A case of late recurrence of FSGS after kidney transplantation maintained in complete remission with rituximab and plasma exchange therapy

Focal segmental glomerulosclerosis (FSGS) is a major cause of nephrotic syndrome and frequently recurs following kidney transplantation. In cases of recurrence immediately after transplantation, anti-nephrin antibodies have been reported to be involved, and in some cases, renal function may be lost due to treatment resistance. On the other hand, there are rare cases of late recurrence after transplantation, but there are very few reported cases and the details are often not well understood.

A 35-year-old man developed nephrotic syndrome at age 13. Initially, he achieved complete remission with corticosteroid therapy, but experienced frequent recurrence, and renal biopsy confirmed FSGS. Despite various immunosuppressive therapies, he progressed to end-stage kidney disease and initiated hemodialysis at age 33, one year prior to kidney transplantation. No causative genetic variants for FSGS were identified. Prior to undergoing ABO-incompatible living-donor kidney transplantation, he received rituximab (RTX, 300 mg), double-filtration plasmapheresis (DFPP, twice), and plasma exchange (PE, once). He achieved complete remission post-transplant and maintained it for one year. One year after transplantation, urinary protein increased to 1.25 g/gCr. Despite intensified conservative therapy—including dietary modification and an increased dose of angiotensin receptor blockers—proteinuria worsened to 2.61 g/gCr. Graft biopsy revealed recurrent primary FSGS without secondary causes. Immunofluorescence staining showed IgG deposition along GBM. No obvious Electron dense deposit was observed by electron microscopy. Serological testing and immunofluorescent staining of biopsy specimens performed at Kobe University revealed both negative serum anti-nephrin antibody titers and negative glomerular staining. Blood tests before RTX administration showed CD19 0.6%, CD20 0.4%.

The patient underwent three sessions of PE, resulting in a marked reduction in proteinuria to 0.32 g/gCr. Subsequent RTX administration (300 mg, once) induced complete remission. Approximately 15 months after RTX administration, the patient developed an infection and his urinary protein rose to 3.15 g/gCr. Although both CD19 and CD20 were 0.1%, RTX (300 mg, once) was administered due to FSGS recurrence. The improvement in urinary protein was slow and the urinary occult blood was positive, so graft biopsy was performed, which revealed recurrent FSGS. Approximately 4 months after RTX administration, the urinary protein achieved complete remission.

As in this case, where Steroid-sensitive nephrotic syndrome progresses to Steroid-resistant nephrotic syndrome and slowly progresses to end-stage renal failure, there is a possibility of late recurrence after kidney transplantation. Humoral factors other than anti-nephrin antibodies may be involved, and treatment with RTX and PE was very effective. While removal of humoral factors by PE was extremely effective, the direct action of RTX, independent of B cell removal, may also improve urinary protein. Treatment intervention before transplantation, early diagnosis at the time of recurrence, and early treatment intervention were highly effective for late recurrence FSGS.