Abstract: PO2000
Compassionate Use Treatment with RNAi Medication (Nedosiran) in Two Patients with Primary Hyperoxaluria Type 1 and Maintenance Hemodialysis
Session Information
- Pediatric Nephrology: Genetics, Kidney Stones, Quality Improvement, and Case Reports
November 04, 2021 | Location: On-Demand, Virtual Only
Abstract Time: 10:00 AM - 12:00 PM
Category: Pediatric Nephrology
- 1700 Pediatric Nephrology
Authors
- Hoppe, Bernd, German Hyperoxaluria Center, Bonn, NRW, Germany
- Schalk, Gesa, Kindernierenzentrum, Bonn, Germany
- Martin Higueras, Cristina, German Hyperoxaluria Center, Bonn, NRW, Germany
Introduction
The primary hyperoxalurias (PH) are three ultra-rare, autosomal recessive genetic disorders characterized by oxalate overproduction in the liver. Hyperoxaluria induces recurrent kidney stones, nephrocalcinosis, progressive renal impairment, and systemic oxalosis, especially in PH1. Nedosiran is an investigational RNA interference (RNAi) therapeutic administered monthly by subcutaneous injection. It reduces hepatic LDHA protein thereby inhibiting the final step responsible of oxalate production in all types of PH.
Case Description
We report on two PH1 patients, a 40 year old woman (a) on hemodialysis (HD) 6 x 3 hours weekly, and a 6.5 year old boy (b) receiving 5 x 5 hours HD, both homozygous for AGXT c.508G>A and treated with pyridoxine. In patient (a), global longitudinal strain (GLS), an index of left ventricular contractibility, was impaired (-13%; normal ≤-18%). Patient (b), has massive oxalate osteopathy, myocardial hypertrophy and cardiac insufficiency (GLS of – 9.98). They received Nedosiran as compassionate use medication for now 6 months. Monthly plasma oxalate (Pox in µmol/l, normal <7.4) was measured, Speckle Echo and/or 3 Tesla bone MRI (left knee) were repeated. Speckle echo improved significantly in both (a: GLS – 23%; b: GLS -16.5%). Bone MRI ameliorated in patient (b) showing a nidus of normal trabecular structure.
Discussion
Clinics improved and Pox declined over the six months of treatment. Pox was influenced in (b) by severe oxalate osteopathy and therefore possibly dissolving oxalate and in (a) when dialysis regimen was reduced to 4 x 3 hours at month 6. We cautiously conclude, that Nedosiran treatment reduces plasma oxalate levels in a way, that liver transplantation may be avoidable in PH1 patients.
Follow up under Nedosiran administration
| Patient | Pox Pre RNAi | Pox Month 1 | Pox Month 2 | Pox Month 3 | Pox Month 4 | Pox Month 5 | Pox Month 6 |
| (a) | 64.2-71.6 | 40.9 | 60.2 | 52.8 | 37.7 | 23.2 | 32.4 |
| (b) | 73.1-101 | 96.5 | 40.6 | 56.9 | 48.1 | 69.7 | 51.3 |