Objective: To compare the safety and efficacy of drug-coated balloon angioplasty (DCBA) versus conventional balloon angioplasty (CBA) in the treatment of autologous arteriovenous fistula (AVF) stenosis in hemodialysis (HD) patients. Methods: A prospective observational cohort study was conducted on 189 hemodialysis (HD) patients aged 18- 80 years with arteriovenous fistula (AVF) stenosis admitted to Nanjing Drum Tower Hospital Group Suqian Hospital from June 2022 to December 2024. The cohort included 107 male (56.6%) and 82 female (43.4%) patients. Patients were stratified into the conventional balloon angioplasty (CBA) group (n = 92) and the drug-coated balloon angioplasty (DCBA) group (n = 97) based on the intervention received. All patients underwent ultrasound-guided percutaneous transluminal angioplasty (PTA), with the DCBA group receiving additional paclitaxel-coated balloon dilation after conventional pre-dilatation. The primary endpoint was 6-month target lesion primary patency (TLPP); secondary outcomes included 3-month TLPP, stenotic segment diameter, HD blood flow, AVF blood flow (AVFB), serum levels of vascular endothelial growth factor-A (VEGF-A), angiotensin II (Ang II), monocyte chemoattractant protein-1 (MCP-1), and complication rates. Results: Baseline characteristics were comparable between the two groups (all P> 0.05). Clinical success rates were 100.00% in both groups. 1-month (P=0.571) and 3-month (P=0.350) TLPP showed no significant differences, but the DCBA group had a significantly higher 6-month TLPP (91.75% vs 80.43%, P=0.022). At 1 and 6 months postoperatively, the DCBA group exhibited larger stenotic segment diameter, higher HD blood flow, and higher AVFB than the CBA group (all P< 0.001). Serum VEGF-A, AngII, and MCP-1 levels in the DCBA group were significantly lower than those in the CBA group at 1 and 6 months postoperatively (all P< 0.001). There were no significant differences in total complication rates (17.53% vs 13.04%, P=0.350) or individual complication incidences (all P> 0.05) between the two groups. Conclusion: Our study suggests that DCBA is superior to CBA in treating AVF stenosis, as it improves long-term hemodynamic parameters, suppresses inflammatory factor levels, and enhances 6-month TLPP while maintaining equivalent safety. It may be a preferred intervention for AVF stenosis in HD patients.

Multiple studies have revealed the critical roles of epigenetic modifications in the development of diabetic nephropathy (DN). Methyltransferase-like 3 (METTL3)-mediated N6-methyladenosine (m6A) RNA modification in podocytes represents a new disease mechanism in DN. The tripartite motif-containing (TRIM) family member TRIM29 was reported to promote podocyte pyroptosis by activating the nuclear factor-κB/NLR family pyrin domain containing 3 (NLRP3) inflammasome pathway. However, whether METTL3-mediated m6A modification of TRIM29 mRNA is involved in podocyte injury remain unknown. Here, we found that METTL3 upregulated the m6A content in mRNA from kidney tissues of mice with streptozotocin-induced DN and in hyperglycemia-induced MPC-5 murine podocytes. METTL3 expression in high glucose-treated MPC-5 cells resulted in elevated release of interleukin (IL)-1β, IL-18, and lactate dehydrogenase and upregulated expression of pyroptosis-associated molecules. Mechanistically, METTL3 was found to directly target TRIM29 for m6A modification and activate TRIM29 transcription. Moreover, the m6A reader YT521-B homology (YTH) domain family member YTHDF1 was recruited by METTL3 to maintain the stability of TRIM29 mRNA, which contributed significantly to increased podocyte pyroptosis. Furthermore, the potent METTL3-specific inhibitor STM2457 prominently alleviated podocyte injury through attenuating activation of the NLRP3 inflammasome/pyroptosis pathway in the DN mouse model. Our results suggest that METTL3 plays a critical role in hyperglycemia-induced podocyte injury through m6A modification of TRIM29 mRNA, which provides new insight for the development of METTL3- and pyroptosis-targeted strategies to treat DN and other diabetic kidney diseases.

Diabetic nephropathy (DN) is one of the most common complications of diabetes. Gradual loss of podocytes is a sign of DN and pyroptosis mechanistically correlates with podocyte injury in DN; however, the mechanism(s) involved remain unknown. Here we reveal that TRIM29 is overexpressed in high glucose (HG)-treated murine podocytes cells and that TRIM29 silencing significantly inhibits podocyte damage due to HG treatment, as evidenced by lower desmin expression and greater nephrin expression. Additionally, flow cytometry analysis showed that TRIM29 silencing significantly inhibited HG treatment-induced pyroptosis, which was confirmed by immunoblotting for NLRP3, active Caspase-1, GSDMD-N, and phosphorylated NF-κB-p65. Conversely, overexpression of TRIM29 could trigger pyroptosis that was attenuated by NF-κB inhibition, indicating that TRIM29 promotes pyroptosis through the NF-κB pathway. Mechanistic studies revealed that TRIM29 interacts with IκBα to mediate its ubiquitination-dependent degradation, which in turn leads to NF-κB activation. Taken together, our data demonstrate that TRIM29 can promote podocyte pyroptosis by activating the NF-κB/NLRP3 pathway. Thus, TRIM29 represents a potentially novel therapeutic target that may also be clinically relevant in the management of DN.

目的 探讨达格列净在2型糖尿病肾病中的应用效果.方法 选取2020年7月至2021年7月南京鼓楼医院集团宿迁医院肾内科收治的40例2型糖尿病肾病患者作为研究对象,采用随机数字表法将其分为对照组(20例)和观察组(20例).对照组患者采用达格列净以外的降糖药物治疗,观察组患者采用达格列净(10 mg,1次/d)降糖治疗.两组患者均予以饮食控制和运动干预.比较两组患者治疗前、治疗12周后的体重指数(BMI)、收缩压(SBP)、舒张压(DBP)、血清空腹血糖(FPG)、糖化血红蛋白(HbA1c)、总胆固醇(TC)、三酰甘油(TG)、高密度脂蛋白(HDL)、低密度脂蛋白(LDL)、血肌酐(SCr)、胱抑素C(CysC)、尿酸(SUA)、B型脑利钠肽(BNP)、肾小球滤过率(eGFR)、尿蛋白/肌酐比值(UACR)、24 h的尿蛋白定量(24 h UAlb)、左心室射血分数(LVEF);比较两组患者的不良反应发生情况.结果 治疗12周后,观察组患者治疗12周后的FPG、HbA1c、UACR、24 h UAlb、SUA、BNP低于治疗前,LVEF高于治疗前,差异有统计学意义(P＜0.05).治疗12周后,观察组患者的HbA1c、UACR、24h UAlb、SUA、BNP低于对照组,LVEF高于对照组,差异有统计学意义(P＜0.05).两组患者治疗12周后的SBP、DBP、体重、BMI、FPG、TC、TG、HDL、LDL、SCr、eGFR、CysC比较,差异无统计学意义(P＞0.05).观察组患者的低血糖发生率低于对照组,差异有统计学意义(P＜0.01).两组患者的泌尿道感染发生率比较,差异无统计学意义(P＞0.05).观察组患者的不良反应总发生率低于对照组,差异有统计学意义(P＜0.05).结论 达格列净可降低2型糖尿病肾病患者的UACR、24 h UAlb、HbA1c、BNP、SUA,提高LVEF,对于2型糖尿病肾病患者的心、肾功能均具有保护作用.

目的:观察碳酸司维拉姆联合西那卡塞治疗腹膜透析患者高磷血症的临床疗效.方法:选取2018年4月～2021年4月收治的维持性腹膜透析高磷血症并发继发性甲状旁腺功能亢进[甲状旁腺激素(iPTH)>300 pg/ml]患者40例的相关临床资料,将患者随机分组,对照组为碳酸司维拉姆治疗组,观察组为碳酸司维拉姆联合西那卡塞治疗组,两组各20例,治疗12周,观察和比较患者的钙、磷、iPTH、B型脑利钠肽(BNP)、左心室室壁厚度(LVDd)和左心室射血分数(LVEF).结果:治疗12周后,两组血磷、iPTH、BNP均较治疗前下降,观察组下降幅度明显大于对照组,两组比较差异有统计学意义(P<0.05);两组血钙均高于治疗前,观察组高于对照组,两组间差异有统计学意义(P<0.05);对照组LVDd无明显减少,观察组LVDd减少,两组比较差异无统计学意义(P>0.05).对照组LVEF无明显升高,观察组LVEF升高,两组比较差异无统计学意义(P>0.05).结论:碳酸司维拉姆联合西那卡塞对腹膜透析患者钙磷代谢及iPTH的改善作用优于单纯使用碳酸司维拉姆,能有效降低腹膜透析患者的BNP,改善腹膜透析患者的肾性骨病和心功能.

Forkhead box M1 (FOXM1) has been reported to play a protective role against acute kidney injury by driving tubular regeneration. This study aims to probe the function of FOXM1 in diabetic nephropathy (DN) and the molecules involved. FOXM1 was poorly expressed in DN-diseased kidney tissues. A murine model of DN was established, and podocytes cells (MPC5) were treated with high-glucose (HG) for in vitro studies. FOXM1 overexpression improved kidney function and reduced pathological changes in mice, and it increased the expression of the podocyte marker Nephrin in kidney tissues. In vitro, FOXM1 increased viability and reduced pyroptosis of the HG-treated MPC5 cells, and it elevated the expression of the podocyte marker Nephrin whereas reduced the expression of pyroptosis-related NLRP3 inflammasome and cleaved caspase 1. FOXM1 bound to the promoter of sirtuin 4 (SIRT4) to induce transcriptional activation. Downregulation of SIRT4 blocked the protective roles of FOXM1 both in vivo and in vitro. Phosphorylation of nuclear factor-kappa B (NF-κB) in HG-treated cells was suppressed by FOXM1 but restored after SIRT4 inhibition. In conclusion, this study suggested that FOXM1 transcriptionally activates SIRT4 and inhibits NF-κB signaling and the NLRP3 inflammasome to alleviate kidney injury and podocyte pyroptosis in DN.

目的 总结阿昔洛韦致急性肾损伤的临床特点,为阿昔洛韦致使用期间急性肾损伤预防提供依据.方法 选取南京鼓楼医院集团宿迁市人民医院2015年10月至2019年10月收治的阿昔洛韦致急性肾损伤患者26例为研究对象,回顾分析其临床特点,主要包括发病年龄、症状表现、治疗方法、治疗前后肾功能指标以及住院时间等.结果 患者在不同年龄段均可发病,平均年龄(52.64±7.29)岁,超过60岁患者12例占46.15％.急性肾损伤典型症状以恶心、纳差、腰痛以及呕吐等为主,分别占到73.07％、73.07％、65.38％、30.76％,其余相关症状所占比例较小;所有患者均采取保肾、降肌酐等对症支持治疗,2例患者实施透析治疗占7.69％,患者治疗后尿素、肌酐较治疗前显著下降,差异有统计学意义(P<0.05);平均住院时间(11.49±3.17)d.结论 不同年龄段患者在使用阿昔洛韦期间均存在急性肾损伤风险,使用阿昔洛韦患者应注重病情观察,如果出现急性肾损伤需要采取积极对症支持治疗,必要时进行透析治疗,保证患者预后良好.

目的 探讨他克莫司联合中等剂量糖皮质激素治疗特发性膜性肾病的疗效与安全性.方法 方便择取2017年1月—2019年12月该院47例特发性膜性肾病患者,随机分为实验组(他克莫司+糖皮质激素治疗,25例)和对照组(他克莫司治疗,22例),评价两组疗效,比较观察实验组不同疗效患者血清抗磷脂酶A2受体抗体水平.结果 实验组治疗后尿蛋白定量(0.68±0.14)g低于对照组(1.25±0.93)g,治疗总有效率84.00％高于对照组63.64％,差异有统计学意义(t=3.052,x2=4.183,P<0.05).实验组治疗后血清抗磷脂酶A2受体抗体转阴4例,治疗有效病例平均抗体水平(57.1±19.3)RU/mL显著低于治疗无效病例(126.7±31.5)RU/mL,差异有统计学意义(t=13.411,P<0.05).结论 他克莫司联合中等剂量糖皮质激素治疗特发性膜性肾病效果优于他克莫司单纯用药,监测血清抗磷脂酶A2受体抗体水平能够为疗效评估提供依据参考.

Objective:To assess the efficacy of peritoneal dialysis( PD) in patients with cardiorenal syndromes. Methods:A retrospective observational study of patients with CRS Ⅱ was performe on PD, and the results were compared with those before PD. Results: Twenty four patients with CRS Ⅱwere treated with PD. Treatment with PD for 12 months was associated with significantly improved B-type natriuretic peptide(BNP) levels(P<0.01), left ventricular end diastolic diameter(LVDd) (P<0.01),left ventricular ejection fraction(LVEF) (P<0.01), pulmonary artery systolic pressure(PAP) (P<0.01),New York Heart Association(NYHA) functional status(P<0.01),serum creatine(P=0.036),blood urea nitrogen(P<0.01),systolic blood pressure (P=0.010) and the number of hospitalizations per year (P<0.01). Conclusion: PD was effective in treating patients with CRS Ⅱ, PD treatment can improve the symptoms of uremic toxin retention and cardiac function.Also can reduce the patient hospitalizations.

目的 探讨血清胱抑素C(Cys C)水平与老年慢性肾脏病(CKD)患者认知功能的相关性.方法 分析251例老年CKD患者近期的血脂、血清Cys C水平和估算的肾小球滤过率(eGFR).将患者分为三组,Cys C浓度分别为＜1.00 mg/L(低Cys C组,86例)、1.00～1.25 mg/L(中Cys C组,82例)和≥1.26 mg/L(高Cys C组,83例),采用简易精神状态检查量表(MMSE)和蒙特利尔智力测试表(MoCA)评估患者认知功能,分析血清Cys C水平与认知功能的相关性.结果 校准年龄、教育程度、疾病并发症多变量因素后,随着血清Cys C水平升高,认知功能评分降低(P＜0.01).校准eGFR后,认知功能评分与血清Cys C水平无明显相关性(P＞0.05).结论 老年CKD患者的血清Cys C水平越高,认知功能越差.