This prospective, randomized, double-blind, placebo-controlled trial investigated the efficacy and safety of thiamin and folic acid for cognitive impairment in maintenance hemodialysis (MHD) patients. A total of 215 MHD patients aged 18-75 with cognitive impairment were randomized to receive either oral thiamin (90 mg/day) plus folic acid (30 mg/day) or a placebo for 96 weeks. The primary endpoint was the change in the Alzheimer's Disease Assessment Scale-Cognitive section (ADAS-Cog) score. After 96 weeks, the treatment group showed a significant improvement in ADAS-Cog scores (from 21.25 ± 9.2 to 15.07 ± 8.38, p < 0.001), whereas the placebo group showed a non‑significant improvement (from 24.53 ± 11.01 to 26.53 ± 14.43, p = 0.077). The treatment group also demonstrated significantly increased blood levels of thiamin (from 5.59 ± 0.95 to 18.21 ± 3.91 ng/mL) and folate (from 12.37 ± 4.62 to 63.33 ± 16.02 ng/mL), and a reduction in homocysteine levels (from 4709.06 ± 353.15 to 2962.68 ± 158.87 ng/mL, p < 0.001), with no significant changes in the placebo group. While mortality was similar between the two groups (12.1% vs. 12.0%, p = 0.978), the incidence of adverse events was significantly lower in the treatment group (31.8% vs. 62.0%, p = 0.0017), particularly cardiovascular and cerebrovascular events (13.1% vs. 25.9%, p = 0.001). The study concludes that combined thiamin and folic acid supplementation improves cognitive function in MHD patients with a favorable safety profile.

BACKGROUND:While the appearance of red clots in the dialyzer and the arterial and venous blood tubing lines is a common phenomenon in every hemodialysis unit, the occurrence of recurrent yellowish-white matter formation in the hemodialysis venous blood pot of a patient is rare. CASE PRESENTATION:We describe a male 69-year-old male with recurrent yellowish-white matter formation in the hemodialysis venous blood pot and red clots in the dialyzer. This was associated with a significant decrease in his red blood cells count. He had no history of thrombus no pro-thrombotic risk factors could be identified. Light microscopic examination of the deposits revealed the presence of large aggregates of neutrophils, large amounts of fibrin. The yellowish-white matter recurred at the next dialysis session. The occurrence of this episode was completely resolved by switching the dialysis filter and could not be avoided by increasing low molecular weight heparin dosage. CONCLUSION:The yellowish-white matter and clotting within the dialyzer, as well as severe anemia, could be prevented by changing the type of dialyzer. Due to the rarity of this dialyzer reaction, it is important that awareness of this reaction by early identification be undertaken.

BACKGROUND:Haemodialysis (HD) patients are predisposed to physical ailments, and their occurrence of coronavirus disease 2019 (COVID-19) could potentially lead to a more unfavourable prognosis. However, the impact of SARS-CoV-2 (Omicron variant) infection on the prognosis of HD patients remains unclear. This study aimed to explore the impact of Omicron variant infection on the prognosis of HD patients. METHODS:Eligible participants were patients undergoing maintenance HD treatment during a large-scale outbreak of COVID-19 (Omicron variant) in Shanghai, China, from April 7 to May 30, 2022. According to SARS-CoV-2 infection status of participants, the HD patients were divided into two groups: a COVID-19 group and a non-COVID-19 group. The primary outcome assessed was in-hospital mortality, and secondary outcomes encompassed the incidence of severe cases, admission to intensive care, length of hospital stay, and blood indices. Statistical analysis was conducted by comparative analysis and multiple logistic regression. RESULTS:This study recruited 588 HD patients, including 199 cases in the COVID-19 group and 389 in the non-COVID-19 group. In the COVID-19 group, the mortality rate was 8.45% (17/199), whereas in the non-COVID-19 group, the rate was 3.34% (13/389) (p < 0.05). Compared with the non-COVID-19 group, the COVID-19 group had a risk ratio (RR) with 95% confidence interval (CI) of 2.56 (1.27-5.15) for mortality, and the absolute risk difference (ARD) with 95% CI of 5.20% (1.34%-9.06%). Multiple logistic regression confirmed Omicron variant as a risk factor for mortality among HD patients. Additionally, the COVID-19 group had a higher proportion of severe cases, intensive care admission, hypocalcaemia and hyperphosphatemia and longer hospitalization duration, compared to the non-COVID-19 group (p < 0.05). CONCLUSIONS:Omicron variant infection was associated with increased mortality risk in HD patients, and Omicron infection worsen the prognosis of HD patients. Enhancing immune protection against SARS-CoV-2 is crucial for HD patients during the ongoing COVID-19 pandemic.

Background: To uncover the diagnostic potential of periph-eral blood microRNA-200b (miRNA-200b) in renal intersti-tial injury in diabetic nephropathy (DN) patients.Methods: A total of 50 diabetes subjects, 50 mild DN sub-jects, 50 moderate-severe DN subjects and 50 healthy sub-jects were included. Peripheral blood level of miRNA-200b in every subject was detected by reverse transcriptase-poly-merase chain reaction (RT-PCR). Serum levels of renal function indicators were determined by enzyme-linked immunosorbent assay (ELISA). Meanwhile, relative levels of fibrosis damage indicators were examined by chemilumi-nescent immunoassay. Diagnostic potentials of miRNA-200b in diabetes, mild DN and moderate-severe DN were assessed by depicting receiver operating characteristic (ROC) curves.Results: Peripheral blood level of miRNA-200b was higher in DN subjects than diabetes subjects without vascular complications, especially moderate-severe DN patients. Peripheral blood level of miRNA-200b in DN subjects was negatively correlated to relative levels of serum creatinine, urinary nitrogen, cystatin, TGF-B, CIV and PCIII. ROC curves demonstrated diagnostic potentials of miRNA-200b in mild and moderate-severe DN.Conclusions: Peripheral blood level of miRNA-200b is closely linked to the degree of renal interstitial injury in DN patients. MiRNA-200b may be a vital indicator in predict-ing the development of DN.

目的 研究血液灌流联合高通量血液透析对尿毒症性皮肤瘙痒(uremic prutitus,UP)的治疗效果及其对患者钙磷代谢和肾功能的影响.方法 选取2016年3月至2018年9月于上海交通大学附属第六人民医院行维持性血液透析并发UP的患者120例为研究对象,按照随机数字表法将入选患者分为观察组和对照组,每组各60例,对照组患者行高通量血液透析,观察组患者行血液灌流联合高通量血液透析.比较两组患者治疗前、治疗1个月和3个月后瘙痒症状、肾功能指标和钙磷代谢指标变化情况.结果 治疗前,两组患者视觉模拟评分法(visual analogue scale,VAS)评分、血尿素氮(blood urea nitrogen,BUN)、血清肌酐(serum creatinine,Scr)、血清甲状旁腺激素(parathyroid hormone,PTH)、血清磷、血清钙水平比较差异均无统计学意义(均P>0.05).治疗1个月和3个月后,观察组患者VAS评分、BUN、Scr、血清PTH、血清磷水平均显著低于同期对照组(均P<0.05),血清钙水平均显著高于同期对照组(均P<0.05).结论 血液灌流联合高通量血液透析对UP的治疗效果较好,且能调节患者钙磷代谢,保护肾功能.

慢性肾脏病(chronic kidney diseases,CKD)进展到终末期,往往需要肾脏替代治疗.血液透析(hemodialysis,HD)是目前主要的肾脏替代方式之一.我国的血液透析主要在医疗机构进行,患者每周需要到医院接受2～3次血液透析.这就意味着患者及其家庭需要承担非常大的人力、物力及财力负担.然而,多数患者经济收入不高,导致其常常因担忧花费而处于焦虑的状态;同时,患者刚进入血液透析状态时,因自身的血透知识、经验相对匮乏,加上需要应对血液透析所造成的自己及家庭生活改变,很多患者在透析过程中普遍表现出不同程度的焦虑,甚至抑郁状态[1].掌握患者在血液透析过程中焦虑情绪和抑郁状态变化规律,发现其影响因素,为更好的照顾患者有重要的现实意义.本文就新入血透患者展开心理状态调查,观察提前血管通路准备对其透析起始阶段的心理状态影响,总结出目前社会状态下患者心理状态变化的普遍规律,增加医患沟通,为更好的服务终末期血液透析患者提供指导.

目的 探讨校正后糖化白蛋白(adjGA)评估糖尿病肾病合并大量蛋白尿患者血糖的价值.方法 共纳入166例24 h尿微量白蛋白(24hUP)＞1.0 g/24 h的糖尿病肾病患者,按其24hUP水平分为显性蛋白尿组(24hUP＜3.5 g,92例)和肾病综合征组(24hUP≥3.5g,74例).测定两组空腹血糖(FBG)、餐后2h血糖(PBG)、糖化血红蛋白(HbA1c)、糖化白蛋白(GA)、体重、血清白蛋白(SA)水平.应用GA的校正公式计算adjGA,并比较两组间差异,分析GA和adjGA与其他因素的相关性.结果 两组的FBG和PBG水平差异均无统计学意义(P值均＞0.05).肾病综合征组的GA和GA/HbA1c水平均显著低于显性蛋白尿组(P值均＜0.01).经过数据校正,两组间adjGA的差异仍有统计学意义(P＜0.05),而adjGA/HbA1c的差异无统计学意义(P=0.445).单因素相关性分析结果表明,在全体患者中GA与FBG、PBG、HbA1c、eGFR和SA均呈显著正相关(R2值分别为0.101、0.067、0.474、0.095、0.072,P值均＜0.01),与24hUP呈显著负相关(R2=0.205,P＜0.01);adjGA与FBG、PBG、HbA1 c、eGFR均呈显著正相关(R2值分别为0.156、0.039、0.469、0.089,P值均＜0.01),与24hUP、SA均无明显相关性(r值分别为0.024,-0.013,P值均＞0.05).多元线性回归分析结果表明,在全体患者中adjGA仅与PBG相关(R2=0.163,回归系数为0.497,P＜0.05).结论 adjGA对评估糖尿病肾病合并大量蛋白尿患者的血糖水平有临床价值,尤其适用于肾病综合征大量蛋白尿患者,但仍需进一步行动态血糖监测数据和大样本研究验证.

Objective:To observe the change of high glucose induced podocyte epithelial-mesenchymal transition (EMT),and AS-Ⅳ inhibit podocyte EMT.Methods:Conditionally immortalized mouse podocytes were randomly divided into 6 group:normal glucose group,high glucose group,mannitol group,HG +30 μg/ml AS-Ⅳ group,HG + 15 μg/ml AS-Ⅳ group and HG +5 μg,/ml AS-Ⅳ group.The expressions of desmin,nephrin were detected by a two-color immunohistochemistry staining technique and real time RT-PCR.Results:The expressions of desmin were enhanced and nephrin was decreased by high glucose,AS-Ⅳ markedly inhibited all of those changes induced by high glucose.Conclusion:The high glucose can induced podocyte EMT,and AS-Ⅳ might inhibit podocyte EMT.

Objective To investigate the prevalence and treatment of hypertension in maintenance hemodialysis (MHD) patients with end stage renal disease (ESRD) caused by diabetic kidney disease (DKD).Methods A total of 558 MHD patients with ESRD caused by DKD were collected from 39 hemodialysis centers in Shanghai.The clinical and laboratory data were statistically analyzed.Results Hypertension was found in 523 patients,with a prevalence of 93.7％.There were no significant differences in the prevalence of hypertension,systolic or diastolic blood pressure between male and female hypertensive patients (P＞0.05).There were 490 patients who were treated with antihypertensive drugs,and the treatment rate was 93.7％ (490/523).No significant difference was found in the treatment rate between men and women (P＞0.05).Calcium channel blocker (CCB) was the most frequently used (in 366 patients,74.7％),followed by angiotensin receptor blockers (ARB,in 166 patients,33.9％) and angiotensin converting enzyme inhibitors (ACEI,in 95 patients,19.4％).CCB was the most popular single drug CCB and ARB were the most frequently chosen pair for combination drug therapy.The blood pressure control target (≤ 140/90 mmHg,1 mmHg=0.133 kPa) was achieved in 128 patients (24.5 ％).There was no significant difference in the control rate between males and females (P＞0.05).The age,urea removal index (KT/V),urea removal rate (URR),and hemoglobin level in the patients with controlled blood pressure were significantly higher than those in the patients without well controlled blood pressure (P＜0.05).The kinds of antihypertensive drug used in the patients with controlled blood pressure were significantly less than that in the patients without well controlled blood pressure (P＜0.05).Single factor Logistic analysis showed that the kind of antihypertensive drug was the risk factor for blood pressure control (OR =1.34,95％ CI 1.07-1.69,P＜0.05),while the age (OR=0.96,95％CI 0.94-0.98,P＜0.05) and hemoglobin level (OR=0.98,95％CI 0.97-0.99,P ＜ 0.05) were the protective factors of blood pressure control.Stepwise multiple Logistic regression analysis showed that blood pressure control was significantly associated with age,the kind of antihypertensive drug and hemoglobin level,and the regression coefficients were-0.40,0.24 and-0.02,respectively (P＜0.05).The blood pressure could not be well controlled in those patients who were younger,took more kinds of antihypertensive drugs,and with lower hemoglobin.Conclusion The prevalence of hypertension and treatment rates are very high in MHD patients with ESRD caused by DKD,but the control rate is low.The control of hypertension is relevant to many factors such as age,antihypertensive therapy,and anemia.

目的 探讨糖化白蛋白(GA)对糖尿病肾病(DN)与非DN的慢性肾脏病(CKD)患者的血糖评估价值及其影响因素.方法 共入选782例CKD患者,其中DN患者579例,非DN患者203例.根据估算肾小球滤过率(eGFR)将患者分为CKD 1至2期组(374例),CKD 3至4期组(207例)和CKD 5期组(201例).CKD 1至2期组中DN患者343例,非DN患者31例;CKD 3至4期组中DN患者108例,非DN患者99例;CKD 5期组中DN患者128例,非DN患者73例.收集所有患者的一般资料,测定其空腹血糖(FBG)、餐后2h血糖(2hPBG)、GA、糖化血红蛋白(HbA1c)、血红蛋白(Hb)、24 h尿蛋白定量(24hUP)和各项生化指标的水平.采用单因素、多因素分析方法分析GA与其他变量间的相关性.结果 CKD 1至2期组、CKD 3至4期组和CKD 5期组中非DN患者的年龄、FBG、2hPBG、HbA1c、GA均显著低于同组DN患者(P值均＜0.01).CKD 3至4期组和CKD 5期组的DN患者的eGFR、FBG、2hPBG、HbA1c、GA、GA/Hb&A1c、血清血蛋白(sA)、Hb均显著低于CKD 1至2期组的DN患者(P值均＜0.01),24hUP均显著高于CKD 1至2期组的DN患者(P值均＜0.01);CKD 3至4期组和CKD 5期组的非DN患者的eGFR、sA、Hb均显著低于CKD 1至2期组的非DN患者(P值均＜0.01),CKD 5期组的非DN患者的24hUP显著高于CKD 1至2期组的非DN患者(P＜0.01).CKD 5期组的DN患者的eGFR、FBG、2hPBG、HbA1c、GA、sA、Hb均显著低于CKD 3至4期组的DN患者(P值均＜0.01),24hUP显著高于CKD 3至4期组的DN患者(P＜0.01);CKD 5期组的非DN患者的eGFR、Hb均显著低于CKD 3至4期组的非DN患者(P值均＜0.01),24hUP显著高于CKD 3至4期组的非DN患者(P＜0.01).在所有患者中,以GA为因变量行单因素线性回归分析显示,GA与FBG(R2 =0.145)、2hPBG (R2=0.174)、HbA1c(R2 =0.649)呈正相关(P值均＜0.01),与24hUP呈负相关性(R2=0.187,P值均＜0.01);多因素回归分析显示,BMI(β=0.278)、FBG(β=0.334)、2hPBG(β=0.388)、24hUP(β=-1.044)和eGFR(β=-0.019)为GA的共同影响因素(R2=0.414,P值均＜0.05).DN患者中GA相关性分析显示,BMI(β=-0.341)、FBG(β=0.254)、2hPBG(β=0.347)、24hUP(β=-1.306)为GA的共同影响因素(R2=0.375,P值均＜0.05).结论 GA在不同CKD分期中均有血糖评估价值,CKD患者的GA除受血糖影响外,还受到BMI、蛋白尿和肾功能的影响.

Background: Epithelial-to-mesenchymal transition (EMT) is a potential pathway leading to podocyte depletion and proteinuria in diabetic kidney disease (DKD). Here, we investigated the protective effects of Emodin (EMO) on high glucose (HG) induced-podocyte EMT in-vitro and in-vivo. Methods: Conditionally immortalized mouse podocytes were exposed to HG with 30μg /ml of EMO and 1μmol/ml of integrin-linked kinase (ILK) inhibitor QLT0267 for 24 h. Streptozotocin (STZ)-induced diabetic rats were treated with EMO at 20 mg· kg-1· d-1 and QLT0267 at 10 mg· kg-1· w-1 p.o., for 12 weeks. Albuminuria and blood glucose level were measured. Immunohistochemistry, immunofluorescence, western blotting and real-time PCR were used to detect expression of ILK, the epithelial marker of nephrin and the mesenchymal marker of desmin in-vitro and in-vivo. Results: HG increased podocyte ILK and desmin expression while decreased nephrin expression. However, EMO significantly inhibited ILK and desmin expression and partially restored nephrin expression in HG-stimulated podocytes. These in-vitro observations were further confirmed in-vivo. Treatment with EMO for 12 weeks attenuated albuminuria, renal histopathology and podocyte foot process effacement in diabetic rats. EMO also repressed renal ILK and desmin expression, preserved nephrin expression, as well as ameliorated albuminuria in STZ-induced diabetic rats. Conclusion: EMO ameliorated glucose-induced EMT and subsequent podocyte dysfunction partly through ILK and desmin inhibition as well as nephrin upregulatiotion, which might provide a potential novel therapeutic option for DKD.

Glomerular mesangial cell (MC) hypertrophy is regarded as one of the earliest pathological characteristics of diabetic nephropathy (DN), which plays a critical role in the pathogenesis of glomerulosclerosis. This study investigated the role of microRNAs (miRNAs) in MC hypertrophy due to exposure to high glucose. With a microarray, we screened the differential profiles of miRNAs in the renal cortex of DN mice, as verified by reverse transcription PCR with subsequent analysis of bioinformatics. We found miR-196a was downregulated remarkably in DN mice and increased the hypertrophy-related gene of p27kip1 in high-enrichment gene ontologies. Furthermore, transfection of the miR-196a mimic greatly inhibited the expression of p27kip1 with recovery of MC hypertrophic morphology. With flow cytometry, we also found that overexpression of miR-196a significantly reduced the percentage of G1 phase arrest in the cell cycle. Cotransfection of the miR-196a mimic with a wild type of 3′ UTR of the p27kip1 vector reduced the activity of the luciferase reporter significantly in contrast to the miR-196a mimic with a mutant of the counterpart in HEK293 cell lines, suggesting that miR-196a directly targets p27kip1. Finally, knockdown of p27kip1 with specific small interfering RNA in MCs substantially reversed MC hypertrophy induced by transfection of the miR-196a inhibitor. This study revealed that miR-196a acts as an important molecular regulator in high glucose-induced MC hypertrophy by targeting p27kip1.

Objective:The antioxidative effects of Astragaloside IV protect against podocyte lesion exposed to high glucose.Methods:Conditionally immortalized mouse podocytes were randomly divided into 7 group: normal glucose group, high glucose group, mannitol group, DMSO group, HG+30 μg/ml AS-IV group, HG+15 μg/ml AS-IV group and HG+5 μg/ml AS-IV group. Cell viability was examined by cell counting Kit-8 (CCK-8) assay. Expression of ILK protein were observed by western blot. SOD ,MDA,CAT and GSH-Px were measured by the assay kits,respectively.Results:Compared with incubated in NG, exposure to HG for 72 h significantly increase in levels of MDA and the expression of ILK, while a dramatical reduction in cell viability and activities of CAT, SOD and GSH-Px. However, HG-induced oxidative stress was partially reduced by AS-IV in a dose-dependent manner. No significant difference were found between NG group and MA group, as well as HG group and DMSO group.Conclusion:The antioxidative effect of AS-IV on podocyte injury under HG stimulation may be involved in ILK inhibition, and maybe a new treatment target in diabetic nephropathy.

<正>糖尿病肾病(diabetickidney disease,DKD)是糖尿病最常见的微血管并发症,已成为终末期肾病最常见的病因。在欧美发达国家,DKD占透析患者总人数的50%以上,在我国目前仅次于慢性肾小球肾炎,为第二位病因。心血管病是我国城市和农村人群首位死亡原因。糖尿病合并蛋白尿患者的心血管疾病所致的相对死亡率较非糖尿病人群高37倍,