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。     

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;     

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。     

尿CD62P检测在小儿原发性肾病综合征中的意义

为探讨尿ＣＤ6 2Ｐ变化在原发性肾病综合征 (ＮＳ)中的临床意义 ,采用流式细胞术对 38例ＮＳ患儿尿ＣＤ6 2Ｐ及外周血血小板ＣＤ6 2Ｐ(简称血ＣＤ6 2Ｐ)阳性细胞率进行分析。一、资料和方法原发性肾病综合征患儿 38例 ,男2 5例 ,女 13例 ,年龄 1 5～ 12岁 ,病程 1周～ 6年。临床表现为单纯性肾病(ＳＮＳ) 2 6例 ,肾炎性肾病 (ＮＮＳ) 12例。肾组织活检 8例 ,系膜增生性肾炎5例 ,ＩｇＭ肾病 2例 ,局灶性节段硬化 1例。2 0例健康儿童为正常对照组 ,年龄 2～ 12岁。所有患儿均接受激素治疗 ,辅以中药 ,难治性肾病加用免疫抑制剂 ;治疗前 (未用…     

C1q肾病17例临床病理分析

目的探讨成人C1q肾病的临床表现、病理改变和治疗效果,以加强对成人C1q肾病的认识。方法选择我院明确诊断为C1q肾病的患者17例,从临床表现、病理改变、治疗效果3个方面进行分析。结果17例C1q肾病者,1例血肌酐超出正常水平。肾脏病理检查显示均为系膜增生性。免疫荧光检查以C1q沉积为主。电子显微镜下,除1例未见肾小球外,其余16例均可见电子致密物分布在系膜区和（或）内皮下。激素治疗效果不好。结论成人C1q肾病临床表现多样化,免疫荧光检查表现为不同的相伴沉积形式。     

C1q的沉积对V型狼疮性肾炎和原发性膜性肾病的鉴别诊断意义

目的:研究C1q在V型狼疮性肾炎、原发性膜性肾病及病理组织学为不典型膜性肾病肾活检标本中的沉积,分析其不同及意义。方法:对V型狼疮性肾炎、原发性膜性肾病和不典型膜性肾病的患者的肾活检组织进行C1q免疫组化染色,并收集临床和血清学指标,进行统计学分析。结果:V型狼疮性肾炎会出现C1q的沉积,原发性膜性肾病不会出现C1q的沉积,一些病理组织学表现不典型的膜性肾病,会出现C1q的沉积,后者阳性率与狼疮性肾炎接近,与膜性肾病相比,差异有统计学意义。结论:C1q阳性且病理组织学为不典型膜性肾病的患者,极有可能是早期的V型LN。     

儿童原发性肾病综合征肾小管功能与病理改变

儿童原发性肾病综合征(NS)是小儿时期常见的泌尿系统疾病，部分病例治疗困难，表现为激素耐药、激素依赖、频繁复发或反复，其原因复杂，除与肾小球病理改变等因素有关外。近年来发现肾小管功能损害及肾小管间质病变也是影响疗效及预后的重要因素。为探讨儿童原发性NS肾小管功能与病理改变，作者对1998年1月～2003年12月收治的治疗困难的22例儿童原发性NS，     

不同年龄原发性膜性肾病的临床病理分析

膜性肾病特征性表现是肾小球上皮细胞下或基底膜外侧有免疫复合物沉积,从而表现为肾小球毛细血管基底膜弥漫性增厚,但缺乏细胞反应.膜性肾病分为原发性及继发性两大类,而原发性膜性肾病是原发性肾病综合征(NS)常见的病理类型.现对我院482例原发性膜性肾病按年龄分组进行分析.     

IgA肾病合并膜性肾病一例

报告1例IgA肾病合并膜性肾病.患者临床肾损害表现为蛋白尿、血尿及肾功能异常,肾组织病理诊断为IgA肾病合并抗磷脂酶A2受体抗体(PLA2R)相关性膜性肾病.半乳糖缺乏IgA1(Gd-IgA1)特异性抗体阳性,亦排除了IgA非特异性沉积的可能.经激素及血管紧张素受体拮抗剂(ARB)等药物治疗后病情快速缓解.提示对于膜性肾病合并肾组织有IgA沉积的患者,除了需排除继发性膜性肾病,鉴别IgA是否为特异性沉积亦具有重要意义,避免不必要的免疫抑制剂使用.     

泼尼松对原发性肾病综合征患儿PBMCHLA表达的调节作用

糖皮质激素具有抗炎和免疫抑制作用,广泛用于治疗免疫相关性疾病。小儿原发性肾病综合征（nephrotic syndrome,NS）是肾小球疾病中最常见的一种类型,发病机制尚未明确,多数学者认为与免疫反应介导的炎症性损伤有关。糖皮质激素为治疗该病的首选药物,小儿微小病变型肾病（MCNS）中90%患儿对其治疗反应良好,但部分表现激素耐药。HLA与NS相关性研究表明,激素敏感型与激素依赖型NS具有不同的免疫遗传机制。     

C1Q nephropathy in children

C1q nephropathy (C1qNP) is a peculiar form of glomerulonephritis characterized by mesangial immunoglobulin and complement deposits, predominantly C1q, with no evidence of systemic lupus erythematosus. We describe the incidence, manifestation, histopathologic findings, follow-up, treatment and outcome of C1qNP. Twelve C1qNP patients were identified among 131 children who had undergone renal biopsy, accounting for a 9.16% incidence of C1qNP. Light microscopy examination showed focal segmental glomerulosclerosis (FSGS) with or without diffuse mesangial proliferation (n=6), minimal change disease (MCD) (n=4) or focal glomerulonephritis (n=2). C1q deposits were found in all, while electron microscopy revealed visible deposits in nine cases. Eight children presented with nephrotic syndrome, while one had nephrotic proteinuria and renal insufficiency that progressed to end-stage renal failure. The remaining three patients presented with nonnephrotic proteinuria associated with microhematuria, hypertension or renal insufficiency. Only one nephrotic syndrome patient responded excellently to corticosteroids, while four became corticosteroid dependent, and three were corticosteroid resistant, showing a very poor response to other immunosuppressive therapy as well. Patients with non-nephrotic proteinuria demonstrated fixed laboratory findings. Most C1qNP patients had FSGS or MCD, the majority of them presenting with corticosteroid-dependent or corticosteroid-resistant nephrotic syndrome. The latter showed a very poor response to any immunosuppressive therapy and high risk for progressive renal insufficiency.     

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 nephropathy in a child presenting with recurrent gross hematuria

C1q nephropathy is a rare glomerular disease characterized by mesangial immune deposits with dominant or codominant staining for C1q. The exact pathogenesis leading to the mesangial immune deposits of C1q remains unknown. C1q nephropathy often presents with proteinuria in the nephrotic range, with an unpredictable or poor response to corticosteroid therapy. It is seen more commonly in older children and young adults and is more common in African Americans compared with Caucasians. We present a 4-year-old African American girl who presented with recurrent gross hematuria in the absence of proteinuria or hypertension and whose renal biopsy demonstrated dominant mesangial deposits of C1q. We conclude that C1q nephropathy should be considered in patients who present with recurrent gross hematuria.     

C1q nephropathy and minimal change nephrotic syndrome

C1q nephropathy (C1qN) is an uncommon disorder seen in children and adults with nephrotic syndrome and non-specific urinary findings. It has been described with minimal change nephrotic syndrome (MCNS), focal segmental glomerulonephritis and isolated mesangial proliferative glomerulonephritis. We describe nine children with MCNS and mesangial C1q deposition. These children had a median age of 2.7 years at diagnosis (range 1.3–15 years), 56% were male and 78% were Hispanic. We compared these children to concurrent patients with nephrotic syndrome and biopsy-proven MCNS. We found that the C1qN patients were more likely than MCNS children to require chronic immunosuppression with calcineurin inhibitors or mycophenolate mofetil to maintain remission. However, all children were able to achieve and sustain clinical remission of nephrotic syndrome. Children with C1qN and minimal change histology have an increased frequency of frequently relapsing and steroid-unresponsive disease, but they can attain prolonged remission and stable renal function with calcineurin inhibitor or mycophenolate mofetil therapy.     

Mesangial IgA deposits with steroid responsive nephrotic syndrome: probable minimal lesion nephrosis

Two children presented with nephrotic syndrome. Renal biopsy demonstrated minimal lesion nephrosis with mesangial IgA deposits. Response to prednisone therapy was prompt in both cases. The clinical and histologic features of these and other reported cases suggested a diagnosis of minimal lesion nephrosis and not IgA nephropathy (Berger's disease).     

A case of congenital nephrotic syndrome associated with positive C1q immunofluorescence

We present a 1-month-old girl with a congenital nephrotic syndrome and unusual histological findings. Immunofluorescence microscopy demonstrated granular mesangial deposition of C1q and electron microscopy revealed electron-dense mesangial deposits. Her heavy proteinuria gradually decreased and the steroid therapy did not have a significant effect. Her renal function was normal throughout the entire period of observation. The clinical evidence and histopathological features of this patient were compatible with C1q nephropathy.     

C1q nephropathy in children: clinical characteristics and outcome

Background

C1q nephropathy has been suggested as a separate disease entity. C1q positivity has also been described in association with nephrotic syndrome (NS) as a potential marker for worse outcome. The aims of this study were to describe the clinical characteristics, laboratory parameters and outcomes of 35 children whose renal histology revealed predominant mesangial C1q deposition and to investigate if the experience at our institution supports the above hypothesis.

Method

Clinical and pathological characteristics of all children whose kidney biopsies showed positive C1q staining were retrospectively recorded. The outcome of children with minimal change nephrotic syndrome (MCNS) and predominant mesangial C1q deposition based on C1q staining was compared with that of a concurrent group of children with MCNS with no such immune staining.

Results

The median age of the patient cohort was 4.5 years (range 6 months to 16 years), 69 % were boys and 88 % presented with nephrotic syndrome (NS). Children with C1q staining and MCNS had more relapses (p?=?0.001) and shorter relapse-free periods (p?=?0.033) than those with negative immunostaining, but the long-term outcomes were similar in both groups.

Conclusion

Our data do not support C1q nephropathy as a separate diagnostic category. Children with MCNS and mesangial C1q deposition (staining) showed more relapses but no difference in long term renal outcome.     

Pathology, clinical presentations, and outcomes of C1q nephropathy

C1q nephropathy is an uncommon glomerular disease with characteristic features on immunofluorescence microscopy. In this report, clinicopathologic correlations and outcomes are presented for 72 patients with C1q nephropathy. The study comprised 82 kidney biopsies from 28 children and 54 adults with male preponderance (68%). Immunofluorescence microscopy showed dominant or co-dominant staining for C1q in the mesangium and occasional glomerular capillary walls. Electron-dense deposits were observed in 48 of 53 cases. Light microscopy revealed no lesions (n = 27), focal segmental glomerulosclerosis (FSGS; n = 11), proliferative glomerulonephritis (n = 20), or various other lesions (n = 14). Clinical presentations in the patients who had no lesions histology were normal urine examination (7%), asymptomatic hematuria and/or proteinuria (22%), and nephrotic syndrome (minimal change-like lesion; 63%), which frequently relapsed. All patients with FSGS presented with nephrotic syndrome. Those with proliferative glomerulonephritis usually presented with chronic kidney disease (75%) or asymptomatic urine abnormalities (20%). Of the patients with sufficient follow-up data, complete remission of the nephrotic syndrome occurred in 77% of those with a minimal change-like lesion, progression to end-stage renal disease occurred in 33% of those with FSGS, and renal disease remained stable in 57% of those with proliferative glomerulonephritis. In conclusion, this study identified two predominant clinicopathologic subsets of C1q nephropathy: (1) Podocytopathy with a minimal change-like lesion or FSGS, which typically presents with nephrotic syndrome, and (2) a typical immune complex-mediated glomerular disease that varies from no glomerular lesions to diverse forms of glomerular proliferation, which typically presents as chronic kidney disease. Clinical presentation, histology, outcomes, and presumably pathogenesis of C1q nephropathy are heterogeneous.     

C1q nephropathy: a distinct pathologic entity usually causing nephrotic syndrome

The presence, distribution, and intensity of glomerular C1q localization were evaluated by direct immunofluorescence microscopy in 800 renal biopsy specimens which were also studied by light and electron microscopy. Identified were 15 patients with extensive (mean: 3.6 + out of 4 +), predominantly mesangial, C1q localization along with C3 and immunoglobulins, but no evidence for systemic lupus erythematosus. Pathologically, this lesion most closely resembled lupus nephritis. Clinical and pathologic data from these 15 C1q nephropathy patients were compared to data from 30 lupus nephritis and 223 other proliferative glomerulonephritis patients, and the C1q nephropathy patients were found to be dissimilar to both groups. The 15 C1q nephropathy patients had an average age of 17.8 years, 8 males, 7 females, 9 Black, 100% had proteinuria (mean 7.5 g/d), 40% hematuria, 0% hypocomplementemia, and 0% antinuclear antibodies. By electron microscopy, 100% had mesangial dense deposits, 20% capillary wall dense deposits, and 0% endothelial tubuloreticular inclusions. Nine patients treated with steroids had no definite resolution of proteinuria. We proposed that C1q nephropathy is a distinct clinicopathologic entity, usually causing steroid-resistant nephrotic syndrome in older children and young adults.