Diabetic kidney disease (DKD) remains the leading cause of chronic kidney disease (CKD) worldwide. The pathogenesis of DKD is influenced by functional, histopathological, and immune mechanisms, including NLRP3 inflammasome activity and oxidative stress. The sodium-glucose cotransporter 2 inhibitors (SGLT2i) have shown metabolic benefits and the ability to slow the progression of DKD in several clinical studies over the years. Recent studies suggest that the antidiabetic activity also extends to inhibition of the inflammatory response, including modulation of the NLRP3 inflammasome, reduction of pro-inflammatory markers and reduction of oxidative stress. Here we review the efficacy of SGLT2i in the treatment of CKD and discuss the role of the inflammatory response in the development of DKD, including its relationship to the NLRP3 inflammasome and oxidative stress.

Acellular amniotic membrane (AM) has been studied, with promising results on the reconstruction of lesioned tissues, and has become an attractive approach for tracheal repair. This study aimed to evaluate the repair of the trachea with human umbilical cord mesenchymal stem cells (hucMSCs) differentiated in chondrocytes, grown on an experimental model. Tracheal defects were induced by surgical tracheostomy in 30 New Zealand rabbits, and the acellular amniotic membrane, with or without cells, was covering the defect. The hucMSCs were isolated and cultivated with chondrogenic differentiation over the culture of 14 days, and then grown on the AM. In this study, the AM was biocompatible and hucMSCs differentiated into chondrocytes. Our results demonstrated an important role for AM with cultured cells in the promotion of immature collagen, known to produce tissue regeneration. In addition, cartilaginous tissue was found at the tracheal defects, demonstrated by immunohistology results. This study suggests that this biomaterial implantation can be an effective future therapeutic alternative for patients with tracheal injury.

Inflammatory response, oxidative stress, and pyroptosis play important roles in the pathogenesis of diabetic kidney disease (DKD), and the NOD-like receptor protein 3 (NLRP3) inflammasome complex and pyroptosis are possible cellular regulators dependent on these processes. Treatment of DKD relies on sodium-glucose cotransporter-2 inhibitors (SGLT2is); however, its effects on oxidative stress and the NLRP3 complex have not yet been fully elucidated. This study aimed to evaluate the role of a SGLT2i in the regulation of the redox system, inflammatory profile, and NLRP3 inflammasome in an experimental model of DKD. Briefly, C57BL/6 mice were subjected to a DKD model induced by the combination of a high-caloric diet and streptozotocin (40 mg/kg). The animals were exposed to empagliflozin 35 mg/kg, and clinical (plasma glucose, water and caloric intake, and weight gain) and functional (glycosuria and albuminuria) parameters were subsequently evaluated. After 25 weeks, the animals were euthanized for evaluation of histological parameters, redox activity, NLRP3 complex activity, and pyroptosis. Our results showed that DKD model animals had clinical features of DKD, namely, high body mass index, glucose levels, albuminuria, and glomerular area. Empagliflozin reduced glycemia levels, glomerular area, H₂O₂ levels, IL-1β, IL-1α, and TNF-α levels, lipid peroxidation, and protein carbonylation. It also improved urinary albumin excretion and decreased gasdermin D levels. No changes were observed in the NLRP3 complex proteins. In conclusion, the SGLT2i empagliflozin improved glycemic control and reduced glomerular damage through control of the redox profile and inflammatory parameters, indicating its potential as a treatment for DKD.

BACKGROUND: Covert hepatic encephalopathy (CHE) is difficult to detect due to the lack of easily applicable screening tools. The Stroop EncephalApp is a smartphone application already validated for CHE screening. However, its applicability to the Brazilian population is not known. OBJECTIVE: To estimate the prevalence of CHE and evaluate the use of Stroop EncephalApp in a cirrhotic population in Brazil. METHODS: In this cross-sectional study, we evaluated 99 patients previously diagnosed with liver cirrhosis in a Private Hospital in Curitiba/PR. Patients were initially submitted to the mini mental state examination (MMSE) to exclude individuals with dementia. After, the Psychometric Hepatic Encephalopathy Score (PHES) test was performed and lastly, the Stroop EncephalApp test. Results were adjusted for age, sex and education levels to evaluate the accuracy of the app on detecting the disease, comparing its results with the gold standard method (PHES). Patients with one or more of the following were excluded: dementia, inadequate MMSE score, illiteracy, color blindness, history of drugs/alcohol abuse within the past 3 months and previous or actual episodes of encephalopathy. The statistical analysis was performed by SPSS 2.0 and the significance adopted by 5%. RESULTS: We included 82 individuals in the final analysis. Among these patients, 29 were diagnosed with CHE by the PHES test (35.36% prevalence) and 28 of those obtained equal diagnosis by the Stroop EncephalApp (96.6% sensitivity). A total of 53 patients obtained negative results for CHE by PHES, while the Stroop test classified 27 of them as having the disease. In the multivariate analysis, high levels of education were associated with better performance during the tests. No significant relationship was observed between age and sex with the probability of diagnosing CHE through the PHES test.

Blume GG, et al. J Cardiovasc Imaging. 2021 May;29:e54. https://doi.org/10.4250/jcvi.2020.0241

Resumo A doença renal do diabetes (DRD) permanece como a principal causa de doença renal crônica (DRC) mundialmente. A patogênese da DRD é influenciada por mecanismos funcionais, histopatológicos e imunológicos, incluindo a atividade do inflamassoma NLRP3 e estresse oxidativo. Os inibidores do cotransportador de sódio-glicose 2 (iSGLT2) demonstraram benefícios metabólicos e a capacidade de retardar a progressão da DRD em diversos estudos clínicos ao longo dos anos. Estudos recentes sugerem que a atividade antidiabética também se estende à inibição da resposta inflamatória, incluindo modulação do inflamassoma NLRP3, redução de marcadores pró-inflamatórios e redução do estresse oxidativo. Aqui, avaliamos a eficácia dos iSGLT2 no tratamento da DRC e discutimos o papel da resposta inflamatória no desenvolvimento da DRD, incluindo sua relação com o inflamassoma NLRP3 e o estresse oxidativo.