Abstract
BACKGROUND: Genetic defects in podocyte proteins account for up to 30% of steroid-resistant nephrotic syndrome (SRNS) in the paediatric population. Most children with genetic SRNS are resistant to immunosuppression and at high risk of progression to stage 5 chronic kidney disease. Kidney transplantation is often the treatment of choice. The possibility of post-transplantation disease recurrence in genetic SRNS remains controversial, and poses fundamental questions about disease biology.
METHODS: We critically evaluated the published cases of post-transplantation recurrence in genetic patients, particularly testing 'mutations' against the most recent population variant databases, in order to clarify the diagnoses, and compare the clinical courses and responses to therapy.
RESULTS: Biallelic pathogenic variants in NPHS1 leading to a complete absence of nephrin were the most commonly reported and best understood instance of nephrotic syndrome occurring post-transplantation. This is an immune-mediated process driven by antibody production against the novel nephrin protein in the allograft. We also identified a number of plausible reported cases of post-transplantation recurrence involving pathogenic variants in NPHS2 (8 patients, biallelic), one in WT1 (monoallelic) and one in NUP93 (biallelic). However, the mechanism for recurrence in these cases remains unclear. Other instances of recurrence in genetic disease were difficult to interpret due to differing clinical criteria, inclusion of patients without true pathogenic variants or the influence of other factors on renal outcome.
CONCLUSIONS: Overall, post-transplantation recurrence remains very rare in patients with genetic SRNS. It appears to occur later after transplantation than in other patients and usually responds well to plasmapheresis with a good renal outcome.
| Original language | English |
|---|---|
| Pages (from-to) | 3757-3769 |
| Number of pages | 13 |
| Journal | Pediatric Nephrology |
| Volume | 36 |
| Issue number | 11 |
| Early online date | 24 May 2021 |
| DOIs | |
| Publication status | Published - Nov 2021 |
Bibliographical note
Funding Information:This research was supported by the Elizabeth Blackwell Institute, University of Bristol, and funded in part by the Wellcome Trust. For the purpose of Open Access, the author has applied a CC BY public copyright licence to any Author Accepted Manuscript version arising from this submission. A.B is funded by Kidney Research UK (Post-doctoral Fellowship). This work was also supported by the Wellcome Trust Institutional Strategic Support Fund.
Publisher Copyright:
© 2021, The Author(s).