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Chronic kidney disease (CKD) and acute kidney injury (AKI) are diseases which affect the urinary tract characterized by the loss of renal function. Their therapy requires different therapeutic goals. Mesenchymal stem cells (MSC) transplantation has spread over the years as a treatment for many diseases. In the urinary tract, studies report anti-inflammatory, antiapoptotic, antifibrotic, antioxidant and angiogenic effects. This work reports the results of a meta-analysis about the effects of the MSC application in serum levels of creatinine in dogs and cats with AKI and CKD. The work followed PRISMA guidelines. Data were screened, selected, and extracted with characteristics about the studies. The kinds of injury were classified according to their identification and the risk of bias was calculated by the system SYRCLE. The results of each group were combined by the inverse variance method. The heterogeneity was evaluated by the I2 test. For the mean of creatinine, a meta-analysis was performed according to the study group and number of applications and separately for the control and treatment groups according to the kind of injury, dose, application route, and moment. At all, 4742 articles were found. Of these, 40 were selected for eligibility, 16 underwent qualitative analysis and 9 to the quantitative. The results denote advantage to the group treated with MSC over placebo. A statistical difference was observed both in combined analysis and in the subgroups division. However, a high heterogeneity was found, which indicates considerable variation between the studies, which indicates caution in generalize the results.

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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.

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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.

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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.

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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).

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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.

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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.

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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.

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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.