Identificación de Factores Clínicos Relacionados a una Mayor Mortalidad Asociada a Insuficiencia Renal Aguda en pacientes de Terapia Intensiva

La insuficiencia renal aguda (IRA) es una de las complicaciones más frecuentes en los pacientes hospitalizados, siendo un factor de riesgo de mortalidad. Es de suma importancia identificar la asociación de factores clínicos que empeoran la mortalidad en pacientes con IRA internados en una unidad de terapia intensiva (UTI). Se incluyeron 218 pacientes, de los cuales el 63,7% (n=139) correspondieron a hombres con un promedio de edad de 43±19 años. El análisis de correlación de variables de control, dependiente e independiente fue a través del coeficiente de Spearman y el OR fue analizado mediante regresión logística. De los 218 pacientes, falleció el 33% (n=72) de los pacientes internados en UTI. La IRA ocurrió en 28,4% (n=62) del total de pacientes y de estos, el 61,3% (n=38) fallecieron, con un OR de 4,94 (p 0,0001). La mayor proporción de fallecidos perteneció a la categoría AKIN 3. Las variables clínicas de ventilación mecánica (PR 3,57, IC 95%, 0,34-37,93), uso de drogas vasoactivas (PR 8,32, IC 95%, 3,20-21,64), puntuación APACHE III (PR 1,12, IC 95%, 1,03-1,23), edad (PR 1,01, IC 95%, 0,99-1,04) y los sometidos a cirugía (PR 0,28, IC 95%, 0,10-0,80) tuvieron asociación positiva y aumentaron la mortalidad. La presencia de variables clínicas de ventilación mecánica, la utilización de drogas vasoactivas, sepsis, el estudio APACHE III, la edad, la categoría AKIN 3, y el antecedente de cirugía previo al ingreso a UTI aumentan significativamente la mortalidad en pacientes con IRA en UTI.

Acute renal failure (ARF) is one of the most frequent complications in hospitalized patients and is a risk factor for mortality. It is extremely important to identify the association of clinical factors that worsen mortality in patients with ARF admitted to an intensive care unit (ICU). A total of 218 patients were included, of which 63.7% (n=139) were men with a mean age of 43±19 years. The correlation analysis of control, dependent, and independent variables was done through Spearman's coefficient and the OR was analyzed through logistic regression. Of the 218 patients, 33% (n=72) died in the ICU. ARF occurred in 28.4% (n=62) of all patients and of these, 61.3% (n=38) died, with an OR of 4.94 (p 0.0001). The highest proportion of deceased patients were in the AKIN 3 category. The clinical variables of mechanical ventilation (PR 3.57, 95% CI, 0.34-37.93), use of vasoactive drugs (PR 8.32, 95% CI, 3.20-21.64), APACHE III score (PR 1.12, 95% CI, 1.03-1.23), age (PR 1.01, 95% CI, 0.99-1.04) and those who underwent surgery (PR 0.28, 95% CI, 0.10-0.80) had a positive association and increased mortality. The presence of clinical variables of mechanical ventilation, the use of vasoactive drugs, sepsis, APACHE III stage, age, AKIN 3 category, and a history of surgery before admission to the ICU significantly increase mortality in patients with ARF in ICU.

Chronic renal failure: perception and knowledge of patients at the terminal stage in Brazzaville

Introduction. Chronic kidney disease (CKD)is a long-term condition in which the kidneys gradually lose their function over time, becomes impaired, leading to a buildup of waste and toxins in the body. This aimed at at evaluating the perception of CKDamong newly diagnosed end-stage chronic renal failure patients. Methodology. This was a descriptive cross-sectional study with prospective data collection, which took place over the period from January 1 to , in the Nephrology department of the Brazzaville university hospital. It covered 128 patients who were exhaustively identified. sociodemographic data and data on illness perception were collected from medical records and during individual interviews using pre-established survey forms. Microsoft Excel 2021 software enabled data analysis and processing. Results. We studied 128participants with a sex ratio of 2.5 and the age was was 50. There was a misperception of CKDamong46.1% of our participants. CKD was thought in curableby 51,6% of them and it was considered a fairly worrying disease by 61.7% of patients. The belief of CKD having a supernatural cause was held by 46.9% of patients. Patients thought that CKD could be treated with traditional medicine (36,7%), modern medicine (27,3%) and through prayer(18%). CKD was unknown before hospitalization by 76,6% of patients. Conclusion. There is a wrong perception of chronic kidney failure by patients in the end stage of their kidney disease due to the general public's low level of knowledge about kidney diseases

Introduction.La maladie rénale chronique (MRC) est une affection à long terme au cours de laquelle les reins perdent progressivement leur fonction au fil du temps, deviennent altérés, ce qui entraîne une accumulation de déchets et de toxines dans le corps. Cette étudevisait à évaluer la perception de la MRC chez les patients atteints d'insuffisance rénale chronique au stade terminal récemment diagnostiqués. Méthodologie.Il s'agissait d'une étude descriptive transversale avec une collecte prospective des données, qui s'est déroulée du 1er janvier au 30 octobre 2023, au service de néphrologie de l'hôpital universitaire de Brazzaville. Elle concernait 128 patients qui ont été identifiés de manière exhaustive. Les données sociodémographiques et les données sur la perception de la maladie ont été collectées à partir des dossiers médicaux et lors d'entretiens individuels à l'aide de formulaires d'enquête préétablis. Le logiciel Microsoft Excel 2021 a permis l'analyse et le traitement des données. Résultats.Nous avons étudié128 participants, avec un ratio homme-femme de 2,5 et un âge médian de 50 ans. Il y avait une méconnaissance de la MRC chez 46,1% de nos participants. 51,6% d'entre eux pensaient que la MRC était incurable et 61,7% des patients considéraient cette maladiecomme assez inquiétante. 46,9% des patients pensaient que la MRC avait une cause surnaturelle. Les patients pensaient que la MRC pouvait être traitée avec la médecine traditionnelle (36,7%), la médecine moderne (27,3%) et par la prière (18%). La MRC étaitméconnue avant l'hospitalisation chez 76,6% des patients. Conclusion.Il existe une perception erronée de l'insuffisance rénale chronique chez les patients en stade terminal de leur maladie rénaledû à la faible connaissance du grand public sur les maladies rénales.

Comparison of Effect of Hirudo， Notoginseng Radix et Rhizoma， and Their Combinations on Renal Fibrosis in Rats with Chronic Renal Failure / 中国实验方剂学杂志

ObjectiveTo observe the effects of Hirudo， Notoginseng Radix et Rhizoma， and drug pair on renal pathological morphology and protein phosphatase 2A （PP2A）/adenylate activated protein kinase （AMPK）/mammalian target of rapamycin （mTOR） signal pathway in rats with chronic renal failure （CRF）. MethodThe 55 male SD rats were randomly divided into a normal group （n=11） and a modeling group （n=44）. The normal group was fed conventionally， and the modeling group was given 0.25 g·kg-1·d-1 adenine by gavage for 28 days to replicate the CRF model. After successful modeling， rats were randomly divided into model group， Hirudo group （3 g·kg-1·d-1）， Notoginseng Radix et Rhizoma group （3 g·kg-1·d-1）， and Hirudo + Notoginseng Radix et Rhizoma group （3 g·kg-1·d-1）， with 9 rats in each group. The normal group and model group were given a constant volume of normal saline by intragastric administration for 30 days. At the end of the experiment， the levels of serum creatinine （SCr） and urea nitrogen （BUN） in all groups were measured. The renal pathological morphology changes were observed by hematoxylin-eosin （HE） staining， Masson staining， and electron microscopy. The mRNA expressions of PP2A， AMPK， and mTOR were detected by Real-time fluorescence quantitative polymerase chain reaction （Real-time PCR）. The protein expression levels of PP2A， AMPK， phosphorylation（p）-AMPK， mTOR， and p-mTOR in renal tissue were detected by Western blot. ResultCompared with the normal group， the renal pathological structure changes were obvious， and the levels of SCr and BUN were significantly increased. The mRNA expression of PP2A， protein expression of PP2A， and p-mTOR/mTOR expression were significantly increased， and the p-AMPK/AMPK was significantly decreased in the model group （P<0.05）. Compared with the model group， the renal pathological morphology changes were significantly improved， and the levels of SCr and BUN were significantly decreased. The mRNA expression of PP2A， protein expression of PP2A， and p-mTOR/mTOR expression in the renal tissue were significantly decreased， and the p-AMPK/AMPK was significantly increased （P<0.05） in all groups after drug intervention. In addition， the effect in the Hirudo+Notoginseng Radix et Rhizoma group was better. The mRNA expression levels of AMPK and mTOR in the renal tissue were not significantly different among the normal group， model group， and other groups. ConclusionThe efficacy of Hirudo and Notoginseng Radix et Rhizoma pairs in improving renal fibrosis in rats with CRF is significantly better than that of the single drug， and its improvement on renal fibrosis in rats with CRF may be related to the regulation of PP2A/AMPK/mTOR signaling pathway.

Síndrome hemolítico urémico secundario a Streptococcus pneumoniae. Reporte de un caso clínico

El síndrome hemolítico urémico secundario a Streptococcus pneumoniae (SHU-Sp) es una complicación poco frecuente de las enfermedades invasoras por S. pneumoniae. Presenta una alta morbimortalidad, con requerimiento de transfusiones de glóbulos rojos y plaquetas, terapia de sustitución de la función renal de inicio precoz y más prolongada, así como mayores complicaciones a largo plazo, comparado con las formas secundarias a infección entérica por Escherichia coli productora de toxina Shiga. Presentamos el caso clínico de una preescolar de dos años, previamente sana, vacunada con tres dosis de PCV13, que desarrolló una insuficiencia renal aguda, anemia hemolítica y plaquetopenia, en el contexto de una neumonía con empiema y bacteriemia por S. pneumoniae.

Streptococcus pneumoniae associated hemolytic uremic syndrome (Sp-HUS) is an uncommon complication of invasive pneumococcal infections. Patients with Sp-HUS have a higher mortality and long term morbidity than those due to HUS from Shiga toxin-producing Escherichia coli infections (STEC-HUS). They often require more red blood cells and platelet transfusions, and early initiation of renal substitution therapy, presenting a higher rate of arterial hypertension and chronic renal disease in the long term, compared to STEC-HUS. We report a healthy 2 year-old infant, vaccinated with three doses PCV13, that developed acute renal failure, hemolytic anemia and thrombocytopenia in the course of a complicated pneumococcal pneumonia with empyema and bacteremia.

Hipopotasemia no medicamentosa como biomarcador de nefropatía crónica temprana en adultos del sur de Honduras

Introducción: La hipopotasemia es un trastorno hidroelectrolítico frecuente, asociado a enfermedades sistémicas y multifactoriales, cuya forma aguda puede complicarse y causar la muerte, pero en su presentación crónica puede ser un marcador de nefropatía. Objetivo: Caracterizar el perfil del paciente con hipopotasemia no medicamentosa atendidos de emergencia. Métodos: Se revisaron los registros de pacientes mayores de 18 años con diagnóstico de hipopotasemia, ingresados en el hospital en el período de junio 2018 a diciembre de 2019. Se colectaron datos demográficos, antecedentes médicos y evolución postratamiento. Se comparó con 108 pacientes sin hipopotasemia atendidos en el período de estudio. Resultados: Se encontraron 87 casos con edad media de 38,5 años. El 90,8 % eran hombres menores de 50 años, de oficio agricultor (29,9 %), con historia de exposición a plaguicidas y a altas temperaturas ambientales. La mayoría de ellos no tenía historia de enfermedad cardiometabólicas o renal previa. El 48,3 % de todos los pacientes con hipopotasemia (n = 42) tenía creatinina mayor a 1,2 mg/dL y 63 % tenía hiponatremia. La hipopotasemia fue moderada en 39 % y severa en 12 %, los hombres 4,7 veces más afectados que las mujeres. Respecto al grupo sin hipopotasemia y creatinina anormal, tenían mayor frecuencia de enfermedad crónica (92,5 % versus 8 %). Conclusiones: Se encontró hipopotasemia no medicamentosa en varones agricultores, sin enfermedad crónica, pero con datos de nefropatía temprana e hiponatremia, se sugirió la posibilidad de nefropatía mesoamericana. Debe establecerse una alerta epidemiológica regional y un programa de prevención y control.

Introduction: Hypokalemia is a frequent hydroelectrolytic disorder, associated with systemic and multifactorial diseases, whose acute form can be complicated and cause death, but in its chronic presentation it can be a marker of nephropathy. Objective: To characterize the profile of the patient with non-drug hypokalemia seen in an emergency. Methods: The records of patients older than 18 years diagnosed with hypokalemia, admitted to the hospital from June 2018 to December 2019, were reviewed. Demographic data, medical history, and post-treatment evolution were collected. It was compared with 108 patients without hypokalemia seen in the same period. Results: 87 cases with mean age of 38.5 years were studied. 90.8% were men under 50 years of age, who worked as farmers (29.9%), with history of exposure to pesticides and high ambient temperatures. Most of them had no history of previous cardiometabolic or renal disease. 48.3% of all patients with hypokalemia (n = 42) had creatinine higher than 1.2 mg/dL and 63% had hyponatremia. Hypokalemia was moderate in 39% and severe in 12%, and it was found that men were affected 4.7 times more than women. Regarding the group without hypokalemia and abnormal creatinine, they had higher frequency of chronic disease (92.5% versus 8%). Conclusions: Non-drug hypokalemia was found in male farmers, without chronic disease, but with evidence of early nephropathy and hyponatremia. The possibility of Mesoamerican nephropathy was suggested. A regional epidemiological alert and a prevention and control program should be established.

Análisis de los factores pronósticos de mortalidad en los pacientes con enfermedad renal crónica en hemodiálisis

Introducción: La enfermedad renal crónica es una de las principales causas de mortalidad en todo el mundo. La estratificación del riesgo a través del análisis de factores pronósticos podría generar un cambio de paradigma. Objetivo: Analizar los factores pronósticos de mortalidad en los pacientes con enfermedad renal crónica en hemodiálisis. Métodos: Se realizó un estudio no experimental, longitudinal de cohorte retrospectivo en los pacientes con enfermedad renal crónica en hemodiálisis en el Hospital General Docente: "Dr. Ernesto Guevara de la Serna" durante el período del 1 de enero de 2017 al 31 de diciembre de 2021. En general, se analizaron los factores pronósticos de mortalidad mediante el análisis multivariado de regresión logística binaria y se determinó el porcentaje correcto de clasificación del modelo de regresión. Resultados: Se analizaron como variables pronosticas de mortalidad la enfermedad cardiovascular [B = 3,831; p = 0,000; Exp (B) = 46,118], Albúmina 17 mmol/L [B = 1,326; p = 0,027; Exp (B) = 3,767], glucemia < 4 mmol/L [B = 1,600; p = 0,015; Exp (B) = 4,955] y ganancia de peso interdialítica excesiva [B = 2,243; p = 0,001; Exp (B) = 9,420]. El porcentaje global de clasificación del modelo de regresión logística binaria fue de 89,5 %. Conclusiones: Se analizó el modelo predictivo de regresión logística que presentó una buena precisión con los factores de pronósticos asociados a la mortalidad en los pacientes en hemodiálisis.

Introduction: Chronic kidney disease is one of the main causes of mortality worldwide. Risk stratification through the analysis of prognostic factors could generate a paradigm shift. Objective: To analyze the prognostic factors of mortality in patients with chronic kidney disease on hemodialysis. Methods: A non-experimental, longitudinal retrospective cohort study was carried out on patients with chronic kidney disease on hemodialysis at Dr. Ernesto Guevara de la Serna General Teaching Hospital from January 2017 to December 31, 2021. The prognostic factors of mortality were analyzed using multivariate binary logistic regression analysis and the correct percentage of classification of the regression model was determined. Results: Prognostic variables of mortality were analyzed, such as cardiovascular disease [B = 3.831; p = 0.000; Exp (B) = 46.118], albumin 17 mmol/L [B = 1.326; p = 0.027; Exp (B) = 3.767], blood glucose < 4 mmol/L [B = 1.600; p = 0.015; Exp (B) = 4.955] and excessive interdialytic weight gain [B = 2.243; p = 0.001; Exp(B) = 9.420]. The overall classification percentage of the binary logistic regression model was 89.5%. Conclusions: The logistic regression predictive model was analyzed, which showed good precision with the prognostic factors associated with mortality in hemodialysis patients.

Inteligencia emocional y calidad de vida en pacientes con insuficiencia renal crónica en hemodiálisis de un hospital de la ciudad del Cusco

Contexto: la investigación busca determinar la relación entre la inteligencia emocional y la calidad de vida en pacientes con insuficiencia renal crónica que reciben tratamiento de hemodiálisis de un hospital de la ciudad del Cusco, considerando el riesgo de la enfermedad para el logro de una mejor vida y los recursos existentes en la psicología de la salud. Metodología: el estudio se ubica en un nivel básico con un alcance correlacional y un diseño no experimental-transversal. Se incluyeron 96 pacientes diagnosticados con insuficiencia renal crónica que asistían a hemodiálisis y que fueron evaluados con el inventario emocional BarOn y el cuestionario KDQOL SF-36 para la calidad de vida. Los datos de identificación de los pacientes fueron obtenidos de las fichas de registro utilizadas, previo consentimiento informado de los evaluados. Posteriormente, para el análisis de datos descriptivos e inferenciales, se emplearon frecuencias y porcentajes; además de estadísticos de asociación, como el tau-b de Kendall, chi cuadrado y d de Somers. Resultados: la relación para inteligencia emocional y calidad de vida muestra un valor de p < 0,05, mediante la prueba de chi cuadrado; el estadístico tau-b de Kendall = 0,340 explica la dirección positiva de la relación e intensidad moderada de la asociación; el estadístico d de Somers = 0,339 ratifica que la inteligencia emocional en general mejora la calidad de vida de los pacientes en una intensidad media. También, se halló una relación significativa para cada una de las dimensiones de la inteligencia emocional con la calidad de vida. Conclusiones: existe relación directa entre inteligencia emocional y calidad de vida en pacientes con insuficiencia renal crónica en hemodiálisis.

Background: The research seeks to determine the relationship between emotional intelligence and quality of life in patients with chronic renal failure who receive hemodialysis treatment at a hospital in the city of Cusco, considering the risk of the disease for achieving a better life and the existing resources in health psychology. Methods: The study is located at a basic level, following a correlational scope and a non-experimental - cross-sectional design. 96 patients diagnosed with chronic renal failure attending hemodialysis were included, who were evaluated with the BarOn Emotional Inventory and the KDQOL SF-36 questionnaire for quality of life. The identification data of the patients were obtained from the registration forms used, with the prior informed consent of those evaluated. Subsequently, for the analysis of descriptive and inferential data, frequencies and percentages were used, in addition to association statistics such as Kendall's Tau-b, Chi square and Somers' D. Results: The relationship for emotional intelligence and quality of life shows a value of p < 0.05, using the Chi-square test, the Kendall Tau-b statistic = 0.340, explains the positive direction of the relationship and moderate intensity of the association. , Somers' D statistic=0.339 confirms that emotional intelligence in general improves the quality of life of patients at a medium intensity. A significant relationship was also found for each of the dimensions of emotional intelligence with quality of life. Conclusions: There is a direct relationship between emotional intelligence and quality of life in patients with chronic renal failure on hemodialysis.

Genetic and phenotypic profile of Fabry disease in the population of Vale do Paraiba and Eastern São Paulo / Perfil genético e fenotípico da doença de Fabry na população do Vale do Paraíba e Zona Leste de São Paulo

ABSTRACT Introduction: Fabry disease (FD) is an inborn error of metabolism characterized by α-galactosidase A deficiency. The primary objective was to evaluate the genetic and phenotypic profile of Fabry disease in hemodialysis. Methods: Observational cohort study to determine the incidence of genetic variations and phenotypic changes for FD in hemodialysis patients in the Paraiba Valley and Eastern São Paulo. Genetic testing for the GLA gene was performed for men and women over 12 years of age at the hemodialysis clinics between January 2016 and December 2019 as a screening protocol. Results: The cases came from screening exams of the index case among patients with chronic kidney disease, resulting in 17 families and totaling 82 patients under study. The classification of the most prevalent variant was that of uncertain significance (54%), followed by the pathogenic variant (46%). Five patients in two families were described with two types of variants not previously described in the literature, with pathogenic behavior. Comparing the types of variants, the presence of a pathogenic variant was associated with higher levels of lysoGB3, lower values for alpha-GAL activity and higher frequency of symptoms related to FD. Conclusion: We characterized an extensive population of patients with FD variants with rich genetic, clinical and biomarker details. We believe that this study can help to better characterize the Brazilian population with FD and the most frequent types of variants.

RESUMO Introdução: A doença de Fabry (DF) é um erro inato do metabolismo caracterizado pela deficiência da enzima α-galactosidase A. O objetivo primário foi avaliar o perfil genético e fenotípico da doença de Fabry em hemodiálise. Métodos: Estudo de coorte observacional para determinar a incidência de variações genéticas e alterações fenotípicas para DF em pacientes em hemodiálise no Vale do Paraíba e Zona Leste de São Paulo. O teste genético para o gene GLA foi realizado para homens e mulheres em todos os pacientes das clínicas de hemodiálise maiores de 12 anos entre janeiro de 2016 a dezembro de 2019 como protocolo de rastreio. Resultados: Os casos foram provenientes de exames de triagem do caso índice entre pacientes portadores de doença renal crônica, resultando em 17 famílias e totalizando 82 pacientes em estudo. A classificação da variante mais prevalente foi a de significado incerto (54%), seguida da variante patogênica (46%). Foram descritos 5 pacientes em duas famílias com dois tipos de variantes ainda não previamente descritos na literatura com comportamento patogênico. Na comparação entre os tipos de variantes, a presença de variante patogênica foi associada a maiores níveis de lysoGB3, menores valores da atividade da alfa-GAL e maior frequência de sintomas relativos à DF. Conclusão: Caracterizamos uma extensa população de pacientes com variantes para DF com riqueza de detalhes de genética, clínica e de biomarcadores. Acreditamos que este estudo possa auxiliar na melhor caracterização da população brasileira com DF e nos tipos mais frequentes de variantes.

Risk Factors for Liver Fibrosis in Diabetic Patients with End-stage Renal Disease

Introduction: Liver cirrhosis is the fourth cause of death in the world. Fatty liver disease is the most common cause of chronic liver disease (CKD) in most countries. Identifying risk factors for liver fibrosis in a population with end-stage renal disease (ESRD) may facilitate early diagnosis of this complication and allow the activation of follow-up protocols to reduce morbidity and mortality in these patients. Materials and methods: A cross-sectional and analytical study was carried out. Patients on hemodialysis, older than 18 years with a diagnosis of diabetes mellitus and ESRD were included. The hypotheses were contrasted through the chi-square test and Student's T-test, as appropriate. Statistical significance was established at a p-value = 0.05. Results: A prevalence of significant liver fibrosis and cirrhosis of 17% was found. Factors associated with liver fibrosis were a history of cerebrovascular disease, peripheral vascular disease, body mass index (BMI), total cholesterol, glycosylated hemoglobin, sodium, and aspartate aminotransferase (AST). No relationship was observed between the NAFLD (non-alcoholic fatty liver disease) score, the APRI index (AST to Platelet Ratio Index), and fibrosis. Conclusion: The prevalence of significant liver fibrosis in patients with diabetes and ESRD is similar to that reported in other populations of patients with diabetes. However, some factors, such as BMI, could behave differently and favor the appearance of liver injury with lower degrees of obesity than previously reported in the literature.

Introducción: la cirrosis hepática es la cuarta causa de muerte en el mundo. Actualmente, la enfermedad hepática por depósito de grasa es la causa más frecuente de hepatopatía crónica en la mayoría de los países. La identificación de factores de riesgo para la presencia de fibrosis hepática en una población con enfermedad renal crónica terminal puede facilitar el diagnóstico temprano de esta complicación y permitir la activación de protocolos de seguimiento para disminuir la morbimortalidad en estos pacientes. Metodología: se realizó un estudio de corte transversal y analítico. Se incluyeron pacientes en hemodiálisis, mayores de 18 años con diagnóstico de diabetes mellitus y de enfermedad renal crónica terminal. El contraste de hipótesis se realizó a través de la prueba de chi cuadrado y la T de Student, según correspondiera. La significación estadística se estableció con un valor p = 0,05. Resultados: se observó una prevalencia de fibrosis hepática significativa y cirrosis del 17%. Los factores asociados a la presencia de fibrosis hepática fueron los antecedentes de enfermedad cerebrovascular, la enfermedad vascular periférica, el índice de masa corporal (IMC), el colesterol total, la hemoglobina glicosilada, el sodio y el aspartato-aminotransferasa (AST). No se observó relación entre el puntaje de NAFLD (enfermedad del hígado graso no alcohólico), el índice APRI (AST to Platelet Ratio Index) y la presencia de fibrosis. Conclusión: la prevalencia de fibrosis hepática significativa en pacientes con diabetes y ERCT es similar a la reportada en otras poblaciones de pacientes con diabetes. Sin embargo, algunos factores, como el IMC, podrían comportarse de forma diferente y favorecer la aparición de lesión hepática con grados menores de obesidad a los reportados previamente en la literatura.

Vasculitis pauciinmune asociada a lupus eritematoso sistémico: a propósito de un caso

Introducción: la poliangeítis microscópica (PAM) hace parte del grupo de vasculitis asociadas a anticuerpos anticitoplasmáticos de neutrófilos (ANCA), cuya presencia de anticuerpos contra mieloperoxidasa (MPO) se observa en la mayoría de los casos (70-95 %), asimismo, el compromiso renal presagia mayores tasas de morbilidad y mortalidad, sin embargo, la coexistencia con lupus eritematoso sistémico (LES) es poco frecuente y con mayor énfasis en la variante de LES del adulto mayor o de inicio tardío. Objetivo: dar a conocer un caso poco común de dos enfermedades autoinmunes, lo cual ha sido reportado como síndrome de superposición y brindar información útil que permita ampliar los diagnósticos diferenciales. Presentación del caso: se presenta el caso de un paciente masculino de 76 años con historia de poliartralgias progresivas en deterioro del estado general, con debut en síndrome confusional agudo, caída de filtrado glomerular, microhematuria y proteinuria casi nefrótica. A la evaluación inicial se encontró anemia y trombocitopenia severa, en perfil inmune ANA 1/320 y complemento consumido, cumpliendo criterios para LES, ANCA reactivo específicamente MPO ANCA (1/320) y sospecha de glomerulonefritis con patrón rápidamente progresivo (GNRP). Dado el contexto clínico, se decidió comenzar con pulsos de metilprednisolona consecutivos, seguidos de prednisolona oral y, como terapia de mantenimiento, se instauró ciclofosfamida. Finalmente, con una biopsia renal se confirmó el diagnóstico de vasculitis sistémica pauciinmune con formación de crescencia celular. La evolución clínica del paciente fue satisfactoria, logrando la estabilización de órganos y la normalización de la función renal, hematopoyética y el estado neurológico. Discusión y conclusión: dado que la presentación clínica de LES es heterogénea, se ha reportado su asociación con vasculitis, las cuales comparten un compromiso común de órganos como articulaciones, piel y riñones. Los hallazgos paraclínicos, como por biopsia, fueron consistentes tanto con PAM como con LES, por lo tanto, se diagnosticó como un caso de superposición. Este caso demuestra el enigma del diagnóstico y la complejidad en el manejo de entidades poco frecuentes, de etiologías inmunológicas superpuestas que ponen en peligro la vida de quien la(s) padece, de no tener un diagnóstico oportuno y un tratamiento temprano.

Introduction: Microscopic polyangiitis (MPA) is part of the group of vasculitis associated with antineutrophil cytoplasmic antibodies (ANCA), whose presence of antibodies against myeloperoxidase (MPO) is observed in most cases (70-95 %), likewise, the renal compromise portends higher rates of morbidity and mortality. However, coexistence with Systemic Lupus Erythematosus (SLE) is infrequent, and with greater emphasis on the older adult or late-onset variant of SLE (1). Purpose: Present a rare case of two autoimmune diseases, which has been reported as overlapping syndrome and provide useful information that allows expanding differential diagnoses. Case report: We present the case of a 76-year-old male patient with a history of progressive polyarthralgias in deteriorating general condition, with debut in acute confusional syndrome, drop in glomerular filtration rate, microhematuria and almost nephrotic proteinuria. At the initial evaluation anemia and severe thrombocytopenia were found, in the immune profile ANA 1/320, complement consumed; fulfilling criteria for SLE, ANCAs reactive specifically MPO ANCA (1/320) and suspected Rapidly Progressive Renal Insufficiency (PRRI). Given the clinical context, it was decided to start consecutive pulses of methylprednisolone followed by oral prednisolone, and cyclophosphamide was established as maintenance therapy. Finally, a renal biopsy confirmed the diagnosis of pauci-immune systemic vasculitis with cell crescent formation. These findings were consistent with both SLE and PAM, thus it was diagnosed as a case of overlap. The clinical evolution of the patient was satisfactory, achieving organ stabilization and normalization of renal function, hematopoietic function, and neurological status. Discussion and conclusion: RPGN associated with ANCA present non-nephrotic proteinuria, glomerular filtration rate drop. The most common is anti-glomerular basement membrane (AMBG) antibodies. Serological detection of antineutrophil cytoplasmic antibodies, PR3 and MPO should be available. Microscopic polyangiitis could be determined by renal biopsy, with the presence of cell growth, absence of immune deposits and MPO ANCA positivity. This case is a diagnostic enigma, and the complexity in the management of rare entities, of immunological etiology, superimposed that endanger the life of those who suffer from it, if they do not have a timely diagnosis and early treatment.

Use of Pre?Operative Hemoglobin A1c to Predict Early Post?Operative Renal Failure and Infection Risks in Patients who are not Diabetics and Undergoing Elective off Pump Coronary Artery Bypass Graft Surgery

Background: Recent studies have indicated that patients, both with and without diabetes with an increased HbA1c, have a higher rate of adverse outcomes following cardiac surgeries. Our study is focused on to evaluate the prognostic impact of admission value of HbA1c in non?diabetic patients for postoperative renal failure and infections. Materials and Methods: Plasma HbA1c levels were collected from 200 consecutive nondiabetic patients who got admitted for elective off pump coronary artery bypass graft (CABG) procedure over a 2?year period under two groups, Group A whose HbA1c was < 6% at admission and Group B whose HbA1c was ?6% and ?6.4% at admission. After surgery, patients were followed up to see if they have got infection or renal failure as postoperative complication. Student抯 unpaired t test was used to test the significance of difference between the quantitative variables, Yate抯 and Fisher抯 chi square tests were used for qualitative variables. Results: We found early postoperative renal failure in 14 (3/96 in Group A and 11/104 in Group B) out of 200 patients (7%) and infection in 21 (8/96 in Group A and 13/104 in Group B) out of 200 patients (10.5%). After data analysis, it was noted that there is a positive correlation between HbA1c and postoperative renal failure (P = 0.0213) whereas no association was found between HbA1c and postoperative infections (P = 0.175) in patients undergoing off?pump CABG surgery. Conclusion: In patients without diabetes, a plasma HbA1c ?6% was a significant independent predictor for early postoperative renal failure.

Milk-Alkali Syndrome: A Century Old Cause of Resurgence of Severe Hypercalcemia Due to Excessive Use of Calcium Supplements

The milk-alkali syndrome (MAS) is characterized by a triad of elevated calcium levels, metabolic alkalosis and acute kidney injury that commonly occurs due to the combined intake of large amounts of calcium and absorbable alkali. The syndrome can have an acute onset with the rapid development of hypercalcemia and, if left untreated, may result in acute renal failure and metastatic calcification. An increased number of cases of MAS have recently been reported. This is likely due to the common use of over the counter (OTC) preparations of calcium for preventing and treating osteoporosis in postmenopausal women. Herein, we report a case of severe hypercalcemia due to prolonged intake of calcium carbonate supplements in the absence of any alkali.

Glomerulonefritis aguda posinfecciosa como riesgo para desarrollar insuficiencia renal crónica en una cohorte pediátrica de un hospital de referencia en Paraguay

Contexto: la glomerulonefritis aguda posinfecciosa (GNPI) representa un riesgo para el desarrollo de insuficiencia renal a largo plazo. Objetivo: describir la incidencia de proteinuria persistente y factores asociados en pacientes con antecedente de GNPI en una cohorte pediátrica de un hospital de referencia en Paraguay. Metodología: se incluyó a 121 pacientes con síndrome nefrítico con C3 disminuido, con normalización a los tres meses, aunque no se haya comprobado etiología estreptocócica. Se excluyó a los pacientes con enfermedad renal previa, con síndrome nefrítico secundario y con menos de seis meses de seguimiento. Se analizaron las características sociodemográficas, infecciones precedentes, aclaramiento de creatinina, días de hipertensión arterial y de internación, además de la relación de estas con la persistencia de proteinuria a los seis meses y más de seguimiento. Resultados: de los 121 pacientes entre 2 a 16 años de edad incluidos, 75 pacientes tuvieron un seguimiento médico entre 6 y 48 meses, de los cuales 43 (57,3 %) desarrollaron proteinuria persistente, la cual se asoció con un menor aclaramiento de creatinina (p = 0,03; 67,74 ± 25,69 mL/min/1,73 m2 SC vs. 80,22 ± 2,98 mL/min/1,73 m2 SC), con el número promedio de convivientes (6,3 ± 2,8 vs. 5,3 ± 2,3; p = 0,027) y el número promedio de hijos (4,3 ± 2,7 vs. 3,6 ± 2,3; p = 0,048). No se encontró asociación con las otras características. Conclusiones: la incidencia de proteinuria se asoció con un menor aclaramiento de creatinina y con una mayor frecuencia de los determinantes sociales en salud.

Background: Acute post-infectious glomerulonephritis (PIGN) represents a risk for the development of long-term renal failure. Purpose: To describe the incidence of proteinuria in patients with a history of PIGN in a pediatric cohort at a referral hospital in Paraguay. Methodology: a total of 121 patients with nephritic syndrome with decreased C3 and normalization at 3 months, although streptococcal aetiology has not been proven were included. Patients with with previous kidney disease, with secondary nephritic syndrome and with less than 6 months of follow up were excluded. Sociodemographic characteristics, previous infection, creatinine clearance, days of arterial hypertension and hospitalization were analyzed, in addition to their relationship with the persistence of proteinuria at 6 months and more of follow-up. Results: Of the 121 patients between 2 and 16 years of age included, 75 patients had a medical follow-up between 6 and 48 months, 43 (57.3 %) of them developed persistent proteinuria, which was associated with lower creatinine clearance (p = 0.03; 67.74 ± 25.69 mL/min/1.73 m2 BM vs 80.22 ± 2.98 mL/min/1.73 m2 BM), higher average number of cohabitants (6.3 ±2.8 vs 5.3±2.3; p= 0.027) and higher average number of children (4.3±2.7 vs 3.6±2.3; p= 0.048). No association was found with other characteristics. Conclusions: the incidence of proteinuria in this series was associated with lower creatinine clearance and a higher frequency of social determinants in health.

Myoglobin cast nephropathy following multiple bee stings

Bee stings usually result in mild allergic reactions; however, mass envenomation can cause severe complications such as rhabdomyolysis, hemolysis, shock, or multi-organ damage. Rhabdomyolysis can result in acute renal failure either by tubular obstruction by myoglobin casts or by direct cytotoxic injury. We present a case of a 12-year-old female child who presented with sudden onset anuria and hypertension following mass envenomation by bees. A renal biopsy was performed, the microscopic evaluation of which revealed tubular injury, with associated intratubular pigmented casts. The casts stained positive for myoglobin immunohistochemical stain, thus confirming a diagnosis of myoglobin cast nephropathy. The patient was given IV steroids and underwent seven sessions of hemodialysis, following which there was complete recovery of renal function.

Evaluación renal y multiorgánica en el paciente con encefalopatía hipóxico-isquémica / Renal and multiorgan evaluation in infants with post-asphyxial hypoxic-ischaemic encephalopathy

Resumen Introducción: La encefalopatía hipóxico-isquémica (EHI) moderada-grave secundaria a asfixia perinatal puede afectar a cualquier órgano, empeorando el pronóstico. Objetivo: Evaluar la afectación renal y multiorgánica de estos pacientes. Material y método: Se incluyó a recién nacidos > 35 semanas con EHI moderada-grave tratados con hipotermia activa entre 2010 y 2020. Se evaluó la creatinina en tres periodos: 48-72 horas de vida, entre el 3.o y 7.o día de vida y del 7.o al 28.o día de vida. Resultados: Se incluyeron 135 pacientes: 112 con EHI moderada y 23 con EHI grave. Al comparar ambos grupos, se obtuvieron diferencias significativas a las 48-72 horas y entre 3.o-7.o día de vida. No hubo diferencias al comparar el método de hipotermia. Los pacientes con EHI grave presentaron mayor afectación hemodinámica, respiratoria y hepática. Conclusiones: Neonatos con EHI grave presentan aumento de los niveles de creatinina sérica y mayor afectación multiorgánica respecto a aquellos con EHI moderada.

Abstract Background: Hypoxic-ischemic encephalopathy (HIE) secondary to perinatal asphyxia can affect any organ, worsening the prognosis. Objective: To describe renal and multiorgan involvement in moderate-severe HIE. Material and method: Newborns > 35 weeks diagnosed with moderate-severe HIE who required active hypothermia between 2010-2020 were included. To assess renal involvement, serum creatinine was measured in three different periods: at 48-72 hours, between the 3rd and the 7th day, and from the 7th to the 28th day. Results: A total of 135 patients were included, 112 (83%) with moderate and 23 (17%) with severe HIE. Significant differences were obtained when comparing median creatinine levels at 48-72 hours and between 3-7 days in both groups. There were no differences in creatinine according to the hypothermia method. Patients with severe HIE presented greater hemodynamic, respiratory, and hepatic involvement. Conclusions: Neonates with severe HIE present increased serum creatinine levels and greater multi-organ involvement than those with moderate HIE.

Vitamin A could be a Therapeutic Agent in Ischemia/Reperfusion Induced Kidney Injury / La vitamina A podría ser un agente terapéutico en la lesión renal inducida por isquemia/reperfusión

ABSTRACT Introduction: Renal ischemia (I) could develop due to decreased or ceased blood flow to the kidney in some clinical conditions such as shock, sepsis, and kidney transplantation. The re-supply of blood to the kidney is called reperfusion (R). Ischemia and reperfusion periods can cause severe kidney damage. Objectives: When we examined the I/R molecular progression, antioxidant molecules such as vitamin A seem promising treatment agents. This study aimed to investigate the effects of vitamin A on renal I/R injury. Material and Methods: In the study, 40 Sprague-Dawley male rats were divided into five groups (n=8): the control group, only I/R, I/R+1000, I/R+3000, and I/R+9000 IU/kg of Vitamin A groups. Vitamin A was administrated to each group for seven days via oral gavage. Blood and kidney tissue samples were collected at the end of the experiment. We took blood samples for Superoxide dismutase (SOD), malondialdehyde (MDA), catalase (CAT), blood urea nitrogen (BUN), and creatinine (Cr) levels, and determined their values. The tissue samples were stained with hematoxylin/eosin to examine the renal changes histopathologically and stereologically under a light microscope. Results: Histopathological changes caused by I/R were decreased with vitamin A administration in a dose-dependent manner (p<0.05). Vitamin A administration decreased MDA levels and increased SOD and CAT activities (p<0.05). The most effective dose among treatment groups was 9000 IU/kg. There was no significant difference between the controls and all other groups regarding BUN and Cr concentrations. Conclusions: Consequently, administration of vitamin A after renal I/R reduced the histological damage and ameliorated the antioxidant state. These results showed that vitamin A could be a promising agent in treating I/R-induced acute kidney injury.

RESUMEN Introducción: La isquemia renal (I) puede desarrollarse debido a la disminución o interrupción del flujo sanguíneo al riñón en algunas condiciones clínicas como shock, sepsis y trasplante renal. El reabastecimiento de sangre al riñón se denomina reperfusión (R). Tanto la isquemia como los períodos de reperfusión pueden causar graves daños renales. Objetivos: Cuando examinamos la progresión molecular I/R, las moléculas antioxidantes como la vitamina A parecen agentes de tratamiento prometedores. El objetivo de este estudio fue investigar los efectos de la vitamina A sobre la lesión renal I/R. Material y Métodos: En el estudio, 40 ratas macho Sprague-Dawley se dividieron en 5 grupos (n=8) como: control, solo I/R, I/R+1000, I/R+3000 e I/R+9000 UI/kg de la Vitamina A. La vitamina A se administró a cada grupo durante 7 días por vía oral forzada. Al final del experimento se recolectaron muestras de sangre y tejido del riñón. A partir de muestras de sangre se determinaron los niveles de superóxido dismutasa (SOD), malondialdehído (MDA), catalasa (CAT), nitrógeno ureico en sangre (BUN) y creatinina (Cr). Las muestras de tejido se tiñeron con hematoxilina/eosina y los cambios en la histología renal se examinaron histopatológicamente y estereológicamente al microscopio de luz. Resultados: Los cambios histopatológicos causados por I/R disminuyeron con la administración de la vitamina A de manera dependiente de la dosis (p<0,05). La administración de la vitamina A disminuyó los niveles de MDA, aumentó las actividades de SOD y CAT (p<0,05). La dosis más eficaz entre los grupos del tratamiento fue de 9000 UI/kg. No hubo una diferencia significativa entre el grupo control y todos los demás grupos con respecto a las concentraciones de BUN y Cr. Conclusiones: Consiguientemente, la administración de la vitamina A, después de I/R renal, redujo el daño histológico y mejoró el estado antioxidante. Estos resultados mostraron que la vitamina A puede ser un agente promisorio en el tratamiento de la lesión renal aguda (LRA) inducida por I/R.

Mechanism of Modified Zhenwutang in Delaying Progression of Chronic Renal Failure Based on Network Pharmacology， Molecular Docking， and Experimental Verification / 中国实验方剂学杂志

ObjectiveTo preliminarily predict the active ingredients， targets， and signaling pathways of modified Zhenwutang in the treatment of chronic renal failure （CRF） based on network pharmacology and explore its potential mechanism for delaying disease progression through molecular docking and animal experiments. MethodThe effective ingredients and targets of modified Zhenwutang were obtained from the HERB database. The targets related to CRF were obtained from the GeneCards. The intersection target genes were obtained using Venny 2.1 software and a protein-protein interaction （PPI） network was constructed using the STRING. The core targets for treating CRF with modified Zhenwutang were screened using Cytoscape 3.9.1 software. The intersection genes were analyzed using Metascape database for gene ontology （GO） analysis and Kyoto Encyclopedia of Genes and Genomes （KEGG） enrichment analysis. Molecular docking validation was performed using AutoDockTools 1.5.6 software for the key targets and active ingredients. An experimental CRF model was established in rats by administering adenine via gavage for 12 weeks， followed by intervention with modified Zhenwutang and benazepril hydrochloride for four weeks. After treatment， the rats were euthanized， and immunohistochemistry （IHC）， immunofluorescence （IF）， real-time quantitative polymerase chain reaction （Real-time PCR）， and western blot were performed to detect the expression levels of prolyl hydroxylase domain-containing proteins 1 （PHD1）， prolyl hydroxylase domain-containing proteins 2 （PHD2）， hypoxia-inducible factor-1α （HIF-1α）， and α-smooth muscle actin （α-SMA） in the renal tissues of the rats. ResultA total of 426 drug target genes of modified Zhenwutang were obtained from the HERB database. A total of 2 698 target genes related to CRF were obtained from the GeneCards database. There were 154 intersection genes between the drug and the disease. Eight core targets were identified， including albumin （ALB）， protein kinase B1 （Akt1）， tumor necrosis factor （TNF）， interleukin-6 （IL-6）， insulin （INS）， vascular endothelial growth factor A （VEGFA）， tumor protein p53 （TP53）， and interleukin-1β （IL-1β）， which might be closely related to the treatment of CRF with modified Zhenwutang. KEGG enrichment analysis predicted that the main mechanism of modified Zhenwutang in treating CRF involved lipid and atherosclerosis， HIF-1 signaling pathway， cell apoptosis， and nuclear factor kappa B （NF-κB） signaling pathway. Molecular docking results showed that the ingredients of modified Zhenwutang had stable binding activity with the core targets ALB， Akt1， TNF， IL-6， INS， VEGFA， TP53， and IL-1β， which may regulate inflammation and cell apoptosis by affecting the target proteins. The animal model validation results demonstrated that modified Zhenwutang could reduce the expression levels of HIF-1α and α-SMA in the renal tissues of CRF rats， increase the expression levels of PHD1 and PHD2， alleviate renal tissue hypoxia injury， reduce myofibroblast formation， and slow down the progression of CRF in rats. ConclusionModified Zhenwutang may improve renal tissue hypoxia， inhibit cell transdifferentiation， cell apoptosis/necroptosis， and inflammation by affecting the expression of target proteins such as ALB， Akt1， TNF， IL-6， INS， VEGFA， TP53， and IL-1β， as well as regulating the HIF-1 signaling pathway， thus delaying the progression of CRF.

Effect of Modified Zhenwutang on Interstitial Fibrosis in Rats with Chronic Renal Failure Based on IL-6/MMP-9/COL-Ⅳ Signaling Pathway / 中国实验方剂学杂志

ObjectiveTo observe the modulatory effect of modified Zhenwutang on the interleukin-6 （IL-6）， matrix metallopeptidase-9（MMP-9）， type Ⅳ collagen（COL-Ⅳ） in rats with chronic renal failure （CRF） and to investigate the potential mechanism of its treatment of CRF. MethodFifty male SD rats were randomly divided into a modeling group of 40 rats and a normal group of 10 rats， and the modeling group was prepared by continuous adenine gavage for 12 weeks. After successful modelling， the modelling group was divided into the model group， the low dose （7.2 g·kg-1·d-1） group， the medium dose （14.4 g·kg-1·d-1） group， the high dose （28.8 g·kg-1·d-1） group and the Benadryl hydrochloride （10 mg·kg-1·d-1） group for gavage according to the random number table method， In the normal group and the model group， equal volume of distilled water was administered by gavage for 4 weeks. After the administration， the levels of blood creatinine （SCr）， blood urea nitrogen （BUN） and 24 h urine protein （24 h-UTP） were measured， the levels of serum IL-6 were measured by enzyme linked immunosorbent assay（ELISA）. Immunohistochemistry （IHC） was used to detect intercellular cell adhesion molecule-1 （ICAM-1）， IL-6， MMP-9， and other molecules in the rat kidney. The expression of ICAM-1 mRNA， IL-6 mRNA， MMP-9 mRNA and COL-Ⅳ mRNA in rat kidney tissues was measured by Real-time fluorescence quantitative polymerase chain reaction （Real-time PCR）. The expression levels of ICAM-1， IL-6， MMP-9 and COL-Ⅳ in rat kidney tissues were measured by Western blot. ResultCompared with the normal group， the levels of SCr， BUN and 24 h-UTP were significantly increased in the model group （P<0.01）； the serum IL-6 level was significantly increased （P<0.01）， the tubular lumen was dilated with atrophy， the tubular epithelial cells were necrotic， swollen and vacuolated， the interstitium was infiltrated by a large number of inflammatory cells and collagen fibers were deposited， the levels of IL-6， ICAM-1 and COL-Ⅳ were strongly positive in the tubular interstitium of the model group （P<0.01）， The levels of ICAM-1 mRNA， IL-6 mRNA and COL-Ⅳ mRNA were significantly increased （P<0.01） and MMP-9 mRNA was significantly decreased （P<0.05） in the model rats. ICAM-1， IL-6 and COL-Ⅳ protein expression was significantly increased （P<0.01） and MMP-9 protein expression was significantly increased （P<0.01） in the renal tissue， and MMP-9 protein expression was significantly decreased （P<0.01）. Compared with the model group， the 24 h-UTP， SCr and BUN levels of rats were significantly reduced after treatment with modified Zhenwutang （P<0.01）， the serum IL-6 level was significantly decreased （P<0.01）， the renal lesions of rats were significantly improved and collagen fiber deposition was reduced； the expression of IL-6， ICAM-1 and COL-Ⅳ in renal tubules and interstitium was weakened， and MMP-9 in ICAM-1 mRNA， IL-6 mRNA and COL-Ⅳ mRNA levels were significantly reduced （P<0.01） and MMP-9 mRNA levels were significantly increased （P<0.05）， ICAM-1， IL-6 and COL-Ⅳ protein expression was significantly reduced （P<0.01） and MMP-9 protein expression was significantly The expression of ICAM-1， IL-6 and COL-Ⅳ proteins was significantly decreased （P<0.01） and MMP-9 protein expression was significantly increased （P<0.01）. ConclusionModified Zhenwutang may regulate the IL-6/MMP-9/COL-Ⅳ signaling pathway， thereby reducing proteinuria， improving renal function， reducing renal pathological damage and delaying the progression of CRF interstitial fibrosis.

Based on Oxidative Stress/NF-κB Exploration of Mechanism of Modified Zhenwutang in Delaying Progression of Chronic Renal Failure Complicated with Cardiac Disease by Inflammatory Factors / 中国实验方剂学杂志

ObjectiveBy observing the effect of modified Zhenwutang on the expression of superoxide dismutase 1（SOD1）， malondialdehyde（MDA）， advanced oxidation protein product（AOPP）， nuclear factor kappa-B（NF-κB） p65，p-p65，IL-1β， TNF-α in serum and renal tissue of adenine-induced chronic renal failure rats and the pathology of heart and kidney tissue， the possible mechanism of modified Zhenwutang delaying the progression of chronic renal failure complicated with heart disease was discussed. MethodFifty SPF male SD rats were divided into normal group 10 and model group 40 according to the random number table method. After one week of adaptive feeding， the experimental chronic renal failure complicated with cardiovascular disease rat model was established by intragastric administration of adenine 150 mg·kg-1·d-1. After the model was completed， 3 rats in the normal group and the model group were randomly selected to detect whether the model was successful. After successful modeling， the rats in the model group were divided into model group ， modified Zhenwutang low-dose group ， modified Zhenwutang medium-dose group， modified Zhenwutang high-dose group and Benazepril hydrochloride group according to the random number table method， with 6 rats in each group. Drugs were administered once a day for 4 weeks. At the end of the 17th week of the experiment， 24-hour urinary total protein（24 h-UTP） and urine creatinine（UCr）were detected. At the end of the 17th week， the rats in each group were anesthetized and the abdominal aorta was taken. After centrifugation， the supernatant was taken to detect triglyceride（TG）， total cholesterol（TC）， serum calcium（Ca）， serum potassium， serum phosphate， serum creatinine（Scr）， blood urea nitrogen（BUN）； the expression levels of serum AOPP， IL-1β and TNF-α were detected by enzyme linked immunosorbent assay（ELISA）. The pathological changes of heart and kidney tissues were observed by hematoxylin-eosin（HE）/Masson method. The ultrastructural changes of proximal renal tubules were observed by transmission electron microscopy . The kidney tissue expressions of SOD1， MDA， AOPP， NF-κB p65，p-p65，IL-1β and TNF-α were observed by immunohistochemistry. The kidney tissue expression levels of SOD1， NF-κB p65， IL-1β and TNF-α mRNA were observed by real-time polymerase chain reaction（Real-time PCR）. The kidney tissue expression levels of SOD1， MDA， NF-κB p65 and p-p65 were detected by Western blot. Result①Compared with the normal group， the experimental rats in the model group showed an increase in 24-hour UTP （P<0.01）and a decrease in UCr（P<0.01）. The experimental rats in the model group showed an increase in Cr， BUN， TG， TC， serum phosphate， and serum potassium（P<0.01）.The levels of AOPP， IL-1β and TNF-α in serum of rats in the model group were significantly increased（P<0.01）. In the model group， the glomerular balloon space was significantly widened， the renal interstitium was significantly widened with a large number of inflammatory cell infiltration， a large number of renal tubular lumens were blocked by brown deposits， and there were a large number of collagen fiber deposition in the renal interstitium. The collagen fibers around the renal vessels， outside the capsule wall of the renal capsule wall， glomerular basement membrane and renal tubular basement membrane were significantly increased， and the cardiac muscle fibers were significantly thickened. There was a small amount of inflammatory cell infiltration around the blood vessels， and a large number of collagen fibers around the cardiac vessels and between the myocardial cells. In the model group， high-density diamond-shaped needle-like crystals were observed in the proximal renal tubular epithelial cells of rats， with increased lysosomes， mitochondrial proliferation， mitochondrial cristae and dense mitochondrial outer membrane. The left ventricular diastolic wall thickness and systolic wall thickness of the experimental rats in the model group was increased in proximal renal tubular epithelial cells and their nuclei.In the model group， the expression of MDA， AOPP， NF-κB p65，p-p65 IL-1β and TNF-α in proximal renal tubular epithelial cells was significantly increased（P<0.01）， the expression of p-p65 in the nucleus of proximal renal tubular epithelial cells was significantly increased（P<0.01）， and the expression of SOD1 in proximal renal tubular epithelial cells was significantly decreased（P<0.01）. The kidney tissue expression of NF-κB p65， IL-1β and TNF-α mRNA in the model group was increased（P<0.01）， and the expression of SOD1 mRNA was decreased（P<0.01）. The kidney tissue expression of SOD1 protein in the model group was significantly decreased（P<0.01）. The kidney tissue expression of MDA， NF-κB p65 and p-p65 protein was increased （P<0.01）. ② Compared with the model group， after the intervention of modified Zhenwutang， 24 h-UTP was decreased （P<0.01）and UCr was increased（P<0.01）. Cr， BUN， TG， TC， serum phosphate， serum potassium was decreased （P<0.01）. Serum AOPP， IL-1β and TNF-α levels were decreased（P<0.01）. Cardiac and Renal pathological damage was reduced； mitochondrial damage in proximal renal tubules was reduced； the expression of MDA， AOPP， NF-κB p65， IL-1β， TNF-α in proximal renal tubular epithelial cells was decreased （P<0.01）， the expression of p-p65 in the nucleus of proximal renal tubular epithelial cells was significantly decreased （P<0.01）， and the expression of SOD1 in proximal renal tubular epithelial cells was significantly increased （P<0.01）. The kidney tissue expression of NF-κB p65， IL-1β， TNF-α mRNA was decreased （P<0.01）， and the expression of SOD1 mRNA was increased（P<0.01）. The kidney tissue expression of SOD1 protein was significantly increased （P<0.01）， and the expression of MDA， NF-κB p65 and p-p65 protein was decreased （P<0.01）. The Chinese medicine group showed a significant dose-effect trend. ConclusionModified Zhenwutang may reduce the production of oxidative stress and mitochondrial damage in proximal renal tubular epithelial cells， thereby reducing oxidative stress products and inhibiting the release of inflammatory factors caused by the activation of NF-κB signaling pathway， reducing the damage to heart and kidney tissues and functions， and delaying the progression of chronic renal failure complicated with heart disease， and the traditional Chinese medicine group has a dose-effect trend.

Mechanism of Modified Zhenwutang in Delaying Renal Interstitial Fibrosis in Chronic Renal Failure Based on Ang Ⅱ/AT1R/NOX4 Signaling Pathway / 中国实验方剂学杂志

ObjectiveTo explore the underlying mechanism of modified Zhenwutang in delaying renal interstitial fibrosis in chronic renal failure （CRF） by observing the effects of modified Zhenwutang on the expression of angiotensin Ⅱ （Ang Ⅱ）， angiotensin Ⅱ type 1 receptor （AT1R）， nicotinamide adenine dinucleotide phosphate （NADPH） oxidase 4 （NOX4）， transforming growth factor-β1 （TGF-β1）， type I collagen （COL1A1）， and type Ⅲ collagen （COL3A1） in the serum and renal tissues of adenine-induced CRF rats. MethodFifty male SPF-grade SD rats were randomly divided into a normal group （n=10） and an experimental group （n=40） using a random number table. After one week of adaptive feeding， the experimental CRF model was established in rats by administering adenine at 150 mg·kg-1·d-1 orally. Three rats from each group were randomly selected to evaluate the model induction. After successful modeling， rats in the experimental group were randomly divided into a model group， low-， medium， and high-dose modified Zhenwutang groups， and a benazepril hydrochloride group， with six rats in each group. The rats were orally administered the corresponding drugs once daily for four weeks. At the end of the first week， 13th week， and 17th week of the experiment， 24 hour urinary protein quantification （24 h-UTP） was measured. At the end of the 17th week， the rats were euthanized， and blood samples were collected from the abdominal aorta for the measurement of total protein （TP）， albumin （ALB）， creatinine （Cr）， and blood urea nitrogen （BUN） in the serum. Enzyme-linked immunosorbent assay （ELISA） was used to measure the expression levels of serum Ang Ⅱ. Hematoxylin-eosin （HE） staining and Masson's trichrome staining were performed to observe the pathological changes in renal tissues. Immunohistochemistry （IHC） was performed to observe the expression of AT1R， NOX4， TGF-β1， COL1A1， and COL3A1. Real-time fluorescence-based quantitative polymerase chain reaction （Real-time PCR） was used to observe the mRNA expression levels of AT1R， NOX4， and TGF-β1. Western blot was conducted to measure the protein expression levels of AT1R， NOX4， and TGF-β1. Result① Compared with the normal group， the model group showed a significant increase in 24 h-UTP （P<0.01）. The levels of Cr and BUN in the model group were significantly higher （P<0.01）， while the levels of TP and ALB were significantly lower （P<0.01）. The serum Ang Ⅱ level in the model group was significantly elevated （P<0.01）. The model group exhibited widening of the renal glomerular mesangial space， necrotic glomeruli， increased interstitial width with extensive inflammatory cell infiltration， brownish precipitates blocking the renal tubular lumens， irregular renal tubules， and significant deposition of collagen fibers in the renal interstitium. Additionally， the collagen fibers around the renal vessels， outside the parietal layer of the renal sacs， glomerular basement membrane， and tubular basement membrane increased significantly. The expression of AT1R and NOX4 in the glomeruli and renal tubules of the model group was significantly enhanced， and TGF-β1 expression also significantly increased in the renal tubules. The expression of COL1A1 and COL3A1 in the renal interstitium significantly increased. The mRNA expression of AT1R and TGF-β1 in the model group significantly increased （P<0.01）， while NOX4 mRNA expression significantly decreased （P<0.01）. The protein expression of AT1R， NOX4， and TGF-β1 was significantly enhanced （P<0.01）. ② Compared with the model group， modified Zhenwutang significantly reduced 24h-UTP （P<0.01）， decreased levels of Cr and BUN （P<0.01）， increased levels of TP and ALB （P<0.01）， reduced serum Ang Ⅱ level （P<0.01）， alleviated renal pathological damage， reduced expression of AT1R， NOX4， TGF-β1， COL1A1， and COL3A1 in the glomeruli， renal tubules， and renal interstitium， reduced mRNA expression of AT1R and TGF-β1 （P<0.01）， increased NOX4 mRNA expression （P<0.01）， and weakened protein expression of AT1R， NOX4， and TGF-β1 （P<0.01）. The modified Zhenwutang groups showed a significant dose-effect trend. ConclusionModified Zhenwutang may delay renal interstitial fibrosis in CRF rats by reducing the expression of Ang Ⅱ， AT1R， NOX4， and TGF-β1 in the serum and renal tissues， thereby alleviating renal pathological damage， reducing proteinuria， protecting renal function， and delaying the progression of CRF. The modified Zhenwutang group exhibited a dose-effect trend.