RECURRENCE OF RECURRENT FSGS POST-TRANSPLANT IN A PEDIATRIC PATIENT: A THERAPEUTIC DILEMMA & CHALLENGES FACED

Introduction:

Recurrence of focal segmental glomerulosclerosis (FSGS) following paediatric kidney transplantation poses a significant risk to graft survival with a reported recurrence rate as high as 86% in idiopathic cases (1). This case highlights the importance of vigilant monitoring post-remission & potential role of long-term plasmapheresis (PEX) in managing the recurrence.

Methods:

Case description

We describe the case of a 10-year-old girl, diagnosed with FSGS on biopsy at 18 months of age. Genetic analysis showed NPHS-2 homozygous mutation with a value of unknown significance. Despite the treatment with RAAS inhibitors, steroids, cyclophosphamide, and calcineurin inhibitors, she responded poorly and  progressed to CKD-V. Following the bilateral nephrectomy, she underwent a live donor kidney transplant at the age of 9 years & experienced a recurrence of FSGS within 24 hours post-transplantation with marked proteinuria (urine protein creatinine ratio -7.32 gm/gm), despite stable eGFR. We describe her second recurrence after the initial response to plasmapheresis, enhanced immunosuppression and the challenges faced.

Results:

Treatment & outcome

Initial treatment involved 3 dosages of pulse methylprednisolone (MPS), daily PLEX for 5 sessions followed by one dose of rituximab (375 mg/m2) and increased immunosuppression (Tacrolimus level 9-10ng/ml). PEX was tapered to alternate days over two weeks & remission was achieved after 3-4 sessions and PEX was tapered and stopped over 12 sessions. The FSGS recurred again within one month of stopping PEX [Figure 1]. The second recurrence was managed with six daily PEX and one dose of rituximab. PEX was tapered to twice weekly over 8 weeks, weekly for 4 weeks & then monthly twice, resulting in sustained remission. PLEX sessions were subsequently tapered once a month, resulting in sustained remission for >18 weeks.

Discussion

Although various treatment options including plasmapheresis (PLEX), immunoadsorption, rituximab, and increased doses of immunosuppressants are being used (2), standard guidelines for treatment and monitoring are lacking.

 Our case highlights the importance of frequent post-remission monitoring to detect early relapse, prompt intervention contributed to maintaining the normal eGFR & achieving sustained remission. We employed a gradual tapering of PEX over several months which supported prolonged remission & better graft survival.

Conclusions:

Frequent monitoring for relapse especially after initial remission, along with a gradual tapering of PEX over an extended period may facilitate sustained remission and improved graft survival in recurrent FSGS post-transplant.

References

(1)  Weber LT, Tönshoff B, Grenda R, Bouts A, Topaloglu R, Gülhan B, Printza N, Awan A, Battelino N, Ehren R, Hoyer PF, Novljan G, Marks SD, Oh J, Prytula A, Seeman T, Sweeney C, Dello Strologo L, Pape L. Clinical practice recommendations for recurrence of focal and segmental glomerulosclerosis/steroid-resistant nephrotic syndrome. Pediatr Transplant. 2021 May;25(3):e13955. doi: 10.1111/petr.13955. Epub 2020 Dec 30. PMID: 33378587.

(2)  Raina R, Jothi S, Haffner D, Somers M, Filler G, Vasistha P, Chakraborty R, Shapiro R, Randhawa PS, Parekh R, Licht C, Bunchman T, Sethi S, Mangat G, Zaritsky J, Schaefer F, Warady B, Bartosh S, McCulloch M, Alhasan K, Swiatecka-Urban A, Smoyer WE, Chandraker A, Yap HK, Jha V, Bagga A, Radhakrishnan J. Post-transplant recurrence of focal segmental glomerular sclerosis: consensus statements. Kidney Int. 2024 Mar;105(3):450-463. doi: 10.1016/j.kint.2023.10.017. Epub 2023 Dec 22.

I have no potential conflict of interest to disclose.

I did not use generative AI and AI-assisted technologies in the writing process.