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Epidemiologic evaluation of acute kidneyi injury in hemato-oncologic patients
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A nível mundial tem-se assistido a um aumento progressivo da incidência e prevalência de neoplasias hematológicas. O transplante de células hematopoiéticas é um procedimento potencialmente curativo para virtualmente todas as neoplasias hematológicas, estando os benefícios terapêuticos relacionados com a possibilidade de realizar quimioterapia em alta dose e com o efeito enxerto versus tumor. Com este aumento epidemiológico das neoplasias hematológicas, o número de doentes a beneficiar de transplante de células hematopoiéticas é crescente. O número de transplantes de células hematopoiéticas tem registado um aumento superior a 7% por ano nos últimos cinco anos em todo o mundo, sendo expetável que esta tendência se mantenha. Este cenário remete-nos para a necessidade de estudar e compreender melhor as complicações associadas ao transplante de células hematopoiéticas. A Lesão Renal Aguda associada ao transplante de células hematopoiéticas ocorre nos primeiros 100 dias após este procedimento e tem sido, recentemente, apontada na literatura como uma complicação frequente e com importante impacto prognóstico a curto e longo prazo. A Lesão Renal Aguda é uma síndrome complexa associada a inúmeras etiologias e resultante de vários mecanismos fisiopatológicos que levam a uma diminuição rápida da função renal. Existem na literatura mais de 35 definições para esta entidade e nesse contexto em 2012 a Kidney Disease Improving Global Outcomes (KDIGO) publicou a classificação KDIGO para a Lesão Renal Aguda. Os objetivos principais desta classificação foram o standardizar e uniformizar a aplicação da de uma única definição nos contextos da prática clínica, da investigação e da saúde pública. Esta classificação engloba dois critérios – o aumento da creatinina sérica e a redução do débito urinário - e contempla três graus de gravidade. A Lesão Renal Aguda ainda não tem um tratamento específico sendo que a prevenção e a deteção e abordagem precoces são as atitudes clínicas mais recomendadas. A Lesão Renal Aguda no transplante de células hematopoiéticas tem sido estudada na última década, mas a utilização de diferentes definições para Lesão Renal Aguda - e todas baseadas apenas no aumento da creatinina sérica - bem como a inclusão de vários diagnósticos hematológicos nas populações dos estudos culminou numa inconsistência de resultados entre estudos. De facto, as incidências publicadas variam entre os 12 e os 80%. Não existe na literatura nenhum score de risco proposto para Lesão Renal Aguda no transplante de células hematopoiéticas.
The incidence and prevalence of hematologic malignancies are increasing throughout the world. Hematopoietic Stem Cell Transplant (HSCT) is a potentially curative treatment for virtually all hematologic cancers, and the therapeutic benefits result from high-dose chemotherapy and the graft versus tumor effect that develops after allografting. With this epidemiologic increase, the overall number of patients requiring HSCT has also evolved, and the number of HSCTs performed has increased by 7% per year worldwide in the last five years. It is assumed that this trend will continue for the next several years. With this scenario arises the need to increase our knowledge on HSCT complications more than ever, and Acute Kidney Injury (AKI) occurring in the first 100 days after this procedure has been recently mentioned in the literature as a complication with an important prognostic impact. AKI is a complex syndrome associated with numerous etiologies and pathophysiological mechanisms that lead to a rapid decrease in renal function. In the literature, we identify more than 35 different definitions for AKI. It was only in 2012 that the Kidney Disease Improving Global Outcomes (KDIGO) classification was proposed with the goal of standardizing the definition throughout the world to allow uniformization and consequently more coherent applicability in clinical practice, research, and public health fields. This classification takes into consideration two criteria—serum creatinine increases and urinary output decreases—and has three degrees of severity. AKI still does not have a specific treatment or prevention, and an early approach is still the best recommended attitude. AKI in HSCT has been studied in the last decade, but the use of different AKI definitions, all based on serum creatinine changes, along with the inclusion of several hematologic diagnoses in the analyzed populations, has resulted in a wide range of results with no predictive risk score available. The main objectives of this dissertation were 1) to evaluate the cumulative incidence, the earlier diagnosis criteria and severity of AKI according to KDIGO classification using both creatinine and urinary output criteria in the first 100 days after HSCT in patients with multiple myeloma undergoing autologous HSCT, in patients with lymphoma undergoing autologous HSCT and in patients with leukemia undergoing allogeneic HSCT; 2) to define risk factors for AKI in each of the above mentioned populations; 3) to study the association of AKI with overall survival, relapse-free survival, and progression to chronic kidney disease in each of the above mentioned populations; 4) to calculate a predictive risk score for AKI considering variables available before the HSCT.
The incidence and prevalence of hematologic malignancies are increasing throughout the world. Hematopoietic Stem Cell Transplant (HSCT) is a potentially curative treatment for virtually all hematologic cancers, and the therapeutic benefits result from high-dose chemotherapy and the graft versus tumor effect that develops after allografting. With this epidemiologic increase, the overall number of patients requiring HSCT has also evolved, and the number of HSCTs performed has increased by 7% per year worldwide in the last five years. It is assumed that this trend will continue for the next several years. With this scenario arises the need to increase our knowledge on HSCT complications more than ever, and Acute Kidney Injury (AKI) occurring in the first 100 days after this procedure has been recently mentioned in the literature as a complication with an important prognostic impact. AKI is a complex syndrome associated with numerous etiologies and pathophysiological mechanisms that lead to a rapid decrease in renal function. In the literature, we identify more than 35 different definitions for AKI. It was only in 2012 that the Kidney Disease Improving Global Outcomes (KDIGO) classification was proposed with the goal of standardizing the definition throughout the world to allow uniformization and consequently more coherent applicability in clinical practice, research, and public health fields. This classification takes into consideration two criteria—serum creatinine increases and urinary output decreases—and has three degrees of severity. AKI still does not have a specific treatment or prevention, and an early approach is still the best recommended attitude. AKI in HSCT has been studied in the last decade, but the use of different AKI definitions, all based on serum creatinine changes, along with the inclusion of several hematologic diagnoses in the analyzed populations, has resulted in a wide range of results with no predictive risk score available. The main objectives of this dissertation were 1) to evaluate the cumulative incidence, the earlier diagnosis criteria and severity of AKI according to KDIGO classification using both creatinine and urinary output criteria in the first 100 days after HSCT in patients with multiple myeloma undergoing autologous HSCT, in patients with lymphoma undergoing autologous HSCT and in patients with leukemia undergoing allogeneic HSCT; 2) to define risk factors for AKI in each of the above mentioned populations; 3) to study the association of AKI with overall survival, relapse-free survival, and progression to chronic kidney disease in each of the above mentioned populations; 4) to calculate a predictive risk score for AKI considering variables available before the HSCT.
Descrição
Tese de doutoramento em Medicina (Nefrologia), Universidade de Lisboa, Faculdade de Medicina, 2024
Palavras-chave
Hematopoietic stem cell transplant Acute kidney injury Epidemiology Predictive risk score Transplante de células hematopoiéticas Lesão renal aguda Epidemiologia Score preditor de risco