Modulação do sistema renina angiotensina em pacientes transplantados renais sob diferentes regimes de imunossupressores
Date
2020-12-18
Authors
Bochio, Filipo [UNIFESP]
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Casarini, Dulce Elena [UNIFESP]
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Tese de doutorado
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Abstract
No Brasil, são realizados aproximadamente cerca de 5500 transplantes renais por ano. Após o transplante os pacientes passam a utilizar imunossupressores, uma classe de medicamentos com a função de modular o sistema imune e evitar a rejeição do enxerto. Drogas imunossupressoras como Everolimo (EVE) e Micofenolato de Sódio (MCO) são administradas na terapia de transplantados para reduzir o risco de rejeição. É sabido da literatura que os pacientes transplantados renais podem vir a desenvolver doenças como hipertensão e diabetes, e que o surgimento dessas patologias pode estar relacionado ao desequilíbrio do sistema renina angiotensina (SRA), surgindo complicações pós transplante. Dentre outros sistemas hormonais, este é um poderoso sistema que libera peptídeos capazes de alterar a função cardíaca e modular o diabetes. O objetivo deste estudo foi verificar se houve mudanças na modulação do SRA entre os pacientes pós-transplante renal, que utilizaram EVE ou MCO. No presente estudo foram incluídos 15 pacientes divididos em dois grupos de acordo com a medicação administrada. Os parâmetros demográficos, clínicos e bioquímicos foram avaliados e também foram analisadas as expressões das enzimas ECA, ECA2, NEP, Renina e Quimase pela técnica de Western Blotting. A quantificação dos peptídeos do SRA foi realizada pela técnica de espectrometria de massas em amostras de plasma coletadas em diferentes tempos do estudo, sendo o sétimo dia pós transplante (D7) determinado como o primeiro dia de coleta para estudo, dando prosseguimento aos outros dias estabelecidos, quatorze dias (D14), um mês (M1), dois meses (M2) e três meses (M3). Todos os pacientes apresentaram diabetes mellitus pós-transplante e hipertensão como doença de base. Nossos resultados mostraram uma maior expressão das ECAs, porém sem relevância estatística e a presença da isoforma da ECA com 90 kDa em ambos os grupos, descrita na literatura como um possível biomarcador para hipertensão. A quantificação dos peptídeos não evidenciou diferença estatisticamente significante entre os grupos e tempos de coleta dentro do mesmo grupo, porém observamos maior concentração da Ang 3-7 no grupo MCO, descrita na literatura como um peptídeo vasoconstritor, e apesar dos dados clínicos não mostrarem significância estatística entre os grupos nos diferentes dias de avaliação, vimos que a pressão arterial no grupo MCO estava mais elevada. Podemos sugerir que este peptídeo pode estar envolvido no agravamento da hipertensão do grupo experimental MCO, o qual mostrou valores elevados para pressão arterial.
In Brazil, approximately 5500 kidney transplants are performed each year. After transplantation, patients start using immunosuppressants, a class of drugs with the function of modulating the immune system and preventing graft rejection. Immunosuppressive drugs such as Everolimos (EVE) and Mycophenolate Sodium (MPS) are administered in transplant therapy to reduce the risk of rejection. It is known from the literature that kidney transplant patients may develop diseases such as hypertension and diabetes, and that the appearance of these pathologies may be related to the imbalance of the Renin-Angiotensin-Aldosterone System (RAAS), resulting in post-transplant complications. Among other hormonal systems, this is a powerful system that releases peptides capable of altering cardiac function and modulating diabetes. The aim of this study was to verify whether there were changes in the modulation of the RAAS among post-kidney transplant patients who used EVE or MPS. The present study included 15 patients divided into two groups according to the medication administered. The demographic, clinical and biochemical parameters were evaluated and the expressions of the enzymes ACE, ACE2, NEP, Renin and Chymase were also analysed using the Western Blotting technique. The quantification of RAS peptides was performed by the technique of mass spectrometry in plasma samples collected at different times of the study, with the seventh day after transplantation (D7) being determined as the first day of collection for study, continuing the other days established, fourteen days (D14), one month (M1), two months (M2) and three months (M3). All patients had posttransplant diabetes mellitus and hypertension as the underlying disease. Our results showed a greater expression of ACE, but without statistical relevance and the presence of the ACE isoform with 90 kDa in both groups, described in the literature as a possible biomarker for hypertension. The quantification of the peptides did not show a statistically significant difference between the groups and collection times within the same group; however, we observed a higher concentration of Ang 3-7 in the MPS group, described in the literature as a vasoconstrictor peptide, and despite the clinical data not showing significance statistics between the groups on the different evaluation days, it was noticeable that blood pressure in the MPS group was higher. We suggest that this peptide may be involved in the worsening of hypertension in the MPS experimental group, which expressed high values for blood pressure.
In Brazil, approximately 5500 kidney transplants are performed each year. After transplantation, patients start using immunosuppressants, a class of drugs with the function of modulating the immune system and preventing graft rejection. Immunosuppressive drugs such as Everolimos (EVE) and Mycophenolate Sodium (MPS) are administered in transplant therapy to reduce the risk of rejection. It is known from the literature that kidney transplant patients may develop diseases such as hypertension and diabetes, and that the appearance of these pathologies may be related to the imbalance of the Renin-Angiotensin-Aldosterone System (RAAS), resulting in post-transplant complications. Among other hormonal systems, this is a powerful system that releases peptides capable of altering cardiac function and modulating diabetes. The aim of this study was to verify whether there were changes in the modulation of the RAAS among post-kidney transplant patients who used EVE or MPS. The present study included 15 patients divided into two groups according to the medication administered. The demographic, clinical and biochemical parameters were evaluated and the expressions of the enzymes ACE, ACE2, NEP, Renin and Chymase were also analysed using the Western Blotting technique. The quantification of RAS peptides was performed by the technique of mass spectrometry in plasma samples collected at different times of the study, with the seventh day after transplantation (D7) being determined as the first day of collection for study, continuing the other days established, fourteen days (D14), one month (M1), two months (M2) and three months (M3). All patients had posttransplant diabetes mellitus and hypertension as the underlying disease. Our results showed a greater expression of ACE, but without statistical relevance and the presence of the ACE isoform with 90 kDa in both groups, described in the literature as a possible biomarker for hypertension. The quantification of the peptides did not show a statistically significant difference between the groups and collection times within the same group; however, we observed a higher concentration of Ang 3-7 in the MPS group, described in the literature as a vasoconstrictor peptide, and despite the clinical data not showing significance statistics between the groups on the different evaluation days, it was noticeable that blood pressure in the MPS group was higher. We suggest that this peptide may be involved in the worsening of hypertension in the MPS experimental group, which expressed high values for blood pressure.