Diabetic kidney disease (DKD), a major microvascular complication of diabetes mellitus, has become the second cause of end-stage renal disease enhancing the mortality rate of diabetes. However, there are still few treatment approaches to combat it. Traditional Chinese medicine (TCM) has been applied for a long time to treat DKD. However, there is a lack of research on how does TCM plays the role in treating DKD due to the complex of composition of TCM. In recent decade, gut microbiota is increasingly recognized for its contributions to host health, and the occurrence of gut–kidney axis also attracts many interests about microbiota in kidney injury. Some of the studies have already revealed that TCM can alleviate the symptoms of DKD through regulating gut microbiota and ameliorate a vicious circle caused by imbalance of gut–kidney axis. However, the problems of which specific species mediates the efficacy of TCM and how gut microbiota influences the process of DKD are urgent to solve. Therefore, this review systematically summarized the application of TCM and the importance of gut microbiota in DKD. More importantly, the review provided a new insight to find biomarkers for diagnosis and treatment of DKD. In future study, targeted manipulation of the gut microbiota will be progressively recognized as a way to enhance human health.

[ABSTRACT]  [FULL TEXT]  [PDF]  [Mobile Full text]  [EPub] [CITATIONS]

[FULL TEXT]  [PDF]  [Mobile Full text]  [EPub] [CITATIONS]

Evidence has been furnished that immune cells, and immune-podocytes interactions have increasingly become the focus of proteinuric kidney diseases, which affect millions of patients worldwide. Podocytes are highly specialized, terminally differentiated epithelial cells that wrap around the glomerulus to maintain the integrity of the glomerular filtration barrier. More recent studies demonstrate that podocytes express many elements of the innate and adaptive immune system including the complement components and receptors, through which podocytes can be involved in immune-mediated glomerular injuries and as a therapeutic target to alleviate the podocyte injury and progression to chronic kidney disease. The present review will shed light on recent findings, which have furthered our understanding of the immune mechanisms involved in podocyte injury, as well as the therapeutic implications in the treatment of immune-mediated glomerular injury.

[ABSTRACT]  [FULL TEXT]  [PDF]  [Mobile Full text]  [EPub] [CITATIONS]

Objective: To explore the potential mechanism of Xiaochaihu decoction (XCHD) in the treatment of diabetic kidney disease (DKD) by network pharmacology and molecular docking technology. Materials and Methods: Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform was used to screen out main active components of XCHD. Gene names of target proteins were obtained with UniProt database. DKD targets were collected by GeneCard database, and common targets were selected through jvenn platform. STRING database was used to construct a protein–protein interaction network. Enrichment analysis was carried out through the Metascape platform. The “drug–component–target” and “component–target–KEGG pathway” networks were constructed using Cytoscape software. Molecular docking analysis was carried out with AutoDockTool software. Results: A total of 195 active components were obtained for XCHD. There were 238 corresponding targets and 128 common targets associated with DKD, and the core targets involved IL6, AKT1, VEGFA, TNF, TP53, PTGS2, and JUN. Gene ontology enrichment analysis revealed 2242 entries for biological processes, 82 entries for cellular components, and 166 items of molecular functions. A total of 333 signal pathways were screened by KEGG pathway enrichment analysis. Molecular docking showed that quercetin, baicalin, luteolin, and wogonin were tightly bound to the key target proteins of PTGS2 and AKT1. Conclusions: 195 active components were screened from XCHD, among which 128 intersections with DKD were identified, and 333 signaling pathways were identified by KEGG pathway enrichment analysis.The key active components in XCHD, such as quercetin, baicalin, luteolin and wogonin, regulate multiple signaling pathways by acting on PTGS2, AKT1 and other targets, for anti-inflammatory, antioxidant, regulating cell factors, improving insulin resistance, and protecting renal function. This study provides a more in-depth scientific basis and research direction for the investigation on XCHD treatment of DKD.

[ABSTRACT]  [FULL TEXT]  [PDF]  [Mobile Full text]  [EPub] [CITATIONS]

Background and Objective: The traditional Chinese Tangshen formula (TSF) has been reported to ameliorate diabetic kidney disease (DKD) in humans and animals. However, the effect of TSF on renal fibrosis remains unclear. Transforming growth factor-β1 (TGF-β1)/Smad3 signaling and lncRNA MEG3 are important in renal fibrosis. In this study, we examined the therapeutic effect of TSF on renal fibrosis and explored whether it was related to the modulation of TGFβ1/Smad3 signaling and lncRNA MEG3 expression. Materials and Methods: Experiments were performed in rats in vivo and in the HK2 cells in vitro. DKD was induced in rats by uninephrectomy combined with a single streptozotocin injection. The HK2 cells were stimulated by high glucose (HG) to explore the mechanism of TSF effects in vitro. Results: TSF significantly attenuated renal injury by lowering proteinuria and renal histological damage in DKD rats. TSF reduced collagen deposition by decreasing the expression of the fibrotic indicators collagen I, collagen IV, and fibronectin at the protein and mRNA levels, which suggested that TSF ameliorated DKD by decreasing renal fibrosis. Furthermore, TSF decreased TGF-β1 expression and suppressed the levels of phosphorylated Smad3 and Smad2/3 in vivo. Moreover, TSF downregulated the lncRNA MEG3 level in DKD rats. TSF reversed the upregulation of collagen I and fibronectin expression and downregulated Smad2/3 phosphorylation in the HK2 cells stimulated with HG. Conclusions: TSF ameliorates renal fibrosis in rats with DKD by suppressing TGF-β1/Smad3 signaling and lncRNA MEG3 expression.

[ABSTRACT]  [FULL TEXT]  [PDF]  [Mobile Full text]  [EPub] [CITATIONS]

Cell death and inflammation are important mechanisms in the induction of acute kidney injury (AKI) and the progression of chronic kidney disease. This focused review examines how the JUN amino terminal kinase (JNK) enzyme contributes to these pathologies. The JNK enzyme is activated in response to cellular stress, being most sensitive to oxidative stress. Biopsy studies have shown that JNK signaling is activated in human AKI and chronic kidney injury. Genetic and pharmacologic strategies have demonstrated a key role for JNK signaling in tubular cell death, inflammation, and loss of renal function in various animal models of AKI. This has been directly attributed to JNK1 signaling in the proximal tubular epithelial cells. JNK inhibition also reduces cell death, inflammation, and fibrosis in several models of progressive kidney disease; however, not all models show benefit with JNK blockade. JNK inhibitors are currently in clinical trials which opens the way for testing JNK-based therapy in selected types of renal injury. Some of the outstanding questions in this field include identifying the JNK1 target(s) in the induction of tubular cell necroptosis, and determining whether the pro-inflammatory actions of JNK signalling depend solely upon activation of JUN/Activator Protein-1.

[ABSTRACT]  [FULL TEXT]  [PDF]  [Mobile Full text]  [EPub] [CITATIONS]

Membranoproliferative glomerulonephritis (MPGN) is usually characterized by refractory nephrotic syndrome and is associated with a poor prognosis. An older patient diagnosed with MPGN had a 20-year history of proteinuria and had clinical manifestations of nephrotic syndrome in the past 2 years. MPGN. Before the patients received an 11-month traditional Chinese medicine (TCM) treatment, the patient was treated with prednisone, tacrolimus, mycophenolate mofetil, and rituximab for 11 months. After 22 months, the urine protein level decreased to <1 g/d, with normal plasma albumin level, and remarkably increased glomerular filtration rate. Combination of TCM with Western medicine for 22 months was effective for the treatment of MPGN.

[ABSTRACT]  [FULL TEXT]  [PDF]  [Mobile Full text]  [EPub] [CITATIONS]

Background and Objectives: Chronic kidney disease (CKD) and acute kidney injury (AKI) increase the risk of serious disease and mortality in severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2)-infected patients. This study evaluated the occurrence and outcome of AKI in CKD and non-CKD patients infected with SARS-CoV-2. Subjects and Methods: We retrospectively analyzed the medical records of 845 patients with SARS-CoV-2 infection regarding the occurrence and outcome of AKI in a coronavirus disease-2019 (COVID-19)-designated hospital in Wuhan, China, from December 31, 2019, to March 20, 2020. Results: Of the 845 COVID-19 patients, 91 had CKD and 754 had no CKD (non-CKD), of whom 22 and 14 developed AKI, respectively. Finally, 36 patients were included in the analysis. Older patients and those with cardiovascular or cerebrovascular diseases were more likely to develop AKI. More CKD patients progressed to critical illness (72.73%) than non-CKD patients (57.14%), but the degree of AKI in CKD patients was lesser than that in non-CKD patients. Higher urea nitrogen, creatinine, and proteinuria levels were observed in CKD patients. More non-CKD patients were treated with human albumin than CKD patients. The survival probability of CKD patients was lower than that of non-CKD patients, but it was not statistically significant. Conclusion: There were significant differences in the incidence rate of AKI after SARS-CoV-2 infection between CKD and non-CKD patients, and the clinical manifestations and treatments of AKI also differed. These results highlight the necessity of variable treatment methods for optimal clinical management.

[ABSTRACT]  [FULL TEXT]  [PDF]  [Mobile Full text]  [EPub] [CITATIONS]

[FULL TEXT]  [PDF]  [Mobile Full text]  [EPub] [CITATIONS]

The prevalence of diabetes has been sharply increasing over the past few decades. Approximately 20%–30% of patients with diabetes progress to evident nephropathy. Kidney cell deaths, for example, ferroptosis, pyroptosis, and apoptosis, are associated with diabetic nephropathy (DN). Ferroptosis is a novel regulated cell death characterized by the increase of oxidative stress and iron-dependent lipid peroxidation. Laboratory or clinical findings indicate that ferroptosis plays an important role in the pathogenesis of DN. This review aimed to summarize the mechanisms of ferroptosis and relevant signaling pathways in DN and provide perspectives and clinical strategies for attenuating ferroptosis-associated DN.

[ABSTRACT]  [FULL TEXT]  [PDF]  [Mobile Full text]  [EPub] [CITATIONS]