趋化因子ENA-78与肾脏疾病

体外实验中,各种肾脏细胞都能在特定刺激下表达趋化因子及受体。动物模型和人类肾脏疾病的肾组织中,炎症细胞浸润同时出现趋化因子及受体表达增多。ENA-78是一种来源广泛、生物功能多样的趋化因子,通过与其受体相互作用,引起中性粒细胞等白细胞的趋化、活化,参与肾脏疾病的发生、发展。     

维吾尔族2 型糖尿病患者糖尿病肾病相关因素分析

目的:探讨维吾尔族2型糖尿病肾病(DN)发病的相关临来因素。方法:分析292例维吾尔族2型糖尿病患者的临床资科。结果:维吾尔族2型糖尿病患者糖尿病肾病(DN)发病率为43.49%(127/292)。DN患者的病程、SBP、TC、TG、FBG、HbAIC、LDL-C、BUN和Cr均显著高于NDN患者(P<0.05);但DBP、HDL-C、BMI之间无统计学差异(P>0.05)。Logistic归分析结果显示,DM病程、患病年龄、SBP、FBP、TC、TG、LDL-C、HbA1c、BUN、Cr是DN的危险因素(OR值>1)。结论:维吾尔族2型糖尿病患者的DM病程、患病年龄、SBP、FBP、TC、TG、LDL-C、HbA1c、BUN、Cr等参数与糖尿病肾病并发率之间有相关性。     

维吾尔族2型糖尿病患者糖尿病肾病相关因素分析

目的：探讨维吾尔族2型糖尿病肾病（DN）发病的相关临来因素。方法：分析292例维吾尔族2型糖尿病患者的临床资科。结果：维吾尔族2型糖尿病患者糖尿病肾病（DN）发病率为43,49％（127／292）。DN患者的病程、SBP、TC、TG、FBG、HbAIC、LDL—C、BUN和Cr均显著高于NDN患者（P〈0．05）;但DBP、HDL．C、BMI之间无统计学差异（P〉0．05）。Logistic归分析结果显示,DM病程、患病年龄、SBP、FBP、TC、TG、LDL—C、HbAlc、BUN、Cr是DN的危险因素（OR值〉1）。结论：维吾尔族2型糖尿病患者的Did病程、患病年龄、SBP、FBP、TC、TG、LDL—C、HbAlc、BUN、Cr等参数与糖尿病肾病并发率之间有相关性。     

西格列汀对2 型糖尿病患者微量白蛋白尿影响的研究

目的:研究西格列汀对2型糖尿病患者微量白蛋白尿的影响,分析其可能机制和临床应用价值。方法:选取160例伴微量白蛋白尿的2型糖尿病患者,随机分为西格列汀组和其他药物组,各80例。比较两组患者治疗前和治疗3个月后血糖水平、尿微量白蛋白、超敏C反应蛋白及血浆还原型谷胱甘肽水平。结果:经3个月治疗,两组患者空腹血糖、餐后2 h血糖、Hb A1c均较治疗前下降,但差异无明显统计学意义(P0.05);西格列汀治疗组患者尿微量白蛋白和血浆Hs-CRP水平明显下降,血浆还原型谷胱甘肽水平明显升高,与其他口服药物治疗组相比差异具有统计学意义(P0.05)。结论:西格列汀可能通过改善机体炎症状态,降低氧化和应激水平等机制降低2型糖尿病患者的尿微量白蛋白水平。     

2型糖尿病与糖尿病肾病患者微炎症及肠道微生物多样性分析

目的 分析2型糖尿病(T2DM)及糖尿病肾病(DKD)患者微炎症情况和肠道微生物多样性。 方法 将2016年4月至2019年7月在我院进行治疗的68例T2DM患者(T2DM组)和57例DKD患者(DKD组)纳入研究,选择同期于我院进行健康体检的36例志愿者作为对照组。收集3组对象一般资料、血液标本和粪便标本,测定血清总胆固醇(TC)、甘油三酯(TG)、低密度脂蛋白胆固醇(LDLC)、高密度脂蛋白胆固醇(HDLC)、糖化血红蛋白(HbAlc)、空腹血糖(FBG)、超敏C反应蛋白(hsCRP)、白细胞介素6(IL6)水平,并对肠道细菌进行16S rDNA序列测序。比较3组对象一般资料,血液指标,肠道菌群门水平构成情况,肠道菌群多样性,肠道菌属差异性,并对患者炎性指标与菌群种类进行相关性分析。 结果 DKD组患者糖尿病病程长于T2DM组(P结论 2型糖尿病患者普遍存在微炎症和肠道菌群失衡,微炎症程度与肾脏病变和肠道菌群数量密切相关。T2DM与DKD患者在肠道菌群结构上具有一致性和差异性,肠道菌群检测有可能成为预测T2DM患者发生肾脏病变的风险指标。     

糖尿病肾病患者与相关细胞因子水平的变化

目的:研究糖尿病肾病(DN)患者的血清肿瘤坏死因子(TNF-α)、干扰素-γ(IFN-γ)、白介素-6(IL-6)、血管内皮生长因子(VEGF)、和肝细胞生长因子(HGF)水平的变化在肾病发生、发展过程中的作用。方法:应用ELISA法分析20例糖尿病肾病患者和20例正常人进行了血清TNF-α、IFN-γ、IL-6、VEGF和HGF水平。结果:糖尿病肾病患者血清中TNF-α、IL-6、VEGF和HGF水平非常显著地高于正常人组(P<0.01),而IFN-γ水平则显著地低于正常人组(P<0.01)。结论:TNF-α、IFN-γ、IL-6、VEGF和HGF水平的变化在糖尿病肾病的发生和发展中相互作用,观察其浓度的变化对探讨其发病机理、预防和指导导用药均有十分重要的临床价值。     

2 型糖尿病患者血浆成纤维细胞生长因子-21 水平的变化及意义

目的:探讨2型糖尿病(type 2 diabetes mellitus,T2DM)患者血浆成纤维细胞生长因子-21(fibroblast growth factor 21,FGF-21)水平变化以及观察短期胰岛素强化治疗对FGF-21水平的影响。方法:选择我院2013年1月至2015年1月收治的T2DM患者64例,其中初诊T2DM患者32例(T2DM组),T2DM合并大血管病变患者32例(合并大血管病变组),并选择同期体检健康者30例(对照组)。采用酶联免疫法测定三组血浆FGF-21水平以及胰岛素强化治疗前后的变化,分析血浆FGF-21水平与体质量指数(BMI)、腰臀比(WHR)、血脂、血糖、空腹血浆胰岛素(FINS)和糖化血红蛋白(Hb A1C)等水平的关系。结果:T2DM组及T2DM合并大血管病变组患者空腹血浆FGF-21水平明显高于对照组(P0.05),T2DM合并大血管病变组患者空腹血浆FGF-21水平明显高于T2DM组和对照组(P0.05)。空腹血浆FGF-21水平与T2DM患者FPG、Hb A1C水平呈明显正相关,WHR、舒张压、Hb A1C是影响血浆FGF-21水平的独立相关因素。经胰岛素强化治疗后,血浆FGF-21水平较治疗前明显下降(P0.05)。结论:T2DM患者血浆FGF-21水平明显升高,可能参与了T2DM及其大血管病变的发生和发展,胰岛素强化治疗可明显降低T2DM患者血浆FGF-21水平,血浆FGF-21可能作为T2DM病情和疗效评估的参考指标。     

糖尿病肾病患者NT-proBNP,Hcy和cTnI的水平变化及其临床意义

目的:观察糖尿病肾病患者血清NT-proBNP,Hcy和cTnI的水平变化情况,分析其与心血管疾病发生的关系,为临床提供指导依据。方法:选择我院2012年3月至2013年9月收治的152例糖尿病肾病患者,根据合并心血管疾病的情况,将所选患者分为并发症组(83例)和无并发症组(69例),另选择同期在我院接受健康体检的志愿者(72例)作为对照组。检测三组对象血清中NT-proBNP,Hcy与cTnI的水平,以及糖尿病肾病患者的肾功能指标。结果:对照组NT-proBNP,Hcy与cTnI水平显著低于其他两组,并发症组患者NT-proBNP,Hcy与cTnI水平高于无并发症组,差异有统计学意义(P0.05)。并发症组患者的BUN,UA及CysC水平显著高于无并发症组,差异有统计学意义(P0.05)。结论:NT-proBNP,Hcy和cTnI在合并心血管疾病的糖尿病肾病患者血清中显著升高,并在一定程度上影响患者的肾功能。     

糖适平对2 型糖尿病合并糖尿病肾病4 期患者血糖、肌酐清除率及尿蛋白水平的影响

目的:探讨糖适平对2型糖尿病合并糖尿病肾病4期患者血糖、肌酐清除率及尿蛋白水平的影响。方法:选择我院收治的2型糖尿病合并糖尿病肾病4期患者100例,按照用药情况分为糖适平实验组和胰岛素对照组,每组50例。对照组患者给予预混人胰岛素及阿卡波糖片,实验组患者给予糖适平及阿卡波糖片。比较治疗前后两组患者空腹血糖(FBG)、肌酐清除率(CCr)、血清肌酐(SCr)、血尿素氮(BUN)及24小时尿蛋白定量(24 h Upro)水平的变化情况。结果:与治疗前相比,两组患者治疗后空腹血糖、血清肌酐、血尿素氮及24小时尿蛋白定量、肌酐清除率均明显改善,差异具有统计学意义(P0.05),但实验组与对照组比较差异无统计学意义(P0.05)。结论:糖适平对2型糖尿病合并糖尿病肾病4期患者无药物积蓄问题,用于治疗2型糖尿病合并糖尿病肾病4期安全有效。     

西格列汀对早期2型糖尿病肾病患者肾功能的影响

目的:研究西格列汀对早期2型糖尿病肾病患者肾小球、肾小管标志性蛋白/酶的影响。方法:早期2型糖尿病肾病患者72例,随机数字表分为对照组36例、治疗组36例;两组均采用糖尿病饮食管理、运动治疗,在控制血糖、血脂、血压的基础上,治疗组给予磷酸西格列汀100 mg 1粒/次,1次/天,持续服药6月。观察治疗前、后两组血肌酐(Scr)、尿素氮(BUN)、糖化血红蛋白(Hb A1c)、血脂、空腹血糖(FBG)、餐后2小时血糖(2 h PBG)、血清胱抑素-C(Cys-C)及24 h尿微量白蛋白(24 h UAE)、尿N-乙酰-β-氨基葡萄糖苷酶(NAG)、尿β2-微球蛋白(β2-MG)的变化。结果:治疗后,治疗组血脂、Hb A1c、FBG、2 h PBG较对照组明显下降,差异有显著性(P0.05)。两组患者24 h UAE、NAG、β2-MG和Cys-C较治疗前均下降,差异有显著性(P0.05);两组治疗后相比,差异具有统计学意义(P0.05)。结论:西格列汀可以有效控制早期DN患者的血糖水平,减少血清Cys-C、尿微量白蛋白水平,减轻肾小管损伤,有利于延缓DN的病程和进展。     

2型糖尿病视网膜病变患者血清和肽素、脂质运载蛋白2水平的表达及其临床意义

摘要 目的：探讨2型糖尿病（T2DM）视网膜病变（DR）患者血清和肽素（copeptin）、脂质运载蛋白2（LCN2）的表达及其临床意义。方法：选取2021年1月~2023年1月期间江南大学附属医院接收的2型糖尿病（T2DM）患者141例，将所有患者分为不合并糖尿病视网膜病变（DR）组（NDR组，n=49）、非增生期DR组（NPDR组，n=45）和增生期DR组（PDR组，n=47），另选取同期行健康体检的志愿者50例作为对照组。比较各组临床指标、生化指标及血清copeptin、LCN2水平，采用Pearson相关性分析血清copeptin、LCN2水平与临床指标及生化指标的相关性，采用多因素Logistic回归分析DR的危险因素。结果：对照组、NDR组、NPDR组、PDR组的血清copeptin、LCN2水平呈逐渐升高趋势（P<0.05）。NDR组、NPDR组、PDR组的体重指数（BMI）、收缩压（SBP）、舒张压（DBP）、甘油三酯（TG）、总胆固醇（TC）、低密度脂蛋白胆固醇（LDL-C）、空腹血糖（FPG）均高于对照组（P<0.05）；对照组、NDR组、NPDR组、PDR组的糖化血红蛋白（HbAlc）、胰岛素抵抗指数（HOMA-IR）呈逐渐升高趋势（P<0.05）；NDR组、NPDR组、PDR组糖尿病病程呈逐渐递增趋势（P<0.05）。Pearson相关性分析显示，copeptin、LCN2水平与HbAlc、HOMA-IR、糖尿病病程呈正相关（P<0.05），与血压、血脂、FPG、BMI无明显相关性（P>0.05）。多因素Logistic回归分析结果显示：糖尿病病程、HbAlc、HOMA-IR、copeptin、LCN2均为DR发生发展的独立危险因素（P<0.05）。结论：高水平copeptin、LCN2可能与DR的发生、发展有关，且与患者糖尿病病程、HbAlc、HOMA-IR关系密切，可用于DR患者的早期诊断及判断其病情的严重程度。     

Significance of Urinary Full-Length Megalin in Patients with IgA Nephropathy

Background and Objectives

Megalin is highly expressed at the apical membranes of proximal tubular epithelial cells. A urinary full-length megalin (C-megalin) assay is linked to the severity of diabetic nephropathy in type 2 diabetes. This study examined the relationship between levels of urinary C-megalin and histological findings in adult patients with IgA nephropathy (IgAN).

Design, Setting, Participants, & Measurements

Urine samples voided in the morning on the day of renal biopsy were obtained from 73 patients with IgAN (29 men and 44 women; mean age, 33 years) and 5 patients with membranous nephropathy (MN). Renal pathologic variables were analyzed using the Oxford classification of IgAN, the Shigematsu classification and the Clinical Guidelines of IgAN in Japan. The levels of urinary C-megalin were measured by sandwich ELISA.

Results

Histological analysis based on the Oxford classification revealed that the levels of urinary C-megalin were correlated with mesangial hypercellularity in IgAN patients (OR = 1.76, 95% CI: 1.04–3.27, P<0.05). There was a significant correlation between the levels of urinary C-megalin and the severity of chronic extracapillary abnormalities according to the Shigematsu classification in IgAN patients (β = 0.33, P = 0.008). The levels of urinary C-megalin were significantly higher in all risk levels of IgAN patients requiring dialysis using the Clinical Guidelines of IgAN in Japan than in the control group. The levels of urinary C-megalin were significantly higher in the high risk and very high risk grades than in the low risk grade (P<0.05). The levels of urinary C-megalin were significantly higher in MN patients compared to the control group.

Conclusions

The levels of urinary C-megalin are associated with histological abnormalities in adult IgAN patients. There is a possibility that urinary C-megalin is an independent predictor of disease progression of IgAN. In addition, our results suggest that urinary C-megalin is a marker of glomerular abnormalities in various glomerular diseases as well as IgAN.     

Elevated Serum Levels of Mannose-Binding Lectin and Diabetic Nephropathy in Type 2 Diabetes

Objective

Inflammation and complement activation initiated by mannose-binding lectin (MBL) may be implicated in the pathogenesis of diabetic vascular complications. We investigated serum MBL levels in type 2 diabetes with diabetic nephropathy (DN) and with persistent normoalbuminuria.

Method

Serum MBL levels were determined in 242 type 2 diabetes with overt nephropathy and 242 type 2 diabetes with persistent normoalbuminuria matched for age, sex, and duration of diabetes, as well as in 100 healthy control subjects. The prediction value of MBL was compared with HbA1c, Hs-CRP and with other known predictors. Multivariate analyses were performed using logistic regression models.

Results

The serum MBL levels were significantly higher in diabetes with DN as compared to with persistent normoalbuminuria (P<0.0001). Multivariate logistic regression analysis adjusted for common factors showed that serum MBL levels≥2950ug/L was an independent indictor of DN (OR=7.55; 95%CI: 3.44–19.04). Based on the ROC curve, the optimal cutoff value of serum MBL levels as an indicator for diagnosis of DN was projected to be 2950ug/L, which yielded a sensitivity of 77.2 % and a specificity of 80.8%, with the area under the curve at 0.809 (95%CI, 0.769—0.848).

Conclusion

Our findings suggested that MBL may be involved in the pathogenesis of DN in type 2 diabetes, and that determination of MBL status might be used to identify patients at increased risk of developing nephropathy complications.     

The Expression of Tristetraprolin and Its Relationship with Urinary Proteins in Patients with Diabetic Nephropathy

Objective

Tristetraprolin (TTP), also known as zinc finger protein 36, is an RNA binding protein that has a significant role in regulating the expression of mRNAs containing AU-rich elements. We postulated that TTP might regulate interleukin (IL)-6 and IL-18 expression in diabetes. This study aimed to test the hypothesis that the levels of TTP are correlated with nephropathy in patients with type 2 diabetes.

Methods

Eighty-seven patients (61.3±9.6 years old) who had been diagnosed with type 2 diabetes mellitus and 41 age and sex matched healthy control subjects were enrolled. The diabetes patients were classified into those without proteinuria, with microalbuminuria, and with clinical proteinuria groups according to the ratio of urinary excretion of albumin/creatinine (ACR).

Results

Serum and urinary levels of IL-6 and IL-18 were significantly elevated, but those of TTP were significantly decreased in patients with diabetes as compared with control subjects. In addition, serum and urinary levels of IL-6 and IL-18 were significantly higher, but those of TTP were significantly lower in patients with proteinuria than in patients without proteinuria or with microalbuminuria. There was a significant correlation between serum TTP and IL-6/IL-18 (correlation coefficients of -0.572 and -0.685, P < 0.05).

Conclusion

These results show that diabetes with clinical proteinuria is accompanied by decreased urinary and serum level of TTP and increased levels of IL-6 and IL-18. Decreased TTP expression might occur prior to the increase in IL-6 and IL-18, and decrease of TTP might provide an earlier marker for glomerular dysfunction than IL-6 and IL-18.     

Association of Levels of Mannose-Binding Lectin and the MBL2 Gene with Type 2 Diabetes and Diabetic Nephropathy

Objective

To investigate the association of Mannose-binding lectin (MBL) and the MBL2 gene with type 2 diabetes and diabetic nephropathy and the influence of MBL2 polymorphisms on serum MBL levels.

Methods

The study population included 675 type 2 diabetic patients with or without nephropathy and 855 normoglycemic controls. The single nucleotide polymorphisms (SNPs) of rs1800450, rs1800451, and rs11003125 of the MBL2 gene were determined by the Multiplex Snapshot method. Serum MBL levels were measured by enzyme-linked immune sorbent assay.

Results

Rs1800450 and rs11003125 SNPs demonstrated strong linkage disequilibrium in the study population (r² = 0.97). The haplotypes constructed from the G allele of rs1800450 and the C allele of rs11003125 increased the risk for type 2 diabetes (OR = 1.2, 95% CI = 1.1–1.4, P = 0.01). For rs1800450, GG and GA genotypes were associated with type 2 diabetes (P = 0.02, 0.01, respectively). For rs11003125, the GC genotype frequency was significantly different between patients and controls (18.1% vs. 24.9%, P = 0.001). Analyses of genotypes and allele frequency distributions among patients with normal UAE, microalbuminuria, and macroalbuminuria showed that there was no obvious evidence of association between the MBL2 gene and diabetic nephropathy. Subjects with the GG genotype of rs1800450 and the CC genotype of rs11003125 had much higher serum MBL levels.

Conclusions

The rs1800450 and rs11003125 SNPs of the MBL2 gene have strong linkage disequilibrium and are associated with type 2 diabetes in the North Chinese Han population. No association was observed between the MBL2 gene and diabetic nephropathy. Subjects with the GG genotype of rs1800450 and the CC genotype of rs11003125 had much higher serum MBL levels. An association between elevated serum MBL and diabetic nephropathy was also observed.     

原发性高血压肾病患者血清CRP、胱抑素C和尿微量白蛋白检测的临床意义

目的:探讨原发性高血压肾病患者血清C反应蛋白(CRP)、胱抑素C和尿微量白蛋白(mALB)水平的改变及其临床意义.方法:采用常规生化法肌酐(Cr)、尿酸(UA)、肌酐清除率(Ccr)、24尿蛋白(U-pro)分别采用免疫比浊法和速率散射比浊法对45例原发性高血压肾病患者治疗前后血清CRP,血清胱抑素C和尿微量蛋白含量变化进行检测,同时选取35例健康正常人作为对照.结果:①经治疗后,原发性高血压肾病患者Cr、UA和U-pro水平均较治疗前明显降低(P<0.05或0.01),Ccr水平显著升高(P<0.01),但Cr、UA和U-pro水平仍显著高于正常对照组,Ccr水平则低于对照组(P<0.01).②患者治疗前后血清CRP,胱抑素C和mALB水平均明显高于对照组(P<0.01),但患者治疗后CRP,胱抑素C和mALB水平明显低于治疗前(P<0.01).③患者血清CRP与胱抑素C和mALB呈明显正相关(P<0.01).结论:检测患者血清CRP、胱抑素C和mALB水平的变化对于监测原发性高血压肾病病程发展,指导临床治疗用药具有重要意义.     

Oral Supplementation with Cholecalciferol 800 IU Ameliorates Albuminuria in Chinese Type 2 Diabetic Patients with Nephropathy

Background

Low vitamin D levels can be associated with albuminuria, and vitamin D analogs are effective anti-proteinuric agents. The aim of this study was to investigate differences in vitamin D levels between those with micro- and those with macroalbuminuria, and to determine whether low dose cholecalciferol increases vitamin D levels and ameliorates albuminuria.

Methods

Two studies were performed in which 25-OH vitamin D₃ (25(OH)D₃) concentrations were determined by electrochemiluminescence immunoassay: 1) a cross-sectional study of patients with type 2 diabetes mellitus (T2DM) (n = 481) and healthy controls (n = 78); and 2) a longitudinal study of T2DM patients with albuminuria treated with conventional doses, 800 IU, of cholecalciferol for 6 months (n = 22), and a control group (n = 24).

Results

1) Cross-sectional study: Compared to controls and T2DM patients with normoalbuminuria, serum 25(OH)D₃ concentrations were significantly lower in patients with macro-albuminuria, but not in those with micro-albuminuria. Serum 25(OH)D₃ levels were independently correlated with microalbuminuria. 2) Longitudinal study: Cholecalciferol significantly decreased microalbuminuria in the early stages of treatment, in conjunction with an increase in serum 25(OH)D₃ levels.

Conclusions

Low vitamin D levels are common in type 2 diabetic patients with albuminuria, particularly in patients with macroalbuminuria, but not in those with microalbuminuria. Conventional doses of cholecalciferol may have antiproteinuric effects on Chinese type 2 diabetic patients with nephropathy.