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Ofatumumab treatment for nephrotic syndrome recurrence after pediatric renal transplantation

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Abstract

Background

Relapsing nephrotic syndrome (NS) after transplantation can be a challenge to treat. The result of the consequent long-lasting proteinuria is the loss of the graft. Disease recurrence after renal transplantation occurs in around half of cases, and the efficacy of therapeutic strategies is often limited. Recently, ofatumumab, a second-generation and fully human anti-CD20 monoclonal antibody, has been shown to be effective in severe situations.

Methods

We retrospectively collected data from the medical records of children with recurrence of NS after renal transplantation treated with ofatumumab in France, after failure of previous treatments.

Results

Six patients were included in this study in five centers with a median duration of follow-up of 10.5 months. Two different ofatumumab regimens were administered. The primary outcome was proteinuria at 6 months after the last dose of ofatumumab. No patient achieved a complete remission, 3/6 had a partial remission, and 3/6 had no response to ofatumumab. Four patients exhibited a minor allergic reaction with the first infusion. One patient died of infection, as a consequence of multiple factors. No malignancies were observed; however, the time of follow-up was not sufficient to see such disease.

Conclusions

Altogether, these results suggest ofatumumab has a poor efficacy in treating recurrence of NS after renal transplantation. However, it could be discussed in multidrug-resistant refractory NS, but infectious complications and overimmunosuppression have to be balanced. There is a need for further studies to confirm these findings and safety and to determine a standardized protocol in this indication.

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Abbreviations

CD:

Cluster of differentiation

CKD 5:

Stage 5 chronic kidney disease

CNI:

Calcineurin inhibitor

CNIL:

National Commission of Information Technology and Liberties

FRNS:

Frequently relapsing nephrotic syndrome

FSGS:

Focal and segmental glomerular sclerosis

IAds:

Immunoadsorption sessions

INS:

Idiopathic nephrotic syndrome

IV:

Intravenous

IVIG:

Intravenous immunoglobulins

mAb:

Monoclonal antibody

MCD:

Minimal change disease

MMF:

Mycophenolate mofetil

NS:

Nephrotic syndrome

RTX:

Rituximab

SDNS:

Steroid-dependent nephrotic syndrome

SRNS:

Steroid-resistant nephrotic syndrome

SSNS:

Steroid-sensitive nephrotic syndrome

UPCR:

Urine protein/creatinine ratio

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Correspondence to Josselin Bernard.

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The data were coded and used in accordance with rule MR004 of the French data protection authority (CNIL). Oral consent was obtained for each patient, in accordance with French ethical standards.

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The authors declare that they have no conflict of interest.

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Bernard, J., Lalieve, F., Sarlat, J. et al. Ofatumumab treatment for nephrotic syndrome recurrence after pediatric renal transplantation. Pediatr Nephrol 35, 1499–1506 (2020). https://doi.org/10.1007/s00467-020-04567-7

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