Background: Diabetic nephropathy (DN) has been recognized as the leading cause of end-stage renal disease. Resveratrol (RSV), a polyphenolic compound, has been indicated to possess an insulin-like property in diabetes. In the present study, we aimed to investigate the renoprotective effects of RSV and delineate its underlying mechanism in early-stage DN. Methods: The protective effects of RSV on DN were evaluated in streptozotocin (STZ)-induced diabetic rats. Results: The plasma glucose, creatinine, and blood urea nitrogen were significantly elevated in STZ-induced diabetic rats. RSV treatment markedly ameliorated hyperglycemia and renal dysfunction in STZ-induced diabetic rats. The diabetes-induced superoxide anion and protein carbonyl levels were also significantly attenuated in RSV-treated diabetic kidney. The AMPK protein phosphorylation and expression levels were remarkably reduced in diabetic renal tissues. In contrast, RSV treatment significantly rescued the AMPK protein expression and phosphorylation compared to non-treated diabetic group. Additionally, hyperglycemia markedly enhanced renal production of proinflammatory cytokine IL-1β. RSV reduced IL-1β but increased TNF-α and IL-6 levels in the diabetic kidneys. Conclusions: Our findings suggest that RSV protects against oxidative stress, exhibits concurrent proinflammation and anti-inflammation, and up-regulates AMPK expression and activation, which may contribute to its beneficial effects on the early stage of DN.

The development of sodium-glucose transporter 2 inhibitor (SGLT2i) broadens the therapeutic strategies in treating diabetes mellitus. By inhibiting sodium and glucose reabsorption from the proximal tubules, the improvement in insulin resistance and natriuresis improved the cardiovascular mortality in diabetes mellitus (DM) patients. It has been known that SGLT2i also provided renoprotection by lowering the intraglomerular hypertension by modulating the pre- and post- glomerular vascular tone. The application of SGLT2i also provided metabolic and hemodynamic benefits in molecular aspects. The recent DAPA-CKD trial and EMPEROR-Reduced trial provided clinical evidence of renal and cardiac protection, even in non-DM patients. Therefore, the aim of the review is to clarify the hemodynamic and metabolic modulation of SGLT2i from the molecular mechanism.

Paraquat poisoning is characterized by multi-organ failure and pulmonary fibrosis with respiratory failure, resulting in high mortality and morbidity. The objective of this study was to identify predictors of mortality in cases of paraquat poisoning. Furthermore, we sought to determine the association between these parameters. A total of 187 patients were referred for management of intentional paraquat ingestion between January 2000 and December 2010. Demographic, clinical, and laboratory data were recorded. Sequential organ failure assessment (SOFA) and acute kidney injury network (AKIN) scores were collected, and predictors of mortality were analyzed. Overall hospital mortality for the entire population was 54% (101/187). Using a multivariate logistic regression model, it was found that age, time to hospitalization, blood paraquat level, estimated glomerular filtration rate at admission (eGFR _{first day}), and the SOFA_48-h score, but not the AKIN_48-h score, were significant predictors of mortality. For predicting the in-hospital mortality, SOFA_48-h scores displayed a good area under the receiver operating characteristic curve (AUROC) (0.795±0.033, P<0.001). The cumulative survival rate differed significantly between patients with SOFA_48-h scores <3 and those ≥3 (P<0.001). A modified SOFA (mSOFA) score was further developed by using the blood paraquat level, and this new score also demonstrated a better AUROC (0.848±0.029, P<0.001) than the original SOFA score. Finally, the cumulative survival rate also differed significantly between patients with mSOFA scores <4 and ≥4 (P<0.001). The analytical data demonstrate that SOFA and mSOFA scores, which are based on the extent of organ function or rate of organ failure, help to predict mortality after intentional paraquat poisoning.