血清胱抑素C与IgA肾病Lee氏分级和牛津分型的相关性

目的探讨血清胱抑素C(Cys C)与IgA肾病(IgAN) Lee氏分级和牛津分型的相关性,为评估该病严重程度提供依据。方法观察2013年1月—2018年1月在上海中医药大学附属龙华医院肾病科进行肾穿刺活检证实为原发性IgAN的患者191例。根据Lee氏分级与牛津分型间质纤维化与小管萎缩(T)分级分为轻、中、重3组,另根据牛津分型新月体(C)分级分为2组,观察患者血清Cys C、血白蛋白(Alb)、血肌酐(SCr)、尿素氮(BUN)、尿酸(UA)、24 h尿蛋白及24 h尿微量白蛋白水平,采用CKD-EPI公式估算肾小球滤过率(eGFR),分析血清Cys C与Lee氏分级、牛津分型之间的关系。结果 Lee氏分级与T的分组中,随着病理损伤程度的加重,患者血清Cys C、SCr、BUN水平逐渐升高,eGFR水平逐渐降低(P 0.01)。Spearman相关分析显示血清Cys C与Lee氏分级、牛津分型中T分级呈正相关(r=0.768,r=0.624,均P 0.01),与eGFR呈负相关(r=-0.804,P 0.01);上述相关性在多元线性回归中得到证实。含有新月体的患者,血清Cys C水平较不含新月体患者的水平升高(P 0.01),Spearman相关分析显示二者亦有一定的相关性(r=0.181,P 0.01),但多元线性回归提示二者相关性不强,故仍需进一步证实。结论血清Cys C可作为反映IgAN早期病理损伤等级尤其是间质小管损伤程度的敏感性指标。     

胰岛素治疗对2型糖尿病肾病血清C反应蛋白水平的影响

目的:比较2型糖尿病(无肾病)及糖尿病肾病(DN)患者血清C反应蛋白(CRP)的水平,观察应用胰岛素治疗后血清CRP水平的变化。方法:2型糖尿病患者共100例,其中糖尿病(无肾病)为DM组40例,糖尿病肾病组为DN组60例。将DN组患者随机分组,口服糖适平组为DN1、胰岛素治疗组为DN2共治疗12周。选取正常对照组(NC)30例,应用化学发光法测定血CRP水平。结果:NC、DM组、DN组血清CRP水平分别为(2.90±1.8)mg/L、(5.8±3.2)mg/L、(9.2±5.6)mg/L逐渐升高,血清CRP水平与总胆固醇(TC)(r=0.510,P<0.01)、空腹血糖(FBG)(r=0.29,P<0.01)呈正相关。血清CRP在DN2组胰岛素治疗前后分别为(9.30±3.78)mg/L、(4.78±2.11)mg/L下降明显,有统计学差异(P<0.01);DN1组糖适平治疗前后(9.04±4.9)mg/L、(8.30±1.8)mg/L下降,无统计学差异(P>0.05)。结论:2型DM(无肾病)及DN组血清CRP水平逐渐升高,且DN经胰岛素治疗后血清CRP水平明显下降。     

2型糖尿病肾病和糖尿病性视网膜病变的相关性研究

目的探讨2型糖尿病肾病和糖尿病性视网膜病变的发病机制及其两者之间的相关性。方法选择2004年1月至2014年12月北京中日友好医院肾内科经肾穿刺活检确诊的2型糖尿病肾病(diabetic nephropathy,DN)患者95例,按照肾脏病理改变程度分为5组,即DNⅠ组10例,DNⅡa组12例,DNⅡb组16例,DNⅢ组54例,DNⅣ组3例;将不同组间视网膜病变进行比较,分析视网膜病变与肾脏损伤之间的关系,以及视网膜病变与常用临床指标[24 h尿蛋白定量、空腹血糖(fasting blood glucose,FBG)、糖化血红蛋白(glycosylated hemoglobin,HbA1c)、血肌酐(SCr)及肌酐清除率(creatinine clearance rate,Ccr)]之间的关系。结果 DN患者肾脏损伤病理分型与视网膜病变呈正相关(r=0.458,P=0.016),但仍有23.2%患者无视网膜病变,分别发生在80.00%的DNⅠ组、33.33%的DNⅡa组、12.50%的DNⅡb组、14.81%的DNⅢ组患者中。临床指标中仅24 h尿蛋白定量与糖尿病视网膜病变的发生和发展相关。结论尽管糖尿病性视网膜病变常被提示DN,但少部分DN不存在视网膜病变的情况也应被重视。     

补体旁路途径过度活化在恶性高血压肾硬化中的作用

目的研究补体旁路途径(alternative complement pathway)过度活化在恶性高血压肾硬化中的作用。方法(1)选取本院经肾穿刺活检证实为恶性高血压肾硬化患者50例为病例组,零点行肾穿刺活检的供肾者25例为正常对照组,采用酶联免疫吸附法(ELISA)检测血浆及尿液中的补体旁路途径活化起始B因子、正向调节P因子、负向调节H因子及补体活化终末产物C3a、C5a水平。(2)免疫组化法检测补体活化终末产物C5b-9、C4d及凝集素途径活化产物甘露糖结合凝集素(MBL)在肾活检组织的沉积;免疫荧光双染检测C5b-9与CD34(内皮细胞标志物)在小动脉内皮及肾小球毛细血管内皮的沉积。结果(1)恶性高血压肾硬化患者血浆及尿液中补体B因子、P因子、C3a及C5a均高于正常对照组(均P<0.05),而H因子则低于正常对照组(P<0.05)。(2)恶性高血压肾硬化患者血浆中补体P因子与24 h尿蛋白量呈正相关(rs=0.465,P=0.001),而补体B因子、H因子、C3a、C5a与血肌酐及24 h尿蛋白量无明显相关性。恶性高血压肾硬化患者尿B因子/尿肌酐、尿P因子/尿肌酐、尿C3a/尿肌酐与血肌酐均呈正相关(rs=0.483,P<0.001;rs=0.352,P=0.012;rs=0.319,P=0.024),尿H因子/尿肌酐与血肌酐及24 h尿蛋白量均呈负相关(rs=-0.299,P=0.035;rs=-0.342,P=0.015),尿C5a/尿肌酐与血肌酐及24 h尿蛋白量均呈正相关(rs=0.525,P<0.001;rs=0.496,P<0.001)。(3)免疫组化显示,恶性高血压肾硬化患者C5b-9沉积于小动脉壁及肾小球毛细血管壁,而正常对照组肾组织中未见沉积。恶性高血压肾硬化患者肾脏C5b-9沉积强度评分与血肌酐及24 h尿蛋白量呈正相关(rs=0.791,P<0.001;rs=0.345,P=0.014)。双重免疫荧光标记法可见C5b-9、CD34沉积于小动脉内皮及肾小球毛细血管内皮。(4)恶性高血压肾硬化患者血浆中B因子与C3a(r=0.331,P=0.022)、P因子与C5b-9评分(rs=0.300,P=0.034)均呈正相关;尿液中补体旁路途径活化B因子与C3a、C5a及C5b-9均呈正相关(rs=0.311,P=0.028;rs=0.465,P=0.001;rs=0.428,P=0.002),P因子与C3a、C5a也均呈正相关(rs=0.307,P=0.030;rs=0.442,P=0.001)。恶性高血压肾硬化患者免疫组化可见C4d沉积于小动脉及肾小球,而未见凝集素途径活化产物MBL沉积。结论补体旁路途径过度活化可能参与恶性高血压肾硬化的发生。恶性高血压肾硬化严重程度与补体旁路途径的活化水平相关。     

RAAS、血清转化生长因子-β_1对糖尿病肾病伴高血压患者肾功能影响研究

目的:探讨肾素-血管紧张素-醛固酮系统(RAAS)、血清转化生长因子-β1(TGF-β1)对糖尿病肾病(DN)伴高血压患者肾功能的影响。方法:选择2012年7月~2014年1月我院收治的DN患者87例作为研究对象,根据是否合并高血压分为单纯DN组(n=44)和DN伴高血压组(n=43),同时选取门诊健康体检者40例作为对照组,比较各组对象肾素、血管紧张素Ⅱ(ATⅡ)、醛固酮(ALD)、尿素氮(BUN)、血肌酐(Scr)、肾小球滤过率(e GFR)、尿白蛋白排泄率(UAER)变化情况。结果:与对照组比较,DN伴高血压组和单纯DN组TGF-β1、肾素、ATⅡ、UAER、Scr均升高,e GFR显著降低(P0.05);DN伴高血压组Ⅰ期、Ⅱ期、Ⅲ期各指标与单纯DN组比较差异无统计学意义(P0.05);DN伴高血压组Ⅳ期、Ⅴ期TGF-β1、肾素、ATⅡ、UAER、Scr、BUN均高于单纯DN组,e GFR均低于单纯DN组,差异有统计学意义(P0.05);肾素、ATⅡ与Scr、UAER、TGF-β1呈显著正相关性(r0,P0.05),与e GFR呈显著负正相关性(r0,P0.05);TGF-β1与Scr、UAER呈显著正相关性(r0,P0.05),与e GFR呈显著负正相关性(r0,P0.05)。结论:在DN伴高血压患者中RAAS和血清TGF-β1水平显著升高,随分期增加,RAAS和血清TGF-β1水平显著增加,二者相互作用可能加重了DN伴高血压患者肾功能损害。     

原发性IgA肾病不同病理分级方法与临床指标及预后的关联性分析

目的探讨原发性IgA肾病不同病理分级方法与临床指标的相关性及对预后的判断。方法收集明确诊断为原发性IgA肾病且随访大于12个月的185例患者的病例资料,分别比较牛津分型、Lee分级及Hass分型与临床指标的相关性以及对预后的判断。结果 (1)牛津分型的系膜细胞增生(M)、内皮细胞增生(E)、节段性小球硬化/黏连(S)、肾小管萎缩/间质纤维化(T)、新月体形成(C)及Lee分级、Hass分型均与血肌酐(serum creatinine, Scr)、24 h尿蛋白定量(24 hour urinary protein quantity, 24h-UP)及估算肾小球滤过率(estimated glomerular filtration rate, eGFR)的差异有统计学意义(P0.05);牛津分型的M、S、T与血尿酸(uric acid, UA)的差异有统计学意义(P0.05);牛津分型的T及Lee分级与平均动脉压(mean arterial pressure, MAP)差异有统计学意义(P0.05)。相关性分析得出牛津分型的T与eGFR负相关关系最强(r=-0.558,P0.001),与尿素氮(blood urea nitrogen, BUN)、Scr、UA正相关关系最强(r=0.424、r=0.554、r=0.407,P均0.001);Lee分级与血红蛋白(hemoglobin, Hb)、白蛋白(albumin, Alb)负相关关系最强(r=-0.217、r=-0.367,P=0.003、P0.001),与24h-UP、MAP正相关关系最强(r=0.312、r=0.202,P0.001、P=0.006)。(2)牛津分级M、E、S组间的肾脏累积生存率差异无统计学意义(P0.05);T2组的肾脏累积生存率较T0组及T1组低(P0.05);C2组的肾脏累积生存率较C0组及C1组低(P0.05)。Lee分级与Hass分级的Ⅰ、Ⅱ、Ⅲ级/型间两两比较及Ⅳ、Ⅴ级/型间的肾脏累积生存率差异无统计学意义(P0.05),Ⅳ、Ⅴ级/型的肾脏累积生存率较Ⅰ、Ⅱ、Ⅲ级/型低(P0.05)。结论原发性IgA肾病病理分级与临床指标具有一定的相关性,其中牛津分型的T在评价肾功能改变方面临床适用性最强,对于伴有血压升高、贫血改变、白蛋白降低及蛋白尿的IgA肾病患者更适宜使用Lee分级进行病理评价。肾小管萎缩/间质纤维化50%、新月体形成25%的患者及Lee分级、Hass分型为Ⅳ、Ⅴ级/型的患者预后较差。     

急性肾损伤患者尿肝脏型脂肪酸结合蛋白的水平变化及其意义

目的探讨急性肾损伤(acute kidney injury,AKI)患者尿肝脏型脂肪酸结合蛋白(livertype fatty acid binding protein,L-FABP)的水平变化及其意义。方法选择2013年10月至2015年12月我院收治的重症住院患者83例,根据患者入院时是否发生AKI分为AKI组和非AKI组,比较2组患者的各项生化指标[尿素氮、血肌酐、尿N-7乙酰-β-D葡萄糖苷酶(N-acetyl-β-D-glucosaminidase,NAG)、胱抑素C(cystatinC,Cys C)、肾小球滤过率]、L-FABP水平的差异,分析尿L-FABP水平与上述各生化指标的相关性以及尿L-FABP水平预测患者发生AKI的ROC曲线分析。结果 AKI组入院后第一次检查的血尿素氮、血肌酐、尿NAG、Cys C均高于非AKI组,差异有统计学意义(P0.05);AKI组的肾小球滤过率低于非AKI组,差异有统计学意义(P0.05);AKI组在入院12 h时尿L-FABP水平开始升高,而非AKI组的尿L-FABP水平维持在较稳定的水平;AKI组入院第12 h、第24 h、第48 h时尿LFABP水平均高于非AKI组,差异有统计学意义(P0.05);AKI患者入院第12 h的尿L-FABP与入院后第一次检查血尿素氮、血肌酐、尿NAG、Cys C均呈正相关(r=0.234,0.308,0.274,0.295),尿LFABP与肾小球滤过率呈负相关(r=-0.485);ROC曲线分析结果显示,诊断阈值为49.46,灵敏度为60.0%,特异度为95.83%,约登指数为0.558,曲线下面积为80.89%。结论 AKI患者的尿L-FABP水平异常升高,尿L-FABP可作为预测患者发生AKI的重要临床指标。     

糖尿病肾病患者肾活检组织血管紧张素受体表达及与肾脏病理损伤的关系

目的:观察糖尿病肾病(DN)患者肾活检组织血管紧张素受体表达情况,并探讨与肾小球及肾间质病理损伤程度的关系。方法:选取2004年1月~2014年9月在中日友好医院肾内科行肾穿刺活检并经临床及病理诊断为DN的患者90例,其中病理分型为Ⅰ型+Ⅱa型14例,Ⅱb型13例,Ⅲ型58例,Ⅳ型5例。使用免疫组化染色分析累积光密度评估肾组织中AT1、AT2及MAS受体表达情况。比较各型患者的临床资料、肾脏AT1、AT2及MAS受体表达,并评估后者与其他肾小球损伤病理指标(缺血肾小球百分比、球性硬化肾小球百分比及新月体百分比)和肾间质损伤病理指标(肾间质纤维化肾小管萎缩评分、肾间质炎症评分及小动脉玻璃样变评分)之间的相关性。结果:肾小球AT1受体表达与缺血肾小球百分比和球性硬化肾小球百分比均存在显著正相关。病理分型为Ⅲ型的患者肾小球和肾间质的AT2受体表达均显著高于Ⅱb型患者,且肾小球AT2受体表达与缺血肾小球百分比呈现显著正相关。结论:DN患者肾组织血管紧张素受体表达与肾脏病理改变存在一定的相关性,为深入了解RAS在DN病理损伤过程的作用提供了依据。     

肾组织补体C3沉积与糖尿病肾病病理及临床表现的关系

目的：探讨肾组织补体C3的沉积与糖尿病肾病病理及临床表现之间的关系。方法：回顾性分析我科2003年1月~2013年1月收治的2型糖尿病患者145例,根据病理分型标准对患者进行病理分型,统计不同病理类型补体C3的沉积情况,并以其为依据,分为C3阳性组及C3阴性组,比较两组在病理及临床指标之间的差异,并比较不同病理类型之间补体C3沉积的差异。结果：145例患者中,肾组织C3阳性者共49例（33.8%）,根据C3沉积情况将患者分为C3阳性组及C3阴性组,两组患者在年龄、糖尿病病程、血压、24 h尿蛋白定量、血清补体C3等方面差异无统计学意义（P〉0.05）,在血浆白蛋白、血清肌酐、估算肾小球滤过率方面的差异有统计学意义（P〈0.05或〈0.01）;随着病理等级的升高,C3沉积率升高,差异有统计学意义（P〈0.05或〈0.01）。结论：肾组织补体C3的沉积可能加重了糖尿病肾病患者的病理及临床改变。     

测定血清胱抑素—C在评估肾脏功能中的意义

目的 探讨血清胱抑素—C(cystatin C，Cys—C)的浓度变化与肾脏功能的关系。方法 将87例多种肾脏疾病患者与24例健康者血清标本在查血肌酐及尿素氮的同时采用ELISA方法检测Cys-C的浓度，其中31例患者同时检测肌酐清除率(Ccr)。结果 血清中Cys—C浓度变化趋势与血清肌酐及尿素氮相同，呈显著相关(r＝0．823，r＝0．715)，Ccr与Cys—C及血肌酐呈显著负相关(r＝—0．922，r＝—0．668)。结论 血清Cys-C浓度可作为评估肾功能的敏感指标。     

糖尿病肾病患者血清C1q/肿瘤坏死因子相关蛋白3的表达及临床意义

目的:探讨血清C1q/肿瘤坏死因子相关蛋白3(CTRP3)的表达水平与糖尿病肾病不同程度肾脏损害的关系。方法:选取2019年1月至2019年5月本院就诊的患者,符合NKF-KDOQI标准的2型糖尿病肾病患者为糖尿病肾病组(DN组,41例),再依据肾小球滤过率估计值(eGFR)将其分为两个亚组{EDN组[21例,肾小球滤...     

Role of C3a and C5a in focal segmental glomerulosclerosis

Objective To study the role of C3a and C5a in focal segmental glomerulosclerosis (FSGS) patients. Methods (1) A total of 66 patients with FSGS confirmed by renal biopsy were selected, including 18 cases of tip lesion, 11 cases of perihilar, 22 cases of not otherwise specified (NOS), 10 cases of cellular, and 5 cases of collapsing FSGS. The normal renal tissue resected from patients with kidney tumor was taken as a negative control. The expression of C3a and C5a in renal tissues was detected by immunohistochemistry. (2) Serum and urine samples from these 66 FSGS patients were collected, and serum and urine samples from 10 healthy adult selected from the same physical examination center in the same term were used as normal controls. The levels of C3a and C5a in serum and urine were detected by enzyme-linked immunosorbent assay (ELISA). Results (1) Immunohistochemical results showed that C3a and C5a were deposited in glomerulus of FSGS patients, and no deposition in normal renal tissues. The semi-quantitative score showed that kidney C3a score was significantly correlated with serum creatinine (r=0.547, P＜0.001) and 24 h urine protein (r=0.329, P=0.007) in FSGS patients, and kidney C5a score was also significantly correlated with serum creatinine (r=0.415, P＜0.001) and 24 h urine protein (r=0.414, P＜0.001) in FSGS patients. (2) The levels of serum C3a and C5a in FSGS patients were higher than those in healthy adults (both P＜0.05), but there was no significant difference among the five pathological types (P＞0.05). The levels of urinary C3a/urinary creatinine, urinary C5a/urinary creatinine were higher in FSGS patients than those in healthy adults (all P＜0.05). The levels of urine C3a/urinary creatinine and urinary C5a/urinary creatinine in collapsing FSGS were higher than other FSGS types (all P＜0.01), but there was no significant difference among the tip lesion, the perihilar, the not otherwise specified and the cellular (P＞0.05). (3) Urinary C3a/urinary creatinine levels were significantly correlated with serum creatinine (r=0.774, P＜0.001) and 24 h urine protein (r=0.430, P＜0.001) in FSGS patients, and urinary C5a/urinary creatinine levels were also significantly correlated with serum creatinine (r=0.677, P＜0.001) and 24 h urine protein (r=0.333, P=0.007) in FSGS patients. Conclusion Complement C3a and C5a may be involved in the pathogenesis of FSGS and may be related to the severity of FSGS.     

系统性红斑狼疮患者贫血和疾病活动及肾脏损害的关系

目的 探讨系统性红斑狼疮(systemic lupus erythematosus,SLE)患者贫血和疾病活动及肾脏损害的关系.方法 选取2016年9月至2019年10月乐山市人民医院收治的187例SLE患者作为SLE组,另选取187名体检健康者作为健康对照组,比较其贫血发生率.根据血红蛋白(hemoglobin,Hb...     

Role and mechanism of C3a-C3a receptor in autosomal dominant polycystic kidney disease

Objective To explore the role and mechanism of C3a-C3a receptor (C3aR) in the progression of autosomal dominant polycystic kidney disease (ADPKD). Methods Renal tissues of ADPKD patients and PKD1 knockout mice were collected. Then the expression of C3a-C3aR, Ki67 and F4/80 in renal tissues was observed. Macrophages were stimulated with lipopolysaccharide (LPS) and interleukin 4 respectively. The expression of C3aR, TNF-α, typing markers and related signal pathway proteins was detected in each group. PKD1 knockout mice were treated with C3aR inhibitor SB290157 (1 mg/kg). Renal pathology, cyst-related indicators and renal function were observed. Results The expression of C3a and C3aR in ADPKD was up-regulated (both P＜0.05); C3aR and F4/80 were co-located in the kidney of polycystic kidney disease (PKD) mice, indicating that C3aR was mainly expressed on membrane of macrophages. In vitro, the expression of C3aR was up-regulated in M1 macrophages (P＜0.05). After the stimulation of C3a, the expression of iNOS, TNF-α and IL-6 mRNA in M1 macrophages were up-regulated (all P＜0.05), as well as the secretion of TNF-α, indicating that C3a not only affected the expression of inflammatory factors of M1 macrophages, but also affected the inflammatory microenvironment. In addition, C3a significantly activated Akt in M1 macrophages (P＜0.05). Compared with the control group, the treatment group showed a decrease in C3a-C3aR as well as serum BUN, Scr, cyst index, and two kidneys weight/body weight (2KW/BW) (all P＜0.05), and ADPKD related pathway protein expression such as p-ERK and p-P65 was significantly down-regulated (all P＜0.05). Conclusions The increased C3a in polycystic kidney tissue causes infiltration and activation of macrophages through C3aR, and then promotes ADPKD progression. The mechanism may be mediated by Akt activation and increased TNF-α production. C3aR antagonist is a potential research direction in the treatment of ADPKD.     

Protective effect of C5a receptor 1 antagonist on ascending urinary tract infection in mice

Objective To investigate the protective effect of complement 5a receptor 1 (C5aR1) antagonist on ascending urinary tract infection in mice. Methods (1) Female C57BL/6 mice were randomly divided into experimental and control groups: 38 mice in each group, and inoculated with E. coli by urethral catheterization to set up the ascending urinary tract infection model. C5aR1 antagonist (W54011 or PMX53) and corresponding control (PBS or control peptide) were initially given either at 2 h before or 3 h after infection by intraperitoneal injection. Mice were sacrificed to assess the infection in bladder and kidney at 24 or 48 h after infection. The bacterial load of bladder and kidney tissue was measured by agar plate assay. The mRNA expression of renal inflammatory factors was detected by real-time RCR. The renal tissue injury and inflammatory cell infiltration were assessed by HE staining and pathological scores. (2) Primary cultured renal tubular epithelial cells were randomly divided into antagonist and control groups to detect and compare the bacterial adhesion to renal tubular epithelial cells in vitro. Results Compared with control groups, the initial delivery of C5aR1 antagonist (W54011 or PMX53) before E.coli inoculation reduced the bacterial load in bladder and kidney tissue 48 h after infection (all P＜0.01). In experimental group given W54011 before infection, the renal pathological scores were reduced (both P＜0.05), as well as renal inflammatory factor expressions: CXCL-1 mRNA, IL-6 mRNA and TNF-α mRNA (all P＜0.05). Compared with corresponding control groups, the initial delivery of PMX53 after E. coli inoculation could also reduce the bacterial load in bladder and kidney tissue 48 h after infection (both P＜0.01). Furthermore, C5aR1 antagonists W54011 and PMX53 could decrease bacteria adhesion to renal tubular epithelial cells in vitro, compared with control groups (both P＜0.05). Conclusions C5aR1 antagonists can significantly attenuate renal tissue injury, ameliorate renal inflammation and the adhesion of bacteria to renal epithelial cells. C5aR1 may be an effective target for the prevention and treatment of urinary tract infection.     

Correlation between serum C3 and glomerular microthrombosis in patients with lupus nephritis

Objective To investigate the correlation between serum C3 and glomerular microthrombosis in patients with lupus nephritis (LN). Methods Patients who were diagnosed as LN by renal biopsy hospitalized in Department of Nephrology, the First Affiliated Hospital of Shenzhen University from January 2010 to February 2019 were retrospectively analyzed and they were divided into glomerular microthrombosis group (GMT group) and non-glomerular microthrombosis group (non-GMT group). The demographic data, clinical characteristics, pathology and prognosis of the two groups were compared. Logistic regression and smooth curve fitting of generalized additive mixed model analysis were used to explore the correlation between serum C3 and glomerular microthrombosis. Renal prognosis of the two groups were compared by the Kaplan-Meier survival curve. Results A total of 116 patients were enrolled, aged (32.79±11.43) years old, in which 108 cases (93.10%) were female. Thirty-seven patients (31.90%) were confirmed to be combined with GMT (GMT group) and 79 cases were not (non-GMT group). Compared with the non-GMT group, patients in the GMT group were relatively older (t=-2.876, P=0.002), with higher proportion of hypertension ( χ2=7.492, P=0.006)，higher urine protein quantitation (Z=-2.115, P=0.003), lower levels of eGFR and serum complement C3 (Z=3.469, P＜0.001; t=1.744, P＜0.001), higher systemic lupus erythematosus disease activity index (t=-2.758, P=0.007). As to the pathological characteristics, type IV LN patients were the majority (72.97%). Proportion of crescents and pathological activity indicators of the GMT group were higher (Z=-1.866, P=0.002; t=-5.005, P＜0.001), nuclear fragmentation, endothelial hyperplasia and renal tubular atrophy were more serious ( χ2=14.987, P＜0.001; χ2=15.695, P＜0.001; χ2=4.130, P=0.042). Multivariate logistic regression analysis indicated that serum complement C3 was a relational factor of the formation of GMT in LN patients (OR=0.966, 95％CI 0.938-0.995, P=0.023). Smooth curve fitting of generalized additive mixed model analysis indicated that level of complement C3 had a linear relationship with the changing trend of GMT. The Kaplan-Meier curve showed that there were statistical differences between the two groups in terms of complete remission of urine protein (Log-rank χ2=5.858, P=0.016) and doubled serum creatinine /end-stage renal disease (Log-rank χ2=3.945, P=0.047). Conclusions Serum C3 is closely related to the formation of GMT in LN patients, and statistical differences were demonstrated in the renal prognosis of GMT group and non-GMT group.     

C4d沉积在抗体介导的慢性排斥反应中的临床意义

目的 探讨移植肾肾小管周围毛细血管补体片段C4d沉积与抗体介导的慢性排斥反应的病理形态、移植肾功能及预后的关系.方法 应用免疫组织化学技术检测77例肾移植受者移植肾肾小管周围毛细血管中C4d的沉积情况,根据检测结果分为C4d阳性组(35例)和C4d阴性组(42例).检测并比较C4d阳性和阴性组受者移植肾的病理形态结构、移植肾功能及预后.结果 与C4d阴性组比较,C4d阳性组受者移植肾肾小管萎缩和肾小球基底膜增生分层的例数明显增多,差异有统计学意义(P＜0.05).C4d阳性组受者的血肌酐水平在移植肾穿刺后12个月时较C4d阴性组受者明显升高,分别为(379.1±260.2)μmol/L和(260.5±175.3)μmol/L,差异有统计学意义(P＜0.05).C4d阳性组受者移植肾穿刺明确C4d阳性后1年内移植肾存活率为62.9%(22/35),而阴性组受者为83.3%(35/42),两组比较,差异有统计学意义(P＜0.05).结论 在抗体介导的慢性排斥反应中,移植肾C4d沉积常见的病理学改变为肾小管萎缩和肾小球基底膜增生分层,C4d阳性抗体介导的体液性慢性排斥反应加快了移植肾功能丧失的进展速度,使C4d阳性受者的移植肾功能丧失率升高,导致存活率降低.     

Transformation of DNA demethylation in the regulatory region of TGFB1 gene in patients with diabetic nephropathy

Objective To investigate the role of DNA methylation changes in the regulatory region of TGFB1 gene in patients with diabetic nephropathy (DN). Methods According to the WHO 1999 guideline for diabetes mellitus diagnosis and classification standard, 91 patients who were hospitalized in June 2013 to May 2015 and diagnosed as diabetes mellitus were selected, including 42 patients with diabetes mellitus (DM group) and 49 with diabetic nephropathy (DN group). Thirty cases with health examination were selected as healthy control group (Con group). DNA was extracted from all the subjects' peripheral blood and modified by sodium bisulfite. DNA methylation status of TGFB1 gene regulatory region was screened by methylation specific PCR and the DNA methylation level was detected by bisulfite sequencing PCR. ELISA was used to test serum TGF-β1. Blood urea nitrogen, creatinine, fasting blood sugar, postprandial blood sugar, glycosylated hemoglobin and urinary albumin to creatinine ratio (UACR) were detected by automatic biochemistry analyzer. Pearson correlation analysis and multiple stepwise regression were used to analysis TGF-β1-related factors, the correlation between the level of serum TGF-β1 and the pathological grade was analyzed in DN patients. Results There were 12.2% patients in DN group with DNA methylation of TGFB1 gene regulation region, lower than those in DM group (42.8%) with Con group (73.3%) (all P＜0.05). The methylation level of TGFB1 regulatory region was 12.5%±8.1% in DN group, significantly lower than those in DM group (35.6%±6.0%) and Con group (66.7%±9.1%) (all P＜0.05). Moreover, compared with that in DM group (1367.22±126.13 ng/L) and Con group [(296.38±74.37) ng/L], TGF-β1 expression was increased significantly in DN group [(2885.73±411.36 ng/L] (all P＜0.01). In DN patients serum TGF-β1 was correlated with eGFR (β=-0.690, P＜0.01) and the methylation (β=-0.302, P＜0.01), and the serum TGF-β1 was negatively correlated with DNA methylation level (r=-0.925, P＜0.01), but positively correlated with the pathological scores among glomerulus, tubulus and arterioles (rs=0.847, P＜0.01). Meanwhile the methylation level related to the pathological grade (χ2=23.667, P=0.04). Conclusion Demethylation in the regulatory region of TGFB1 may play an important role in the activation of TGFB1 induced by high glucose in mesangial cells, so as to participate in the occurrence and development of DN.     

来氟米特对糖尿病大鼠肾脏Podocalyxin表达的影响

目的：研究来氟米特对糖尿病大鼠肾脏Podocalyxin蛋白表达的影响。方法：48只雄性Wistar大鼠随机分为正常对照组、糖尿病肾病模型组、来氟米特干预组、氯沙坦干预组,每组12只。腹腔注射STZ建立糖尿病肾病大鼠模型,给予药物干预。观察各组大鼠血糖、24h尿微量白蛋白量的变化,8周、12周末各组大鼠血尿素氮（BUN）、肌酐（Scr）、肾脏组织病理变化及肾组织Podocalyxin表达水平。结果：8周、12周末模型组、来氟米特干预组、氯沙坦干预组24h尿微量白蛋白定量较正常对照组显著增高（P〈0.05）,肾组织病理损伤明显,大鼠Podocalyxin蛋白表达均显著低于正常对照组（P〈0.05）。8周、12周末干预组24h尿微量白蛋白定量、BUN、Scr水平显著低于同期模型组（P〈0.05）,肾组织病理损伤较模型组明显减轻,大鼠肾组织Podocalyxin蛋白表达显著高于同期模型组（P〈0.05）。结论：来氟米特能够上调糖尿病大鼠肾组织Podocalyxin表达水平,对糖尿病肾脏损伤有保护作用。     

递增式血液透析对终末期肾病患者肾功能、微炎症及死亡率的影响

目的研究递增式血液透析(IHD)对终末期肾病(ESRD)患者肾功能、微炎症及死亡率的影响。 方法选取2017年7月至2021年6月于我院行血液透析(HD)治疗的ESRD患者84例,按照随机数字表法将84例ESRD患者分为递增组(n＝42)与常规组(n＝42)。治疗前及治疗6个月后,观察两组透析充分及生存情况、血尿素氮(BUN)、胱抑素C(CysC)、血清肌酐(Scr)、残余尿量(RUV)、尿素氮下降率(URR)、Kt/V等肾功能指标,血清C反应蛋白(CRP)、白细胞介素-6(IL-6)、肿瘤坏死因子-α(TNF-α)和β2微球蛋白(β2-MG)等微炎症指标,以及透析期间不良反应。 结果与常规组相比,递增组透析充分率增高,死亡率降低(P<0.05)。治疗6个月后,与常规组相比,递增组的BUN、CysC、Scr、RUV降低;URR、Kt/V增高(P<0.05);血清CRP、IL-6、TNF-α及β2-MG水平降低(P<0.05);不良反应发生率降低(P<0.05)。 结论IHD可以保护ESRD患者的残余肾功能,抑制机体微炎症,降低不良反应率和死亡率。