Cyclosporin in Idiopathic Nephrotic Syndrome

Idiopathic nephrotic syndrome encompasses two main forms of glomerular diseases, minimal change nephropathy and focal segmental glomerulosclerosis. Minimal change nephropathy is a disease of children which generally responds to corticosteroids. After remission, nowever, many patients show frequent relapses or steroid dependency. In these patients, cyclosporine may obtain remission of proteinuria in 80% of cases, although relapse usually occurs when the drug is stopped. Focal glomerulosclerosis is generally resistant to corticosteroids. Under cyclosporine some 40% of patients may attain complete or partial remission of the nephrotic syndrome particularly if low-dose prednisone is associated. Relapse of proteinuria usually occurs after stopping the drug. As cyclosporine may expose to chronic nephrotoxicity some guidelines should be followed to prevent this complication: - the doses should not exceed 5 mg/Kg/day - they should be adjusted whenever an increase in plasma creatinine of ± 30% over the baseline values occurs - treatment should be stopped if there is no response within 3 months - a careful monitoring of patient under the supervision of a clinician trained with the use of cyclosporine is necessary.     

The Effects of Inflammation on Lipid Accumulation in the Kidneys of Children with Primary Nephrotic Syndrome

This study aimed to characterize the relationship between inflammation and lipid accumulation in children with primary nephrotic syndrome (PNS). Local expression of interleukin-1β (IL-1β), transforming growth factor-β1 (TGF-β1), low-density lipoprotein receptor (LDLr), sterol regulatory element binding protein-2 (SREBP-2), SREBP cleavage-activating protein (SCAP), and apolipoprotein B100 (apoB100) was analyzed by immunohistochemistry in kidney tissues obtained from children with PNS. Renal histopathology was evaluated by hematoxylin and eosin and periodic acid-Schiff staining. Serum levels of IL-1β and TGF-β1 were measured by enzyme-linked immunosorbent assays. Expression of IL-1β, TGF-β1, LDLr, SREBP-2, SCAP, and apoB100 was higher in samples from patients with non-minimal change necrotic syndrome (NMCNS) compared to both controls and patients with minimal change necrotic syndrome. Deposition of apoB100 was significantly correlated with expression of IL-1β, TGF-β1, LDLr, SREBP-2, and SCAP and with the glomerulosclerosis index, but not with plasma lipid levels. Expression of IL-1β and TGF-β1 was significantly correlated with expression of LDLr, SREBP-2, and SCAP. These findings suggest that inflammation leads to lipid accumulation in the kidney through disruption of the expression of proteins in the SCAP/SREBP-2/LDLr signaling pathway, which may underlie glomerulosclerosis and tubulointerstitial fibrosis in NMCNS.     

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。     

肾小管标志物测定在原发性肾病综合征治疗前后的意义

目的:通过测定肾小管标志物判断原发性肾病综合征(PNS)病人的肾小管受损程度,以期探讨在不同疗效的病人治疗前后的意义.方法:应用放射免疫分析测定白介素-6(IL-6)、内皮素-1(ET-1)、α1-微球蛋白(α1-m)、β2-微球蛋白(β2-m);用ELISA测定纤维蛋白原降解产物(FDP);速率法测定N-乙酰β-D氨...     

成人肾病综合征患者高尿酸血症的发病率及相关因素分析

目的 探讨成人原发性肾病综合征(primary nephrotic syndrome,PNS)患者高尿酸血症(hyperuricemia,HUA)的发病率及其相关影响因素.方法 回顾性分析2010年1月至2012年3月在我院首次诊断为PNS的成人患者共306例,分别测定其血尿酸(serum uric acid,SUA)、白蛋白(albumin,ALB)、血清肌酐(serum creatinine,Scr)、甘油三酯(triglyceride,TG)、总胆固醇(total cholesterol,TC)、同型半胱氨酸(homocysteine,Hcy)等指标,以328例“健康”体检者作为对照组,进行HUA发病率调查及相关因素分析.结果 PNS组的平均SUA水平及HUA的发病率明显高于对照组(P均＜0.001);PNS组中,男性平均SUA水平及HUA发病率明显高于女性(P ＜0.001;P =0.008);各病理类型中,以局灶节段性肾小球硬化症的HUA发病率最高,但与其它病理类型间的差异无统计学意义(P＞0.05).PNS组SUA水平与TG、Scr、Hcy呈显著正相关关系(P =0.022;P ＜0.001;P＜0.001),而与ALB、TC无显著相关性(P =0.422;P=0.325).结论 成人PNS患者HUA的发病率明显高于正常人群,SUA水平与TG、Scr、Hcy水平相关.     

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.     

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.     

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.     

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.     

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。     

Pathology of the Glomerulus in Sickle Cell Anemia With and Without Nephrotic Syndrome

Glomeruli from 6 cases of sickle cell disease (SS) with the nephrotic syndrome (NS) were compared histologically and quantitatively with glomeruli from 9 cases of SS, 10 cases of sickle cell trait (SCT), 4 cases of other hemoglobinopathies, all without NS, and normal controls. Five of 6 patients with SS and NS had extensive reduplication of their glomerular basement membranes and mild mesangial proliferation. Similar but milder lesions occurred in SS without NS but not in SCT or controls. Incidental renal disease occurred in 1 patient with SS and NS. Nephrotic syndrome was probably secondary to effects of sickle cell disease. Glomeruli in SS were significantly larger (>70%) than in SCT and controls. Mean total glomerular area per unit area of cortex in SS with normal BUN significantly exceeded that of SCT, which, in turn, was significantly greater than that of controls. Mechanisms for the histologic lesions and hypertrophy of the glomeruli were suggested.     

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.     

原发性肾病综合征患儿肾组织P-gp170蛋白和mRNA表达与临床病理及预后的关系

目的 观察原发性肾病综合征患儿肾组织中P-糖蛋白170的表达,分析肾组织中P-gp170表达与临床和病理的关系,探讨P-gp170表达在PNS 患儿GC耐药中的作用。方法 采用肾活检术取得96例处于不同病程的PNS患儿肾组织标本,进行常规病理学诊断和肾脏病理定量分析;应用免疫组织化学及原位杂交法分别检测PNS患儿肾组织中P-gp170蛋白及mRNA的表达,比较不同肾脏病理类型及病理积分患儿P-gp170的表达;比较未用GC与应用GC后PNS患儿肾组织P-gp170的表达。结果 ①正常肾脏即有一定量的P-gp170表达;未用GC组即高于正常对照,差异有统计学意义(P＜0.05）;②病理积分较高者P-gp170表达阳性量高于病理积分低者,差异有统计学意义(P＜0.05）;不同病理类型P-gp170的表达有差异,局灶节段硬化(FSGS）、膜性肾病(MN）和硬化性肾病(SGN）表达较高,组间比较差异无统计学意义(P＞0.05）,微小病变(MCD）和系膜增生型(MsPGN）者表达较低,两者比较差异无统计学意义(P＞0.05）;而前三者与后两者差异有统计学意义(P＜0.05）;③未用GC者较应用GC后的PNS患儿肾组织P-gp170表达量低,差异有统计学意义(P＜0.05）。结论 P-gp170在PNS患儿肾组织的表达可能与肾病病损有关,可结合病理类型和病理损伤程度同时检测肾组织P-gp170预测不同患儿GC反应性; P-gp170的表达增高可能与PNS活动和复发有关,可作为临床预测预后的指标。     

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.