 8.2] mg/mg creatinine, and eGFR 49.2 [IQR 26.2 – 79.1] ml/min/1.73m2 (CKiD U25). Biopsies identified FSGS recurrence (21/38), rejection (19/38), and BK nephropathy (1/38). At the end of follow-up, patients who had not experienced allograft loss had a median eGFR 68.2 [IQR 55.5 – 93.6] ml/min/1.73m2 (CKiD U25). Patients with FSGS recurrence were most likely to experience allograft loss, which was seen in 28/105 (26.6%) of patients at a median 2.98 [IQR 1.37 – 7.3] years after transplant. Three patients died (13 mo, 3 years, and 14 years post-transplant), however the etiology of their death is not available.

We found no differences in recurrence rates by race/ethnicity, age, donor type, or induction agent. Among the pediatric kidney transplant recipients who experienced recurrence post-transplant, we found heterogeneity in histopathology and no features on LM or EM were significantly associated with long-term outcomes, although patients with C4d on biopsy were more likely to experience graft failure, but primarily due to rejection. As would be expected, those with genetic FSGS had a significantly lower risk of recurrence but not zero as 3/32 patients with genetics variants in ACTN4, INF2, and COL4A4 respectively experienced a recurrence.

Conclusions: We did not identify any features on kidney biopsy after FSGS recurrence that were predictive of long-term outcomes, however our analysis is hampered by a lower rate of FSGS recurrence than anticipated. We plan to expand the cohort to include several more centers and will perform the analysis again when we have accrued a larger sample size. Future analysis will also examine HLA expression and mismatch as risk factors for recurrence.