Charge and size selectivity of proteinuria in children with idiopathic nephrotic syndrome

 Experimental studies have pointed to charge selectivity as an important determinant of glomerular permeability to macromolecules. Loss of glomerular basement membrane (GBM) polyanion has been proposed as a cause of the selective proteinuria in minimal change nephrotic syndrome (MCNS). However, the presence of less-anionic albumin in urine than plasma from MCNS and focal and segmental glomerulosclerosis (FSGS) patients has been interpreted both as evidence for partial maintenance of charge selectivity and for involvement of other pathogenic mechanisms. The exact role of charge selectivity in the pathogenesis of nephrotic proteinuria remains controversial. We have examined the clearance of endogenous proteins of differing size and charge in children with idiopathic nephrotic syndrome (NS). Chromatofocusing was used to determine the isoelectric points (pIs) of albumins in paired plasma and urine samples from patients with FSGS (n = 6) and MCNS (n = 6). Charge selectivity was assessed by comparing the pIs of the fractions with the highest albumin concentration (modal pI) in plasma and urine. The difference between the modal pIs was defined as the delta modal pI. Charge selectivity was also assessed from the albumin/transferrin and IgG4/IgG1 clearance ratios; size selectivity from the IgG1/albumin and IgG1/transferrin as well as the IgG4/albumin and IgG4/transferrin clearances. In children with FSGS, the mean (± SD) delta modal pI was  – 0.05 ± 0.16, and in MCNS  – 0.05 ± 0.11. Neither value differed significantly from zero. The albumin/transferrin clearance ratio showed no significant difference between FSGS and MCNS, but the IgG4/IgG1 clearance ratio was significantly higher in MCNS (P<0.05). Size selectivity was significantly reduced in FSGS compared with MCNS (for IgG1/transferrin P<0.01 and for IgG1/albumin P<0.05). For IgG4/transferrin and IgG4/albumin, P was <0.05. In conclusion, there was no evidence for residual charge selectivity in idiopathic NS associated with either MCNS or FSGS during nephrotic-range proteinuria. There was a significant loss of GBM size selectivity in children with FSGS with heavy proteinuria compared with children with MCNS with heavy proteinuria. Received August 7, 1996; received in revised form and accepted December 16, 1996     

肾病患儿免疫细胞对肾小球上皮细胞合成基质的影响

目的为了明确免疫细胞对肾小球上皮细胞（ｇｌｏｍｅｒｕｌａｒｅｐｉｔｈｅｌｉａｌｃｅｌＧＥＣ）合成功能的直接作用。方法应用肾小球细胞体外培养，同位素掺入及放射免疫技术，以总胶原，层粘连蛋白，Ⅲ型前胶原及Ⅳ型胶原的合成为观察指标，动态研究了不同病理类型原发性肾病综合征（ＩＮＳ）患儿外周血单个核细胞（ｐｅｒｉｐｈｅｒａｌｂｌｏｏｄｍｏｎｏｎｕｃｌｅａｒｃｅｌＰＢＭＣ）对ＧＥＣ生物功能的影响。结果（１）肾病极期未经激素治疗组（未治组）ＰＢＭＣ上清明显促进了ＧＥＣ合成层粘连蛋白；（２）未治ＰＢＭＣ上清抑制了ＧＥＣ合成总胶原；（３）未治组ＰＢＭＣ上清促进了Ⅲ型前胶原的合成，而对Ⅳ型胶原的合成无明显影响；（４）肾病患儿ＰＢＭＣ的上述作用与是否足量激素治疗有关，而与尿蛋白能否阴转、肾组织病理类型、肾病临床类型等无直线相关关系。结论原发性肾病患儿循环免疫细胞可影响ＧＥＣ合成细胞外基质的功能。免疫细胞的这种活性可被激素治疗改变。     

儿童系膜增殖性肾小球肾炎临床与病理关系的研究

３５例儿童非ＩｇＡ系膜增殖性肾小球肾炎，主要表现为肾病综合征、血尿及蛋白尿三种类型。对以肾病综合征表现的ＭｓＰＧＮ使用激素或细胞毒性药物治疗，其中轻度系膜病变不伴有局灶硬化者治疗效果及预后好；重度系膜增殖伴有明显局灶硬化、肾小球囊壁粘连、间质纤维化者治疗及预后均差，说明治疗效果及预后与病理形态改变轻重有关。     

GREB1L基因突变致后天性单侧肾萎缩一例报道并文献复习

肾发育不良和肾发育不全（RAH）是先天性肾脏与尿路畸形（CAKUT）的主要表现之一,是导致儿童慢性肾脏病的重要原因。遗传因素与发病密切相关,随着全基因检测技术的发展,越来越多与RAH相关的基因突变被报道,GREB1L基因突变已被证实可导致RAH。本研究报道了1例后天性单侧肾萎缩GREB1L基因c.4688A>G杂合突变患儿,并复习相关文献。该患儿基因突变源自母亲,该变异为罕见变异,并且具有不完全外显特性,多种蛋白质危害预测软件预测该突变为有害变异。本文发现了新的GREB1L基因突变位点,可能拓展了与RAH相关的基因突变谱和临床谱。     

The mechanism of hyperlipidaemia in the nephrotic syndrome

The mechanism of hyperlipidaemia in the nephrotic syndrome has not been fully established. We propose that it results from hypoalbuminaemia due to inhibition of the reaction catalysed by lecithin cholesterol acyltransferase converting cholesterol of high density lipoproteins to cholesterol esters and to an inhibition of high density lipoprotein particle formation from very low density lipoproteins due to reduced activity of lipoprotein lipase.     

An electron microscopic study of glomerular lesions in hereditary nephrotic mice (ICGN strain)

Summary Glomerular lesions in hereditary nephrotic mice (ICGN strain) were investigated by electron microscopy. The glomeruli of unaffected animals, which appeared normal by light microscopy, had developed an ultrastructural change in the glomerular capillary basement membrane (GCBM). There was a partial thickening of the GCBM with bilaminar splitting of the lamina densa and an electron-dense fibrillar material exhibiting cross-striations. In affected animals, light microscopy revealed a marked thickening of GCBM and an increase of mesangial matrix without cellular proliferaton. By electron microscopy, multilaminar splitting of the lamina densa in the thickened GCBMs and fusion of the epithelial foot processes were observed. In some severely affected animals, immune complex deposition was found in GCBM, but little if any was observed in other animals. In the end, the glomeruli were globally sclerosed. Our findings suggest that initial structural abnormalities in GCBM may play an important role in the onset and development of the disease, though subsequent events such as immune complex deposition would modify the disease.     

肾病综合征患者焦虑因素分析

目的探讨肾病综合征患者焦虑的影响因素及对策.方法应用状态-特质焦虑问卷(STAI)、社会支持评定量表(SSRS)、生活事件量表(LES)等对80例肾病综合征患者进行测查.结果肾病综合征患者状态焦虑问卷(SAI)分值明显高于正常人群(49.55±8.18Vs39.31±8.66)(P＜0.01).逐步回归分析发现,患者焦虑的主要因素为性格内向、社会支持状况差、负性生活事件多、担心治疗效果不好、担心医生治疗水平不高等.结论肾病综合征患者有明显的焦虑情绪,受多种因素影响,加强心理干预,配合药物治疗,能收到较好效果.     

儿童肾病综合征患者血小板和血浆von Willebrand因子的变化

目的：观察儿童肾病综合征患者血小板计数和血浆von Willebrand因子的变化,方法,采用ELISA法检测58例NS患儿血浆vWF及血小板计数,并与正常对照组进行比较,结果：NS患儿vwF水平及血小板计数均明显高于正常对照组,两组有显著性差异（P＜0．01）,结论,血浆vWF与血小板计同步升高与NS患儿的高凝状态及血栓形成有一定的关系。     

Lipoprotein(a) : new insights into an atherogenic lipoprotein

Lipoprotein(a) constitutes a macromolecular complex in human plasma that combines structural features from the blood clotting and the lipoprotein systems. Aside from the discovery of lipoprotein(a) [Lp(a)] as a potential independent risk factor for premature cardiovascular disease its physiological role and activity remains obscure. Since the site of catabolism has not yet been fully characterized, there is intensive search for factors which influence plasma Lp(a) levels. Several clinical conditions and metabolic states have been identified to be added to the disorders of the lipid metabolism itself that modulate Lp(a) plasma levels. Diseases of the kidney and their accompanying factors (proteinuria and nephrotic syndrome) as well as end-stage renal disease and their treatment modalities (hemodialysis, peritoneal dialysis, and kidney transplantation) have all been found to increase Lp(a) plasma levels substantially. Fluctuations in Lp(a) also seem to occur in states of hormonal changes, such as in diabetes mellitus, after estrogen treatment, and during pregnancy. Recently a plausible mechanism for the atherogenic activity of Lp(a) has been ascribed to the inhibiting effect of Lp(a) on plasminogen activation, thus decreasing plasmin formation which in turn reduces the activation of transforming growth factor , a potent inhibitor of smooth muscle cell proliferation. Lp(a) exerts its pathological effect at plasma levels in the range of 20–30 mg/dl. Therefore, it seems mandatory to quantitate Lp(a) levels in patients who are at risk of developing progressive atherosclerotic disease to identify those with high levels of this unique atherogenic lipoprotein. Since plasma levels of Lp(a) are insensitive to diet, exercise, and most lipid-lowering drugs, the reduction of other risk factors that predispose to atherosclerotic disease is the only clinical strategy at present.Abbreviations apo(a) apolipoprotein(a) - apoB apolipoprotein B - CAPD continuous ambulatory peritoneal dialysis - ESRD end-stage renal disease - FCHL familial combined hyperlipidemia - FH familial hypercholesterolemia - HD hemodialysis - HGF hepatocyte growth factor - HMG-CoA 3-hydroxy-3-methyl glutaryl coenzyme A - LDL low-density lipoprotein - Lp(a) lipoprotein(a) - TGF-R transforming growth factor- - TGRLP triglyceride-rich lipoproteins