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Evidence for the use of a nonsteroidal mineralocorticoid receptor antagonist for the treatment of chronic kidney disease
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Resumo(s)
A doença renal crónica associa-se a importante morbimortalidade, reforçando a necessidade em desenvolver novos fármacos que controlem o seu impacto em resultados clínicos. Recentemente, vários fármacos demonstraram resultados promissores.
Este trabalho sintetiza a evidência para uso de antagonistas dos recetores dos mineralocorticóides não esteróides na doença renal crónica, nomeadamente de fármacos já aprovados (finerenona e esaxerenona) e não aprovados (apararenona e ocedurenona).
Para isto, foi realizada uma pesquisa no PubMed e ClinicalTrials.gov com palavras-chave relevantes, de ensaios clínicos e estudos observacionais, terminados ou em andamento, nos últimos cinco anos.
A finerenona está aprovada para nefropatia diabética com albuminúria, com resultados provenientes de dois ensaios clínicos de fase três e uma meta-análise a demonstrar melhoria em outcomes renais e cardiovasculares e perfil de segurança adequado, nomeadamente em termos de potássio sérico. O uso combinado de finerenona com inibidores da proteína de transporte sódio-glucose 2 está a ser estudado num ensaio clínico de fase dois. Relativamente à nefropatia não diabética, parece haver benefício na combinação previamente descrita, no entanto estes dados provêm de estudo não controlado com placebo. Adicionalmente, está a decorrer um ensaio clínico de fase três a estudar o uso de finerenona na população com nefropatia não diabética. A esaxerenona está aprovada para hipertensão no Japão, com evidência em nefropatia diabética proveniente de dois ensaios clínicos de fase três, sendo eficaz e seguro na remissão de albuminúria. No entanto, estes decorreram numa população japonesa, limitando a sua validade externa. A ocedurenona é adequada na hipertensão refratária na doença renal crónica. A aparenanona está a ser investigada para a nefropatia diabética, tendo bons resultados de um ensaio clínico de fase dois, limitado por apenas incluir população japonesa.
Com esta revisão é dada uma visão global destes fármacos, ajudando num uso baseado na evidência e apontando para a necessidade de mais investigação.
Chronic kidney disease (CKD) morbimortality drives the interest in developing new drugs to better control its impact on clinical outcomes. Recently, new drugs have shown promising results. This work summarizes the evidence on the use of non-steroidal mineralocorticoid receptor antagonists on CKD, outlining the data on the clinically approved drugs (finerenone and esaxerenone) and on the not yet approved drugs (apararenone and ocedurenone). A search was performed on PubMed and ClinicalTrials.gov using relevant keywords for clinical trials and observational studies, finished or ongoing, developed on the last five years. Finerenone is currently approved for diabetic kidney disease with albuminuria, with results from two phase three trials and a meta-analysis, presenting satisfactory results on renal and cardiovascular outcomes and an appropriate safety profile, namely regarding serum potassium levels. Its combined use with sodium glucose transport protein 2 inhibitors is presently being studied on a phase two trial. Regarding nondiabetic kidney disease, there appears to be beneficial combining sodium glucose transport protein 2 inhibitors and finerenone, although these results came from non placebo controlled trials. An ongoing phase three trial is assessing finerenone efficacy and safety on the nondiabetic population. Esaxerenone is approved for hypertension in Japan and its evidence on diabetic kidney disease comes from two phase three clinical trials, showing its efficacy and safety on albuminuria remission. These trials were developed with a Japanese population, limiting its widespread application. Ocedurenone presents results from a phase two trial on managing refractory hypertension on chronic kidney disease. Apararenone is being investigated for diabetic kidney disease, with good results from a phase two study, limited for being developed only in Japan. With this review we will provide a global view on these drugs, aid on an evidence-based use, and point the need for the development of more evidence.
Chronic kidney disease (CKD) morbimortality drives the interest in developing new drugs to better control its impact on clinical outcomes. Recently, new drugs have shown promising results. This work summarizes the evidence on the use of non-steroidal mineralocorticoid receptor antagonists on CKD, outlining the data on the clinically approved drugs (finerenone and esaxerenone) and on the not yet approved drugs (apararenone and ocedurenone). A search was performed on PubMed and ClinicalTrials.gov using relevant keywords for clinical trials and observational studies, finished or ongoing, developed on the last five years. Finerenone is currently approved for diabetic kidney disease with albuminuria, with results from two phase three trials and a meta-analysis, presenting satisfactory results on renal and cardiovascular outcomes and an appropriate safety profile, namely regarding serum potassium levels. Its combined use with sodium glucose transport protein 2 inhibitors is presently being studied on a phase two trial. Regarding nondiabetic kidney disease, there appears to be beneficial combining sodium glucose transport protein 2 inhibitors and finerenone, although these results came from non placebo controlled trials. An ongoing phase three trial is assessing finerenone efficacy and safety on the nondiabetic population. Esaxerenone is approved for hypertension in Japan and its evidence on diabetic kidney disease comes from two phase three clinical trials, showing its efficacy and safety on albuminuria remission. These trials were developed with a Japanese population, limiting its widespread application. Ocedurenone presents results from a phase two trial on managing refractory hypertension on chronic kidney disease. Apararenone is being investigated for diabetic kidney disease, with good results from a phase two study, limited for being developed only in Japan. With this review we will provide a global view on these drugs, aid on an evidence-based use, and point the need for the development of more evidence.
Descrição
Trabalho Final do Curso de Mestrado Integrado em Medicina, Faculdade de Medicina, Universidade de Lisboa, 2024
Palavras-chave
Antagonistas do recetor de mineralocorticóides não esteróides Doença renal crónica Nefropatia diabética Nefropatia não diabética Nefrologia