The potency of PLGA-Encapsulated Epigallocatechin Gallate (EGCG) as adjuvant therapy for chronic kidney disease

Chronic kidney disease (CKD) prevalence keeps increasing worldwide and being particular concern due to its morbidity and mortality. However, current CKD therapy are known to be economically costly and not necessarily provide better outcomes. Epigallocatechin gallate (EGCG) is one of the substances that widely studied as perspective therapeutic agents of CKD due to its anti-inflammatory, antioxidant, and enhancing mitochondrial function ability. However, the use of EGCG is limited to low bioavailability and poor pharmacokinetic profile. Encapsulation of EGCG with PLGA is expected to increase the efficacy of EGCG especially for its use as the kidney protective agent and optimize therapy of CKD. Thus, this study aims to analyze the potency of PLGA-encapsulated EGCG as the adjuvant therapy for CKD. This study was a narrative review summarizes studies related to current adjuvant therapy of CKD. EGCG has beneficial effects in reducing pro-inflammatory cytokines among chronic kidney disease. EGCG also can increase scavenging of free radicals to decrease reactive oxygen species. EGCG is known to enhance mitochondrial function and increase mitochondrial protection to prevent apoptosis in various kidney diseases. Combination of PLGA encapsulation with EGCG has a beneficial effect in improving the delivery, bioavailability, stability, and the pharmacokinetic profile of EGCG. PLGA-encapsulated EGCG also provides a better therapeutic effect on preventing and decreasing progression of kidney damage. Finally, this study concluded that combination of PLGA-encapsulated EGCG has a potency as the adjuvant therapy of CKD.

Covid Adult Mortality in Brazil: An Analysis of Multiple Causes of Death

ObjectiveThis study aimed to analyze the chain of events and contributing causes associated with COVID-19 adult mortality (30–69 years old), based on qualified data on CoD from three Brazilian capitals cities, Belo Horizonte, Salvador, and Natal, in 2020.MethodsData of all deaths among residents in the three capitals in 2020 were provided by these municipalities' routine Mortality Information System (SIM). Mentions B34.2 with the markers U07.1 and U07.2 in the death certificate identified COVID-19 deaths. We used a multiple-cause-of-death approach better to understand the complexity of the morbid process of COVID-19. Conditions that appeared more frequently in the same line or above the COVID-19 mentions in the death certificate were considered a chain-of-event. Conditions that occurred more often after the codes for COVID-19 were considered as contributing.ResultsIn 2020, 7,029 records from COVID-19 as the underlying cause of death were registered in SIM in the three capitals. Among these, 2,921 (41.6%) were deceased between 30 and 69 years old, representing 17.0% of deaths in this age group. As chain-of-events, the most frequent conditions mentioned were sepsis (33.4%), SARS (32.0%), acute respiratory failure (31.9%), unspecified lower respiratory infections (unspecified pneumonia) (20.1%), and other specified respiratory disorders (14.1%). Hypertension (33.3%), diabetes unspecified type (21.7%), renal failure (12.7%), obesity (9.8%), other chronic kidney diseases (4.9%), and diabetes mellitus type 2 (4.7%) were the most frequent contributing conditions. On average, 3.04 conditions were mentioned in the death certificate besides COVID-19. This average varied according to age, place of death, and capital.ConclusionThe multiple-cause analysis is a powerful tool to better understand the morbid process due to COVID-19 and highlight the importance of chronic non-communicable diseases as contributing conditions.

Epidemiology of Chronic Obstructive Pulmonary Disease (COPD) Comorbidities in Lithuanian National Database: A Cluster Analysis

Various comorbidities and multimorbidity frequently occur in chronic obstructive pulmonary disease (COPD), leading to the overload of health care systems and increased mortality. We aimed to assess the impact of COPD on the probability and clustering of comorbidities. The cross-sectional analysis of the nationwide Lithuanian database was performed based on the entries of the codes of chronic diseases. COPD was defined on the code J44.8 entry and six-month consumption of bronchodilators. Descriptive statistics and odds ratios (ORs) for associations and agglomerative hierarchical clustering were carried out. 321,297 patients aged 40–79 years were included; 4834 of them had COPD. A significantly higher prevalence of cardiovascular diseases (CVD), lung cancer, kidney diseases, and the association of COPD with six-fold higher odds of lung cancer (OR 6.66; p < 0.0001), a two-fold of heart failure (OR 2.61; p < 0.0001), and CVD (OR 1.83; p < 0.0001) was found. Six clusters in COPD males and five in females were pointed out, in patients without COPD—five and four clusters accordingly. The most prevalent cardiovascular cluster had no significant difference according to sex or COPD presence, but a different linkage of dyslipidemia was found. The study raises the need to elaborate adjusted multimorbidity case management and screening tools enabling better outcomes.

Pharmaceutical nanotechnology: from the bench to the market

Background Nanotechnology is considered a new and rapidly emerging area in the pharmaceutical and medicinal field. Nanoparticles, as drug delivery systems, impart several advantages concerning improved efficacy as well as reduced adverse drug reactions. Main body Different types of nanosystems have been fabricated including carbon nanotubes, paramagnetic nanoparticles, dendrimers, nanoemulsions, etc. Physicochemical properties of the starting materials and the selected method of preparation play a significant aspect in determining the shape and characteristics of the developed nanoparticles. Dispersion of preformed polymers, coacervation, polymerization, nano-spray drying and supercritical fluid technology are among the most extensively used techniques for the preparation of nanocarriers. Particle size, surface charge, surface hydrophobicity and drug release are the main factors affecting nanoparticles physical stability and biological performance of the incorporated drug. In clinical practice, many nanodrugs have been used for both diagnostic and therapeutic applications and are being investigated for various indications in clinical trials. Nanoparticles are used for the cure of kidney diseases, tuberculosis, skin conditions, Alzheimer’s disease, different types of cancer as well as preparation of COVID-19 vaccines. Conclusion In this review, we will confer the advantages, types, methods of preparation, characterization methods and some of the applications of nano-systems.

Activation of Notch3 in Renal Tubular Cells Leads to Progressive Cystic Kidney Disease

Background: Polycystic kidney disease (PKD) is a genetic disorder affecting millions of people worldwide that is characterized by fluid-filled cysts and leads to end-stage renal disease (ESRD). The hallmarks of PKD are proliferation and dedifferentiation of tubular epithelial cells, cellular processes known to be regulated by Notch signaling. Methods: We found increased Notch3 expression in human PKD and renal cell carcinoma biopsies. To obtain insight into the underlying mechanisms and the functional consequences of this abnormal expression, we developed a transgenic mouse model with conditional overexpression of the intracellular Notch3 (ICN3) domain specifically in renal tubules. We evaluated the alterations in renal function (creatininemia, BUN) and structure (cysts, fibrosis, inflammation) and measured the expression of several genes involved in Notch signaling and the mechanisms of inflammation, proliferation, dedifferentiation, fibrosis, injury, apoptosis and regeneration. Results: After one month of ICN3 overexpression, kidneys were larger with tubules grossly enlarged in diameter, with cell hypertrophy and hyperplasia, exclusively in the outer stripe of the outer medulla. After three months, mice developed numerous cysts in proximal and distal tubules. The cysts had variable sizes and were lined with a single- or multilayered, flattened, cuboid or columnar epithelium. This resulted in epithelial hyperplasia, which was observed as protrusions into the cystic lumen in some of the renal cysts. The pre-cystic and cystic epithelium showed increased expression of cytoskeletal filaments and markers of epithelial injury and dedifferentiation. Additionally, the epithelium showed increased proliferation with an aberrant orientation of the mitotic spindle. These phenotypic tubular alterations led to progressive interstitial inflammation and fibrosis. Conclusions: In summary, Notch3 signaling promoted tubular cell proliferation, the alignment of cell division, dedifferentiation and hyperplasia, leading to cystic kidney diseases and pre-neoplastic lesions.

Chronic kidney disease biomarkers and mortality among older adults: A comparison study of survey samples in China and the United States

Objectives Among older adults in China and the US, we aimed to compare the biomarkers of chronic-kidney-diseases (CKD), factors associated with CKD, and the correlation between CKD and mortality. Setting China and the US. Study design Cross-sectional and prospective cohorts. Participants We included 2019 participants aged 65 and above from the Chinese Longitudinal Healthy Longevity Study (CLHLS) in 2012, and 2177 from US National Health and Nutrition Examination Survey (NHANES) in 2011–2014. Outcomes Urinary albumin, urinary creatinine, albumin creatinine ratio (ACR), serum creatinine, blood urea nitrogen, plasma albumin, uric acid, and estimated glomerular filtration rate (eGFR). CKD (ACR ≥ 30 mg/g or eGFR< 60 ml/min/1.73m2) and mortality. Analytical approach Logistic regression and Cox proportional hazard models. Covariates included age, sex, race, education, income, marital status, health condition, smoking and drinking status, physical activity and body mass index. Results Chinese participants had lower levels of urinary albumin, ACR, and uric acid than the US (mean: 25.0 vs 76.4 mg/L, 41.7 vs 85.0 mg/g, 292.9 vs 341.3 μmol/L). In the fully-adjusted model, CKD was associated with the risk of mortality only in the US group (hazard ratio [HR], 95% CI: 2.179, 1.561–3.041 in NHANES, 1.091, 0.940–1.266 in CLHLS). Compared to eGFR≥90, eGFR ranged 30–44 ml/min/1.73m2 was only associated with mortality in the US population (HR, 95% CI: 2.249, 1.141–4.430), but not in the Chinese population (HR, 95% CI: 1.408, 0.884–2.241). Conclusions The elderly participants in the US sample had worse CKD-related biomarker levels than in China sample, and the association between CKD and mortality was also stronger among the US older adults. This may be due to the biological differences, or co-morbid conditions.

Complicações renais decorrentes da infecção por SARS-CoV-2 em pessoas com COVID-19 hospitalizadas: scoping review

Objetivos: Identificar complicações/sequelas renais decorrentes da infecção por SARS-CoV-2 em pessoas com COVID-19; e descrever a característica de idade da população estudada. Metodologia: Scoping Review realizada nas bases de dados Web of Science, BVS, Cochrane Library, MEDLINE/PubMed, CINAHL, SCOPUS, Embase, LILACS. E nos sites online: ProQuest Dissertations and Theses, Grey Literature e Google Scholar. Os descritores utilizados foram (comorbidity OR sequel OR complications), (kidney diseases OR glomerular disease OR acute kidney injury OR nephropathy) AND (coronavirus OR SARS-CoV-2 OR COVID-19). Critérios de inclusão: artigos em português, inglês e espanhol, com abordagens metodológicas diversas, disponíveis na íntegra, online, publicados no período de 01 de janeiro de 2020 a 29 de setembro de 2021. E de exclusão: pessoas com diagnósticos prévios de patologias renais agudas e/ou crônicas; cartas ao editor; artigos de opinião; editoriais; e notas. Resultados: Selecionaram-se 10 artigos, que evidenciaram que o processo infeccioso causado pelo SARS-CoV-2 pode iniciar com uma leve proteinúria e hematúria, e evoluir para uma injúria renal aguda causada pela diminuição da capacidade de filtração glomerular, que favorece a retenção de algumas escórias nitrogenadas, causando o aumento dos níveis de creatinina e de ureia. Ademais, informaram que indivíduos entre 52-69 anos foram os mais acometidos. Considerações finais: As complicações/sequelas renais decorrentes da infecção por SARS-CoV-2 são: deposição de imunocomplexos nas células renais, proteinúria, hematúria, aumento da creatinina sérica, aumento da ureia nitrogenada no sangue, diminuição da TFG, e IRA estágio 1, 2 e 3. Tais complicações ocorreram principalmente em pessoas com idade ≥ 52 anos.

Abnormal Iron and Lipid Metabolism Mediated Ferroptosis in Kidney Diseases and Its Therapeutic Potential

Ferroptosis is a newly identified form of regulated cell death driven by iron-dependent phospholipid peroxidation and oxidative stress. Ferroptosis has distinct biological and morphology characteristics, such as shrunken mitochondria when compared to other known regulated cell deaths. The regulation of ferroptosis includes different molecular mechanisms and multiple cellular metabolic pathways, including glutathione/glutathione peroxidase 4(GPX4) signaling pathways, which are involved in the amino acid metabolism and the activation of GPX4; iron metabolic signaling pathways, which are involved in the regulation of iron import/export and the storage/release of intracellular iron through iron-regulatory proteins (IRPs), and lipid metabolic signaling pathways, which are involved in the metabolism of unsaturated fatty acids in cell membranes. Ferroptosis plays an essential role in the pathology of various kidneys diseases, including acute kidney injury (AKI), chronic kidney disease (CKD), autosomal dominant polycystic kidney disease (ADPKD), and renal cell carcinoma (RCC). Targeting ferroptosis with its inducers/initiators and inhibitors can modulate the progression of kidney diseases in animal models. In this review, we discuss the characteristics of ferroptosis and the ferroptosis-based mechanisms, highlighting the potential role of the main ferroptosis-associated metabolic pathways in the treatment and prevention of various kidney diseases.

Weight Change Alters the Small RNA Profile of Urinary Extracellular Vesicles in Obesity

Introduction: Various kidney diseases reportedly show different urinary extracellular vesicles (EVs) RNA profiles. Although obesity is one of the main causes of chronic kidney disease, the expression pattern of urinary EVs RNA in obesity is uncertain. Our aim was to sequence the small RNA profiles of urinary EVs in obese patients before and after weight reduction and compared them to those of healthy volunteers (HVs). Methods: We recruited age-sex matched obese patients and HVs. The small RNA profiles of urinary EVs were analyzed using RNA sequencing. To evaluate the effect of weight reduction, small RNA profiles of urinary EVs 6 months after bariatric surgery were also analyzed. Results: The proportion of urinary EVs transfer RNA and microRNA of obese patients differed from that of HVs. Obese patients showed differential expression of 1343 small RNAs in urinary EVs compared to HVs (|fold change| ≥ 2 and p value < 0.05). Among those, 61 small RNAs were upregulated in obese patients and downregulated after weight reduction, whereas 167 small RNAs were downregulated in obese patients and upregulated after weight reduction. RNA sequencing revealed the correlation between the specific urinary EVs small RNAs and clinical parameters including body weight, low-density lipoprotein cholesterol, triglyceride, high-density lipoprotein cholesterol, serum glucose, estimated glomerular filtration rate, and albuminuria. Conclusion: Obese patients showed distinct urinary EVs small RNA profiles compared to HVs. Weight reduction altered urinary EVs small RNA profiles in obese patients.