The Place of Cyclosporin in the Management of Primary Nephrotic Syndrome

The 3 main causes of primary nephrotic syndrome are minimal change nephropathy, focal segmental glomerulosclerosis and membranous nephropathy. Corticosteroids result in remission of proteinuria in most patients with minimal change nephropathy. Many patients, however, develop corticosteroid dependency. A course of cytotoxic drugs can also achieve remission but these agents cannot be administered for prolonged periods or in repeated cycles because their toxicity is cumulative. Review of the available literature indicates that cyclosporin may maintain remission of nephrotic syndrome in about 80% of patients with corticosteroid-sensitive disease, indicating an important role for this drug in patients with frequent relapses or corticosteroid dependency. Although cyclosporin is less effective in patients with focal segmental glomerulosclerosis, which is often corticosteroid-resistant, a number of studies indicate that it may be successful both in the few steroid-sensitive patients with frequent relapses and in some corticosteroid-resistant patients. In patients with membranous nephropathy, a 6-month course of corticosteroids and cytotoxic agents may favour remission of nephrotic syndrome and protect renal function. Several studies have shown that cyclosporin can improve proteinuria, and there is a tentative suggestion that it might also protect against renal function deterioration. The risk of nephrotoxicity can be minimised if cyclosporin is used at the correct doses and if renal function is carefully monitored during treatment. In summary, cyclosporin can be considered a useful tool for treating patients with nephrotic syndrome associated with primary glomerulonephritis.     

低CD40L表达在儿童单纯性肾病综合征低IgG血症发生中的作用

为研究单纯性肾病综合征低IgG血症的发生机制。采用逆转录多聚酶链反应 (RT PCR ) ,流式细胞术 (FCM )等方法检测患儿外周血T淋巴细胞表面CD40配体 (CD40L )表达。结果在发作期CD40LmRNA及蛋白质表达降低 ,恢复期其表达可接近正常水平 ,且CD40L表达量与血清IgG水平呈显著正相关。体外实验中加入CD40单克隆抗体 (CD40mAb )可使患儿PBMC产生IgG及其亚类水平增高 ,但仍未达正常水平。单纯性肾病综合征低IgG血症的发生是综合因素作用的结果 ,CD40L信号减弱导致免疫球蛋白 (Ig )同种型转换障碍是因素之一。     

肾病综合征患儿行为问题及其影响因素

目的探讨肾病综合征患儿的行为问题及影响因素。方法选择52例肾病综合征患儿,应用自编的一般状况问卷及Rutter儿童行为问卷(父母问卷)调查其行为问题。并按11配比性别、年龄相同健康幼儿为对照组。结果52例病综合征患儿中,20例(38.46%)存在行为问题,显著高于对照组6例(11.54%)(χ2=10.05,P<0.005)。多元逐步回归显示,促发行为问题的因素有肾病综合征发病持续时间、总复发次数、总住院天数、体重与年龄比、总激素持续时间、总激素使用量(标化回归系数依次为0.39、0.47、0.11、0.40、0.47、0.60),而患儿父母受学校正规教育年限、坚持学习与应学习时间比例、一天平均户外活动时间、每天坚持体育锻炼时间是保护因素(标化回归系数依次为-0.26、-0.25、-0.50、-0.20)。未发现本次发病的尿常规蛋白量、24小时尿蛋白量、血浆总蛋白水平、血浆白蛋白水平、血清胆固醇水平及水肿程度等与行为问题有关。结论肾病综合征患儿存在较为严重的行为问题,其病程关系越长越明显,而与目前病情严重程度关系不大。     

Antibody Status in Children with Steroid-Sensitive Nephrotic Syndrome

Purpose

The pathophysiology of hypogammaglobulinemia in nephrotic syndrome (NS) remains unknown. We evaluated the differences in the distribution of anti-bacterial antibodies and anti-viral antibodies, and those of immune antibodies and natural antibodies in steroid-sensitive NS.

Materials and Methods

We examined the antibody status of 18 children who had routine vaccinations. The levels of immnunoglobulin G (IgG), the IgG subclasses, and the antibodies induced by vaccinations such as diphtheria-pertussis-tetanus and measles-mumpsrubella were analyzed in children with steroid-sensitive NS.

Results

There was a positive correlation between the albumin and IgG values (r = 0.6, p < 0.01), and the four IgG subclasses were all evenly depressed in the nephrotic children during the acute stage of the disease. The antibodies induced by bacterial antigens were depressed and the seropositivity of anti-viral antibodies tended to be lower than those of age-matched control children during the acute stage. The depressed immune antibody status recovered rapidly in the remission stage of NS, despite corticosteroid treatment.

Conclusions

IgG levels correlated positively with albumin levels, and all antibodies, including immune and natural antibodies, were depressed in the acute stage of NS. Our results suggest that hypogammaglobulinaemia in NS may be associated with intravascular homeostasis of oncotic pressure.     

The Nephrotic Syndrome is an immunoinflammatory disorder

The Nephrotic Syndrome is still a therapeutic and physiopathological challenge. The clinical response to systemic immunosuppression shows that an immunoinflammatory disorder supports the nephrotic syndrome. Experimental (in vitro and in vivo) studies show that proteinuria may induce kidney secretion of proinflammatory and profibrotic cytokines and subsequent renal inflammation mediated by leukocyte recruitment. In turn,the infiltrating leukocytes contribute to renal damage by releasing proinflammatory and profibrotic cytokines (kidney acute remodelling). Chronic proteinuria maintains continuous local cytokine secretion and leukocyte influx into the glomerulus or the interstitial space (kidney chronic remodelling). In glomerular injury (podocyte injury), proteinuria itself, as well as glomerular secreted cyotokines, stimulates downstream tubular epithelial cells to secrete cytokines,as well. The mutual stimulation between proteinuria-cytokines-podocyte dysfunction-infiltrating leukocytes supports progressive tubular damage, renal fibrosis and glomerulosclerosis. Interfering with the cytokine network by inhibition/blockade of the cytokine receptor and its synthesis (via NFkB and the JAK/STAT intracellular signalling pathway) may represent a promising therapeutic option for systemic immunosuppression. Renal cytokine escape into systemic circulation may provide to hypercytokinemia stress syndrome,which could help to explain the increase in efferent renal sympathetic nerve activity (physiopathological sympathetic overactivity) observed during experimental nephrotic edema.     

HLA Antigens and Steroid Responsive Nephrotic Syndrome of Childhood

Fifty-four unrelated children with steroid responsive nephrotic syndrome of childhood were studied for 24 alleles at the HLA–A and B loci. A significantly increased incidence of HLA–B8 ( P _c < 0.01) was observed compared to controls.
No association between response to cyclophosphamide therapy and HLA antigens was seen.     

Lymphocyte Transformation Test in Adult Patients with Minimal Change Nephrotic Syndrome

The lymphocyte transformation test was used to evaluate the cellular immune response in 31 adult patients with MCNS in comparison with 30 normal control and 49 patient (CRF, FSGN. MGN) control groups. The results showed that the stimulation indices of the lymphocytes in MCNS group were significantly lower than those of the normal control and patient control groups with the exception of CRF group.
In cross studies, lymphocytes obtained from normal individuals were incubated in homologous serum obtaitied from MCNS patients in relapse, and lymphocytes from MCNS patients in relapse were incubated in normal homologous AB serum. In both circumstances there was a depressed lymphocyte function which indicates that there is a defect in lymphocyte itself as well as a serum inhibitory factor(s) during the active stage of the MCNS. This depressed cellular immune response returned to normal level during remission of the patients with MCNS.     

Value of Electron Microscopy in the Diagnosis of Childhood Nephrotic Syndrome

The value of the ultrastructural study of the renal biopsy was investigated in a series of pediatric patients with nephrotic syndrome. Forty-eight cases of renal biopsies with clinical data were reviewed and divided into diagnostic groups. The contribution of electron microscopy to the final diagnosis was graded as essential — diagnosis could not be reached without it; supportive — it increased the level of confidence in the final diagnosis; and noncontributory. In this series of renal biopsies from 48 children with nephrotic syndrome resistant or nonresponsive to therapy, the mostfrequent diagnosis was minimal change disease, present in 42%of the patients. The contribution of the electron microscopic study to the final diagnosis was essential in 73%of the series, and was supportive in a further 27%.Therefore, it is concluded that the ultrastructural study was an essential component in the study of the renal biopsy in children with nephrotic syndrome, suggesting that electron microscopy needs to continue to be performed for all these patients.     

Adult Nephrotic Syndrome and Acquired Coagulopathies: Hageman Factor Deficiency

Analysis of tests of coagulation and fibrinolysis from 20 adult nephrotics prior to the onset of therapy disclosed that 40 percent had low factor XII levels. The mean factor XI was normal. The platelet count and fibrinogen concentration were elevated. The findings of this study on adults are similar to those of Honig and Lindley²¹ in the nephrotic syndrome of childhood. Subjects with minimal change disease constituted a small (15 percent) but readily segregated subpopulation without evidence of fibrinolysis in association with low factor XII activity. Prolongation of the activated partial thromboplastin time corresponded in every instance with factor XII activities of ≤30 percent. Lengthening of the one stage prothrombin time was not directly attributable to factor deficiencies.     

Expression and Function of Monocyte Chemoattractant Protein-1 in Experimental Nephrotic Syndrome

This study investigates the expression and function of monocyte chemoattractant protein-1 (MCP-1) in rats with aminonucleoside nephrosis induced by a single intraperitoneal injection of puromycin aminonucleoside (PAN). On Day 7, PAN-treated rats had a sixfold increase in renal MCP-1 messenger (m)RNA levels and a twofold increase in interleukin-1β mRNA levels. During the course of PAN nephrosis, most of thede novoMCP-1 protein resembled protein droplets that were prominent in glomeruli between Days 3 and 14 and weaker but visible in tubules between Days 5 and 10. In addition, occasional tubules showed a cytoplasmic staining pattern for MCP-1. Two studies evaluated the effect of MCP-1 neutralization on renal monocyte recruitment. In the first study, PAN-treated rats were treated with affinity-purified MCP-1-neutralizing rabbit IgG on Days 0, 1, 3, and 5; kidneys were harvested on Day 7. There was no difference in the mean number of interstitial macrophages [119 ± 28 vs 88 ± 9 ED-1⁺cells/1000 tubulointerstitial (TI) cells; 106 ± 28 vs 119 ± 33 Ia⁺cells/1000 TI cells] or intraglomerular macrophages [2.0 ± 0.9 vs 1.7 ± 0.5 ED-1⁺cells/glomerular cross section (gcs); 1.2 ± 0.3 vs 1.1 ± 0.4 Ia⁺cells/gcs] compared with nephrotic rats treated with nonimmune rabbit IgG. In the second study, a group of PAN-treated rats was treated with MCP-1-neutralizing IgG administered continuously by an intraperitoneal miniosmotic pump for 7 days and was compared with a control group treated in an identical fashion with PAN and nonimmune IgG. On Day 7 there was no difference in the mean number of interstitial macrophages (55 ± 45 vs 67 ± 16 ED-1⁺and 70 ± 63 vs 61 ± 13 Ia⁺cells/1000 TI cells) and intraglomerular macrophages (1.0 ± 0.4 vs 1.6 ± 0.9 ED-1⁺and 0.6 ± 0.1 vs 1.1 ± 0.7 Ia⁺cells/gcs). The results of this study suggest that although MCP-1 gene and protein expression are increased in the kidneys of rats with aminonucleoside nephrosis, MCP-1 does not appear to play an essential role in early renal monocyte recruitment in this model.     

金水宝片对原发性肾病综合征患者血液流变学的影响

目的 探讨金水宝片对原发性肾病综合征患者血液流变学的影响。方法 选取2018年1月~2019年2月我院收治的原发性肾病综合征患者患者78例,按照随机数字表法分为对照组和研究组,各39例。两组均给予常规治疗,对照组给予泼尼松龙片治疗,研究组在对照组基础上给予金水宝片治疗,比较两组血液流变学及肾功能指标变化。结果 研究组全血粘度低切、全血粘度高切、血浆粘度及红细胞压积均低于对照组[（8.42±2.03）mPa·s vs（10.59±2.14）mPa·s]、[（3.94±1.22）mPa·s vs（6.36±1.30）mPa·s]、[（1.32±0.21）mPa·s vs（1.80±0.34）mPa·s]、[（42.10±2.53）% vs（46.18±2.89）%],差异有统计学意义（P＜0.05）。研究组24hUPQ低于对照组[（1.05±0.73）g vs（1.96±0.82）g],ALB高于对照组[（32.75±5.13）g/L vs（24.83±5.54）g/L],差异有统计学意义（P＜0.05）;两组Scr比较,差异无统计学意义（P＞0.05）。结论 金水宝片治疗原发性肾病综合征可改善患者血液流变学指标及肾功能,改善预后。     

Morphologic considerations on the placenta in Congenital Nephrotic Syndrome of Finnish type

Summary We have studied the morphological aspects of a thirty-six week gestational age placenta in the Congenital Nephrotic Syndrome of Finnish type. The study, conducted with histological, histochemical, morphometric and ultrastructural methods, demonstrates the presence of primary disorders of placentation consisting of persistent embryonic villi, arrested ramification and chorionangiomatosis. The villous development is compatible with the first-second trimester of pregnancy. Vasculo-syncytial membranes are quantitatively increased. Histochemical findings document placental immaturity further: Perls' reaction was positive for the trophoblast basement membrane (this is normally not observed beyond the second trimester), Alcian Blue positivity at pH 1 was also evident and was observed in three month gestational age placentae and in controls. Periodic Acid Silver Methenamine and Thioaldehyde Fuchsin documented abnormal thickenings of the trophoblast basement membrane. Electron microscopic observation reveals that the trophoblast basement membrane is thickened. Osmiophilic bodies are distributed throughout the trophoblast basement membrane and also within the basement membrane like material. Abundant microfibrils are present in the villous stroma. Lamination of basement membrane like material is observed in a subendothelial position. On the basis of their findings and in conjunction with the data in the literature regarding biochemical alterations of renal glomerular basement membranes in Congenital Nephrotic Syndrome Finnish type, the Authors suggest that a primitive membranopathy forms the basis for this pathological condition.     

防己黄芪汤加减治疗原发性肾病综合征水肿期的疗效分析

目的 对原发性肾病综合征水肿期患者接受防己黄芪汤加减治疗的临床效果,为临床中医用药治疗提供依据。 方法 根据2016年1月~12月我院接收的原发性肾病综合征水肿期患者36例开展研究,将患者按照数字随机法分成对照组和观察组,每组18例。为对照组患者提供常规西医治疗方式,为观察组患者提供常规西医治疗和黄芪汤增减治疗,对两组的治疗有效率,治疗前后24 h尿蛋白定量进行对比。 结果 治疗后对照组有效率70.00%,低于观察组95.00%。差异有统计学意义（P＜0.05）,对照组治疗前24 h尿蛋白定量（1.36±0.24）g/L,治疗后（0.64±0.13）g /24 h,观察组治疗前为（1.38±0.28）g/L,治疗后为（0.22±0.14）g/24 h;两组治疗前对比,差异无统计学意义（P＞0.05）,两组治疗后对比,差异有统计学意义（P＜0.05）。结论 原发性肾病综合征水肿期患者接受防己黄芪汤加减治疗效果明显,安全可靠,患者的水肿期症状得到缓解。     

肾病综合征合并肾静脉血栓应用阿加曲班疗效评价

目的 探讨肾病综合征合并肾静脉血栓治疗中应用选择性抗凝剂阿加曲班的临床疗效。方法 选择我院2015年3月~2018年2月诊断为肾病综合征合并肾静脉血栓患者56例,采用随机抽样法分为两组,对照组采用低分子肝素抗凝治疗,研究组在对照组治疗基础上联合阿加曲班治疗,记录两组血尿素氮、肌酐、血白蛋白、24 h尿蛋白定量、血小板、纤维蛋白原、甘油三酯结果,进行对比分析。结果 研究组总有效率高于对照组（P＜0.05）;两组患者治疗后Cr、Upro、ALB、BUN指标较治疗前有改善,研究组改善情况优于对照组（P＜0.05）。两组患者治疗前后TG、FIB、PLT无明显变化（P＞0.05）。两组患者均未出现与抗凝相关的严重并发症。结论 由于阿加曲班选择性抗凝作用、出血风险小,阿加曲班联合低分子肝素治疗肾病综合征合并肾静脉血栓疗效明显,安全可靠。     

A Case of Idiopathic Hypereosinophilic Syndrome Presenting With Acute Respiratory Distress Syndrome

Although idiopathic hypereosinophilic syndrome(IHES) commonly involves the lung, it is rarely associated with acute respiratory distress syndrome (ARDS). Here we describe a case of IHES presented in conjunction with ARDS. A 37-year-old male visited the emergency department at Samsung Medical Center, Seoul, Korea, with a chief complaint of dyspnea. Blood tests showed profound peripheral eosinophilia and thrombocytopenia. Patchy areas of consolidation with ground-glass opacity were noticed in both lower lung zones on chest radiography. Rapid progression of dyspnea and hypoxia despite supplement of oxygen necessitated the use of mechanical ventilation. Eosinophilic airway inflammation was subsequently confirmed by bronchoalveolar lavage, leading to a diagnosis of IHES. High-dose corticosteroids were administered, resulting in a dramatic clinical response.     

肾病综合征患者血栓形成与血液还原粘度和血清胱抑素C的关系

目的:观察肾病综合征(NS)患者体外血栓形成与血液还原粘度和血清胱抑素C(CysC)水平变化的相关性。方法:采集60例NS患者静脉血液,每份标本分成三份,一份进行体外血栓形成试验(测量血栓长度、湿重和干重),第二份采用肝素抗凝后检测血液粘度,第三份分离血清检测CysC含量;对照组采用体检健康人群新鲜血液。将NS组的三类指标与对照组比较(t检验)后,再行相关性分析。结果:NS组体外血栓干重(32.00±12.46mg)明显高于对照组(12.00±2.00mg),差异有非常显著性意义(P<0.01);NS组低切还原粘度(43.37±11.08mPa.s)亦高于对照组(38.52±10.20mPa.s)(P<0.05);NS组CysC(4.02±0.91mg/L)较对照组(0.67±0.26mg/L)有非常显著性升高(P<0.01)。NS组血栓干重与低切还原粘度及CysC水平呈明显正相关,r分别为0.8920、0.5463,P均<0.01。结论:血液还原粘度和血清CysC水平升高是促进NS患者血栓形成的重要因素。