Renal involvement in PMM2-CDG,a mini-review

Phosphomannomutase 2 deficiency (PMM2-CDG) is the most common N-linked glycosylation disorder. The majority of patients present with a multisystem phenotype, including central nervous system involvement, hepatopathy, gastrointestinal and cardiac symptoms, endocrine dysfunction and abnormal coagulation. Renal abnormalities including congenital malformations and altered renal function are part of the multisystem manifestations of congenital disorders of glycosylation.We reviewed the literature on 933 patients with molecularly and/or enzymatically confirmed PMM2 deficiency to evaluate the incidence of renal involvement in PMM2-CDG.Renal abnormalities were reported in 56 patients. Congenital abnormalities were present in 41 out of these 55. Cystic kidney and mild proteinuria were the most common findings. One of the most severe renal manifestations, congenital nephrotic syndrome, was detected in 6 children. Renal manifestations were not associated with the presence of specific PMM2 alleles.This review summarizes the reported renal abnormalities in PMM2-CDG and draws attention to the pathophysiological impact of abnormal glycosylation on kidney structure and function.     

小儿局灶节段性肾小球硬化38例临床表现与病理特点

目的　了解小儿局灶节段性肾小球硬化 (FSGS)的临床与病理特点。方法　 38例临床诊断为原发性肾病综合征 (NS)或蛋白尿 ,病理确诊为原发性FSGS的患儿 ,进行回顾性分析、总结。结果　FSGS年龄 ( 8.9± 3.7)岁 ,男∶女比为 1 92 ,临床诊断为孤立蛋白尿 3例 ,蛋白尿伴血尿 1例 ,NS34例 (单纯型 16例 ,肾炎型 18例 )。临床伴血尿 2 4例 ( 6 3% ) ,高血压 11例 ( 2 9% ) ,肌酐清除率降低7例 ( 18% )。病理分型为门型 17例 ,周围型 14例 ,Tip型 7例。 38例FSGS中 ,2 1例伴有系膜细胞增生。临床疗效 :34例NS中 ,激素初治敏感 12例 ,观察期末对激素治疗敏感者 6例。 4例非NS中 ,3例激素治疗无效 ,1例不详。应用CTX共 18例次 ,4 4 %缓解或部分缓解 ;应用甲泼尼龙加环磷酰胺冲击或口服环孢霉素A治疗 12例 ,83%缓解或部分缓解。结论　小儿FSGS学龄儿童多见 ,临床多表现为NS ,血尿常见 ,高血压及肾功能不全相对少见 ,病理可表现为多种病变 ,甲泼尼龙加环磷酰胺冲击或口服环孢霉素A治疗方案相对好     

Distribution of renal integrin receptors and their ligands in congenital nephrotic syndrome of the finnish type

The aim of this study was to examine the distribution of 1 and v integrins (Ints) and some of their ligands in the kidneys of patients with congenital nephrotic syndrome of the Finnish type (CNF) and in controls using indirect immunofluorescence with monoclonal antibodies. The mesangial reactivity of Int 1 and Int 1 subunits was more variable and an increased glomerular reactivity with Int 3 and Int-6 antibodies was found in CNF kidneys than in controls. Int 2 subunit was either completely missing from or found in significantly lesser amounts in CNF kidney glomeruli. The immunoreactivity for Int v was more variable, fainter and also more granular in CNF samples than in control kidneys. The glomerular reactivity for Int 5 was more diffuse and weaker, and in sclerotic Bowman's capsules more intense in CNF kidneys than in controls. Immunoreactivity for Int 6 was restricted and was comparable in extent in CNF and control kidneys. Of the extracellular matrix components studied, the expression of EDAFn, EDBFn, OncFn, Ln 2 chain, Ln 1 chain and tenascin was increased. This is also seen in several glomerular diseases with inflammation and sclerosis. Immunoreactivity for vitronectin was decreased. Several differences were found in the intensity or location of the immunostaining for the 1 and v Ints and their ligands in CNF kidneys compared with controls, which have not been found in any other proteinuric disease. Disturbed Int expression pattern in CNF may specifically reflect the disturbance of glomerular function caused by the primary defect in this disease.     

Nephrotic syndrome with a nephritic component associated with toxoplasmosis in an immunocompetent young man.

Introduction:

Although the association of infection by toxoplasmosis with the development of nephrotic syndrome is uncommon, cases of this association have nevertheless been reported in the literature for more than two decades, not only for congenital toxoplasmosis, but also in acquired cases, and occasionally in immunocompetent patients.

Development:

A case is presented of an immunocompetent patient aged 15 with clinical and laboratory indications of nephrotic/nephritic syndrome, in whom serological tests showed Toxoplasma infection.

Conclusion:

The presentation of nephrotic syndrome in ages where it is not commonly seen, leads to clinical suspicion of secondary causes. Active search for possible causes should include common tropical infections.     

细胞骨架蛋白巢蛋白在人肾足细胞中的表达及意义

目的 检测细胞骨架蛋白巢蛋白在成人正常及病理状态肾组织中的表达,并观察其表达水平与患者尿蛋白的关系,初步探讨巢蛋白与足细胞损伤的关系.方法 正常对照肾组织(外科手术切除)6例,应用免疫组织化学(SP法)和免疫电镜检测巢蛋白的表达;病理状态肾组织:IgA肾病(无蛋白尿,电镜观察无足突融合,IrA-np)4例;IgA肾病(有蛋白尿,IgA-P)17例;膜性肾病8例;局灶性节段性肾小球硬化3例.应用免疫组织化学及即时RT-PCR的方法检测巢蛋白在肾组织中的表达并进行半定量、定量分析,与患者尿蛋白水平进行比较,分析两者之间相关关系.结果 巢蛋白表达在成人正常肾组织的足细胞初级足突中;免疫组织化学半定量及即时RT-PCR结果显示:IgA-np中巢蛋白的表达水平与正常肾组织差异无统计学意义;IgA-P、局灶性节段性肾小球硬化、膜性肾病中,巢蛋白的表达比正常肾组织显著降低(P<0.05),并与24 h尿蛋白呈负相关(r=-0.43,P<0.05).结论 巢蛋白在足细胞中低表达与肾小球中足细胞的损伤有关.     

2型糖尿病肾病病理分型特点与尿蛋白的关系

目的 探讨2型糖尿病肾病患者各个分型的病理特征与尿蛋白的关系.方法 将确诊为2型糖尿病肾病(2TDN)的患者根据24小时尿蛋白分为A、B、C、D四组,分别为A蛋白尿组(尿蛋白/24h＜2000mg)、B蛋白尿组(尿蛋白/24h2000～＜4000mg)、C蛋白尿组(尿蛋白/24h 4000～6000mg)、D蛋白尿组(尿蛋白/24h＞ 6000mg).对四组患者分别检测尿素氮(BUN)、血肌酐(Scr)、白蛋白(Alb),光镜下分别观察各组患者肾组织HE、PAS、PASM、Masson染色结果变化,电镜下观察各组患者肾组织超微结构的改变以及测量各组肾小球基底膜厚度.结果 各组DN患者经病理分型后,A组Ⅰ型6例(20％),Ⅱa型7例(23％),Ⅱb型6例(20％),Ⅲ型10例(33％),Ⅳ型1例(3％);B组Ⅰ型2例(7％),Ⅱa型3例(10％),Ⅱb型10例(33％),Ⅲ型14例(47％),Ⅳ型1例(3％);C组Ⅰ型1例(3％),Ⅱa型3例(10％),Ⅱb型5例(17％),Ⅲ型20例(67％),Ⅳ型1例(3％);D组Ⅰ型0例(0％),Ⅱa型1例(3％),Ⅱb型3例(10％),Ⅲ型17例(57％),Ⅳ型9例(30％).B、C、D组与A组相比较,血清Alb皆降低,差异有统计学意义(P＜0.05);D组与A组相比较,血清BUN、Scr升高,差异有统计学意义(P＜0.05);D组与B、C组相比较,血清Alb皆降低,差异有统计学意义(P＜0.05),Scr升高,差异有统计学意义(P＜0.05).随着蛋白尿的升高,各组DN患者的基底膜厚度相应增加,病理分型也相应严重.结论 DN患者肾脏的病理变化与蛋白尿的进展有一定的内在联系,对DN患者进行病理分型,有助于深入了解患者病情,为早期诊断和治疗提供依据.     

Clinical features of abruptio placentae as a prominent cause of cerebral palsy

Background

Although abruptio placentae causes hypoxia in the infant and thus leading to cerebral palsy (CP), its incidence and clinical features at a nationwide level have not been demonstrated.

Aims

To determine the proportion of abruptio placentae among antenatal and intrapartum causative factors leading to cerebral palsy (CP) and clinical features of such abruptio placentae.

Study design

A review was conducted in 107 infants with CP in whom CP was determined to be due to antenatal and or intrapartum hypoxic conditions by the Japan Council for Quality Health Care until April 2012.

Results

Abruptio placenta was responsible for 28 (26%) of the 107 CP infants, and was the single leading causative factor of CP. Of these 28 women, 22 (79%) exhibited non-reassuring fetal status on admission to obstetric facilities at 36.2 ± 2.6 weeks of gestation and had neonates with umbilical cord arterial blood pH (base excess) of 6.728 ± 0.164 (− 25 ± 5.4 mmol/L). In these 22 women, strong abdominal pain and/or profuse vaginal bleeding occurred 159 ± 99 min prior to admission to an obstetric facility, and the interval until delivery after admission was 47 ± 31 min. Hypertension or isolated proteinuria preceded clinical events in one (4.5%) and five (23%) of these 22 women, respectively.

Conclusions

Abruptio placentae was responsible for CP in one quarter of all cases determined to be due to antenatal and/or intrapartum hypoxic conditions in Japan. New strategies to shorten the interval until admission to an obstetric facility after onset of symptoms are urgently needed.     

In situ glomerular expression of activated NF-κB in human lupus nephritis and other non-proliferative proteinuric glomerulopathy

Nuclear Factor-κB (NF-κB) has been suggested to play a role in the cellular and molecular mechanisms underlying glomerular injury. We investigated the potential role of NF-κB activation in the pathogenesis of glomerular injury in 31 patients with class III–V lupus nephritis (LN), 14 patients with non-proliferative proteinuric glomerulopathy and six normal controls. The expression of NF-κB subunits p65 and p50, and the NF-κB regulated proinflammatory mediators tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), interleukin-6 (IL-6) and intercellular adhesion molecule-1 (ICAM-1) as well as CD68 and synaptopodin was examined by Southwestern histochemistry (SWH) or immunohistochemistry. In contrast to non-proliferative glomerulopathy and normal controls, NF-κB activation (both p65 and p50) was enhanced in glomerular endothelial, mesangial cells or infiltrating cells in class IV LN, along with upregulation of TNF-α, IL-1β, IL-6 and ICAM-1 expression. Glomerular endothelial and mesangial activation of NF-κB and mesangial ICAM-1 expression correlated with disease activity and the level of glomerular macrophage infiltration. Podocyte NF-κB overactivation (predominantly p65) paralleled podocyte expression of TNF-α and IL-1β in patients with LN and non-proliferative glomerulopathy. Podocyte staining scores of NF-κB and p65 were positively correlated with the severity of proteinuria in LN and non-proliferative glomerulopathy. These results suggest a pathogenic role for NF-κB in glomerular injury by multiple mechanisms.     

尿蛋白与急性缺血性脑梗死预后的相关性研究

目的 探讨尿蛋白与急性缺血性脑梗死(acute ischemic stroke,AIS)患者短期预后的相关性.方法 连续收集2015-08—2016-08民航总医院住院诊断为AIS患者386例(后期排除12例),回顾分析其入院后尿蛋白水平、入院及出院时生活活动量表(ADL)得分.其中出院较入院评分改善≥5分者定义为短期预后改善,评分<5分者定义为短期预后不良.采用Logistic回归方法分析尿蛋白与所评价的预后功能之间的相关性.结果 本研究374例患者中,预后改善319例,其中男225例(70.5%),女94例(29.5%);年龄≤65岁151例(47.3%),>65岁168例(52.7%);高血压238例(74.6%),糖尿病128例(40.1%),高血脂274例(85.9%),尿蛋白阳性者119(37.3%).预后未改善55例,其中男34例(61.8%),女21例(38.2%);年龄≤65岁19例(34.5%),>65岁36例(65.5%);高血压46例(83.6%),糖尿病26例(47.3%),高血脂73例(48.2%),尿蛋白阳性31例(56.4%).通过Logistic回归分析显示,年龄>65岁(P=0.016)、尿蛋白阳性者(P=0.009)急性缺血性脑梗死患者短期预后较差,提示尿蛋白是急性缺血性脑梗死患者短期预后不良的独立危险因素.结论 尿蛋白提示急性缺血性脑梗死患者短期预后不良.     

Blood hyperviscosity and its relationship to progressive renal failure in patients with diabetic nephropathy

Blood rheology was investigated in patients with diabetic nephropathy and progressive renal insufficiency, and compared with similar non-diabetic patients and healthy control subjects. Plasma viscosity and whole blood viscosity at standardized haematocrit were elevated to a comparable degree in the two patient groups, but erythrocyte deformability was normal. In diabetic patients, the rate of progression of renal failure showed weak, but significant, correlations with plasma viscosity (rs = 0.50, p = 0.005), standardized whole blood viscosity (rs = 0.41, p = 0.021), plasma fibrinogen (rs = 0.46, p = 0.010), C reactive protein (rs = 0.40, p = 0.023), and proteinuria (rs = 0.52, p = 0.003). Both plasma viscosity and plasma fibrinogen correlated significantly with proteinuria (rs = 0.45, p = 0.012 and 0.40, p = 0.027, respectively). Rheological abnormality is probably a manifestation of increased acute phase proteins, but it remains to be determined whether these are the cause or the effect of the renal injury. Abnormal blood rheology may be a risk factor for the progression of renal failure in diabetic nephropathy.