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Left ventricular remodeling commonly complicates end-stage renal disease following chronic kidney disease (CKD). This study investigated the therapeutic efficacy of resveratrol (RSV), a polyphenolic compound, on left ventricular remodeling in subtotal nephrectomy rats and sought to uncover the underlying molecular mechanisms. Subtotal nephrectomy caused renal dysfunction, such as gradual increases in serum creatinine and blood urea nitrogen, glomerular sclerosis, and tubulointerstitial fibrosis. In addition, subtotal nephrectomy also resulted in significant increases in myocyte cross-sectional area, interstitial and perivascular fibrosis, and left ventricular dilatation. All these detrimental effects were alleviated in the presence of RSV. Mechanistically, RSV treatment led to the upregulation of manganese-containing superoxide dismutase (MnSOD) in the heart. Coimmunoprecipitation studies showed that silent information regulator 1 (Sirt1) bound forkhead box protein O1 (FoxO1) and thus reduced acetylated FoxO1. RSV strengthened this interaction between Sirt1 and FoxO1. Loss of one allele of Sirt1 aggravated renal damage, myocyte hypertrophy, and interstitial fibrosis in nephrectomized mice. Taken together, our data show that Sirt1 is an important mediator for the protective roles of RSV on renal and heart damage in CKD rodent model, and FoxO1 and MnSOD are likely downstream targets of Sirt1. Therefore, Sirt1 might be a potential therapeutic target for the treatment of left ventricular remodeling caused by CKD.

Transforming growth factor β1 (TGF-β1) plays a central role in chronic kidney diseases. TGF-β1 induction causes podocyte injury, which results in proteinuria and renal failure. However, the effect of the prostaglandin E2 /E-prostanoid receptor (EP2) on TGF-β1-induced podocyte injury remains unknown. Previous studies have shown that phosphoinositide 3-OH kinase (PI3K)/Akt is widespread in cells, and is vital for the regulation of cell proliferation, differentiation, apoptosis and metabolism. In this study, we cultured immortalized mouse podocytes in vitro in different groups: control group; TGF-β1 (5ng/ml) group; EP2 agonist Butaprost treatment (10−7, 10−6, or 10-5mol/L) +TGF-β1 group; EP2 antagonist AH6809 treatment (10−7, 10−6, or 10-5mol / L) + TGF-β1 group. We found that compared with the control group, proliferation of podocytes in the TGF-β1 group significantly decreased and apoptosis increased. Expression of cAMP decreased, whereas PGE2 increased. Meanwhile, expressions of nephrin, podocin and CD2AP mRNA and protein were dramatically downregulated, activated caspase-3 was increased, and activated PI3K/Akt activity were depressed. Butaprost intervention promoted podocyte proliferation with reduced apoptosis. Conversely, AH6809 intervention led to opposite results (P<0.05). Our findings suggested that EP2 agonist protects podocytes by increasing expression of cAMP, which creates feedback of inhibiting PGE2 expression. This causes the interaction of nephrin, podocin and CD2AP resulting the inhibition of apoptosis induced by activation of the PI3K / Akt signaling pathway.

Cardiovascular and renal inflammation induced by Aldosterone (Aldo) plays a pivotal role in the pathogenesis of hypertension and renal fibrosis. GSK‐3β contributes to inflammatory cardiovascular and renal diseases, but its role in Aldo‐induced hypertension, and renal damage is not clear. In the present study, rats were treated with Aldo combined with SB‐216763 (a GSK‐3β inhibitor) for 4 weeks. Hemodynamic, cardiac, and renal parameters were assayed at the indicated time. Here we found that rats treated with Aldo presented cardiac and renal hypertrophy and dysfunction. Cardiac and renal expression levels of molecular markers attesting inflammation and fibrosis were increased by Aldo infusion, whereas the treatment of SB‐216763 reversed these alterations. SB‐216763 suppressed cardiac and renal inflammatory cytokines levels (TNF‐a, IL‐1β, and MCP‐1). Meanwhile, SB‐216763 increased the protein levels of LC3‐II in the cardiorenal tissues as well as p62 degradation, indicating that SB‐216763 induced autophagy activation in cardiac, and renal tissues. Importantly, inhibition of autophagy by 3‐MA attenuated the role of SB‐216763 in inhibiting perivascular fibrosis, and tubulointerstitial injury. These data suggest that SB‐216763 protected against Aldo‐induced cardiac and renal injury by activating autophagy, and might be a therapeutic option for salt‐sensitive hypertension and renal fibrosis.

Objective To establish a simple model for predicting postoperative acute kidney injury (AKI) requiring renal replacement therapy (RRT) in patients with renal insufficiency (CKD stages 3–4) who underwent cardiac surgery. Methods A total of 330 patients were enrolled. Among them, 226 were randomly selected for the development group and the remaining 104 for the validation group. The primary outcome was AKI requiring RRT. A nomogram was constructed based on the multivariate analysis with variables selected by the application of the least absolute shrinkage and selection operator. Meanwhile, the discrimination, calibration, and clinical power of the new model were assessed and compared with those of the Cleveland Clinic score and Simplified Renal Index (SRI) score in the validation group. Results: The rate of RRT in the development group was 10.6% ( n = 24), while the rate in the validation group was 14.4% ( n = 15). The new model included four variables such as postoperative creatinine, aortic cross‐clamping time, emergency, and preoperative cystatin C, with a C-index of 0.851 (95% CI, 0.779–0.924). In the validation group, the areas under the receiver operating characteristic curves for the new model, SRI score, and Cleveland Clinic score were 0.813, 0.791, and 0.786, respectively. Furthermore, the new model demonstrated greater clinical net benefits compared with the Cleveland Clinic score or SRI score. Conclusions We developed and validated a powerful predictive model for predicting severe AKI after cardiac surgery in patients with renal insufficiency, which would be helpful to assess the risk for severe AKI requiring RRT.