A new animal model of cardiorenal syndrome could be established by inducing heart failure through coronary artery ligation in spontaneously hypertensive rats.

In rats with unilateral nephrectomy and cardiac dysfunction, renal function deteriorates at an accelerated rate, as evidenced by increased proteinuria. Whether myocardial infarct-induced heart failure (HF) exacerbates renal injury in hypertensive rats with mild renal injury has not been reported. Rats underwent either coronary ligation or sham surgery. Thirty spontaneously hypertensive rats (SHRs) aged 8 weeks were randomly divided into two groups. Group 1 was the sham group, in which the rats underwent thoracotomy without ligation of the coronary artery. Group 2 underwent coronary artery ligation. The rats in group 2 underwent coronary artery ligation on week 0. The experiment lasted 12 weeks. Urine was collected in metabolic cages over a 24-h period. Urine was collected from the rats 2 days before the end of the experiment, and the ratio of urinary protein to urinary creatinine was measured in the clinical laboratory. All rats were examined by echocardiogram one day before the end of the experiment. On the last day of the experiment, blood was collected and sent to the laboratory for analysis. Hematoxylin-eosin (HE) and periodic acid-Schiff (PAS) staining were performed on heart and kidney sections. The ejection fraction in group 2 was lower than that in group 1 (P < 0.001). The urinary albumin to creatinine ratio in group 2 was greater than that in group 1 (P < 0.001). The urea and creatinine levels in group 1 were significantly lower than those in group 2 (P < 0.01). The levels of brain natriuretic peptide (BNP), neutrophil gelatinase-associated lipocalin (NGAL) and cystatin C were greater in the second group than in the first group (P < 0.05). The interleukin-1ß (IL-1ß) and interleukin-6 (IL-6) levels in group 2 were significantly greater than those in group 1 (P < 0.001). The malondialdehyde (MDA) levels in Group 2 were greater than those in Group 1 (P < 0.01). The glutathione peroxidase (GSH-Px) levels in Group 2 were lower than those in Group 1 (P < 0.05). The level of angiotensin II (AT-II) in group 1 was lower than that in group 2 (P < 0.001). Cardiac dysfunction secondary to myocardial infarction could induce cardiorenal interactions in SHRs. It could be interpreted by the activation of oxidative stress, changes in inflammation and alteration of renin-angiotensin-aldosterone system.

Biomarker for cardiorenal syndrome risk in patients with liver cirrhosis and type 2 diabetes in Saudi Arabia.

OBJECTIVES: To evaluate the correlation between different attributes, levels of biomarkers, and the probability of developing cardiorenal syndrome (CRS) in patients who have been diagnosed with type 2 diabetes mellitus (T2DM) and liver cirrhosis (LC). The hypothesis suggests that liver illness may be linked to renal impairment, cardiac dysfunction, and the development of cardiorenal syndrome METHODS: The current study retrospectively assessed the medical records of patients who had LC and T2DM diagnoses and were hospitalized at Al Madina Al Munwara hospitals in 2022 and 2023. RESULTS: This research investigated T2DM patients with physician-confirmed to have LC. Poor glycemic control is indicated by high blood glucose and glycated hemoglobin (HbA1c) readings in research participants. High blood pressure, atherogenic plasma indicator (AIP), and obesity plagued most of these individuals. High creatinine, moderate estimated Glomerular Filtration Rate (eGFR) decline, and a modest urinary albumin-to-creatinine (UACR) rise were the most prevalent variables in LC and T2DM patients. Cardiorenal syndrome risk factors, including elevated blood pressure, triglyceride levels, body mass index (BMI), and high-sensitivity C-reactive protein (hs-CRP) concentrations, were identified through logistic regression. It has been demonstrated that the prevalence of these risk factors increases with age; women may be at a greater risk for developing CRS. Specific biomarker evaluations classified 108 (22.6%) LC and T2DM patients at high risk for chronic kidney disease (CKD), 100 (20%) at risk for cardiovascular disease (CVD), and 91 (18.2%) at risk for CRS. CONCLUSION: The current assessment included 500 patients with T2DM and LC. The risk factors for CRS identified in this study included elevated cholesterol and triglyceride levels, high BMI, and elevated blood pressure, with age being a significant factor, particularly in female patients. Early identification of these characteristics in patients with LC and T2DM could aid in mitigating the progression of chronic illnesses and their associated complications.

Risk factors and early prediction of cardiorenal syndrome type 3 among acute kidney injury patients: a cohort study.

BACKGROUND: Type 3 cardiorenal syndrome (CRS type 3) triggers acute cardiac injury from acute kidney injury (AKI), raising mortality in AKI patients. We aimed to identify risk factors for CRS type 3 and develop a predictive nomogram. METHODS: In this retrospective study, 805 AKI patients admitted at the Department of Nephrology, Second Hospital of Shanxi Medical University from 1 January 2017, to 31 December 2021, were categorized into a study cohort (406 patients from 2017.1.1-2021.6.30, with 63 CRS type 3 cases) and a validation cohort (126 patients from 1 July 2021 to 31 Dec 2021, with 22 CRS type 3 cases). Risk factors for CRS type 3, identified by logistic regression, informed the construction of a predictive nomogram. Its performance and accuracy were evaluated by the area under the curve (AUC), calibration curve and decision curve analysis, with further validation through a validation cohort. RESULTS: The nomogram included 6 risk factors: age (OR = 1.03; 95%CI = 1.009-1.052; p = 0.006), cardiovascular disease (CVD) history (OR = 2.802; 95%CI = 1.193-6.582; p = 0.018), mean artery pressure (MAP) (OR = 1.033; 95%CI = 1.012-1.054; p = 0.002), hemoglobin (OR = 0.973; 95%CI = 0.96--0.987; p < 0.001), homocysteine (OR = 1.05; 95%CI = 1.03-1.069; p < 0.001), AKI stage [(stage 1: reference), (stage 2: OR = 5.427; 95%CI = 1.781-16.534; p = 0.003), (stage 3: OR = 5.554; 95%CI = 2.234-13.805; p < 0.001)]. The nomogram exhibited excellent predictive performance with an AUC of 0.907 in the study cohort and 0.892 in the validation cohort. Calibration and decision curve analyses upheld its accuracy and clinical utility. CONCLUSIONS: We developed a nomogram predicting CRS type 3 in AKI patients, incorporating 6 risk factors: age, CVD history, MAP, hemoglobin, homocysteine, and AKI stage, enhancing early risk identification and patient management.

Rat Models of Cardiorenal Syndrome and Methods for Functional Assessment.

Cardiorenal syndrome (CRS) is a clinical disorder involving combined heart and kidney dysfunction, which leads to poor clinical outcomes. To understand the complex pathophysiology and mechanisms that lie behind this disease setting, and design/evaluate appropriate treatment strategies, suitable animal models are required. Described here are the protocols for establishing surgically induced animal models of CRS including important methods to determine clinically relevant measures of cardiac and renal function, commonly used to assess the degree of organ dysfunction in the model and treatment efficacy when evaluating novel therapeutic strategies.

Biomarkers of cardio-renal syndrome in uremic myocardiopathy animal model / Biomarcadores de síndrome cardiorrenal em modelo animal de miocardiopatia urêmica

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.

Síndrome cardiorrenal / Cardiorenal syndrome

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)

Insuficiencia cardíaca aguda. ¿Tenemos por fin una verdadera oportunidad de mejorar el pronóstico? / No disponible

No disponible

Daño orgánico y síndrome cardiorrenal en la insuficiencia cardíaca aguda / Organ damage and cardiorenal syndrome in acute heart failure

La insuficiencia cardíaca es un síndrome complejo que afecta prácticamente la totalidad de órganos y sistemas de la economía. En los frecuentes episodios de agudización o descompensación, la afectación orgánica se acentúa o incluso se hace patente por vez primera. De entre los órganos más íntimamente relacionados con las descompensaciones, es el riñón el que juega un papel más protagonista. La coexistencia en la afectación de ambos órganos, sea cual sea el inicialmente involucrado y sea cual sea el estadio evolutivo de su disfunción, es lo que en los últimos años se ha denominado como síndrome cardiorrenal. La investigación sobre los mecanismos que regulan la compleja relación entre ambos órganos está propiciando una intensa búsqueda de nuevos biomarcadores que permitan detectar el daño renal en estadios subclínicos. Algo que permitirá, en un futuro inmediato, actuar protegiendo los riñones mucho antes de la pérdida de su función. En la presente revisión se ofrece una visión general de dicho síndrome y se repasan los mecanismos fisiopatológicos involucrados, con especial énfasis en el papel de la congestión visceral como uno de los mecanismos emergentes en el síndrome cardiorrenal (AU)

Heart failure is a complex syndrome that affects almost all organs and systems of the body. Signs and symptoms of organ dysfunction, in particular kidney dysfunction, may be accentuated or become evident for the first time during acute decompensation of heart failure. Cardiorenal syndrome has been defined as the simultaneous dysfunction of both the heart and the kidney, regardless of which of the two organs may have suffered the initial damage and regardless also of their previous functional status. Research into the mechanisms regulating the complex relationship between the two organs is prompting the search for new biomarkers to help physicians detect renal damage in subclinical stages. Hence, a preventive approach to renal dysfunction may be adopted in the clinical setting in the near future. This article provides a general overview of cardiorenal syndrome and an update of the physiopathological mechanisms involved. Special emphasis is placed on the role of visceral congestion as an emergent mechanism in this síndrome (AU)

Alternativas al tratamiento diurético convencional en insuficiencia cardíaca / Alternatives to conventional diuretic therapy in heart failure

A pesar de que el tratamiento de la insuficiencia cardíaca agudizada se sustenta, fundamentalmente, en la administración de diuréticos de asa de forma intravenosa, la evidencia científica que apoya esta práctica todavía es escasa y hay cierta incertidumbre respecto a las dosis y posología óptimas. La existencia de un porcentaje considerable de pacientes con resistencia al tratamiento diurético y el desarrollo de insuficiencia renal asociada al uso de estos fármacos, con posibles implicaciones sobre la mortalidad a medio plazo, han promovido la búsqueda de alternativas más eficaces y seguras. Técnicas de depuración extracorpórea, como la ultrafiltración, han demostrado eficacia, aunque no una clara superioridad, cuestionada por los posibles efectos adversos asociados a la técnica. El uso de dopamina a dosis bajas no se ha demostrado superior al tratamiento diurético convencional transcurridas las primeras horas de tratamiento. Por otra parte, la combinación con furosemida y suero salino hipertónico podría constituir una alternativa válida para la congestión refractaria en pacientes con fracción de eyección deprimida y creatinina plasmática ≤ 2,5 mg/dl, aunque precisa de más estudios antes de su generalización. El uso de tolvaptán puede ser una alternativa eficaz a corto plazo; sin embargo, su coste puede limitar su utilización. Debe considerarse que todavía hay controversia acerca de si el tratamiento con diuréticos de asa se asocia a mayor mortalidad en todos los grupos de pacientes con insuficiencia cardíaca agudizada. Futuros ensayos clínicos deberán aclarar estas controversias (AU)

Although treatment of acute heart failure is based primarily on the administration of intravenous loop diuretics, evidence supporting this practice is still scarce and there is uncertainty about the optimal dose. The existence of a considerable percentage of patients refractory to diuretic therapy and worsening of renal failure associated with the use of these drugs, with possible implications for medium-term mortality, have prompted the search for more effective and safer alternatives. Extracorporeal purification techniques, such as ultrafiltration, have demonstrated efficacy, although their superiority is unclear, due to the possible adverse effects associated with the procedure. The use of low-dose dopamine is not superior to conventional diuretic therapy after the first few hours of treatment. Moreover, combination with furosemide and hypertonic saline could be a valid alternative for patients with refractory congestion and depressed ejection fraction and serum creatinine ≤ 2.5 mg/dL, but further studies are needed before its widespread use. The use of tolvaptan may be an effective alternative in the short-term but its use may be limited by its price. There is still controversy about whether treatment with loop diuretics is associated with higher mortality in all groups of patients with HF exacerbations. These controversies should be clarified by future clinical trials (AU)

Tratamiento complementario de la insuficiencia cardíaca aguda en el paciente con diabetes, enfermedad pulmonar obstructiva crónica o anemia / Complementary treatment of acute heart failure in patients with diabetes, chronic obstructive pulmonary disease or anemia

La diabetes, la enfermedad pulmonar obstructiva crónica (EPOC) y la anemia son comorbilidades con elevada prevalencia e impacto en la insuficiencia cardíaca (IC). El pronóstico de la IC aguda empeora considerablemente ante la presencia de estas comorbilidades. Los pacientes diabéticos tienen mayor probabilidad de desarrollar clínica de IC, y tanto el tratamiento de la diabetes como el de la IC aguda se ven alterados ante la coexistencia de ambas entidades. Los objetivos glucémicos en pacientes con IC aguda no están bien definidos, pero podrían comportarse con una curva en U. La hiperglucemia de estrés en pacientes con IC aguda no diabéticos también tiene un efecto muy deletéreo en el pronóstico a medio plazo. La interrelación entre EPOC e IC aguda dificulta la fase diagnóstica al compartir síntomas, signos y estudios complementarios. El tratamiento de la IC aguda también se ve modulado por la presencia de la EPOC. La anemia es muy prevalente y, a menudo, es la causa directa de la descompensación de la IC, siendo la ferropenia la etiología más frecuente. Las terapias de reposición de hierro, concretamente la disposición de preparados de administración intravenosa, han contribuido a mejorar el pronóstico de la IC aguda (AU)

Diabetes, chronic obstructive pulmonary disease (COPD) and anemia are comorbidities with a high prevalence and impact in heart failure (HF). The presence of these comorbidities considerably worsens the prognosis of HF. Diabetic patients have a higher likelihood of developing symptoms of HF and both the treatment of diabetes and that of acute HF are altered by the coexistence of both entities. The glycemic targets in patients with acute HF are not well-defined, but could show a U-shaped relationship. Stress hyperglycemia in non-diabetic patients with HF could also have a deleterious effect on the medium-term prognosis. The inter-relationship between COPD and HF hampers diagnosis due to the overlap between the symptoms and signs of both entities and complementary investigations. The treatment of acute HF is also altered by the presence of COPD. Anemia is highly prevalent and is often the direct cause of decompensated HF, the most common cause being iron deficiency anemia. Iron replacement therapy, specifically intravenous forms, has helped to improve the prognosis of acute HF (AU)

Tratamiento organoprotector. ¿Un nuevo tratamiento a incorporar en la insuficiencia cardíaca aguda? / No disponible

A diferencia del beneficio prolongado en el tiempo que ofrece el tratamiento de la insuficiencia cardíaca (IC) crónica, los tratamientos para la IC aguda evaluados a lo largo de la última década no han demostrado ser capaces (más allá de mejorar en algún caso los síntomas durante el episodio agudo) de reducir el riesgo más elevado de morbimortalidad a medio-largo plazo que experimentan estos pacientes tras un episodio de descompensación. En la actualidad está cobrando fuerza la hipótesis de que para alcanzar este objetivo un tratamiento efectivo debería ser capaz no solo de controlar los síntomas de descompensación, sino también de ofrecer una "protección" prolongada en el tiempo ante los cambios hemodinámicos y la activación secundaria de mecanismos neurohumorales e inflamatorios perjudiciales para el organismo que presentan, durante y tras el episodio clínico de descompensación, los pacientes con IC aguda. La serelaxina, molécula relacionada con el grupo de péptidos endógenos de la familia de la relaxina humana, con múltiples efectos beneficiosos para el miocardio, el árbol vascular y el riñón, además de otros órganos y tejidos, constituye el primer ejemplo documentado de éxito de un tratamiento con este perfil "organoprotector". Su uso en pacientes con IC aguda ha mostrado ya algunos beneficios clínicos prometedores a medio plazo, lo que la convierte en un serio candidato a ocupar un papel de primera línea para mejorar el pronóstico de estos pacientes (AU)

Unlike the prolonged benefit produced by the treatment of chronic heart failure, newer drugs tested for the treatment of acute heart failure in the last decade have failed to provide evidence of clinical benefit beyond some improvement in symptom relief. In particular, no drug has shown the ability to reduce the higher medium- and long-term risk of morbidity and mortality in these patients after an episode of decompensation. Current understanding of the pathophysiology of acute heart failure and its consequences has led to the hypothesis that, beyond symptom control, effective therapies for this syndrome should target not only the hemodynamic changes of the initial phase of the syndrome but should also "protect" the organism from the activation of neurohumoral and inflammatory pathways triggered by the decompensation episode, which persist in time and confer a risk of deleterious effects in several organs and tissues. Serelaxin, a new drug related to the peptidic endogenous hormones of the relaxin family, has recently been shown to provide multiple beneficial effects in terms of "organ protection" - not only in the cardiovascular and renal systems - from these acute heart failure-related deleterious changes. This drug has already been tested in acute heart failure patients with encouraging results in terms of medium-term clinical benefit, rendering serelaxin as a serious candidate for first-line, prognosis-modifying therapy in this syndrome (AU)