Iron deficiency is highly prevalent in patients with heart failure (HF) complicated by chronic kidney disease (CKD), yet the efficacy of intravenous (IV) iron therapy remains unclear. We performed a meta-analysis of randomized controlled trials (RCTs) retrieved from Embase, PubMed, and the Cochrane Library from inception to January 1, 2026. A total of 8 RCTs involving 7009 participants were included. Clinical outcomes were assessed by generating forest plots using the random-effects model and pooling relative risks (RRs) or mean differences (MDs). IV iron therapy showed a significantly reduced incidence of first heart failure hospitalization or cardiovascular death (RR = 0.79, 95

Chronic kidney disease (CKD) is traditionally studied through an organ‑centric paradigm, despite its frequent coexistence with intestinal dysbiosis and metabolic dysfunction‑associated steatotic liver disease, which confers a 38% increased CKD risk. Multi‑organ crosstalk along the gut‑liver‑kidney axis remains inadequately addressed in current guidelines. The present study aimed to establish the gut‑liver‑kidney axis as an integrated systems biology framework for understanding CKD progression and to translate this framework into diagnostic, therapeutic and clinical trial strategies. The present review aimed to combine mechanistic summaries with systems biology perspectives, including weighted gene co‑expression network analysis, Bayesian causal inference and ordinary differential equation‑based dynamic modeling, to map bidirectional signaling across microbial, metabolic, inflammatory and hemodynamic dimensions, with diabetic kidney disease (DKD) as the principal exemplar. The axis operates through anatomically and molecularly defined positive feedback loops in which gut dysbiosis drives barrier failure and endotoxemia, amplifying hepatic lipotoxicity and bile acid dysregulation, precipitating renal tubular injury and fibrosis. This self‑perpetuating cycle, sustained by uremic toxin signaling, dysregulated peroxisome proliferator‑activated receptor/farnesoid X receptor (FXR)/Takeda G protein‑coupled receptor 5 (TGR5) pathways and trained immunity (a persistent hyperinflammatory state of innate immune cells driven by epigenetic and metabolic reprogramming), is most pronounced in DKD. Microbiome‑targeted interventions and FXR/TGR5 modulators are as the most clinically advanced axis‑directed strategies, though most remain at preclinical or early‑phase stages. Reframing CKD as gut‑liver‑kidney axis dysfunction enables systems‑level mechanistic integration, precision diagnostics through composite microbiome‑metabolomic signatures, and adaptive trial designs targeting upstream pathology, providing a foundation for incorporating axis‑based approaches into future CKD management.

Background:The gut microbiota-derived metabolite butyrate has been implicated in maintaining renal homeostasis through anti-inflammatory and immunomodulatory pathways. However, evidence from large-scale human studies, especially in high-risk diabetic populations, remains limited. This study aimed to investigate the association between butyrate exposure and renal function in adults with diabetes, using a dual-cohort design. Methods:We analyzed data from 7,723 adults with diabetes across ten NHANES cycles (1999-2018) to evaluate the association of dietary butyrate intake with estimated glomerular filtration rate (eGFR) and albuminuria. Multivariable linear regression, restricted cubic spline modeling, and subgroup analyses were performed with survey weighting. For external validation, we recruited a Chinese cohort of 70 patients with diabetic kidney disease (DKD) and measured serum butyrate and isobutyrate concentrations using UPLC-MS/MS. Associations with eGFR and 24-h urinary protein were assessed using adjusted regression models. Results:In the NHANES cohort, higher dietary butyrate intake was independently associated with a higher eGFR (β = 1.61; 95% CI: 0.29-2.92; p = 0.02), with a significant nonlinear dose-response (P for non-linearity = 0.0006). No significant associations were found with albuminuria. In the Chinese cohort, serum butyrate was positively associated with eGFR (β = 0.05; 95% CI: 0.01-0.08; p = 0.02), but not with proteinuria. Serum isobutyrate also showed a positive association with eGFR (β = 0.15; 95% CI: 0.02-0.28; p = 0.02). Sensitivity analyses confirmed the robustness of these findings among participants with both diabetes and CKD. Conclusion:This dual-cohort study provides the first epidemiological evidence that higher levels of butyrate-whether from dietary intake or serum concentration-are independently associated with better renal function in adults with diabetes. These findings underscore the relevance of the gut-kidney axis in diabetic kidney disease and suggest that enhancing endogenous butyrate production through diet or microbiota-targeted strategies may offer a novel avenue for renoprotection.

BACKGROUND AND PURPOSE:Extensive evidence indicates that lipid accumulation causes renal tubular injury, which further contributes to diabetic nephropathy (DN) progression. Short-chain fatty acids (SCFAs) play an important role in the maintenance of cellular metabolic health. Previous studies have found a significant deficiency of SCFAs in DN patients, although their effects on lipid accumulation in renal tubules have not been investigated. We have investigated the effect of sodium butyrate (NaB), one of the most abundant SCFAs, on renal tubular lipid accumulation in DN and elucidated its underlying protective mechanisms. EXPERIMENTAL APPROACH:The effects of NaB were investigated on renal tubular lipid accumulation in vitro (using a glucolipotoxicity-treated HK-2 cell line) and DN progression in vivo (with streptozotocin injection combined with a high-fat diet in C57BL/6J mice). RNA sequencing, surface plasmon resonance, pulldown MS assay, and molecular docking were applied to explore specific molecular mechanisms. KEY RESULTS:Our findings revealed that serum butyrate levels were reduced in DN patients and inversely correlated with DN severity. NaB supplementation improved renal tubular lipid accumulation and injury in HK-2 cells and DN mice. The protective effects of NaB were largely abrogated in kidney-specific Tfeb knockout mice. NaB directly interacted with PPP2R1A to promote the formation and activation of PP2A heterotrimers, thereby facilitating the dephosphorylation of TFEB and promoting lipophagy. CONCLUSIONS AND IMPLICATIONS:NaB functions as a PP2A-TFEB axis activator to restore lipophagy and ameliorate lipid accumulation in tubular epithelial cells, pointing to NaB as a promising protective agent against renal injury in DN patients.

Cardiovascular-renal-metabolic (CKM) syndrome substantially elevates the risk of cardiovascular disease (CVD). Environmental air pollution, especially particulate matter (PM), is a key contributor, yet its long-term effects across CKM stages remain unclear. This study aimed to evaluate the association between long-term exposure to different sizes of particulate matter (PM1, PM2.5, PM10) and CVD risk across the four stages of CKM syndrome. We conducted a nationwide prospective cohort study using data from the China Health and Retirement Longitudinal Study (CHARLS, 2011–2018), including 5,824 participants aged 45 years or older. CKM stages (0 to 3) were classified according to American Heart Association guidelines. Annual average concentrations of PM1, PM2.5, and PM10 were used to estimate individual exposure. Cox proportional hazards models were used to calculate adjusted hazard ratios (HRs), and population attributable fractions (PAFs) were estimated to assess the burden of air pollution on CVD. During a median follow-up of 7 years, participants in the highest exposure group of PM2.5 had significantly increased CVD risk (HR = 2.31, 95

ObjectiveThe aim of this study was to investigate the causal relationship between microbiota, diabetic nephropathy, and blood metabolites through a randomized Mendelian study.MethodsIn this study, we used 412 microbiota as exposures, 1,400 blood metabolites as intermediaries, and diabetic nephropathy as the outcome. We conducted a two-way Mendelian randomization (MR) analysis to explore the causal relationship between microbiota and diabetic nephropathy, followed by mediation analyses and two-step MR to identify potential blood metabolites.ResultsThere is a causal relationship between microbiota and diabetic nephropathy. Specific bacteria and metabolites, such as Escherichia coli str. K-12 substr. MG1655, Listeria monocytogenes 10403S, g_Adlercreutzia, g_Haemophilus, g_Bacteroides, and Escherichia coli CFT073, and metabolites like pyrraline, glycocholenate sulfate, alpha-ketoglutarate, tetradecadienoate (14:2), Cys-gly oxidized, methylsuccinate, and various others, were identified. Escherichia coli str. K-12 substr. MG1655 is positively related to alpha-ketoglutarate levels, while alpha-ketoglutarate levels and Sphingomyelin (d18:1/18:1, d18:2/18:0) are negatively related. The bacterial microbiota involved in fatty acid oxidation is associated with diabetic kidney disease (DKD) progression, positively correlated with glycocholenate sulfate levels, and negatively correlated with the phosphate linoleyl-tetraenyl-glycerol (18:2 to 20:4) ratio. Additionally, Listeria monocytogenes 10403S is positively correlated with N-acetyl-isoputreanine and negatively correlated with X-12462. Anaerobic fermentation-related bacteria were positively related to N-acetylcarnitine and 5-acetylamino-6-formyluracil and negatively correlated with 5-acetamino-6-amino-3-methyluracil (X-24243). Escherichia coli CFT073 was positively associated with X-16580. Interactions between Bacillus species and metabolites such as d18:1/18:1, d18:2/18:0, 2-aminophenol sulfate, and cholate were negative when compared to tetradecadienoate (14:2). g_Adlercreutzia is positively correlated with N-delta-acetylornithine, methylsuccinate, and N-acetyl-isoputreanine but negatively correlated with N-acetylglucosamine and N-acetylgalactosamine. g_Haemophilus was positively associated with arachidoylcarnitine but negatively correlated with X-24531. The results were heterogeneous and multi-efficacious.ConclusionsFor the first time, MR analysis provides supportive evidence for a bidirectional causal relationship between microbiota and diabetic nephropathy and identifies specific genes associated with the disease. The results suggest that probiotic therapy may play a significant role in preventing diabetic nephropathy and improving the quality of life and survival rates of affected patients. Furthermore, this study provides additional evidence of a causal relationship between specific microbiota, diabetic nephropathy, and blood metabolites.

The stress hyperglycemia ratio (SHR) is an emerging biomarker used to assess blood glucose levels under acute stress conditions and has been linked to the incidence of adverse clinical outcomes. However, the precise role of SHR in patients with diabetic kidney disease (DKD) and chronic kidney disease (CKD), particularly in relation to mortality, remains poorly understood. This study seeks to investigate the clinical value of SHR as a predictive tool for all-cause and cardiovascular mortality in these patient groups. This study analyzed data from the National Health and Nutrition Examination Survey (NHANES) spanning from 1999 to 2018, encompassing 3,507 individuals diagnosed with diabetic kidney disease (DKD) or chronic kidney disease (CKD). The primary endpoints included all-cause mortality and cardiovascular mortality, with mortality data obtained from the National Death Index (NDI) through December 31, 2019. Participants were categorized into quartiles based on the stress hyperglycemia ratio (SHR), and Cox proportional hazards regression models were employed to examine the association between SHR and mortality. Model 1 did not account for any covariates, Model 2 adjusted for age, sex, and race, while Model 3 additionally incorporated adjustments for educational attainment, marital status, body mass index, smoking behavior, hypertension, hyperlipidemia, and cardiovascular disease. The study comprised 3,507 patients with a mean age of 60.7 years, of whom 56

RATIONALE:Diabetic nephropathy (DN) is a significant clinical and public health burden worldwide whose magnitude underscores the urgent need for more effective treatment options. Excessive lipid accumulation in renal tubular cells leads to their injury and dysfunction, thereby contributing to DN progression, suggesting that the alleviation of renal tubular lipid accumulation is a potential strategy for treating DN. METHODS:The effects of paeonol (PAE), a natural phenolic compound, on renal tubular lipid accumulation were evaluated using a glucolipotoxicity-treated HK-2 cell line and C57BL/6 J mice treated with streptozotocin (STZ) injection combined with a high-fat diet (HFD). Autophagic flux and lipophagy were assessed through immunofluorescence, adenoviral mRFP-GFP-LC3 transfection, and western blotting. Small interfering RNA (siRNA) was used for in vitro experiments to silence Tfeb in HK-2 cells, while a Cre-loxP system was employed to induce Tfeb knockout specifically in renal tubules in vivo, to validate the therapeutic target of PAE. RNA sequencing, pulldown assays, surface plasmon resonance (SPR), and molecular docking were utilized to further explore the specific molecular mechanisms involved. RESULTS:We found that PAE dose-dependently alleviated renal tubular lipid accumulation in glucolipotoxicity-treated HK-2 cells and the DN mouse model. Mechanistically, PAE directly binds to RHEB, functioning as an mTOR suppressor, thereby activating TFEB to promote lysosome biogenesis and lipophagy, subsequently alleviating renal tubular lipid accumulation and DN progression. CONCLUSIONS:Per our findings, PAE holds promise as a therapeutic agent for DN, with the unique mechanism of activating renal TFEB-mediated lipophagy.

Background:At present, the side effects of hormonal and immunosuppressant therapy for intermediate-to-high risk primary membranous nephropathy (PMN) are relatively large, and the remission rate is limited, so more safe and effective regimens are needed. Methods:This study is a clinical prospective case series study. 31 patients were finally included. The intervention was cyclophosphamide (CTX) combined with "Shuli Fenxiao formula(SLFX formula)", and the patients were treated for 24 weeks. The observation nodes were baseline, 2 weeks、12weeks and 24weeks after treatment. Results:At 12 weeks of treatment, 38.7% of patients achieved partial response. At 24 weeks of treatment, 61.3% of patients achieved partial response and 24.5% achieved complete response. All Anti-phosholipase A2 Receptor Antibody (Anti-PLA2R) seropositive patients achieved immune remission. 24-hour urine total protein quantification (24hUTP) decreased from a median of 6.1 (IQR, 4.6-8.4) g/d to 2.7 (IQR, 0.6-8.7) g/d (P<0.001). Serum albumin (ALB) increased from 27.2 ± 6.4 g/L to 31.9 ± 8.0 (P<0.05). Within 24 weeks of follow-up after discharge, no patients relapsed. During the treatment follow-up period, 6 adverse events occurred in 31 patients, 1 patient developed heart failure during the treatment period, which was not considered to be clearly associated with treatment regimen or nephrotic syndrome (NS), 3 patients were infected, and 2 patients had liver impairment. Conclusion:The results suggest that the combination of CTX and SLFX formula dramatically decreased Anti-PLA2R titers and 24hUTP levels, increased ALB in short term. The combination was safe and had few adverse effects. It has the potential to be used as a potential option for the clinical treatment of intermediate-to-high risk PMN patients, particularly for elderly patients with contraindications to corticosteroid use or those with refractory disease. International Traditional Medicine Clinical Trial Registry:http://itmctr.ccebtcm.org.cn/, identifier ITMCTR2025000355.

Long-term exposure to ambient air pollution is a recognized environmental risk factor for chronic kidney disease (CKD), but its dynamic effects on kidney function remain incompletely understood. This nationwide longitudinal study included 5,306 participants from the China Health and Retirement Longitudinal Study (CHARLS) to examine associations between five major air pollutants (PM1, PM2.5, PM10, NO2, and O3) and kidney function decline, measured by the annual slope of estimated glomerular filtration rate (eGFR). Air pollutant exposures were assessed both as continuous variables and dichotomized by median levels. Higher exposure to PM1, PM2.5, PM10, and NO2 was consistently associated with faster eGFR decline. In fully adjusted models, each 1 μg/m3 increase in PM2.5 corresponded to a steeper decline in eGFR (β = -0.02; 95% CI: -0.03 to -0.02), while participants in high PM2.5 areas had an annual decline of -0.51 mL/min/1.73 m2 (95% CI: -0.72 to -0.31). O3 showed a significant association only in binary models. Weighted quantile sum regression identified PM2.5 and PM1 as dominant contributors. A favorable lifestyle markedly mitigated pollution-related decline; under high PM1 exposure, eGFR declined by -0.69 (95% CI: -1.06 to -0.33) in those with favorable lifestyles versus -2.20 (95% CI: -2.65 to -1.75) in those with unfavorable lifestyles. These findings were robust across multiple sensitivity analyses. These findings emphasize the adverse impact of long-term air pollution exposure on kidney function and suggest that healthy lifestyle behaviors may offer significant protective benefits.

Objective: To explore the neuroprotective effects of the Shaoyao Gancao decoction (SGD) against excitatory damage in PC12 cells and the role of the Src-NR2-nNOS pathway mediation by SGD in regulating γ-aminobutyric acid (GABA)-glutamate (Glu) homeostasis. Methods: N-Methyl-d-aspartic acid (NMDA) was used to establish a PC12 cell excitability injury model. To investigate the neuroprotective effect of SGD, a cell counting kit-8 (CCK-8) assay was used to determine PC12 cell viability, Annexin V/Propidium Iodide (Annexin V/PI) double staining was used to determine PC12 cell apoptosis, and Ca2+ concentration was observed using laser confocal microscopy. GABA receptor agonists and antagonists were used to analyze the neuroprotective interactions between γ-aminobutyric acid (GABA) and NMDA receptors. Additionally, molecular biology techniques were used to determine mRNA and protein expression in the Src-NR2-nNOS pathway. We analyzed the correlations between the regulatory sites of GABA and NMDA interactions, excitatory neurotoxicity, and brain damage at the molecular level. Results: NMDA excitotoxic injury manifested as a significant decrease in cell activity, increased apoptosis and caspase-3 protein expression, and a significant increase in intracellular Ca2+ concentration. Administration of SGD, a GABAA receptor agonist (muscimol), or a GABAB receptor agonist (baclofen) decreased intracellular Ca2+ concentrations, attenuated apoptosis, and reversed NMDA-induced upregulation of caspase-3, Src, NMDAR2A, NMDAR2B, and nNOS. Unexpectedly, a GABAA receptor antagonist (bicuculline) and a GABAB receptor antagonist (saclofen) failed to significantly increase excitatory neurotoxicity. Conclusions: Taken together, these results not only provide an experimental basis for SGD administration in the clinical treatment of central nervous system injury diseases, but also suggest that the Src-NR2A-nNOS pathway may be a valuable target in excitotoxicity treatment.

Introduction: The rising prevalence and severe consequences of nonalcoholic fatty liver disease (NAFLD) have driven the quest for preventive medications. Complanatoside A (CA) is the marked flavonoid of Astragali complanati semen, a traditional Chinese herb that acts on the liver meridian and is widely used to treat liver problems. CA has been proven to have considerable lipid-lowering and liver-protective effects in vitro. However, the efficacy of CA in preventing NAFLD has yet to be shown in vivo. Methods: First, the effectiveness of CA against NAFLD was assessed using a high-fat diet (HFD) mouse model. Second, the CA protective mechanism against NAFLD was investigated using a combined metabolomics and network pharmacology strategy. Differential metabolites were identified by metabolomics-based analyses, and metabolic pathway analysis was accomplished by MetaboAnalyst. Potential therapeutic targets were obtained through network pharmacology. Finally, key targets were identified via compound-target networks and validated by molecular docking and western blotting. Results: CA prevented NAFLD mainly by reducing liver lipid accumulation in HFD mice. Metabolomics identified 22 potential biomarkers for CA treatment of NAFLD, primarily involving glycerophospholipid and arachidonic acid metabolism. Fifty-one potential targets were determined by network pharmacology. Co-analysis revealed that albumin, peroxisome proliferator-activated receptor-alpha, retinoid X receptor alpha, interleukin-6, and tumor necrosis factor alpha were key targets. Conclusion: This experiment revealed that CA has a preventive effect on NAFLD, primarily by regulating the peroxisome proliferator-activated receptor-alpha/retinoid X receptor alpha pathway. Furthermore, it provides evidence supporting the potential use of CA in the long-term prevention of NAFLD.

Background Herbal nanoparticles are made from natural herbs/medicinal plants, their extracts, or a combination with other nanoparticle carriers. Compared to traditional herbs, herbal nanoparticles lead to improved bioavailability, enhanced stability, and reduced toxicity. Previous research indicates that herbal medicine nanomaterials are rapidly advancing and making significant progress; however, bibliometric analysis and knowledge mapping for herbal nanoparticles are currently lacking. We performed a bibliometric analysis by retrieving publications related to herbal nanoparticles from the Web of Science Core Collection (WoSCC) database spanning from 2004 to 2023. Data processing was performed using the R package Bibliometrix, VOSviewers, and CiteSpace.Results In total, 1876 articles related to herbal nanoparticles were identified, originating from various countries, with China being the primary contributing country. The number of publications in this field increases annually. Beijing University of Chinese Medicine, Shanghai University of Traditional Chinese Medicine, and Saveetha University in India are prominent research institutions in this domain. The Journal "International Journal of Nanomedicine" has the highest number of publications. The number of authors of these publications reached 8234, with Yan Zhao, Yue Zhang, and Huihua Qu being the most prolific authors and Yan Zhao being the most frequently cited author. "Traditional Chinese medicine," "drug delivery," and "green synthesis" are the main research focal points. Themes such as "green synthesis," "curcumin," "wound healing," "drug delivery," and "carbon dots" may represent emerging research areas.Conclusions Our study findings assist in identifying the latest research frontiers and hot topics, providing valuable references for scholars investigating the role of nanotechnology in herbal medicine.

Background: The gut-kidney axis refers to the interaction between the gastrointestinal tract and the kidneys, and its disorders have become increasingly important in the development of kidney diseases. The aim of this study is to identify current research hotspots in the field of the gut-kidney axis from 2003 to 2022 and provide guidance for future research in this field.Methods: We collected relevant literature on the gut-kidney axis from the Web of Science Core Collection (WoSCC) database and conducted bibliometric and visualization analyses using biblioshiny in R-Studio and VOSviewer (version 1.6.16).Results: A total of 3,900 documents were retrieved from the WoSCC database. The publications have shown rapid expansion since 2011, with the greatest research hotspot emerging due to the concept of the "intestinal-renal syndrome," first proposed by Meijers. The most relevant journals were in the field of diet and metabolism, such as Nutrients. The United States and China were the most influential countries, and the most active institute was the University of California San Diego. Author analysis revealed that Denise Mafra, Nosratola D. Vaziri, Fouque, and Denis made great contributions in different aspects of the field. Clustering analysis of the keywords found that important research priorities were "immunity," "inflammation," "metabolism," and "urinary toxin," reflecting the basis of research in the field. Current research frontiers in the field include "hyperuricemia," "gut microbiota," "diabetes," "trimethylamine n-oxide," "iga nephropathy," "acute kidney injury," "chronic kidney disease," "inflammation," all of which necessitate further investigation.Conclusion: This study presents a comprehensive bibliometric analysis and offers an up-to-date outlook on the research related to the gut-kidney axis, with a specific emphasis on the present state of intercommunication between gut microbiota and kidney diseases in this field. This perspective may assist researchers in selecting appropriate journals and partners, and help to gain a deeper understanding of the field's hotspots and frontiers, thereby promoting future research.

Background: Autophagy is an essential cellular process involving the self-degradation and recycling of organelles, proteins, and cellular debris. Recent research has shown that autophagy plays a significant role in the occurrence and development of kidney diseases. However, there is a lack of bibliometric analysis regarding the relationship between autophagy and kidney diseases.Methods: A bibliometric analysis was conducted by searching for literature related to autophagy and kidney diseases in the Web of Science Core Collection (WoSCC) database from 2000 to 2022. Data processing was carried out using R package “Bibliometrix”, VOSviewers, and CiteSpace.Results: A total of 4,579 articles related to autophagy and kidney diseases were collected from various countries. China and the United States were the main countries contributing to the publications. The number of publications in this field showed a year-on-year increasing trend, with open-access journals playing a major role in driving the literature output. Nanjing Medical University in China, Osaka University in Japan, and the University of Pittsburgh in the United States were the main research institutions. The journal “International journal of molecular sciences” had the highest number of publications, while “Autophagy” was the most influential journal in the field. These articles were authored by 18,583 individuals, with Dong, Zheng; Koya, Daisuke; and Kume, Shinji being the most prolific authors, and Dong, Zheng being the most frequently co-cited author. Research on autophagy mainly focused on diabetic kidney diseases, acute kidney injury, and chronic kidney disease. “Autophagy”, “apoptosis”, and “oxidative stress” were the primary research hotspots. Topics such as “diabetic kidney diseases”, “sepsis”, “ferroptosis”, “nrf2”, “hypertension” and “pi3k” may represent potential future development trends. Research on autophagy has gradually focused on metabolic-related kidney diseases such as diabetic nephropathy and hypertension. Additionally, PI3K, NRF2, and ferroptosis have been recent research directions in the field of autophagy mechanisms.Conclusion: This is the first comprehensive bibliometric study summarizing the relationship between autophagy and kidney diseases. The findings aid in identifying recent research frontiers and hot topics, providing valuable references for scholars investigating the role of autophagy in kidney diseases.

Background The incidence of diabetic kidney disease (DKD) is increasing, which has become a major cause of end-stage renal disease. DKD has an insidious onset, and progresses rapidly since the presence of proteinuria, it is difficult to slow down its progression with conventional therapy especially when renal function is significantly impaired. Therefore, it is urgently necessary to explore an effective treatment for delaying the progression of advanced DKD. The Xiezhuoxiaozheng therapy, proposed by Professor WANG Yaoxian in accordance with the pathogenesis of advanced DKD manifested by turbid poison and mass signs and symptoms (zhengjia) , has proven to be effective in clinical treatment of advanced DKD. Objective To assess the clinical efficacy and safety of Xiezhuoxiaozheng therapy in advanced DKD based on the theory of "latent internal heat causing renal collateral mass". Methods A real-world, prospective cohort study design was used to investigate the clinical efficacy and safety of Xiezhuoxiaozheng therapy for advanced DKD in seven hospitals (Dongzhimen Hospital, Beijing University of Chinese Medicine, Guang'anmen Hospital, China Academy of Chinese Medical Sciences, Beijing Hospital of Traditional Chinese Medicine, Wangjing Hospital of CACMS, Xiyuan Hospital of CACMS, Beijing Hospital of Integrated Traditional Chinese and Western Medicine, and Beijing Fangshan District Hospital of Traditional Chinese Medicine) from 2016 to 2020. Patients with DKD who met the inclusion criteria were recruited and divided into a control group (basic western medical treatment) and a test group (basic western medical treatment plus Xiezhuoxiaozheng therapy) taking the method of Xiezhuoxiaozheng and eliminating symptoms as the exposure factor, and received 24-week interventions. At baseline, and the end of 4, 12, and 24 weeks of interventions, serum creatinine (Scr) , blood urea nitrogen (BUN) , 24-hour urine protein, and total cholesterol (TC) , estimated glomerular filtration rate (eGFR) were measured, TCM symptom score was assessed. HbA1c was measured at baseline, and the end of 12, and 24 weeks of interventions. Adverse events were recorded during treatment, and safety was evaluated. Results A total of 59 cases completed the study, including 36 in the test group and 23 in the control group. The intervention duration had significant main effect on eGFR, Scr, and BUN levels in both groups (P<0.05) . The intervention therapy and duration had significant interaction effect on the change in the TCM symptom score in both groups (P<0.05) . The control group had increased BUN level at the end of 12 weeks of intervention, and increased BUN, Scr and heat syndrome score at the end of 24 weeks of intervention (P<0.05) . In contrast, the test group had increased eGFR at the end of 4 weeks of intervention (P<0.05) . The test group had higher eGFR and lower Scr, BUN and TCM symptom score at the end of intervention than did the control group (P<0.05) . The incidence of adverse reactions was 21.74% (5/23) in the control group and 8.33% (3/36) in the experimental group. There was no significant difference between the two groups (χ2=2.15, P=0.14) . Conclusion For advanced DKD, Xiezhuoxiaozheng therapy combined with usual western medicine treatment may be superior to usual western medicine treatment alone in delaying the decrease of eGFR, slowing down the increase of Scr and BUN levels, protecting kidney function, reducing the heat syndrome score and improving the TCM symptoms, which could improve the clinical efficacy.

在肾纤维化过程中,内皮细胞与上皮细胞的持续性损伤、炎症细胞的募集以及肌成纤维细胞的活化、肾小管上皮细胞凋亡发挥了重要作用.研究发现与肾纤维化进展相关的主要分子和细胞,有血管紧张素Ⅱ、转化生长因子β、结缔组织生长因子(CTGF)、纤溶酶原激活物抑制剂-1(PAI1)、核因子-κB(NFκB)、成纤维细胞和蛋白质等.目前进入临床试验的药物主要靶向是对促纤维化分子机制进行阻断,主要有以下几类药物.

Diabetic kidney disease (DKD) is a leading cause of chronic kidney disease in China, which greatly negatively impacts public health and patients' quality of life. Recently, multiple guidelines have updated their recommendations to optimize the treatment and management of individuals with DKD. New antihyperglycemic drugs offer new options for DKD. Traditional Chinese medicine (TCM) has a long history in treating DKD, and relevant theories have been continuously enriched and developed. Along with the increasing application of evidence-based medicine in TCM research, the benefits of TCM treatments in DKD have been gradually recognized and valued, such as relieving fatigue, edema, backache and other symptoms, lowering protein in the urine, protecting kidney function, enhancing treatment efficiency, reducing the risk of end-stage renal disease, and improving the long-term prognosis. This article gave a summary and strengths analysis of the latest advances in TCM and Western medicine treatments for DKD.

Background Recently, several systematic reviews (SRs) and meta-analyses (MAs) of Tripterygium wilfordii polyglycoside (TWP) have reported significant benefits on diabetic kidney disease (DKD). However, the adoption of TWP for DKD remains uncommon. This study aimed to evaluate and summarize the current evidence on TWP for DKD. Methods We searched PubMed, Web of Science, SINOMED, Embase, Cochrane Library, CNKI database, Wan Fang database, and VIP database, up to June 4, 2022. SRs of TWP on DKD were included. Two authors independently assessed eligibility, extracted data, and graded the quality of evidence. We appraised the reporting and methodological quality of the included studies based on the PRISMA statement and AMSTAR 2. Results We included 19 SRs and MAs. Seventeen MAs of proteinuria were identified; all suggested TWP exhibited anti-proteinuria function on DKD. Of these, only 2 were graded as moderate quality of evidence. Eighteen MAs estimated the reno-protective effect of TWP; nine of them showed that TWP improved renal function, including 2 MAs rated as moderate quality of evidence. Eleven SRs showed the serum albumin level was elevated in the TWP group. Of those, four were rated as moderate quality of evidence. Fourteen MAs of the incidence of adverse events were included. Twelve MAs indicated TWP increased the risk of adverse events, of which 4 were graded with moderate quality of evidence. Twenty of the 27 items in the PRISMA checklist were adequately reported with more than 75% compliance among the included SRs, while five of the 12 items in the PRISMA checklist for abstract were found to have less than 50% compliance. The overall reporting quality of SRs published in English was higher than that in Chinese. The methodological quality of the included SRs appraised by AMSTAR-2 ranged from critically low to moderate. Conclusion TWP appears effective for DKD on improving proteinuria and increasing the level of serum albumin, accompanied by a higher risk of adverse events. The evidence would be more credible and valuable to guide decision if the quality of the SRs and primary studies is improved. Systematic review registration PROSPERO CRD42021249560