Amorphophallus campanulatus tuber extract protects diabetic nephropathy in streptozotocin-induced diabetic nephropathy rat model by regulating oxidative stress and TNF-α inflammatory pathway

ABSTRACT Purpose: To assess the effect of Amorphophallus campanulatus tuber (Ac) extract in the protection of diabetic nephropathy in streptozotocin (STZ) induced diabetic nephropathy (DN) rat model. Methods: Diabetes was induced with STZ (60 mg/kg, i.p.), and DN was confirmed after six weeks of STZ administration with the estimation of kidney function test. Further rats were treated with Ac 250 and 500 mg/kg p.o. for next four week. Oxidative stress and level of inflammatory cytokines were estimated in the kidney tissue of DN rats. Histopathology of kidney tissue was performed using hematoxylin and eosin staining. Results: There was improvement in the body weight of Ac treated groups than DN group of rats. Blood glucose level was observed to be reduced in Ac treated groups than DN group on 42nd and 70th day of protocol. Treatment with Ac ameliorated the altered level of kidney function tests (creatinine and BUN), enzymes of liver function (aspartate aminotransferase and alanine aminotransferase), and lipid profile in the serum of DN rats. Oxidative stress parameters (malondialdehyde and reactive oxygen species enhances and reduction in the level of glutathione and superoxide dismutase) and inflammatory cytokines such as interleukin-6, tumour necrosis factor-α, and monocyte chemoattractant protein-1 reduces in the tissue of Ac treated group than DN group. Treatment with Ac also attenuates the altered histopathological changes in the kidney tissue of DN rats. Conclusions: The report suggests that Ac protects renal injury in DN rats by regulating inflammatory cytokines and oxidative stress.

Association of the rs5186 polymorphism of the AGTR1 gene with decreased eGFR in patients with type 2 diabetes from Mexico City.

BACKGROUND: Early biomarkers search for Diabetic Kidney Disease (DKD) in patients with Type 2 Diabetes Mellitus (T2DM), as genetic markers to identify vulnerable carriers of the disease even before Glomerular Filtration Rate (GFR) decline or microalbuminuria development, has been relevant during the last few years. The rs5186 (A116C) polymorphism of the Angiotensin II Receptor Type I gene (AGTR1), has been associated to multiple effects of renal injury risk, commonly detected in patients with Diabetes Mellitus (DM). It has been described that rs5186 could have an effect in stability proteins that assemble Angiotensin II Receptor Type I (AT1), modifying its action, which is why it should be considered as a risk factor for Chronic Kidney Disease (CKD), characterized by a GFR progressive reduction. Even though, the association between rs5186 AGTR1 gene polymorphism and DKD in patients with T2DM has been controversial, inconclusive, and even absent. This disputable issue might be as a result of association studies in which many and varied clinical phenotypes included are contemplated as CKD inductors and enhancers. Although, the sample sizes studied in patients with T2DM are undersized and did not have a strict inclusion criteria, lacking of biochemical markers or KDOQI classification, which have hindered its examination. OBJECTIVE: The aim of our study was to establish an association between rs5186 AGTR1 gene polymorphism and GFR depletion, assessed as a risk factor to DKD development in patients with T2DM. METHODS: We analyzed 297 not related patients with T2DM, divided into 221 controls (KDOQI 1) and 76 cases (KDOQI 2). Arterial pressure, anthropometric and biochemical parameters were measured. rs5186 of AGTR1 genotyping was performed by TaqMan assay real-time PCR method. Allele and genotype frequencies, and Hardy-Weinberg equilibrium were measured. Normality test for data distribution was analyzed by Shapiro-Wilk test, variable comparison by Student's t-test for continuous variables, and Chi-squared test for categorical variables; ANOVA test was used for mean comparison of more than two groups. Effect of rs5186 to DKD was estimated by multiple heritability adjustment models for risk variables of DKD. Statistical significance was indicated by p<0.05. Data was analyzed using Statistical Package STATA v11 software. RESULTS: Dominant and Over-dominant models showed a likelihood ratio to GFR depletion of 1.89 (1.05-3.39, p=0.031) and 2.01 (1.08-3.73, p=0.023) in patients with T2DM. Risk factor increased to 2.54 (1.10-5.89) in women in Over-dominant model. CONCLUSION: In clinical practice, most of nephropathies progress at a slow pace into a total breakdown of renal function, even asymptomatic. This is the first study, reporting that rs5186 polymorphism of AGTR1 gene contribution to GFR depletion, and this could be evaluated as a predisposing factor for DKD in patients with T2DM.

Is screening for chronic kidney disease in patients with diabetes mellitus being properly conducted in primary care? / O rastreio da doença renal crônica nos pacientes com diabetes mellitus está sendo realizado adequadamente na atenção primária?

Abstract Introduction: Screening patients with diabetes mellitus (DM) for chronic kidney disease (CKD) enables early diagnosis and helps to establish adequate treatment and avoid possible damages to health associated with disease progression. This study aimed to verify whether screening for CKD has been properly conducted in populations with diabetes mellitus seen at primary care clinics. Methods: This descriptive study included 265 individuals with DM seen at Basic Healthcare Clinics in Divinópolis, MG, Brazil. Clinical and laboratory data were collected from the Integrated Health System. Frequency of testing and kidney function evaluations performed within the last 12 months were calculated along with the proportion of patients with increased urinary albumin excretion (UAE) and decreased glomerular filtration rate (GFR) to determine the proportion of patient with kidney involvement. Results: We found that 41.2% of the patients had kidney involvement and that 61.2% of the individuals with kidney involvement were on nephroprotective medication. Of the 21.9% tested for isolated albuminuria, 46.5% had increased UAE. The albumin-to-creatinine ratio (ACR) was measured in 12.1% of the patients, with 43.8% having an increased ACR. We found that 89.0% of the patients had their serum creatinine levels measured, and that 33.1% had a decreased GFR. Conclusion: CKD screening was more frequently performed via the GFR than UAE, a parameter analyzed only in a small proportion of patients. Therefore, CKD screening for patients with diabetes is not being performed properly in primary care.

Resumo Introdução: O rastreio da doença renal crônica (DRC) em pacientes com diabetes (DM) possibilita o diagnóstico precoce e ajuda a estabelecer um tratamento adequado, evitando possíveis danos à saúde pela progressão da doença. O objetivo deste trabalho foi verificar se o rastreio da DRC está sendo feito de maneira adequada entre diabéticos acompanhados na atenção primária à saúde. Métodos: Estudo descritivo com 265 pacientes com DM atendidos nas Unidades Básicas de Saúde de Divinópolis, MG. A coleta de dados clínicos e laboratoriais foi realizada por meio de consulta ao Sistema Integrado de Saúde. Foram calculadas a frequência de realização dos exames de avaliação da função renal nos últimos 12 meses e a frequência de pacientes com excreção urinária de albumina (EUA) aumentada e a taxa de filtração glomerular (TFG) reduzida, e assim determinada a frequência de pacientes com comprometimento renal. Resultados: Foi observado que 41,2% dos pacientes têm comprometimento renal; dentre esses, 61,2% utilizam algum medicamento nefroprotetor. Apenas 21,9% realizaram o exame de albuminúria isolada, dos quais 46,5% apresentaram albuminúria aumentada. O exame de relação albumina/creatinina (RAC) foi realizado por 12,1% dos pacientes, dos quais 43,8% apresentaram RAC aumentada. Foi observado que 89,0% dos pacientes realizaram o exame de creatinina sérica, dos quais 33,1% apresentaram TFG reduzida. Conclusão: Foi observado maior índice de rastreio da DRC por meio da TFG em relação ao rastreio por meio da EUA, o qual foi realizado por pequeno número de pacientes. Portanto, o rastreio da DRC não está sendo realizado adequadamente na atenção básica ao diabético.

Clinical and histopathological characteristics of diabetic patients with nephrotic proteinuria. A case series / Características clínicas e histopatológicas de pacientes diabéticos con proteinuria nefrótica. Una serie de casos

Abstract Objective: to describe the clinical and histopathological characteristics of diabetic patients with nephrotic-range proteinuria. Materials and methods: the kidney biopsies of diabetic patients with nephrotic proteinuria were reviewed. Descriptive analyses were performed along with a comparison of three groups according to the histopathological findings. Results: the medical charts of 19 patients from 2018 through 2020 were collected, most of whom (94.7%) were diagnosed with type 2 diabetes mellitus (DM), with an average age of 58 years, and an average duration of DM of 9.9 years (SD: ±7.3). The findings from biopsies performed throughout the years prior to data collection showed that 26.3% had diabetic nephropathy as the only finding, 31.6% had a nephropathy other than diabetic nephropathy, and 42.1% had findings of both diabetic and nondiabetic nephropathy. A comparison of the groups showed a significant difference in the duration of DM, which was greater in patients with diabetic nephropathy (16.4 vs. 5 vs. 9.5 years, respectively, p: 0.024). Conclusions: we present a case series of diabetic patients with nephrotic-range proteinuria in Colombia, showing that kidney biopsy lesions other than diabetic nephropathy may be a cause of proteinuria. We found that patients with a report of DN alone had a much longer duration of diabetes. (Acta Med Colomb 2022; 47. DOI:https://doi.org/10.36104/amc.2022.2231).

Resumen Objetivo: describir las características clínicas e histopatológicas de pacientes diabéticos con proteinuria en rango nefrótico. Material y métodos: se revisaron biopsias renales de pacientes diabéticos con proteinuria ne frótica, se realizaron análisis descriptivos y comparación entre tres grupos de acuerdo con hallazgos histopatológicos. Resultados: se recolectaron historias de 19 pacientes, entre los años 2018 y 2020, la mayoría (94.7%) con diagnóstico de diabetes mellitus (DM) tipo 2, edad promedio de 58 años, con un tiempo de evolución de la DM en promedio de 9.9 años (DE: ±7.3). En los hallazgos de la biopsia, practica das a lo largo de años anteriores a la recolección, se encontró que 26.3% tenían nefropatía diabética como único hallazgo, el 31.6% otra nefropatía diferente a la diabética y 42.1% hallazgos tanto de nefropatía diabética como no diabética. Al comparar los grupos se encontró diferencia significativa en el tiempo de evolución de la DM, siendo mayor en pacientes con nefropatía diabética (16.4 vs 5 vs 9.5 años respectivamente, p: 0.024). Conclusiones: se presenta una serie de casos de pacientes diabéticos con proteinuria en rango nefrótico en Colombia, mostrando que existen lesiones diferentes a la nefropatía diabética en la biopsia renal como posible causa de la proteinuria. Se encontró que los pacientes en quienes se reportó ND únicamente, tenían un tiempo de evolución de la diabetes mucho mayor. (Acta Med Colomb 2022; 47. DOI:https://doi.org/10.36104/amc.2022.2231).

Frecuencia de complicaciones crónicas en pacientes con diabetes mellitus tipo 2 en un hospital de tercer nivel

RESUMEN Introducción: la diabetes mellitus es considerada un grave problema en Salud Pública porque genera un gran impacto en la demanda de servicios médicos. Además, es incapacitante, causal de ausentismo laboral, disminuye la calidad de vida y, finalmente, causa una alta tasa de mortalidad por sus complicaciones. Objetivos: determinar la frecuencia de complicaciones crónicas en pacientes con diabetes mellitus tipo 2. Métodos: diseño de tipo observacional, descriptivo, de corte trasversal, en pacientes adultos de ambos sexos con diabetes mellitus tipo 2, internados en el Hospital Nacional de Itauguá en periodo 2020-2021. El estudio se basa en la recopilación de datos de las fichas clínicas. Resultados: se evaluaron 106 pacientes, con una edad promedio de 59 ± 13 años, el 60% corresponde al sexo masculino, 80% procede de la zona urbana y solo el 3% tiene nivel educativo universitario. El 82% se conocía portador de diabetes mellitus, de los cuales solo el 87% recibía algún tratamiento, siendo irregular el mismo en el 58% de ellos. El 75% de los casos está asociado a otras comorbilidades como hipertensión arterial y obesidad. En cuanto al control laboratorial, la mayoría tenía mal control glicémico al ingreso, solo el 19% tenía hemoglobina glicada menor a 7%, 15% tenía hipercolesterolemia y 50% hipertrigliceridemia. En cuanto a las complicaciones crónicas, se encontraron presentes en el 96% de los pacientes. Conclusión: existe una alta frecuencia de complicaciones crónicas en los diabéticos tipo 2, predominando la retinopatía, seguida de la nefropatía y las cardiopatías estructurales.

ABSTRACT Introduction: diabetes mellitus is considered a serious problem in public health because it generates a great impact on the demand for medical services. In addition, it is disabling, causes work absenteeism, decreases quality of life and, finally, causes a high mortality rate due to its complications. Objectives: To determine the frequency of chronic complications in patients with type 2 diabetes mellitus. Methods: Observational, descriptive, cross-sectional study carried out in adult male and female patients with type 2 diabetes mellitus, admitted to the Hospital Nacional of Itauguá in the 2020-2021 period. The study was based on the collection of data from clinical records. Results: One hundred and six patients were evaluated, with an mean age of 59±13 years, 60% were male, 80% came from urban areas and only 3% had a university education level. Eighty two percent were known carriers of diabetes mellitus, of which only 87% received some treatment, being irregular in 58% of them. Seventy five percent of the cases were associated with other comorbidities such as high blood pressure and obesity. Regarding laboratory control, most had poor glycemic control at admission, only 19% had glycated hemoglobin less than 7%, 15% had hypercholesterolemia, and 50% hypertriglyceridemia. Regarding chronic complications, they were present in 96% of the patients. Conclusion: There is a high frequency of chronic complications in type 2 diabetics, predominantly retinopathy, followed by nephropathy and structural heart disease.

Genistein improves mitochondrial function and inflammatory in rats with diabetic nephropathy via inhibiting MAPK/NF-κB pathway

Purpose: To investigate the effect of genistein on inflammation and mitochondrial function of diabetic nephropathy. Methods: Diabetic nephropathy model was established in Sprague-Dawley rats. Automatic biochemical analyzer was employed to detect the kidney function index, serum creatinine, serum urea nitrogen, and 24 h-urine protein and blood glucose. Hematoxylin and eosin staining and periodic acid Schiff staining were used to observe renal morphology. Mitochondrial changes and podocyte integrity were monitored by transmission electron microscope. The expression levels of mfn2, NOX4, P53, MAPK, and NF-κB were detected by Western blotting. The changes of mitochondrial membrane potential were measured by JC-1. The level of mfn2 was assessed by immunofluorescence assay. Results: Genistein ameliorated the kidney function with reduced Scr and blood glucose. The expressions of NOX4, MAPK, p65 and p53 were downregulated, while the expression of mnf2 was the opposite in genistein-treated kidneys. Further investigations revealed that genistein reduced expansion of mesangial matrix and oxidative stress, protected podocyte integrity and increased mitochondrial membrane potential. Conclusions: Genistein could alleviate diabetic nephropathy through inhibiting MAPK/NF-κB pathway, improving mitochondrial function and anti-inflammatory.To investigate the effect of genistein on inflammation and mitochondrial function of diabetic nephropathy. Diabetic nephropathy model was established in Sprague-Dawley rats. Automatic biochemical analyzer was employed to detect the kidney function index, serum creatinine, serum urea nitrogen, and 24 h-urine protein and blood glucose. Hematoxylin and eosin staining and periodic acid Schiff staining were used to observe renal morphology. Mitochondrial changes and podocyte integrity were monitored by transmission electron microscope. The expression levels of mfn2, NOX4, P53, MAPK, and NF-κB were detected by Western blotting. The changes of mitochondrial membrane potential were measured by JC-1. The level of mfn2 was assessed by immunofluorescence assay. Genistein ameliorated the kidney function with reduced Scr and blood glucose. The expressions of NOX4, MAPK, p65 and p53 were downregulated, while the expression of mnf2 was the opposite in genistein-treated kidneys. Further investigations revealed that genistein reduced expansion of mesangial matrix and oxidative stress, protected podocyte integrity and increased mitochondrial membrane potential. Genistein could alleviate diabetic nephropathy through inhibiting MAPK/NF-κB pathway, improving mitochondrial function and anti-inflammatory.

Proteoma urinario en la enfermedad renal diabética. Estado del arte

La enfermedad renal diabética (ERD) es la principal complicación microvascular de los pacientes con diabetes mellitus; esta es una entidad que genera un aumento significativo en la mortalidad de origen cardiovascular de este grupo de pacientes, aunque su diagnóstico temprano impacta de forma significativa en la evolución a enfermedad renal terminal y, por lo tanto, en la mortalidad. La detección de albuminuria en la orina y el deterioro de la tasa de filtración glomerular estimada son las principales técnicas diagnósticas que se utilizan en la práctica clínica para establecer la presencia de ERD; sin embargo, estas tienen limitaciones y por lo tanto es importante resaltar que el daño renal suele ser irreversible una vez están presentes. Durante los últimos años, numerosos estudios se han enfocado en detectar nuevos biomarcadores para detectar ERD y es aquí donde aparece como nueva herramienta la proteómica urinaria, una tecnología emergente que permite identificar en una muestra de orina proteínas que sugieren la presencia de esta enfermedad de manera temprana. Asimismo, el descubrimiento de biomarcadores basados en proteómicos representa una estrategia novedosa para mejorar el diagnóstico, pronóstico y tratamiento de la nefropatía diabética; sin embargo, los enfoques basados en la proteómica aún no están disponibles en la mayoría de los laboratorios de química clínica.

Diabetic kidney disease (DKD) is the main microvascular complication in patients with diabetes mellitus; it is an entity that generates a significant increase in mortality of cardiovascular origin in this group of patients, although its early diagnosis has a significant impact on the evolution to end-stage kidney disease and, therefore, on mortality. The detection of albuminuria in urine and the deterioration of the estimated glomerular filtration rate are the main diagnostic techniques that are used in clinical practice to establish the presence of DKD; however, they have limitations and therefore it is important to note that kidney damage is usually irreversible once they are present. Over the last few years, numerous studies have focused on the discovery of new biomarkers to detect DKD and this is where the urinary proteomics appears as a new tool, an emerging technology that allows the identification of proteins in a urine sample that strongly suggest the early presence of this disease. Likewise, the discovery of proteomic-based biomarkers represents a novel strategy to improve the diagnosis, prognosis and treatment of diabetic nephropathy; however, proteomics-based approaches are not yet available in the majority of clinical chemistry laboratories.

Modelo ideal de nefroprevención para Colombia

La enfermedad renal crónica (ERC) es una patología altamente prevalente en países en vía de desarrollo como Colombia, en donde afecta a gran parte de la población. Esta es una enfermedad que afecta la calidad de vida y la longevidad de los pacientes, así como los costos del sistema de salud. La ERC tiene un carácter progresivo e irreversible, por lo que intervenirla en etapas tempranas resulta ser una medida altamente costo-efectiva; a partir de esto surge el concepto de nefroprevención, mediante la cual, teniendo en cuenta los niveles de prevención primaria, secundaria y terciaria, se puede lograr una identificación precoz y la interrupción o enlentecimiento de la progresión, y además se puede implementar un manejo oportuno e integral del daño renal según el estadio de la enfermedad. Esto es posible haciendo una búsqueda activa de casos, realizando pruebas de cribado y haciendo intervenciones interdisciplinarias que incluyan educación de la población y del personal en salud, para así promover el autocuidado y realizar un seguimiento que impacte de forma positiva en la calidad de vida de los pacientes, en los desenlaces de la enfermedad y en la economía de los países en vía de desarrollo, los cuales deben optimizar sus limitados recursos e invertir en los procesos que generen mayor costo-efectividad.

Chronic kidney disease (CKD) is a highly prevalent entity in developing countries, affecting a large part of the Colombian population, which affects the quality of life, longevity and health costs. It has a progressive and irreversible character, so that intervening in early stages, turns out to be a highly cost-effective measure, from this, the concept of nephro-prevention arises, in which taking into account the levels of primary, secondary and tertiary prevention, it is possible to obtain an early identification, interruption or slowing down of progression, and timely and comprehensive management of kidney damage according to the stage of their disease; taking into account an active search for cases, carrying out screening tests and an interdisciplinary intervention that includes education of the population and health personnel, in order to generate self-care and follow-up that positively impacts quality of life, outcomes and finally the economy of developing countries, which those who, with limited resources, must optimize and invest in the processes that generate greater cost-effectiveness.

Assessment of estimated glomerular filtration rate based on cystatin C in diabetic nephropathy / Avaliação da taxa de filtração glomerular estimada com base na cistatina C em nefropatia diabética

Abstract Introduction: GFR is estimated by using creatinine and cystatin C to determine renal dysfunction. Our aim was to evaluate estimated GFR (eGFR) based on cystatin C in type 2 diabetic patients with diabetic nephropathy (DN). Methods: Study group included 52 controls (46% male, age: 54.5±12.4) and 101 diabetic patients (46.5% male, age: 58.2±11). The diabetics were divided into three subgroups according to 24-hour urine albumin: normal to mildly increased (A1) (n=51), moderately increased (A2) (n=25), severely increased (A3) (n=25) albuminuria. Creatinine clearance (CrCl) was determined. Correlations between CrCl and eGFRs estimated according to the CKD-EPI, MDRD, and Cockcroft-Gault (CG) formulas, and ROC curves were evaluated. Data were analyzed using SPSS 22.0. Results: Only CKD-EPI-cys eGFR was significantly lower in the A1 group than the controls (p=0.021). All GFRs were lower in the A3 group than the control (CKD-EPI-cr, MDRD, CKD-EPI-cys, CKD-EPI-cr-cys: p=0.0001, CG and CrCl: p=0.001) and A1 (for all GFRs p=0.0001) groups. CKD-EPI-cr (p=0.004), MDRD (p=0.01), CG (p=0.037), CKD-EPI-cys (p=0.033), and CKD-EPI-cr-cys (p=0.016) eGFRs in the A2 group were significantly different from the A1 group. All eGFRs showed a moderate correlation with CrCl in the A1group (CKD-EPI-cr and CKD-EPI-cr-cys: r=0.49, p=0.0001, MDRD: r=0.44, p=0.001, CG r=0.48, p=0.0001: CKD-EPI-cys r=0.40, p=0.004). The area under the CKD-EPI-cys ROC curve was the highest and found to be 0.847 (95%CI 0.763-0.931, p=0.0001). Conclusions: Our results showed that the CKD-EPI-cys eGFR can be useful in detecting the early stage of DN and more predictive than the others for prediction of DN.

Resumo Introdução: A TFG é estimada usando creatinina e cistatina C para determinar a disfunção renal. Nosso objetivo foi avaliar a TFG estimada (TFGe) com base na cistatina C em pacientes com diabetes do tipo 2 com nefropatia diabética (ND). Métodos: O grupo de estudo incluiu 52 controles (46% homens, idade: 54,5±12,4) e 101 pacientes diabéticos (46,5% homens, idade: 58,2±11). Os diabéticos foram divididos em três subgrupos de acordo com a albumina na urina de 24 horas: albuminúria normal a levemente aumentada (A1) (n=51), moderadamente aumentada (A2) (n=25) e severamente aumentada (A3) (n=25). Foi determinado o clearance de creatinina (Clcr). As correlações entre Clcr e TFGe calculadas de acordo com as fórmulas CKD-EPI, MDRD, e Cockcroft-Gault (CG), e as curvas ROC foram avaliadas. Os dados foram analisados usando o SPSS 22.0. Resultados: Somente a TFGe CKD-EPI-cis foi significativamente menor no grupo A1 do que nos controles (p=0,021). Todas as TFGs foram mais baixas no grupo A3 do que no grupo controle (CKD-EPI-cr, MDRD, CKD-EPI-cis, CKD-EPI-cr-cis: p=0,0001, CG e Clcr: p=0,001) e no grupo A1 (para todas as TFGs p=0,0001). As TFGes CKD-EPI-cr (p=0,004), MDRD (p=0,01), CG (p=0,037), CKD-EPI-cis (p=0,033), e CKD-EPI-cr-cis (p=0,016) no grupo A2 foram significativamente diferentes do grupo A1. Todas as TFGes mostraram uma correlação moderada com Clcr no grupo A1 (CKD-EPI-cr e CKD-EPI-cr-cis: r=0,49, p=0,0001, MDRD: r=0,44, p=0,001, CG r=0,48, p=0,0001: CKD-EPI-cis r=0,40, p=0,004). A área sob a curva ROC CKD-EPI-cis foi a mais alta e foi considerada 0,847 (95%IC 0,763-0,931, p=0,0001). Conclusões: Nossos resultados mostraram que a TFGe CKD-EPI-cis pode ser útil na detecção do estágio inicial de ND e com maior valor de predição do que as outras para a predição da ND.

Fishing nets and video creation: diabetic nephropathy education on screen / Redes de pesca e a criação de vídeo: em tela a educação na nefropatia diabética

Abstract: Introduction: Noncommunicable Chronic Diseases (NCDs), such as Diabetes and Hypertension are responsible for 2/3 of deaths in the world, with Diabetic Nephropathy (DN) representing the most important cause of chronic kidney disease. Health Literacy (HL) is one of the social determinants of health. To guide and expand the knowledge of patients and teams involved in the care of people with NCDs, and for a better approach to chronic complications of Diabetes and Hypertension, the development of learning objects (LO) was proposed. Experience Report: this study involved the construction of an educational video by a group of five students during the academic program of undergraduate Medical School in 2019. They proposed a guiding question in relation to DN from a theoretical material. The chosen question was: "What is the level of understanding of patients with diabetic nephropathy in relation to their own disease?". They developed a questionnaire on diabetes and hypertension and their complications, which was answered by patients with diabetes who were treated at the specialized outpatient clinic, aiming to answer the proposed problem. They drew a synthesis from the analysis of the responses, of the possible gaps in relation to the understanding of the diseases. Then, a script was created with the description of these gaps with the medical explanation and an analogy was made with fishing nets for the video production, containing narratives, texts, audios and images. Finally, the video was presented to teachers and students in the classroom. Discussion: The characterization of the video as an LO implies constructing it as an educational component, self-sufficient, reusable and with the possibility of combining it with other LOs as new educational tools. Conclusion: The educational material was characterized as an LO. It allows pointing out aspects of the progression of DN and recommended medical orientations for the disease. It establishes a tool for group discussions and isolated actions based on succinct and evidence-based medical information. The video validation is undergoing validation for use in health services.

Resumo: Introdução: As doenças crônicas não transmissíveis (DCNT), como diabetes e hipertensão, são responsáveis por dois terços das mortes no mundo, sendo a nefropatia diabética (ND) a principal causa de doença renal crônica. O letramento em saúde (LS) constitui um dos determinantes sociais da saúde. Para orientação e ampliação de conhecimento dos pacientes e das equipes envolvidas no cuidado de pessoas com DCNT, e para uma melhor abordagem das complicações crônicas do diabetes e da hipertensão, foi proposta a elaboração de objetos de aprendizagem (OA). Relato de experiência: O presente trabalho envolveu a construção de um vídeo educacional por um grupo de cinco alunos durante as atividades acadêmicas do curso de Medicina em 2019. Esses alunos propuseram uma questão norteadora em relação à ND a partir de um material teórico. A questão escolhida foi: "Qual é o nível de entendimento dos pacientes com nefropatia diabética em relação à própria doença?". Elaboraram um questionário sobre diabetes e hipertensão e suas complicações, o qual foi respondido por pacientes com diabetes atendidos no ambulatório especializado, buscando atender à problemática proposta. Extraíram uma síntese, a partir da análise das respostas, das possíveis lacunas em relação ao entendimento sobre as doenças. A partir disso, produziram um roteiro e atribuíram uma explicação médica a tais lacunas. O vídeo foi construído com base em uma analogia com redes de pesca e composto por narrativas, textos, áudios e imagens. Ao final, apresentaram o vídeo aos docentes e discentes em sala de aula. Discussão: Para que se possa caracterizar o vídeo como um OA, ele precisa se configurar como componente educacional, autossuficiente, passível de reusabilidade e com possibilidade de combinação com outros OA, formando novos objetos educacionais. Conclusão: O material educativo construído pode ser caracterizado como um OA. Tal material pontua aspectos da evolução da ND, bem como traz orientações médicas preconizadas para a doença, podendo ser usado em discussões em grupo ou em ações isoladas, visto que apresenta informações sucintas e embasadas em literatura. Está em curso o processo de validação do vídeo para uso nos serviços de saúde.

Morphofunctional study on the effects of passive smoking in kidneys of rats / Estudo morfofuncional sobre os efeitos do tabagismo passivo em rins de ratos

ABSTRACT Objective To analyze whether passive inhalation of cigarette smoke causes morphological, structural, and functional changes in kidneys of rats. Methods Wistar rats, aged eight weeks, weighing on average 260g, were divided into Control Group and Smoking Group. Each group was subdivided into four groups of ten animals for morphofunctional analysis, in a period of seven and 28 days. The Smoking Group was exposed to smoke of 40 cigarettes per day, at certain times and in automated equipment for cigarette burning, called smoking machine (SM-MC-01). After the exposure period, urine and blood samples were collected for the functional analyses, and the kidneys were dissected and submitted to histological procedures for morphoquantitative analyses. Results After exposure of animals of the Smoking Group, the following were observed: lower weight gain; lower water and feed intake; decreased renal weight, diameter, and volume; reduction in cortical thickness and glomerular volume density; decrease in glomerular and capsular diameter; increase in mesangial density; decreased urine volume; increased levels of glucose, serum creatinine and microalbuminuria; decreased urinary creatinine levels and creatinine clearance rate. Conclusion Passive smoking negatively influences renal morphology and glomerular filtration rate, with effects similar to those described in the literature regarding active smoking.

RESUMO Objetivo Analisar se a inalação passiva da fumaça do cigarro proporciona alterações morfológicas, estruturais e funcionais nos rins de ratos. Métodos Ratos Wistar, com oito semanas de idade, pesando, em média, 260g, foram divididos em Grupo Controle e Grupo Tabagista. Cada grupo foi subdividido em quatro grupos de dez animais para análise morfofuncional, em um período de sete e 28 dias. O Grupo Tabagista foi exposto à fumaça de 40 cigarros por dia, em horários determinados e equipamento automatizado de queima de cigarros, denominado smoking machine (SM-MC-01). Após o período de exposição, foram coletadas amostras de urina e sangue para as análises funcionais, e os rins foram dissecados e submetidos a procedimentos histológicos para análises morfoquantitativas. Resultados Após a exposição dos animais do Grupo Tabagista, observou-se menor ganho de peso; menor consumo de água e ração; menor peso, diâmetro e volume renal; redução em espessura cortical e densidade de volume glomerular; diminuição no diâmetro glomerular e capsular; aumento na densidade mesangial; volume urinário diminuído; níveis aumentados de glicose, creatinina sérica e microalbuminúria; níveis reduzidos de creatinina urinária e redução da taxa de depuração da creatinina. Conclusão O tabagismo passivo influencia negativamente na morfologia renal e na taxa de filtração glomerular, com efeitos semelhantes aos descritos na literatura em relação ao tabagismo ativo.

Making a case for the combined use of SGLT2 inhibitors and GLP1 receptor agonists for cardiorenal protection / Argumentando a favor do uso combinado de inibidores de SGLT2 e agonistas do receptor GLP1 para proteção cardiorrenal

ABSTRACT Sodium glucose cotransporter-2 (SGLT2) inhibitors and glucagon-like peptide-1 receptor agonists (GLP-1RA) were initially approved to improve glycemic control in the treatment of type 2 diabetes. Clinical trials have also demonstrated beneficial effects with regards to cardiovascular and renal parameters. Beyond improving glycemic control, these therapies promote weight loss and lower blood pressure when used individually, and in an additive manner when used together. Accordingly, taking advantage of complementary mechanisms of action with the combined use of these two classes of agents to further improve cardiorenal outcomes is conceptually appealing, but has yet to be explored in detail in clinical trials. In this review, we discuss proposed mechanisms for renal protection, clinical benefits, and adverse events associated with the individual and combined use of SGLT2 inhibitors and GLP-1RA. The management of type 2 diabetes has significantly changed over the last few years, moving away from solely glycemic control towards the concurrent management of associated comorbidities in a patient population at significant risk of cardiovascular disease and progression of chronic kidney disease. It is from this perspective that we seek to outline the rationale for the sequential and/or combined use of SGLT2 inhibitors and GLP-1RA in patients with type 2 diabetes.

RESUMO Inibidores do cotransporter-2 de glicose sódica (SGLT2) e agonistas do receptor peptídeo-1 do tipo glucagon (GLP-1RA) foram inicialmente aprovados para melhorar o controle glicêmico no tratamento da diabetes tipo 2. Os ensaios clínicos também demonstraram efeitos benéficos em relação aos parâmetros cardiovasculares e renais. Além de melhorar o controle glicêmico, essas terapias promovem perda de peso e redução da pressão arterial quando usadas individualmente, e de forma aditiva quando usadas em conjunto. Consequentemente, tirar proveito de mecanismos de ação complementares com o uso combinado dessas duas classes de agentes para melhorar ainda mais os resultados cardiorrenais é conceitualmente atraente, mas ainda precisa ser explorado em detalhes em ensaios clínicos. Nesta revisão, discutimos os mecanismos propostos para proteção renal, benefícios clínicos e eventos adversos associados ao uso individual e combinado de inibidores de SGLT2 e GLP-1RA. O tratamento do diabetes tipo 2 mudou significativamente nos últimos anos, passando do controle exclusivamente glicêmico para o tratamento simultâneo de comorbidades associadas em uma população de pacientes com risco significativo de doença cardiovascular e progressão da doença renal crônica. É nessa perspectiva que procuramos delinear a justificativa para o uso sequencial e/ou combinado de inibidores de SGLT2 e GLP-1RA em pacientes com diabetes tipo 2.

Idiopathic nodular glomerulosclerosis and differential diagnosis / Glomerulosclerose nodular idiopática e diagnóstico diferencial

ABSTRACT Introduction: Idiopathic nodular glomerulosclerosis (ING) is a condition that has a vasculopathic glomerular histological pattern. Case presentation: The authors present the case of a 44-year-old Hispanic smoker female with hypertension and peripheral arterial disease who presented nephrotic syndrome for 2 weeks. The patient was diagnosed with ING by percutaneous renal biopsy results, which showed global nodular mesangial matrix expansion, with linear staining accentuation of glomerular and tubular basement membrane for Immunoglobulin G (IgG) and albumin on immunofluorescence. Conclusions: ING is a rare disease with a poor renal prognosis and wide diagnostic approach; we highlight the importance of analyzing every piece of detail together to reach a definitive diagnosis.

RESUMO Introdução: A glomerulosclerose nodular idiopática (GNI) tem um padrão histológico glomerular vasculopático. Apresentação do caso: Os autores apresentam o caso de uma mulher latino-americana, de 44 anos, fumante, com hipertensão e doença arterial periférica; com síndrome nefrótica por 2 semanas. Ela foi diagnosticada com GNI por biópsia renal percutânea, que mostrou expansão generalizada da matriz mesangial nodular, com acentuação de coloração linear na membrana basal glomerular e tubular para imunoglobulina G (IgG) e albumina à imunofluorescência. Conclusões: A GNI é uma doença rara, com mau prognóstico renal, e com necessidade de uma ampla abordagem diagnóstica. Demonstramos aqui a importância de se analisar todos os detalhes em conjunto para realizar um diagnóstico definitivo.

Effect of febuxostat on renal function in patients from South China with CKD3 diabetic nephropathy / Efeito do febuxostat na função renal em pacientes do sul da China com nefropatia diabética com DRC3

ABSTRACT Objective: To investigate the efficacy and safety of febuxostat on renal function in CKD stage 3 diabetic nephropathy patients. Methods: Patients in our hospital with chronic kidney disease (CKD) stage 3 diabetic nephropathy (DN) complicated by high serum uric acid (360 µmol/L) were recruited. Patients were then divided into treatment group and control group according to the random number table method. All the patients received low purine diet, renin-angiotensin-aldosterone system (RAAS) inhibitors, and adequate routine hypoglycemic treatment. Febuxostat was employed only in the treatment group. The levels of blood uric acid (sUA), serum creatinine (Scr), cystatin C (cys-c), eGFR, 24-hour urine protein quantification, albuminuria, and creatinine ratio (ACR) were evaluated in all patients before and after treatment at 4, 8, 12, and 24 week. Results: No difference was found before treatment between the two groups. After treatment at 4, 8, 12, and 24 week, the levels of sUA, SCr, cys-c, and eGFR between the two groups were significant different (P<0.05). There was no difference in 24-hour urine protein quantification, albuminuria, and creatinine ratio between two groups before treatment, and significant differences were observed after treatment. Fifty percent of patients from the treatment group achieved the treatment goal with 20 mg febuxostat at 4 weeks. Tubular markers were also decreased with the treatment. Conclusions: Febuxostat can reduce uric acid and improve renal function effectively in patients with CKD stage 3 diabetic nephropathy, while being well tolerated. However, the conclusion is still uncertain due to the short term of the study.

RESUMO Objetivo: Investigar a eficácia e segurança do febuxostat na função renal em pacientes com DRC estágio 3, com nefropatia diabética. Métodos: Foram recrutados pacientes em nosso hospital com nefropatia diabética (DN) estágio 3 de doença renal crônica (DRC) complicada por ácido úrico sérico alto (360 µmol/L). Os pacientes foram então divididos em grupo de tratamento e grupo controle, de acordo com o método da tabela de números aleatórios. Todos os pacientes receberam dieta pobre em purinas, inibidores do sistema renina-angiotensina-aldosterona (RAAS) e tratamento hipoglicêmico de rotina. O Febuxostat foi empregado apenas no grupo de tratamento. Os níveis de ácido úrico no sangue (AIU), creatinina sérica (Scr), cistatina C (cys-c), TFGe, quantificação de proteínas na urina em 24 horas, razão albumina e creatinina (ACR) foram avaliados em todos os pacientes antes e após o tratamento às 4, 8, 12 e 24 semanas. Resultados: Nenhuma diferença foi encontrada antes do tratamento entre os dois grupos. Após o tratamento nas 4, 8, 12 e 24 semanas, os níveis de sUA, SCr, cys-c e TFGe entre os dois grupos foram significativamente diferentes (P <0,05). Não houve diferença na quantificação de proteínas na urina em 24 horas, albuminúria e razão de creatinina entre dois grupos antes do tratamento, e diferenças significativas foram observadas após o tratamento. Cinquenta por cento dos pacientes do grupo de tratamento atingiram a meta de tratamento com 20 mg de febuxostat em 4 semanas. Marcadores tubulares também foram reduzidos com o tratamento. Conclusões: O Febuxostat pode reduzir o ácido úrico e melhorar a função renal efetivamente em pacientes com nefropatia diabética estágio com DRC no estágio 3, sendo bem tolerado. No entanto, a conclusão ainda é incerta devido ao curto prazo do estudo.

Zinc alpha 2 glycoprotein as an early biomarker of diabetic nephropathy in patients with type 2 diabetes mellitus / Zinco-alfa2-glicoproteina (ZAG) como biomarcador precoce de nefropatia diabética em pacientes com diabetes mellitus tipo 2

Abstract Introduction: Although microalbuminuria remains the gold standard for early detection of diabetic nephropathy (DN), it is not a sufficiently accurate predictor of DN risk. Thus, new biomarkers that would help to predict DN risk earlier and possibly prevent the occurrence of end-stage kidney disease are being investigated. Objective: To investigate the role of zinc-alpha-2-glycoprotein (ZAG) as an early marker of DN in type 2 diabetic (T2DM) patients. Methods: 88 persons were included and classified into 4 groups: Control group (group I), composed of normal healthy volunteers, and three patient groups with type 2 diabetes mellitus divided into: normo-albuminuria group (group II), subdivided into normal eGFR subgroup and increased eGFR subgroup > 120 mL/min/1.73m2), microalbuminuria group (group III), and macroalbuminuria group (group IV). All subjects were submitted to urine analysis, blood glucose levels, HbA1c, liver function tests, serum creatinine, uric acid, lipid profile and calculation of eGFR, urinary albumin creatinine ratio (UACR), and measurement of urinary and serum ZAG. Results: The levels of serum and urine ZAG were higher in patients with T2DM compared to control subjects and a statistically significant difference among studied groups regarding serum and urinary ZAG was found. Urine ZAG levels were positively correlated with UACR. Both ZAG levels were negatively correlated with eGFR. Urine ZAG levels in the eGFR ˃ 120 mL/min/1.73m2 subgroup were higher than that in the normal eGFR subgroup. Conclusion: These findings suggest that urine and serum ZAG might be useful as early biomarkers for detection of DN in T2DM patients, detectable earlier than microalbuminuria.

Resumo Introdução: Embora a microalbuminúria continue sendo o padrão ouro para a detecção precoce da nefropatia diabética (ND), ela não é um preditor suficientemente preciso do risco de ND. Assim, novos biomarcadores para prever mais precocemente o risco de ND e possivelmente evitar a ocorrência de doença renal terminal estão sendo investigados. Objetivo: Investigar a zinco-alfa2-glicoproteína (ZAG) como marcador precoce de ND em pacientes com debates mellitus tipo 2 (DM2). Métodos: Os 88 indivíduos incluídos foram divididos em quatro grupos: grupo controle (Grupo I), composto por voluntários saudáveis normais; e três grupos de pacientes com DM2 assim divididos: grupo normoalbuminúria (Grupo II), subdivididos em TFG normal e TFG > 120 mL/min/1,73 m2), grupo microalbuminúria (Grupo III) e grupo macroalbuminúria (Grupo IV). Todos foram submetidos a urinálise e exames para determinar glicemia, HbA1c, função hepática, creatinina sérica, ácido úrico, perfil lipídico, cálculo da TFG, relação albumina/creatinina (RAC) e dosagem urinária e sérica de ZAG. Resultados: Os níveis séricos e urinários de ZAG foram mais elevados nos pacientes com DM2 em comparação aos controles. Foi identificada diferença estatisticamente significativa entre os grupos estudados em relação aos níveis séricos e urinários de ZAG. Os níveis urinários de ZAG foram positivamente correlacionados com a RAC. Ambos os níveis de ZAG foram negativamente correlacionados com TFG. Os níveis urinários de ZAG no subgrupo com TFG ˃ 120 mL/min/1,73m2 foram maiores do que no subgrupo com TFG normal. Conclusão: Constatamos que a ZAG sérica e urinária pode ser um útil biomarcador precoce para detecção de ND em pacientes com DM2, sendo detectável mais precocemente que microalbuminúria.

MicroRNAs: new biomarkers and promising therapeutic targets for diabetic kidney disease / MicroRNAs: novos biomarcadores e alvos terapêuticos promissores da doença renal do diabetes

Abstract Diabetic kidney disease (DKD) is a chronic complication of diabetes mellitus associated with significant morbidity and mortality regarded as a global health issue. MicroRNAs - small RNA molecules responsible for the post-transcriptional regulation of gene expression by degradation of messenger RNA or translational repression of protein synthesis - rank among the factors linked to the development and progression of DKD. This study aimed to offer a narrative review on investigations around the use of microRNAs in the diagnosis, monitoring, and treatment of DKD. Various microRNAs are involved in the pathogenesis of DKD, while others have a role in nephroprotection and thus serve as promising therapeutic targets for DKD. Serum and urine microRNAs levels have also been considered in the early diagnosis and monitoring of individuals with DKD, since increases in albuminuria, decreases in the glomerular filtration rate, and progression of DKD have been linked to changes in the levels of some microRNAs.

Resumo A doença renal do diabetes (DRD) é uma complicação crônica do diabetes mellitus associada à elevada morbidade e mortalidade, considerada um problema de saúde mundial. Dentre os fatores associados ao desenvolvimento e à progressão da DRD, destacam-se os microRNAs, que consistem em pequenas moléculas de RNA que regulam a expressão gênica por meio da degradação pós-transcricional do RNA mensageiro ou inibição translacional da síntese proteica. Este estudo teve como objetivo realizar uma revisão narrativa buscando investigar os microRNAs como auxiliares no diagnóstico, monitoramento e tratamento da DRD. Vários microRNAs estão envolvidos na patogênese da DRD, enquanto que outros têm papel nefroprotetor, consistindo assim em alvos terapêuticos promissores para o tratamento da DRD. A dosagem laboratorial dos microRNAs no soro e na urina também é muito promissora para o diagnóstico precoce e o monitoramento da DRD, já que os níveis de alguns microRNAs se alteram antes do aumento da albuminúria e da diminuição da taxa de filtração glomerular e podem ainda se alterar com a progressão da DRD.

Macrophage migration inhibitory factor antagonist (p425) ameliorates kidney histopathological and functional changes in diabetic rats / Antagonista (p425) do fator de inibição da migração de macrófagos (MIF) melhora as alterações histopatológicas e funcionais renais em ratos diabéticos

Abstract Introduction: It is hypothesized that increased macrophage migration inhibitory factor (MIF) expression may contribute to diabetic nephropathy (DN) pathogenesis. The aim of the present study was to investigate the renal effects of MIF inhibition in a diabetic experimental model. Methods: Eighteen male Wistar rats (230 ± 20 g) were divided into three groups: 1) control, 2) diabetic (STZ, 50 mg/kg, dissolved in saline, ip), 3) diabetic + MIF antagonist (p425, 1 mg/kg per day, ip, on the 21th day, for 21 consecutive days). The treatment started since we founwd a significant increase in urine albumin excretion (UAE) rate in the diabetic rats in comparison with the control rats. The rats were kept individually in metabolic cages (8 AM-2 PM) and urine samples were collected in the 21 and 42th day. At the end, blood and tissue samples were collected for biochemical (BS, UPE, urine GAG, BUN, Cr, Na, and K) and histological analyses. Results: The results of this study showed that MIF antagonist (p425) significantly decreased urine protein and GAG excretion, urine protein/creatinine ratio, and serum BUN and Cr in the streptozotocin-induced DN in the rats. Pathological changes were significantly alleviated in the MIF antagonist (p425)-administered DN rats. Conclusion: Collectively, these data suggested that MIF antagonist (p425) was able to protect against functional and histopathological injury in the DN.

Resumo Introdução: Supõe-se que elevações da expressão do fator de inibição da migração de macrófagos (MIF) possam contribuir para a patogênese da nefropatia diabética (ND). O objetivo do presente estudo foi investigar os efeitos renais da inibição do MIF em um modelo experimental diabético. Métodos: Dezoito ratos Wistar machos (230 ± 20g) foram divididos em três grupos: 1) controle, 2) diabético (STZ 50 mg/kg dissolvida em soro fisiológico, IP), 3) diabético + antagonista do MIF (p425 1 mg/kg por dia IP no 21o dia por 21 dias consecutivos). O tratamento começou após a identificação de aumento significativo na albuminúria nos ratos diabéticos em relação aos controles. Os ratos foram mantidos individualmente em gaiolas metabólicas (8h-14h) e amostras de urina foram colhidas no 21o e no 42o dia. Ao final do estudo, amostras de sangue e tecido foram colhidas para análises bioquímicas (BS, excreção urinária de proteína, excreção urinária de GAGs, BUN, Cr, Na e K) e histológicas. Resultados: O presente estudo demonstrou que o antagonista do MIF (p425) diminuiu significativamente proteinúria, excreção urinária de GAGs , relação proteína/creatinina na urina, BUN e Cr no grupo com ND induzida por estreptozotocina. As alterações patológicas foram significativamente abrandadas nos ratos com ND que receberam antagonista do MIF (p425). Conclusão: Coletivamente, os dados sugerem que o antagonista do MIF (p425) teve efeito protetor contra lesões funcionais e histopatológicas da ND.

Is Uric Acid elevation a random finding or a causative agent of diabetic nephropathy?

SUMMARY OBJECTIVE In this study, we aimed to analyze the relationship between serum uric acid (UA) and microalbuminuria as a marker of renal injury in type 2 diabetes mellitus. METHODS A total of 100 patients with type 2 diabetes mellitus were enrolled in the study. Participants were divided into two groups according to the urinary microalbumin/creatinine ratio: diabetic nephropathy and non-nephropathy group. UA and microalbuminuria were compared between the study groups. RESULTS Serum UA levels of diabetic nephropathy patients were significantly higher than those in the non-nephropathy group (UA in patients with diabetic nephropathy groups: 6.3 (1.82) mg/dl, UA in patients of the non-nephropathic group: 4.85 (1.92) mg/dl) (p<0.001). There was a correlation between microalbuminuria and UA (r=0.238). This correlation was statistically significant (p=0.017). CONCLUSION UA levels may be an important predictor of nephropathy in diabetic patients.

RESUMO OBJETIVO O objetivo deste estudo foi analisar a relação entre o ácido úrico sérico e a microalbuminúria como marcador de lesão renal no diabetes mellitus tipo 2. MÉTODOS Um total de 100 pacientes com diabetes mellitus tipo 2 foram inscritos no estudo. Os grupos de estudo foram divididos em dois, de acordo com a relação microalbumina/creatinina na urina: nefropatia diabética e grupo não nefropático. UA e microalbuminúria foram comparados entre os grupos de estudo. RESULTADOS Os níveis séricos de AU de pacientes com nefropatia diabética foram significativamente maiores do que o grupo sem nefropatia (AU em pacientes com grupos de nefropatia diabética: 6,3 (1,82) mg/dl, AU em pacientes com grupos não nefropáticos: 4,85 (1,92) mg/dl ) (p<0,001). Houve correlação entre microalbuminúria e AU (r=0,238). Essa correlação foi estatisticamente significativa (p=0,017). CONCLUSÃO Os níveis de AU podem ser um importante preditor de nefropatia em pacientes diabéticos.

Ramipril can alleviate the accumulation of renal mesangial matrix in rats with diabetic nephropathy by inhibiting insulin-like growth factor-1

Purpose:To investigate the impact of Ramipril (RAM) on the expressions of insulin-like growth factor-1 (IGF-1) and renal mesangial matrix (RMM) in rats with diabetic nephropathy (DN).Methods:The Sprague Dawley rats were divided into normal control (NC) group (n = 12), DN group (n = 11), and DN+RAM group (n = 12). The ratio of renal weight to body weight (RBT), fasting blood glucose (FBG), HbA1c, 24-h urine protein (TPU), blood urea nitrogen (BUN), creatinine (Cr), renal pathological changes, the levels of IGF-1, fibronectin (FN), type IV collagen (Col-IV), and matrix metalloproteinases (MMP)-2 were compared among the groups.Results:Compared with NC group, the RBT, FBG, HbA1c, TPU, BUN, Cr, and RMM in DN group were significantly increased (P < 0.05), the IGF-1, FN, and Col-IV were significantly upregulated (P < 0.05), while MMP was significantly downregulated (P < 0.05). Compared with DN group, the indexes except for the FBG and HbA1c in DN+RAM group were significantly improved (P < 0.05), among which IGF-1 exhibited significant positive correlation with TPU(r=0.937), FN(r=0.896) and Col-IV(r=0.871), while significant negative correlation with MMP-2 (r=-0.826) (P<0.05).Conclusion:RAM may protect the kidneys by suppressing IGF-1 and mitigating the accumulation of RMM.(AU)

Ramipril can alleviate the accumulation of renal mesangial matrix in rats with diabetic nephropathy by inhibiting insulin-like growth factor-1

Abstract Purpose: To investigate the impact of Ramipril (RAM) on the expressions of insulin-like growth factor-1 (IGF-1) and renal mesangial matrix (RMM) in rats with diabetic nephropathy (DN). Methods: The Sprague Dawley rats were divided into normal control (NC) group (n = 12), DN group (n = 11), and DN+RAM group (n = 12). The ratio of renal weight to body weight (RBT), fasting blood glucose (FBG), HbA1c, 24-h urine protein (TPU), blood urea nitrogen (BUN), creatinine (Cr), renal pathological changes, the levels of IGF-1, fibronectin (FN), type IV collagen (Col-IV), and matrix metalloproteinases (MMP)-2 were compared among the groups. Results: Compared with NC group, the RBT, FBG, HbA1c, TPU, BUN, Cr, and RMM in DN group were significantly increased (P < 0.05), the IGF-1, FN, and Col-IV were significantly upregulated (P < 0.05), while MMP was significantly downregulated (P < 0.05). Compared with DN group, the indexes except for the FBG and HbA1c in DN+RAM group were significantly improved (P < 0.05), among which IGF-1 exhibited significant positive correlation with TPU(r=0.937), FN(r=0.896) and Col-IV(r=0.871), while significant negative correlation with MMP-2 (r=-0.826) (P<0.05). Conclusion: RAM may protect the kidneys by suppressing IGF-1 and mitigating the accumulation of RMM.