Kidney Week

Abstract: TH-PO521

Narsoplimab Treatment for Recurrent IgA Nephropathy Stabilized eGFR and Proteinuria

Session Information

• Glomerular Diseases: Clinical, Outcomes, Trials - I
  November 03, 2022 | Location: Exhibit Hall, Orange County Convention Center‚ West Building
  Abstract Time: 10:00 AM - 12:00 PM

Category: Glomerular Diseases

• 1303 Glomerular Diseases: Clinical‚ Outcomes‚ and Trials

Authors

• Storrar, Joshua, Northern Care Alliance NHS Foundation Trust, Salford, Manchester, United Kingdom

Joshua Storrar,

• Rainone, Francesco, Northern Care Alliance NHS Foundation Trust, Salford, Manchester, United Kingdom

Francesco Rainone,

• Middleton, Rachel, Northern Care Alliance NHS Foundation Trust, Salford, Manchester, United Kingdom

Rachel Middleton,

• Barratt, Jonathan, Leicester General Hospital, Leicester, Leicester, United Kingdom

Jonathan Barratt,

Introduction

IgA nephropathy (IgAN) recurrence is a risk post-transplantation, and treatment options are limited. The complement system plays an important role in the pathogenesis of IgAN. Narsoplimab is an investigational mAb that targets the effector enzyme of the lectin pathway of complement, MASP-2. We present the first report of a complement inhibitor being used for treatment of recurrent IgAN.

Case Description

A 53-year-old male with hypertension diagnosed with IgAN in 2010 underwent a live related kidney transplant in 2014. Transplant biopsy in 2019 due to rising proteinuria (peak urine protein:creatinine ratio [uPCR] 429 g/mol) revealed strong mesangial positivity for IgA with weaker C3 staining. EM supported diagnosis of recurrent IgAN. The patient was monitored for 17 months with repeat biopsy undertaken in Nov 2020 due to falling estimated glomerular filtration rate (eGFR, 30 ml/min/1.73m²), rising uPCR (818 g/mol), and symptomatic worsening oedema.
The patient was treated with budesonide, along with compassionate use narsoplimab, which was started Feb 2021 for 18 weeks, and completed Jul 2021 (Fig). eGFR from start to end of treatment remained stable from 21 ml/min/1.73m² to 18 ml/min/1.73m², whereas it dropped significantly in the 6 months prior from 36 ml/min/1.73m² to 21 ml/min/1.73m². uPCR from start to end of treatment dropped significantly from 1,191 g/mol to 467 g/mol. A biopsy taken in Jul 2021 showed features of advanced recurrent IgAN. The patient received 5 more infusions of narsoplimab between Dec 2021 and Jan 2022, but subsequently progressed to end-stage kidney disease and began dialysis.

Discussion

This is the first time narsoplimab has been reported to stabilize eGFR and uPCR in a patient with recurrent IgAN. The lack of complement degradation products seen with IF on kidney biopsy post-treatment suggests that stabilization is due to complement inhibition. Further reports of narsoplimab use in progressive recurrent IgAN are eagerly awaited.