糖尿病肾病中足细胞损伤机制的研究进展

糖尿病肾病（ diabetic nephropathy,DN）是糖尿病重要的微血管并发症之一,也是终末期肾衰竭重要的病因。足细胞（ podocyte）在DN进展过程中发挥了重要作用,并且足细胞损伤涉及多条信号通路的共同影响,比如Rho／ROCK信号通路、炎症反应、氧化应激及线粒体损伤等。本文就这些机制进行论述,旨在阐明足细胞损伤在DN发病过程中的重要作用,为进一步研究DN的病理生理机制及防治带来新的理论依据。     

维生素D受体在糖尿病肾病足细胞损伤及蛋白尿缓解中的作用

目的探讨维生素D受体(VDR)在糖尿病肾病(DKD)足细胞中的表达水平及在足细胞损伤及蛋白尿缓解中的作用。方法(1)本研究纳入了65例诊断患有2型糖尿病(伴或不伴蛋白尿)的患者,并纳入了25例年龄和性别相匹配的健康体检者为对照组。根据白蛋白/肌酐(ACR)的尿排泄比例对2型糖尿病患者进行分组,分别为无蛋白尿(ACR<30 mg/g,n=24)、微量白蛋白尿(ACR 30~300 mg/g,n=18)和临床蛋白尿(ACR>300 mg/g,n=23)。另选择25例经肾活检确诊的DKD患者作为DKD组。正常肾脏组织标本均取自泌尿外科同一时期肾脏肿瘤切除患者10例。将各组检测指标进行对比,同时采用实时定量PCR、ELISA法和免疫组化法检测VDR在各组患者的血液、尿液样本和肾脏组织中的表达情况,以及使用Pearson相关分析分析VDR与尿蛋白的相关性。(2)在2型糖尿病肾病小鼠模型中对上述结果进行验证,将遗传背景均为C57BLKs/J的雄性db/db小鼠及同窝出生的db/m小鼠,随机分为正常对照组(A组)、DKD对照组(B组)、DKD二甲基亚砜处理组(C组)、DKD帕立骨化醇(VDR激动剂)处理组(D组),C、D组连续腹腔注射处理8周,对照组不做任何处理。小鼠10周龄时开始连续干预8周,在小鼠22周龄(开始干预后12周)检测各组小鼠体重、血、尿生化指标对比;Western印迹法检测β⁃catenin、VDR的变化;免疫荧光观察足细胞标志蛋白podocin及足细胞损伤蛋白α⁃SMA的表达变化。结果(1)与正常健康对照组相比,无蛋白尿组、微量白蛋白尿组和临床蛋白尿组的糖尿病患者血浆中VDR的mRNA和蛋白水平均较低(均P<0.05);与无蛋白尿组的糖尿病患者相比,微量白蛋白尿组和临床蛋白尿组的糖尿病患者血浆中VDR的mRNA和蛋白水平均较低(均P<0.05)。(2)与正常健康对照组相比,无蛋白尿糖尿病组和DKD组患者血浆中VDR的mRNA和蛋白水平均较低(均P<0.05);与无蛋白尿糖尿病组患者相比,DKD组患者血浆中VDR的mRNA和蛋白水平亦较低(均P<0.05)。(3)免疫组化结果显示,DKD组肾组织中VDR的表达明显少于正常对照组。(4)DKD患者血浆中VDR mRNA相对水平与ACR呈负相关(r=-0.342,P<0.05)。(5)各组尿液上清液中VDR的水平与血浆中的水平呈相反趋势。(6)Western印迹结果显示,B组、C组肾小球足细胞β⁃catenin蛋白表达高于D组(均P<0.05),VDR蛋白的表达低于D组(均P<0.05);免疫荧光结果显示,B组、C组肾小球足细胞podocin的表达低于D组(均P<0.05),α⁃SMA的表达高于D组(均P<0.05)。结论VDR高表达缓解DKD足细胞损伤及蛋白尿。     

益肾胶囊对糖尿病肾病大鼠足细胞损伤的影响

目的：观察益肾胶囊对糖尿病肾病大鼠足细胞损伤的影响。方法：32只大鼠随机分为正常对照组、糖尿病肾病模型组（模型组）、益肾胶囊组、苯那普利组,每组各8只。益肾胶囊组每日每只灌胃益肾胶囊（2.5g·kg^-1·d^-1）,苯那普利组每日每只灌胃苯那普利（2.5g·kg^-1·d^-1）,正常对照组及模型组每日给予等量的蒸镏水。测定血压、24h尿蛋白定量、血肌酐（Scr）、尿素氮（BUN）,并计算内生肌酐清除率（Ccr）;光镜检查肾组织病理变化,电镜及免疫荧光法检测肾组织及尿液中足细胞变化等。结果：实验24周后,模型组大鼠血压、24h尿蛋白定量、BUN、Scr较正常对照组明显增高（均P〈0.05）,益肾胶囊组和苯那普利组可降低糖尿病肾病大鼠血压、24h尿蛋白定量、BUN、Scr（均P〈0.05）等;模型组足细胞podocalyxin蛋白表达明显低于正常对照组（P〈0.05）,益肾胶囊组及苯那普利组大鼠足细胞podocalyxin蛋白表达较模型组显著增加（P〈0.05）;两治疗组之间比较无统计学差异。正常对照组尿液偶见podocalyxin阳性足细胞,模型组尿液足细胞排泄较正常对照组明显增多（P〈0.05）,益肾胶囊组及苯那普利组,大鼠尿液足细胞排泄减少（P〈0.05）。结论：益肾胶囊可通过减轻糖尿病肾病大鼠足细胞损伤而具有一定的肾保护作用。     

ARBs和活性维生素D在糖尿病肾病治疗中的新进展

糖尿病肾病作为糖尿病的微血管并发症,是导致终末期肾病的主要原因之一.肾素血管紧张素(RAS)在糖尿病肾病肾脏损伤过程中扮演重要作用.RAS抑制剂在临床广泛使用,但却会引起肾素补偿性增加,从而限制了RAS抑制剂的疗效.维生素D通过抑制肾素表达从而能负性调节RAS.RAS抑制剂联合维生素D类似物能显著改善糖尿病肾病的肾脏损...     

足细胞在糖尿病肾病中损伤机制研究进展

流行病学研究结果发现,糖尿病肾病是目前导致终末期肾功能衰竭的主要原因之一.微量蛋白尿的产生不仅可以作为临床糖尿病肾病早期诊断指标之一,其持续的存在也是肾脏病进行性发展的独立危险因子.以往肾小球血流动力学的改变被认为是蛋白尿产生的基础,现在足细胞病变在蛋白尿形成中的作用越来越受到重视.探讨足细胞损伤机制不仅有利于阐明糖尿...     

糖尿病肾病大鼠足细胞自噬的变化

目的:研究糖尿病肾病大鼠足细胞自噬标志物LC3、P62蛋白表达的改变,探讨糖尿病肾病可能的发病机制。方法:将清洁级雄性SD大鼠20只随机分为正常对照组(n=10只)、造模组(n=10只)。采用高糖高脂饲料结合一次性腹腔注射链脲佐菌素制备糖尿病动物模型。造模成功后于第12周结束时留取大鼠尿标本,检测大鼠尿微量白蛋白、尿肌酐,摘取肾脏称量重量,分别计算尿蛋白肌酐比和肾重体重比;HE染色、PAS染色观察肾脏组织病理变化;Western-blot检测肾小球LC3、P62蛋白表达。结果:与正常对照组相比,尿蛋白肌酐比、肾重体重比在造模组均显著增加(P<0.05);P62蛋白表达亦较正常组表达显著增加(P<0.05);造模组大鼠肾脏病理在光镜下可见明显的系膜增生、基质增多。结论:糖尿病肾病大鼠肾脏足细胞自噬较正常组减低,可能是糖尿病肾病发病的机制之一。     

全反式维甲酸对糖尿病大鼠足细胞损伤的保护作用

目的探讨全反式维甲酸(ATRA)对糖尿病大鼠足细胞损伤的保护作用。方法24只链脲佐菌素(STZ)诱导的糖尿病大鼠模型,随机分为糖尿病组(DM)和治疗组(T)各12只,另以12只正常大鼠作为对照组(N)。T组给予ATRA 20 mg·kg-1·d-1灌胃。于第4、8周末检测各组大鼠尿蛋白定量(24 h)、Cer、肾重/体重、尿中足细胞以及肾脏病理改变。结果DM组尿蛋白定量(24 h)、Ccr、肾重/体重、尿中足细胞数[8周时,0．84(0．60～1．50)个/ml]均显著高于同期N组[0．03(0-0．15)个/m1],而肾小球足细胞数(8周时,11．27±2．15)显著低于同期N组(14．07±2．07),且足细胞足突增宽、融合。T组尿蛋白定量(24 h)、Cer、肾重/体重、尿中足细胞数较同期DM组显著降低[0．46(0．25～0．70)个/ml],且病理改变减轻。结论ATRA可以减少糖尿病大鼠尿足细胞的排泄、降低尿蛋白,对肾脏足细胞损伤具有保护作用。     

氟伐他汀对糖尿病肾病大鼠足细胞分布及排泄的影响

目的探讨氟伐他汀对DN大鼠足细胞分布及排泄的影响。方法将大鼠分为3组：对照组、DN模型组、氟伐他汀治疗组。腹腔注射链脲菌素（STZ）诱导DN大鼠模型。实验10周末测24小时尿蛋白定量（TP）、血清总胆固醇（TC）,间接免疫荧光法检测尿沉渣足细胞特异性标志蛋白podocalyxin（PCX）以检测尿液足细胞（UPC）水平;免疫荧光染色观察肾小球上皮细胞蛋白-1（GLEPP1）的分布。结果DN模型组UPC、TP、TC较对照组均明显升高;氟伐他汀治疗组TC、UPC及TP较DN模型组均降低;对照组GLEPP1正常、DN模型组呈节段性明显缺失、氟伐他汀治疗组缺失较轻。UPC与TP呈正相关,与TC无显著相关性。结论尿液中脱落足细胞检测可作为判断DN病情活动性的标志之一。氟伐他汀可减轻DN大鼠尿蛋白、降低胆固醇、减少足细胞脱落及排泄。     

雷公藤多苷对糖尿病肾病大鼠足细胞病变的影响

目的 探讨雷公藤多苷（TWP）对糖尿病肾病大鼠足细胞病变的影响。 方法 SD大鼠100只,按随机数字表法分为正常对照组（A组）、糖尿病组（B组）与TWP治疗组（C组）。并将C组按4、8、16 mg?kg-1?d-1不同给药剂量分为3组（Ca、Cb、Cc）。糖尿病组与TWP治疗组大鼠分别给予链脲菌素（STZ）一次性腹腔注射建立糖尿病大鼠模型。12周后检测24 h尿蛋白量、血肌酐（Scr）、尿素氮（BUN）、外周血白细胞（WBC）、血糖（Glu）、肾质量/体质量（KW/BW）的变化;HE染色检测肾组织病理变化;透射电镜测量足细胞超微结构变化;免疫荧光法检测肾皮质nephrin和podocin蛋白表达。 结果 （1）与A组比较,B组及C组Scr、BUN增高（P ＜ 0.05）;Glu、KW/BW和24 h尿蛋白量显著增高（P ＜ 0.01）,除Cc组（3/20）出现肝酶（ALT、AST）增高及WBC下降外,各组ALT、AST、WBC差异无统计学意义;肾脏皮质nephrin和podocin蛋白表达减少,肾小球、小管间质及足细胞病变明显。（2）与B组比较,C组KW/BW和24 h尿蛋白量降低（P ＜ 0.01）,肾脏皮质nephrin和 podocin蛋白表达增高（均P ＜ 0.01）,肾小球、小管间质及足细胞病变明显减轻,并随雷公藤多苷剂量的增加而越加明显。 结论 TWP对糖尿病大鼠足细胞病变具有保护作用,并与剂量相关。其部分机制可能与上调nephrin和podocin蛋白表达有关。     

活性维生素D改变FSGS大鼠肾小球整合素连接激酶的表达

目的观察整合素连接激酶（ILK）在局灶节段性肾小球硬化（FSGS）大鼠肾小球的表达以及活性维生素D[1,25-（OH2D3]对其表达的影响。方法SD大鼠随机分为对照组、模型组和治疗组,每组10只。采用左肾摘除、阿霉素重复注射诱导FSGS大鼠模型。治疗组皮下埋置渗透性微量泵,给予1,25-（OH）：D30．03ng·g^-1·d^-1,连用8周。检测3组大鼠尿蛋白、尿足细胞。血清白蛋白（SA）及半胱氨酸蛋白酶抑制剂（CysC）,测定。肾小球硬化指数（GSI）,电镜检测每视野足细胞数、足突平均宽度,间接免疫荧光检测肾小球ILK蛋白的表达,WT-1免疫组化染色观察每个肾小球足细胞数目。结果①与对照组相比较,模型组大鼠尿蛋白、尿足细胞、Cyst、GSI明显增加,SA、肾小球足细胞数目减少,足突宽度增加,肾小球ILK表达明显降低;②与模型组相比较,治疗组尿蛋白、尿足细胞排泄明显减少,GSI明显降低,肾小球足细胞数目增多,足突宽度减小,肾小球ILK表达明显增加。结论1,25-（OH2）D3可增加照;S大鼠肾小球ILK的表达,减少足细胞脱落,维持肾小球足细胞数量。     

Active vitamin D reduces macrophage infiltration by TREM-1 in renal tissue of diabetic nephropathy rats

Objective To investigate the effects of active vitamin D (VD) on the expression of triggering receptor expressed on myeloid cells-1 (TREM-1) in renal tissue of diabetic nephropathies (DN) rats and to explore the impact of TREM-1 on adhesion and migration capacity of macrophage. Methods DN rat models were established by streptozotocin. Rats were randomly distributed into four groups: control (NC) group, VD group, DN group and DN+VD group (DN rats with 0.1 μg?kg-1?d-1 calcitriol by gavages). Rats were sacrificed respectively at 8 weeks and 12 weeks after treatment. Pathological changes in kidney tissue were detected and the expressions of CD68 and TREM-1 were acquired by immunohistochemistry stain and Western blotting. In vitro, RAW264.7 cells were divided into NC group, VD group, high glucose (HG) group and HG+VD group. In HG+VD group rats were treated by high glucose with 10-8 mol/L 1,25(OH)2D3. TREM-1 expression was measured by immunohistochemistry stain and Western blotting, and the ability of macrophage in migration and adhesion was evaluated by Transwell migration assay and adhesion assay. TREM-1 siRNA was transferred to silence TREM-1 expression, while plasmid of TREM-1 was transferred for high expression. Their ability of adhesion and migration in macrophage and the effect of 1,25(OH)2D3 were examined. Results (1) Compared with the NC group, the expressions of CD68 and TREM-1 were increased in DN group (P＜0.05), whereas markedly decreased in DN+VD group (P＜0.05). (2) The number of adhesion and migration cells, and the expression of TREM-1 protein in macrophage were obviously increased in HG group as compared with those in NC group (all P＜0.05); whereas above changes were markedly decreased in HG+VD group than those in HG group (P＜0.05). (3) The number of adhesion and migrated macrophage was reduced after TREM-1 siRNA intervention (all P＜0.05). VD could significantly decrease the effect of high glucose on adhesion and migrated macrophages after TREM-1 siRNA (all P＜0.05). (4) Adhesion and migration of macrophage were increased via TREM-1 overexpression (all P＜0.05), but the effects of VD on high glucose-induced adhesion and migration of macrophage were disappeared. Conclusions VD can suppress the adhesion and migration of macrophage via reducing the expression of TREM-1, and inhibit infiltration of macrophage in renal tissue of DN rats.     

Inhibition of cyclooxygenase-2 expression contributes to podocyte injury in streptozotocin-induced diabetic rats

Objective To investigate the role of cyclooxygenase-2 (COX-2) in podocyte injury in diabetic rats mediated by the disruption of low-density lipoprotein receptor (LDLr) pathway. Methods Eight-week old male Sprague-Dawley (SD) rats were treated for 12 weeks by dividing into three groups: control rats, streptozotocin (STZ) induced diabetic rats (DM), and diabetic rats treated with aspirin (DM+Aspirin). The plasma lipid profile was checked by clinical biochemistry assay. The ratio of urinary microalbumin to creatinine (ACR) was detected by enzyme-linked immunosorbent assay. Intracellular lipid accumulation was evaluated by Oil Red O staining and a free cholesterol quantitative assay. The glomerular podocyte injury and the expression of molecules related with LDLr pathway were evaluated by electron microscope, immunohistochemical staining, immunofluorescent staining, and Western blotting. Results There were increased levels of urinary ACR (P＜0.01) and podocyte injury(P＜0.01) in DM rats compared with the controls. Additionally, lipid accumulation in kidneys of DM rats were significantly increased (P＜0.01), due to increased protein expressions of COX-2, LDLr, sterol regulatory element–binding protein (SREBP) cleavage activating protein (SCAP), and SREBP-2 (P＜0.01). However, these changes were significantly inhibited by an inhibitor of COX-2, Aspirin (P＜0.05). It's worth noting that, COX-2 protein expression was closely correlated with LDLr protein expression (r=0.85, P＜0.01). Conclusion Dysregulation of LDLr pathway contributes to podocyte injury in diabetic nephropathy, which may be mediated through the increased COX-2 expression.     

Tacrolimus protects podocytes by up-regulating autophagy in type 2 diabetic model rats

Objective To assess the effects of tacrolimus (FK506) on podocyte in type 2 diabetic model rats and to explore the potential mechanism. Methods The model rats were fed with high fat and high sugar food and combining with a low-dose of streptozotocin (STZ). They were then randomly divided into a diabetic mellitus group (DM group) and a FK506 group. A normal control group (NC group) was also set. The rats in FK506 group were given with 0.5 mg?kg-1?d-1 FK506 for 8 weeks. The biochemical parameters were measured. The changes of renal pathology and ultrastructure of podocyte were observed by the light and electron microscopy. The expression of nephrin and LC3-Ⅱ was determined by immunohistochemistry and Western blotting. Results (1) Compared with those in NC group, KW/BW, systolic blood pressure (SBP), fasting blood glucose (FBG), triglyceride (TG), total cholesterol (TC), urinary albumin excretion rate (UAE) and creatinine clearance rate (Ccr) in DM group were significantly increased (all P＜0.05). And the KW/BW, UAE and Ccr were decreased in FK506 group compared to those in DM group (all P＜0.05), while other parameters had no significant difference (all P＞0.05). (2) Compared with those in NC group, the glomerular volume, mesangial cell proliferation and accumulation of mesangial matrix were increased, and the foot process became disorder and fusion in DM group, while these changes were significantly reduced in FK506 group. (3) Compared with that in NC group, the expression of nephrin and LC3-Ⅱ was decreased in DM group (all P＜0.05), and both of parameters were higher in FK506 group than those in DM group (all P＜0.05). Conclusion FK506 may enhance podocyte autophagy in type 2 diabetic model rats and attenuate podocyte injury.     

抗氧化治疗对糖尿病肾脏病患者肾功能的保护作用

目的探讨维生素E联合维生素C抗氧化治疗对2型糖尿病肾脏病患者肾功能的保护作用。方法选择我院2型糖尿病肾脏病患者80例,随机分为2组,对照组（A组）接受常规治疗;抗氧化治疗组（B组）除常规治疗外,口服维生素E（0．1g／次,每日1次）、维生素C（0．2g／次,每日3次）。每3个月随访1次,观察记录患者的肾功能,以血肌酐（SCr）升高1倍为随访终点,SCr升高1倍所经历的时间为肾功能生存时间,最长随访时间为2年。结果A组肾功能平均生存时间为（14．78±0．64）个月;B组平均生存时间为（18．16±0．68）个月,2组比较有统计学差异（P〈0．05）。结论维生素E联合维生素c抗氧化治疗对糖尿病肾脏病患者肾功能具有保护作用。     

帕立骨化醇对糖尿病肾病大鼠蛋白尿的影响

目的 研究维生素D类似物帕立骨化醇对糖尿病肾病(DN)大鼠蛋白尿的影响,并探讨其可能机制.方法 用链脲菌素(STZ)腹腔注射法构建DN大鼠动物模型,将造模成功的大鼠随机分为帕立骨化醇组(P组)、DN组(D组),并设置健康对照组(N组).给药12周后检测24 h尿蛋白量及血生化指标.用ELISA法检测肾组织肾素和血管紧张素Ⅱ(AngⅡ)水平.免疫组化和实时PCR检测肾小球基底膜乙酰肝素酶(HPA)、足细胞podocin蛋白及mRNA的表达.结果 D组和P组24h尿蛋白量、Scr、肾素及AngⅡ水平均显著高于N组,而D组显著高于P组,差异均有统计学意义(均P＜ 0.05).D组和P组HPA蛋白及mRNA表达均显著高于N组,而D组显著高于P组;D组和P组podocin蛋白及mRNA表达较低,D组显著低于P组,差异均有统计学意义(均P＜ 0.05).肾素水平与HPA蛋白表达呈正相关(r=0.78,P＜0.05);与podocin蛋白表达呈负相关(r=-0.63,P＜0.05);而与两者mRNA表达无相关.结论 帕立骨化醇可显著减少DN大鼠早期蛋白尿,其机制可能与通过抑制肾组织肾素表达,下调肾小球基底膜HPA,上调足细胞podocin蛋白表达有关.     

脂联素及其受体对糖尿病肾病大鼠的保护作用

目的 探讨脂联素（ADPN）及其受体（AdipoR）对糖尿病肾病的保护作用及其可能机制。 方法 （1）64只雌性SD大鼠被随机均分入对照组和实验组：实验组一次性空腹腹腔注射链脲菌素（STZ) 60 mg/kg,诱导糖尿病大鼠模型;对照组腹腔注射等体积的枸橼酸缓冲液。于糖尿病大鼠成模后第2、6、10、12周两组分别测体质量、肾质量、空腹血糖、24 h尿白蛋白排泄量;心内采血检测空腹血清胰岛素;ELISA法检测血、尿脂联素浓度;取肾脏常规制作PAS染色,免疫组化SP法检测肾脏脂联素受体1和2（AdipoR1和AdipoR2）的表达。（2）将NRK-52E细胞分别用含5 mmol/L葡萄糖（正常对照组）、30 mmol/L葡萄糖（高糖组）、30 mmol/L葡萄糖+不同浓度ADPN（终浓度分别为1 mg/L、5 mg/L、10 mg/L）培养,12 h后RT-PCR法检测单核细胞趋化蛋白1（MCP-1） mRNA表达。 结果 （1）造模成功后6、10、12周实验组血清和尿ADPN水平均高于对照组（P < 0.01）,并随着肾脏病变进展而逐渐升高。（2）实验组各时期AdipoR1和AdipoR2在肾脏的表达高于对照组,并随时间逐渐增强,其与血清脂联素水平呈正相关（r = 0.666,P < 0.01;r = 0.684,P < 0.01）。（3）MCP-1 mRNA在高糖组表达较高,加入脂联素以后MCP-1 mRNA表达显著减少（P < 0.05）。 结论 血和尿脂联素水平随糖尿病肾病病程进展而升高,与AdipoR1和AdipoR2的表达亦呈正相关,推测脂联素通过AdipoR直接作用于肾小管,通过减少MCP-1的表达对肾脏起保护作用。     

Analysis of clinical manifestations and outcomes of idiopathic membranous nephropathy compared with diabetic nephropathy in patients with type 2 diabetes

Objective To evaluate the predictive factors and renal outcomes of idiopathic membranous nephropathy (IMN) in patients with type 2 diabetes (T2DM). Methods In this retrospective study, clinical data of 101 IMN patients with T2DM and 96 patients with diabetic nephropathy (DN) were consecutively collected. Logistic regression was used to assess potential clinical factors indicating IMN and COX regression was employed to analyze risks of IMN in developing to end-stage renal disease (ESRD), as compared with that of DN, in patients with T2DM. Results In a multivariate model, age≥55 years old, presence of nephrotic syndrome, estimated glomerular filtration rate (eGFR)＞60 ml?min-1?(1.73 m2)-1, duration of diabetes≤5 years and absence of diabetic retinopathy, were associated with IMN, as compared with DN, in patients with T2DM. In T2DM patients presented with nephrotic syndrome, age≥55 years old, eGFR＞60 ml?min-1?(1.73 m2)-1, duration of diabetes≤5 years and absence of diabetic retinopathy, were also associated with IMN, as compared with DN. Receiver operating characteristic curve (ROC) showed eGFR 65.5 ml?min-1?(1.73 m2)-1 was an optimal cutoff in differentiating DN and IMN. DN was associated with 16.8 times as high risk of incident ESRD as compared with IMN in T2DM patients. Conclusions In patients with T2DM, age≥55 years, presence of nephrotic syndrome, early stage of CKD, duration of diabetes≤5 years and absence of retinopathy, may indicate IMN rather than DN. T2DM patients with IMN have much better renal prognosis as compared with DN.