Abstract

Introduction

Methods

Results

Case 1

Case 2

Case 3

Case 4

Case 5

Case 6

Case 7

Discussion

Conclusion

References

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Abstract

Background
Steroid-resistant nephrotic syndrome (SRNS), commonly caused by focal segmental glomerulosclerosis (FSGS), is associated with progression to stage 5 chronic kidney disease, requirement for kidney replacement therapy and a risk of disease recurrence post-kidney transplantation. Ofatumumab (OFA) is a fully humanised monoclonal antibody to CD20, with similar mechanisms of action to rituximab (RTX).

Methods
We report a case series of seven UK patients (five paediatric, two adult), all of whom developed FSGS recurrence after kidney transplantation and received OFA as part of their therapeutic intervention. All also received concomitant plasmapheresis. The 2-year outcome of these seven patients is reported, describing clinical course, kidney function and proteinuria.

Results
Four patients (all paediatric) achieved complete urinary remission with minimal proteinuria 12 months post-treatment. Three of those four also had normal graft function. Two patients showed partial remission—brief improvement to non-nephrotic proteinuria (197 mg/mmol) in one patient, maintained improvement in kidney function (estimated glomerular filtration rate 76 ml/min/1.73 m2) in the other. One patient did not demonstrate any response.

Conclusions
OFA may represent a useful addition to therapeutic options in the management of FSGS recurrence post-transplantation, including where RTX has shown no benefit. Concomitant plasmapheresis in all patients prevents any definitive conclusion that OFA was the beneficial intervention.

Introduction
Steroid-resistant nephrotic syndrome (SRNS) is defined as proteinuria > ۲۰۰ mg/mmol creatinine, hypoalbuminaemia and clinical oedema with no remission of proteinuria following 4 weeks of high-dose (2 mg/kg) corticosteroids, or subsequent loss of steroid responsiveness over time. In childhood, focal segmental glomerulosclerosis (FSGS) is the most common histological finding in SRNS. Progression to stage 5 chronic kidney disease (CKD 5) and requirement for kidney replacement therapy is common in FSGS—۴۳–۹۴% of patients enter CKD 5 within 10 years of diagnosis, depending on immunosuppressant response [1].