Review on Ammonia as a Potential Fuel: From Synthesis to Economics

Ammonia, a molecule that is gaining more interest as a fueling vector, has been considered as a candidate to power transport, produce energy, and support heating applications for decades. However, the particular characteristics of the molecule always made it a chemical with low, if any, benefit once compared to conventional fossil fuels. Still, the current need to decarbonize our economy makes the search of new methods crucial to use chemicals, such as ammonia, that can be produced and employed without incurring in the emission of carbon oxides. Therefore, current efforts in this field are leading scientists, industries, and governments to seriously invest efforts in the development of holistic solutions capable of making ammonia a viable fuel for the transition toward a clean future. On that basis, this review has approached the subject gathering inputs from scientists actively working on the topic. The review starts from the importance of ammonia as an energy vector, moving through all of the steps in the production, distribution, utilization, safety, legal considerations, and economic aspects of the use of such a molecule to support the future energy mix. Fundamentals of combustion and practical cases for the recovery of energy of ammonia are also addressed, thus providing a complete view of what potentially could become a vector of crucial importance to the mitigation of carbon emissions. Different from other works, this review seeks to provide a holistic perspective of ammonia as a chemical that presents benefits and constraints for storing energy from sustainable sources. State-of-the-art knowledge provided by academics actively engaged with the topic at various fronts also enables a clear vision of the progress in each of the branches of ammonia as an energy carrier. Further, the fundamental boundaries of the use of the molecule are expanded to real technical issues for all potential technologies capable of using it for energy purposes, legal barriers that will be faced to achieve its deployment, safety and environmental considerations that impose a critical aspect for acceptance and wellbeing, and economic implications for the use of ammonia across all aspects approached for the production and implementation of this chemical as a fueling source. Herein, this work sets the principles, research, practicalities, and future views of a transition toward a future where ammonia will be a major energy player. Aircraft Noise and Climate Effect

Sparsentan in patients with IgA nephropathy: a prespecified interim analysis from a randomised, double-blind, active-controlled clinical trial

Background: Sparsentan is a novel, non-immunosuppressive, single-molecule, dual endothelin and angiotensin receptor antagonist being examined in an ongoing phase 3 trial in adults with IgA nephropathy. We report the prespecified interim analysis of the primary proteinuria efficacy endpoint, and safety. Methods: PROTECT is an international, randomised, double-blind, active-controlled study, being conducted in 134 clinical practice sites in 18 countries. The study examines sparsentan versus irbesartan in adults (aged ≥18 years) with biopsy-proven IgA nephropathy and proteinuria of 1·0 g/day or higher despite maximised renin-angiotensin system inhibitor treatment for at least 12 weeks. Participants were randomly assigned in a 1:1 ratio to receive sparsentan 400 mg once daily or irbesartan 300 mg once daily, stratified by estimated glomerular filtration rate at screening (30 to 1·75 g/day). The primary efficacy endpoint was change from baseline to week 36 in urine protein-creatinine ratio based on a 24-h urine sample, assessed using mixed model repeated measures. Treatment-emergent adverse events (TEAEs) were safety endpoints. All endpoints were examined in all participants who received at least one dose of randomised treatment. The study is ongoing and is registered with ClinicalTrials.gov, NCT03762850. Findings: Between Dec 20, 2018, and May 26, 2021, 404 participants were randomly assigned to sparsentan (n=202) or irbesartan (n=202) and received treatment. At week 36, the geometric least squares mean percent change from baseline in urine protein-creatinine ratio was statistically significantly greater in the sparsentan group (-49·8%) than the irbesartan group (-15·1%), resulting in a between-group relative reduction of 41% (least squares mean ratio=0·59; 95% CI 0·51-0·69; p<0·0001). TEAEs with sparsentan were similar to irbesartan. There were no cases of severe oedema, heart failure, hepatotoxicity, or oedema-related discontinuations. Bodyweight changes from baseline were not different between the sparsentan and irbesartan groups. Interpretation: Once-daily treatment with sparsentan produced meaningful reduction in proteinuria compared with irbesartan in adults with IgA nephropathy. Safety of sparsentan was similar to irbesartan. Future analyses after completion of the 2-year double-blind period will show whether these beneficial effects translate into a long-term nephroprotective potential of sparsentan. Funding: Travere Therapeutics