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Evidência para a utilização de inibidores do co-transportador de sódio-glucose como fármacos nefroprotetores : revisão narrativa
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Introdução: A doença renal crónica apresenta um enorme peso no panorama da saúde atual. A sua elevada prevalência e incidência, associadas a desfechos altamente desfavoráveis levam a que seja considerada um problema de saúde pública global. A progressão da doença renal crónica culmina na doença renal terminal com necessidade de terapêutica de substituição da função renal, contudo, ao longo de todo o espectro da doença, assistese a crescente risco cardiovascular, com todas as consequências associadas, nomeadamente, um maior risco de morte. Neste sentido, é crucial a otimização de terapêuticas que impeçam a progressão da nefropatia tendo em conta a atual incapacidade de reversão da doença renal crónica. Apesar dos esforços para contrariar esta evolução, uma percentagem de importante de doentes continua a progredir para a doença renal terminal. Recentemente, os inibidores do co-transportador sódio-glucose 2, uma nova classe de antidiabéticos orais, demonstraram efeitos promissores a nível cardiovascular e renal, que vão para além do estado glicémico doente. Desta forma, direcionam-se para uma posição basilar na abordagem da doença renal crónica, independentemente da sua etiologia. Objetivos /Métodos: O objetivo principal desta revisão prende-se na revisão dos mecanismos de ação dos inibidores SGLT2, da identificação e comparação da evidência disponível sobre o seu efeito nefroprotetor, independentemente do diagnóstico de Diabetes Mellitus. Tendo em conta a relação entre a doença cardiovascular e a doença renal associou-se o estudo da evidência sobre o impacto desta classe farmacológica na proteção cardiovascular. Foram ainda revistos e descritos outros potenciais efeitos pleiotrópicos desta classe farmacológica assim como analisado o seu perfil de segurança. Para alcançar este objetivo foram utilizadas bases de dados online com a identificação dos ensaios clínicos mais recentes sobre o tópico.Discussão: Durante a elaboração da revisão narrativa, foi possível observar o efeito dos inibidores co transportador sódio-glucose 2 nível renal, com resultados que aparentam ser um efeito de classe na redução do risco de progressão da doença renal e ainda a nível da mortalidade global e por causas renais, principalmente em doentes com proteinúria, independentemente de serem diabéticos. A nível cardiovascular, foi notório o impacto na redução do risco de hospitalização por insuficiência cardíaca e com benefício ainda na ocorrência de eventos cardiovasculares major. Relativamente aos efeitos adversos, tratam-se de fármacos bem tolerados e com excelente perfil de segurança. Conclusão: Em conclusão, os inibidores SGLT2 apresentam um benefício a nível da progressão da doença renal crónica pelo que se justifica a sua introdução como terapêutica modificadora de prognóstico, tanto em doentes diabéticos como não diabéticos, principalmente nos doentes que apresentem proteinuria.
Chronic kidney disease has a large impact on the current health landscape. It’s high prevalence and incidence, combined with unfavorable prognosis leads to a significant global public health issue. The progression of chronic kidney disease leads to end-stage kidney disease and the need for kidney replacement therapy and simultaneously to a growing cardiovascular risk, with all the associated consequences, including higher mortality. For these reasons it is crucial to optimize therapies that prevent the progression of this condition, given the current inability of reversing it. Despite the efforts put in place, a significant percentage of patients still progresses to end stage kidney disease. Recently, the sodium-glucose cotransporter 2 inhibitors, a new class of oral antidiabetics, have shown promising effects on a renal and cardiovascular level, which go beyond their glycemic impact, positioning themselves as a base approach to chronic kidney disease, despite its etiology. Objectives/ Methods: The main goal behind this review is to identify the action mechanism and compare the information available on the nephroprotective effects of sodium-glucose cotransporter 2 inhibitors, both in diabetic and non-diabetic patients. Regarding the relation between cardiovascular and renal disease, it was also included the evidence of their cardioprotective action. It was also reviewed and described the other potential pleotropic effects from these types of drugs and their safety profile. To achieve this goal were used online data bases to identify the most recent clinical trials regarding this topic. During the review process, it was possible to observe the renal effect of the sodiumglucose cotransporter 2 inhibitors, with an apparent class effect on risk reduction of kidney disease progression, overall, and kidney related mortality, mainly on patients with proteinuria and independently of their diabetic status. On a cardiovascular level, it was remarkable the impact on risk reduction of heart failure hospitalization and has shown benefit on major cardiovascular events reduction. Regarding side effects, these drugs are well tolerated and have an excellent safety profile. Conclusion: In conclusion, SGLT2 inhibitors have shown benefit on the progression of chronic kidney disease, what argues their introduction as prognostic modifying treatment in diabetic and non-diabetic patients, especially when presenting proteinuria.
Chronic kidney disease has a large impact on the current health landscape. It’s high prevalence and incidence, combined with unfavorable prognosis leads to a significant global public health issue. The progression of chronic kidney disease leads to end-stage kidney disease and the need for kidney replacement therapy and simultaneously to a growing cardiovascular risk, with all the associated consequences, including higher mortality. For these reasons it is crucial to optimize therapies that prevent the progression of this condition, given the current inability of reversing it. Despite the efforts put in place, a significant percentage of patients still progresses to end stage kidney disease. Recently, the sodium-glucose cotransporter 2 inhibitors, a new class of oral antidiabetics, have shown promising effects on a renal and cardiovascular level, which go beyond their glycemic impact, positioning themselves as a base approach to chronic kidney disease, despite its etiology. Objectives/ Methods: The main goal behind this review is to identify the action mechanism and compare the information available on the nephroprotective effects of sodium-glucose cotransporter 2 inhibitors, both in diabetic and non-diabetic patients. Regarding the relation between cardiovascular and renal disease, it was also included the evidence of their cardioprotective action. It was also reviewed and described the other potential pleotropic effects from these types of drugs and their safety profile. To achieve this goal were used online data bases to identify the most recent clinical trials regarding this topic. During the review process, it was possible to observe the renal effect of the sodiumglucose cotransporter 2 inhibitors, with an apparent class effect on risk reduction of kidney disease progression, overall, and kidney related mortality, mainly on patients with proteinuria and independently of their diabetic status. On a cardiovascular level, it was remarkable the impact on risk reduction of heart failure hospitalization and has shown benefit on major cardiovascular events reduction. Regarding side effects, these drugs are well tolerated and have an excellent safety profile. Conclusion: In conclusion, SGLT2 inhibitors have shown benefit on the progression of chronic kidney disease, what argues their introduction as prognostic modifying treatment in diabetic and non-diabetic patients, especially when presenting proteinuria.
Descrição
Trabalho Final do Curso de Mestrado Integrado em Medicina, Faculdade de Medicina, Universidade de Lisboa, 2022
Palavras-chave
Inibidores SGLT2 Nefroproteção Doença renal crónica Diabetes mellitus Cardioproteção Nefrologia