Abstract: FR-PO751
Opening New Frontiers: Nedosiran Enables Kidney-Only Transplantation for Primary Hyperoxaluria Type 1: A Case Report
Session Information
- Post-Transplantation and Case Reports
November 03, 2023 | Location: Exhibit Hall, Pennsylvania Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Transplantation
- 2102 Transplantation: Clinical
Authors
- Nasir, Asma, Ajmera Transplant Centre and Division of Nephrology, University Health Network, University of Toronto, Toronto, Ontario, Canada
- Harvey, Elizabeth A., Division of Nephrology, The Hospital for Sick Children, Toronto, Ontario, Canada
- Lieske, John C., Division of Nephrology and Hypertension, Mayo Clinic, Rochester, Minnesota, United States
- Avila-Casado, Carmen, Department of Pathology, University Health Network, University of Toronto, Toronto, Ontario, Canada
- Chan, Christopher T., Department of Medicine, Division of Nephrology, University Health Network, University of Toronto, Toronto, Ontario, Canada
- Mucsi, Istvan, Ajmera Transplant Centre and Division of Nephrology, University Health Network, University of Toronto, Toronto, Ontario, Canada
- Lemaire, Mathieu JM, Division of Nephrology, The Hospital for Sick Children, Toronto, Ontario, Canada
Group or Team Name
- Ajmera Transplant Centre and Division of Nephrology, University Health Network, University of Toronto, Canada.
Introduction
Primary hyperoxaluria type 1 (PH1) is a genetic disorder caused by deficient activity of the liver enzyme alanine-glyoxylate aminotransferase (AGT) encoded by AGXT. PH1 is associated with overproduction of oxalate that is excreted into the urine, increasing the risk for formation of calcium oxalate crystals, nephrocalcinosis, urinary stones, and kidney failure. Recent short-term placebo-controlled trials have shown the efficacy of two new siRNA-based therapies, lumasiran and nedosiran, in reducing plasma oxalate concentrations and hyperoxaluria. While combined liver-kidney transplantation has been the preferred approach for PH1 patients with kidney failure, kidney-only transplantation may be a safe alternative for those who have responded well to siRNA-based therapy. Here we describe a successful kidney-only transplant in a PH1 patient treated with nedosiran.
Case Description
This adult male had recurrent (calcium oxalate) kidney stones from 2 years of age and was diagnosed with PH1 based on reduced AGT enzyme on liver biopsy; subsequently, AGXT mutations (c.508G>A, p.G170R, and C.744_delC) were confirmed. Although partially responsive to pyridoxine, he progressed to CKD. In early 2021, he was enrolled in a phase III study to receive nedosiran monthly. Due to an acute on chronic kidney injury, he began hemodialysis in July 2021. He received a living donor kidney transplant at age 29 in early 2023 while remaining on nedosiran. Immediately post-transplant, serum creatinine level plateaued at ~150 µmol/L. A transplant biopsy revealed minimal oxalate crystal deposition. Thus, daily hemodialysis was resumed on post-transplant day 6 for two weeks. Serum creatinine remained stable, and plasma oxalate remained low at 4-8 µmol/L, as did the urine oxalate/creatinine ratio <80μmol/mmol at three months post-transplant.
Discussion
We present a patient with PH1 who underwent a successful kidney-only transplant while receiving nedosiran to reduce hepatic oxalate production. To our knowledge, this is the first reported case of kidney-only transplant after initiating this agent. If long-term safety and efficacy are confirmed, a siRNA-based approach will change the care of PH1 patients with kidney failure since kidney-only transplantation is safer than combined liver-kidney transplantation.