RESUMEN
Clinical Background: The heart can cause kidney disease, and the kidney can cause heart disease. As an example of the first situation, we can mention dilated cardiomyopathies, which can lead to renal failure of the pre-renal type due to the state of renal hypoflow. As an example of the second situation, we can remember that renal failure is a risk factor for cardiovascular diseases, such as coronary heart disease, due to the acceleration in the process of atherosclerosis that it promotes. Epidemiology: In this chapter, we will address what we consider to be the two main aspects of the interrelationships between heart and kidney disease that are "cardiorenal syndrome (CRS)" and "chronic kidney disease (CKD) and coronary heart disease (CHD)." Challenges: For CRS, we discuss its epidemiology, types, pathophysiological mechanisms common to CRS types 1, 2, 3 and 4 and pathogenesis of CSR type 5. Treatment: For "CKD and CHD" we discuss the association of CKD and CHD in community-based populations, traditional risk factor in CKD, non-traditional risk factor in CKD, reduced risk of CHD in patients with CKD, statin treatment, hypertension treatment, anti-platelet aggregation therapy, treatment of CHD in patients with CKD and prognosis of CHDF in CKD patients.
Asunto(s)
Aterosclerosis , Síndrome Cardiorrenal , Insuficiencia Renal Crónica , Síndrome Cardiorrenal/complicaciones , Síndrome Cardiorrenal/etiología , Humanos , Riñón , Insuficiencia Renal Crónica/complicaciones , Insuficiencia Renal Crónica/epidemiología , Factores de RiesgoRESUMEN
Renal injury caused by renal ischemia and reperfusion strongly influences heart morphology, electrophysiology, and redox unbalance. The so-called cardiorenal syndrome is an important class of dysfunction since heart and kidneys are responsible for hemodynamic stability and organ perfusion through a complex network. In the present work we investigate the vibrational spectral features probed by Fourier-Transform Raman (FT-Raman) spectroscopy due to physiological alterations induced by renal ischemic reperfusion aiming to detect molecular markers related to progression of acute to chronic kidney injury and mortality predictors as well. C57BL/6J mice were subjected to unilateral occlusion of the renal pedicle for 60 min and reperfusion for 5, 8, and 15 days. Biopsies of heart and kidney tissues were analyzed. Our findings indicated that cysteine/cystine, fatty acids, methyl groups of Collagen, α-form of proteins, Tyrosine, and Tryptophan were modulated during renal ischemia and reperfusion process. These changes are consistent with fibroblast growth factors and Collagen III contents changes. Interestingly, Tyrosine and Tryptophan, precursor molecules for the formation of uremic toxins such as indoxyl sulfate and p-cresyl sulfate were also modulated. They are markers of kidney injury and their increase is strongly correlated to cardiovascular mortality. Regarding this aspect, we notice that monitoring the Tyrosine and Tryptophan bands at 1558, 1616, and 1625 cm-1 is a viable and and advantageous way to predict fatality in cardiovascular diseases both "in vivo" or "in vitro", using the real-time, multiplexing, and minimally invasive advantages of FT-Raman spectroscopy.
Asunto(s)
Biomarcadores , Enfermedades Renales/etiología , Enfermedades Renales/metabolismo , Triptófano/metabolismo , Tirosina/metabolismo , Animales , Síndrome Cardiorrenal/diagnóstico , Síndrome Cardiorrenal/etiología , Síndrome Cardiorrenal/metabolismo , Manejo de la Enfermedad , Susceptibilidad a Enfermedades , Enfermedades Renales/diagnóstico , Masculino , Ratones , Especificidad de Órganos , Daño por Reperfusión/complicaciones , Análisis Espectral/métodos , Triptófano/análisis , Tirosina/análisisRESUMEN
ABSTRACT Introduction: Cardio-renal syndrome subtype 4 (CRS4) is a condition of primary chronic kidney disease that leads to reduction of cardiac function, ventricular hypertrophy, and risk of cardiovascular events. Objective: Our aim was to understand the mechanisms involved on the onset of CRS4. Methods: We used the nephrectomy 5/6 (CKD) animal model and compared to control (SHAM). Serum biomarkers were analyzed at baseline, 4, and 8 weeks. After euthanasia, histology and immunohistochemistry were performed in the myocardium. Results: Troponin I (TnI) was increased at 4 weeks (W) and 8W, but nt-proBNP showed no difference. The greater diameter of cardiomyocytes indicated left ventricular hypertrophy and the highest levels of TNF-α were found at 4W declining in 8W while fibrosis was more intense in 8W. Angiotensin expression showed an increase at 8W. Conclusions: TnI seems to reflect cardiac injury as a consequence of the CKD however nt-proBNP did not change because it reflects stretching. TNF-α characterized an inflammatory peak and fibrosis increased over time in a process connecting heart and kidneys. The angiotensin showed increased activity of the renin-angiotensin axis and corroborates the hypothesis that the inflammatory process and its involvement with CRS4. Therefore, this animal study reinforces the need for renin-angiotensin blockade strategies and the control of CKD to avoid the development of CRS4.
RESUMO Introdução: A síndrome cardiorrenal (SCR) tipo 4 é uma afecção da doença renal crônica primária que leva a redução da função cardíaca, hipertrofia ventricular e risco de eventos cardiovasculares. Objetivo: O objetivo do presente estudo foi compreender os mecanismos envolvidos no surgimento da SCR tipo 4. Métodos: Um modelo animal de nefrectomia 5/6 (DRC) foi comparado a animais de controle (Placebo). Biomarcadores séricos foram analisados no início do estudo e com quatro e oito semanas de estudo. Após eutanásia, foram realizados exames histológicos e de imunoistoquímica no tecido miocárdico. Resultados: Troponina I (TnI) estava aumentada nas semanas quatro (S4) e oito (S8), mas o NT-proBNP não apresentou diferenças. O diâmetro maior dos cardiomiócitos indicava hipertrofia ventricular esquerda. Os níveis mais elevados de TNF-α foram identificados na S4 com redução na S8, enquanto fibrose foi mais intensa na S8. A expressão de angiotensina mostrou elevação na S8. Conclusões: TnI parece sugerir lesões cardíacas em consequência da DRC, porém o NT-proBNP não sofreu alterações por refletir alongamento. O TNF-α evidenciou um pico inflamatório e a fibrose aumentou ao longo do tempo devido ao processo de conexão entre rins e coração. A angiotensina mostrou aumento da atividade do eixo renina-angiotensina, corroborando a hipótese do processo inflamatório e seu envolvimento com SCR tipo 4. Portanto, o presente estudo em modelo animal reforça a necessidade de em adotar estratégias com bloqueadores de renina-angiotensina e controle da DRC para evitar o desenvolvimento de SCR tipo 4.
Asunto(s)
Animales , Masculino , Ratas , Fragmentos de Péptidos/sangre , Factor de Necrosis Tumoral alfa/sangre , Troponina I/sangre , Péptido Natriurético Encefálico/sangre , Síndrome Cardiorrenal/etiología , Síndrome Cardiorrenal/sangre , Uremia/complicaciones , Uremia/sangre , Biomarcadores/sangre , Ratas Wistar , Modelos Animales de Enfermedad , Cardiomiopatías/etiología , Cardiomiopatías/sangreRESUMEN
INTRODUCTION: Cardio-renal syndrome subtype 4 (CRS4) is a condition of primary chronic kidney disease that leads to reduction of cardiac function, ventricular hypertrophy, and risk of cardiovascular events. Objective: Our aim was to understand the mechanisms involved on the onset of CRS4. METHODS: We used the nephrectomy 5/6 (CKD) animal model and compared to control (SHAM). Serum biomarkers were analyzed at baseline, 4, and 8 weeks. After euthanasia, histology and immunohistochemistry were performed in the myocardium. RESULTS: Troponin I (TnI) was increased at 4 weeks (W) and 8W, but nt-proBNP showed no difference. The greater diameter of cardiomyocytes indicated left ventricular hypertrophy and the highest levels of TNF-α were found at 4W declining in 8W while fibrosis was more intense in 8W. Angiotensin expression showed an increase at 8W. CONCLUSIONS: TnI seems to reflect cardiac injury as a consequence of the CKD however nt-proBNP did not change because it reflects stretching. TNF-α characterized an inflammatory peak and fibrosis increased over time in a process connecting heart and kidneys. The angiotensin showed increased activity of the renin-angiotensin axis and corroborates the hypothesis that the inflammatory process and its involvement with CRS4. Therefore, this animal study reinforces the need for renin-angiotensin blockade strategies and the control of CKD to avoid the development of CRS4.
Asunto(s)
Síndrome Cardiorrenal/sangre , Síndrome Cardiorrenal/etiología , Péptido Natriurético Encefálico/sangre , Fragmentos de Péptidos/sangre , Troponina I/sangre , Factor de Necrosis Tumoral alfa/sangre , Animales , Biomarcadores/sangre , Cardiomiopatías/sangre , Cardiomiopatías/etiología , Modelos Animales de Enfermedad , Masculino , Ratas , Ratas Wistar , Uremia/sangre , Uremia/complicacionesRESUMEN
BACKGROUND: Acute Kidney Injury (AKI), a common complication of acute coronary syndromes (ACS), is associated with higher mortality and longer hospital stays. The role of cytokines and other mediators is unknown in AKI induced by an ACS (ACS-AKI), leading to several unanswered questions. The worsening of renal function is usually seen as a dichotomous phenomenon instead of a dynamic change, so evaluating changes of the renal function in time may provide valuable information in the ACS-AKI setting. The aim of this study was to explore inflammatory factors associated to de novo kidney injury induced by de novo cardiac injury secondary to ACS. METHODS: One hundred four consecutive patients with ACS were initially included on the time of admission to the Coronary Unit of the Instituto Nacional de Cardiología in Mexico City, from February to May 2016, before any invasive procedure, imaging study, diuretic or anti-platelet therapy. White blood count, hemoglobin, NT-ProBNP, troponin I, C-reactive protein, albumin, glucose, Na+, K+, blood urea nitrogen (BUN), total cholesterol, HDL, LDL, triglycerides, creatinine (Cr), endothelin-1 (ET-1), leukotriene-B4, matrix metalloproteinase-2 and -9, tissue inhibitor of metalloproteinases-1, resolvin-D1 (RvD1), lipoxin-A4 (LXA4), interleukin-1ß, -6, -8, and -10 were measured. We finally enrolled 78 patients, and subsequently we identified 15 patients with ACS-AKI. Correlations were obtained by a Spearman rank test. Low-rank regression, splines regressions, and also protein-protein/chemical interactions and pathways analyses networks were performed. RESULTS: Positive correlations of ΔCr were found with BUN, admission Cr, GRACE score, IL-1ß, IL-6, NT-ProBNP and age, and negative correlations with systolic blood pressure, mean-BP, diastolic-BP and LxA4. In the regression analyses IL-10 and RvD1 had positive non-linear associations with ΔCr. ET-1 had also a positive association. Significant non-linear associations were seen with NT-proBNP, admission Cr, BUN, Na+, K+, WBC, age, body mass index, GRACE, SBP, mean-BP and Hb. CONCLUSION: Inflammation and its components play an important role in the worsening of renal function in ACS. IL-10, ET-1, IL-1ß, TnI, RvD1 and LxA4 represent mediators that might be associated with ACS-AKI. IL-6, ET-1, NT-ProBNP might represent crossroads for several physiopathological pathways involved in "de novo cardiac injury leading to de novo kidney injury".
Asunto(s)
Síndrome Coronario Agudo/complicaciones , Lesión Renal Aguda/etiología , Síndrome Cardiorrenal/etiología , Citocinas/sangre , Mediadores de Inflamación/sangre , Inflamación/etiología , Riñón/fisiopatología , Síndrome Coronario Agudo/sangre , Síndrome Coronario Agudo/diagnóstico , Lesión Renal Aguda/sangre , Lesión Renal Aguda/diagnóstico , Lesión Renal Aguda/fisiopatología , Anciano , Biomarcadores/sangre , Síndrome Cardiorrenal/sangre , Síndrome Cardiorrenal/diagnóstico , Síndrome Cardiorrenal/fisiopatología , Femenino , Humanos , Inflamación/sangre , Inflamación/diagnóstico , Inflamación/fisiopatología , Masculino , México , Persona de Mediana Edad , Pronóstico , Mapas de Interacción de Proteínas , Factores de Riesgo , Transducción de SeñalRESUMEN
Fundamento: el Síndrome cardiorrenal explica la evidente existencia de una interrelación fisiopatológica entre corazón y riñón.Objetivo: realizar una revisión bibliográfica actualizada sobre este síndrome.Método: se realizó una revisión de la literatura de los últimos diez años que incluyó 1034 artículos publicados, de las bases Pub Med, Medline, Lilacs y Scielo mediante el localizador de información Endnote, con los descriptores, Syndrome cardiorrenal, concepto, epidemiología, fisiopatología, clasificación, pronóstico, tratamiento. Se utilizaron 33 referencias bibliográficas para la redacción del artículo, de ellas 15 artículos originales, 16 trabajos de revisión y dos presentaciones de casos.Desarrollo: se exponen brevemente los antecedentes históricos y entre las definiciones, la más reconocida en la actualidad, como los trastornos del corazón y de los riñones donde la disfunción aguda o crónica de un órgano, puede inducir disfunción aguda o crónica del otro su presentación es frecuente, se muestra la clasificación de Ronco en cinco tipos y el manejo integral y multidisciplinario.Conclusiones: el Síndrome cardiorrenal es un fenómeno frecuente, pero aún no bien definido ni reconocido. Un mejor conocimiento de su fisiopatología y evolución natural, haría posible un uso más apropiado de las diferentes opciones terapéuticas para cada paciente individual. El manejo terapéutico emergente del síndrome cardiorrenal, puede ayudar a que la mejoría funcional de ambos órganos colabore a un mejor pronóstico de este grupo de pacientes(AU)
Background: cardiorenal syndrome explains the evident existence of a physiopathologic interrelation between heart and kidney.Objective: to make an updated bibliographic review about this syndrome.Method: a review of the literature from the last ten years was made. The review included 1034 published articles from the data bases Pub Med, Medline, Lilacs, and Scielo through the information locator Endnote with the descriptors cardiorenal syndrome, concept, epidemiology, physiopathology, classification, prognosis, treatment. Thirty-three bibliographic references were used for the writing of the article; 15 references of them were original articles, 16 were review articles and two were case presentations.Development: the historical background is briefly explained and among the definitions, the most recognized one nowadays states that: in heart and kidney disorders the acute or chronic dysfunction of one of these organs can produce acute or chronic dysfunction on the other one; its onset is frequent. Ronco's five-type classification and the comprehensive and multidisciplinary handling are also discussed.Conclusions: cardiorenal syndrome is a frequent phenomenon but still not well defined or recognized. Knowing better its physiopathology and natural evolution would make possible a more appropriate use of the different therapeutic options for each patient. The resulting therapeutic handling of the cardiorenal syndrome may facilitate that the functional improvement of both organs contribute to a better prognosis of these patients(AU)