IgA肾病预后不良因素与肾血管病变相关性分析

目的：探讨IgA肾病（IgAN）肾血管病变的危险因素。方法选择宁夏人民医院肾脏内科2010年10月至2013年7月经肾活检确诊的原发性IgAN患者100例,并将其分为肾血管病变组和无肾血管病变组,进行对照研究,比较肾血管病变与各项临床指标、病理改变之间的关系。结果100例IgAN患者中有肾血管病变者70例（70%）,无肾血管病变者30例（30%）。单因素分析结果表明,肾血管病变组24h尿蛋白、血尿酸、血肌酐均高于无肾血管病变组（P＜0.05）,血清白蛋白低于无肾血管病变组（P＜0.05）;病理学检查显示肾小球硬化、肾间质纤维化、新月体形成、炎性细胞浸润、肾小管萎缩严重病理表现发生率,肾血管病变组明显高于无肾血管病变组（P＜0.05）。多因素非条件logistic回归分析结果表明,高血压（OR＝7.728,95%CI 1.708～34.964）、24h尿蛋白定量（OR＝20.022,95%CI 3.869～103.623）、肾小球硬化（OR＝12.093,95%CI 2.431～60.149）、肾间质纤维化（OR＝8.511,95%CI 1.332～54.396）是IgAN肾血管病变加重的危险因素。结论 IgAN预后不良因素为高血压、24h尿蛋白定量、肾小球硬化、肾间质纤维化,上述指标与IgAN肾血管病变密切相关,进一步证实了肾血管病变可作为判断预后的一项重要病理指标。     

尿视黄醇结合蛋白、N-乙酰-β-D-氨基葡萄糖苷酶及尿蛋白检测在IgA肾病患者肾小管间质损害中的临床意义

目的 探讨尿视黄醇结合蛋白（RBP）、N-乙酰-β-D-氨基葡萄糖苷酶（NAG）及24小时尿蛋白定量（UPE）等指标判断IgA肾病（IgAN）患者肾小管间质损害程度的临床意义.方法 收集我院2010年5月～2013年2月114例住院IgAN患者的临床及病理资料,依据Lee氏病理分级系统将患者分为Lee I～Ⅱ级27例（A组）、LeeⅢ级46例（B组）和LeeⅣ～V级41例（C组）,分析不同分级IgAN肾小管间质病变情况与尿RBP、NAG、UPE等指标之间的相关性.结果 各组间血红蛋白（Hb）、白蛋白（ALB）、前白蛋白（pre-ALB）、血肌酐（SCr）、尿素氮（BUN）、总胆固醇（TC）、UPE、尿RBP及NAG等指标比较差异有统计学意义（P＜0.01）,镜下血尿及高血压的发生率随病理程度加重而上升（P＜0.01）,肾小管萎缩、肾间质炎细胞浸润、肾间质纤维化及动脉硬化在各组间比较差异均有统计学意义（P＜0.01）,相关性分析显示尿RBP、NAG与肾小管萎缩、肾间质炎症细胞浸润、肾间质纤维化及动脉硬化程度呈正相关;UPE与肾小管萎缩程度呈负相关（r=-0.213,P＜0.05）,尿RBP、NAG水平与eGFR呈负相关.结论 IgAN患者高血压及血尿发生率、Hb、ALB、TC、肾功能、RBP、NAG、UPE等指标与肾脏病理损伤程度有关,尿RBP、NAG及UPE联合检测对判断肾小管病理损伤程度及肾功能有临床意义.     

血小板源性生长因子BB与IgA肾病的关系

目的:探讨IgA肾病(IgA nephropathy,IgAN)患者血清中血小板源性生长因子BB(PDGF-BB)与肾脏不同病理改变的关系,旨在寻找一种能反映IgAN肾损害程度的非创伤性临床检测指标.方法:应用酶联免疫吸附法(ELISA)测定92例IgAN患者、30例微小病变性肾病(MCD)患者、30例健康对照的PDGF-BB水平并进行比较;将92例1gAN患者的肾脏病理按Lee氏分级分为A组(Lee氏Ⅰ级或Ⅱ级)16例,B组(Lee氏Ⅲ级)43例,C组(Lee氏Ⅳ级或Ⅴ级)33例,并进行katafuchi半定量评分,观察血清PDGF-BB水平与IgAN不同肾脏病理改变的关系.结果:(1) IgAN患者血清PDGF-BB的含量(746.530 t 293.012) ng/L明显高于MCD组(208.910±118.56)ng/L及正常对照组(215.320±124.064) ng/L(P＜0.05);MCD组(208.910±118.56) ng/L与正常对照组(215.320±124.064)ng/L对比无统计学意义(P＞0.05);(2)IgAN者中血清PDGF-BB的浓度C组(926.443±237.162)ng/L明显高于B组(693.103±284.608) ng/L及A组(519.043±198.671) ng/L(P <0.05);同时B组(693.103±284.608)ng/L高于A组(519.043±198.671) ng/L(P <0.05);(3) Pearson相关分析:血清PDGF-BB水平与平均动脉压、血肌酐,24h尿蛋白定量,尿素氮均呈正相关(r = 0.353,0.342,0.270,0.261; P均＜0.05);与肾小球滤过率呈负相关性(r=-0.414,P＜0.05);(4)多元线性回归分析:平均动脉压及Lee氏分级是血清PDGF-BB升高的独立危险因素.结论:血清PDGF-BB浓度可反映IgAN肾脏病理改变的严重程度,可做为IgAN肾损害的非创伤性临床检测指标.     

前列腺素E1在糖尿病肾病不同时期的疗效观察

目的 观察前列腺素E1(PGEl)治疗老年人糖尿病肾病的疗效.方法 将糖尿病肾病Ⅲ、Ⅳ、Ⅴ期患者随机分为4组,即对照组和PGE1、PGE1+血管紧张素转换酶抑制剂(ACEI)及ACEI不同治疗方案的治疗组,测定各组治疗前及治疗后15 d、3个月、6个月时24 h尿蛋白和24 h尿微量白蛋白.结果 (1)在糖尿病肾病Ⅲ期及Ⅳ早期(尿蛋白＜2.5 g/d)患者中,PGEl+ACEI组和PGE1组治疗15天、3个月、6个月时尿蛋白及尿微量白蛋白均明显下降(P＜0.01),比对照组及ACEI组下降大于10%;(2)在糖尿病肾病Ⅳ晚期(尿蛋白＞2.5 g/d)患者中,PGE1+ACEI组及PGE1组尿蛋白和尿微量白蛋白治疗后3个月、6个月时效果不如Ⅳ早期,而对照组均增加10%以上(P＜0.05或P＜0.01);(3)在糖尿病肾病V期患者中,治疗组治疗后15 d、3个月及6个月时尿蛋白及尿微量白蛋白下降程度明显减慢;对照组治疗3个月及6个月后,上述2项指标增加10%以上(P＜0.01).结论 前列腺素E1对糖尿病肾病具有较好治疗效果,且对早期糖尿病肾病治疗效果优于晚期.     

安体舒通在糖尿病肾病治疗中的应用效果观察

目的 研究对在已应用血管紧张素转化酶抑制剂(ACEI)和(或)血管紧张素Ⅱ受体拮抗剂(ARB)治疗且尿蛋白仍在0.5 g/24 h以上的糖尿病肾病(DN)患者加用小剂量安体舒通,观察其对尿蛋白及肾功能的影响.方法 按开放、随机、对照的方法将临床确诊为DN患者38例分为安体舒通组和对照组.安体舒通组在原应用ACEI和(或)ARB基础上加用安体舒通20 mg/d,对照组继续按原量服用ACEI和(或)ARB药物.于治疗第0、4、8、12、16周检测24h尿蛋白、血清肌酐、血清钾、血浆醛固酮、血压,并根据血清肌酐计算肾小球滤过率(eGFR).结果 治疗后安体舒通组尿蛋白较前明显下降(P＜0.05),而对照组蛋白尿无明显下降.两组肾功能、eGFR、血钾、血浆醛固酮水平、血压治疗前后变化水平无统计学差异.结论 在应用ACEI和(或)ARB基础上加用安体舒通可明显降低DN患者尿蛋白水平.     

雷公藤多甙联合苯那普利和大黄素治疗IgA肾病的前瞻性临床研究

目的观察雷公藤多甙联合苯那普利和大黄素(三联疗法)对IgA肾病(IgAN)的临床疗效及肾组织病理改变的影响.方法经肾活检并结合临床确诊为原发性IgAN的患者24例,年龄14～55岁,尿蛋白≥1.0g/d,血肌酐(SCr)≤267μmol/L,肾活检病理Lee氏Ⅲ级以上.根据尿蛋白、SCr及肾病理配对分为治疗组(n=12)和对照组(n=12),治疗组接受雷公藤多甙、苯那普利和大黄素三联治疗,对照组接受强的松和苯那普利治疗.疗效分为缓解(尿蛋白＜0.4g/d,血浆白蛋白＞35.0g/L,SCr＜110μmol/L)、部分缓解(尿蛋白＞0.4g/d,但下降＞基础值的50%,肾功能稳定,SCr上升＜基础值的25%)及无效(尿蛋白＞1.0g/d,或SCr上升＞基础值的50%).治疗12个月后9例治疗组和4例对照组患者接受重复肾活检,利用Scion Image 4.02 β软件进行病理图像分析肾小球指数(GI)、肾小管间质慢性化病变指数(TI)以及间质血管病变指数(Ⅵ).结果治疗6个月时治疗组5例(42%)缓解,6例(50%)部分缓解,1例(8%)无效,对照组分别为2例(17%)、7例(58%)和3例(25%).治疗组尿蛋白下降快于对照组,治疗0、1、3、6、9、12个月时治疗组尿蛋白分别为(2.04±0.76)g/d、(0.76±0.45)g/d、(0.51±0.31)g/d、(0.57±0.31)g/d、(0.55±0.43)g/d、(0.81±1.09)g/d,对照组分别为(1.88±0.67)g/d、(1.43±0.74)g/d、(0.79±0.58)g/d、(0.68±0.34)g/d、(2.03±1.90)g/d、(1.27±1.45)g/d.治疗组6例肾功能不全患者治疗12个月后SCr保持稳定[(140.6±19.0)μmol/L vs(134.1±24.1)μmol/L,P＞0.05],对照组5例肾功能不全患者SCr无变化[(126.6±19.6)μmol/Lvs (129.5±26.6)μmol/L,P＞0.05].重复肾活检病理定量分析发现治疗组GI显著降低(0.314±0.054 vs 0.243±0.042,P＜0.05),对照组GI则增加(0.274±0.065 vs 0.304±0.056,P＞0.05).治疗组TI由0.183±0.112降至0.148±0.100(P＞0.05),对照组TI无明显改变(0.278±0.102 vs 0.273±0.141,P＞0.05).两组患者治疗后Ⅵ均下降,但无统计学差异.结论雷公藤多甙联合苯那普利及大黄素三联疗法能有效减少IgAN的蛋白尿、稳定肾功能并减轻肾脏纤维化病变.     

复方丹参注射液治疗糖尿病肾病的临床观察

目的探讨复方丹参注射液治疗非胰岛素依赖型糖尿病肾病的临床疗效。方法选取非胰岛素依赖型糖尿病肾病50例,随机分为治疗组及对照组。治疗组使用血管紧张素转换酶抑制剂(ACEI)药物+复方丹参注射液治疗,对照组单用血管紧张素转换酶抑制剂(ACEI)药物治疗。结果治疗组血肌酐、尿素氮及24h尿蛋白总量在治疗前的基础上均用不同程度降低,对照组血肌酐、尿素氮及24h尿蛋白总量在治疗前的基础上均用不同程度升高。结论中西结合治疗非胰岛素依赖型糖尿病肾病具有减少尿蛋白排泄,改善肾功能,延缓非胰岛素依赖型糖尿病肾病进程的疗效。     

IgA肾病患者补体经典途径在血液及尿液中的活化及与肾损伤的关系

目的 研究循环系统中经典途径补体活化及调节方式在IgA肾病（IgAN）中的致病作用及与肾损伤的关系.方法 IgA肾病组30例,10例狼疮性肾炎（LN）患者作阳性对照,30例健康体检者作对照组.采用ELISA试剂盒检测IgA肾病患者和对照组血及尿液中经典途径补体激活标志物C1q、经典途径调节因子（sCR）1,分析补体浓度与肾组织病理结果及临床生化指标的相关性.将IgA肾病组患者按照病理Lee氏结果进行分组,Lee氏Ⅰ～Ⅲ级定为轻度损伤组,Lee氏Ⅳ～Ⅴ级定为重度损伤组,比较两组间的补体浓度差异.分析血C1q与sCR1间相关性.结果 IgA肾病组患者血清C1q及sCR1水平均高于对照组（P＜0.05）,而IgA肾病组与LN组间比较差异无统计学意义（P ＞0.05）;LN组患者尿液C1q浓度明显高于另外2组（P＜0.01）.当血清肌酐＞ 133μmol/L时,血C1q与肌酐水平呈显著负相关（P＜0.05）.尿C1q与肌酐水平呈显著正相关（P＜0.05）.Lee氏Ⅳ～Ⅴ级组患者血液及尿液C1q均明显低于Lee氏Ⅰ～Ⅲ级组（P＜0.05）.血sCR1与血C1q间呈显著正相关（P＜0.05）.结论 IgA肾病患者循环系统中可能存在补体经典途径激活通路,尤其是在肾损伤严重组,且与疾病的严重程度相关.IgA肾病中可溶型CR1对C1q存在介导调节作用.     

NF-κB在IgA肾病中的表达及意义

采用免疫组化法观察36例IgA肾病(IgAN)肾组织中核因子-kB(NF-kB)的表达.结果 :在正常肾组织及IgAN Ⅰ级病变组肾组织中NF-kB的表达较弱.在IgAN Ⅱ～Ⅲ级组、Ⅳ～Ⅴ级组肾小球及肾小管间质中NF-kB表达均较对照组增强,随着肾组织病变加重其表达增强;Pearson相关分析表明NF-kB的表达与24 h尿蛋白定量和内生肌酐清除率紧密相关.认为NF-kB参与IgAN的进展,NF-kB的表达与IgAN进行性损伤有关.     

依那普利联合科素亚对原发性高血压早期肾损害的影响

目的 探讨依那普利联合科素亚对原发性高血压病人早期肾功能损害的保护作用。方法 将76例高血压病早期肾损害病人随机分为依那普利组和联合治疗组，两组于治疗前及治疗2个月后行24h动态血压监测。于治疗前及治疗6个月后测肌酐清除率、24h尿蛋白定量、尿微量白蛋白、β2-微球蛋白。结果 两组治疗2个月后24h收缩压（24hSBP）、24h舒张压（24h DBP）较治疗前明显下降（P〈0．05），治疗6个月后肾功能损害各指标较治疗前均明显改善（P〈0．05），且联合治疗组效果优于依那普利组（P〈0、05）。结论 血管紧张素转换酶抑制荆（ACEI）和血管紧张素Ⅱ-1型受体桔抗荆（ARB）联合应用，在达到同等降压水平同时可减少ACEI的用量，降低其副反应的发生率。     

肾小球疾病间质泡沫细胞的分布及其与临床指标的关系

目的观测各种病理类型肾小球疾病间质泡沫细胞的分布特点及其与临床参数间的关系。方法选取2862名肾活检患者为研究对象,观察间质泡沫细胞浸润常见的病理类型及泡沫细胞的分布特点。对诊断明确的Aploa综合征（AS）5例,膜增生性肾小球肾炎（MPGN）28例,局灶节段硬化性肾小球肾炎（FSGS）144例,特发性膜性肾病（IMN）132例,IgA肾病（IgAN）893例按间质是否存在泡沫细胞进行临床参数的比较。结果（1）非继发性肾小球疾病泡沫细胞浸润高发的病理类型依次为AS（100％）、MPGN（46．43％）、FSGS（21．32％）、IMN（13．64％）、IgAN（6．69％）;（2）泡沫细胞浸润组24小时尿蛋白定量、血胆固醇水平以及反映肾小管功能损伤的指标均高于无泡沫细胞组（P〈0．05）。结论肾间质泡沫细胞浸润常见于AS,但在MPGN、FSGS、IMN和IgAN患者中均可出现,大量蛋白尿与高脂血症是导致泡沫细胞浸润的两大因素。间质泡沫细胞的浸润与间质损害有一定的关联。     

Effects of angiotensin inhibitors on renal injury and angiotensin receptor expression in early hypertensive nephrosclerosis.

Angiotensin converting enzyme inhibitors (ACEI) are known to inhibit the progression of established renal failure. The aim of this study was to compare the efficacy of an ACEI and an AT1 receptor antagonist (AT1R-Ant) in preventing the development of renal disease, at an early stage of hypertensive nephrosclerosis. SHRSP/Izm rats (n = 61) were treated from 10 wk until 22 wk with the ACEI delapril (40 mg/kg/d) or the AT1R-Ant candesartan cilexetil (1 mg/kg/d). Proteinuria, and structural/ultrastructural changes were assessed at 14 and 22 wk. Treatment with either agent resulted in reductions in blood pressure and cardiovascular hypertrophy. Neither proteinuria nor major renal histological changes were evident at 14 wk. At 22 wk, however, proteinuria accompanied by nephrosclerotic changes was seen in the untreated SHRSP/Izm. Treatment with either ACEI or AT1R-Ant resulted in similar reductions in proteinuria (untreated, 32.2 +/- 7.4; delapril-treated, 5.5 +/- 1.2; candesartan-treated, 3.9 +/- 0.3 mg/100 g/d). Prominent sclerosis of small-to-medium sized renal arteries was seen in the untreated SHRSP/Izm at 22 wk, but was similarly attenuated by the ACEI and AT1R-Ant. The glomerular ultrastructure was comparable between the two groups. No significant changes in renal AT1a or AT1b receptor subtype mRNA expression were seen throughout the course of the study. In contrast, a decrease in AT2 receptor mRNA was seen in the drug-treated groups at 14 wk but not at 22 wk. These results suggest that both ACEI and AT1R-Ant have similar efficacy in attenuating the onset of renal injury in early hypertensive nephrosclerosis, and that treatment with either agent is associated with a transient decrease in AT2 receptor mRNA expression.     

Heterogeneity of prognosis in adult IgA nephropathy, especially with mild proteinuria or mild histological features

OBJECTIVE: The present study was undertaken to clarify the clinical course and prognosis of adult patients with primary IgA nephropathy (IgAN), especially with mild proteinuria or mild histological alternations. PATIENTS AND METHODS: A population of 735 IgAN patients whom we were able to observe for more than two years was examined. RESULTS: A total of 115 patients (15.6%) was on dialysis during the observation period. The overall 5-year renal survival rate was 92.0%. On the other hand, 166 patients (22.6%) were in clinical remission. A group with mild proteinuria included 197 patients (26.8%). Forty-seven patients of this group showed minor glomerular abnormalities, whereas 12 patients with mild proteinuria showed severe mesangial involvement. Three patients with mild proteinuria were on dialysis during the observation period, whose proteinuria was increased during the clinical course. A group with minor glomerular abnormalities included 82 patients (11.2%). Forty-seven patients of this group showed mild proteinuria, of whom 12 patients showed moderate proteinuria. However, three patients with minor glomerular abnormalities who were not on dialysis showed loss of renal function. CONCLUSION: These results indicated the heterogeneity of the course and prognosis in IgAN. Even if a patient's initial clinical or histological findings are comparatively mild, strict follow-up management is needed.     

Histopathologic Features Aid in Predicting Risk for Progression of IgA Nephropathy

Background and objectives: IgA nephropathy (IgAN) is the most common primary glomerular disease worldwide. Accurately identifying patients who are at risk for progressive disease is challenging. The extent to which histopathologic features improves prognostication is uncertain.Design, setting, participants, & measurements: We studied a retrospective cohort with biopsy-proven IgAN in Calgary, Canada. Renal biopsies were reviewed by a nephropathologist with histopathologic data abstracted using a standardized form. The primary outcome was the composite of doubling of serum creatinine, ESRD, or death. Spline models defined significant levels of interstitial fibrosis, glomerulosclerosis, hypertension, proteinuria, and creatinine. The prognostic significances of clinical and histopathologic parameters were determined using Cox proportional hazards models.Results: Data from 146 cases were available for analysis with a median follow-up of 5.8 years. Greater than 25% interstitial fibrosis, >40% glomerular sclerosis, and a systolic BP >150 mmHg were risk thresholds. In univariable analyses, baseline creatinine, proteinuria, systolic BP, glomerular sclerosis, interstitial fibrosis, and crescentic disease were predictors of the primary outcome. In multivariable models adjusted for clinical characteristics, interstitial fibrosis (hazard ratio [HR]2.7; 95% confidence interval [CI] 1.2 to 6.0), glomerular sclerosis (HR 2.6; 95% CI 1.2 to 4.5), and crescents (HR 2.4; 95% CI 1.2 to 5.1) remained independent predictors of the primary outcome and significantly improved model fit compared with clinical characteristics alone.Conclusions: Baseline histopathologic parameters are independent predictors of adverse outcomes in IgAN even after taking into consideration clinical characteristics. Relatively small degrees of interstitial fibrosis confer an increased risk for progressive IgAN.IgA nephropathy (IgAN) is the most common primary glomerulonephritis worldwide. Patients with IgAN have a variable clinical course with between 6 and 43% progressing to ESRD over 10 yr (1–5). Given this variability, identifying reliable prognostic factors is important to help stratify clinical monitoring and treatment regimens.Previous studies have identified clinical features including high-grade proteinuria, reduced kidney function, and hypertension at the time of diagnosis as predictors of adverse outcomes (4–7). Studies have identified interstitial fibrosis and glomerular sclerosis as poor prognostic features (8–10). This is not surprising considering that these features are a common final result of damage from glomerulonephritis; however, histopathologic features frequently correlate with serum creatinine, and whether they add prognostic values beyond the measurement of serum creatinine is uncertain. Histopathologic features are commonly categorized on the basis of arbitrary thresholds to denote significant degrees of damage (3,5,11), a factor that may contribute to poor performance in multivariable models of risk prediction in IgAN and result in an underestimation of their ability independently to predict outcomes. We performed a retrospective study using detailed baseline clinical data and quantitative analysis of renal biopsies, including the degree of interstitial fibrosis and glomerulosclerosis, to assess the factors that determine adverse outcomes including chronic kidney disease (CKD) progression and death.     

Renal protective effects of blocking the intrarenal renin-angiotensin system.

It has been well demonstrated that angiotensin-converting enzyme inhibitors (ACEIs) can retard the progression of renal failure and kidney sclerosis in patients and animal models with glomerular diseases. The aim of this study was to observe the influences of ACEI on intrarenal Ang II and TGFbeta1 local formation and their relation to renal protective effects. Experimental glomerulosclerosis with nephrotic syndrome was induced in unilateral nephrectomized rats with repeated injections of adriamycin. Rats were randomly divided into three groups: 1) a sham-operated control group (n=8); 2) an NS group treated with ACEI (benazepril 4 mg/kg/d) (n=10), and 3) an NS group not treated (n=10). After 8 wk, serum, urine and renal tissue were collected for study. ACE activity and Ang II concentration in renal tissue were measured by colorimetry and radioimmunoassay, respectively. Immunohistochemistry staining was employed for transforming growth factor-beta1 (TGFbeta1) and extracellular matrix (ECM) examination. TGFbeta1 mRNA was assessed by in situ hybridization. Compared with those of non-treated nephropathy rats, ACE activity (13.39+/-5.02 vs. 49.13+/-12.92 U/ml, p< 0.01) and Ang II (402.61+/-80.22 vs. 751.63+/-137.45 pg/mg/pr p < 0.01) in renal tissue were significantly inhibited in the rats treated with ACEI. At the same time, proteinuria was significantly reduced (155.06+/-103.56 vs. 421.11+/-148.45 mg/24 h, p < 0.01) and renal function improved (Scr 76.3+/-33.1 vs. 107.1+/-71.0, p < 0.05), concomitant with a reduction in the glomerular sclerosis index (30.6+/-19.5 vs. 120.3+/-61.9, p < 0.01) and a reduction in ECM accumulation such as Col IV, III, LN and FN (29.2+/-9.8 vs. 76.8+/-12.4; 29.5+/-12.4 vs. 85.9+/-11.5; 26.0+/-5.1 vs. 69.6+/-1.73; 32.4+/-12.4 vs. 70.5+/-13.5; p< 0.01 in all cases). In the ACEI treated group, these histologic benefits coincided with a reduced expression of TGFbeta1 in both tubular cells and sclerosed glomeruli in protein as well as mRNA level. These findings provide further evidence that ACEI (benazepril) can prevent the progression of renal damage in both the function and morphologic changes which associated with a down-regulation of intrarenal Ang II level through the relative inhibition of renal ACE activity. The blocking of the intrarenal renin angiotensin system (RAS) might contribute to the inhibition of TGFbeta1 local formation and the TGFbeta1-mediated ECM accumulation that are related to the renal protective effects of ACEI.     

Apelin和APJ在IgA肾病中的表达及与肾间质纤维化相关性研究

目的探讨多肽Apelin及其受体APJ在IgA肾病(IgAN)患者血浆及肾组织中的表达情况,分析其与患者临床指标及肾间质纤维化程度之间的相关关系。方法选取2018年1月至2018年12月在北京友谊医院经肾活检确诊的原发性IgAN患者56例,按2009年IgAN牛津病理分型中的肾小管萎缩/肾间质纤维化程度标准,将患者分为3组:T0组(20例)、Tl组(17例)和T2组(19例);选取同期该院肾活检确诊的微小病变性肾病(MCD)患者20例作为对照。收集患者一般资料和常规临床指标,留取血浆和肾组织标本,采用酶联免疫吸附法检测血浆Apelin-12水平,免疫组织化学法观察肾脏APJ受体的表达。对各组指标进行比较,Pearson和Spearman相关分析明确IgAN患者肾组织APJ的表达量与血浆Apelin-12、肾间质纤维化面积及常规临床指标的相关性;多元线性回归分析影响IgAN患者肾组织APJ表达的相关因素。结果 T0组、T1组和T2组血浆Apelin-12和肾组织APJ表达量的差异有统计学意义(均P<0.05),随着肾间质纤维化程度的加重,血浆Apelin-12的浓度逐渐降低,肾脏APJ的表达逐渐增加(均P<0.05)。相关分析显示:IgAN患者肾脏APJ的表达量与肾间质纤维化面积(r=0.930, P<0.001)、血肌酐(r=0.739, P<0.001)、尿素氮水平(r=0.659, P<0.001)呈正相关,与血浆Apelin-12水平(r=-0.712, P<0.001)和估算肾小球滤过率(eGFR)(r=-0.882, P<0.001)呈负相关。多元线性回归分析显示:IgAN患者肾脏APJ的表达量与肾间质纤维化面积呈正相关(β=0.749, P<0.001)。结论 IgAN患者血浆Apelin水平降低,机体上调肾组织APJ受体表达,且APJ的表达量与肾间质纤维化程度呈正相关。提示在IgAN肾间质纤维化的病理过程中,内源性Apelin/APJ系统发挥一定的自身调节作用。     

阿利吉仑对阿霉素肾病小鼠肾脏的保护作用

目的：探讨阿利吉仑对阿霉素肾病小鼠肾脏的保护作用。方法通过尾静脉注射阿霉素建立阿霉素肾病模型小鼠24只,随机分为阿霉素肾病组、阿利吉仑组、缬沙坦组及阿利吉仑＋缬沙坦组各6只,另取同龄BALB/c小鼠6只作为正常对照组。比较各组阿霉素注射后第2、6周24 h尿蛋白定量及肾功能的差异;处死小鼠后,取各组肾组织石蜡包埋,切片行PAS、HE和Masson染色,观察肾小球硬化程度和肾小管损害程度。结果阿霉素肾病小鼠表现为蛋白尿、低蛋白血症并伴有进行性肾功能下降,出现肾小球硬化及小管间质损害。与阿霉素肾病组比较,阿利吉仑组、缬沙坦组及阿利吉仑＋缬沙坦组24 h尿蛋白均有显著改善,血清白蛋白明显上升（P均＜0．05）。与阿霉素肾病组比较,阿利吉仑组、缬沙坦组及阿利吉仑＋缬沙坦组均可明显减轻肾小球硬化和肾小管间质损害（P均＜0．05）,但阿利吉仑＋缬沙坦组可明显改善肾间质纤维化（P均＜0．05）。结论阿利吉仑对阿霉素肾病小鼠具有肾脏保护作用,与缬沙坦联合应用可明显改善肾间质纤维化程度。     

Immunoglobulin A nephropathy in a patient with neurofibromatosis type 1: A case report and literature review

Rationale:Neurofibromatosis type 1 (NF-1) is an autosomal-dominant neurocutaneous disorder that affects the skin, bones, and nervous system. The most common manifestation of kidney involvement is renal artery stenosis; glomerulonephritis is extremely rare. In this case report, we present a patient with NF-1 and immunoglobulin A nephropathy (IgAN).Patient concerns:A 51-year-old Korean man previously diagnosed with NF-1 presented with persistent proteinuria and hematuria identified during a routine medical check-up. He had no history of hypertension or diabetes, and denied a history of alcohol use or smoking.Diagnosis:The contrast-enhanced computed tomography scan revealed normal-sized kidneys and no evidence of renal artery stenosis. On the day of the kidney biopsy, laboratory tests showed a serum creatinine level of 1.1 mg/dL, urine protein/creatinine ratio of 1.3 g/g, and urine red blood cell count of >10 to 15/HPF. The kidney biopsy sample revealed IgAN grade III, according to Lee glomerular grading system.Intervention:The patient was advised to take 4 mg of perindopril.Outcome:Three months after the treatment, the urine protein/creatinine ratio decreased to 0.6 g/g, with no change in the serum creatinine level (1.03 mg/dL).Lessons:A genetic link between NF-1 and IgAN or other glomerular diseases is not established. However, activation of the mTOR pathway may explain this association.