Resumo Introdução: O objetivo deste estudo foi investigar o papel do fenofibrato, um agonista do receptor ativado por proliferadores de peroxissoma-α, na lesão renal induzida por obesidade (lipotoxicidade) em camundongos submetidos à uninefrectomia. Métodos: Camundongos C57BL/6 foram submetidos a uninefrectomia e cirurgias simuladas (sham) e alimentados com dietas normocalóricas ou rica em gordura. Após 10 semanas, os camundongos obesos receberam fenofibrato a 0,02% por 10 semanas. Avaliamos função e morfologia renal, bem como níveis de mediadores inflamatórios e fibróticos e marcadores do metabolismo lipídico. Resultados: Camundongos alimentados com dieta rica em gordura desenvolveram obesidade e hiperlipidemia características, com subsequente acúmulo de lipídios e danos renais, incluindo expansão mesangial, fibrose intersticial, inflamação e proteinúria. Essas alterações foram maiores em camundongos obesos uninefrectomizados do que em camundongos obesos sham. O tratamento com fenofibrato preveniu hiperlipidemia e lesões glomerulares, reduziu o acúmulo de lipídios, melhorou a disfunção renal e atenuou a inflamação e fibrose renal. Além disso, o tratamento com fenofibrato reduziu a expressão no tecido renal do inibidor do ativador do plasminogênio-1, da proteína quimiotática de monócitos-1 e a expressão local do fator de crescimento de fibroblastos-21. Conclusão: A ativação do receptor ativado por proliferadores de peroxissoma-α pelo fenofibrato, com subsequente lipólise, atenuou lesões glomerulares e tubulointersticiais induzidas por lipotoxicidade renal, protegendo, assim, os rins de camundongos uninefrectomizados contra lesões induzidas por obesidade. Os achados do estudo sugerem uma via na ação farmacológica do fenofibrato, fornecendo insights sobre os mecanismos envolvidos no dano renal causado pela obesidade em doadores renais. Introdução peroxissomaα, peroxissomaα peroxissoma α, α (lipotoxicidade Métodos C57BL6 CBL C57BL 6 C BL C57BL/ sham (sham 1 semanas 002 0 02 0,02 lipídico Resultados características renais mesangial intersticial proteinúria disso plasminogênio1, plasminogênio1 plasminogênio 1, plasminogênio-1 monócitos1 monócitos monócitos- fibroblastos21. fibroblastos21 fibroblastos 21. 21 fibroblastos-21 Conclusão lipólise protegendo assim 00 0,0 plasminogênio- fibroblastos2 2 fibroblastos-2 0, fibroblastos-

Abstract Introduction: The objective of this study was to investigate the role of fenofibrate, a peroxisome proliferator-activated receptor-α agonist, in obesity-induced kidney damage (lipotoxicity) in mice with uninephrectomy. Methods: C57BL/6 mice underwent uninephrectomy and sham surgeries and were fed normocaloric or high-fat diets. After 10 weeks, obese mice were administered 0.02% fenofibrate for 10 weeks. Kidney function and morphology were evaluated, as well as levels of inflammatory and fibrotic mediators and lipid metabolism markers. Results: High-fat diet-fed mice developed characteristic obesity and hyperlipidemia, with subsequent renal lipid accumulation and damage, including mesangial expansion, interstitial fibrosis, inflammation, and proteinuria. These changes were greater in obese uninephrectomy mice than in obese sham mice. Fenofibrate treatment prevented hyperlipidemia and glomerular lesions, lowered lipid accumulation, ameliorated renal dysfunction, and attenuated inflammation and renal fibrosis. Furthermore, fenofibrate treatment downregulated renal tissue expression of plasminogen activator inhibitor-1, monocyte chemoattractant protein-1, and local expression of fibroblast growth factor-21. Conclusion: Peroxisome proliferator-activated receptor-α activation by fenofibrate, with subsequent lipolysis, attenuated glomerular and tubulointerstitial lesions induced by renal lipotoxicity, thus protecting the kidneys of uninephrectomy mice from obesity-induced lesions. The study findings suggest a pathway in the pharmacological action of fenofibrate, providing insight into the mechanisms involved in kidney damage caused by obesity in kidney donors. Introduction proliferatoractivated proliferator activated receptorα receptor α agonist obesityinduced lipotoxicity (lipotoxicity Methods C57BL6 CBL C57BL 6 C BL C57BL/ highfat high fat diets 1 weeks 002 0 02 0.02 evaluated markers Results Highfat High dietfed diet expansion fibrosis proteinuria dysfunction Furthermore inhibitor1, inhibitor1 inhibitor 1, inhibitor-1 protein1, protein1 protein protein-1 factor21. factor21 factor 21. 21 factor-21 Conclusion lipolysis donors 00 0.0 inhibitor- protein- factor2 2 factor-2 0. factor-

ABSTRACT BACKGROUND: Epidemiological studies involving large samples usually face financial and operational challenges. OBJECTIVES: To describe the planning and execution of ADHERE Brazil, an epidemiological study on 1,105 kidney transplant patients, and report on how the study was structured, difficulties faced and solutions found. DESIGN AND SETTING: Cross-sectional multicenter study in 20 Brazilian kidney transplantation centers. METHODS: Actions developed in each phase of implementation were described, with emphasis on innovations used within the logistics of this study, aimed at estimating the prevalence of nonadherence to treatment. RESULTS: Coordination of activities was divided into four areas: general, regulatory, data collection and statistics. Weekly meetings were held for action planning. The general coordination team was in charge of project elaboration, choice of participating centers, definition of publication policy and monitoring other coordination teams. The regulatory team provided support to centers for submitting the project to ethics committees. The data collection team prepared a manual on the electronic collection system, scheduled web meetings and was available to respond to queries. It also monitored the data quality and reported any inadequacies found. Communication with the centers was through monthly reports via e-mail and distribution of exclusive material. The statistical team acted in all phases of the study, especially in creating the data analysis plan and data bank, generation of randomization lists and data extraction. CONCLUSIONS: Through these logistics, we collected high-quality data and built a local research infrastructure for further studies. We present supporting alternatives for conducting similar studies. CLINICAL TRIAL ANNOTATION: http://clinicaltrials.gov/ on October 10, 2013; NCT02066935.