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Oxidative stress plays a key role in chronic kidney disease (CKD) development and progression, inducing kidney cell damage, inflammation, and fibrosis. However, effective therapeutic interventions to slow down CKD advancement are currently lacking. The multifaceted pharmacological effects of molecular hydrogen (H2) have made it a promising therapeutic avenue. H2 is capable of capturing harmful •OH and ONOO- while maintaining the crucial reactive oxygen species (ROS) involved in cellular signaling. The NRF2-KEAP1 system, which manages cell redox balance, could be used to treat CKD. H2 activates this pathway, fortifying antioxidant defenses and scavenging ROS to counteract oxidative stress. H2 can improve NRF2 signaling by using the Wnt/β-catenin pathway and indirectly activate NRF2-KEAP1 in mitochondria. Additionally, H2 modulates NF-κB activity by regulating cellular redox status, inhibiting MAPK pathways, and maintaining Trx levels. Treatment with H2 also attenuates HIF signaling by neutralizing ROS while indirectly bolstering HIF-1α function. Furthermore, H2 affects FOXO factors and enhances the activity of antioxidant enzymes. Despite the encouraging results of bench studies, clinical trials are still limited and require further investigation. The focus of this review is on hydrogen's role in treating renal diseases, with a specific focus on oxidative stress and redox signaling regulation, and it discusses its potential clinical applications.

Plastic waste accumulation and its degradation into microplastics (MPs) and nanoplastics (NPs) pose environmental concerns. Previous studies have indicated that polystyrene (PS)-MPs harm living animals. Extracellular vesicles (EVs) are associated with metabolic reprogramming and mitochondrial dysfunction in various kidney diseases. In this article, we evaluated how PS-MPs affected tubular cells and fibroblasts. The results demonstrated that PS-MPs increased EV production in human tubular cells and caused endoplasmic reticulum (ER) stress-related proteins without inducing inflammation-related proteins in human tubular cells. The uptake of PS-MPs and incubation with the conditioned medium of PS-MPs induced reactive oxygen species (ROS) production and ER stress-related proteins in fibroblast cells. The fibroblast cells treated with the conditioned medium of PS-MPs also increased the expression of fibrosis-related proteins. Our findings suggested that the expression of EV-related markers increased in tubular cells via Beclin 1 after PS-MP treatment. In addition, PS-MPs induced ROS production in vitro and in vivo. We found that PS-MPs also altered the expression of EV markers in urine, and CD63 expression was also increased in vitro and in vivo after PS-MP treatment. In conclusion, PS-MP-induced EVs lead to ER stress-related proteins, ROS production and fibrosis-related proteins in tubular cells and fibroblasts.

Renal inflammation and fibrosis are significantly correlated with the deterioration of kidney function and result in chronic kidney disease (CKD). However, current therapies only delay disease progression and have limited treatment effects. Hence, the development of innovative therapeutic approaches to mitigate the progression of CKD has become an attractive issue. To date, the incidence of CKD is still increasing, and the biomarkers of the pathophysiologic processes of CKD are not clear. Therefore, the identification of novel therapeutic targets associated with the progression of CKD is an attractive issue. It is a critical necessity to discover new therapeutics as nephroprotective strategies to stop CKD progression. In this research, we focus on targeting a prostaglandin E2 receptor (EP2) as a nephroprotective strategy for the development of additional anti-inflammatory or antifibrotic strategies for CKD. The in silico study identified that ritodrine, dofetilide, dobutamine, and citalopram are highly related to EP2 from the results of chemical database virtual screening. Furthermore, we found that the above four candidate drugs increased the activation of autophagy in human kidney cells, which also reduced the expression level of fibrosis and NLRP3 inflammasome activation. It is hoped that these findings of the four candidates with anti-NLRP3 inflammasome activation and antifibrotic effects will lead to the development of novel therapies for patients with CKD in the future.

Drug-induced nephrotoxicity remains a common problem after exposure to medications and diagnostic agents, which may be heightened in the kidney microenvironment and deteriorate kidney function. In this study, the toxic effects of fourteen marked drugs with the individual chemical structure were evaluated in kidney cells. The quantitative structure–activity relationship (QSAR) approach was employed to investigate the potential structural descriptors of each drug-related to their toxic effects. The most reasonable equation of the QSAR model displayed that the estimated regression coefficients such as the number of ring assemblies, three-membered rings, and six-membered rings were strongly related to toxic effects on renal cells. Meanwhile, the chemical properties of the tested compounds including carbon atoms, bridge bonds, H-bond donors, negative atoms, and rotatable bonds were favored properties and promote the toxic effects on renal cells. Particularly, more numbers of rotatable bonds were positively correlated with strong toxic effects that displayed on the most toxic compound. The useful information discovered from our regression QSAR models may help to identify potential hazardous moiety to avoid nephrotoxicity in renal preventive medicine.

Deposition of extracellular matrix (ECM), epithelial-mesenchymal transition (EMT) and inflammation are crucial processes in chronic kidney disease (CKD) progression. The matrix metalloproteinases (MMPs) belong to a major enzyme group of proteinases that are involved in ECM degradation. MMP controls multiple biological processes, such as cell proliferation, EMT and apoptosis. The present study identified the roles of MMP7 in CKD progression. We demonstrated the transcriptional profiles of MMPs in kidney tissues of CKD patients in the Gene Expression Omnibus (GEO) data repository. MMP7 mRNA level was markedly upregulated in kidney tissues of CKD patients. MMP7 overexpression activated the NLRP3 and NLRP6 inflammasomes and increased fibrosis-related proteins in kidney cells. MMP7 inhibited oxidative stress-induced apoptosis and rapamycin-induced autophagy. We found that MMP7 expression in the kidney was increased in various CKD animal models. Knockdown of MMP7 affected renal function and renal fibrosis in a folic acid-induced CKD model. The inhibition of MMP7 decreased fibrosis and NLRP3 and NLRP6 inflammasomes and induced autophagy in kidney tissues. Taken together, these results provide insight into targeting MMP7 as a therapeutic strategy for CKD.

Background: Despite having a well-established pre-end-stage kidney disease (pre-ESKD) care program, Taiwan has a high incidence of ESKD. Unrecovered incident dialysis may lead to the maintenance of dialysis. Contrast medium (CM) or general anesthesia (GA) may also induce dialysis. We aimed to examine the trends for incident dialysis, use of CM or GA, and its long-term trajectory outcomes. Methods: Patients who received at least one dialysis intervention between 2010 and 2017 were identified using the National Health Insurance Research Database. We collected information on age, sex, comorbidities, causes of dialysis in outpatient or inpatient settings, use of CM or GA or pre-ESKD program enrolment before incident dialysis, and trajectory outcomes. Results: Incident dialysis occurred more frequently in elderly inpatients with infectious diseases or previous chronic kidney disease (CKD). The number of patients who had a pre-ESKD care plan before incident dialysis increased from 25% in 2010 to 41% in 2017 (P