Farming and the geography of nutrient production for human use: a transdisciplinary analysis

Background: Information about the global structure of agriculture and nutrient production and its diversity is essential to improve present understanding of national food production patterns, agricultural livelihoods, and food chains, and their linkages to land use and their associated ecosystems services. Here we provide a plausible breakdown of global agricultural and nutrient production by farm size, and also study the associations between farm size, agricultural diversity, and nutrient production. This analysis is crucial to design interventions that might be appropriately targeted to promote healthy diets and ecosystems in the face of population growth, urbanisation, and climate change. Methods: We used existing spatially-explicit global datasets to estimate the production levels of 41 major crops, seven livestock, and 14 aquaculture and fish products. From overall production estimates, we estimated the production of vitamin A, vitamin B12, folate, iron, zinc, calcium, calories, and protein. We also estimated the relative contribution of farms of different sizes to the production of different agricultural commodities and associated nutrients, as well as how the diversity of food production based on the number of different products grown per geographic pixel and distribution of products within this pixel (Shannon diversity index [H]) changes with different farm sizes. Findings: Globally, small and medium farms (≤50 ha) produce 51–77% of nearly all commodities and nutrients examined here. However, important regional differences exist. Large farms (>50 ha) dominate production in North America, South America, and Australia and New Zealand. In these regions, large farms contribute between 75% and 100% of all cereal, livestock, and fruit production, and the pattern is similar for other commodity groups. By contrast, small farms (≤20 ha) produce more than 75% of most food commodities in sub-Saharan Africa, southeast Asia, south Asia, and China. In Europe, west Asia and north Africa, and central America, medium-size farms (20–50 ha) also contribute substantially to the production of most food commodities. Very small farms (≤2 ha) are important and have local significance in sub-Saharan Africa, southeast Asia, and south Asia, where they contribute to about 30% of most food commodities. The majority of vegetables (81%), roots and tubers (72%), pulses (67%), fruits (66%), fish and livestock products (60%), and cereals (56%) are produced in diverse landscapes (H>1·5). Similarly, the majority of global micronutrients (53–81%) and protein (57%) are also produced in more diverse agricultural landscapes (H>1·5). By contrast, the majority of sugar (73%) and oil crops (57%) are produced in less diverse ones (H≤1·5), which also account for the majority of global calorie production (56%). The diversity of agricultural and nutrient production diminishes as farm size increases. However, areas of the world with higher agricultural diversity produce more nutrients, irrespective of farm size. Interpretation: Our results show that farm size and diversity of agricultural production vary substantially across regions and are key structural determinants of food and nutrient production that need to be considered in plans to meet social, economic, and environmental targets. At the global level, both small and large farms have key roles in food and nutrition security. Efforts to maintain production diversity as farm sizes increase seem to be necessary to maintain the production of diverse nutrients and viable, multifunctional, sustainable landscapes. Funding: Commonwealth Scientific and Industrial Research Organisation, Bill & Melinda Gates Foundation, CGIAR Research Programs on Climate Change, Agriculture and Food Security and on Agriculture for Nutrition and Health funded by the CGIAR Fund Council, Daniel and Nina Carasso Foundation, European Union, International Fund for Agricultural Development, Australian Research Council, National Science Foundation, Gordon and Betty Moore Foundation, and Joint Programming Initiative on Agriculture, Food Security and Climate Change—Belmont Forum

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