Rivfloza (nedosiran) / Alnylam, Novo Nordisk - LARVOL DELTA

Medical Management of Kidney Stones: AUA Guideline (2026) Part II: Treatment and Follow-Up of Kidney Stones. (PubMed, J Urol) - "The statements were developed based on the evidence base for this Guideline. Using the best available evidence and the expert opinion of the Panel, this Guideline offers recommendations for the initiation of dietary measures and drug therapy are provided to allow for active treatment of motivated and high-risk patients with the goal of reducing the risk of stone recurrence."

Journal • Infectious Disease • Nephrology • Renal Calculi

Early Recognition and RNAi-Based Management of Primary Hyperoxaluria Presenting as Delayed Graft Function After Kidney Transplantation (ATC 2026) - "After genetic confirmation, the patient was transitioned to RNAi-based therapy with Rivfloza® (nedosiran)... Our case and other recent literature recognize the association of Oxalate Nephropathy with DGF. Routine assessment of oxalate levels in unexplained DGF and early incorporation of genetic testing—particularly in younger candidates with unclear etiology for ESRD—can guide therapy, optimize graft outcomes, and support family counseling. Timely intervention with Oxalate lowering therapies may facilitate recovery of allograft function"

Chronic Kidney Disease • Nephrology • Renal Calculi • Transplantation

Comparative evaluation of ultrafiltration and EMSA formats for siRNA plasma protein binding: Methodological determinants and artifacts. (PubMed, Drug Metab Dispos) - "We compared ultrafiltration, agarose gel electrophoretic mobility shift assay (EMSA), and native polyacrylamide gel ESMA using the N-acetylgalactosamine (GalNAc)-conjugated siRNA, nedosiran, to identify method-dependent artifacts and guide reliable assessment...SIGNIFICANCE STATEMENT: Although general limitations of electrophoretic mobility shift assay have been reported previously, this study systematically quantifies the significant methodological divergence between agarose-based and PAGE-based electrophoretic mobility shift assay formats for small interfering RNA. By benchmarking against ultrafiltration, we reveal distinct artifact profiles for each gel matrix, providing critical guidance for interpreting discrepant plasma protein binding data in oligonucleotide development."

Journal

DCR-PHXC-301: Study for patients with Primary Hyperoxaluria to evaluate the Long-Term Safety and Efficacy of DCR-PHXC Solution for Injection (clinicaltrialsregister.eu) - P2/3 | N=29 | Active, not recruiting | Sponsor: Dicerna Pharmaceuticals Inc. | Recruiting ➔ Active, not recruiting

Enrollment closed • Nephrology

A computational model-powered platform to inform the development of GalNAc-conjugated siRNA therapeutics. (PubMed, Mol Ther Nucleic Acids) - "This platform integrates preclinical and clinical data from all seven FDA-approved GalNAc-siRNA drugs-fitusiran, givosiran, inclisiran, lumasiran, vutrisiran, nedosiran, and plozasiran-spanning multiple species (mouse, rat, monkey, and human). The platform successfully predicted the PK and simulated the PD profiles of SAL0132 in humans, which demonstrated model-informed strategies to support efficient drug development of this modality. In conclusion, this platform enables users to predict GalNAc-siRNA PK/PD profiles across species by inputting specific model parameters, providing a powerful resource to guide the development of next-generation GalNAc-siRNA therapeutics."

Journal

Isolated Kidney Transplant in Primary Hyperoxaluria-1 Enabled by Small Interfering RNA (siRNA) Therapy. Is It Time for Change? Case Report and Review of the Literature. (PubMed, Pediatr Transplant) - "This report enriches the limited experience of RNAi-enabled kidney-only transplantation in PH1. RNA interference therapy has the potential to challenge the current standard of dual liver and kidney transplantation in children and young adults with this devastating disease but requires uninterrupted access to the drug with individualized, eGFR and oxalate level adjusted dosing, continued vigilance, and reporting of long-term outcomes."

Journal • Review • Genetic Disorders • Metabolic Disorders • Nephrology • Renal Calculi • Transplantation • LDHA

KIDNEY-ALONE TRANSPLANTATION WHILE ON SIRNA THERAPY FOR PRIMARY HYPEROXALURIA TYPE 1: A MULTINATIONAL RETROSPECTIVE CASE SERIES FROM THE PH1NITX WORKING GROUP (ISN-WCN 2026) - "Lumasiran and nedosiran, which inhibit glycolate oxidase and lactate dehydrogenase A, respectively, effectively reduce oxalate burden. Summary of general characteristics:Abbreviations: AGXT, alanine-glyoxylate aminotransferase gene; CLKTx, combined liver-kidney transplantation; GFR, glomerular filtration rate; IHD, intermittent hemodialysis; IQR, interquartile range; PD, peritoneal dialysis; siRNA, small interfering ribonucleic acid.Conclusion This large international case series suggests that KATx, when paired with siRNA therapy, is emerging as a compelling alternative to LKTx for PH1 patients with KF - even when the diagnosis is made post-transplant. Based on these favorable outcomes and our collective experiences, we offer a practical checklist to assist with pre- and post-transplant planning and recommend continued vigilance for both known and unexpected complications as the treatment paradigm evolves."

Retrospective data • Genetic Disorders • Infectious Disease • Nephrology • Transplantation • LDHA

The oxalobiome: unraveling the role of gut microbiota in oxalate metabolism and its implications for kidney health and disease management. (PubMed, Clin Chim Acta) - "Innovative strategies, including RNA interference therapies (e.g., lumasiran, nedosiran), engineered probiotics, and gene-editing technologies, show promise in managing conditions like primary hyperoxaluria. Future studies should focus on mechanistic insights, standardized methodologies, and targeted microbiome-based therapies to optimize management strategies for hyperoxaluria and related systemic diseases. A comprehensive understanding of the oxalobiome is essential for developing precision medicine approaches that effectively address oxalate dysregulation and improve patient outcomes."

Journal • Review • Nephrology • Renal Calculi

Primary hyperoxaluria(s): from trials to real-life data and pipeline therapies. (PubMed, Kidney Int) - "Lumasiran, approved for PH1, inhibits glycolate oxidase and has demonstrated sustained reductions in urinary oxalate, stabilization of renal function, and reduced nephrocalcinosis in pivotal trials and in most patients in real-life. Nedosiran, targeting lactate dehydrogenase A, shows promise for PH1...Additionally, ensuring equitable access to expensive therapies presents a worldwide healthcare challenge. This mini-review summarizes recent milestones in PH pathophysiology, diagnostics, and therapeutics, emphasizing the transformative impact of RNAi therapies and future directions in managing this ultra-rare but devastating kidney disease."

Journal • Metabolic Disorders • Nephrology • Renal Calculi • Renal Disease • Transplantation • LDHA

Small RNA or oligonucleotide drugs and challenges in evaluating drug-drug interactions. (PubMed, Front Pharmacol) - "Widespread adoption of these strategies has further enabled the application of oligonucleotides as viable drugs and expanded the class of RNA therapeutics, with thirteen antisense oligonucleotides (ASOs) (fomiversen, mipomersen, nusinersen, inotersen, eteplirsen, golodirsen, casimersen, viltolarsen, tofersen, eplontersen, olezarsen, and donidalorsen), seven small interfering RNAs (siRNAs) (patisiran, givosiran, lumasiran, inclisiran, vutrisiran, nedosiran, and fitusiran), and two aptamers (pegaptanib and avacincaptad pegol) that have been approved by the United States Food and Drug Administration (FDA). This article provides an overview of FDA-approved oligonucleotide therapies, emphasizing chemical modifications, molecular targets for mechanistic actions, and available ADME and PK/PD properties, followed by the discussion of critical needs for risk assessment strategies suited for this unique modality that focuses on possible DDIs with concomitant drugs. The latter may..."

Journal • Review

PHYOX8: Nedosiran in Pediatric Patients with Primary Hyperoxaluria (KIDNEY WEEK 2025) - P2 | "Conclusion Nedosiran was well-tolerated in children aged from 10 months to 11 years with PH1. Nedosiran treatment resulted in a notable reduction of mean Uox:Cr in this population."

Clinical • Late-breaking abstract • Genetic Disorders • Metabolic Disorders • Musculoskeletal Pain • Nephrology • Pediatrics • Renal Calculi • LDHA

Evaluating Physician Preferences for siRNA Therapy in Patients with Primary Hyperoxaluria Type 1 (KIDNEY WEEK 2025) - "The small interfering RNA (siRNA) therapies lumasiran and nedosiran are effective treatment options. Conclusion Physicians prioritized patient-related factors and regimen complexity when selecting a PH1 treatment. They preferred an siRNA treatment that was easy to use, required minimal HCP involvement/allowed for self-administration and did not negatively impact the patient's daily activities, including school or work."

Clinical • Hepatology • Nephrology

PEDIATRIC PRIMARY HYPEROXALURIA TYPE 1: A CLINICAL REVIEW OF CONVENTIONAL AND EMERGING THERAPIES (ESPN 2025) - "While 2 patients had rising oxalate levels after 2 years of treatment, one was switched to nedosiran with slight improvement...Two patients treated with lumasiran showed improved nephrocalcinosis, while the patient on conventional treatment also showed improved ultrasound lesions... PH1 has a variable prognosis, emphasizing the importance of early diagnosis. This condition should be suspected after lithiasis events or nephrocalcinosis. Conventional treatment is essential for reducing oxalate levels, but often insufficient."

Clinical • Review • Acute Kidney Injury • Chronic Kidney Disease • Genetic Disorders • Infectious Disease • Metabolic Disorders • Nephrology • Pediatrics • Renal Calculi • Renal Disease

RNA interference medication and transplantation procedures in patients with primary hyperoxaluria type 1 (PH1). (PubMed, Nephrol Dial Transplant) - "Pox should not be the sole parameter to decide on Tx procedure. In patients with minor oxalate deposition, no SOG deterioration and sensitivity to vitamin B6 or under efficacious RNAi treatment, iKTx can be considered. Severe (and deteriorating) systemic oxalosis, high Pox during RNAi treatment and maximum dialysis, makes us reconsider combined or sequential LKTx rather than iKTx. Patients with severe systemic oxalosis at time of diagnosis still have a high mortality rate."

Journal • Nephrology • Renal Disease • Transplantation

Primary hyperoxaluria type 1 - an unexpected diagnosis after kidney transplantation. (PubMed, Kidney Blood Press Res) - "Currently, we have access to novel RNA interference (RNAi) therapeutics such as lumasiran and nedosiran, which reduce hepatic oxalate production, however, they are prohibitively expensive in most countries. This case highlights the importance of early diagnosis, which allows optimal supportive and/or RNAi therapy and appropriate qualification for kidney transplantation in cases of end-stage kidney disease. This is particularly important as isolated kidney transplantation (without concomitant liver transplantation) can lead to rapid loss of graft function and may ultimately prove futile."

Journal • Chronic Kidney Disease • Inflammation • Metabolic Disorders • Nephrology • Renal Calculi • Transplantation

Updates on Pharmacological Therapy for Urolithiasis (UAA 2025) - "In primary hyperoxaluria (PH), novel RNA interference (RNAi) agents like lumasiran and nedosiran significantly lower urinary oxalate levels, offering promising alternatives for patients unresponsive to pyridoxine...Xanthine oxidase inhibitors (allopurinol, febuxostat) are reserved for hyperuricemic patients...Medical expulsive therapy (MET) with alpha-blockers (tamsulosin) remains effective for distal ureteral stones (5–10 mm), reducing time to expulsion and need for surgery...Operative times vary, with suction PCNL often being faster for large stones (47–82 min) but requiring fluoroscopy, while suction RIRS avoids tract-related risks but may necessitate staged procedures for stones >2 cm. Cost-effectiveness analyses favor suction PCNL due to fewer retreatments, though RIRS reduces radiation exposure."

Infectious Disease • Nephrology • Renal Calculi • Urolithiasis

Suction PCNL vs Suction RIRS? Do We Have a Winner (UAA 2025) - "In primary hyperoxaluria (PH), novel RNA interference (RNAi) agents like lumasiran and nedosiran significantly lower urinary oxalate levels, offering promising alternatives for patients unresponsive to pyridoxine...Xanthine oxidase inhibitors (allopurinol, febuxostat) are reserved for hyperuricemic patients...Medical expulsive therapy (MET) with alpha-blockers (tamsulosin) remains effective for distal ureteral stones (5–10 mm), reducing time to expulsion and need for surgery...Operative times vary, with suction PCNL often being faster for large stones (47–82 min) but requiring fluoroscopy, while suction RIRS avoids tract-related risks but may necessitate staged procedures for stones >2 cm. Cost-effectiveness analyses favor suction PCNL due to fewer retreatments, though RIRS reduces radiation exposure."

Infectious Disease • Nephrology • Renal Calculi • Urolithiasis

PHYOX3: Nedosiran Long-Term Safety and Efficacy in Patients With Primary Hyperoxaluria Type 1. (PubMed, Kidney Int Rep) - P1, P2, P3 | "Four participants discontinued treatments (1 pregnancy and 3 withdrawals), and no deaths were reported. Nedosiran was well-tolerated, reduced average Uox levels, reduced kidney stone occurrence, and maintained stable renal function for over 3 years."

Journal • Genetic Disorders • Metabolic Disorders • Nephrology • Renal Calculi • Renal Disease

Population Pharmacokinetic and Pharmacodynamic Modelling and Simulation for Nedosiran Clinical Development and Dose Guidance in Pediatric Patients with Primary Hyperoxaluria Type 1. (PubMed, Clin Pharmacokinet) - P1, P2, P3 | "Simulations based on the final Pop-PK/PD model support the 3.5 mg/kg Q1M dosing regimen in children aged 2 to < 12 years with PH1 and relatively intact kidney function (eGFR ≥30 mL/min/1.73 m2)."

Journal • PK/PD data • Nephrology • Pediatrics • Renal Disease

PHYOX 3: Long Term Extension Study in Patients With Primary Hyperoxaluria (clinicaltrials.gov) - P3 | N=75 | Active, not recruiting | Sponsor: Dicerna Pharmaceuticals, Inc., a Novo Nordisk company | Enrolling by invitation ➔ Active, not recruiting

Enrollment closed • Genetic Disorders • Nephrology • Renal Disease

PHYOX8: Nedosiran in Pediatric Patients From Birth to 11 Years of Age With PH and Relatively Intact Renal Function (clinicaltrials.gov) - P2 | N=25 | Completed | Sponsor: Dicerna Pharmaceuticals, Inc., a Novo Nordisk company | Recruiting ➔ Completed

Trial completion • Nephrology • Pediatrics

Treatment preferences among individuals with primary hyperoxaluria type 1 (PH1): a real-world study. (PubMed, Orphanet J Rare Dis) - "This study shows that patients with PH1 value treatments that are convenient and fit their lifestyle."

Journal • Real-world evidence • Genetic Disorders • Nephrology

The efficacy and safety of RNA interference for the treatment of primary hyperoxaluria: a systematic review and meta-analysis. (PubMed, Clin Kidney J) - "Furthermore, high-dose and long time-duration RNAi therapy may have a better clinical effect, and acceptable safety. The efficacy of RNAi combined with hemodialysis seems to be promising in PH treatment."

Journal • Retrospective data • Review • Genetic Disorders • Hepatology • Nephrology • Renal Disease

A Targeted Release Capsule of Lanthanum Carbonate: a New Efficient Cheap Treatment for Primary Hyperoxalurias. (PubMed, Kidney Int Rep) - "Recently, a substantial progress in the treatment of this deadly disease has been made that consists of the introduction of the RNA inhibitors, lumasiran and nedosiran, which deplete the substrate for oxalate synthesis. is a promising repurposed, efficient, nontoxic, and cheap drug, lacking serious side effects in the treatment of any type of PH in whatever place in the world. A randomized controlled trial supporting this proof-of-concept is the next step."

Journal • Gastrointestinal Disorder • Nephrology • Renal Disease

Concomitant Treatment With Lumasiran and Nedosiran in a Child With Primary Hyperoxaluria Type 1. (PubMed, Kidney Int Rep) - No abstract available

Journal • Nephrology