Abstract: SA-PO813
Novel Therapy for Recurrent Dense Deposit Disease in an Adolescent Kidney Transplant Recipient
Session Information
- C3G, TMA, MGRS, Amyloidosis, and More
October 26, 2024 | Location: Exhibit Hall, Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Glomerular Diseases
- 1402 Glomerular Diseases: Clinical, Outcomes, and Therapeutics
Authors
- Wei, Khaing San, University of Arkansas System, Little Rock, Arkansas, United States
- Nester, Carla M., University of Iowa Health Care, Iowa City, Iowa, United States
- Khan, Nasir, University of Arkansas System, Little Rock, Arkansas, United States
Introduction
Dense deposit disease (DDD) is a rare C3 glomerulopathy caused either by genetic or acquired drivers of overactivation of the alternative complement pathway.It most frequently affects children and young adults,and 50% progress to ESKD within 10 yrs of diagnosis.It poses a significant challenge in post-kidney transplant care due to high recurrence rates associated with allograft failure.To date, no specific targeted interventions have consistently improved outcomes for either primary or recurrent C3G.We present a compelling case of early recurrent DDD in a renal transplant adolescent recipient managed with Iptacopan, an oral complement factor B inhibitor.
Case Description
A 19-year-old Caucasian female diagnosed with hypocomplementemic DDD at the age of 6. Disease was associated with high titer nephritic factors and normal genetic studies. She was initially treated with cyclosporine and later switched to tacrolimus (Tac). Persistent proteinuria with UPCR15mg/mg led to a switch to mycophenolate (MMF). Her renal function progressively declined necessitating PD dependence for ESKD at age 14.She underwent DDKT 1.5 months before turning 19. She received ATG and prednisone taper for induction and post-transplant immunosuppressants, including Tac, MMF and prednisone. She suffered primary allograft dysfunction necessitating HD on post-op day 4. An allograft biopsy was performed 1 week postoperatively, which showed recurrent DDD and was negative for acute rejection. The patient was started on Iptacopan 200 mg BID on day 26th post- transplant. Prior to Iptacopan, her C3 was 8, C5 was 8.7, FB was 18.7, soluble C5b-9 was 0.69. 3 days after Iptacopan, C3 increased to 90, C5 to 19.9, FB to 24. C5b-9 decreased to 0.12. After 1 week, C3 increased to 111 and creatinine decreased from 2.6 to 1.8 mg/dl and proteinuria decreased.
Discussion
Iptacopan is an oral, first-in-class and selective inhibitor of factor B, a key component of the alternative pathway. In our patient, after failed conventional treatments, leading to a quick recurrence of disease in the allograft.Iptacopan lead to a significant clinical and biochemical remission of disease. Our case highlights the possibility that this aggressive renal disease is salvable even in the transplant settings by using a targeted treatment approach and further supplements the clinical trial results from native kidney C3G.