Adherence to treatment in patients with chronic kidney disease undergoing hemodialysis / Adesão ao tratamento de pacientes com doença renal crônica em hemodiálise

Objective: To identify the adherence to therapeutic regimens in patients with chronic kidney disease undergoing hemodialysis (HD). Method: This is a descriptive, cross-sectional study using a quantitative approach developed at an HD center in the south of Minas Gerais, Brazil. The study participants were 51 patients undergoing HD. Personal, socioeconomic, and objective data were collected, and the End-Stage Renal Disease Adherence Questionnaire (ESRD-AQ) was applied. The analysis was performed using simple descriptive statistics. Result: The average age was 56.7 years, and 58% of the patients were male. The percentages of non-adherence were diet (35.4%), hemodialysis (21.6%), fluid intake (15.7%), and medication (13.7%). Conclusion: Therapeutic adherence is a complex process that requires constant monitoring by a multidisciplinary team.

Objetivo: Identificar a adesão ao regime terapêutico de pacientes com doença renal crônica em hemodiálise. Método: Trata-se de um estudo descritivo, transversal, com abordagem quantitativa, desenvolvido em um centro de hemodiálise situado no sul de Minas Gerais. Os participantes do estudo foram 51 pacientes em tratamento hemodialítico. Foram coletados dados pessoais, socioeconômicos, objetivos aplicado o "Questionário de avaliação sobre a adesão do portador de doença renal crônica em hemodiálise". A análise foi realizada por meio de estatística descritiva simples. Resultado: A média de idade foi de 56,7 anos e 58% dos pacientes foram do sexo masculino. Os percentuais de não aderência encontrados foram dieta (35,4%), hemodiálise (21,6%), ingestão de líquidos (15,7%) e medicação (13,7%). Conclusão: A adesão terapêutica é um processo complexo, e por isso necessita de acompanhamento constante pela equipe multiprofissional.

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.

Study on the Relationship Between OAT1 Expression and Renal Osteodystrophy in Rats with Chronic Renal Failure / 昆明医科大学学报

Objective To investigate the changes of OAT expression in bone cells in chronic renal failure(CRF)and involved mechanism,and to explore the effect of OAT expression on bone metabolism.Methods Ra-ndomly divide the rats into a control group(n=6)and a model group(n=6).The model group established a rat chronic renal failure model using"single nephrectomy+adenine gavage"method,and the red blood cell(RBC)and hemoglobin(HGB)of the rat body were measured using a blood routine analyzer;Measure indicators such as creatinine(Cr),urea nitrogen(BUN),uric acid(UA),blood calcium(Ca2+),and blood phosphorus(P3+)using a fully automated biochemical analyzer;Pathological examination of rat kidneys;X-ray examination of rat tibia;Immunohistochemical examination of bone tissue OAT1 level.Results The bone density of the model group rats is lower than that of the control group;The calcium and phosphorus metabolism of rats in the model group was in metabolic disorder,and the OAT1 value of bone tissue binding was much lower than that of the control group(P= 0.0018),which was statistically significant.(P=0.0018)Conclusion Chronic renal failure affected the binding ability of OAT1 in bone tissue,leading to the metabolic disorder for calcium absorption and phosphorus metabolism,thus aggravating renal osteodystrophy(P<0.05).

Effects of Sanqi on Sortilin,TLRs and vascular calcification in rats with chronic renal failure / 实用医学杂志

Objective Taking Sortilin as the entry point,this study aims to explore the mechanism of vascular calcification in chronic renal failure(CRF)and explore the influence of Sanqi on Sortilin,TLRs and vascular calcification,and to provide an effective method for clinical reduction of cardiovascular events in CRF.Methods Thirty-six male SD rats were randomly divided into normal group,model group,low-,medium-and high-dose Sanqi group and calcitriol group,with 6 rats in each.The replicative CRF vascular calcification rat model was fed with adenine combined with high phosphorus diet.Aortic calcium salt deposition,serum creatinine(Scr),urea nitrogen(BUN),blood calcium(Ca),blood phosphorus(P),total cholesterol(TC),triglyceride(TG),TLRs and Sortilin protein in aorta and inflammatory factors were detected.Results In the model group,renal fibrosis was obvious and many adenine crystals were found in renal interstitium.Large deposits of calcium salts were found.Renal fibrosis and calcium salt deposition were alleviated in different degrees in all treatment groups.Compared with those in the normal group,the level of BUN,Cr,P,TG,TC,IFN-γ,IL-6,IL-10 and IL-17A in the serum of the model group was ascended(P<0.01),while the level of Ca was descended(P<0.01).Compared with those in the model group,the level of BUN,Cr,P,TG,TC,IFN-γ,IL-6,IL-10 and IL-17A in the serum of rats in the Sanqi medium and high dose group and calcitriol group was significantly decreased(P<0.01),and the contents of Ca were significantly increased(P<0.05 or P<0.01).Compared with those in the normal group,the protein expression of BMP2,RUNX2,Sortilin,TLR7 and TLR9 in aortic tissue of rats in the model group was elevated(P<0.01),while the protein expression of SM22α was declined(P<0.01).Compared with those in the model group,the protein expression of BMP2,RUNX2,Sortilin,TLR7,and TLR9 in the low-,medium-,and high-dose Sanqi group and calcitriol group was decreased significantly(P<0.01);the protein expression of SM22α was increased significantly(P<0.05 or P<0.01),and the high-dose Sanqi group and calcitriol group had more significant effects.Conclusion Sanqi can improve renal fibrosis and vascular calcification in CRF model rats,and its mechanism may be related to the regulation of biological functions of Sortilin and TLRs.

Inhibitory effect of Heidihuang Pills on renal fibrosis in a rat model of chronic renal failure via regulation of IGF-1 expression / 中成药

AIM To explore the effect of Heidihuang Pills on renal fibrosis in a rat model of chronic renal failure(CRF)and its mechanism.METHODS Wistar rats were randomly divided into the blank group for normal feeding and the model group for the establishment of CRF rat models by 5/6 nephrectomy.Subsequently,the successfully established rat models were randomly divided into the model group,the Heidihuang Pills group(10.43 g/kg),and the Heidihuang Pills+IGF-1R blocker(JB1)group for a regimen of 7-day subcutaneous injection of 18 μg/kg JB1 followed by gavage of 10.43 g/kg Heidihuang Pills.Eight weeks after the administration,the rats had their serum levels of Scr and BUN detected;their pathological changes of renal tissue observed by HE and Masson staining;their renal protein expressions of TGF-β,HIF-1α and α-SMA detected by immunohistochemistry;their renal protein expressions of IGF-1R and TGF-β detected by Western blot;and their renal mRNA expressions of IGF-1R and TGF-β detected by RT-qPCR.RESULTS Compared with the blank group,the model group displayed increased serum levels of Scr and BUN(P＜0.05);increased,degree of renal fibrosis,and renal fibrosis area(P＜0.05);increased renal expressions of TGF-β,HIF-1α,α-SMA proteins and TGF-β mRNA(P＜0.05);and decreased expressions of IGF-1R mRNA and protein(P＜0.05).Compared with the model group,the Heidihuang Pills group displayed decreased serum Scr and BUN levels(P＜0.05);decreased inflammatory cells in renal interstitium and the fibrosis degree(P＜0.05);decreased renal expressions of TGF-β,HIF-1α,α-SMA proteins and TGF-β mRNA(P＜0.05);and increased expressions of IGF-1R mRNA and protein(P＜0.05).However,the administration of JB1 could weaken the improvement effect of Heidihuang Pills on renal fibrosis in CRF rats(P＜0.05).CONCLUSION Heidihuang Pills can inhibit the renal fibrosis in CRF rats,and the inhibition process is related to up-regulated IGF-1 expression and promoted combination of IGF-1 and IGF-1R.

Effect and mechanism of pachymic acid on renal function and fibrosis in rats with chronic renal failure / 中国药房

OBJECTIVE To investigate the effect of pachymic acid （PA） on renal function and fibrosis in chronic renal failure （CRF） rats and its potential mechanism based on the Ras homolog gene family member A （RhoA）/Rho-associated coiled-coil forming protein kinase （ROCK） signaling pathway. METHODS Using male SD rats as subjects， the CRF model was established by 5/6 nephrectomy； the successfully modeled rats were divided into model group， PA low-dose， medium-dose and high-dose groups （5， 10， 20 mg/kg PA）， high-dose PA+ROCK pathway activator lysophosphatidic acid （LPA） group （20 mg/kg PA+1 mg/kg LPA）， with 15 rats in each group. Another 15 rats were selected as the sham operation group with only the kidney exposed but not excised. The rats in each drug group were gavaged and/or injected with the corresponding liquid via the caudal vein， once a day， for 12 consecutive weeks. During the experiment， the general condition of rats was observed in each group. After the last administration， the serum renal function indexes （blood urea nitrogen， serum creatinine， uric acid） of rats in each group were detected， the renal histopathological changes were observed； the renal tubule injury score and the area of renal fibrosis were quantified. The levels of oxidative stress indexes [malondialdehyde （MDA）， superoxide dismutase （SOD）] and inflammatory factors （tumor necrosis factor-α， interleukin-1β， interleukin-6）， the positive expression rates of connective tissue growth factor （CTGF） and collagen Ⅰ were detected as well as the expression levels of pathway-related proteins （RhoA， ROCK1） and fibrosis- related proteins （transforming growth factor-β1， bare corneum homologs 2， α-smooth muscle actin） were determined. RESULTS Compared with the sham operation group， the rats in model group had reduced diet， smaller body size， listless spirit and sluggish response， reduced and atrophied glomeruli， dilated renal tubules with chaotic structure， and a large number of inflammatory cells infiltrated interstitium； the serum levels of renal function indexes， renal tubule injury score， renal fibrosis area proportion， the levels of MDA and inflammatory factors， the positive expression rates of CTGF and collagen Ⅰ， and the expression levels of pathway-related proteins and fibrosis-related proteins in renal tissues were significantly increased， while SOD level was significantly decreased （P＜0.05）. Compared with the model group， the general condition and pathological injuries of kidney tissue of rats in PA groups were improved to varying degrees，and the above quantitative indexes were significantly improved in a dose-dependent manner （P＜0.05）. LPA could significantly reverse the improvement effect of PA on the above indicators （P＜0.05）. CONCLUSIONS PA can improve renal function and alleviate renal fibrosis in CRF rats， which may be related to inhibiting the activation of RhoA/ROCK signaling pathway.

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.

Comparação de fórmulas para cálculo da taxa de filtração glomerular estimada e seus limiares diagnósticos para doença renal crônica em pessoas idosas: um estudo transversal / Comparison of formulas for calculating estimated glomerular filtration rate and its diagnostic thresholds for chronic kidney disease in older adults: a cross-sectional study

Resumo Objetivo Avaliar e comparar as fórmulas CKD-EPI, BIS1 e MDRD e o limiar diagnóstico de 45 e 60 ml/min/1,73m2 em pacientes idosos. Método Estudo observacional do tipo transversal, de caráter descritivo e analítico. Foram incluídos pacientes atendidos em ambulatório de referência entre janeiro/2020 e junho/2022, com idade ≥65 anos. Foram excluídos pacientes com apenas uma dosagem de creatinina ou com alterações transitórias da TFG. Resultados Observou-se que entre o grupo de pacientes com idade entre 65-74 anos e 75-84 anos as estimativas da TFG feitas pela fórmula CKD-EPI foram superiores às fórmulas BIS1 e MDRD. Enquanto, no grupo de pacientes com 85-94 anos a CKD-EPI não apresentou diferença quando comparada com MDRD, permaneceu com estimativas maiores apenas quando comparada com a BIS1. Observamos maior dispersão entre CKD-EPI e BIS1, mostrando menor concordância entre essas fórmulas, confirmada pelo teste Kappa (76,7%) e a concordância quase perfeita entre CKD-EPI e MDRD. Conclusão A fórmula BIS1 apresentou melhor correlação da diminuição da TFGe conforme o avanço das faixas etárias, podendo-se relacionar com o processo de envelhecimento renal fisiológico, podendo ser uma ferramenta auxiliar na estimativa da TFG em idosos, auxiliando no diagnóstico mais preciso da DRC, assim como, no planejamento de intervenções que possam retardar a progressão da DRC e prever risco de mortalidade por doenças cardiovasculares.

Abstract Objective To evaluate and compare the CKD-EPI, BIS1 and MDRD formulas and diagnostic thresholds of 45 and 60 ml/min/1.73m2 in older patients. Method A cross-sectional, descriptive, analytical observational study was conducted. Patients aged ≥65 years treated at a referral outpatient clinic between January 2020 and June 2022, were assessed. Patients with only one creatinine level or with transient GFR abnormalities were excluded. Results The GFR estimates using the CKD-EPI formula were higher than both the BIS1 and MDRD formulas in patient groups aged 65-74 years and 75-84 years. In the group of patients aged 85-94 years, the CKD-EPI showed no difference when compared with the MDRD, yielding higher estimates only compared with the BIS1. Greater dispersion was found between the CKD-EPI and BIS1, showing less agreement between these formulas, as confirmed by the Kappa test (76.7%), while there was almost perfect agreement between the CKD-EPI and MDRD. Conclusion The BIS1 formula showed stronger correlation of the decrease in eGFR with advancing age, reflecting the physiological renal aging process and serving as a potentially useful tool for estimating GFR in older adults. The formula can help provide a more accurate diagnosis of CKD and aid planning of interventions to slow the progression of CKD and predict the risk of mortality from cardiovascular diseases.

Análisis de los factores pronósticos de mortalidad en los pacientes con enfermedad renal crónica en hemodiálisis / Analysis of Mortality Prognostic Factors in Patients with chronic Kidney Disease on Hemodialysis

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 por ciento. 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(AU)

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 89.5percent. Conclusions: The logistic regression predictive model was analyzed, which showed good precision with the prognostic factors associated with mortality in hemodialysis patients(AU)

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.

Hipopotasemia no medicamentosa como biomarcador de nefropatía crónica temprana en adultos del sur de Honduras / Non-drug Hypokalemia as Biomarker of Early Chronic Kidney Disease in Adults from Southern 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 por ciento eran hombres menores de 50 años, de oficio agricultor (29,9 por ciento), 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 por ciento de todos los pacientes con hipopotasemia (n = 42) tenía creatinina mayor a 1,2 mg/dL y 63 por ciento tenía hiponatremia. La hipopotasemia fue moderada en 39 por ciento y severa en 12 por ciento, 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 por ciento versus 8 por ciento). 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(AU)

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 (29.9percent), with history of exposure to pesticides and high ambient temperatures. Most of them had no history of previous cardiometabolic or renal disease. 48.3percent of all patients with hypokalemia (n = 42) had creatinine higher than 1.2 mg/dL and 63percent had hyponatremia. Hypokalemia was moderate in 39% and severe in 12percent, 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 (92.5percent versus 8percent). 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(AU)

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.

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.

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.

Effect of Dahuang Xiezhuo Prescription on Inflammation and SOCS3/TLR4 Pathway in Rats with Chronic Renal Failure / 中国实验方剂学杂志

ObjectiveTo observe the intervention effect of Dahuang Xiezhuo prescription （DHXZ） on inflammation and suppressor of cytokine signaling 3 （SOCS3）/Toll-like receptor 4 （TLR4） pathway in rats with chronic renal failure （CRF）， and to explore its molecular mechanism in alleviating renal inflammatory response. MethodThe 90 male SD rats， 15 were randomly selected as sham group， and the remaining 75 were used as modeling group to replicate CRF rat model by 5/6 nephrectomy. After successful modeling， the rats were randomly divided into model group， DHXZ low-， medium-， high-dose groups （6.825， 13.65， 27.3 g·kg-1） and Niaoduqing Granules group （2.6 g·kg-1）. The drug intervention groups received corresponding drugs by gavage for 8 consecutive weeks. After administration， hematoxylin-eosin （HE） staining and Masson staining were used to observe the morphological changes of rat renal tissue， and blood creatinine （SCr）， blood urea nitrogen （BUN） and blood uric acid （UA） were tested. Enzyme-linked immunosorbent assay （ELISA） was performed to detect the serum contents of interleukin-6 （IL-6）， tumor necrosis factor-α （TNF-α） and C-reactive protein （CRP）. The mRNA expressions of SOCS3 and TLR4 in renal tissue were detected by Real-time fluorescence quantitative polymerase chain reaction （Real-time PCR）， and the protein expressions of SOCS3， TLR4， nuclear transcription factor （NF-κB） and myeloid differentiation factor （MyD88） were detected by Western blot. Immunohistochemistry was used to determine the protein expressions of NF-κB， MyD88， NOD-like receptor protein 3 （NLRP3） and melanoma deficiency factor 2 （AIM2）. ResultCompared with the sham group， the model group had a significant inflammatory response in renal tissue， and an increase in blood SCr， BUN， UTP， IL-6， TNF-α and CRP （P<0.05）. The protein and mRNA expressions of SOCS3 in renal tissue of rats in the model group were lower while the protein expressions of TLR4， NF-κB， MyD88， NLRP3 and AIM2 and the mRNA expression of TLR4 were higher than those in the sham group （P<0.05）. Compared with the model group， DHXZ and Niaoduqing granules groups presented markedly reduced inflammatory response in renal tissue and decreased blood SCr， BUN， UTP， IL-6， TNF-α and CRP （P<0.05）. Additionally， DHXZ and Niaoduqing granules up-regulated the protein and mRNA expressions of SOCS3 in renal tissue while down-regulated the protein expressions of TLR4， NF-κB， MyD88， NLRP3 and AIM2 and the mRNA expression of TLR4 （P<0.05）. ConclusionDHXZ can reduce the release and expression of inflammatory factors， inhibit the inflammatory response and improve renal function， and the mechanism may be related to the regulation of SOCS3/TLR4 signaling pathway.

A Rat Model of Adenine-induced Chronic Renal Failure Complicated with Cardiovascular Disease / 中国实验方剂学杂志

ObjectiveTo explore the preparation method of a rat model of adenine-induced chronic renal failure complicated with cardiovascular disease by investigating the effect of different time points of adenine gastric lavage on general vital signs， biochemical indicators， and cardiac and renal tissue structure and function of model rats. MethodRats in the model group were administered adenine at 150 mg·kg-1·d-1 by gavage for 16 weeks， while those in the normal group were given an equal volume of 0.5% carboxymethyl cellulose sodium solution by gavage. At weeks 5， 13， 17， 24-hour urinary protein quantification （24 h-UTP）， biochemical indicators， cardiac ultrasound， and changes in cardiac and renal tissue structure and function were measured in both the model and normal groups. Blood pressure was measured at weeks 5 and 13 in both groups. Weekly changes in body weight were recorded， and general conditions of the rats were observed daily. Result① Compared with the normal group， the model group showed a significant decrease in body weight （P<0.05）. ② Rats in the model group exhibited a significant increase in urine volume， and proteinuria appeared at week 13. ③ Compared with the normal group， the model group showed significant differences in triglyceride （TG）， total cholesterol （TC）， creatinine （Cr）， blood urea nitrogen （BUN）， blood potassium， and blood phosphorus at week 5 （P<0.05）， which increased gradually over time. At week 17， uric acid levels were significantly elevated （P<0.05）， and blood calcium levels were reduced at the end of week 17 （P<0.01）. ④ Compared with the normal group， the model group showed a significant increase in blood pressure at week 5 （P<0.05）， which progressively worsened. ⑤ There was no statistically significant difference in left ventricular wall thickness between the model and normal groups at week 5， but a significant difference was observed at week 13 （P<0.05）. ⑥ Fibrosis appeared in the kidneys of rats in the model group at week 5 and gradually worsened， while obvious fibrosis occurred around the cardiovascular system at week 13 as compared with the results in the normal group. ⑦ In the proximal tubular epithelial cells of the model group， there was an increasing presence of high-density rhomboid needle-shaped crystals， damaged cell membrane integrity， increased cell spacing， increased lysosomes， increased mitochondrial proliferation， denser mitochondrial cristae， and outer mitochondrial membrane. ⑧ Compared with the rats in the normal group， rats in the model group exhibited depressed spirits， significantly reduced activity， hunched posture， dry fur， pale ears and toes， swollen cheeks， increased nocturnal urination， and dark and viscous blood. ConclusionAdenine by gavage at 150 mg·kg-1·d-1 for 12 weeks can be used to establish a rat model of chronic renal failure complicated with cardiovascular disease， which can be used for the prevention and treatment research on chronic renal failure and its associated cardiovascular complications. The syndrome of adenine-induced rat model of chronic renal failure belongs to the deficiency of spleen and kidney， turbidity and stasis obstruction， and can be used to study the mechanisms of warming and tonifying the spleen and kidney， resolving stasis， and eliminating turbidity in the treatment of chronic renal failure.

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.

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.

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.

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.