Necrostatin-1 (Nec-1) inhibits necroptosis and is usually regarded as having no effect on other cell deaths. Here, this study explored whether the addition of Nec-1 has an effect on cell death induced by simulated ischemia injury in rat tubular cell line NRK-52E. In addition, we also investigated the mechanism of Nec-1 attenuates cell death in this renal ischemia model. The NRK-52E cells were incubated with TNF-α + antimycinA (TA) for 24 h with or without Nec-1. Cell death was observed under fluorescent microscope and quantified by flow cytometry. Cell viabilities were detected by MTT assay. The protein expression of dynamin-related protein 1 (Drp1) was detected by Western blotting and immunofluorescence assay. Increased cell death in simulated ischemia injury of NRK-52E cells were markedly attenuated in the Nec-1 pretreated ischemia injury group. Meanwhile, cell viability was significantly improved after using Nec-1. In addition, we also observed that the protein expression of Drp1, a mediator of mitochondrial fission, was significantly increased in simulated ischemia injury group. Increased Drp1 expression in the ischemia injury group can be abolished by Nec-1 or Drp1-knock down, accompanied with decreased cell death and improved cell viabilities. These results suggest that Nec-1 may inhibit cell death induced by simulated ischemia injury in the rat tubular cell line NRK-52E through decreased Drp1 expression.

Podocyte apoptosis is a major mechanism that leads to proteinuria in many kidney diseases. However, the concert mechanisms that cause podocyte apoptosis in these kidney diseases are not fully understood. RhoA is one of Rho GTPases that has been well studied and plays a key role in regulating cytoskeletal architecture. Previous study showed that insufficient RhoA could result in rat aortic smooth muscle cell apoptosis. However, whether RhoA is involved in podocyte apoptosis remains unknown. Culture podocytes were treated with LPS, ADR or siRNA for 48 h before harvest. Subcellular immunoblotting, qRT-PCR, immunofluorescence and flow cytometry were used to exam the expression and function of RhoA or YAP in podocytes. We found that the expression of RhoA and its activity were significantly decreased in LPS or ADR-injured podocytes, accompanying loss of stress fibers and increased cell apoptosis. Knocking down RhoA or its downstream effector mDia expression by siRNA also caused loss of stress fibers and podocyte apoptosis. Moreover, our results further demonstrated that RhoA deficiency could reduce the mRNA and protein expression of YAP, which had been regarded as an anti-apoptosis protein in podocyte. Silenced dendrin expression significantly abolished RhoA, mDia or YAP deficiency-induced podocyte apoptosis. RhoA deficiency could disrupt podocyte cytoskeleton and induce podocyte apoptosis by inhibiting YAP/dendrin signal. RhoA/mDia/YAP/dendrin signal pathway may potentially play an important role in regulating podocyte apoptosis. Maintaining necessary RhoA would be one potent way to prevent proteinuria kidney diseases.

Background: The correlation between proteinuria and contrast-induced acute kidney injury (CI-AKI) in patients with cerebrovascular disease is still unknown.Objective: To determine whether proteinuria is a risk factor for CI-AKI and death in patients with stroke undergoing cerebral angiography.Methods: Data from 2015 patients with stroke undergoing cerebral angiography between January 2009 and December 2013 were retrospectively collected. Clinical parameters were obtained from the hospital's computerized database. All variables were analyzed by univariate analysis and multivariate logistic regression analysis.Results: CI-AKI was seen in 85 patients (4.2%). After adjustment for potential confounding risk factors, patients with proteinuria had a fivefold higher risk of CI-AKI than patients without proteinuria (OR=5.74; 95% CI 2.23 to 14.83; p<0.001). Other independent risk factors for CI-AKI were estimated glomerular filtration rate <60 mL/min/1.73 m², anemia, and a high National Institute of Health Stroke Scale score. Proteinuria did not increase in-hospital mortality (OR=1.25; 95% CI 0.49 to 3.17; p=0.639) but did increase 1-year mortality (HR=2.30, 95% CI 1.55 to 3.41, p<0.001).Conclusions: Proteinuria is an independent risk factor for CI-AKI and 1-year mortality in patients with stroke undergoing cerebral angiography. More attention should be paid to the development of CI-AKI in patients with stroke with proteinuria.

Monocyte-to-lymphocyte ratio (MLR) and neutrophil-to-lymphocyte ratio (NLR) are considered as surrogate inflammatory indexes. Previous studies indicated that NLR was associated with the development of septic acute kidney injury (AKI). The objective of the present study was to explore the value of MLR and NLR in the occurrence of AKI in intensive care unit (ICU) patients. The clinical details of adult patients (n = 1500) who were admitted to the ICU from January 2016 to December 2019 were retrospectively examined. AKI was diagnosed according to the Kidney Disease: Improving Global Outcomes criteria. The development of AKI was the main outcome, and the secondary outcome was in-hospital mortality. Overall, 615 (41%) patients were diagnosed with AKI. Both MLR and NLR were positively correlated with AKI incidence (p < 0.001). Multivariate logistic regression analysis suggested that the risk value of MLR for the occurrence of AKI was nearly three-fold higher than NLR (OR = 3.904, 95% CI: 1.623‒9.391 vs. OR = 1.161, 95% CI: 1.135‒1.187, p < 0.001). The areas under the receiver operating characteristic curve (AUC) for MLR and NLR in the prediction of AKI incidence were 0.899 (95% CI: 0.881‒0.917) and 0.780 (95% CI: 0.755‒0.804) (all p < 0.001), with cutoff values of 0.693 and 12.4. However, the AUC of MLR and NLR in the prediction of in-hospital mortality was 0.583 (95% CI: 0.546‒0.620, p < 0.001) and 0.564 (95% CI: 0.528‒0.601, p = 0.001). MLR, an inexpensive and widely available parameter, is a reliable biomarker in predicting the occurrence of AKI in ICU patients.