ESPN 51th Annual Meeting

ESPN 2018


 
Rituximab for induction in Nephrotic Syndrome: How many rounds of fire are necessary?
PER WITTENHAGEN 1 METTE NELAND 1

1- HC ANDERSEN CHILDRENS HOSPITAL, ODENSE UNIVERSITY HOSPITAL
 
Introduction:

Relapsing nephrotic syndrome (NS) despite use of prednisolone, CNI, MMF and cyclophosphamide is associated with the worst renal outcomes. Rituximab has substantially improved treatment outcome for these patients, but reports have emerged of Rituximab-resistant NS.

Material and methods:

Case reports of successful induction of remission in prednisolone- and CNI-resistant NS.

Results:

Case 1: 4 years old boy with CNI-treated steroid-dependent NS. During a relapse with massive proteinuria he developed steroid resistance without response to repeated IV methylprednisolone (15 mg/kg). Case 2: 11 months old boy with only partial remission to oral prednisolone (2 mg/kg). Because of steroid toxicity (extreme failure to thrive) CNI was attempted without remission. Biopsy in both children showed MCN, no mutations for NS were found. The course of Rituximab induction therapy with (375mg/m2) and the proteinuria (albumin/creatinine ratio) is shown in the figure below. The CD19-positive cells were cleared within 2 weeks of starting treatment but remission occurred 2-3 weeks after completing the 6 doses of Rituximab.

Conclusions:

We here demonstrate 2 successful treatments using 6 weekly doses of Rituximab for the induction of remission in children with life threatening symptoms due to therapy resistant NS. The plasma half-life of Rituximab in patients with severe proteinuria is less than a day compared to 20-30 days in the non-proteinuric patient. Since case reports have suggested the term “Rituximab-resistant nephrotic syndrome” we would like to emphasize the importance of both dosing and frequency of CD20 depleting drugs. Previous reports of remission after usage of Ofatunomab could possibly be a result of continuation of CD20 depletion and not a true improved effect of this new anti-CD20 antibody. A clear definition of the term “Rituximab resistance in NS” is needed for further studies.