Abstract
BACKGROUND: Focal segmental glomerulosclerosis (FSGS), a clinicopathological condition characterized by nephrotic-range proteinuria and presenting microscopically as focal segmental sclerosis of the glomerulus, often progresses to end-stage renal disease. Patients with primary FSGS who undergo kidney transplantation often experience recurrence, leading to graft function loss and ultimately a shortened life span. However, the pathogenesis about post-transplant recurrence of FSGS remains unclear. SUMMARY: The mainstream hypothesis is the circulating factor, which mediates podocyte injury. Although a unified gold standard circulating factor has yet to be established, several candidate circulating factors have been proposed, including soluble urokinase plasminogen activator receptor (suPAR), the CD40-CD40L axis, cardiotrophin-like cytokine factor 1 (CLCF-1), apolipoprotein A-Ib (ApoA-Ib), and anti-nephrin antibody. These candidates have demonstrated associations with recurrent FSGS in clinical or basic research, but each has certain limitations. Additionally, advancements in renal biopsy, podocyte molecular signaling targets, and microRNAs provide support for the development of novel molecular biomarkers. Currently, there is no unified guideline for the treatment of post-transplant recurrent FSGS. Common therapeutic options include plasma exchange, calcineurin inhibitors, corticosteroids, and rituximab. KEY MESSAGES: This article summarizes the latest research advancements of circulating factors in post-transplant recurrence of FSGS and also highlights recent discoveries in potential molecular biomarkers and therapeutic approaches. Post-transplant recurrence of FSGS is a rare and complex heterogeneous disease that seriously affects the health of patients. The review aimed to provide valuable and up-to-date information support for researchers in this field and give potential research perspectives in the future.