原发性肾病综合征并发急性肾损伤患者血清及肾组织中NGAL的表达及意义

 目的：检测原发性肾病综合征（PNS）患者血清及肾组织中中性粒细胞明胶酶相关脂质运载蛋白（NGAL）的水平,探讨PNS合并急性肾损伤（AKI）时患者血清及肾组织中NGAL浓度的变化。方法：72例PNS患者根据病理结果分为：(1) PNS合并急性肾小管坏死（ATN）组15例,其中微小病变（MCD）合并ATN 10例,系膜增生（MsPGN）合并ATN 5例;(2) PNS不合并ATN组57例,其中MCD组24例,膜性肾病（MN）组23例和MsPGN组10例。15例健康体检者的血液及5例正常肾组织作为正常对照组。采用ELISA检测血清NGAL的水平;采用免疫组化法检测肾组织中NGAL的表达。结果：(1) PNS患者血清NGAL水平及肾组织中NGAL表达明显高于正常对照组（P<0.05）,其中MN组较MCD组和MsPGN组血清NGAL水平明显升高（P<0.05）。(2) MCD合并ATN组和MsPGN合并ATN组血清NGAL水平及肾组织中NGAL表达较不合并ATN组显著升高（P<0.05）。(3)血清中NGAL与24 h尿蛋白定量、血尿素氮和血肌酐呈正相关（P<0.05）,与血清白蛋白和β2微球蛋白无明显相关性（P>0.05）;血清中NGAL与肾组织NGAL的表达呈正相关（P<0.01）。结论：血清NGAL可能作为判断原发性肾病综合征并发急性肾损伤的早期、无创、敏感指标。     

糖尿病性多神经病合并腕管综合征患者SCV分段检测的意义

目的：应用正中神经、尺神经不同节段感觉神经传导速度(SCV)检测,探索鉴别糖尿病多发性神经病(DPN)是否合并腕管综合征(CTS)的方法。方法：研究分为六组：A组：健康对照组；B组：单纯糖尿病(DM)组；C组：单纯CTS组；D组：CTS-DM组；E组：DPN组；F组：DPN-CTS组。各组分别进行了正中神经、尺神经SCV的检测,其中包括指1—腕,指3—腕,指3—掌,掌—腕正中神经不同节段SCV,指4—腕正中神经和尺神经等长SCV,指5—腕的尺神经SCV及波幅。结果：有关DM的组(B、D、E和F)指3—掌节段正中神经SCV较健康对照组比较有减慢,差异有显著意义(P＜0．05),特别是E、F组有显著减慢,差异有极显著意义(P＜0．001)；有关CTS的组(C、D及F组)掌—腕节段正中神经SCV较健康对照组明显减慢(P＜0．001),指4—腕节段尺神经和正中神经等长距离的SCV差值与对照组比较差异有显著意义(P＜0．001)；有关DPN的组(E、F组)指5—腕节段尺神经SCV与健康对照组比较差异有显著意义(P＜0．05)。感觉波幅也有显著差异(P＜0．001)。结论：①CTS-DM组较单纯CTS组的正中神经不同节段SCV差异无显著意义；②指3—掌,掌—腕正中神经SCV,指4—腕尺神经和正中神经等长距离的SCV差值在鉴别DPN合并CTS有旨定的价值。     

Posterior reversible encephalopathy syndrome in a child with steroid-resistant nephrotic syndrome: a case report and review of literature

Posterior reversible encephalopathy syndrome (PRES) is a rare and serious syndrome of central nervous system that can develop in both adults and children. It is characterized by acute onset of headache, confusion, seizures or focal neurological deficits along with radiological findings of white matter abnormalities in the parietal and occipital lobes. In the past ten years, this syndrome has been described mainly in adults, rare in children. Here, we report a case of PRES presenting in a 12-year-old girl with steroid-resistant nephrotic syndrome. Her neurological symptom was rapidly recovered after control of hypertension without discontinuation of cyclosporine A.     

新生儿弥漫性系膜硬化型先天性肾病综合征一例报告并文献复习

目的报道一例新生儿弥漫性系膜硬化型先天性肾病综合征,以提高对该病的认识。方法收集一例于2010年10月在中山大学附属第一医院儿科住院确诊为先天性肾病综合征弥漫性系膜硬化型的患儿临床资料,并复习文献,总结弥漫性系膜硬化型先天性肾病综合征的病因、临床表现、病理特点及预后。结果患儿生后即有水肿、大量蛋白尿等肾病综合征表现,并很快出现肾功能不全,进展至肾功能衰竭,肾活检病理符合弥漫性系膜硬化型,2个多月后死亡。结论先天性肾病综合征弥漫性系膜硬化型的临床表现为出生时或幼儿期内出现肾病综合征的特征,起病时可已有肾功能不全,进行性肾功能减退,确诊须肾穿病理,本病预后差,目前无特殊治疗。     

A thalamic component of the cervical evoked potential in man

Somatosensory evoked potentials (SEPs) were recorded simultaneously from scalp and neck locations following median nerve stimulation. By subtracting the latency of the major negative peak of the cervical SEP (N13) from that of the primary cortical response (N20), the central somatosensory conduction time was calculated (5.9 ms). On the descending slope of the cervical SEP was superimposed a positive potential of probable thalamic origin (P17). By subtracting the latency of N13 from that of P17 and P17 from that of N20 respectively, the transit time for the afferent volley both within the brainstem (3.9 ms) and the thalamo-cortical radiation (2.0 ms) was obtained.     

CD2相关蛋白在肾病综合征中的表达及意义

目的观察不同病理类型的原发性肾病综合征(nephrotic syndrome,NS)患者肾小球足细胞中CD2相关蛋白(CD2AP)的表达,探讨其与足细胞损伤的关系。方法选取原发性NS患者54例,10例同期肾肿瘤切除患者正常肾组织作为对照。肾活检后常规染色观察肾脏组织病理改变,肾组织行免疫荧光法CD2AP和肾小球上皮细胞蛋白-1(GLEPP1)双重标记,对肾小球CD2AP的表达进行定位;分别用real time PCR和免疫组化SP法检测组织中CD2AP的表达,采用real time PCR检测nephrin的表达,透射电镜观察足细胞的结构变化,并定量测量足突密度。结果 (1)NS患者肾小球中CD2AP的表达及nephrin的表达下调,足细胞足突不同程度融合,足突密度降低。(2)病理表现为微小病变性肾病(minimal change disease,MCD)、局灶性节段性肾小球硬化(focal segmental glomerulosclerosis,FSGS)和膜性肾病(membranous nephropathy,MN)的NS患者CD2AP表达及nephrin表达较对照组明显降低,且CD2AP与nephrin表达呈正相关,病理表现为MCD和FSGS的NS患者CD2AP表达与足突密度呈正相关。结论本研究首次发现原发性NS患者肾小球足细胞中CD2AP的表达降低,且在MCD和FSGS中与足细胞病变程度相关,提示CD2AP低表达在足细胞病变为主的肾小球疾病中发挥重要作用。CD2AP有利于诊断足细胞病变的早期检测,对CD2AP表达减低进行早期干预可能有助于延缓疾病进展。     

Cell coat of podocytes in patients with nephrotic syndrome

Renal biopsies from 23 patients with the nephrotic syndrome and five patients with slight or no proteinuria were examined for the presence of cell coat of podocytes by light and electron microscopy. Of those with nephrotic syndrome, five had minimal change disease, nine focal glomerular sclerosis, six membraneous nephropathy and three amyloidosis. Colloidal iron and phosphotungstic acid stains were used for the demonstration of anionic and neutral polysaccharide components of the cell coat. On light microscopy, the colloidal iron reaction showed a reduction in intensity of the stain in glomeruli of patients with massive proteinuria, as compared to those with slight or no proteinuria. On electron microscopy, only the cell coat lining the surface of the foot processes disappeared parallel to the loss of these structures, while the coat covering the surface facing the urinary space remained unchanged with both stains.     

Plasma inhibition of lymphocyte proliferation in nephrotic syndrome: Correlation with hyperlipidemia

Plasma-mediated inhibition of normal lymphoproliferation is an unexplained immunologic abnormality frequently observed in nephrotic syndrome. Since hyperlipidemia, also common in nephrotic syndrome, has been linked within vitro andin vivo immunodeficiency in other diseases, we have quantitated plasma-mediated inhibition of lymphoproliferation and related it to the degree of hyperlipidemia in 19 patients with nephrotic syndrome. Fifteen patients were hyperlipidemic; the plasma of 9 of these 15 caused >60% inhibition of antigen-specific proliferative responses of normal lymphocytes. None of the four normolipidemic plasmas, nor a hyperlipidemic plasma depleted of lipoproteins by ultracentrifugation, was inhibitory. A highly significant correlation between the degree of inhibition and the plasma triglyceride levels in patients with nephrotic syndrome was observed (P<0.001). The results suggest that elevated plasma lipids may be the cause of the plasma-mediated inhibition of lymphoproliferation in nephrotic syndrome.     

Prevalence of Helicobacter pylori infection among children with primary nephrotic syndrome: a cross-sectional study

BackgroundLimited data are available about the prevalence of helicobacter pylori (H.pylori) infection among primary NS children.ObjectivesTo assess the frequency and risk factors of H.pylori infection among children with primary NS.MethodsA cross-sectional study was carried out in Mansoura University Children''s Hospital, Egypt during the period from 2017 to 2019 including 100 NS children (NS group) and 100 healthy controls. NS group included 88 steroid sensitive (SSNS) and 12 steroid resistant (SRNS) cases. All patients were assessed for H.pylori infection using H.pylori stool antigen (HpSA) test. Statistical analysis was done using chi-square, fisher exact and Mann-Whitney tests.ResultsWith regard to HpSA test results, no significant differences were detected between control and NS groups (p = 0.193) and between SSNS and SRNS groups (p = 0.286). Concerning total biopsied cases and MCD (proven plus presumed) cases, no significant differences were found between those with positive and negative HpSA test (p = 0.648 and 0.126, respectively). The high dose of steroid therapy was associated with a higher risk of H.pylori infection among NS group (Odds ratio = 3.8; 95% confidence interval = 1.3–11.3).ConclusionThe current study negates the increased risk of H.pylori infection in children with primary NS.     

原发性肾病综合征患者免疫指标变化的临床意义探讨

目的:探讨原发性肾病综合征(primary nephrotic syndrome,PNS)患者体液免疫指标、T细胞亚群、调节性T细胞(Treg)在外周血中表达情况及其临床意义。方法:选择2009年2月至2010年7月住我院初次诊治的PNS患者52例(PNS组),男30例,女22例,平均年龄为27.7±12.30岁。其中A组(普通型24/52)、B组(重症型28/52),另设C组(对照组50例)。观察指标包括:①临床指标:浮肿程度及激素疗效。②实验室指标:24小时尿蛋白定量、血浆白蛋白(A)、IgG、IgA、IgM、胆固醇(CH)、甘油三酯(TG)、C3、C4、尿素氮(BUN)、肌酐(Cr)、CD3%、CD4%、CD8%、CD4/CD8的比值、CD4+CD25+highCD127low/CD4(Treg/CD4)。③肾穿刺活检。结果:1.体液免疫指标:①PNS患者较C组,外周血中IgG、C3、C4明显降低(P<0.01);IgM显著升高(P<0.01);②B组与A组相比,C3明显下降(P<0.05),而其他体液免疫指标IgA、IgM、IgG、C4改变无统计学意义(P>0.05)。2.T细胞亚群及Treg/CD4:①PNS患者与C组相比,CD4%、CD4/CD8比值降低,CD8%增高,差异有统计学意义(P<0.05);CD3%、Treg/CD4比值改变无统计学意义(P>0.05)。②PNS患者治疗后与治疗前相比,CD4%、CD4/CD8的比值增高,CD8%下降,差异有统计学意义(P<0.05);CD3%、Treg/CD4改变无统计学意义(P>0.05)。③B组与A组相比,CD4/CD8明显降低,差异有统计学意义(P<0.05);CD3%、CD4%、CD8%、Treg/CD4比值改变无统计学意义(P>0.05)。结论:PNS患者存在体液免疫指标的改变、T细胞数量的异常、T细胞亚群间的比例失调,糖皮质激素治疗可明显改善PNS的免疫异常。Treg可能不参与PNS的发病。     

环指感觉神经传导速度检测对诊断轻度腕管综合征的价值

目的：探讨环指感觉神经传导速度（SCV）测定对诊断轻度腕管综合征（CTS）的敏感性。方法：临床症状体征符合CTS,正中神经运动末端潜伏期正常的59例（62手）患者和50名（100手）年龄性别相匹配的健康对照参与本研究,采用顺向SCV测定法分别测定环指（指4）正中神经和尺神经SCV,指3正中神经SCV。结果：指4尺神经SCV〉46．6m／s,指4正中神经SCV〈44．6m／s,和（或）尺神经SCV与正中神经SCV差值〉8．1m／s（x＋2s）,符合CTS。正中神经SCV指3测定阳性率为70％,指4测定阳性率为82％,指4正中神经与尺神经SCV差值阳性率为96％。指4刺激可在29例（48手）患者腕部正中神经处记录到双峰电位,对照组未见。结论：比较指4正中神经和尺神经SCV的差值在鉴别轻度CTS方面是一个非常敏感的方法,腕部正中神经处记录到双峰电位是CTS确诊的明确指标。     

Differential microRNA expression in the serum of patients with nephrotic syndrome and clinical correlation analysis

Many different microRNAs existed in nephrotic syndrome patients, and they may be involved in nephrotic syndrome occurrence. In order to further clarify miRNAs expression changes in nephrotic syndrome patients and their correlation with clinical features, this study investigated differential microRNA expression in the peripheral serum of patients with nephrotic syndrome and analyzed the correlation between miRNA with largest overexpression level and clinical features. miRNAs microarray was applied to screen different expressed miRNAs in nephrotic syndrome patients. Real-time PCR was performed to verify miRNA expression level. SPSS software was used to analyze correlation between miRNA expression and clinical features. Compared with healthy subjects, 35 miRNAs overexpressed and 24 miRNAs down-regulated in patients. After real-time PCR verification, 6 miRNAs up-regulated in nephrotic syndrome patients, including hsa-miR-181a, hsa-miR-210, hsa-miR-30a, hsa-miR-942, hsa-miR-192 and hsa-miR-586. miRNA-30a significantly overexpressed in nephrotic syndrome patients and with no difference between genders. miRNA-30a expression level in drug resistant nephrotic syndrome patients was obviously higher than the drug sensitive patients. miRNA-30a up-regulated most significantly in mesangial proliferative glomerulonephritis among different pathology types, while it decreased most obviously in glomerular lesions. miRNA differently expressed in the serum of nephrotic syndrome patients. miRNA-30a could be treated as the molecular marker in predict drug resistance and pathological type of nephrotic syndrome.     

Fever of unknown origin characterized by acute kidney injury and nephrotic syndrome diagnosed as intravascular large B-cell lymphoma of kidney: case report and literature review

A 60-year-old Chinese female patient was admitted to the hospital with complaint of intermittent fever for more than seven months. The main clinical manifestations were acute kidney injury and nephrotic syndrome which developed into a hemophagocytic syndrome. The symptoms did not improve with antibiotics. Moreover, prednisone could only reduce the fever. Finally, a kidney biopsy showed many CD20-positive cells in the glomerulus and some in the peritubular capillaries. This led to a diagnosis of renal intravascular large B-cell lymphoma.     

Clinicopathologic characteristics and steroid response of IgM nephropathy in children presenting with idiopathic nephrotic syndrome

There is no detailed information on clinical and immunopathologic features of immunoglobulin M nephropathy (IgMN) in children with idiopathic nephrotic syndrome (INS) in Pakistan. We reviewed our native renal biopsies over 15 years (July 1995-July 2010) and identified 135 cases of IgMN in nephrotic children (≤17 years). Their demographic, clinical and immunopathologic data were retrieved from biopsy reports and case notes. Mean age of this cohort was 7.6 ± 4.2 years. Males were 92 (68.1%) and females were 43 (31.9%). Steroid-dependent NS was seen in 88 (65.2%) cases and steroid-resistant NS in 47 (34.2%). Hematuria was found in 42 cases (31.2%) and hypertension in 27 (19.5%). The most common morphologic change was glomerular mesangial proliferation, found in 89 (65.9%) biopsies. Minor changes were seen in 46 (34.1%) cases and focal segmental glomerulosclerosis (FSGS) in 37 (27.4%). Immunofluorescence microscopy showed diffuse mesangial positivity of IgM in all cases. C3 and C1q were found in 72 (53.3%) and 40 (29.7%) cases, respectively. Our results show that IgMN is a fairly common cause of INS in children in Pakistan. It shows a spectrum of morphologic changes ranging from minor changes to FSGS.     

Failure of regulation results in an amplified oxidation burst by neutrophils in children with primary nephrotic syndrome

The mechanism responsible for proteinuria in non‐genetic idiopathic nephrotic syndrome (iNS) is unknown. Animal models suggest an effect of free radicals on podocytes, and indirect evidence in humans confirm this implication. We determined the oxidative burst by blood CD15⁺ polymorphonucleates (PMN) utilizing the 5‐(and‐6)‐carboxy‐2′,7′‐dichlorofluorescin diacetate (DCF‐DA) fluorescence assay in 38 children with iNS. Results were compared with PMN from normal subjects and patients with renal pathologies considered traditionally to be models of oxidative stress [six anti‐neutrophil cytoplasmic autoantibody (ANCA) vasculitis, seven post‐infectious glomerulonephritis]. Radicals of oxygen (ROS) production was finally determined in a patient with immunodeficiency, polyendocrinopathy, enteropathy X‐linked (IPEX) and in seven iNS children after treatment with Rituximab. Results demonstrated a 10‐fold increase of ROS production by resting PMN in iNS compared to normal PMN. When PMN were separated from other cells, ROS increased significantly in all conditions while a near‐normal production was restored by adding autologous cells and/or supernatants in controls, vasculitis and post‐infectious glomerulonephritis but not in iNS. Results indicated that the oxidative burst was regulated by soluble factors and that this regulatory circuit was altered in iNS. PMN obtained from a child with IPEX produced 100 times more ROS during exacerbation of clinical symptoms and restored to a near normal‐level in remission. Rituximab decreased ROS production by 60%. In conclusion, our study shows that oxidant production is increased in iNS for an imbalance between PMN and other blood cells. Regulatory T cells (T_regs) and CD20 are probably involved in this regulation. Overall, our observations reinforce the concept that oxidants deriving from PMN are implicated in iNS.     

Effect of angiotensin converting enzyme gene I/D polymorphism in South Indian children with nephrotic syndrome

Nephrotic syndrome is one of the most common childhood kidney diseases. It is mostly found in the age group of 2 to 8 years. Around 10%–15% of nephrotic syndrome cases are non-responders of steroid treatment (SRNS). Angiotensin converting enzyme (ACE) (I/D) gene association studies are important for detecting kidney disease and herein we assessed the association of ACE (I/D) polymorphism with nephrotic syndrome in South Indian children. We recruited 260 nephrotic syndrome (162 boys and 98 girls) and 218 (140 boys and 78 girls) control subjects. ACE I/D polymorphism was analyzed by PCR using genotype allele specific primers. In ACE (I/D), we did not find significant association for the ungrouped data of nephrotic syndrome children and the control subjects. Kidney biopsies were done in 86 nephrotic syndrome cases (minimal change disease, n = 51; focal segmental glomerulosclerosis, n = 27; diffuse mesangial proliferation, n = 8). We segregated them into the minimal change disease / focal segmental glomerulosclerosis groups and observed that the ACE 'D' allele was identified with borderline significance in cases of focal segmental glomerulosclerosis and the 'Ⅰ' allele was assessed as having very weak association in cases of minimal change disease. 'Ⅱ' genotype was weakly associated with minimal change disease. Gender specific analysis revealed weak association of 'ID' genotype with female nephrotic syndrome in females. Dominant expression of DD genotype was observed in males with nephrotic syndrome. Our finding indicated that ACE (I/D) has moderate association with focal segmental glomerulosclerosis. However, due to the limited number of biopsy proven focal segmental glomerulosclerosis subjects enrolled, further studies are required to confirm these results.