Dysfunction of the Monocyte-Macrophage System in the Idiopathic Minimal Change Nephrotic Syndrome

ABSTRACT. We studied the function of phagocytes and the distribution of lymphocyte subpopulations in 23 patients with Idiopathic Minimal Change Nephrotic Syndrome. All the patients were in relapse at the time of the study. The latter was performed before specific therapy was started. Our control group consisted of 26 normal children who were studied while undergoing routine analysis prior to plastic surgery. Polymorphonuclear leukocytes from the patients showed no alterations in their ability to ingest and to kill Candidas. On the contrary, peripheral blood monocytes had a normal phagocytic function with a decreased candidacidal activity when compared to normal controls (p<0.001). No correlation was found between serum immunoglobulin levels and the monocyte lytic function. The absolute number of B lymphocytes was significantly increased     

Clinical Course and Renal Function in Minimal Change Nephrotic Syndrome

Thirteen unselected children with the minimal change nephrotic syndrome were followed for 11 months-7.5 years, during which time 32 renal function tests were performed. Glomerular filtration rate (GFR) was determined as clearance of inulin using a standard clearance technique. The children had between zero and 34 relapses and three developed steroid resistance. Three patients had severe but reversible complications related to the corticosteroid therapy. Chlorambucil was given to four patients, of whom three with steroid resistance had lasting remissions, whereas one patient with frequent relapses had only transient improvement. The GFR was decreased at the first episode in six patients, whose clinical course did not differ from that of the others. None had a decreased GFR later in the course of the disease. It is concluded that reduced GFR at the onset of the minimal change nephrotic syndrome is reversible and does not imply an unfavourable outcome.     

Clinicl Significance of Mesangial IgM Deposits in Minimal Change Nephrotic Syndrome

The clinicopathologic features and the response to corticosteroid therapy were compared in 9 patients with minimal change nephrotic syndrome (MCNS) and diffuse mesangial IgM deposits (Group I) and in 32 of those without IgM deposits (Group II). However, serum IgM levels in Group I in both relapse and remission were significantly higher than those of Group II and controls (p<0.001). In Group I mesangial IgM deposits were diffuse in 9 (100%), mesangial C_1q was present in 4, IgA and fibrinogen were each observed in 1, respectively. Electron dense deposits in the mesangium were also present in 2 to 5 patients in Group I. No significant differences were found between the two groups in age of onset, sex ratio, laboratory data except for serum IgM level, duration before biopsy, follow-up periods, outcome, and response to steroid therapy. Our data suggest that a more severe degree of either impairment of mesangial clearance of IgM or overproduction of IgM may be involved in patients with MCNS and mesangial IgM deposits but that these patients could not be considered a distinct group of patients.     

儿童微小病变型肾病综合征致病相关基因筛查

目的比较微小病变型肾病综合征(MCNS)患儿与正常健康儿童外周血单个核细胞(PBMC)的基因表达谱变化,筛查MCNS相关致病基因,为揭示MCNS的发病分子机制和临床治疗提供线索。方法原发性MCNS患儿7例,正常同年龄对照组7例,Trizol法抽提PBMC总RNA;采用人类基因组表达谱芯片检测MCNS及正常健康儿童PBMC基因mRNA水平;采用逆转录-聚合酶链反应(RT-PCR)和荧光定量PCR检测部分基因转录水平,鉴定芯片相关检测结果。结果在33 000个基因转录本中,有969个转录本在MCNS患儿PBMC中存在表达差异,其中表达上调552个,表达下调417个。RT-PCR和荧光定量PCR检测结果与基因芯片较为一致。结论采用人类基因组表达谱芯片可快速有效地检测MCNS患儿PBMC中基因表达谱的变化,进而证实MCNS的发生、发展是涉及多基因改变的复杂过程。     

Renal Function and Albumin Excretion during Exercise in Children during Remission of the Minimal Change Nephrotic Syndrome

ABSTRACT. Six patients with the minimal change nephrotic syndrome in remission and seven healthy controls were investigated with regard to renal haemodynamics and albumin excretion before, during and after exercise. The glomerular filtration rate and effective renal plasma flow were determined by a standard clearance method, employing continuous infusion of inulin and para-aminohippuric acid. Microalbuminuria was measured by an immunoturbidimetric method. The work load was standardized at 70% of the maximal working capacity and was applied for 20 min. During exercise there was a significant fall in the glomerular filtration rate and effective renal plasma flow and a significant rise in the filtration fraction. The pattern of renal haemodynamic changes did not differ between the groups. Nor was there any statistically significant difference in urinary albumin excretion, although the exercise-induced increase in albumin excretion of the controls did not reach statistical significance. It is concluded that the renal haemodynamics and urinary albumin excretion of children having long remissions of the minimal change nephrotic syndrome are normal at rest as well as during and after a submaximal exercise test.     

Thromboembolic Complications in Children with Nephrotic Syndrome

ABSTRACT. Coagulation studies were performed in 16 children with steroid responsive minimal change nephrotic syndrome in order to elucidate the incidence of thromboembolic complications. Fibrinogen and a2-macroglobulin concentrations were inversely correlated with serum albumin concentrations, antithrombin III correlated positively ( p <0.001). Factor VIII:R:AG concentration was elevated. Coagulation disturbances in children are not less severe than in adults with nephrotic syndrome. Combined scintigraphic pulmonary ventilation and perfusion studies were employed in 26 children to detect noninvasively events of pulmonary embolism, respectively their residual changes. The lung scintigraphic investigation demonstrated a pattern consistent with pulmonary embolism in 7 patients (27.9%), residual changes in 10 (38.5%) and normal findings in 9 (34.9%). The incidence of thromboembolic complications in children with severe nephrotic syndrome is as high as reported for adults. Pulmonary symptoms may well be due to pulmonary embolism.     

Nephrotic syndrome in mesangial proliferative lupus nephritis

Renal involvement is a major complication of systemic lupus erythematosus (SLE) and occurs in 30-70% of patients with SLE. Lupus nephritis is classified into six classes (I-VI) by the International Society of Nephrology and Renal Pathology Society (ISN/RPS). Although nephrotic syndrome is commonly associated with diffuse (ISN/RPS class IV) or membranous (ISN/RPS class V) lupus nephritis, several reports have described nephrotic syndrome in adult patients with minimal mesangial lupus nephritis (ISN/RPS class I) or mesangial proliferative lupus nephritis (ISN/RPS class II). However, nephrotic syndrome in mesangial proliferative lupus nephritis has rarely been reported in children. Although the pathogenesis of nephrotic syndrome with mesangial lupus nephritis is incompletely understood, three potential mechanisms have been postulated including lupus nephritis itself, non-steroidal anti inflammatory drug (NSAID)-induced minimal change nephrotic syndrome (MCNS) and coincidental occurrence of MCNS. We describe here a child with mesangial proliferative lupus nephritis who developed MCNS.     

Immunoregulation with Levamisole in Children with Frequently Relapsing Steroid Responsive Nephrotic Syndrome

ABSTRACT. The immunological and clinical effects of levamisole were studied in 10 children with frequently relapsing steroid responsive nephrotic syndrome (SRNS). The efficacy of the drug was tested during remission of the disease with all patients on alternate day steroid therapy. The lymphocyte proliferative response to phytohemagglutinin (PHA), concanavalin-A (Con-A) and pokeweed mitogen (PWM) were normal. The Con-A induced suppressor T-lymphocyte activity of 7 patients was low before treatment with levamisole 8±3.7% and increased to normal values during therapy 34±6%; p <0.001 (control 32±5%). In these 7 children prednisolone dosage could be decreased significantly or discontinued altogether (44.1±5.3%). Patients without immunoregulatory abnormalities did not respond to levamisole. In 3 out of 4 children tested the percentage of OKT8⁺ cells rose during levamisole therapy from 19.7±2.1 to 37±2.3 ( p <0.001), thus correcting the elevated pre-treatment OKT4⁺/OKT8⁺ ratio from 3.1±0.2 to 1.5±0.2; p <0.001 (control 1.47±0.2). These data support the hypothesis that abnormal immunoregulation may play a role in the pathogenesis of SRNS. Treatment with levamisole can be useful in some patients with the frequently relapsing form of the disease.     

T Cell Subset and Steroid Sensitivity in Idiopathic Nephrotic Syndrome in Children

The relationship between T cell subset of peripheral blood lymphocytes and steroid sensitivity was studied in children with idiopathic nephrotic syndrome (INS). The subjects were 28 INS children, aged 2 to 16 years. T cells bearing receptors for IgG (Tγ) were identified by double rosette assay with sheep erythrocytes and IgG-sensitized ox erythrocytes. T cells bearing receptors for IgM (Tμ) were identified by IgM-sensitized ox erythrocytes rosette assay in purified T cells after incubating overnight. In steroid sensitive INS children, decreased numbers of Tγ cells and increased numbers of Tμ cells in onset or relapse were found and they were normalized with corticosteroid administration. Tγ cells of steroid nonsensitive INS children remained decreased even after steroid therapy. Tγ cells have been suggested to be, at least in part, suppressor T cells. Alteration of peripheral blood Tμ cells in this observation therefore may suggest the abnormality of suppressor T cells in INS children.     

肾病综合征脂蛋白脂酶和肝脂酶活性测定

目的探讨肾病综合征脂质代谢紊乱的发病机制。方法对62例肾病综合征和30例正常小儿测定血脂及脂蛋白脂酶和肝脂酶。结果肾病组脂蛋白脂酶及肝脂酶活性低于对照组,而胆固醇、三酰甘油、低密度脂蛋白均高于对照组。脂蛋白脂酶和肝脂酶与三酰甘油和低密度脂蛋白呈负相关。结论肾病综合征脂蛋白脂酶和肝脂酶活性降低为高三酰甘油血症的病因之一。     

未变性乳清蛋白佐治单纯型肾病综合征的疗效

目的研究未变性乳清蛋白对单纯型肾病综合征(NS)的疗效及可能机制。方法将36例NS患儿随机分为2组。对照组单用泼尼松口服治疗,治疗组在激素治疗基础上加用未变性乳清蛋白治疗,随访观察1年,观察指标为复发及上呼吸道感染频率,并动态检测红细胞浆还原型谷胱甘肽(GSH)水平。结果未变性乳清蛋白可有效提高单纯性NS患儿红细胞浆GSH水平,治疗组的复发频率及上呼吸道感染频率均较对照组明显减少。结论未变性乳清蛋白可有效减少肾病复发,其机制与提高细胞GSH水平进而改善抗氧化能力有关。     

瘦素及可溶性瘦素受体在原发性肾病综合征患儿血脂升高中的作用

目的探讨瘦素(Leptin)及可溶性瘦素受体(sOBR)在儿童原发性肾病综合征(PNS)血脂升高中的作用。方法检测23例未经治疗的PNS患儿空腹血清血脂、血浆清蛋白、Leptin、sOBR、胰岛素及尿Leptin、sOBR水平,并与在年龄、性别、体质量指数(BMI)均匹配的15例正常儿童比较。结果肾病组血胆固醇(TC)、三酰甘油(TG)、低密度脂蛋白(LDL)、载脂蛋白B(apoB)水平增高,血浆清蛋白、胰岛素水平较对照组降低。空腹血清总Leptin水平肾病组与对照组相当,而尿Leptin水平肾病组高于对照组;血清sOBR水平肾病组降低,尿sOBR水平二者无差异;血清游离Leptin指数(FLI)肾病组高于对照组。肾病组游离Leptin指数(FLI)与血浆清蛋白、HDL、apoA呈正相关,与LDL、胰岛素呈负相关。结论PNS患儿血清sOBR减少,游离瘦素增多可能为一抗高脂血症的代偿机制,但其纠正PNS脂代谢紊乱的能力并不完全。     

霉酚酸酯治疗儿童激素依赖性肾病综合征的疗效

目的观察和评价霉酚酸酯(MMF)对儿童激素依赖性肾病综合征(SDNS)的疗效及安全性。方法选取SDNS住院患儿16例。男12例,女4例;发病年龄(5.0±1.6)岁。采用MMF[25 mg/(kg.d)]联合小剂量糖皮质激素治疗,0.5年后MMF减半量,维持3个月停药。同时服用泼尼松0.5~1.0 mg/(kg.d),平均0.67 mg/(kg.d),根据病情定期减量。定期复查尿、血常规2、4 h尿蛋白定量、血清肌酐和尿素氮、肝功能,治疗3个月后进行疗效及安全性评价。结果治疗3个月后16例中完全有效13例,部分有效3例。MMF联合小剂量激素治疗前后24 h尿蛋白定量和血清清蛋白出现显著差异(P<0.01)。2例分别出现胃肠道症状和一过性白细胞减少。结论MMF是治疗儿童SDNS的一种有效、安全的免疫抑制剂。     

环孢素治疗激素耐药型肾病综合征的研究进展

儿童激素耐药型肾病综合征(SRNS)的治疗相对棘手,目前治疗上常用的免疫抑制剂有环孢素(CsA)、环磷酰胺、他克莫司等。CsA的药物代谢动力学不稳定,需定期监测其血药水平。CsA对SRNS儿童的诱导缓解率优于安慰剂及环磷酰胺,与他克莫司相当。SRNS儿童在CsA停药后易出现复发,其复发率为45%～64%。为增强CsA的疗效、减少其肾毒性,推荐应用小剂量、长疗程CsA治疗儿童SRNS的方案。     

利妥昔单抗治疗儿童原发性肾病综合征研究进展

原发性肾病综合征(PNS)是儿童时期常见的肾小球疾病,约25%的频复发型肾病综合征(FRNS)或激素依赖型肾病综合征(SDNS)患儿在成年期仍需用激素和(或)免疫抑制剂(ISA)维持治疗;约35%的激素耐药型肾病综合征(SRNS)患儿加用免疫抑制剂仍不缓解.利妥昔单抗是一种人鼠嵌合型抗CD20单克隆抗体,作为PNS的三线药物用于治疗对ISA如环磷酰胺、环孢素、他克莫司、霉酚酸酯等反应不佳、且不良反应严重的FRNS/SDNS和SRNS患儿,已取得较好的近期疗效,其远期疗效及安全性尚需多中心、前瞻性、大样本的随机对照试验证实.     

先天性梅毒致继发性先天性肾病综合征5例

目的探讨先天性梅毒致继发性先天性肾病综合征（NS）的临床特点、诊断、治疗及预后。方法对本院2000～2006年收治5例先天性梅毒致继发性先天性NS患儿的临床表现、诊断及治疗、预后进行综合分析,并结合文献进行回顾性研究。结果发病年龄21d～5个月,平均2.8个月。均有梅毒接触史,临床以腹胀、水肿为主要表现,符合先天性NS的主要诊断标准。患者均伴肝脾大,4例有皮疹、脱皮及贫血。3例青霉素足量治疗,疗效较佳,不需激素治疗,预后良好;并肺部感染死亡、自动出院失访各1例。结论对于早期发生NS伴肝脾大、皮疹患儿应考虑到梅毒肾病可能,并对患儿父母进行梅毒血清学检查,注意鉴别诊断。治疗关键在于驱梅疗法,而非激素治疗。多数患儿早期经足量足疗程驱梅治疗症状消失,预后良好。     

环磷酰胺冲击治疗儿童激素耐药型肾病综合征的疗效

目的 探讨激素耐药型肾病综合征(SRNS)患儿大剂量环磷酰胺(CTX)冲击治疗的疗效及影响疗效的相关因素.方法 总结本院2004年12月～2009年12月收治的资料完整并进行CTX静脉冲击治疗的38例SRNS患儿的病例资料及随访情况,并就其缓解情况及与临床分型、病理类型、临床指标之间的关系及药物不良反应进行回顾性分析.结果 1.本组完全缓解18例(47%),部分缓解11例(29%),总有效率76%;部分缓解患儿均发生于疗程6个月内,延长疗程无累积缓解率增加;未缓解患儿1例在起病5 a内进展至终末期肾病.2.SRNS患儿单纯型肾病组缓解率高于肾炎型肾病组.3.SRNS病理改变以非微小病变肾病为主,即以系膜增生性肾小球肾炎(MsPGN)、局灶节段性肾小球硬化(FSGS)为主;其中MsPGN缓解率较高,而FSGS缓解率相对较低.4.不良反应发生率为53%,最常见不良反应为一过性胃肠道反应,占36%,其次为轻度脱发(10%)、白细胞降低(7%),无严重感染、出血性膀胱炎发生.结论 CTX冲击联合激素治疗SRNS疗效肯定;临床类型、病理类型等因素可能与疗效及预后有关,单纯型肾病、MsPGN有效率较高,FSGS患儿CTX冲击疗效较差,发展为终未期肾病的风险较高.     

辛伐他汀治疗难治性肾病综合征患儿高脂血症的疗效

目的 观察辛伐他汀治疗难治性肾病综合征(RNS)患儿高脂血症的疗效及其对预后的影响.方法 对在本科住院的27例RNS患儿应用辛伐他汀(年龄<10岁,0.3 mg·kg<'-1>·d<'-1>;≥10岁,10 mg·d<'-1>)降脂治疗2周,检测其治疗前后血清总胆同醇(TC)、三酰甘油(TG)、高密度脂蛋白(HDL)、低密度脂蛋白(LDL)、极低密度脂蛋白(VLDL)、PLT、ALT、SCr变化,并观察其临床不良反应情况.结果 辛伐他汀干预前,TC为(10.68±4.23)mmol·L<'-1>、PLT为(155.21±34.43)×10<'9>L<'-1>、HDL为(1.46±0.61)mmol·L<'-1>、VLDL为(2.47±1.31)mmol·L<'-1>、LDL为(6.74±3.96)mmol·L<'-1>、TG为(4.56±1.83)mmol·L<'-1>、ALT为(24.11±6.15)IU·L<'-1>、SCr为(91.32±6.15)μmol·L<'-1>.辛伐他汀干预1周后代为(9.36±3.46)mmol·L<'-1>,与干预前比较,差异有统计学意义(P<0.05),PLT为(123.34±31.32)×10<'9>L<'-1>、TG为(3.03±0.74)mmol·L<'-1>、VLDL为(1.36±0.33)mmol·L<'-1>、LDL为(6.21±3.21)mmol·L<'-1>、HDL为(1.82±0.90)mmol·L<'-1>、ALT为(25.32±4.14)IU·L<'-1>、SCr为(94.54±6.43)μmol·L<'-1>,与干预前比较,差异均无统计学意义(P<,a>>0.05).辛伐他汀干预2周后TC为(7.28±2.01)mmol·L<'-1>、PLT为(86.65±34.23)×10<'9>L<'-1>、TG为(2.36±1.16)mmol·L<'-1>、VLDL为(1.25±0.99)mmol·L<'-1>、LDL为(4.21±2.01)mmol·L<'-1>、HDL为(2.23±0.93)mmol·L<'-1>,与干预前比较,差异均有统计学意义(P<,a><0.05),ALT为(25.31±5.14)IU·L<'-1>、SCr为(94.53±6.23)μmol·L<'-1>,与干预前比较差异均无统计学意义(P<,a>>0.05).2例患儿服药后出现胃肠不适、1例患儿出现一过性ALT升高.该3例患儿停用辛伐他汀1周后均恢复正常,无其他不良反应.结论 辛伐他汀干预能使RNS高脂血症缓解,其高凝状态亦明显改善,并能够使病情缓解,改善预后,同时无明显不良反应.     

儿童微小病变型肾病综合征的诊断和治疗

微小病变型肾病综合征（MCNS）对糖皮质激素敏感,但极易复发,可转变为对激素依赖或激素耐药,治疗非常棘手。该病诊断标准国内外基本一致,但均无最优治疗方案。本文介绍国内外诊断标准,并重点比较治疗方案。国外所选药物与国内基本一致,但剂量和疗程差异较大。建议个体化及综合治疗,根据不同个体或同一个体不同病程、病理类型改变、药物反应、药物不良反应来不断调整用药,特别要强调坚持治疗和随访的重要性。     

学龄期肾病综合征患儿及其主要照顾者的心境现状

目的探讨学龄期肾病综合征(NS)患儿及其主要照顾者的心境现状,并分析影响学龄期NS患儿及其主要照顾者心境现状的相关因素。方法 NS患儿43例。采用问卷调查法,基本资料采用自设问卷,患儿采用国际公认的儿童抑郁障碍自评量表(DSRSC)、儿童焦虑性情绪障碍筛查量表(SCARED),主要照顾者采用成人焦虑自评量表(SAS),抑郁自评量表(SDS)。采用SPSS14.0软件进行统计分析。结果 1.学龄期NS患儿的心境问题发生率为32.6%(14/43例),其主要照顾者的发生率为44.2%(19/43例),患儿及其主要照顾者焦虑、抑郁分值、阳性发生率明显高于国内常模,且有显著统计学意义。2.学龄期NS患儿心境状况与年龄、性别、母亲文化程度、家庭经济状况、居住地、近0.5 a来复发次数、服药种类、照顾者焦虑抑郁状况无相关,患儿主要照顾者的心境状况与照顾者类型、患儿病情近0.5 a复发次数、居住地相关。结论对NS患儿及其主要照顾者的心境状况应给予临床关注,早期认识和及时治疗对于不同人群应采用个性化、有针对性的干预措施可提高患儿及家庭的生活质量。