Abstract: SA-PO856
Kidney Only Transplantation in Primary Hyperoxaluria Type 1: A Novel Approach in the siRNA Therapy Era
Session Information
- Transplantation: Clinical - Case Reports
November 05, 2022 | Location: Exhibit Hall, Orange County Convention Center‚ West Building
Abstract Time: 10:00 AM - 12:00 PM
Category: Transplantation
- 2002 Transplantation: Clinical
Authors
- Breeggemann, Matthew Clarence, University of California San Francisco, San Francisco, California, United States
- Gluck, Stephen L., University of California San Francisco, San Francisco, California, United States
- Stoller, Marshall L., University of California San Francisco, San Francisco, California, United States
- Lee, Marsha May, University of California San Francisco, San Francisco, California, United States
Introduction
Primary hyperoxaluria type 1 (PH1) is a disease of impaired hepatic glyoxylate metabolism due to a deficiency in alanine glyoxylate aminotransferase (AGT) activity. PH1 is a major risk factor for calcium oxalate kidney stones, nephrocalcinosis, and end stage renal disease (ESRD). Following the onset of chronic kidney disease (CKD), plasma oxalate levels rise and oxalate deposition may occur in a variety of tissues. Oxalosis causes significant morbidity and mortality in this patient population and oxalate levels can continue to accumulate even with aggressive dialysis. The current surgical management of PH1 is combined liver-kidney transplantation. With the advent of silent RNA (siRNA) therapies targeting the hepatic overproduction of oxalate, kidney only transplantation is a practical novel approach for managing PH1 patients with severe renal impairment. We present the first known case of kidney only transplantation in a PH1 patient receiving siRNA therapy.
Case Description
A 17 year old patient with PH1 developed ESRD and was started on hemodialysis (HD). Three months after HD initiation, they started nedosiran on a compassionate use basis and declined an offer for a combined liver-kidney transplant in favor of waiting for a kidney only transplant. At age 19 years, they received a deceased donor kidney transplant and maintained on hemodialysis post-operatively to decrease oxalate burden (goal pre-HD plasma oxalate < 3 umol/L) while continuing nedosiran. Subsequently, HD frequency decreased significantly and will likely be discontinued altogether at approximately six weeks post-transplantation.
Discussion
PH1 is a devasting kidney stone disease. Prior to 2020, there were no FDA approved drugs to treat PH1 and limited medical therapies aimed at delaying the onset of CKD and oxalosis were available. Definitive treatment in those with CKD has been combined liver-kidney transplantation to simultaneously replace the hepatic AGT deficiency and treat the renal impairment. Available novel siRNA therapies not only offer hope to the community of this ultra-rare disease but potentially eliminate the need for liver transplantation. This case is the first known kidney only transplant in a PH1 patient on siRNA therapy and may represent a major shift in the management of this vulnerable patient population.