儿童C1q肾病的临床病理特点及治疗

目的 探讨儿童C1q肾病的临床、病理特点及治疗方法。 方法 回顾性分析本院8年来经肾活检确诊的23例C1q肾病患儿临床、病理和预后资料。 结果 C1q肾病占同期肾活检的原发性肾小球疾病的4.78%。23例患儿中,男15例,女8例;年龄10个月~12岁5个月,平均发病年龄（5.0±3.4）岁;肾病综合征（NS） 18例（2例伴镜下血尿）,肾病水平蛋白尿4例（1例伴镜下血尿）,单纯镜下血尿1例。1例NS起病前曾服用2周中药,发病时同时并发急性肾功能不全。3例患儿有肾脏病家族史,其中2例（肾病水平蛋白尿）为姐弟,父亲亦有蛋白尿,基因检测证实为家族性Denys-Drash综合征并发C1q肾病。1例患儿（NS）姐姐亦有大量蛋白尿（未行肾活检）。所有患儿起病时血压均正常,补体正常,抗核抗体、抗dsDNA抗体、抗Sm抗体及乙肝两对半均阴性。18例NS中13例激素耐药（72.2%）,4例激素依赖,1例激素敏感。光镜下,13例为微小病变（MCD）（其中1例伴间质性肾炎）;6例为系膜增生性肾小球肾炎（MsPGN）;4例为局灶节段性肾小球硬化（FSGS）。另9例患儿伴有不同程度的小管萎缩和间质纤维化。免疫荧光下,所有患儿均见系膜区弥漫性C1q≥2+沉积,其中伴IgG沉积18例,IgM沉积18例,IgA沉积8例,C3沉积11例,6例患儿呈“满堂亮”表现。除4例患儿电镜下未见肾小球外,其余19例中4例系膜区见电子致密物沉积。12例激素耐药（包括2例肾病水平蛋白尿者）及3例激素依赖患儿在激素治疗基础上加用静脉CTX冲击;3例激素耐药者加用环孢素A（CsA）口服;1例激素依赖患儿给予足量激素重新诱导;1例单纯镜下血尿患儿及2例Denys-Drash综合征并发C1q肾病患儿仅给予血管紧张素转换酶抑制剂（ACEI）治疗。其中1例患儿CTX冲击满疗程无效后换用CsA治疗;1例患儿CTX冲击满疗程无效后换用FK506治疗。23例患儿中,1例失访,1例治疗时间<3个月未纳入随访对象,2例Denys-Drash综合征目前不能通过药物治疗好转未纳入疗效统计,余19例中,15例完全缓解（78.9%）,2例部分缓解（10.5%）,2例无效（10.5%）。NS患儿总缓解比例94.4%（17/18）,肾病水平蛋白尿患儿总缓解比例50.0%（2/4）。病理为MCD者总缓解比例100.0%,MsPGN者缓解比例83.4%,FSGS缓解比例50.0%。随访末所有患儿血压、肾功能均正常,自身抗体均阴性,补体水平均正常。 结论 C1q肾病罕见,临床以NS或肾病水平蛋白尿为主,且往往激素耐药或激素依赖;病理以MCD为主,也可表现为MsPGN或FSGS。加用其他免疫抑制剂治疗后,MCD和MsPGN者多可获缓解,但FSGS预后欠佳。     

儿童C1q肾病临床病理研究

目的 :探讨儿童C1q肾病临床病理特征及诊断与治疗。方法 :分析 8例C1q肾病患儿临床病理特点及激素或免疫抑制剂治疗效应 ,并与同期 77例原发性NS患儿作比较。结果 :8例C1q肾病患儿临床上大多表现为原发性NS(6例 ) ,仅 2例表现为肾炎综合征和单纯性血尿。LM主要包括MC(3例 )、MsPGN(2例 )、FSGS(2例 )和ECPGN(1例 )。IF显示明显的系膜区C1q沉积 ,伴或不伴有Ig和补体沉积。EM检查仅 1例有系膜区和内皮下电子致密物沉积。与原发性NS相比 ,6例表现为NS的C1q肾病患儿对泼尼松初次治疗产生耐药的相对危险度为 2 1(P <0 .0 0 1) ,但对免疫抑制剂治疗均敏感。结论 :儿童C1q肾病临床上以对激素耐药的NS为常见表现 ,IF是其主要诊断依据 ,使用免疫抑制剂治疗有效     

C1q肾病的儿科临床病理研究

Clq肾病是一种免疫复合物(IC)介导的肾小球病变,患者的尿蛋白量常在肾病综合征(NS)范围。Jennette和Hipp首先报道15例年龄14～27岁的本病患者时使用这一名称。ClqNP在免疫荧光(IF)检查中都可见到非全身性系膜病变的肾小球肾炎。ClqNP与其它原因引起的NS不同,其特点为,IF可见系膜区形成明显的Clq沿着免疫球蛋白沉积,而无膜增殖性肾小球炎(MPGN)的特征性肾小球毛细血管壁损伤和SLE的临床表现。 15例ClqNP患儿年龄2～16岁,男女之比1∶2。其中3例持续肾小球炎患儿表现为中度蛋白尿、血尿和细胞管型;1例肾炎性肾病;9例特发性NS;     

幼儿C1q肾病一例

C1q肾病是一种临床上罕见的免疫复合物介导的肾小球疾病,由Jennette和Hipp于1985年首次命名[1],国内仅有个案报道,国内外例数不足50例,本院收治1例,报告如下.     

524例IgA肾病的临床与病理分析

目的 回顾性地总结我科１０多年来所积累的ＩｇＡ肾病资料,包括各年龄组的发病率、临床、病理特点及其相关性。方法 ５２４例ＩｇＡ肾病按照年龄分成３组,根据各年龄组的临床及其组织学特点进行分析。结果 少儿组复发性肉眼血尿发生率最高为４７．２％,慢性肾损害为４．６％。青壮年恶性高血压的发生率为３．８％,也称为恶性ＩｇＡ肾病。老年组肾病综合征和急性肾功能衰竭的发生率高于上述两组。结论 随着肾活栓的广泛开展,     

肾炎症性肌纤维母细胞瘤临床病理分析

目的探讨肾炎症性肌纤维母细胞瘤的病理学特点、临床表现和预后。方法总结1例罕见的肾炎症性肌纤维母细胞瘤,结合文献对其临床表现、组织形态、免疫组化特点、治疗及预后等进行分析和探讨。结果患者女性,58岁,无明显诱因出现排酱油色尿,伴尿频、尿急、尿痛。CT提示＂右肾盂输尿管交界处占位性病变＂,行右侧肾切除术。肾肿物大小为9cm×7cm×6cm,圆形,灰白色,质地较硬,无包膜,与周围界限欠清。肿物切面为灰白色,实性,部分区域粘液变性、出血及坏死。镜下见肿瘤细胞呈梭形,肿瘤细胞呈束状或编织状排列,伴较多淋巴细胞和浆细胞浸润。免疫组化显示Vimentin及SMA呈阳性表达。病理诊断：肾炎症性肌纤维母细胞瘤。结论肾炎症性肌纤维母细胞瘤是非常少见的低度恶性肿瘤,确诊需依靠病理诊断,治疗多采用外科手术切除。     

18例IgA肾病的临床与病理

原发性ＩｇＡ肾病是最常见的肾小球疾病 ,它主要表现肾小球系膜区以ＩｇＡ为主的免疫球蛋白沉积为主要特点和主要诊断依据。临床症状几乎包括了肾小球肾炎的各种表现 ,本病又是导致肾小球硬化 ,肾小管间质纤维化和终末期肾衰的常见重要病因。而免疫病理却是多变。下面我们对18例肾穿确诊的ＩｇＡ肾病进行临床和免疫病理总结 ,报告如下。资料与方法1　研究对象　 2 0 0 0年在本科住院肾穿诊断的ＩｇＡＮ11例 ,外院 7例 ,共 18例。其中男 11例 ,女 7例 ;年龄 18岁～6 6岁之间 ,平均年龄 33岁。排除了慢性肝病 ,ＳＬＥ和紫癜肾等继发性病因。2…     

原发性肾病综合征并发急性肾损伤48例临床病理分析

目的探讨原发性肾病综合征合并急性肾损伤的临床及病理特点,提高此类并发症的防治水平。方法对我院原发性肾病综合征合并急性肾损伤患者的临床和病理改变进行回顾性分析。结果原发性肾病综合征合并急性肾损伤的临床特征表现为大量蛋白尿、高度水肿,常合并胸腹腔积液。肾脏病理类型：系膜增生性肾小球肾炎、肾小球微小病变及IgA肾病多见。其中系膜增生性肾小球肾炎22例,占46%;微小病变型10例,IgA肾病9例。所有患者均依据病理分型给予激素和（或）细胞毒药物,同时行利尿、控制感染、抗凝等综合治疗,其中5例进行血液透析治疗,肾损伤大多好转,但增生硬化型肾炎等预后较差。结论原发性肾病综合征并发急性肾损伤临床并不少见,多发生于系膜增生性肾小球肾炎、肾小球微小病变及IgA肾病,尽早明确病理诊断和去除诱因,并予相应治疗,大多患者预后良好,肾功能可恢复正常。     

Clinicopathological and prognostic analysis of children with primary IgA nephropathy with C1q deposition

Objective To investigate the clinical and pathological features and prognosis of children with IgA nephropathy with C1q deposition. Methods The children with IgA nephropathy diagnosed by renal biopsy from January 1, 2000 to December 30, 2017 were retrospectively analyzed and divided into C1q deposit group and C1q negative group according to glomerular immunofluorescence examination. Follow-up until the patient's serum creatinine doubled, glomerular filtration rate decreased by more than 50%, entering end-stage kidney disease, renal replacement therapy or death. Kaplan-Meier survival analysis was used to evaluate the renal survival rate in two groups. Univariate and multivariate Cox proportional hazard regression models were used to analyze the effect of C1q deposition on the prognosis of patients with IgA nephropathy. Results There were 60 cases in C1q deposition group and 60 cases in C1q negative group. (1) the initial eGFR and plasma albumin in C1q deposition group were lower than those in C1q negative group, while the levels of serum creatinine, serum cholesterol and 24 hour urinary protein in C1q group were higher than those in C1q negative group (all P＜0.05). (2) pathological indexes: Mesangial cell proliferation, tubular atrophy/interstitial fibrosis, and cell/fibrocytic crescein score in C1q negative group were significantly higher than those in C1q negative group (all P＜0.0.5). (3) Kaplan-Meier analysis showed that there was significant difference in renal cumulative survival rate between the two groups (Log-rank test: χ2=6.801, P=0.009). Cox proportional hazard regression model showed that the risk of renal end-point events in IgAN children with C1q deposition group was 5.772 times higher than that in C1q negative group (HR=5.772, 95%CI: 1.353-24.6211, P=0.018). Conclusion C1q deposition is an independent risk factor for the progress of renal function in IgA nephropathy children.     

C1q nephropathy in two young sisters

C1q nephropathy (C1qNP) is a controversial and uncommon form of glomerulonephritis, characterized by mesangial immunoglobulin and complement deposits, predominantly C1q, with no evidence of systemic lupus erythematosus. Clinically, it may present as nephrotic syndrome and non-nephrotic proteinuria per se or associated with microhematuria, hypertension, or renal insufficiency. We describe two sisters with C1qNP, who presented with steroid-resistant nephrotic syndrome. Both sisters presented before the age of 2 years, and they showed a poor response to other immunosuppressive therapy. Both girls had normal serum complement levels, negative antinuclear antibodies (ANAs) and negative hepatitis B antigen. Renal biopsy in both patients showed histological features of mesangioproliferative glomerulonephritis, with diffuse “full-house” positive immunofluorescence reaction in the mesangial area. The immunofluorescence reaction for C1q was most intense and co-dominant with IgG in both patients. Correspondingly, electron microscopy demonstrated dense deposits mainly in the mesangial areas too. We report on two young sisters with the characteristic features of C1qNP presented in early childhood. To the best of our knowledge, this is the first report of C1qNP in siblings.     

C1q肾病的诊断及治疗

C1q肾病是一种以系膜增生为主的肾小球疾病,其特点为免疫荧光染色可见系膜区高强度C1q沉积,电镜下可见系膜区电子致密物沉积,根据组织病理学特点主要分为3类,包括微小病变(MCD)、局灶节段性肾小球硬化(FSGS)和免疫介导的增生性肾小球肾炎。C1q肾病的临床表现具有多样性,可表现为肾炎或肾病范围内蛋白尿,伴有或不伴有血尿和肾功能损伤。虽然目前糖皮质激素是治疗C1q肾病的主要方法,但多数研究认为C1q肾病对糖皮质激素治疗反应较差。中西医结合治疗有望提高C1q肾病的疗效。     

Different patterns of renal immunofluorescence staining for IgG subclasses in idiopathic and secondary membranous nephropathy

Objective To evaluate the diagnostic accuracy of IgG subclasses in differentiating membranous lupus nephritis (MLN) fromidiopathic membranous nephropathy (IMN). Methods A total of 214 patients with membranous nephropathy (MN) who underwent renal biopsy at Peking Union Medical College Hospital from October 2011 to December 2012 were included. All renal biopsy specimens were examined and immunofluorescence staining against IgG1, IgG2, IgG3, IgG4 as well as C3, C1q and C4 were evaluated. Clinical manifestations and pathological features were compared between MLN patients and IMN patients. Diagnostic accuracy of IgG subclasses and complements were evaluated. Results Among all the patients selected in this study, 81% were diagnosed IMN while 14% were diagnosed MLN. The immunofluorescence staining showed that IgG4 tended to be highly expressed in IMN and its intensity was significantly higher than that in MLN (P＜0.01). The intensity of IgG3 was higher than other subclasses in MLN. The AUC of IgG4 intensity was 0.814 and its sensitivity was 91.8% and 84.2%, the specificity was 46.7% and 70.0%, when the cut?off point was 1 and 2 respectively. The AUC of the intensity difference between IgG4 and IgG3 was 0.793 and its sensitivity was 91.8% and the specificity was 66.7% when the cut?off point was 0. The sensitivity of IgG4≥1 and IgG4≥IgG3 was 88.9% and the specificity was 70.0%. The AUC of C1q intensity was 0.979 and its sensitivity was 93.3% and the specificity was 94.2% when cut?off point was 1. The sensitivity of IgG4≥1 and C1q＜1 was 87.7% and the specificity was 93.3%. Conclusions IgG4 is highly expressed in IMN while IgG3 is highly expressed in MLN by means of immunofluorescence staining. Intensity of IgG4, intensity difference between IgG4 and IgG3 and intensity of C1q are of high diagnostic value in MN. The combination of IgG4 intensity and the latter two markers could be helpful in differentiating MLN from IMN.     

C1q nephropathy with asymptomatic urine abnormalities

We found four cases of C1q nephropathy (C1qN) among a total of 193 pediatric series of first renal biopsies. Among them, 94 biopsies were performed because of asymptomatic urine abnormalities detected by school urinary screening program in Japan; three cases out of these 94 biopsies (3.2%) met the criteria of C1qN. One case out of the remaining 99 biopsies with symptomatic renal diseases (1%) also met the criteria of C1qN. Three cases with asymptomatic onset presenting with mild proteinuria with or without hematuria equally showed histologic features of membranoproliferative glomerulonephritis and showed improvements in urinalysis without corticosteroid treatment. Our data suggest that membranoproliferative glomerulonephritis may be a common histological feature of asymptomatic pediatric C1qN in Japan and that this type of glomerulopathy may follow a relatively good clinical course without steroid therapy.