Acute kidney injury (AKI) is a prevalent renal disorder that poses a significant risk to patient survival, yet current therapeutic strategies remain limited efficacy. Emerging evidence suggests that dysregulated glucose metabolism contributes to AKI progression. Here, we found that pyruvate kinase 2 (PKM2) expression was markedly increased in the kidneys of both I/R model mice and AKI patients. Correspondingly, the downstream metabolites pyruvate and lactate were elevated. Shikonin treatment alleviated renal injury in ischemia/reperfusion (I/R) model mice. Furthermore, shikonin markedly reduced ferroptosis in I/R model mouse kidneys, an effect further confirmed in cultured cells and shown to depend on PKM2 inhibition. Mechanistically, PKM2 upregulation led to lactate accumulation, which disrupted mitochondria integrity and function, leading to cytoplasmic accumulation of mitochondrial DNA (mtDNA) and mitochondrial reactive oxygen species (ROS) production. Cytosolic mtDNA subsequently activated the cGAS-STING pathway, thereby increasing proinflammatory cytokine expression. Together with ROS, this cascade ultimately triggered ferroptosis in the kidney. Shikonin treatment effectively attenuated these detrimental effects. Our findings indicate that shikonin protects AKI-induced renal injury by repressing the PKM2-lactate-mtDNA-cGAS-STING axis. These results indicate that PKM2 may represent a viable target for future anti-AKI therapies.

Introduction:WS016 is a highly selective cation exchanger which traps potassium in the intestinal tract, reducing serum potassium levels in patients with hyperkalemia. This study aimed to evaluate the efficacy and safety of WS016 in hyperkalemic patients. Methods:One hundred forty eligible patients were randomized to receive either WS016 (3 g, 6 g, or 12 g), thrice daily, or placebo for 48 hours. Among those who achieved normokalemia, patients were randomized to WS016 (3 g, 6 g, and 12 g), once daily for 12 days. The primary outcome was the exponential rate of change in serum potassium levels from baseline over the acute and maintenance treatment period, respectively. Results:During the acute treatment phase, the mean exponential rates of reduction from baseline were 0.19% (P = 0.27), 0.17% (P = 0.35), and 0.33% (P < 0.0001) per hour in the WS016 3 g, 6 g, and 12 g group, respectively, compared with a 0.13% with placebo. In contrast, during the maintenance phase, all WS016 groups showed a numerically slower mean daily increase in serum potassium compared with their corresponding placebo groups. The daily increase rate was 0.90% with WS016 12 g versus 1.24% with placebo, the difference was -0.34% (95% confidence interval [CI]: -1.30% to 0.63%; P = 0.49). The overall incidence of adverse events was comparable between WS016 and placebo groups as follows: 26.9% (WS016) versus 20.0% (placebo) during the acute phase and 27.0% versus 31.3% in the maintenance phase. Conclusion:WS016 reduced serum potassium levels rapidly and maintained more patients within the normokalemic range.

BackgroundSepsis and acute kidney injury (AKI) are life-threatening conditions often coexisting as sepsis-associated AKI (S-AKI). However, their shared molecular mechanisms and immune heterogeneity remain unclear. This study aims to identify robust diagnostic biomarkers applicable to both conditions and to elucidate their diverse immune microenvironments using integrated transcriptomic approaches.MethodsTranscriptomic datasets for sepsis and AKI were analyzed, with multiple cohorts used for training and external validation. Differential gene expression and WGCNA identified key modules, while LASSO and Random Forest algorithms screened shared hub genes. A diagnostic nomogram was constructed and evaluated using ROC and decision curve analyses. Single-cell RNA sequencing data were further analyzed to determine cellular localization, functional pathways, and intercellular communication.ResultsFour hub genes (FBXO21, FLOT1, TMC6, and KLRB1) were identified as robust diagnostic biomarkers for both sepsis and AKI, demonstrating strong predictive performance across validation cohorts. Single-cell analysis revealed that these genes were enriched in specific immune cell populations and injured renal cells, and were closely associated with T-cell activation and immune signaling pathways. Cell-cell communication analysis further inferred distinct ligand–receptor interactions that may underlie immune crosstalk in both conditions.ConclusionWe identified a reliable four-gene diagnostic signature shared by sepsis and AKI and characterized their shared immune heterogeneity and inferred intercellular communication networks. These findings provide potential targets for early diagnosis and therapeutic intervention in sepsis-associated renal injury.

Renal fibrosis is an irreversible pathological process that leads to progressive kidney dysfunction, and effective disease-modifying therapies are still lacking. Chemerin is an adipokine predominantly produced by adipose tissue. In our previous study, we demonstrated that chemerin inhibits ferroptosis in renal tubular epithelial cells and protects the kidney from acute injury. Here, we investigated whether chemerin also exerts nephroprotective effects in chronic kidney disease (CKD). Our results revealed a pronounced reduction in chemerin levels in kidney tissues from individuals with CKD and in a murine model of unilateral ureteral obstruction (UUO). Functionally, exogenous chemerin administration alleviated renal insult and fibrosis in mice undergoing UUO. Moreover, chemerin suppressed M2 macrophage-to-myofibroblast transition (MMT) in the UUO kidneys. In cultured macrophages, chemerin engages chemerin chemokine-like receptor 1 (CMKLR1) to suppress polarization and activation toward M2 phenotype. This inhibitory effect was abolished upon CMKLR1 knockdown. Together, these results indicate that chemerin mitigates kidney injury and fibrosis in CKD, primarily by restraining M2 macrophage polarization and the subsequent MMT.

The chronic kidney disease (CKD) situation remains severe globally. The prevention and management of CKD continue to be long-term and challenging tasks. A disintegrin and metalloprotease 9 (ADAM9) is a key factor in the progression of fibrosis and acts through multiple mechanisms, making it an important target in the study of fibrotic diseases. Thus, therapeutic strategies targeting ADAM9 hold promise for treating fibrotic disorders. This study aimed to utilize nanoparticle complexes coated with macrophage membranes (designated M2M@NP complexes) to deliver small interfering RNAs (siRNAs) targeting ADAM9 expression in the kidney. This approach was intended to exert a therapeutic effect on the progression of kidney disease. In vivo imaging confirmed that the macrophage membrane carrier exhibited excellent inflammation-targeting properties. In vitro and in vivo characterization confirmed that M2M@NPs possessed superior transfection efficiency and safety. The experimental results indicated that M2M@NP-ADAM9 siRNA complexes effectively reduced ADAM9 expression, thereby inhibiting the protein kinase B (AKT)/nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) pathway and reducing Ras-related C3 botulinum toxin substrate 1 (RAC1) and tumor necrosis factor receptor-associated factor 6 (TRAF6) expression. These complexes also reduced macrophage infiltration and M1 polarization, leading to attenuated renal inflammation and fibrosis. Our findings suggest that the M2M@NP delivery system has broad potential for treating CKD.

Background This study investigated the diagnostic utility of multi-parametric magnetic resonance imaging (mp-MRI) for early diabetic kidney disease (DKD). We aimed to assess renal impairment by combining parameters from non-enhanced T1 mapping, diffusion tensor imaging (DTI), and diffusion kurtosis imaging (DKI). Methods We prospectively recruited 63 patients with type 2 diabetes, who were divided into three groups based on urine albumin-creatinine ratio: Group 0 (simple diabetes, n = 11), Group 1 (early DKD, n = 20), and Group 2 (advanced DKD, n = 32). All patients underwent renal mp-MRI. Parameters were correlated with clinical indicators (e.g., eGFR, Scr) and, in 11 patients, with histopathology scores from renal biopsy. Receiver operating characteristic (ROC) analysis was used to evaluate diagnostic performance. Results MRI parameters correlated significantly with clinical indicators and key pathology scores. For distinguishing Group 0 from Group 1, mean diffusivity (MD) from DTI (AUC = 0.948) and mean kurtosis (MK) from DKI (AUC = 0.945) were the most effective single parameters. For distinguishing Group 1 from Group 2, MK (AUC = 0.934) and T1 (AUC = 0.878) showed the highest performance. A combined model integrating T1, DTI, and DKI to distinguish Group 0 from Group 1 achieved an AUC of 0.982, with 95.0 % sensitivity and 81.8 % specificity. Conclusion The combined use of T1 mapping, DTI, and DKI provides a non-invasive method for diagnosing early DKD that outperforms any single MRI parameter.

To assess the effectiveness and safety of Sacubitril/Valsartan in reducing blood pressure in individuals with non-dialysis-dependent chronic kidney disease (NDD-CKD) Stage 3-5 complicated by hypertension. This study was a multicenter retrospective analysis conducted from March 1, 2022 to March 31, 2024, involving adult patients with NDD-CKD Stage 3-5 and hypertension, who received Sacubitril/Valsartan either as a monotherapy or in addition to current antihypertensive treatments that were insufficient. The main outcomes measured were blood pressure control, changes in blood pressure and laboratory parameters within 8 weeks post-treatment initiation, and incidence of adverse events. The study included a total of 459 individuals with NDD-CKD Stage 3-5 and hypertension. At the study endpoint, mean systolic blood pressure, diastolic blood pressure, and pulse pressure were markedly reduced compared to baseline (all p < 0.001). The average blood pressure reductions were 12.17 (4.66, 22.00), 6.00 (0.67, 12.66), and 6.67 (0.08, 14.00) mmHg, respectively. Throughout the study period, 96 patients (20.92%) with NDD-CKD Stage 3-5 developed worsening renal function, 15 patients (3.27%) developed hyperkalemia, and 49 patients (10.68%) experienced symptomatic hypotension. Overall, there were no significant differences in the changes in serum creatinine, estimated glomerular filtration rate, and serum potassium before and after treatment (p = 0.28, p = 0.91, p = 0.61, respectively). Sacubitril/Valsartan significantly lowers blood pressure in patients with NDD-CKD Stage 3-5 complicated by hypertension, with good safety profiles. Trial Registration: ClinicalTrials.gov identifier: ChiCTR2400086079

Background:This monocentric, cross-sectional study explored the use of diffusion kurtosis imaging (DKI) as a non-invasive means to diagnose and monitor diabetic nephropathy (DN). Methods:Patients with diabetes mellitus (DM, n = 11), mild DN (N = 14), and severe DN (n = 29) were recruited. Eight DKI metrics (MK, MD, Da, Dr, Ka, Kr, FA, FAk) were determined from the imaging results, and their correlations with routine laboratory results were analyzed. The receiver operating characteristic (ROC) curves were plotted, and the diagnostic value of the DKI metrics was analyzed. In addition, renal biopsy was carried out for ten DN patients who had appropriate indications. Their interstitial fibrosis and tubular atrophy (IFTA) score and the fibrosis ratio of cortical area (F%) were analyzed in combination with the DKI metrics. Results:The progression of DN, reflected by the estimated glomerular filtration rate (eGFR), was accompanied by rising mean kurtosis (MK) and axial kurtosis (Ka) along with decreasing mean diffusivity (MD), axial diffusivity (Da), and radial diffusivity (Dr). Whereas MK was correlated negatively with hemoglobin (Hb) and eGFR and positively with neutrophil gelatinase-associated lipocalin (NGAL), cystatin C (CysC), and serum creatinine (Scr), MD, Da, and Dr were positively correlated with Hb and eGFR and negatively correlated with CysC and Scr. For the biopsied patients, MK was positively correlated with IFTA, and fractional anisotropy of kurtosis (FAk) was negatively correlated with F% and IFTA. Among the DKI indicators, MK had the highest AUC (0.922, 95% CI: 0.843-1.000). Conclusion:The noninvasive monitoring of DN was feasible with DKI, and MK could indicate the renal function and fibrosis of DN patients. Changes in MK may also serve as a biomarker to assess treatment response (eg, microstructural improvement) after therapeutic interventions (eg, drug therapy for diabetic nephropathy, anti-fibrotic therapy).

Chronic nephritis management remains challenging due to the compromised therapeutic efficacy and severe systemic complications of conventional glucocorticoid therapy. Here, we developed a bioinspired platelet-mediated delivery system (LN-DEX@PLT) that leverages platelet tropism toward injured glomeruli for precision drug delivery. This system integrates lipid nanoemulsion encapsulation with platelet-mediated hitchhiking delivery to achieve three key functionalities: (1) enhanced renal targeting demonstrated by 2.2-fold higher glomerular accumulation compared to free dexamethasone via In vivo imaging, (2) effective mitigation of glucocorticoid-induced metabolic toxicity evidenced by reduced fasting plasma glucose (5.2 ± 0.3 vs 8.3 ± 0.7 mmol/L in free DEX), suppression of hepatic gluconeogenic enzymes (PEPCK expression decreased by 43 %, G-6 Pase by 51 %, both p < 0.001), and suppressed body weight (-23.1 % versus free DEX group), and (3) dual-pathway therapeutic effects through IL-6/TNF-α suppression and p53-p21Cip1-mediated senescence delay. In Adriamycin-based chronic nephritis models, LN-DEX@PLT demonstrated superior renal protection with 81 % reduction in proteinuria (vs 33 % for free DEX). In LPS-induced and Adriamycin-based chronic nephritis models, LN-DEX@PLT demonstrated suppression of renal inflammation markers (IL-6 expression decreased to 68 %, TNF-α to 51 %) and macrophage infiltration (F4/80+ cells decreased 5.3-fold). This platelet-biohybrid system provides a clinically translatable paradigm for precision glucocorticoid therapy with reduced dosing frequency.

Background Macrophage-myofibroblast transition (MMT) plays a significant role in the progression of renal fibrosis in chronic kidney disease (CKD), making inhibition of MMT a promising therapeutic strategy. Pyruvate kinase M2 (PKM2) and its metabolite lactate are implicated in the pathogenesis of renal fibrosis; however, the mechanisms through which they contribute to this process remain poorly understood. Purpose To investigate the effects of PKM2 inhibition by shikonin on renal fibrosis and the underly mechanisms. Methods Mice were subjected to unilateral ureteral obstruction (UUO) to establish a CKD model. Renal fibrosis was assessed using histochemistry and western blotting. The MMT and histone lactylation levels were evaluated by immunofluorescence and western blotting. The interaction between the Tgfb1 promoter and lactylated histone H3 (K18) was examined using chromatin Immunoprecipitation (ChIP). Results PKM2 expression was significantly elevated in the renal tubular cells of UUO mouse kidneys, resulting in increased pyruvate and lactate production. Similarly, lactate levels were elevated in TGF-β1-treated TCMK-1 cells and in the serum of CKD patients. In UUO mice, treatment with shikonin, a potent PKM2 inhibitor, effectively reduced lactate production, alleviated renal fibrosis, decreased TGF-β1 expression, and suppressed the MMT process. Mechanistic studies revealed that lactate treatment stimulates Tgfb1 expression in TCMK-1 cells. Consequently, TGF-β1 in conditioned media from lactate-treated TCMK-1 cells promoted M2 macrophage polarization and upregulated fibrotic gene expression in RAW264.7 cells. Pharmacological intervention demonstrated that TGF-β1 activates the Smad3 pathway to drive the MMT process. In TCMK-1 cells, both lactate treatment and PKM2 overexpression induced Tgfb1 expression by promoting histone H3K18 lactylation. Conclusions Our findings indicate that PKM2-induced excessive lactate production renal tubular cells contributes to renal fibrosis. Lactate promotes histone lactylation, leading to TGF-β1 expression in these cells, which subsequently activates the Smad3 pathway in macrophages, driving the MMT and fibrosis in the kidney. Therefore, targeting PKM2, as with shikonin treatment, may represent an effective therapeutic strategy for managing renal fibrosis in CKD.

Acute kidney injury (AKI) is a critical clinical condition, with high morbidity and mortality globally, and also often worsening or progresses to chronic kidney disease (CKD). Despite advances in supportive and replacement therapy, specific interventions remain limited, in term of targeting a molecule (s) involved in the mechanism underlying AKI and its chronic progression. Recent developments in the technology of RNA interference (RNAi), particularly small interfering RNA (siRNA), offer promising avenues for the specific modulation of genes involved in AKI. This review highlights the potential of siRNA-mediated gene therapy to mitigate AKI and prevent its worsening. Here, the properties and advantages of siRNA agents were addressed. More importantly, the existing research on siRNA chemical modifications and delivery systems enabled specific and precise treatments for AKI, while some extensively studied therapeutic approaches were addressed. Furthermore, the challenges and future prospects of siRNA-based drug development for AKI were discussed, with aims to nourish re-searchers and clinicians alike, and promote establishing efficient organ/cell targeted delivery systems and accelerate potential clinical applications.

Sepsis-associated acute kidney injury (AKI) has high morbidity and mortality, but without cause-specific treatment. Erythropoietin derived Helix B surface peptide (HBSP) alleviates AKI, whereas its underlying mechanisms remain to be further explored. Here, the effects of HBSP on pyroptosis, apoptosis, macrophage polarization and repair were investigated in lipopolysaccharide (LPS)-induced AKI mouse model and cultured kidney epithelial cells. Systemic inflammation, compromised renal function and histology were demonstrated in LPS-treated mice, with upregulated pyroptotic and apoptotic key proteins in the kidneys including GSDMD-N, cleaved IL-1β, IL-18 and caspase-3. These proteins were localized in tubular areas and colocalized with aquaporin-1 (AQP1), with increased F4/80 + M1 macrophages. However, HBSP mitigated pyroptosis, apoptosis and inflammation, and promoted macrophage M2 polarization. In addition, HMGB1 and erythropoietin receptor (EPOR) were increased by LPS and decreased by HBSP, both of which were positively correlated with pyroptotic and apoptotic proteins. Moreover, HBSP reduced TNF-α and IL-6 mRNA levels, as well as pyroptosis and apoptosis in LPS-stimulated TCMK-1 cells. In conclusion, HBSP inhibited tubular pyroptosis and apoptosis, EPOR expression, promoted macrophage M2 polarization, and protected against LPS-induced AKI. These findings provide new mechanistic insights into the renoprotection of HBSP, and facilitate its potential for clinical applications and therapeutic strategies in sepsis-associated AKI.

The progression of renal fibrosis to end-stage renal disease (ESRD) is significantly influenced by transforming growth factor-beta (TGF-beta) signal pathway. This study aimed to develop nanoparticles (PMVs@PLGA complexes) with platelet membrane camouflage, which can transport interfering RNA to target and regulate the TGF-β1 pathway in damaged renal tissues. The aim is to reduce the severity of acute kidney injury and to reduce fibrosis in chronic kidney disease. Hence, we formulated PMVs@TGF-β1-siRNA NP complexes and employed them for both in vitro and in vivo therapy. From the experimental findings we know that the PMVs@siRNA NPs could effectively target the kidneys in unilateral ureteral obstruction (UUO) mice and ischemia/reperfusion injury (I/R) mice. In animal models of treatment, PMVs@siRNA NP complexes effectively decreased the expression of TGF-β1 and mitigated inflammation and fibrosis in the kidneys by blocking the TGF-β1/Smad3 pathway. Therefore, these PMVs@siRNA NP complexes can serve as a promising biological delivery system for treating kidney diseases.

Acute kidney injury (AKI) is a common and life-threatening condition associated with cell death, where ferroptosis plays a critical role. Chemerin, primarily produced in white adipose tissue, has multiple biological functions in renal pathophysiology. However, to date, whether and how chemerin regulates the progression of AKI remain unclear. Here, we found that chemerin expression was reduced in both AKI model mice and cells. Similarly, serum chemerin levels were also decreased in AKI patients. The administration of recombinant chemerin improves renal function in ischemia-reperfusion (I/R) model mice. Chemerin significantly attenuates ferroptosis in kidneys. In TCMK-1 cells, chemerin knockdown further aggravates ferroptosis. Mechanistically, chemerin activates AMP-activated protein kinase (AMPK), which induces the phosphorylation of nuclear factor erythroid 2-related factor 2 (NRF2) in renal tubular cells. Subsequently, NRF2 translocates into the nucleus, where it stimulates the expression of cystine/glutamate antiporter solute carrier (SLC7A11). As a result, cystine uptake and glutathione (GSH) biosynthesis in renal tubular cells were increased, which confers cells with higher capacity against ferroptosis. Overall, our findings indicate that chemerin plays a protective role in AKI by repressing ferroptosis in renal tubular cells, which is likely due to the activation in the AMPK/NRF2/SLC7A11 axis.

Inflammatory factors have emerged as key pathophysiological molecules involved in the progression of acute and chronic kidney disease. However, the anti-inflammatory effect of interleukin-10 (IL-10) is largely attenuated because of its insufficient concentration in an injured kidney. To overcome this challenge, we demonstrate in this study that platelet (PLT) camouflaged IL-10 (IL-10@PLT) can selectively accumulate in injured kidneys for treating kidney inflammation and resulting complications. In this system, the PLT drug carrier maintained its original attributes over the study duration, with a good inflammation target effect, confirmed by in vivo imaging. IL-10@PLT could be activated and aggregated, and also released IL-10 at the injury site in the kidney because of high levels of Tumor Necrosis Factor-alpha (TNF-alpha). Compared with free IL-10, IL-10@PLT displayed a higher anti- inflammatory effect with fewer mitochondrial disorders (P < 0.01) and lower expression of NOD-like receptor (NLR)-P3 (NLRP3) (P < 0.05), resulting in reduced inflammation and pyroptosis in ischemia/reperfusion injury (I/R) mice. Treatment with IL-10@PLT also exhibited significantly reduced nuclear factor kappa-B (NF-kB) expression, reduced inflammatory response, as well as improved renal fibrosis (P < 0.05) in the recovery phase in unilateral ureteral obstruction (UUO) mice. At the same time, IL-10@PLT therapy continued to exhibit a favorable safety profile. This study established a promising approach for I/R- and UUO-induced kidney injury and fibrosis by taking advantage of the high accumulation and strong anti-inflammatory of IL-10@PLT. Our study also reveals the importance PLT as an effective drug carrier for targeted therapies.

目的 探讨白藜芦醇治疗维持性血液透析(MHD)合并肌少症患者的临床效果.方法 52例MHD合并肌少症患者随机均分为白藜芦醇组和对照组.对照组采取常规治疗,白藜芦醇组在对照组基础上口服白藜芦醇;两组连续治疗12周.记录治疗前后生化指标、骨骼肌质量指数(SMI)、握力(HGS)、6-m步行速度以及IL-6、TNF-α、超敏CRP(hsCRP)水平变化.结果 两组治疗前和治疗后Hb、白蛋白、TC、TG、HDL、LDL、SCr、血清钙、血清磷、全段甲状旁腺激素水平差异均无统计学意义(P＞0.05).白藜芦醇组治疗后SMI、HGS和6-m步行速度高于治疗前以及对照组(P＜0.05).与治疗前相比,两组治疗后IL-6、TNF-α和hsCRP水平均降低(P＜0.05),白藜芦醇组各指标降低更加显著(P＜0.05).结论 白藜芦醇治疗MHD合并肌少症可有效降低TNF-α、IL-6和hsCRP水平,减轻炎症反应,改善肌肉功能.

目的:探讨白藜芦醇(resveratrol,RSV)对5/6肾切除大鼠肌肉萎缩的保护作用及对肌营养不良蛋白(dys-trophin)、肌 肉环状脂蛋白-1(musclering finger-1,MuRF-1)、肌肉萎缩蛋白-1(MAF-bx,又名Atrogin-1)及肌肉生长抑制素(Myostatin)的影响.方法:采用两步法建立雄性Sprague-Dawley大鼠5/6肾切除模型.术后1周开始予20 mg/(kg·d)RSV灌胃,至术后12周处死大鼠,随机分为3组:对照组(Sham组,n=10)、5/6肾切除组(Nx组,n=10)、5/6肾切除+RSV干预组(Nx+RSV组,n=10),收集血液检测血清肌酐(serum creatinine,SCr)、血尿素氮(blood urea nitrogen,BUN)含量,取肾脏组织行过碘酸-雪夫(periodic acid-schiff,PAS)染色、Masson染色观察肾脏病理变化,取胫骨前肌用于HE染色观察肌纤维的形态和大小,免疫组织化学法观察肌肉中dystrophin表达及分布情况.Western Blot分析检测大鼠肌肉组织中肌萎缩相关蛋白MuRF-1、Atrogin-1、Myostatin的表达.结果:(1)与Sham组相比,Nx组大鼠在术后12周开始出现SCr、BUN水平升高,RSV干预可改善肾功能.(2)Nx组大鼠肾小球硬化指数(glomerular sclerosis index,GSI)及肾小管间质纤维化指数(tubulointerstitial fibrosis index,TFI)升高,RSV干预后得到改善.(3)Nx组大鼠胫骨前肌出现肌纤维横截面积缩小,dystrophin表达减少,Atrogin-1、MuRF-1、Myostatin表达增加,RSV干预后改善了肌纤维萎缩,上调了 dystrophin表达,降低Atrogin-1、MuRF-1、Myostatin表达.结论:RSV可改善5/6肾切除大鼠的肾功能及肌肉萎缩,其机制可能与上调dys-trophin 表达,降低Atrogin-1、MuRF-1、Myostatin表达有关,提示 RSV可能是5/6肾切除肌肉萎缩的一个潜在治疗药物.

Impaired mitochondrial function and dysregulated energy metabolism have been shown to be involved in the pathological progression of kidney diseases such as acute kidney injury (AKI) and diabetic nephropathy. Hence, improving mitochondrial function is a promising strategy for treating renal dysfunction. NADH: ubiquinone oxidoreductase core subunit V1 (NDUFV1) is an important subunit of mitochondrial complex I. In the present study, we found that NDUFV1 was reduced in kidneys of renal ischemia/reperfusion (I/R) mice. Meanwhile, renal I/R induced kidney dysfunction as evidenced by increases in BUN and serum creatinine, severe injury of proximal renal tubules, oxidative stress, and cell apoptosis. All these detrimental outcomes were attenuated by increased expression of NDUFV1 in kidneys. Moreover, knockdown of Ndufv1 aggravated cell insults induced by H2 O2 in TCMK-1 cells, which further confirmed the renoprotective roles of NDUFV1. Mechanistically, NDUFV1 improved the integrity and function of mitochondria, leading to reduced oxidative stress and cell apoptosis. Overall, our data indicate that NDUFV1 has an ability to maintain mitochondrial homeostasis in AKI, suggesting therapies by targeting mitochondria are useful approaches for dealing with mitochondrial dysfunction associated renal diseases such as AKI.

目的 分析了解海安地区糖尿病肾病危险因素,为制定针对性预防策略提供参考.方法 回顾性分析2016年1月—2021年12月期间在南通大学附属海安市人民医院就诊的714例糖尿病患者临床资料,根据尿微量白蛋白排泄率(urinary albumin ejection rate,UAER)检查结果:UAER≥20(ig/min 作为糖尿病肾病组,UAER 不足 20 μg/min 作为单纯糖尿病组;比较两组一般资料与实验室检查结果,并采用多因素logistic回归分析糖尿病肾病发病危险因素.结果 UAER结果显示,糖尿病肾病患者339例,单纯糖尿病患者375例.两组性别、年龄、甘油三酯、低高密度脂蛋白等比较差异无统计学意义(P＞0.05);两组糖尿病病程、BMI、吸烟史、饮酒史、空腹血糖、糖化血红蛋白、总胆固醇、尿酸、肌酐等比较差异有统计学意义(P＜0.05).经多因素logistics回归分析,BMI＞28(OR=2.589,95％CI:1.598～4.192)、糖尿病病程≥10年(OR=3.180,95％CI:1.396～7.244)、有吸烟史(OR=1.725,95％CI:1.221～2.435)、糖化血红蛋白(OR=4.195,95％CI:1.860～9.463)、总胆固醇(OR=2.509,95％CI:1.507～4.177)与血尿酸(OR=2.367,95％CI:1.517～3..695)水平升高为糖尿病肾病发病的危险因素.结论 糖尿病肾病是糖尿病病程、肥胖、吸烟等多因素作用结果,早期检测并控制危险因素可延缓疾病发展.

Accumulating evidence indicates that the extracellular matrix (ECM) is not only a consequence of fibrosis, but also contributes to the progression of fibrosis, by creating a profibrotic microenvironment. Tenascin-C (TNC) is an ECM glycoprotein that contains multiple functional domains. We showed that following kidney injury, TNC was markedly induced in fibrotic areas in the kidney from both mouse models and humans with kidney diseases. Genetically deletion of TNC in mice significantly attenuated unilateral ureteral obstruction-induced kidney fibrosis. Further studies showed that TNC promoted the proliferation of kidney interstitial cells via STAT3 activation. TNC-expressing cells in fibrotic kidney were activated fibroblast 2 (Act.Fib2) subpopulation, according to a previously generated single nucleus RNA-seq dataset profiling kidney of mouse UUO model at day 14. To identify and characterize TNC-expressing cells, we generated a TNC-promoter-driven CreER2-IRES-eGFP knock-in mouse line and found that the TNC reporter eGFP was markedly induced in cells around injured tubules that had lost epithelial markers, suggesting TNC was induced in response to epithelium injury. Most of the eGFP-positive cells were both NG2 and PDGFRβ positive. These cells did not carry markers of progenitor cells or macrophages. In conclusion, this study provides strong evidence that matrix protein TNC contributes to kidney fibrosis. TNC pathway may serve as a potential therapeutic target for interstitial fibrosis and the progression of chronic kidney disease.