少量蛋白尿和（或）血尿IgA肾病临床病理分析

目的 了解表现为少量蛋白尿和（或）血尿IgA肾病（IgAN）患者的肾脏病理特征及其与临床表现的关系。 方法 对1993年1月至2009年10月肾活检确诊为IgAN,且表现为少量蛋白尿 （<1 g/24 h）和（或）血尿,Scr<133 μmol/L的患者的临床和病理资料进行回顾性分析。病理学分级参照Lee分级及Katafuchi半定量积分标准。应用多因素logistic回归法分析肾脏病理损伤的危险因素。 结果 符合入选标准共316例,男123例,女193例,肾穿时年龄（33.10±10.69）岁。蛋白尿伴血尿占84.5%、单纯血尿占7.6%、单纯蛋白尿占7.9%。16.5%患者伴有高血压。CKD1、2、3期分别占76.9%、20.9%和2.2%。Lee Ⅲ级及以上患者占31.3%。52.8%患者有不同程度肾小球硬化;20.3%伴新月体形成;22.5%伴小管萎缩;16.8%有间质纤维化;24.7%有血管病变。肾小球硬化积分与估算肾小球滤过率（eGFR）呈负相关;与蛋白尿及平均动脉压（MAP）呈正相关。肾小管间质病变积分与eGFR及血红蛋白(Hb)呈负相关;与尿蛋白量呈正相关。血管病变积分与MAP呈正相关;与eGFR呈负相关(均P < 0.05)。多因素logistic回归分析结果显示,肾活检时尿蛋白量（OR = 8.564,P < 0.01）、Scr（OR = 1.031,P< 0.01）及Hb（OR = 0.975,P < 0.01）是肾脏病理损伤（LeeⅢ级以上）的独立危险因素。 结论 部分表现为少量蛋白尿和（或）血尿IgAN患者的病理改变并不轻,且肾功能已减退。尿蛋白量、Scr、Hb是预测肾脏病理损伤程度的独立危险因素。肾活检对这些患者明确诊断、判断病情和预后、制定个体化治疗方案十分重要。     

Clinical and pathological features of hyperuricemia in children with IgA nephropathy at a single center

Objective To investigate the clinical, pathological features and risk factors of hyperuricemia in children with IgA nephropathy (IgAN). Methods A retrospective study of 269 primary IgAN children diagnosed between January 1, 2006 to December 31, 2017 at the Children Kidney Disease Center, the First Affiliated Hospital of Sun Yat-sen University, was performed in the hyperuricemia group (uric acid＞350 μmol/L) and the normal uric acid group. The clinical and pathological characteristics were analyzed, and the risk factors of hyperuricemia were analyzed by using multivariate logistic regression analysis. Results There were 185 males and 84 females in the 269 IgAN children with age of (9.2±3.1) years old, among whom there were 70 patients (26.0%) accompanied by hyperuricemia. Clinical indicators such as hypertension, urea nitrogen, serum creatinine, blood lipids, urinary protein in hyperuricemia group were higher than those in normal uric acid group (all P＜0.05), while estimated glomerular filtration rate, serum total protein and albumin were less (all P＜0.05). There were 58 patients (23.0%) and 12 patients (70.5%) associated with hyperuricemia among IgAN children with CKD 1-2 and CKD 3-5. The proportion of hyperuricemia in CKD stage 3-5 IgAN children was statistically higher than that in normal uric acid group (P＜0.01). The hyperuricemia group had a higher proportion of Lee IV and V grade, and a lower proportion of the Lee III grade than the normal uric acid group (all P＜0.05). According to the Oxford pathological classification score, there was no significant difference in total scores of renal lesions, glomerular score, and tubulointerstitial score between the two groups (all P＞0.05). According to the Katafuchi semi-quantitative score, there was no significant difference in the total scores of renal lesions, glomeruli, and tubulointerstitial scores (all P＞0.05), while the hyperuricemia group had higher renal vascular scores than the normal uric acid group (P＜0.01). Multivariate logistic regression analysis showed that hypertension (OR=12.596, 95%CI 1.778-89.243, P=0.011), higher total cholesterol (OR=1.192, 95%CI 1.064-1.336, P=0.002), higher urea nitrogen (OR=1.273, 95%CI 1.104-1.468, P=0.001), proteinuria 3+(OR=1.875, 95%CI 1.309-2.684, P=0.001), proteinuria 4+(OR=1.627, 95%CI 1.241-2.134, P＜0.001) and CKD stage 3 (OR=3.355, 95%CI 1.376-8.181, P=0.008) were the risk factors of hyperuricemia in children with IgAN. Conclusions Twenty-six percent IgAN children patients are accompanied by hyperuricemia, and their clinical parameters and pathological changes are more severe than those in normal uric acid group. Hypertension, higher total cholesterol, higher urea nitrogen, proteinuria 3+/4+ and CKD stage 3 are the risk factors of hyperuricemia in children with IgAN.     

Related factors of hyperuricemia in IgA nephropathy patients

Objective To investigate the influencing factors of hyperuricemia in patients with IgA nephropathy (IgAN). Methods A retrospective study was performed in patients with renal biopsy diagnosed as IgAN in the Department of Nephrology, Provincial Hospital of Anhui Medical University from January 2016 to October 2018. According to the blood uric acid level, they were divided into two groups: patients with hyperuricemia and patients without hyperuricemia. The general clinical indicators and renal pathological data were compared between the two groups. Logistic regression model was used to analyze the influencing factors of hyperuricemia in IgAN patients. Results A total of 125 IgAN patients with age of (35.70±11.16) years old were enrolled, including 63 males and 62 females. The morbidity of hyperuricemia was 44.0%(55/125). Compared with the normal blood uric acid group, the blood urea nitrogen, serum creatinine and the proportion of chronic kidney disease (CKD) stage 3-5, small arterial wall thickening, fibrous crescents/globules, renal interstitial fibrosis, renal tubular atrophy, glomerular sclerosis and inflammatory cell infiltration in the hyperuric acid group were higher, while the level of estimated glomerular filtration rate (eGFR) was lower. And the differences were statistically significant (all P＜0.05). Multivariate logistic regression analysis showed that the level of serum creatinine was an independent related factor of hyperuricemia in IgAN patients (OR=1.034, 95%CI 1.005-1.064, P=0.021). Conclusions IgAN patients with hyperuricemia presented more severe glomerular, tubular and interstitial lesions, and the level of serum creatinine is an independent related factor of hyperuricemia in IgAN patients. High uric acid level may have an important influence on the progression of IgAN, so good control of serum uric acid may improve the prognosis of patients with IgAN.     

移植肾IgA肾病临床病理及预后分析

目的探讨移植肾IgA肾病(IgAN)复发或新发的诱因及移植肾生存的危险因素。方法选取2012年11月至2018年12月浙江大学医学院附属第一医院经肾活检确诊为移植肾IgAN的患者,按照血肌酐(Scr)增高水平、估算肾小球滤过率(eGFR)下降率分为稳定组(Scr升高值<20μmol/L,eGFR下降率<10%)和进展组(Scr增高但未达翻倍值,30%相似文献   

儿童无症状尿检异常IgA肾病的临床病理和预后分析

目的 探讨儿童无症状尿检异常的IgA肾病的临床病理特征和预后。 方法 对54例IgA肾病儿童的临床和病理特征进行分析。根据起病时有无临床症状分为无症状尿检异常组和有症状肾炎组。组织病理学分级参照Lee氏和Katafuchi氏半定量积分法。 结果 无症状尿检异常组18例，有症状肾炎组36例。有症状肾炎组尿蛋白量（24 h）明显高于无症状尿检异常组[（2.3±2.2） g比（0.4±0.3） g，P < 0.05]。无症状尿检异常的IgA肾病儿童表现为镜下血尿者，87％有尿微量白蛋白增高。无症状尿检异常IgA肾病患儿病理表现以Lee 氏Ⅰ~Ⅱ级为主，2例表现为Lee氏Ⅳ~Ⅴ级和 5例发生Katafuchi Ⅱ~Ⅲ级肾小管间质病变。有症状肾炎组Lee氏病理分级以Ⅱ~Ⅲ级为主，两者病理分级分布差异无统计学意义（P > 0.05）。全组患儿平均随访（26.9±8.8）月后，1例病理为Lee 氏Ⅴ级患儿进入终末期肾衰竭，其余患儿Scr均无升高1倍以上。 结论 无症状尿检异常的儿童IgA肾病虽临床症状轻微，但可出现病理损害严重的病例，并影响其预后。     

少量蛋白尿IgA肾病患者镜下血尿与病理指标的相关性分析

目的探索少量蛋白尿IgA肾病(IgAN)患者镜下血尿发生与病理指标的相关性。 方法回顾性分析2007年1月1日至2012年12月31日在解放军总医院经肾穿刺活检首次诊断的原发性IgAN、尿蛋白<0.5 g/24 h且无肉眼血尿患者。采集患者肾穿刺活检前1周内的血压、尿蛋白定量、尿红细胞形态及计数、肾功能等指标。肾活检后的病理指标按照IgAN牛津分型更新版评价,采用Poisson回归分析镜下血尿水平与病理指标的相关性。 结果共纳入尿蛋白<0.5 g/24 h的IgAN患者88例,其中无镜下血尿组22例,非满视野镜下血尿组58例,满视野镜下血尿组8例。Poisson回归分析显示在校正患者的尿蛋白和肾功能(eGFR)水平后,新月体形成(OR 6.55,95%CI 2.68～15.98)和系膜细胞增殖(OR 4.92,95%CI 1.75～13.83)与IgAN患者镜下血尿水平相关,系膜细胞增殖病变与节段硬化或球囊粘连病变存在交互作用(OR 3.82,95%CI 1.30～11.25)。 结论在蛋白尿少于0.5 g/d的IgAN患者中,患者镜下血尿水平相关的病理因素主要是增殖性病变,包括系膜细胞增殖和新月体形成。系膜细胞增殖病变合并节段硬化和(或)球囊粘连病变,与镜下血尿水平的相关性显著增加。     

IgA肾病伴部分性新月体形成的临床病理分析

目的：探讨原发性IgA肾病伴部分性新月体形成的临床和病理特点。方法：选取79例经肾活检确诊伴部分性新月体形成IgA肾病患者,分析其临床和病理特点,并根据新月体形成所累及肾小球的比例分组：≥10%为A组,31例;≤10%为B组,48例。结果：（1）临床表现：79例均有血尿＋蛋白尿,蛋白尿〉1g/24h者48例（60.8%）;两组比较,A组蛋白尿〉1g/24h28例（89.3%）,B组蛋白尿〉1g/24h20例（41.7%）,A组大量蛋白尿、肉眼血尿、高血压、肾衰竭发生率均高于B组（P〈0.05）。（2）病理表现：79例新月体形成累及肾小球3.3%～29.0%,均以细胞性为主,几乎均有肾小球硬化、内皮细胞及系膜细胞增生、球囊黏连、灶性肾小管萎缩、以及炎性细胞浸润;两组比较A组中、重度系膜细胞及内皮细胞增生、炎性细胞浸润,细胞新月体所占比例均较B组明显;病理改变硬化肾小球占55例（69.6%）。结论：IgA肾病伴部分性新月体形成患者临床均有血尿＋蛋白尿,尤其大量蛋白尿;病理改变以局灶节段性肾小球硬化常见;炎性细胞浸润、内皮细胞及系膜细胞增生等活动性病变易见并影响新月体形成;新月体的多少及纤维化程度影响临床病理表现,≥10%较≤10%严重。     

IgA肾病患者扁桃体B1a细胞和IgA1阳性细胞表达及相关因素分析

目的 研究B1a和IgA1阳性细胞在IgA肾病患者扁桃体中的表达及B1a细胞与血尿、蛋白尿和病理Lee分级的关系。 方法 肾活检确诊为原发性IgA肾病及非肾炎慢性扁桃体炎患者各8例为对象,用免疫荧光法和激光共聚焦显微镜对其扁桃体组织进行B1a及IgA1细胞定位和定量计算,并按蛋白尿程度和Lee分级标准与IgA肾病组B1a细胞数量行统计学分析。 结果 B1a细胞主要分布在扁桃体生发中心和小结帽;IgA1细胞主要分布在上皮内、上皮下,以上皮和淋巴组织交界区为多。与慢性扁桃体炎组比较,IgA肾病组两种细胞表达明显增多（P < 0.01）,且呈正相关（r = 0.778,P = 0.023）。在血尿伴蛋白尿和Lee≥Ⅲ级组B1a细胞显著高于单纯血尿和Lee<Ⅲ级组（P < 0.05）。 结论 IgA肾病患者扁桃体中IgA1可能是B1a细胞分泌的。B1a细胞数量随着患者蛋白尿的出现和病理严重程度的加重而增加,可能在疾病发生和进展过程中起着重要的作用。     

Analysis of the clinical pathological characteristics and prognosis of primary IgA nephropathy with hypertension

Objective To investigate the clinic-pathological features and prognostic risk factors of IgA nephropathy (IgAN) with hypertension (HTN). Methods Primary IgAN patients diagnosed with biopsy from January 2016 to December 2017 were recruited. Patients were divided into IgAN with normal blood pressure (IgAN-NTN) group and IgAN with hypertension (IgAN-HTN) group based on the pressure value when performing the kidney biopsy. The clinical and pathological data were collected and compared between the two groups. Kaplan-Meier method was conducted for renal results, whereas the Cox regression model was exploited to analyze the prognostic factors in the progression of IgAN-HTN patients. Results The total number of enrolled patients was 275 cases, 170 (61.82%) of which had normal pressure and 105 individuals (38.18%) resulted in hypertension. The IgAN-HTN group in terms of male proportion, age, systolic pressure, diastolic pressure, serum urea nitrogen, serum creatinine, serum uric acid, 24 h urinary protein, triacylglycerol, complement C4 and so on were higher than those in the IgAN-NTN group (all P＜0.05). The incidence of gross hematuria and the level of estimated glomerular filtration rate (eGFR) were significantly lower than those in the NTN group (all P＜0.001). For the aspect of light microscope pathological manifestations, IgAN-HTN group exhibited more severe histological lesions including glomerular sclerosis, renal tubular atrophy or renal interstitial fibrosis, interstitial vascular injury than IgAN-NTN group (all P＜0.05). Immunofluorescence examination results showed that the deposition ratio of C1q in IgAN-HTN group was higher than that in IgAN-NTN group (P=0.015). By employing Kaplan-Meier method, the cumulative renal survival rate in the HTN group was much lower than that in the NTN group (Log-rank test: χ2=6.456, P=0.011). For the patients in IgAN-HTN group, the cumulative renal survival rate in the dyslipidemia group was much lower than that in the ortholiposis group (Log-rank test: χ2=5.093, P=0.024). There was no significant difference in the cumulative renal survival rate between the blood pressure control group and the unqualified group (Log-rank test: χ2=1.036, P=0.309). As a result of univariate and multivariable Cox regression analysis, total cholesterol, eGFR and 24 h urinary protein were risk factors for renal progression of IgAN patients with hypertension. Conclusions The clinical manifestations and renal pathological changes in patients with IgAN-HTN are more serious than those in IgAN-NTN patients, which result in worse prognosis. IgAN-HTN patients should be paid more attention to the management of serum lipid level during treatment and follow-up.     

Clinico-pathological features and renal outcomes of primary IgA nephropathy with IgM deposition

Objective To investigate the clinico-pathological features and renal outcomes of primary IgA nephropathy (IgAN) with glomerular IgM deposition. Methods Primary IgAN diagnosed with biopsy from January 2006 to December 2011 were recruited. Patients were divided into groups according to IgM deposition (Group A) and without IgM deposition (Group B). In addition, Group A was subdivided into two groups based on the position of IgM deposits as the mesangium (Group A1) and both mesangium and capillary wall (Group A2). Renal outcomes were defined as end stage renal disease (ESRD) and/or the doubling of baseline serum creatinine. Clinico-pathological features were retrospectively compared. Kaplan-Meier was conducted for renal outcomes, and Cox regression model was used to analyze the prognostic value of IgM deposition and the position of IgM deposition in the progression of nephropathy in IgAN patients. Results 939 patients were enrolled with 422 (44.9%) having IgM deposition (Group A). Of the 422 patients, 382 patients were divided as Group A1, whereas 40 patients were noted as Group A2. Compared to Group B, hemoglobin, serum protein, albumin and serum IgG levels in group A were significantly lower, and the cholesterol and serum IgM levels were significantly higher (all P＜0.05). There was no significant difference in serum creatinine, estimated glomerular filtration rate (eGFR), urinary protein, blood pressure and uric acid between group A and B. In terms of pathological manifestations, patients in Group A exhibited more severe histological lesions including glomerular sclerosis, S1, M1 and interstitial inflammatory cell infiltration (all P＜0.05). Immunofluorescence showed that the proportion of IgG, C1q and Fg deposition in group A was significantly higher than that in group B (all P＜0.05). By Kaplan-Meier, cumulative renal survival rate has no significant difference between Group A and B (Log-rank test χ2=0.019, P=0.891). Univariate and multivariable Cox regression analysis showed that IgM deposition had no significant effect on the renal progression in IgAN patients. Subgroup analysis showed that patients in Group A2 exhibited higher urine protein, creatinine and blood pressure, and lower eGFR and serum albumin, also had worse histological lesions including M1, E1 and T1-2 of Oxford classification (all P＜0.05), Immunofluorescence showed that the proportion of IgG, C1q and Fg deposition in group A2 was significantly higher than that in group A1 (all P＜0.05). By Kaplan-Meier, renal survival rates calculated from outcomes were lower in Group A2 (Log-rank test χ2=18.207, P＜0.001). In addition, IgM deposited both in the mesangium and capillary wall was a risk factor for renal progression of IgAN patients with IgM deposition by a univariate Cox hazards regression mode and multivariable-adjusted Cox models (HR=3.621, 95%CI 1.924-6.814, P＜0.001; HR=2.309, 95%CI 1.176-4.533, P=0.015 respectively). Conclusions The IgAN patients with IgM deposition relatively had more severe clinico-pathological changes, especially those with IgM deposited both in the mesangium and capillary wall. In this study, IgM deposition was not found to be an independent risk factor for the prognosis of kidney in IgAN patients. However, IgM deposited both in the mesangium and capillary wall was an independent risk factor for renal prognosis in IgAN patients with IgM deposition.     

150例原发性IgA肾病临床与病理的回顾性研究

目的 分析原发性IsAN的临床和病理特点,为其诊断和治疗提供依据。方法 对150例原发性IgAN患者的临床和病理特点进行回顾性分析。结果 本组患者伴有血尿者114例,男性44例,女性70例,女性患者多于男性患者(p＜0.01);有44例患者发生肉眼血尿,其中24例肉眼血尿与急性扁桃体炎有关。临床与病理相关性分析显示,肾...     

RGC-32在儿童IgA肾病肾组织中的表达及意义

目的 研究RGC-32（response gene to complement 32）在IgA肾病(IgAN) 儿童及正常肾组织中的表达及其意义。 方法 用免疫组织化学方法观察IgAN儿童及正常肾组织中RGC-32蛋白的表达与分布,并与α平滑肌肌动蛋白(α-SMA)、转化生长因子β1（TGF-β1）的表达、IgAN肾组织病理损伤程度及临床相关指标进行统计学分析。 结果 RGC-32蛋白在IgAN及正常肾组织的肾小管均明显表达,而在肾小球、肾小管间质及肾血管未见表达。RGC-32 在正常肾组织、IgAN轻度、中度及重度损伤组中的阳性表达指数分别为（18.29±6.22）%、（23.90±9.65）%、（31.23±9.86）%和（34.52±10.63）%。RGC-32在IgAN儿童肾组织的阳性表达指数与肾小球评分、肾小管间质评分均呈正相关（r = 0.385,0.347,P < 0.05）;与α-SMA、TGF-β1表达亦呈正相关（r = 0.594,0.521,P < 0.01）;而与Scr、尿NAG/Cr、尿Alb/Cr、尿 IgG/Cr、尿α1微球蛋白/Cr均无相关（r = 0.117,-0.115,-0.138,-0.176,-0.028,P均>0.05)。 结论 首次发现RGC-32蛋白在IgAN儿童和正常肾组织中表达于肾小管,而在肾小球、肾小管间质及肾血管未见表达。RGC-32可能参与了IgAN患儿的肾小管间质损伤,尤其是TGF-β1诱导的肾小管上皮细胞-间充质转分化（EMT）过程。     

Association between obesity and absolute renal risk factors in patients with IgA nephropathy

Objective To investigate the influence of obesity on renal lesion in IgA nephropathy (IgAN) patients by analyzing the association between obesity and absolute renal risk factors (ARR). Method Clinical-pathological data of IgAN patients diagnosed by renal biopsy in General Hospital of Ningxia Medical University were collected retrospectively. According to the body mass index (BMI), patients were divided into non-obese group (BMI＜28, N-OB group) and obese group (BMI≥28, OB group). Their clinical characteristics, pathological index and ARR scores were compared. The relationship of BMI and ARR was analyzed by ordinal logistic regression models. Results (1) A total of 674 IgAN patients with mean age of 35.5±11.3 years were enrolled, including 94 in OB group and 580 in N-OB group respectively. Compared with those in the N-OB group, the proportion of male, age, mean arterial pressure, blood uric acid, blood triglyceride, diabetes mellitus and hypertension increased in OB group (all P＜0.01). Patients in OB group had lower estimated glomerular filtration rate (eGFR) and higher ARR score than those in N-OB group (all P＜0.05). (2) More severe thickening renal small artery wall and hyaline degeneration were observed in the OB group than in the N-OB group (all P＜0.01). There was no statistical difference between the two groups in Lee classification, Oxford classification, mesangial cell proliferation, glomerular sclerosis, crescent formation, renal tubular atrophy, interstitial inflammatory cell in filtration and endothelial cell proliferation. (3) After adjusting for age, sex, blood uric acid, serum albumin, eGFR, low density lipoprotein, glomerular sclerosis, interstitial inflammatory cell infiltration, renal tubular atrophy and vascular wall thickening, BMI was still an independent risk factors for ARR in IgAN patients (OR=1.09, 95%CI 1.03-1.14). Conclusions BMI is an independent risk factors for ARR in IgAN patients. Early prevention and control of obesity and its associated risk factors may improve outcomes of IgAN patients.     

Crescents proportion no lower than 14% were significantly associated with renal function and outcomes of IgA nephropathy patients

Objective To explore the clinicopathological features and outcomes of IgA nephropathy patients with different proportions of crescents. Methods A total of 270 patients who were diagnosed as IgA nephropathy by renal biopsies from January 2010 to December 2015 in the First Affiliated Hospital of Shenzhen University were enrolled. All patients were divided into 3 groups according to the optimal cutoff level of crescents proportion in the Receiver Operating Characteristic Curve (ROC) as follows: 0%, ＜14%; ≥14%. The endpoint was defined as the doubling of baseline serum creatinine (Scr) and/or end-stage renal disease (ESRD). Kaplan-Meier curve and Cox regression model were used to analyze the renal survival among three groups. Results One hundred and four patients (38.5%) without any crescents; 84 patients (31.1%) with crescents proportion＜14% and 82 patients (31.4%) with crescents proportion ≥14%. Patients with crescents proportion ≥14% group were older and had higher level of systolic blood pressure and diastolic blood pressure, 24-hour urine protein and serum uric acid level; more patients treated with RAS blocker, glucocorticoid and immunotherapy, but lower eGFR, hemoglobin and serum albumin level than those with crescents proportion＜14%. Compared with those without crescents and crescent proportion＜14%, patients with crescent proportion ≥ 14% also had higher proportion of global glomerulosclerosis, more endocapillary hypercellularity and severe tubulointerstitial lesions, higher degree of IgA and C3 depositions in renal. 24-hour proteinuria, serum uric acid level, low hemoglobin level, endocapillary hypercellularity and renal C3 depositions were risk factors for crescents formation. Patients were followed-up for a median of (31.7±21.0) months, and Kaplan-Meier analysis revealed that renal survival rate was significantly lower in patients with crescents proportion ≥14% compared with other groups (P=0.001). But there was no significant difference between no crescent group and crescents proportion＜14% group. However, multivariate Cox analysis showed no significant difference between crescents proportion and renal survival. Conclusion Crescents proportion is associated with higher risk of renal function and renal progression.     

Clinical and pathological significance of circadian blood pressure rhythm change in IgA nephropathy patients with hypertension

Objective To investigate whether the clinical and pathological injury of kidney in IgA nephropathy (IgAN) patients with hypertension is associated with circadian blood pressure rhythm change, particularly with elevated nocturnal blood pressure (BP). Methods This study was a retrospective cross-sectional study. Clinic and renal histopathological injury data were obtained from 83 IgAN patients with hypertension. First, 24 h ambulatory BP monitoring (ABPM) data were analyzed. Second, all these IgAN patients were divided into two groups, elevated nocturnal BP group and nocturnal normotensive BP group, and the clinical and pathological differences between this two groups were analyzed. Third, logistic regression analysis was used to analyze the influencing factors of renal tubulointerstitial injury in IgAN patients with hypertension. At last, all these IgAN patients were divided into two groups according to the level of estimated glomerular filtration rate (eGFR), group of patients with eGFR≥60 ml?min-1?(1.73 m2)-1 and the other group with eGFR＜60 ml?min-1?(1.73 m2)-1, and the 24 h ABPM data were compared. Results (1) The proportion of non-dipper circadian rhythm of BP in IgAN patients with hypertension was 79.5%. (2) Compared with nocturnal normotensive BP group, patients in elevated nocturnal BP group had significantly higher levels of 24-hour urinary protein quantity and blood uric acid (both P＜0.05), and lower eGFR and urine osmotic pressure clinically (both P＜0.05). Index of interstitial fibrosis and tubular atrophy was significantly higher in nocturnal normotensive BP group (P＜0.05), while the proportion of glomerular ischemia lesion was not significantly different between two groups. (3) Multivariate logistic regression analysis showed that elevated nocturnal BP was an independent risk factor for severe tubulointerstitial injury of IgAN (OR=1.113, 95%CI 1.038-1.192, P=0.002). (4) Compared with the group of eGFR≥60 ml?min-1?(1.73 m2)-1, 24-hour systolic blood pressure (SBP) and diastolic blood pressure (DBP), daytime SBP and DBP, nocturnal SBP and DBP were significantly higher in group of eGFR＜60 ml?min-1?(1.73 m2)-1 (all P＜0.05). Conclusion The proportion of non-dipper circadian rhythm of BP in IgAN patients with hypertension is as high as 79.5%. Elevated nocturnal BP is associated with the severity of renal damage, and elevated nocturnal BP is an independent risk factor for severe tubulointerstitial injury in IgAN patients with hypertension. Therefore, 24 h ABPM should be emphasized, and elevated nocturnal BP should be well controlled to slow the progression of IgAN.     

伴足细胞尿的IgA肾病的临床病理特征

目的 探讨伴足细胞尿的IgA肾病（IgAN）患者的临床病理特点。方法 入选IgAN患者36例,其中男性20例,女性16例,平均年龄（34．1±12．2）岁。10例健康志愿者为健康对照。足细胞排泄的定量检测采用尿沉渣涂片免疫组化染色直接计数。进行尿液足细胞排泄与肾脏病理的相关分析。结果 （1）IgAN患者尿细胞podocalyxin阳性率为61%,健康对照组为0（P＜0．05）。（2）与非大量蛋白尿（＜3．0 g/24 h）IgAN患者比较,大量蛋白尿（≥3．0 g/24 h）IgAN患者的尿液足细胞检测阳性率、尿液足细胞排泄数、足细胞与尿肌酐的比值以及足细胞占尿液小管上皮细胞的百分数均显著增高（P＜0．05）。IgAN患者足细胞排泄水平与蛋白尿水平呈正相关（r=0．446,P=0．007）。（3）与无足细胞尿的患者比较,伴足细胞尿的IgAN患者的蛋白尿水平显著增高,血浆白蛋白水平显著降低,肾小管上皮细胞与尿肌酐的比值亦显著增高（P＜0．05）。但伴与不伴足细胞尿的2组IgAN患者在年龄、性别、血压、Scr、血红蛋白水平以及血浆脂质代谢等方面差异均无统计学意义（P＞0．05）。（4）尿足细胞的排泄与细胞新月体或细胞纤维性新月体、小球血管襻腔狭窄和足突广泛融合病变有关,而与系膜、内皮细胞病变及局灶基底膜增厚无关。伴足细胞尿的患者肾小球和肾小管间质纤维化更明显（P＜0．05）。伴有新月体的患者其尿液足细胞排泄水平、尿液上皮细胞和管型的排泄均增加（P＜0．05）。结论 足细胞尿不仅是IgAN患者肾小球损伤的结果,也是IgAN患者活动性损伤的指标。足细胞尿排泄的水平与蛋门尿水平呈正相关,与肾脏病理类型也有一定的关系。     

Clinicopathological features and renal outcomes of IgA nephropathy with acute tubulointerstitial nephropathy

Objective To evaluate the clinicopathological characteristics and outcomes of IgA nephropathy (IgAN) with acute tubulointerstitial nephropathy (ATIN). Methods Patients who were diagnosed as IgAN with ATIN and IgAN without ATIN by renal biopsy in Peking University First Hospital were enrolled. There were 74 cases of IgAN with ATIN, and seventy-four cases of IgAN without ATIN were enrolled based on stratified sampling (chosen by 1∶1). The two groups were well matched with age, gender, follow-up time, mesangial hypercellularity(M), endocapillaryhypercellularity(E), segmental glomerulosclerosis(S), tubular atrophy/interstitial fibrosis(T) and cellular/fibrocellular crescent(C). The clinicopathological characteristics and outcomes of two groups were retrospectively analyzed. A composite end point, defined as 30% or 50% estimated glomerular filtration rate (eGFR) decline and end stage renal disease (ESRD) was used. Renal function and proteinuria during follow-up were observed. Renal survival was calculated by Kaplan-Meier survival analysis and risk factors of progression were analyzed by using univariate and multivariate Cox regression models. Results Seventy-four cases of IgAN with ATIN and seventy-four cases of IgAN without ATIN were enrolled. Serum creatinine [(185.6±83.2) μmol/L vs (146.3±69.2) μmol/L, P=0.010] and incidence of acute kidney disease (AKD) (31.1% vs 5.4%, P＜0.001) were higher in IgAN with ATIN group than those in IgAN without ATIN group. Patients in ATIN group received more immunosuppressive treatment (86.5% vs 58.1%, P＜0.001). During 1 year after biopsy, mean eGFR increased significantly in IgAN with ATIN group [(39.7±14.6) ml?min-1?(1.73 m2)-1 vs (47.2±19.9) ml?min-1?(1.73 m2)-1, P=0.017], but mean eGFR was not statistic different in IgAN without ATIN group [(60.0±30.5) ml?min-1?(1.73 m2)-1 vs (59.0±31.7) ml?min-1?(1.73 m2)-1, P=0.567]. Median follow-up was 23.0 months in IgAN with ATIN group, and Median follow-up was 30.0 months in IgAN without ATIN group. Incidence of composite end point had no significant differences between two groups. IgAN with ATIN was not the independent risk factor for end point. IgAN patients with ATIN were divided into two groups (with AKD and without AKD), then renal survival rate was higher (Log-rank test, χ2=5.293, P=0.021) and the risk for composite end point decreased by 79.2% (HR=0.208, 95%CI 0.046-0.939, P=0.041) in the group with AKD. Conclusions In IgAN, there is a subgroup of patients with the specific pathological phenotype combined with ATIN. Compared with those without AKD, the risk for composite end point of IgAN patients with ATIN and AKD showed a 79.2% decrease.     

Factors predicting progression of IgA nephropathies

The difficulties in defining the natural history of primary IgA nephropathy (IgAN) depend upon the pre-selection of patients for renal biopsy, a true individual variability - ranging from asymptomatic to rapidly progressive forms - as well as the use of different classifications of the renal lesions and statistical analyses sometimes carrying incorrect modalities. Long-term natural history studies have demonstrated that the rate of progression has an extremely wide range, from 5 to 25% after 10 years and 25-50% at 20 years, and complete remission is reported as well in 5 to 30% of cases. A geographic variability has been confirmed in a tri-continental study, explainable only partly by the earlier referral. Among the factors predicting progression, the more frequent in cohorts showing worse actuarial survival at 10 years are those associated with the advanced phases of renal damage, as increased creatinine level, arterial hypertension and nephrotic range proteinuria. A multivariate statistical approach showed the relevance of proteinuria during follow-up (percent duration of massive proteinuria or proteinuria at 1 year) more than proteinuria at the onset. Mean blood pressure value (MAP) and proteinuria during follow-up were independent predictors of end-stage CKD. Note the predictive value of severe microscopic hematuria in several studies. As far as histological features are concerned, strong independent predictors of progression at Cox multivariate analysis are the severity of glomerular sclerosis and interstitial fibrosis. The presence of crescents was a risk factor in almost all studies at univariate analysis, but did not maintain a significant predictor value at multivariate analysis. Conversely the association between crescents and tuft adhesions, possibly resulting from previous segmental necrosis, was found to be a significant risk factor. The extent of mesangial proliferation and parietal expansion of deposits was not significantly associated to unfavourable prognosis at multivariate analysis. The analysis of risk factors for progression of IgAN related to Henoch-Schoenlein purpura (HSP) failed to demonstrate any prognostic value for the presence and severity of extra-renal signs of vasculitis or presence of triggering factors. At multivariate Cox analysis, age and mean proteinuria during follow-up were powerful independent prognostic predictors. Proteinuria at baseline was not significantly related to renal progression, nor were hypertension or impaired renal function at onset. It is of interest that data at onset and at renal biopsy (renal function impairment, hypertension, nephrotic-range proteinuira) were not significantly related with renal detrimental progression. Neither had prognostic value the finding of crescents involving up to 75% of glomeruli.     

Natural history of primary IgA nephropathy

Primary IgA nephropathy (IgAN) is the most frequent type of primary glomerulonephritis worldwide. The characteristic presentation is gross hematuria at the time of an infectious episode. A renal biopsy still is mandatory for the diagnosis. The natural history of the disease is characterized by clinical and pathologic progression over time, which can vary from a few years to more than 50 years. It is possible to make a broad prediction at the time of diagnosis of the long-term (20 years) risk of progressive chronic kidney disease, and then to end-stage renal disease requiring renal replacement therapy (20-year cumulative end-stage renal disease risk range, 14%-39%). The 3 major independent risk factors are arterial hypertension, proteinuria more than 1 g/d, and severe renal histopathologic lesions including hyalinosis, crescents, or defined by histopathologic scoring systems. When any clinical risk factors are present, patients should be targeted closely by appropriate treatments in the following order: (1) precise control of hypertension, (2) control of proteinuria when persisting for greater than 1 g/d, and (3) evidence-based treatment where available for severe lesions. This is a symptomatic treatment strategy because pathogenesis and etiology still remain unclear.     

Clinical remission and pathological progression after tonsillectomy in a renal transplant patient with recurrent IgA nephropathy

Abstract:  We discuss a renal transplant patient with recurrent IgA nephropathy (IgAN) before and after tonsillectomy. A 36-year-old man started on hemodialysis support in 1996 due to biopsy-proven IgAN, living related renal transplantation was then performed in 1997. Six years after transplantation, the patient presented with microhematuria and proteinuria. Graft biopsy for these urinary abnormalities showed recurrent IgAN. Tonsillectomy was subsequently performed in December 2003, proteinuria remitted 6 months after the tonsillectomy and microhematuria disappeared three years later. Protocol graft biopsy was subsequently performed twice, at 2 yr after the tonsillectomy (2005) and 4 yr after (2008). Comparing the findings of the pre-tonsillectomy biopsy and the two post-tonsillectomy biopsies, an increase in mesangial cells and matrix in 2005, and an expansion of the mesangial matrix and proliferation of mesangial interposition in 2008. In addition, global sclerosis of glomeruli increased over time, the area of tubulointerstitial damage has extended as well. While the tonsillectomy led to clinical remission of recurrent IgAN, the chronicity progressed on these protocol biopsies. This is the first report of the efficacy and the limitations of tonsillectomy in a case of recurrent IgAN in a transplant patient.