MP47-17 NEDOSIRAN DRAMATICALLY REDUCES SERUM OXALATE IN DIALYSIS-DEPENDENT PRIMARY HYPEROXALURIA 1: A COMPASSIONATE USE CASE REPORT

Abstract

You have accessJournal of UrologyPediatric Urology III (MP47)1 Sep 2021MP47-17 NEDOSIRAN DRAMATICALLY REDUCES SERUM OXALATE IN DIALYSIS-DEPENDENT PRIMARY HYPEROXALURIA 1: A COMPASSIONATE USE CASE REPORT Kevin Shee, Justin Ahn, Fadl Hamouche, Jorge Mena, Thomas Chi, and Marshall Stoller Kevin SheeKevin Shee More articles by this author , Justin AhnJustin Ahn More articles by this author , Fadl HamoucheFadl Hamouche More articles by this author , Jorge MenaJorge Mena More articles by this author , Thomas ChiThomas Chi More articles by this author , and Marshall StollerMarshall Stoller More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000002068.17AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Primary hyperoxaluria 1 (PH1) is a rare but devastating condition, involving recurrent urolithiasis, nephrocalcinosis, early end-stage renal disease (ESRD), and multisystemic deposition of calcium oxalate crystals. Clinical management of PH1 typically involves conservative management, dialysis, and eventual combined kidney and liver transplant (CKLT). Emerging therapeutics for PH1 target key synthesis steps of oxalate production; for example, anti-LDH RNAi Nedosiran inhibits the conversion from glyoxylate to oxalate, the final step in the oxalate synthesis pathway. In this study we sought to determine whether Nedosiran could meaningfully impact the clinical course of a 17-year-old female patient with PH1 and resultant ESRD, awaiting CKLT. METHODS: An Emergency Investigational New Drug (EIND) application was filed and approved by the Food and Drug Administration (FDA). Local institutional review board (IRB) approval and patient consent were obtained. The patient received monthly abdominal subcutaneous injection from July 2020 to present. Plasma oxalate levels, drawn before and after each dialysis appointment and before each Nedosiran injection, were monitored. RESULTS: Monthly Nedosiran injections led to dramatically decreased plasma oxalate levels, from 55.5 μmol/L to 13.9 μmol/L between July and December 2020 (Figure 1). This resulted in decreased frequency of weekly hemodialysis sessions from six to three, and deferral of a combined kidney and liver transplant offer in favor of continued Nedosiran treatment. No adverse events were reported other than temporary injection site discomfort. Since starting Nedosiran, the patient has not had new nephrolithiasis events. CONCLUSIONS: Nedosiran treatment completely transformed the clinical outcome of our PH1 patient with ESRD. Rationally targeting the oxalate synthesis pathway with Nedosiran thus represents a novel and impactful treatment strategy for PH1 patients with advanced disease. These results warrant further exploration in a larger cohort of PH1 patients to determine generalizability and to identify clinical and molecular characteristics associated with response. Source of Funding: Drug doses were provided by Dicerna pharmaceuticals © 2021 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 206Issue Supplement 3September 2021Page: e830-e830 Advertisement Copyright & Permissions© 2021 by American Urological Association Education and Research, Inc.MetricsAuthor Information Kevin Shee More articles by this author Justin Ahn More articles by this author Fadl Hamouche More articles by this author Jorge Mena More articles by this author Thomas Chi More articles by this author Marshall Stoller More articles by this author Expand All Advertisement Loading ...