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Nefrotoxicidade induzida por cisplatina: mecanismos de ação e biomarcadores
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Apesar de a cisplatina ser reconhecida há muitos anos pela sua eficácia em
quimioterapia, existem diversos efeitos adversos indesejáveis, entre os quais a
nefrotoxicidade. A lesão renal induzida pela cisplatina é iniciada com a acumulação
deste composto nas células renais, sendo depois desencadeados diversos eventos que
incluem stress oxidativo, lesão no DNA, disfunção mitocondrial e morte celular.
Existem algumas estratégias utilizadas correntemente na prática clínica para minorar a
lesão renal aguda associada à cisplatina (e.g. hidratação do doente ou diurese forçada).
No entanto, estas opções nem sempre são eficazes sendo necessário desenvolver novas
abordagens terapêuticas e conhecer com mais detalhe os mecanismos de
nefrotoxicidade. Estão reportados alguns avanços na investigação destas novas
abordagens, sendo ainda necessários mais dados, particularmente obtidos no âmbito de
estudos clínicos.
É também da maior importância, investir na prevenção de formas graves de
nefrotoxicidade. Para tal, é necessário a monotorização com recurso a biomarcadores
mais sensíveis e específicos que os tradicionalmente utilizados para avaliação da função
renal (i.e. níveis séricos de creatinina e ureia). Proteínas específicas da urina têm sido
alvo de estudo, pois permitem não só detetar lesões renais mais cedo do que os
biomarcadores tradicionais, como também indicar especificamente em que segmento
do rim ocorreu a lesão. Estes tópicos de grande importância no contexto da
quimioterapia baseada em cisplatina, serão abordados na presente revisão de conjunto,
com especial destaque para os mecanismos envolvidos na nefrotoxicidade e para os
novos biomarcadores disponíveis.
Although cisplatin is recognized for many years for its efficiency in chemotherapeutics, there are many unwanted adverse effects, specifically nephrotoxicity. Kidney injury induced by cisplatin is initiated by the accumulation of cisplatin in kidney cells, which then triggers a series of events that include oxidative stress, damage to DNA, mitochondrial disfunction and cell death. There are a few strategies used currently in clinical practice to treat acute kidney injury induced by cisplatin (e.g. patient hydration and forced diuresis). However, these strategies can be ineffective making it necessary to develop new therapeutic approaches and deepen our knowledge about the mechanisms involved in nephrotoxicity. Some progress has been made in the investigation of these new approaches, but more data is necessary, particularly in clinical studies. It is also of the utmost importance to invest in the prevention of severe forms of nephrotoxicity. In order to achieve such, it is necessary to monitor more sensitive and specific biomarkers compared to the ones traditionally used to evaluate kidney function (i.e. creatinine and urea serum levels). Specific urinary proteins have been a target of investigation as they allow the detection of kidney injuries sooner than traditional biomarkers, as well as indicate specifically in which segment of the kidney the injury happened. These topics of great importance in the context of cisplatin based chemotherapeutics, will be discussed in the present review document, especially the mechanisms involved in the nephrotoxicity and the new available biomarkers.
Although cisplatin is recognized for many years for its efficiency in chemotherapeutics, there are many unwanted adverse effects, specifically nephrotoxicity. Kidney injury induced by cisplatin is initiated by the accumulation of cisplatin in kidney cells, which then triggers a series of events that include oxidative stress, damage to DNA, mitochondrial disfunction and cell death. There are a few strategies used currently in clinical practice to treat acute kidney injury induced by cisplatin (e.g. patient hydration and forced diuresis). However, these strategies can be ineffective making it necessary to develop new therapeutic approaches and deepen our knowledge about the mechanisms involved in nephrotoxicity. Some progress has been made in the investigation of these new approaches, but more data is necessary, particularly in clinical studies. It is also of the utmost importance to invest in the prevention of severe forms of nephrotoxicity. In order to achieve such, it is necessary to monitor more sensitive and specific biomarkers compared to the ones traditionally used to evaluate kidney function (i.e. creatinine and urea serum levels). Specific urinary proteins have been a target of investigation as they allow the detection of kidney injuries sooner than traditional biomarkers, as well as indicate specifically in which segment of the kidney the injury happened. These topics of great importance in the context of cisplatin based chemotherapeutics, will be discussed in the present review document, especially the mechanisms involved in the nephrotoxicity and the new available biomarkers.
Descrição
Trabalho Final de Mestrado Integrado, Ciências Farmacêuticas, 2021, Universidade de Lisboa, Faculdade de Farmácia.
Palavras-chave
Quimioterapia Cisplatina Lesão renal Mecanismos de nefrotoxicidade Biomarcadores Mestrado integrado - 2021