Regulação autonômica cardiovascular em repouso e durante manobras simpatoexcitatórias em pacientes com doença renal policística autossômica dominante normotensos
Arquivos
Data
2024-07-30
Autores
Rocha, Daniel Ribeiro da 
Orientadores
Heilberg, Ita Pfeferman
Tipo
Tese de doutorado
Título da Revista
ISSN da Revista
Título de Volume
Resumo
A Doença Renal Policística Autossômica Dominante (DRPAD) é a doença monogênica renal mais frequente, com evolução para perda de função renal progressiva. A hipertensão arterial (HA) é uma das manifestações extra-renais mais comuns e de aparecimento precoce, sendo sua patogênese multifatorial. A desregulação autonômica associa-se a um risco aumentado para todos os eventos cardiovasculares na população em geral, tendo sido já descrita entre pacientes com DRPAD com HA e com função renal reduzida. O presente estudo teve como objetivo investigar a regulação autonômica cardiovascular na DRPAD antes do desenvolvimento de HA. Parâmetros da modulação autonômica cardiovascular em repouso, sensibilidade barorreflexa (SBR) e reatividade cardiovascular foram avaliados em pacientes jovens (18 a 40 anos) com DRPAD, normotensos e com função renal preservada. O grupo controle constituiu-se de indivíduos saudáveis, pareados por idade, sexo e índice de massa corpórea (IMC). A Variabilidade da Frequência Cardíaca (VFC) e da Pressão Arterial (VPA) e SBR espontânea durante o repouso de 5 minutos foram determinadas. A análise da SBR durante a Manobra de Valsalva (MV) e da reatividade cardiovascular (RCV) durante e após manobras simpatoexcitatórias com o emprego do Stroop test, Cold pressor test (CPT) e Handgrip (HG) foram avaliadas. Os pacientes com DRPAD foram classificados como lentos ou rápidos progressores de acordo com os critérios de imagem da Clínica Mayo (MIC). No total, foram avaliados 37 indivíduos, sendo 18 com DRPAD (11F/7M, 27,7±6,4 anos) e 19 controles (9F/10M, 25,7±3,8 anos), sem diferenças estatísticas nas distribuições de sexo, idade, médias de IMC e taxa de filtração glomerular estimada. A VFC e VPA não demonstraram diferenças estatísticas tanto no domínio do tempo quanto no domínio da frequência, demonstrando que o balanço simpatovagal foi semelhante entre os grupos. Os valores da SBR espontânea e durante a MV foram semelhantes entre os grupos, evidenciando uma resposta adequada do barorreflexo no repouso e à queda brusca da pressão arterial. A RCV durante as manobras simpatoexcitatórias não revelou diferenças entre os grupos. Também não se observaram diferenças estatísticas dos resultados de todos estes testes dentro dos subgrupos com DRPAD com lenta versus rápida progressão. Os marcadores séricos de inflamação, função endotelial e hormonais, como o neuropeptídeo Y (NPY) e o angiotensinogênio (AGT), não diferiram entre DRPAD e controles. Porém, os níveis de AGT urinário e albuminúria foram significantemente maiores em DRPAD versus Controles. Em conclusão, o presente estudo não evidenciou desregulação autonômica cardiovascular em pacientes com DRPAD normotensos com função renal preservada, mas o aumento do AGT urinário sugeriu ativação do SRA intrarrenal já em fases precoces da doença.
Autosomal Dominant Polycystic Kidney Disease (ADPKD) is the most common monogenic kidney disease, leading to progressive loss of kidney function. Arterial hypertension (AH) is one of the most common and early-onset extrarenal manifestation, whose pathogenesis is multifactorial. Autonomic dysregulation is associated with an increased risk for all cardiovascular events in the general population, having already been described among ADPKD patients with AH and reduced renal function. The present study aimed to investigate cardiovascular autonomic regulation in ADPKD before the development of AH. Cardiovascular autonomic modulation parameters at rest, baroreflex sensitivity (BRS), and cardiovascular reactivity were evaluated in young patients (18 to 40 years old) with ADPKD, normotensive, and with preserved renal function. The control group consisted of healthy individuals, matched by age, sex, and body mass index (BMI). Heart Rate Variability (HRV), Blood Pressure Variability (BPV), and spontaneous BRS during the 5-minute rest were determined. The analysis of BRS during the Valsalva Maneuver (VM) and cardiovascular reactivity (CVR) during and after sympathoexcitatory maneuvers using the Stroop test, Cold pressor test (CPT), and Handgrip (HG) were also evaluated. ADPKD patients were classified according to Mayo Clinic imaging criteria (MIC) as between slow or rapid progressors. A total of 37 individuals were evaluated, 18 with ADPKD (11F/7M, 27.7±6.4 years) and 19 controls (9F/10M, 25.7±3.8 years), with no statistical differences in the distributions of sex, age, and mean BMI and estimated glomerular filtration rate. HRV and BPV did not reveal statistical differences in either the time or frequency domains, demonstrating that the sympathovagal balance was similar among groups. The values of spontaneous BRS and the ones presented during the VM were similar between groups, suggesting an adequate baroreflex response at rest and to the sudden drop in blood pressure. CVR during sympathoexcitatory maneuvers revealed no differences between groups. The results of all these tests also did not show statistical differences between subgroups of ADPKD patients with slow versus rapid progression. Serum markers of inflammation, endothelial function, and hormones, such as neuropeptide Y (NPY) and angiotensinogen (AGT) did not differ between ADPKD and controls. However, urinary AGT and albuminuria levels were significantly higher in ADPKD versus Controls. In conclusion, the present study did not show cardiovascular autonomic dysregulation in normotensive ADPKD patients with preserved renal function, but the increase in urinary AGT suggested activation of the intrarenal RAS already in early stages of the disease.
Autosomal Dominant Polycystic Kidney Disease (ADPKD) is the most common monogenic kidney disease, leading to progressive loss of kidney function. Arterial hypertension (AH) is one of the most common and early-onset extrarenal manifestation, whose pathogenesis is multifactorial. Autonomic dysregulation is associated with an increased risk for all cardiovascular events in the general population, having already been described among ADPKD patients with AH and reduced renal function. The present study aimed to investigate cardiovascular autonomic regulation in ADPKD before the development of AH. Cardiovascular autonomic modulation parameters at rest, baroreflex sensitivity (BRS), and cardiovascular reactivity were evaluated in young patients (18 to 40 years old) with ADPKD, normotensive, and with preserved renal function. The control group consisted of healthy individuals, matched by age, sex, and body mass index (BMI). Heart Rate Variability (HRV), Blood Pressure Variability (BPV), and spontaneous BRS during the 5-minute rest were determined. The analysis of BRS during the Valsalva Maneuver (VM) and cardiovascular reactivity (CVR) during and after sympathoexcitatory maneuvers using the Stroop test, Cold pressor test (CPT), and Handgrip (HG) were also evaluated. ADPKD patients were classified according to Mayo Clinic imaging criteria (MIC) as between slow or rapid progressors. A total of 37 individuals were evaluated, 18 with ADPKD (11F/7M, 27.7±6.4 years) and 19 controls (9F/10M, 25.7±3.8 years), with no statistical differences in the distributions of sex, age, and mean BMI and estimated glomerular filtration rate. HRV and BPV did not reveal statistical differences in either the time or frequency domains, demonstrating that the sympathovagal balance was similar among groups. The values of spontaneous BRS and the ones presented during the VM were similar between groups, suggesting an adequate baroreflex response at rest and to the sudden drop in blood pressure. CVR during sympathoexcitatory maneuvers revealed no differences between groups. The results of all these tests also did not show statistical differences between subgroups of ADPKD patients with slow versus rapid progression. Serum markers of inflammation, endothelial function, and hormones, such as neuropeptide Y (NPY) and angiotensinogen (AGT) did not differ between ADPKD and controls. However, urinary AGT and albuminuria levels were significantly higher in ADPKD versus Controls. In conclusion, the present study did not show cardiovascular autonomic dysregulation in normotensive ADPKD patients with preserved renal function, but the increase in urinary AGT suggested activation of the intrarenal RAS already in early stages of the disease.
Descrição
Citação
ROCHA, Daniel Ribeiro da. Regulação autonômica cardiovascular em repouso e durante manobras simpatoexcitatórias em pacientes com doença renal policística autossômica dominante normotensos. 2024. 116 f. Tese (Doutorado em Nefrologia) - Escola Paulista de Medicina, Universidade Federal de São Paulo (UNIFESP). São Paulo, 2024.