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.

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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.

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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.

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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.

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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.

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Coronavirus disease 2019 (COVID-19) is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). It has resulted in an ongoing worldwide pandemic since it was first recognized in December 2019. The kidney is one of the organs most easily affected by COVID-19. The injury of the kidney by COVID-19 manifested as hematuria, proteinuria, serum creatinine fluctuations, and even acute kidney injury (AKI). Critically ill patients with COVID-19 are much more prone to suffer from AKI. Moreover, AKI is related to poor outcomes in the patients infected with SARS-CoV-2. Therefore, early detection and active prevention of kidney injury are very important. In this article, we reviewed the epidemiology, clinical characteristics, pathogenesis, pathological manifestations, treatment, and prognosis of kidney injury in patients with COVID-19. It is expected to provide valuable insights for disease prevention and control from the perspective of nephrologists.

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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.

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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.

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Objective: The aim of the study was to analyze the clinical features of elderly patients with coronavirus disease 2019 (COVID-19) and to explore the relationship between COVID-19 patients and kidney injury. Methods: A total of 188 elderly patients with confirmed COVID-19 enrolled in this study were hospitalized for at least 1 week in the Central Theater Command General Hospital of Chinese People's Liberation Army from January 3, 2020 to March 14, 2020. The recorded information included clinical data and results of kidney-related laboratory tests. Retrospective analysis was performed. Results: The median age of the patients was 69 years (interquartile range 65–78, range: 60–97 years); 31.4% were 60–74 years old, and 68.6% were over 75 years old. A total of 12.8% and 18.6% of the patients were in critical and severe stages of COVID-19, respectively. The proportions of patients using mechanical ventilators and deaths were 9.5% and 8.5%, respectively. A total of 26.1% and 8.5% of the patients showed mild elevation of blood urea nitrogen (BUN) and serum creatinine (SCr) levels at admission. A total of 18.6% and 5.9% of the patients had elevated BUN and SCr 1 week after admission, respectively. A total of 3.1% of the patients were diagnosed with acute kidney injury, and 75% of those patients had chronic kidney disease before admission. Compared with the patients aged 60–74 years, those over 75 years exhibited significantly increased proportions of elevated BUN levels, critical illness, use of mechanical ventilated, and death. Multivariate logistic regression analysis revealed that an elevated BUN level at admission and 1 week after admission were independent risk factors for death in the elderly patients with COVID-19. Conclusion: There were more critical cases and a high mortality in elderly patients with COVID-19. An increased BUN level was an independent risk factor for death in elderly patients with COVID-19.

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Premature ejaculation (PE) is a frequently reported sexual dysfunction that has received considerable clinical attention in China. Being intrinsically related to cultural aspects, PE in the Chinese scientific environment is often treated using a combination of traditional Chinese medicine (TCM) techniques and a Western biomedical approach. In this perspective article, we highlight the most recent effects of the use of acupuncture, herbal medicine, and Fangzhongshu techniques, each alone and in combination with Western medicine, for delaying ejaculation; however, the efficacy of such therapies is not always supported by high-quality randomized control trials. To bridge the traditional holistic, individual-targeted perspective of TCM with Western biomedical approaches, we present the paradigm of the new Systems Sexology, derived from the well-known systems medicine, which may fill this gap by perfectly blending the most advanced technologies for an innovative, integrative, and interdisciplinary approach.

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Drug-induced nephrotoxicity is a common cause of acute kidney injury (AKI), and drug-induced AKI (DI-AKI) is becoming a serious public health concern. DI-AKI can be triggered by multiple drugs, alone or in combination. The incidence, pathological mechanisms, and risk factors of DI-AKI are largely unknown. Thus, there is a need for greater monitoring of DI-AKI to reduce the risks of serious complications and other hazards related to DI-AKI. This review summarizes the epidemiology of DI-AKI, along with its potential pathogenesis, associated drugs, independent risk factors, and possible early biomarkers. Additionally, because certain traditional Chinese medicine (TCM) prescriptions and their components have been reported to prevent and treat some types of DI-AKI (e.g., contrast-induced AKI), this review summarizes TCM methods for the prevention and treatment of DI-AKI.

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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.

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Background and Objectives: Patients on maintenance hemodialysis (MHD) are at high risk for coronavirus disease 2019 (COVID-19). However, patients undergoing MHD who are infected with COVID-19 are not fully studied. The objective of this study is to describe the characteristics of patients with COVID-19 undergoing MHD and provide a basis for the recognition and prevention of COVID-19 infection. Materials and Methods: Patients undergoing MHD were assigned into the normal group (537 cases), diagnosed group (66 cases), and suspected group (24 cases). General data, clinical symptoms, hemodialysis indicators, and laboratory indicators were collected and compared. Results: A total of 627 patients undergoing MHD were evaluated. The prevalence of COVID-19 was 10.53% (66/627), mortality was 18.18% (12/66), and death rate was 1.91% (12/627). In addition, 26% of patients were asymptomatic. Cough was the most common symptom (36%), followed by fatigue (16%), dyspnea (16%), and fever (13%). Ultrafiltration volume, ultrafiltration rate, and the duration of weekly dialysis in the diagnosed group were significantly lower than those in the other two groups. Moreover, neutrophil ratio and neutrophil, monocyte, and total carbon dioxide levels in the diagnosed group were significantly higher than those in the normal group, and the lymphocyte ratio was considerably lower than in the normal group. Sixty-five of the suspected and diagnosed patients had positive pulmonary CT findings. Conclusion: Compared with the general population, patients on hemodialysis have a significantly higher risk of contracting COVID-19 and postinfection mortality. Moreover, most patients undergoing hemodialysis have no obvious clinical symptoms after infection with COVID-19 but only have pulmonary changes which make it particularly important to screen and manage patients undergoing hemodialysis on outpatient basis.

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The etiology of the epidemics of obesity and diabetes has commonly been attributed to the western diet rich in sugars and fat. More recent studies suggest that the epidemic may have evolutionary origins. Specifically, fructose appears to be a unique nutrient that acts to reduce ATP levels in the cell, creating an alarm signal that activates an orchestrated response that includes hunger, foraging, the stimulation of fat accumulation in the adipose, liver and blood, the development of insulin resistance, a rise in blood pressure, and systemic inflammation. This constellation of findings is similar to what is called as the metabolic syndrome, but is a protective system to aid survival in settings of food shortage. Uric acid generated from ATP depletion appears to be central in driving the biologic process. Here we discuss the role of uric acid in obesity, metabolic syndrome and chronic kidney disease. A key finding is that a mutation in uric acid metabolism occurring during our past that aided survival but that today is acting as an amplifier driving the obesity response to western diet. Uric acid is emerging as a key target in the mechanisms driving metabolic syndrome and kidney disease.

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Coronavirus disease 2019 (COVID-19) has a broad spectrum of clinical manifestations involving the respiratory, cardiovascular, renal, neuropsychiatric, gastrointestinal, and dermatological systems. Some patients with COVID-19 experience acute infection and post-COVID-19 syndrome. There is increasing evidence that TGF-β signaling plays an important role in the pathogenesis of both acute and chronic COVID-19 infection. The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) nucleocapsid protein was reported to interact with Smad3, a key downstream mediator of TGF-β signaling, thereby promoting TGF-β1/Smad3 signaling and causing cell death during the acute phase of COVID-19 infection. Because activation of TGF-β/Smad3 signaling has an essential role in multiple organ fibrosis, it is possible that overreactive TGF-β/Smad3 signaling may cause tissue fibrosis in the lung, heart, and kidney after SARS-CoV-2 infection. Thus, not only administration of antiviral drugs and traditional Chinese medicines, but also targeting of TGF-β signaling components, particularly Smad3, with various therapeutic strategies involving OT-101, pirfenidone, and specific Smad3 inhibitors, such as SIS3, may provide novel and specific therapies for COVID-19 patients.

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Background and Objectives: Older adults are more susceptible to coronavirus disease 2019 (COVID-19). Interleukin-6 (IL-6) is an important cytokine in the cytokine release syndrome (CRS), and tocilizumab blocks the IL-6 receptor. The objective is to analyze the effect of tocilizumab on CRS in older patients with severe COVID-19. Materials and Methods: Between February 10 and March 21, 2020, a total of 19 patients aged ≥60 years with severe or critical COVID-19 met the study inclusion criteria at the Tongji Hospital in Wuhan City, Hubei Province, China. The patients were divided into two groups: the tocilizumab group, with IL-6 levels, which exceeded the upper limit of normal by >10-fold and non-tocilizumab group. Results: Patients in the tocilizumab group were older (73.20 ± 4.44 vs. 66.21 ± 5.06 years, P = 0.014), had lower lymphocyte counts (0.71 ± 0.18 vs. 1.18 ± 0.59 × 10⁹/L, P = 0.016), and higher high-sensitivity C-reactive protein (hsCRP) levels (94.04 ± 57.24 vs. 51.65 ± 45.37 mg/L, P = 0.035). Increases in ferritin (FER) and hsCRP levels in patients in the tocilizumab group were marked. Except for one patient who died, IL-6, FER, hsCRP levels, and the neutrophil/lymphocyte ratio in the remaining four patients decreased following treatment with tocilizumab. Tocilizumab did not cause any serious adverse reactions. There were no differences in mortality, days until lung computerized tomography improvement, or renal function between the two groups. The total mortality rate was 10.53%. Conclusions: Our results support the therapeutic efficacy and safety of tocilizumab in older patients with severe COVID-19.

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Coronavirus disease (COVID-19) has spread worldwide and has resulted in high mortality, increased pressure on medical systems, and severe global economic losses. Hemodialysis patients may be highly susceptible to infections due to old age, immunocompromised status, preexisting comorbidities, and frequent hospital visits. Moreover, the closed and crowded environment of dialysis rooms increases the risk of cross-infections. The Wuhan Hemodialysis Quality Control Center has accumulated valuable experience in the prevention and control of the COVID-19 epidemic and has normalized management of the epidemic since early 2020. In this review, we garnered experiences and knowledge from China and worldwide to summarize an approach to COVID-19 prevention, control, and management in hemodialysis patients under normalized epidemic conditions.

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Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus-2, is a major public health threat worldwide. However, there are no clinically approved antiviral drugs for COVID-19. Traditional Chinese medicine (TCM) is an important part of complementary and alternative medicine. Based on the TCM principles of pathogenesis, our team proposed “San Tong strategies” (san tong liao fa) and the “Truncation and Reversion strategy” (jie duanniu zhuan ce lve) and developed a Chinese herbal medicine formula to dispel external pathogens, clear heat, drain fire, and detoxify. A 50-year-old man with severe COVID-19 was admitted and received our oral Chinese herbal formula, acupoint plaster application, and moxibustion for 14 days. The computed tomography manifestations of COVID-19 showed marked improvements, and the patient achieved complete remission of fever, cough, fatigue, dizziness, nasal congestion, and rhinorrhea. This case provides a specific TCM treatment plan and effective reference for the treatment of COVID-19.

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Diabetic nephropathy (DN) is a severe microvascular complication of diabetes mellitus that is one of the main causes of end-stage renal disease, causing considerable health problems as well as significant financial burden worldwide. The pathological features of DN include loss of normal nephrons, massive fibroblast and myofibroblast hyperplasia, accumulation of extracellular matrix proteins, thickening of the basement membrane, and tubulointerstitial fibrosis. Renal fibrosis is a final and critical pathological change in DN. Although progress has been made in understanding the pathogenesis of DN fibrosis, current conventional treatment strategies may not be completely effective in preventing the disease’s progression. Traditionally, Chinese herbal medicines (CHMs) composed of natural ingredients have been used for symptomatic relief of DN. Increasing numbers of studies have confirmed that CHMs can exert a renoprotective effect in DN, and antifibrosis has been identified as a key mechanism. In this review, we summarize the antifibrotic efficacy of CHM preparations, single herbal medicines, and their bioactive compounds based on their effects on diminishing the inflammatory response and oxidative stress, regulating transforming growth factor, preventing epithelial-mesenchymal transition, and modulating microRNAs. We intend to provide patients of DN with therapeutic interventions that are complementary to existing options.

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The Omicron variant of severe acute respiratory syndrome coronavirus 2 remains a global problem. Current data indicate that the Omicron variant causes mild clinical symptoms and few severe cases and deaths. Traditional Chinese medicine (TCM) has demonstrated definite efficacy and distinct advantages in the prevention and treatment of coronavirus disease 2019 (COVID-19). Thus, by focusing on the pathogenic characteristics of the Omicron variant, the Emergency Professional Committee of the World Federation of Chinese Medicine Societies, Emergency and Critical Care Institute of the Shanghai University of Traditional Chinese Medicine, and American Traditional Chinese Medicine Society have brought together clinical experts on the TCM prevention and control of COVID-19 to formulate an expert consensus on the prevention and treatment of Omicron variant infections based on the Diagnosis and Treatment Protocol for COVID-19 (Trial Version 9). This review provides a comprehensive Coronavirus disease 2019 (COVID-19) is an acute respiratory infectious disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The main symptoms of interpretation of this expert consensus, covering topics such as discussing the pathogenic characteristics of the Omicron variant from the TCM perspective of “epidemic disease of pathogenic wind,” prevention plans for vulnerable populations, and stratified treatment plans for infected populations. We hope that this review can serve as a reference for the clinical prevention and treatment of the Omicron variant.

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