Opening New Frontiers: Nedosiran Enables Kidney-Only Transplantation for Primary Hyperoxaluria Type 1: A Case Report
Bibliographic record
Abstract
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.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.002 |
| Meta-epidemiology (narrow) | 0.002 | 0.001 |
| Meta-epidemiology (broad) | 0.002 | 0.003 |
| Bibliometrics | 0.002 | 0.001 |
| Science and technology studies | 0.003 | 0.002 |
| Scholarly communication | 0.002 | 0.003 |
| Open science | 0.002 | 0.002 |
| Research integrity | 0.008 | 0.005 |
| Insufficient payload (model declined to judge) | 0.003 | 0.001 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".