Significance of mesangial IgA deposition in minimal change nephrotic syndrome: a study of 60 cases

We studied 60 cases of minimal change nephrotic syndrome (MCNS) with mesangial IgA deposits occurring over a 6 year period. There were 43 adults and 17 children. Hematuria occurred in 69.0% of the adults and 88.2% of the children. Two adults and six children had gross hematuria during the course of the disease. Mesangial IgA deposits were noted in 100% of the cases, and concomitant IgG or IgM deposits were found in 78.6% of adults and 73.7% of children. The fluorescent intensity of mesangial IgA deposits was trace (+/-) to 1+ in 86.1% and 70.6% of the adults and children respectively. Most of the patients showed electron microscopic findings consistent with minimal change nephrotic syndrome. We speculate that most of our cases are variants of minimal change nephrotic syndrome but are neither IgA nephropathy nor an overlapping syndrome, and that environmental or genetic factors may be related to the deposition of IgA in these MCNS patients.     

2013~2017年我院402例肾活检临床病理分析

目的 分析北部湾沿海钦州地区肾脏疾病临床及病理特点。方法 对广西钦州市第一人民医院2013年~2017年共402例肾活检患者的临床和病理资料进行回顾性分析。结果 402例肾活检患者,原发性肾小球疾病(PGN)297例,占73.88%;继发性肾小球疾病(SGN)88例,占21.89%。PGN病理分型中最常见为膜性肾病,其次为微小病变型肾病及IgA肾病,SGN中狼疮性肾炎居于首位,其次为乙肝相关性肾炎。结论 本地区肾活检患者临床表现以肾病综合征为主,PGN最常见的病理类型是膜性肾病,非肾病综合征最常见的病理类型是IgA肾病,本地区无症状尿检异常有肾活检指征患者检出率低。     

Thin basement membrane nephropathy as a cause of recurrent haematuria in childhood

A survey of 69 children presenting with recurrent or persistent haematuria and submitted to percutaneous renal biopsy at this hospital over a 17-year period, was performed to establish the incidence of thin basement membrane nephropathy (TBMN). A diagnosis of primary glomerular disease was established in 44 (IgA nephropathy in 16, Alport's syndrome in 13 and other varieties of glomerulonephritis in 15). Of the remaining 25 patients in whom light microscopical and immunochemical examination revealed no abnormalities, material for electron microscopy was available in 11. In eight of these (five of whom had a family history), TBMN was diagnosed on the basis of ultrastructural morphometric evaluation of glomerular basement membrane thickness. Assuming a similar proportion of the remaining 14 patients with renal biopsy specimens normal by light microscopy had TBMN, the probable frequency of this abnormality in the whole series would be 26%, very similar to that of IgA nephropathy. In the eight TBMN patients the mean glomerular basement membrane thickness ranged between 181 and 236 nm, whilst in 'control' biopsies from children with 'minimal change' nephrotic syndrome or IgA nephropathy, the mean thickness ranged between 242 and 333 nm.     

膜性肾病合并IgA肾病的临床病理特点

目的探讨膜性肾病合并IgA肾病的临床病理特点。方法回顾性研究北京大学第一医院肾内科和北京大学肾脏病研究所1998年1月—2006年4月问的肾活检病例9572例,对11例膜性肾病合并IgA肾病的临床病理特点进行分析,结合免疫电镜标记方法,对其病理诊断及发病机制进行探讨。结果11例患者以中年为发病高峰,平均年龄39．9岁,女性多于男性（男：女为1：2．9）,临床表现为蛋白尿,其中7例（63．6％）出现肾病综合征水平的蛋白尿,7例（63．6％）合并镜下血尿,肾功能均正常,除外了肝炎病毒感染、系统性红斑狼疮等继发性疾病。光镜下可见肾小球基底膜空泡变性和增厚,系膜细胞和基质轻度增生,2例可见少数肾小球伴有新月体形成。免疫荧光检查见IgG和c3颗粒样沿肾小球毛细血管壁沉积;IgA团块状在肾小球系膜区沉积。电镜检查可见肾小球上皮细胞下多数块状电子致密物沉积,系膜区可见团块状电子致密物沉积。免疫电镜标记结果显示,IgG定位于肾小球上皮细胞下的电子致密物,IgA定位于肾小球系膜区的电子致密物。结论膜性肾病合并IgA肾病兼具有膜性肾病和IgA肾病的临床病理特点,其发生过程可能为各自独立发生的两种疾病的叠加所致。     

Second-hand smoke worsens allergies

Glomerular diseases with severe defects in glomerular permeability give rise to heavy proteinuria and can present as nephrotic syndrome. There are many different causes of the nephrotic syndrome and a renal biopsy is nearly always needed to elucidate the underlying disease. During the last decade, substantial advances have occurred in the understanding of the pathophysiological mechanisms involved in immune-mediated glomerular diseases. Here, we review the diagnostic and prognostic implications of recent progress on the understanding of membranous nephropathy, minimal change disease, focal segmental glomerulosclerosis, amyloidosis, IgA nephropathy and membranoproliferative glomerulonephritis.     

The clinicopathological characteristics of IgA nephropathy in Hong Kong

The clinicopathologic data of 237 Chinese patients with IgA nephropathy from Hong Kong are reviewed in an attempt to identify the features pertinent to Chinese patients. Although the nephropathy is commonest in the 26-35 year age group, 11% of the IgA nephritic patients were children below 16 years. The male predilection reported in Caucasian populations is not observed and the male:female ratio is 0.94 in our series. The commonest renal manifestation is microscopic hematuria (25%) and 19% of the patients present with macroscopic hematuria, not infrequently synpharyngitic. Nephrotic syndrome occurs in 15% of our patients and proteinuria more than 1 gm/day is documented in 58% of these IgA nephritic patients. The degree of proteinuria does not correlate with prognosis. A small proportion of these nephrotic patients respond to steroid therapy, suggesting a variant of IgA nephropathy that resembles lipoid nephrosis in its steroid-responsiveness. Seventeen percent of the patients (18/104) are hepatitis B virus carriers and 61% of these patients demonstrate viral antigens in their renal biopsies, indicating that hepatitis B virus infection may sometimes play a pathogenetic role.     

The effect on patient management of temporary non-availability of immunofluorescence for renal biopsy reporting.

Delay in reporting the immunofluorescence findings on renal biopsies, owing to an interruption in supply of reagents, made possible a retrospective analysis of the effect of the lack of this information on patient management. Hospital case records of the 39 patients so affected were reviewed to determine what changes in their management took place after the immunofluorescence findings became available. The clinical, laboratory, and light microscopic findings in all except a case of pauci-immune crescentic glomerulonephritis allowed management decisions to be made that were not influenced by immunofluorescence findings. This was owing to correct prediction of the immunofluorescence findings, as in cases of IgA nephropathy presenting with recurrent haematuria; the adequacy of light microscopy in the interpretation of graft biopsies, in classifying lupus nephritis and in most cases of nephrotic syndrome; and the absence of entities identifiable only by immunofluorescence among these patients.     

B lymphocyte subset patterns and their significance in idiopathic glomerulonephritis.

The proportion of B lymphocyte subsets with surface immunoglobulin G (sIgG) was significantly increased in minimal change nephrotic syndrome (MCNS), membranous nephropathy, IgA nephropathy and mesangiocapillary glomerulonephritis (MCGN) and with sIgA in IgA nephropathy and MCGN, and with sIgE in MCNS. Increased subsets in membranous nephropathy, IgA nephropathy and MCGN corresponded to the immunoglobulins deposited in the glomeruli, and the increased subset of sIgE in MCNS was correlated with the elevation of serum IgE. These results suggest that each disease studied has a characteristic subset pattern of B lymphocyte response. This may have an important role in determining the histological type of idiopathic glomerulonephritis.     

IgA-IgM nephropathy. A subgroup of primary mesangial glomerulonephritis

The renal biopsy material of Tampere University Central Hospital comprises 1992 renal biopsy specimens, accessioned during the years 1978-1989. Among these, there were three cases of mesangial glomerulonephritis with a peculiar type of immunofluorescent reactivity. Striking mesangial deposits of both IgA and IgM were found in glomeruli, whereas C3 deposits were absent or present in slight amounts. The light microscopic findings ranged from mild mesangial glomerulonephritis to more advanced forms of sclerosing glomerulopathy. Electron microscopic examination disclosed an increase of mesangial matrix, together with mesangial and paramesangial electron-dense deposits. Two of the patients had microscopic hematuria associated with proteinuria, and one had isolated proteinuria. The authors propose that this group of cases may represent a new subgroup of primary mesangial glomerulonephritis that has not been described previously. They differ immunohistologically from both IgA nephropathy and IgM nephropathy, and therefore could be designated as IgA-IgM nephropathy.     

Cyclosporin-A in the treatment of nephrotic syndrome: the importance of monitoring C0 (trough) and C2 (two hours after its administration) blood levels

Cyclosporin-A (CsA) is often used in the treatment of nephrotic syndrome. The effectiveness of CsA and the value of C2 blood levels in the treatment of nephrotic syndrome, due to various glomerular diseases, were studied. Forty-two nephrotic patients (M/F 21/21), with well-preserved renal function (creatinine clearance 87+/-20 ml/min) were included in the study. The original diagnoses were minimal change disease (MCD), focal segmental glomerulosclerosis (FSGS), membranous nephropathy (MN), IgA nephropathy (IgAN), and lupus nephritis (LN). All patients were treated with prednisolone and CsA for 24 months. Cyclosporin-A C0 and C2 blood levels were determined at regular intervals. Remission of the nephrotic syndrome was observed in all patients with MCD, IgAN and LN, in 75% with FSGS and in 83% with MN. Relapses were observed in some patients with MCD (25%) and MN (36%). The C0 levels were 93+/-15 ng/ml and the corresponding C2 levels were 498+/-110 ng/ml. However, significantly lower (340+/-83 ng/ml) or higher (680+/-127 ng/ml) to the average C2 levels were found in 6 patients (14%). No relation of C0 and C2 levels with the remission and relapse rate of the nephrotic syndrome and with renal function impairment was observed. Small doses of CsA with prednisolone are effective in the treatment of nephrotic syndrome. Although an individual variation of C2 was observed for the same target C0 levels, no relation of C2 levels was found with the remission or relapse rate of the nephrotic syndrome.     

Etiology of IgA nephropathy syndrome

Since Berger's original paper on mesangial IgA-IgG deposition with hematuria, there have been a number of clinical and pathological studies regarding IgA immune complexes, the mechanisms of glomerular IgA deposition leading to glomerular injury and animal models of IgA nephropathy. During the last quarter of this century, glomerular changes such as IgA nephropathy have also been observed in cases associated with other diseases, such as systemic lupus erythematosus, Schoenlein-Henoch purpura, liver cirrhosis and chronic inflammatory diseases of the lung. This evidence supports the idea of an IgA nephropathy syndrome. On the other hand, IgA is thought to be an important humoral factor at the mucosal immune system and appears to have an antibody function against various etiologic candidates of extrinsic or intrinsic substances at the mucosal and systemic immune system. Glomerular IgA deposition in IgA nephropathy syndrome is thought to result from elevated levels of circulating immune complexes or aggregated IgA due to an overproduction of polymeric IgA as antibodies in the serum and due to the clearance impairment of IgA immune complexes in the hepatic and splenic phagocytic system. The glomerular IgA subclass is not one-sided, but should be evaluated in comparison with the age of patients at renal biopsy; this indicates the approximate age of onset. Cirrhotic IgA glomerulonephritis is not related to Hepatitis B or C virus infection, but to the pathophysiologic condition of liver cirrhosis. Various etiologic candidates such as viral, microbial, dietary antigens or auto-antigens have been listed and experimental models of IgA nephropathy syndrome have provided some clues in understanding the etiology of primary IgA nephropathy. However much still remains to be clarified and some specific epitopes common among these etiologic candidates will have to be identified.     

Pattern of glomerulonephritis in Hong Kong

A retrospective analysis of all renal biopsies (961) performed in two regional hospitals in Hong Kong during 1977-1985 revealed that IgA nephropathy was the most frequently encountered glomerulopathy. Lipoid nephrosis (minimal change nephrotic syndrome) remained the commonest cause of nephrotic syndrome in children. The frequencies of mesangiocapillary glomerulonephritis, focal glomerulosclerosis, and idiopathic membranous nephropathy were lower than in other populations. Membranous nephropathy was frequently associated with hepatitis B virus antigenemia, especially in children. Other chronic infections did not have a significant pathogenetic role in glomerular diseases. Lupus nephritis was the commonest secondary glomerular disease in our study, and over seventy percent of the renal biopsies showed advanced pathologies with either diffuse proliferative glomerulonephritis or membranous nephropathy.     

免疫球蛋白沉积类型在IgA肾病中的意义

３１例小儿ＩｇＡ肾病报道结果表明：免疫球蛋白沉积类型与临床表现及组织损伤程度有一定关系。单纯系膜区ＩｇＡ沉积，组织损伤程度轻，临床多表现为单纯性血尿，预后较好，ＩｇＡ合并ＩｇＧ及／ＩｇＭ沉积者，易合并补体的沉积，组织损伤程度重，临床表现以肾病综合征及血尿合并蛋白尿发生率高。免疫复合物不仅沉积在系膜区，也可沉积在内皮下，并有相应的基底膜损伤。     

Fibrillary glomerulonephritis mimicking membranous nephropathy – A diagnostic pitfall

Kidney biopsies in 2 females with nephrotic syndrome were suggestive of membranous nephropathy at routine light microscopy and immunohistochemistry. Electron microscopy on re-embedded paraffin tissue, however, revealed that the light microscopic pattern was due to a fibrillary glomerulonephritis with a dominant membranous manifestation.     

显微镜型多血管炎肾活检病例的临床病理分析

目的探讨血清抗中性粒细胞胞质抗体（ANCA）及肾小球内有无免疫球蛋白（Ig）沉积在显微镜型多血管炎（MPA）肾活检病例中的病理诊断价值及其临床病理意义。方法34例MPA均为该系2000年1月至2007年3月7年间的就诊患者,其临床资料比较完整,后经肾穿刺活检而确诊者,分别对其血清ANCA阳性和阴性及肾小球内有无Ig沉积的临床病理特点进行比较。结果34例MPA患者,约1／5—1／2病例伴有各种肾外症状;经血清ANCA检测,阳性者26例（76．5％）;阴性者8例（23．5％）;其尿蛋白多呈轻一中度,呈肾病综合征者仅3例;肾功能减退者32例。经病理检查显示,24例为新月体性肾炎,8例为局灶节段性肾炎,其他类型者仅2例;伴肾血管坏死或内膜炎症7例,内膜增厚24例;伴间质炎性细胞浸润29例,其中21例伴有中性粒细胞浸润。经临床与病理比较分析,发现ANCA阳性组的新月体形成率显著高于ANCA阴性组（P〈0．05）;在26例ANCA阳性组病例中,肾小球Ig沉积者的尿蛋白定量显著高于无Ig沉积组（P〈0．05）,其中1例合并IgA肾病。结论对MPA的诊断有赖于对患者血清ANCA的检测和肾活检组织的病理学检查;ANCA是促进肾小球新月体形成的一个重要因素;Ig在肾小球内的沉积对患者蛋白尿的加重起促进作用。     

The ultrastructural characteristics of minor glomerular abnormalities]

Among 1168 patients in whom clinical data and light microscopic, immunofluorescence and electron microscopic findings of renal biopsies were available, 329 had minor glomerular abnormalities. These 329 cases included 38 with glomerular minimal change (MC), 32 with glomerular minor lesion, 143 with mild mesangioproliferative GN, 14 with mild mesangioproliferative IgM nephropathy, 4 with C1q nephropathy, 37 with IgA nephropathy, 12 with Henoch-Sch?nlein purpura GN, 17 with lupus nephritis, 16 with early stage membranous nephropathy (eMN), 4 with Alport's syndrome (ALS), 7 with thin basement membrane nephropathy (TMN) and 5 with nonglomerular haematuria. Their histologic appearances were nearly normal, and immunofluorescence was negative or mild positive. But electron microscopic appearances were diagnostic. Electron microscopy is the only diagnostic method for MC, ALS, TMN and eMN.     

Renal diseases associated with hematuria in children and adolescents: a brief tutorial

The detection of microscopic hematuria in a child's urine prompts evaluation for renal and urinary bladder causes. Microscopic hematuria identified during a routine physical examination by the pediatrician is much more common than macroscopic hematuria. Persistent microscopic hematuria is particularly worrisome and may require a percutaneous needle core kidney biopsy to determine whether the etiology is secondary to glomerular disease, tubulointerstitial disease, urinary tract infection, urinary tract structural abnormalities, medications, or toxins. This paper reviews the epidemiology, pathologic features, pathogenesis, treatment, and outcome of familial hematuria (Alport syndrome [hereditary nephritis]), thin basement membrane nephropathy), IgA nephropathy, Henoch-Sch?nlein purpura, and acute postinfectious glomerulonephritis.     

T cell subset alterations in idiopathic glomerulonephritis

Peripheral blood lymphocytes from 15 healthy controls and 59 patients with idiopathic glomerulonephritis were studied to determine whether an imbalance exists among human T cell subsets in these diseases. Twenty of the patients studied had a minimal change nephropathy (10 with nephrotic syndrome and 10 in sustained remission); 27 had a membranous glomerulonephritis (12 with nephrotic syndrome, six with isolated proteinuria and nine in complete remission); 12 patients had an IgA glomerulonephritis with heamaturia and mild proteinuria. Monoclonal antibodies directed at human T lymphocyte subsets termed OKT3, OKT4 and OKT8 were used in an indirect immunofluorescence assay in all cases. Patients with minimal change nephropathy, with or without nephrotic syndrome and patients with IgA glomerulonephritis showed mean values of OKT3⁺ cells (total peripheral T cells), helper OKT4⁺ cells, suppressor OKT8⁺ cells and OKT4⁺/OKT8⁺ cell ratio, in the normal range. Only the group of patients with membranous glomerulonephritis and nephrotic syndrome presented a mean OKT4⁺/OKT8⁺ ratio greater than the normal group (percentages: 2·43±0·3 vs 1·6±0·1 s.e.m.; P<0·02). This increased ratio was due to a reduction in the OKT8⁺ cell subset compared to the healthy subjects (percentages: 27·6±2·9 vs 36·8±1·4 s.e.m.; P<0·01). Our data shows that the functional lymphocyte disorders previously described in minimal change nephropathy and IgA glomerulonephritis are not due to a numerical imbalance of lymphocyte subsets. Such an imbalance of lymphocyte subsets was specifically observed in membranous glomerulonephritis with nephrotic syndrome. The true significance of this finding has to be clarified by longitudinal studies and functional tests.     

Diabetic nephropathy associated with fibrin formation

This communication describes the electron microscopic study of a renal biopsy specimen from a patient with diabetic nephropathy, the nephrotic syndrome, and renal insufficiency. There were large amounts of electron dense materials within glomerular basement membranes and masses of fibrin within glomerular capillaries and Bowman's spaces. The presence of glomerular fibrin suggests that thrombosis may be pathogenetically related to diabetic nephropathy.     

Identification of an electron densification of the glomerular basement membrane in renal biopsy specimens

Ultrastructural examination of renal biopsy specimens is often necessary to establish a diagnosis. We have noted, in some renal biopsies, that normal-appearing glomerular basement membrane (GBM) shows an electron densification. The aim of this study was to describe this phenomenon and assess the degree of its occurrence. We reviewed ultrastructural pathology records of 153 renal biopsy patients with special reference to the careful examination of the electron micrographs. Of these, 28 cases (18%) showed a definite and homogeneous electron densification of normal-appearing GBM in the glomeruli. The pathological diagnosis in these cases was IgA nephropathy in 15, minimal change nephrotic syndrome in 6, interstitial nephritis in 3, membranoproliferative glomerulonephritis in 2, and nephritis of Henoch-Schonlein purpura and membranous nephropathy in 1 case each. In addition, frequent deposition of IgG without C3 in the GBM (86%) and glomerular endothelial cell edema (96%) were observed. No apparent correlation could be ascertained between the presence of the electron densification and pathological diagnosis. It is suggested that electron densification of the GBM may be caused by the penetration of some electron-dense materials into the GBM as a result of an abnormality in the glomerular filtration barrier and that this could be considered as a sign of altered properties of the lamina densa.