Age-related markers and predictors of diabetic kidney disease progression in type 2 diabetes patients: a retrospective cohort study.

Background: Diabetic kidney disease (DKD) is characterized by reduced estimated glomerular filtration rate (eGFR) and albuminuria, which play a pivotal role in both diagnosing and determining the disease's progression. This study aimed to assess the trajectory of these markers concerning age in individuals with DKD and identify predictive factors for the decline in eGFR decline, variation in albuminuria, mortality, and progression to renal replacement therapy (RRT). Design: This retrospective cohort encompassed patients with type 2 diabetes (T2D), divided into two age categories: <75 and ⩾75 years old. Methods: Over a 3-year span, the study evaluated eGFR (CKD-EPI) and 24-h albuminuria. Univariate and multivariate analyses were employed to pinpoint factors associated with deteriorating renal function and mortality. Significance was set at p < 0.05, and Kaplan-Meier survival curves were constructed to illustrate renal and overall survival. Results: The analysis comprised 304 patients. Comparable eGFR declines were evident in both age groups during the transition from the first to the second year and from the second to the third year. Nonetheless, a more pronounced rise in albuminuria was evident in the ⩾75 years group during the first to the second year. Multivariate analysis unveiled that systolic blood pressure (SBP) measurements in the first year positively forecasted eGFR decline. Age was associated with heightened albuminuria and mortality, while hospitalizations linked to cardiovascular causes robustly predicted mortality. Hospitalizations due to sepsis and cardiovascular reasons, coupled with first-year SBP measurements, served as predictive indicators for progression to RRT. Conclusion: Both age groups experienced similar declines in eGFR, though the ⩾75 years group displayed a more significant increase in albuminuria during the first to the second year. Age, hospitalizations, and higher blood pressure levels were correlated with exacerbated renal function deterioration and/or elevated mortality in DKD. Timely intervention and tailored management strategies stand as critical components for enhancing outcomes among DKD patients.

Diabetic kidney disease: aging and progression Diabetic kidney disease (DKD) is characterized by a reduced estimated glomerular filtration rate (eGFR) and albuminuria. This study aims to evaluate the follow-up of these renal markers in relation to age among individuals with DKD and identify factors predisposing to eGFR loss, increased albuminuria, mortality, and the need for dialysis. We conducted an observational and retrospective study in Brazil, including patients with type 2 diabetes, divided into two age groups: < 75 and ⩾ 75 years. The patients were followed for three years, and a total of 304 patients were evaluated. We observed a similar decline in eGFR in both age groups from the 1st to the 2nd year and from the 2nd to the 3rd year. However, worsening of albuminuria was more frequent in the ⩾ 75 years old group from the 1st to the 2nd year. Elevated blood pressure levels were associated with eGFR decline. Age was associated with increased albuminuria and mortality. Hospitalizations for cardiovascular causes strongly predicted mortality. Hospitalizations for sepsis and cardiovascular causes, along with higher blood pressure levels, were associated with the need for dialysis. Hence, establish approaches to enhance the health in individuals with DKD is of paramount importance.

Assessing the influence of graft loss on 4-year patient survival after simultaneous pancreas-kidney transplantation: Kaplan-Meier versus Competing Risk Analysis model.

BACKGROUND: Graft loss increases the risk of patient death after simultaneous pancreas-kidney (SPK) transplantation. The relative risk of each graft failure is complex due to the influence of several competing events. METHODS: This retrospective, single-center study compared 4-year patient survival according to the graft status using Kaplan-Meier (KM) and Competing Risk Analysis (CRA). Patient survival was also assessed according to five eras (Era 1: 2001-2003; Era 2: 2004-2006; Era 3: 2007-2009; Era 4: 2010-2012; Era 5: 2012-2015). RESULTS: Between 2000 and 2015, 432 SPK transplants were performed. Using KM, patient survival was 86.5% for patients without graft loss (n = 333), 93.4% for patients with pancreas graft loss (n = 46), 43.7% for patients with kidney graft loss (n = 16), and 25.4% for patients with pancreas and kidney graft loss (n = 37). Patient survival was underestimated using KM versus CRA methods in patients with pancreas and kidney graft losses (25.4% vs. 36.2%), respectively. Induction with lymphocyte depleting antibodies was associated with 81% reduced risk (HR.19, 95% CI.38-.98, p = .0048), while delayed kidney function (HR 2.94, 95% CI 1.09-7.95, p = .033) and surgical complications (HR 2.94, 95% CI 1.22-7.08, p = .016) were associated with higher risk of death. Four-year patient survival increased from Era 1 to Era 5 (79% vs. 87.9%, p = .047). CONCLUSION: In this cohort of patients, kidney graft loss, with or without pancreas graft loss, was associated with higher mortality after SPK transplantation. Compared to CRA, the KM model underestimated survival only among patients with pancreas and kidney graft losses. Patient survival increased over time.

Scientists of Tomorrow/ Cientistas do Amanhã : a project to inspire, stimulate scientific thinking, and introduce scientific methodology for young students.

The Scientists of Tomorrow/ Cientistas do Amanhã project is an immersive science training program developed by the Program of Post-Graduation in Health Sciences at Hospital Israelita Albert Einstein. This program was conducted in partnership with Volunteering and Escola Municipal de Ensino Fundamental Professor Paulo Freire in Paraisópolis, São Paulo, Brazil. The Scientists of Tomorrow Program comprised a short training period conducted in May 2022 involving 37 students, and a long training period from August to December 2022, which included 15 students. It aimed to popularize science through practical activities; transfer knowledge to young students; sensitize and guide them to pursue academic-scientific careers; reduce stereotypes about scientific work and scientists; and help students understand the social, political, and ethical roles of science within society. All activities were led by postgraduate students and professors from our postgraduate program, physicians, nurses, physiotherapists, biomedicals, and veterinarians from Hospital Israelita Albert Einstein, as well as medical students from Faculdade Israelita de Ciências da Saúde Albert Einstein . Activities in the short training included lectures on cinema and science, strategies to combat fake news, non-violent communication, innovation, design-thinking framework, and developing a scientific project. During the long training period, discussions were focused on nanotechnology, animal research, big data, bioinformatics, meditation, blood and bone marrow donation, telemedicine, sex and sexually-transmitted infections, rehabilitation, career opportunities, and scientific integrity. In addition, practical activities were further expanded using optical and confocal microscopy, cytometry, and basic concepts regarding the structure and function of living cells. The program also included the launching of the open-air outreach Education E-natureza activity, which turned students into ambassadors of nature. In conclusion, the Scientists of Tomorrow Program was innovative and enabled young students to learn that science is a collective activity that can enhance public health. In Brief Rangel et al. enumerated the Scientists of Tomorrow/Cientistas do Amanhã program, an immersive science initiative conducted in collaboration with a public school. The program, which involved 15 students, aimed to promote science, share knowledge, inspire academic paths, and underscore societal impacts. Led by postgraduates, professors, and healthcare experts, the program included diverse lectures and practical laboratory activities. Highlights Every research endeavor commences with a fundamental question. Sharing of findings by researchers and students contributes toward the expansion of knowledge. Teaching scientific methodology is a pivotal step in nurturing critical thinking skills. Science permeates our daily lives and plays a crucial role in addressing societal issues.

Understanding the Elevated Lethality of COVID-19 in Liver Transplant Recipients: Does Immunosuppression Management Matter? Results from a Brazilian Multicentric Historical Cohort.

BACKGROUND: Infections by SARS-CoV-2 in liver transplant recipients (LT) patients are of particular concern, notably due to perceived added risks related to immunosuppression and comorbidity burden. Current literature on this topic often relies on small, non-standardized, and geographically limited studies. This manuscript describes COVID-19 presentations and causes for elevated mortality in a large cohort of LT recipients. METHODS: This study was designed as a multicentric historical cohort, including LT recipient patients with COVID-19 in 25 study centers, with the primary endpoint being COVID-related death. We also collected demographic, clinical, and laboratory data regarding presentation and disease progression. RESULTS: Two hundred and thirty-four cases were included. The study population was predominantly male and White and had a median age of 60 years. The median time from transplantation was 2.6 years (IQR 1-6). Most patients had at least one comorbidity (189, 80.8%). Patient age (P = .04), dyspnea (P < .001), intensive care unit admission (P < .001), and mechanical ventilation (P < .001) were associated with increased mortality. Modifications of immunosuppressive therapy (P < .001), specifically the suspension of tacrolimus, maintained significance in multivariable analysis. CONCLUSIONS: Attention to risk factors and the individualization of patient care, especially regarding immunosuppression management, is crucial for delivering more precise interventions to these individuals.

Antimicrobial oral lavage reduces the SARS-CoV-2 load in intubated patients: randomized clinical trial.

Background: The oral cavity can be a reservoir for SARS-CoV-2 and may play a crucial role in the viral transmission in the hospital environment. Objective: To investigate whether an oral hygiene protocol with chlorhexidine (CHX) used alone and in combination with hydrogen peroxide (HP) in the intensive care unit was effective in reducing the SARS-CoV-2 viral load in the oral cavity. Methods: SARS-CoV-2 viral load was measured on oral fluid samples collected from patients undergoing orotracheal intubation. The study sample was randomly in: CHX group (n = 19) - oral rinse using only 0.12% CHX solution; HP+CHX group (n = 24) - oral rinse with 1.5% HP and 0.12% CHX. The samples were collected before the interventions (T0), immediately (T1), 30 minutes (T2) and 60 minutes (T3) after the procedure. Results: A significant viral load reduction was observed at T1 (mean ± SD:-0.57 ± 0.19 log10;-73.2%;p = 0.022) in the HP+CHX group. No statistically significant differences between any time points were observed in the CHX group. Conclusion: The HP+CHX oral rinses significantly reduced the SARS-CoV-2 viral load in the oral fluid immediately after the procedure. The CHX oral rinse alone did not result in any significant viral load reductions.

Scientists of Tomorrow/ Cientistas do Amanhã : a project to inspire, stimulate scientific thinking, and introduce scientific methodology for young students

ABSTRACT The Scientists of Tomorrow/ Cientistas do Amanhã project is an immersive science training program developed by the Program of Post-Graduation in Health Sciences at Hospital Israelita Albert Einstein. This program was conducted in partnership with Volunteering and Escola Municipal de Ensino Fundamental Professor Paulo Freire in Paraisópolis, São Paulo, Brazil. The Scientists of Tomorrow Program comprised a short training period conducted in May 2022 involving 37 students, and a long training period from August to December 2022, which included 15 students. It aimed to popularize science through practical activities; transfer knowledge to young students; sensitize and guide them to pursue academic-scientific careers; reduce stereotypes about scientific work and scientists; and help students understand the social, political, and ethical roles of science within society. All activities were led by postgraduate students and professors from our postgraduate program, physicians, nurses, physiotherapists, biomedicals, and veterinarians from Hospital Israelita Albert Einstein, as well as medical students from Faculdade Israelita de Ciências da Saúde Albert Einstein . Activities in the short training included lectures on cinema and science, strategies to combat fake news, non-violent communication, innovation, design-thinking framework, and developing a scientific project. During the long training period, discussions were focused on nanotechnology, animal research, big data, bioinformatics, meditation, blood and bone marrow donation, telemedicine, sex and sexually-transmitted infections, rehabilitation, career opportunities, and scientific integrity. In addition, practical activities were further expanded using optical and confocal microscopy, cytometry, and basic concepts regarding the structure and function of living cells. The program also included the launching of the open-air outreach Education E-natureza activity, which turned students into ambassadors of nature. In conclusion, the Scientists of Tomorrow Program was innovative and enabled young students to learn that science is a collective activity that can enhance public health.

Diabetes tipo 2 e transplante renal: estudo comparativo sobre adesão medicamentosa / Diabetes tipo 2 y trasplante renal: estudio comparativo sobre la adhesión farmacológica / Type 2 diabetes and kidney transplant: comparative study on medication adherence

Resumo Objetivo Investigar a adesão medicamentosa no Diabetes Mellitus tipo 2 entre transplantados renais e não transplantados. Métodos Estudo comparativo entre pacientes assistidos no Centro de Diabetes (Grupo 1 sem transplante renal) e no Ambulatório de Pós-Transplante Renal do Hospital do Rim e da Hipertensão (Grupo 2 com transplante renal), ambos na cidade de São Paulo. A amostra foi composta por maiores de 18 anos, com diagnóstico de diabete tipo 2 prévio e em uso de medicamentos para o controle glicêmico. A coleta de dados ocorreu de outubro de 2017 a outubro de 2018. Aplicou-se aos participantes: formulário sócio clínico, instrumento de Medida de Adesão ao Tratamento Medicamentoso no Diabetes Mellitus (antidiabéticos orais e insulina) e a escala de Ansiedade e Depressão. O projeto foi aprovado no Comitê de Ética e Pesquisa como 0712/2017. Resultados Amostra composta de 107 pacientes (Grupo 1: 56 e Grupo 2: 51), maior porcentagem de homens, média de idade de 63,3 anos, provenientes da região metropolitana de São Paulo, aposentados, casados, com sobrepeso, sem sintomas de ansiedade e depressão. Os pacientes autorreferiram ter adesão aos medicamentos para o controle do diabetes, porém os resultados da hemoglobina glicada variaram entre 8,3 e 8,7% entre os grupos, ambos acima de 7%. Conclusão Ao analisar a relação entre a adesão autorreferida, hemoglobina glicada, ansiedade e depressão não foi possível evidenciar correlação estatisticamente significante. Os parâmetros avaliados neste estudo não permitiram estabelecer a relação de causa e efeito.

Resumen Objetivo Investigar la adhesión farmacológica en la Diabetes mellitus tipo 2 en trasplantados renales y no trasplantados. Métodos Estudio comparativo entre pacientes atendidos en el Centro de Diabetes (Grupo 1 sin trasplante renal) y en los Consultorios Externos de Postrasplante Renal del Hospital del Riñón y de la Hipertensión (Grupo 2 con trasplante renal), ambos en la ciudad de São Paulo. La muestra fue formada por mayores de 18 años, con diagnóstico previo de diabetes tipo 2 y en uso de medicamentos para control glucémico. La recopilación de datos se realizó de octubre de 2017 a octubre de 2018. Se aplicaron los siguientes instrumentos a los participantes: formulario socio-clínico, instrumento de Medida de Adhesión al Tratamiento Farmacológico (antidiabéticos orales e insulina) y escala de Ansiedad y Depresión. El proyecto fue aprobado por el Comité de Ética e Investigación con el número 0712/2017. Resultados Muestra formada por 107 pacientes (Grupo 1: 56 y Grupo 2: 51), mayor porcentaje de hombres, promedio de edad 63,3 años, provenientes de la región metropolitana de São Paulo, jubilados, casados, con sobrepeso, sin síntomas de ansiedad y depresión. Los pacientes autodeclararon adherir a los medicamentos para el control de la diabetes, pero los resultados de la hemoglobina glicosilada variaron entre 8,3 y 8,7 % entre los grupos, más de 7 % en ambos. Conclusión Al analizar la relación entre la adhesión autodeclarada, la hemoglobina glicosilada, la ansiedad y la depresión, no se observó correlación estadísticamente significativa. Los parámetros evaluados en este estudio no permitieron establecer una relación de causa y efecto.

Abstract Objective To investigate medication adherence in type 2 Diabetes Mellitus among kidney transplant recipients and non-transplant recipients. Methods Comparative study between patients assisted at the Diabetes Center (Group 1 without kidney transplant) and at the Post-Renal Transplant Outpatient Clinic of the Hospital do Rim e da Hipertensão (Group 2 with kidney transplant), both in the city of São Paulo. The sample consisted of people over 18 years of age with a previous diagnosis of type 2 diabetes using medication for glycemic control. The data collection period was from October 2017 to October 2018. The following was applied to participants: socio-clinical form, instrument for Measuring Adherence to Medication Treatment in Diabetes Mellitus (oral antidiabetics and insulin) and the Anxiety and Depression scale. The project was approved by the Research Ethics Committee as 0712/2017. Results Sample composed of 107 patients (Group 1: 56 and Group 2: 51), higher percentage of men, mean age of 63.3 years, from the metropolitan region of São Paulo, retired, married, overweight, without symptoms of anxiety and depression. Even though patients self-reported adherence to medication for diabetes control, results of glycated hemoglobin ranged between 8.3 and 8.7% between groups, both above 7%. Conclusion When analyzing the relationship between self-reported adherence, glycated hemoglobin, anxiety and depression, a statistically significant correlation could not be found. The parameters evaluated in this study did not allow establishing a cause and effect relationship.

A Machine Learning Model for Predicting Hospitalization in Patients with Respiratory Symptoms during the COVID-19 Pandemic.

A machine learning approach is a useful tool for risk-stratifying patients with respiratory symptoms during the COVID-19 pandemic, as it is still evolving. We aimed to verify the predictive capacity of a gradient boosting decision trees (XGboost) algorithm to select the most important predictors including clinical and demographic parameters in patients who sought medical support due to respiratory signs and symptoms (RAPID RISK COVID-19). A total of 7336 patients were enrolled in the study, including 6596 patients that did not require hospitalization and 740 that required hospitalization. We identified that patients with respiratory signs and symptoms, in particular, lower oxyhemoglobin saturation by pulse oximetry (SpO2) and higher respiratory rate, fever, higher heart rate, and lower levels of blood pressure, associated with age, male sex, and the underlying conditions of diabetes mellitus and hypertension, required hospitalization more often. The predictive model yielded a ROC curve with an area under the curve (AUC) of 0.9181 (95% CI, 0.9001 to 0.9361). In conclusion, our model had a high discriminatory value which enabled the identification of a clinical and demographic profile predictive, preventive, and personalized of COVID-19 severity symptoms.

The 2021-2022 position of Brazilian Diabetes Society on diabetic kidney disease (DKD) management: an evidence-based guideline to clinical practice. Screening and treatment of hyperglycemia, arterial hypertension, and dyslipidemia in the patient with DKD.

BACKGROUND: Diabetic kidney disease is the leading cause of end-stage renal disease and is associated with increased morbidity and mortality. This review is an authorized literal translation of part of the Brazilian Diabetes Society (SBD) Guidelines 2021-2022. This evidence-based guideline provides guidance on the correct management of Diabetic Kidney Disease (DKD) in clinical practice. METHODS: The methodology was published elsewhere in previous SBD guidelines and was approved by the internal institutional Steering Committee for publication. Briefly, the Brazilian Diabetes Society indicated 14 experts to constitute the Central Committee, designed to regulate methodology, review the manuscripts, and make judgments on degrees of recommendations and levels of evidence. SBD Renal Disease Department drafted the manuscript selecting key clinical questions to make a narrative review using MEDLINE via PubMed, with the best evidence available including high-quality clinical trials, metanalysis, and large observational studies related to DKD diagnosis and treatment, by using the MeSH terms [diabetes], [type 2 diabetes], [type 1 diabetes] and [chronic kidney disease]. RESULTS: The extensive review of the literature made by the 14 members of the Central Committee defined 24 recommendations. Three levels of evidence were considered: A. Data from more than 1 randomized clinical trial or 1 metanalysis of randomized clinical trials with low heterogeneity (I2 < 40%). B. Data from metanalysis, including large observational studies, a single randomized clinical trial, or a pre-specified subgroup analysis. C: Data from small or non-randomized studies, exploratory analyses, or consensus of expert opinion. The degree of recommendation was obtained based on a poll sent to the panelists, using the following criteria: Grade I: when more than 90% of agreement; Grade IIa 75-89% of agreement; IIb 50-74% of agreement, and III, when most of the panelist recommends against a defined treatment. CONCLUSIONS: To prevent or at least postpone the advanced stages of DKD with the associated cardiovascular complications, intensive glycemic and blood pressure control are required, as well as the use of renin-angiotensin-aldosterone system blocker agents such as ARB, ACEI, and MRA. Recently, SGLT2 inhibitors and GLP1 receptor agonists have been added to the therapeutic arsenal, with well-proven benefits regarding kidney protection and patients' survival.

Hyperkalemia in Diabetes Mellitus Setting.

Diabetes mellitus is a global health problem that affects 9.3% of the worldwide population and is associated with a series of comorbidities such as heart failure (HF) and chronic kidney disease (CKD). Diabetic patients, especially those with associated CKD, are more susceptible to present potassium disorders, in particular hyperkalemia due to kidney disease progression or use of renin-angiotensin-aldosterone blockers. Hyperkalemia is a potentially life-threatening condition that increases the risk of cardiac arrhythmia episodes and sudden death, making the management of potassium levels a challenge to reduce the mortality rate in this population. This review aims to briefly present the potassium physiology and discuss the main conditions that lead to hyperkalemia in diabetic individuals, the main signs, symptoms, and exams for the diagnosis of hyperkalemia, and the steps that should be followed to manage patients with this potentially life-threatening condition.

Hypokalemia in Diabetes Mellitus Setting.

Diabetes mellitus is a public health problem that affects millions of people worldwide regardless of age, sex, and ethnicity. Electrolyte disturbances may occur as a consequence of disease progression or its treatment, in particular potassium disorders. The prevalence of hypokalemia in diabetic individuals over 55 years of age is up to 1.2%. In patients with acute complications of diabetes, such as diabetic ketoacidosis, this prevalence is even higher. Potassium disorders, either hypokalemia or hyperkalemia, have been associated with increased all-cause mortality in diabetic individuals, especially in those with associated comorbidities, such as heart failure and chronic kidney disease. In this article, we discuss the main conditions for the onset of hypokalemia in diabetic individuals, briefly review the pathophysiology of acute complications of diabetes mellitus and their association with hypokalemia, the main signs, symptoms, and laboratory parameters for the diagnosis of hypokalemia, and the management of one of the most common electrolyte disturbances in clinical practice.

Evaluation of psychological symptoms in patients before and after simultaneous pancreas-kidney transplantation: a single-center cross-sectional study

Purpose: Simultaneous pancreas-kidney transplantation (SPKT) brings several benefits for insulin-dependent type-1 diabetic patients associated with end-stage renal disease (ESRD). However, data on psychological outcomes for the waiting list and the transplanted patients are still lacking. Methods: Using the psychological Beck inventories of anxiety (BAI) and depression (BDI), 39 patients on the waiting list were compared to 88 post-transplanted patients who had undergone SPKT. Results: Significant differences were found regarding depression (p = 0.003) but not anxiety (p = 0.161), being the pretransplant patients more vulnerable to psychological disorders. Remarkable differences were observed relative to the feeling of punishment (p < 0.001) and suicidal thoughts (p = 0.008) between the groups. It was observed that patients who waited a longer period for the transplant showed more post-transplant anxiety symptoms due to the long treatment burden (p = 0.002). Conclusions: These results demonstrated the positive impact of SPKT on psychological aspects related to depression when comparing the groups. The high number of stressors in the pretransplant stage impacts more severely the psychosocial condition of the patient.

Therapeutic Potential of Mesenchymal Stem Cells in a Pre-Clinical Model of Diabetic Kidney Disease and Obesity.

Diabetic kidney disease (DKD) is a worldwide microvascular complication of type 2 diabetes mellitus (T2DM). From several pathological mechanisms involved in T2DM-DKD, we focused on mitochondria damage induced by hyperglycemia-driven reactive species oxygen (ROS) accumulation and verified whether mesenchymal stem cells (MSCs) anti-oxidative, anti-apoptotic, autophagy modulation, and pro-mitochondria homeostasis therapeutic potential curtailed T2DM-DKD progression. For that purpose, we grew immortalized glomerular mesangial cells (GMCs) in hyper glucose media containing hydrogen peroxide. MSCs prevented these cells from apoptosis-induced cell death, ROS accumulation, and mitochondria membrane potential impairment. Additionally, MSCs recovered GMCs' biogenesis and mitophagy-related gene expression that were downregulated by stress media. In BTBRob/ob mice, a robust model of T2DM-DKD and obesity, MSC therapy (1 × 106 cells, two doses 4-weeks apart, intra-peritoneal route) led to functional and structural kidney improvement in a time-dependent manner. Therefore, MSC-treated animals exhibited lower levels of urinary albumin-to-creatinine ratio, less mesangial expansion, higher number of podocytes, up-regulation of mitochondria-related survival genes, a decrease in autophagy hyper-activation, and a potential decrease in cleaved-caspase 3 expression. Collectively, these novel findings have important implications for the advancement of cell therapy and provide insights into cellular and molecular mechanisms of MSC-based therapy in T2DM-DKD setting.

COVID-19: angiotensin-converting enzyme 2 (ACE2) expression and tissue susceptibility to SARS-CoV-2 infection.

COVID-19 pandemic is caused by the novel coronavirus SARS-CoV-2. Angiotensin-converting enzyme 2 (ACE2) is not only an enzyme but also a functional receptor on cell surfaces through which SARS-CoV-2 enters the host cells and is highly expressed in the heart, kidneys, and lungs and shed into the plasma. ACE2 is a key regulator of the renin-angiotensin-aldosterone system (RAAS). SARS-CoV-2 causes ACE/ACE2 balance disruption and RAAS activation, which leads ultimately to COVID-19 progression, especially in patients with comorbidities, such as hypertension, diabetes mellitus, and cardiovascular disease. Therefore, ACE2 expression may have paradoxical effects, aiding SARS-CoV-2 pathogenicity, yet conversely limiting viral infection. This article reviews the existing literature and knowledge of ACE2 in COVID-19 setting and focuses on its pathophysiologic involvement in disease progression, clinical outcomes, and therapeutic potential.

Klotho and Mesenchymal Stem Cells: A Review on Cell and Gene Therapy for Chronic Kidney Disease and Acute Kidney Disease.

Chronic kidney disease (CKD) and acute kidney injury (AKI) are public health problems, and their prevalence rates have increased with the aging of the population. They are associated with the presence of comorbidities, in particular diabetes mellitus and hypertension, resulting in a high financial burden for the health system. Studies have indicated Klotho as a promising therapeutic approach for these conditions. Klotho reduces inflammation, oxidative stress and fibrosis and counter-regulates the renin-angiotensin-aldosterone system. In CKD and AKI, Klotho expression is downregulated from early stages and correlates with disease progression. Therefore, the restoration of its levels, through exogenous or endogenous pathways, has renoprotective effects. An important strategy for administering Klotho is through mesenchymal stem cells (MSCs). In summary, this review comprises in vitro and in vivo studies on the therapeutic potential of Klotho for the treatment of CKD and AKI through the administration of MSCs.

Modifiable Variables Are Major Risk Factors for Posttransplant Diabetes Mellitus in a Time-Dependent Manner in Kidney Transplant: An Observational Cohort Study.

Modifiable and nonmodifiable risk factors for developing posttransplant diabetes mellitus (PTDM) have already been established in kidney transplant setting and impact adversely both patient and allograft survival. We analysed 450 recipients of living and deceased donor kidney transplants using current immunosuppressive regimen in the modern era and verified PTDM prevalence and risk factors over three-year posttransplant. Tacrolimus (85%), prednisone (100%), and mycophenolate (53%) were the main immunosuppressive regimen. Sixty-one recipients (13.5%) developed PTDM and remained in this condition throughout the study, whereas 74 (16.5%) recipients developed altered fasting glucose over time. Univariate analyses demonstrated that recipient age (46.2 ± 1.3vs. 40.7 ± 0.6 years old, OR 1.04; P = 0.001) and pretransplant hyperglycaemia and BMI ≥ 25 kg/m2 (32.8% vs. 21.6%, OR 0.54; P = 0.032 and 57.4% vs. 27.7%, OR 3.5; P < 0.0001, respectively) were the pretransplant variables associated with PTDM. Posttransplant transient hyperglycaemia (86.8%. 18.5%, OR 0.03; P = 0.0001), acute rejection (P = 0.021), calcium channel blockers (P = 0.014), TG/HDL (triglyceride/high-density lipoprotein cholesterol) ratio ≥ 3.5 at 1 year (P = 0.01) and at 3 years (P = 0.0001), and tacrolimus trough levels at months 1, 3, and 6 were equally predictors of PTDM. In multivariate analyses, pretransplant hyperglycaemia (P = 0.035), pretransplant BMI ≥ 25 kg/m2 (P = 0.0001), posttransplant transient hyperglycaemia (P = 0.0001), and TG/HDL ratio ≥ 3.5 at 3-year posttransplant (P = 0.003) were associated with PTDM diagnosis and maintenance over time. Early identification of risk factors associated with increased insulin resistance and decreased insulin secretion, such as pretransplant hyperglycaemia and overweight, posttransplant transient hyperglycaemia, tacrolimus trough levels, and TG/HDL ratio may be useful for risk stratification of patients to determine appropriate strategies to reduce PTDM.

Anticancer Activities of the Quinone-Methide Triterpenes Maytenin and 22-ß-hydroxymaytenin Obtained from Cultivated Maytenus ilicifolia Roots Associated with Down-Regulation of miRNA-27a and miR-20a/miR-17-5p.

Natural triterpenes exhibit a wide range of biological activities. Since this group of secondary metabolites is structurally diverse, effects may vary due to distinct biochemical interactions within biological systems. In this work, we investigated the anticancer-related activities of the quinone-methide triterpene maytenin and its derivative compound 22-ß-hydroxymaytenin, obtained from Maytenus ilicifolia roots cultivated in vitro. Their antiproliferative and pro-apoptotic activities were evaluated in monolayer and three-dimensional cultures of immortalized cell lines. Additionally, we investigated the toxicity of maytenin in SCID mice harboring tumors derived from a squamous cell carcinoma cell line. Both isolated molecules presented pronounced pro-apoptotic activities in four cell lines derived from head and neck squamous cell carcinomas, including a metastasis-derived cell line. The molecules also induced reactive oxygen species (ROS) and down-regulated microRNA-27a and microRNA-20a/miR-17-5p, corroborating with the literature data for triterpenoids. Intraperitoneal administration of maytenin to tumor-bearing mice did not lead to pronounced histopathological changes in kidney tissue, suggesting low nephrotoxicity. The wide-ranging activity of maytenin and 22-ß-hydroxymaytenin in head and neck cancer cells indicates that these molecules should be further explored in plant biochemistry and biotechnology for therapeutic applications.

Mesenchymal stem cell therapy in acute kidney injury (AKI): review and perspectives.

INTRODUCTION: Acute kidney injury (AKI) is highly prevalent today. It has a multifactorial aetiology and affects people of all ages, genders and ethnicities. Its treatment is essentially supportive of renal function substitution, so new treatment alternatives such as mesenchymal stem cell therapy (MSCs) should be investigated. METHODS: This review encompasses our understanding of the main mechanisms of action of MSCs in preclinical models of AKI by renal pedicle clamping ischemia-reperfusion, chemotherapy (cisplatin) and kidney transplantation in small and large animals, as well as outcomes in patients with AKI due to ischemia and kidney transplantation. RESULTS: Cellular therapy with MSCs has benefits in preclinical studies of AKI through various mechanisms, such as anti-inflammatory, antiapoptotic, oxidative anti-stress, antifibrotic, immunomodulatory and proangiogenic. In humans, MSC therapy is safe and effective. However, the challenges of MSC cell therapy include investigating protocols about the optimal dose of these cells, the route and frequency of appropriate administration, and the design of further biodistribution studies over a long follow-up period. In addition, a better understanding of molecular signalling and cellular interactions in the microenvironment of each organ and tissue is needed in order to define the best time to administer MSCs. Another challenge would be to mitigate the heterogeneity of the profile of cultured MSCs through preconditioning approaches. CONCLUSIONS: Cellular therapy with MSCs is very promising and should be part of the treatment of AKI patients in combination with other approaches already available, helping to accelerate recovery and/or slow the progression to chronic kidney disease. Randomized, multicentre controlled studies are needed to develop robust protocols that validate population-based cell therapy with MSCs.

The quality of life in type I diabetic patients with end-stage kidney disease before and after simultaneous pancreas-kidney transplantation: a single-center prospective study.

Simultaneous pancreas-kidney transplantation (SPKT) aimed at increasing the life expectancy for diabetic patients with end-stage kidney disease (ESKD). However, the risks of surgery complications and immunosuppression therapy make it unclear if the SPKT positively impacts patient's quality of life (QoL). Using the Kidney Disease Quality of Life-Short-Form Health Survey (KDQOL-SF36) and Problems Areas in Diabetes (PAID) measurement tools, we compared the QoL of 57 patients on the pretransplant waiting list with that of 103 patients who had undergone SPKT. Posttransplantation patients were assessed within different time intervals (<1, 1-3, and >3 years). Mean KDQOL-SF36 scores were better among posttransplantation patients in the SF36 and KDQOL domains. It was also observed patients' stress reduction in PAID mean score (P = 0.011) after SPKT. We concluded that patients receiving SPKT had a better perception of QoL than did patients on the waiting list, and this positive perception remained almost entirely comparable over the three different intervals of the posttransplantation time. These positive results showed better outcomes when excluding patients that lost pancreas graft function. Further research is needed to compare diabetic patients with kidney transplant alone using specific measurement tools to evaluate patient's QoL.

Mesenchymal stem cell therapy in acute kidney injury (AKI): review and perspectives

SUMMARY INTRODUCTION: Acute kidney injury (AKI) is highly prevalent today. It has a multifactorial aetiology and affects people of all ages, genders and ethnicities. Its treatment is essentially supportive of renal function substitution, so new treatment alternatives such as mesenchymal stem cell therapy (MSCs) should be investigated. METHODS: This review encompasses our understanding of the main mechanisms of action of MSCs in preclinical models of AKI by renal pedicle clamping ischemia-reperfusion, chemotherapy (cisplatin) and kidney transplantation in small and large animals, as well as outcomes in patients with AKI due to ischemia and kidney transplantation. RESULTS: Cellular therapy with MSCs has benefits in preclinical studies of AKI through various mechanisms, such as anti-inflammatory, antiapoptotic, oxidative anti-stress, antifibrotic, immunomodulatory and proangiogenic. In humans, MSC therapy is safe and effective. However, the challenges of MSC cell therapy include investigating protocols about the optimal dose of these cells, the route and frequency of appropriate administration, and the design of further biodistribution studies over a long follow-up period. In addition, a better understanding of molecular signalling and cellular interactions in the microenvironment of each organ and tissue is needed in order to define the best time to administer MSCs. Another challenge would be to mitigate the heterogeneity of the profile of cultured MSCs through preconditioning approaches. CONCLUSIONS: Cellular therapy with MSCs is very promising and should be part of the treatment of AKI patients in combination with other approaches already available, helping to accelerate recovery and/or slow the progression to chronic kidney disease. Randomized, multicentre controlled studies are needed to develop robust protocols that validate population-based cell therapy with MSCs.