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。

Clinicopathological features and treatment of C1q nephropathy in children

Objective To investigate the clinicopathological characteristics and treatment of C1q nephropathy in children. Methods Data of 23 C1q nephropathy cases in Nanjing Children's Hospital during recent eight years were retrospectively reviewed. Results The incidence of C1q nephropathy was 4.78％ in primary glomerulonephritis proven by biopsy.Among 23 patients,15 were boys and 8 were girls.The mean age at onset was (5.0±3.4) years old with a range of 0.9-12.4 years.The clinical manifestations included nephrotic syndrome (NS) in 18 cases (78.3％),nephrotic-range proteinuria in 4 cases (17.4％) and microhematuria in 1 case.Two patients with NS and one patient with nephrotic-range proteinuria also presented microhematuria.One patient with NS who received oral herbal medicine for two weeks developed acute renal insufficiency at the same time of diagnosis.Three cases had a family history of kidney disease,among them two patients (presented nephrotic range proteinuria) were siblings,their father had proteinuria as well,and routine genetic examination confirmed familial Denys-Drash syndrome in association with C1q nephropathy.One NS patient's sister had nephrotic-range proteinuria too,but renal biopsy was not performed.No patient had hypertension.None of the patients had low C3 or C4 levels,and serological markers of systemic lupus erythematosus were absent.Light microscopy showed minimal change disease (MCD) in 13 cases (56.5％), mesangial proliferative glomerulonephritis (MsPGN) in 6 (26.1％) and focal segmental glomerulosclerosis (FSGS) in 4(17.4％).Immunofluorescence displayed C1q co-deposits of IgG (78.3％),IgM (78.3％),IgA (34.8％) and C3 (47.8％),and a "full-house" pattern was found in 6 patients (26.1％).Electron microscopy revealed 4 out of 19 had mesangial deposits,except for 4 patients whose glomerulus could not be found.Children with either NS (18 cases) or nephrotic-range proteinuria (2 cases)received prednisone,among them,15 were steroid-resistant,4 were steroid-dependent,only 1 was steroid-sensitive.Those with steroid-resistant (15 cases) or steroid-dependent (3 cases) received further immunosuppression with cyclophosphamide (CTX) or cyclosporine A (CsA).One NS case of steroid-dependent received prednisone re-induction therapy.The siblings associated with DenysDrash syndrome and one case presented microhematuria were commenced on angiotensin-converting enzyme inhibitor (ACEI).Of the 19 patients with sufficient follow-up date,15 cases (78.9％)achieved complete remission,2 cases(10.5％) achieved partial remission,and 2 cases (10.5％) were ineffective.Median follow-up was 15 months.Remission of the NS occurred in 94.4％ (17/18)while nephrotic-range proteinuria was 50.0％(2/4).Remission of MCD was 100.0％,MsPGN was 83.4％(5/6),but FSGS was only 50.0％(2/4). Conclusions C1q nephropathy is rare,and often manifests as steroid-resistant or steroid-dependent NS and nephrotic-range proteinuria.The most common histological feature is MCD,and some as MsPGN or FSGS.A combination of prednisone and immunosuppressive agent is always effective for MCD and MsPGN,but FSGS always has a poor response.