老年肾脏病肾活检的诊断价值与风险评估

目的探讨肾活检在老年肾脏病中的诊断价值与风险评估。方法回顾性分析我科住院行肾活检,且年龄≥60岁的123例老年肾脏病患者的临床病理资料及安全性。结果肾活检术成功率100％,肾活检取材肾小球数目均≥10个,共有6例出现轻度并发症,其中一过性肉眼血尿2例（占1．6％）,肾周小血肿4例（占3．2％）,余无严重并发症。123例患者中原发性肾小球疾病为105例（占85．4％）,而继发性肾脏病为18例（占14．6％）。在原发性肾小球疾病中最常见的病理类型是膜性肾病26例（占26．0%）,IgA。肾病25例（占25．0％）,其次为系膜增生性肾小球肾炎19例（占19％）。而继发性肾脏病中病理类型以糖尿病肾脏病11例最多见（占47．8％）。最常见的临床表现是肾病综合征（占39．8oA）和慢性肾小球肾炎（占33．3％）。临床诊断与肾活检结果尚存在差异（P〈0．05）。结论肾活检在老年性肾脏疾病患者中应用的成功率高而并发症少且大多较轻,其病理结果对明确诊断和决定治疗方案具有重要指导意义。     

Recurrence of IgA nephropathy with crescents in kidney transplants

Crescentic IgA nephropathy is an uncommon finding in native kidneys (3%-5%) and in renal transplants. This study was performed to determine the frequency of relapsing crescentic IgA nephropathy after kidney transplantation. Over a 15-year period, 42 patients (25 men, 17 women) of age range 17 to 59 years with biopsy-proven IgA nephropathy in their native kidneys were entered into this retrospective study, because they had undergone kidney transplantation and had sequential allograft biopsies during their follow-up. Mean follow-up after transplantation was 8.9 years (range, 1-15 years). In their native kidneys, 5 patients (12%) had more than 20% crescents, and only 2 (5%) had more than 50% of glomeruli involved. As expected, 52.4% of recipients showed recurrent mesangial IgA deposits in their kidney grafts. The 2 patients with diffuse crescentic IgA nephropathy in their native kidneys experienced acute graft dysfunction at 15 and 47 months. Graft biopsy showed recurrent IgA deposits with cellular crescents in 30% and 20% of glomeruli, respectively. Despite corticosteroid pulse therapy, graft failures occurred 2 and 27 months later. No crescentic proliferation was observed during follow-up in any other case. Only 5 other grafts failed because of chronic allograft nephropathy, without any relationship to the relapse of IgA deposits. These data suggested for the first time that only diffuse crescentic IgA nephropathy in the native kidneys was associated with the occurrence of crescents in the kidney transplants, a finding that raises the possibility of a particular subgroup of IgA nephropathies.     

The clinical course of IgA nephropathy after kidney transplantation and its management

Immunoglobulin (Ig) A nephropathy is one of the most common primary glomerulonephritides worldwide causing end stage renal disease in up to 20–40% of affected patients, nearly two decades post diagnosis. Kidney transplantation is the treatment of choice for patients with renal failure, secondary to glomerular diseases. However, IgA nephropathy has a strong tendency to recur in the graft, and although initially thought to be a benign condition, several reports of graft loss, due to recurrent IgA nephropathy, there have been over the last three decades. Overall graft survival has been significantly improved in kidney transplantation, as a result of reduced incidence of acute rejection, as more potent and more specific immunosuppressive agents are now available in clinical practice. Thus, the rates of IgA nephropathy and other glomerulonephritides recurrence are expected to increase, since graft survival has been improved. However, the reported incidence of IgA nephropathy recurrence in the graft varies substantially across centers, as a consequence of different levels of interest, diverse biopsy policies and differing durations of follow up, of the published studies. Notably, recurrence rates of patients receiving graft biopsies by clinical indication only, ranges from 13% to 50% with graft loss being between 1.3% and 16%. The aim of this review is to underline important pathogenetic insights of IgA nephropathy, describe the clinical course of the disease after kidney transplantation, with emphasis on the incidence of recurrence and the associated risk factors, and finally provide all available options for its management in transplant recipients.     

Binding sites for carrier-immobilized carbohydrates in the kidney: implication for the pathogenesis of Henoch-Sch?nlein purpura and/or IgA nephropathy.

BACKGROUND: Henoch-Sch?nlein purpura is a common vasculitis of childhood affecting the skin, joints, gastrointestinal tract, and kidney. The mesangial deposition of IgA1 is the most critical factor for the prognosis of patients with this disease. The aberrant glycosylation of the IgA1 subclass with the absence of terminally located galactose and presence of only alpha-N-acetylgalactosamine in O-linked oligosaccharides in the hinge region of IgA1 represents a prominent difference from the normal IgA1. These alterations prompt the supposition that the sugar part may guide IgA deposition by recognition of endogenous lectins on the mesangium. METHODS: Owing to the limited knowledge about the expression of carbohydrate-binding sites in the human kidney we initiated the study of this aspect with a class of tools which are suitable to map the lectinome of cells. Employing biotinylated neoglycoconjugates, glycosaminoglycans, and sulphated polysaccharides we monitored the presence of accessible carbohydrate-binding sites in control kidneys represented by tumour-free areas of kidneys with Grawitz tumour and in biopsies from patients with Henoch-Sch?nlein purpura-associated IgA nephropathy. RESULTS: Using frozen sections, no expression of any tested carbohydrate-binding site(s) was observed in the endothelial and the mesangial cells in glomeruli of the control kidneys as well as in the biopsies from Henoch-Sch?nlein purpura IgA nephropathic kidneys, in contrast to the tubules. The N-acetylgalactosamine-binding sites were expressed only in the inner layer of Bowman's capsule of 20% of glomeruli of the control kidney from one patient with Grawitz tumour and one biopsy from a patient with Henoch-Sch?nlein purpura-associated IgA nephropathy. However, the macrophages in the glomeruli of patients with IgA nephropathy and interstitial macrophages from both studied groups, i.e. without and with IgA nephropathy, harbour capacity to recognize carrier-immobilized alpha-N-acetylgalactosamine. Access to this binding site for the neoligand conjugate can be blocked by the monoclonal antibody MEM-18 recognizing CD14 antigen. CONCLUSION: The possibility for a participation of macrophage deposition of IgA1 in mesangium via a lectin mechanism involving this binding capacity warrants further studies.     

Cu, Zn-superoxide dismutase, glutathione peroxidase location in kidney of IgA nephropathy]

To study the role of reactive oxygen species (ROS) in chronic renal disease, we studied the localization of Cu, Zn-Superoxide dismutase (SOD) and Glutathione peroxidase (GSH-Px) in glomeruli of patients with IgA nephropathy by immunohistochemical method. Thirty three kidney specimens were used consisting of 28 IgA nephropathy and, normal parts of the 5 resected kidneys with renal tumors as controls. To evaluate the change of renal function and renal histological grade, creatine clearance (Ccr) and histological grade were assessed at the time of biopsy. In normal kidney, Cu, Zn-SOD and GSH-Px was localized in tubular cells, and not in glomeruli. In the kidney with IgA nephropathy, Cu, Zn-SOD and GSH-Px were detected in epithelial side of the glomerular capillary wall in addition to the tubular cells. The positive correlation was observed between the glomerular localization of Cu, Zn-SOD and that of GSH-Px. As for the relation between the extent of localization of these enzymes and clinical findings at the time of biopsy, the following results was obtained. When Cu, Zn-SOD and GSH-Px was strongly stained in glomeruli, histological change of glomeruli was milder. These results suggest that Cu, Zn-SOD and GSH-Px have the beneficial actions for renal function as anti-oxidative factors.     

IgA nephropathy is not a rare disease in the United Kingdom

A retrospective analysis of all renal biopsies performed in the Grampian Region of Scotland during 1977-1980 revealed that IgA nephropathy was the most frequently encountered glomerular lesion. The commonest indications for renal biopsy were the presence of asymptomatic urinary abnormalities (90/184; 48.9%) especially asymptomatic haematuria (42/184; 22.8%). A histological diagnosis was made in 36 of the 42 patients presenting with asymptomatic haematuria (85.7%); 16 of the 26 cases of IgA nephropathy presented in this way. Overall, IgA nephropathy was detected in 14.1% of all biopsies and accounted for 21.8% of primary glomerular diseases. This study indicates that IgA nephropathy is apparently more common in Grampian than elsewhere in the United Kingdom. However, it is suggested that this does not represent a true variation in the prevalence of the condition; IgA nephropathy is probably a common cause of haematuria in the United Kingdom.     

肾活检患者451例临床与病理构成对比分析

目的 分析珠海地区肾脏疾病的病理及临床特点.方法 回顾性分析我院451例肾活检患者的临床及病理资料,探讨其病因、临床特点及病理类型的关系.结果 451例肾活检患者中,男、女高峰发病年龄为19～37岁,分别占59%及65%.原发性肾小球疾病共369例（占81.81%）,临床类型排在前3位的依次为无症状血尿、蛋白尿149例（占40.38%）、慢性肾小球肾炎104例（占28.18%）、肾病综合征76例（占20.60%）,病理类型排在前3位的依次为IgA肾病251例（占68.02%）、系膜增生性肾小球肾炎（MsPGN）33例（占8.94%）、微小病变型肾病（MCD）24例（占6.50%）;继发性肾小球疾病69例（占15.30%）,临床类型排在前3位的依次为狼疮肾炎26例（占37.68%）、乙型肝炎相关性肾小球肾炎24例（占34.78%）、紫癜肾炎9例（占13.04%）.结论 原发性肾小球疾病是目前最主要的肾小球疾病,IgA肾病在原发性肾脏疾病中发病率最高,继发性肾小球疾病中狼疮肾炎排在首位.     

Is IgA nephropathy the commonest primary glomerulopathy among young adults in the USA?

Over the past decade, focal segmental glomerulosclerosis (FSGS) has emerged as the most common primary glomerulopathy in adults in the USA. However in our practice, we became aware of increased numbers of patients with IgA nephropathy (IgAN). In order to further examine this, a retrospective analysis of renal biopsy diagnoses from adults was done from our biopsy database. Adult renal biopsies received from 3/1/2001 to 2/28/2005 were analyzed to determine the frequency of common primary glomerulopathies, which included FSGS, IgAN, membranous nephropathy (MN), minimal change disease, and membranoproliferative glomerulonephritis Type I (MPGN). The patients were grouped as all adults (>or=20 years) and young adults (20-39 years). The distribution of common primary glomerulopathies among the two age groups, expressed as a percentage of all non-transplant diagnoses (n = 4,504), was IgAN 6.9/3.4%, FSGS 9.6/3.2%, MN 6.8/1.6%, minimal change disease 2.5/0.9%, MPGN 1.2/0.2%. IgAN was as common as FSGS in young adults in our biopsy population (IgAN/FSGS 154/143 1.08:1). IgAN was the most common primary glomerulopathy in young adult Caucasians (IgAN/FSGS 2.1:1). IgAN was also the most common cause of end-stage renal disease (ESRD) in young adult Caucasians. In contrast, IgAN was rare in African Americans in whom FSGS remains more common (FSGS/IgAN 9.7:1). These findings from a large renal biopsy referral center serving 24 Midwestern and Southern states suggest that IgAN may be the most common primary glomerulopathy and the most common cause of ESRD in young adult Caucasians in the USA.     

Percutaneous renal biopsy results: a retrospective analysis of 511 consecutive cases

To determine the patterns of the prevalent glomerulonephritis (GN) in our region, we studied the results of 511 consecutive renal biopsies performed on patients with proteinuria, hematuria and mild to moderate renal impairment at the Aga Khan University Hospital during a period of 18 years from January 1990 to December 2008. Primary glomerular disease accounted for two-thirds of the glomerular diseases, which in turn constituted 49% of all renal biopsies. The most common histological lesion was membranoproliferative disease (28%). Membranous GN was the second most common lesion (19%), followed by minimal change disease (16%) and focal segmental GN (11%). Secondary glomerular disease comprised 30% of glomerular diseases (21% of all the renal biopsies), with lupus nephritis forming the most common lesion (34%) followed by amyloidosis (22%), diabetic nephropathy (10%), Wagener's granulomatosus and post-infectious GN (9% each). Tubulointerstitial diseases accounted for 16% of all the renal biopsies. We conclude that there exists a wide variability in the different categories of primary and secondary glomerular diseases in our region as compared with different parts of the world. Future studies should be directed to analyze the causes for these variations.     

Paulista Registry of glomerulonephritis: 5-year data report.

BACKGROUND: The Paulista Registry of Glomerulopathies was created in May 1999 and comprises several centres of S?o Paulo, the most populous Brazilian State, that concentrates people from all regions of the country who look for health care. METHODS: This report includes data from 2086 patients from Brazil submitted to renal biopsy due to the presumed diagnosis of glomerular diseases, registered prospectively since May 1999 until January 2005. Data were collected by the integrants of the 11 centres involved, utilizing a standardized questionnaire. RESULTS: The mean age of the patients was 34.5+/-14.6 years. Primary glomerular diseases were more frequent in males (55.1%) than in females; on the other hand, secondary glomerular diseases were more frequent in females (71.8%). The most common clinical presentation was nephrotic syndrome and the frequency of hypertension, at this time, was 55.5%. There was a predominance of indication of biopsies in the third, fourth and fifth decades of life. The most common primary glomerular diseases were focal and segmental glomerulosclerosis (29.7%), followed by membranous nephropathy (20.7%), IgA nephropathy (17.8%), minimal change disease (9.1%), membranoproliferative glomerulonephritis (7%), crescentic glomerulonephritis (4.1%), advanced chronic glomerulopathy (4%), non-IgA mesangial glomerulonephritis (3.8%), diffuse proliferative glomerulonephritis (2.5%), focal segmental proliferative glomerulonephritis (1%) and others (0.3%). The most frequent secondary glomerular disease was lupus nephritis, corresponding to 66.2% of the cases, followed by post-infectious glomerulonephritis (12.5%), diabetic nephropathy (6.2%), diseases associated to paraproteinaemia (4.9%), hereditary diseases (4.6%), vasculitis (3.2%), malignancies (0.9.%), secondary focal segmental glomerulosclerosis (0.6%) and others (0.9%). CONCLUSION: Focal segmental glomerulosclerosis was the most frequent primary glomerular disease, followed by membranous nephropathy and IgA nephropathy. Lupus nephritis predominated over all the other secondary glomerular diseases.     

Glomerular atrial natriuretic factor receptors in primary glomerulopathies: studies on human renal biopsies

Human renal biopsies are currently used to provide information about morphologic changes, chronicity of disease, patterns of inflammation, and immunoglobulin deposition. This practice has provided only limited insight into functional aberrations and has failed to provided information necessary for disease classification based on pathophysiology. To expand the potential of the renal biopsy in this regard and to determine whether differences in glomerular atrial natriuretic factor (ANF) binding exist in different forms of primary renal disease, quantitative autoradiography and 125I-human ANF (1-28) were used to determine the location and pharmacological characteristics of ANF binding sites in the normal human kidney. Specific ANF binding was highest in the glomeruli, but lower levels of specific binding were localized to the inner medulla and the interlobular arteries. ANF binding sites in the human kidney were found to be highly stable and similar in both location and pharmacology to those observed in experimental animals. As determined by saturation experiments, the equilibrium dissociation constants for glomeruli, inner medulla, and interlobular arteries were almost identical at 4.0 x 10(-11) mol/L. Competitive binding inhibition studies with unlabeled human ANF (1-28) demonstrated highly specific binding shared by the glomerulus, inner medulla, and interlobular artery, with apparent half-maximal inhibition concentrations of 9.2 x 10(-10) mol/L, 8.0 x -10 mol/L, and 8.2 x 10(-10) mol/L, respectively. Quantitation of specific binding of ANF to glomeruli in needle biopsy specimens of three primary glomerulopathies, ie, minimal-change disease, membranous nephropathy, and focal glomerulosclerosis, showed no differences among the groups. This study demonstrates the feasibility of studying receptor physiology on biopsy specimens of the human kidney and should allow renal diseases, particularly of glomerular origin, to be characterized according to differences in hormone binding and hormone responsiveness. The absence of significant differences in glomerular ANF binding in the primary glomerulopathies studied is consistent with other studies that have failed to delineate important pathophysiological differences in renal function and volume homeostasis in these disease states.     

Pattern of double glomerulopathy in children

Occasional case reports have been issued on children with double glomerulopathy, involving either the coexistence of two different glomerulopathies or superimposition of a second glomerulopathy onto a first. A retrospective clinicopathological review of 294 children who had received renal biopsies resulted in 9 (3.1%) being confirmed to have double glomerulopathy. Superimposed glomerulopathy was diagnosed by a second renal biopsy in two cases, and coexistence of two glomerulopathies was confirmed by single biopsy in seven. Original glomerulopathies were those with a chronic course, such as Alport syndrome, IgA nephropathy, relapsing minimal-change nephrotic syndrome, Frasier syndrome, and thin basement membrane nephropathy. The superimposing glomerulopathies were common types in children, such as postinfectious glomerulonephritis, IgA nephropathy, and Henoch-Schönlein nephritis. Thus, the pattern of double glomerulopathy was considered to be due to the chance occurrence of two different glomerulopathies without a common pathogenesis. Acute nephritic symptoms of superimposed glomerulopathies resolved almost completely during follow-up in most cases. Double glomerulopathies are not rare in children and may occur by chance alone in most cases. The possibility of superimposed glomerulopathy should be suspected if the clinical course of a glomerulopathy changes atypically. However, the long-term influence of a superimposed glomerulopathy on renal functional deterioration remains unclear.     

Tubular staining of modified C-reactive protein in diabetic chronic kidney disease.

BACKGROUND: Serum levels of C-reactive protein (CRP) increase during various atherosclerotic as well as kidney diseases. Whether CRP plays a pathophysiological role or rather serves as a marker is unknown. Here, we investigated the role of CRP in diabetic patients with chronic kidney disease. METHODS: Kidney biopsies from 20 diabetic patients, six with IgA nephropathy and six controls (absence of disease) were stained using a commercially available anti-CRP antibody (clone 8). We characterized this antibody by ELISA and found that it mainly recognized 'modified' CRP (mCRP), the conformational isoform of CRP that occurs after dissociation of the pentameric isomer. RESULTS: A specific CRP signal was observed in the cytoplasma of tubules in 17 out of 20 kidney biopsies from diabetic patients, while all glomeruli, vessels and interstitium stained CRP-negative. This signal was absorbed against the mCRP protein suggesting that the detected tissue-based antigen is more closely related to the mCRP conformer than to the native CRP conformer. Almost all patients (eight out of nine) with severe chronic kidney disease [glomerular filtration rate (GFR) <30 ml/min/1.73 m(2)] strongly stained for the mCRP antigen, whereas only four out of 11 patients with mild and moderate chronic kidney disease (GFR >/=30 ml/min/1.73 m(2)) demonstrated a strong CRP signal. Normal renal tissue and most biopsies with IgA nephropathy were mCRP negative. Severity of histologic changes as assessed by histology score and mCRP staining correlated significantly, but no correlation was evident between tubular mCRP staining and serum levels of CRP or proteinuria. CONCLUSIONS: The present group of diabetic patients showed progressive tubular mCRP staining with declining renal function and increasing severity of histological lesions. Further studies in less proteinuric patients should clarify whether tubular mCRP expression constitutes a progression factor. It also needs to be demonstrated whether mCRP accumulates in tubuli to further stimulate interstitial fibrosis or is mandatory for the resolution of the process. Since mCRP staining was independent of proteinuria we suggest that mCRP is locally produced.     

Basic and translational concepts of immune-mediated glomerular diseases

Genetically modified immune responses to infections and self-antigens initiate most forms of GN by generating pathogen- and danger-associated molecular patterns that stimulate Toll-like receptors and complement. These innate immune responses activate circulating monocytes and resident glomerular cells to release inflammatory mediators and initiate adaptive, antigen-specific immune responses that collectively damage glomerular structures. CD4 T cells are needed for B cell-driven antibody production that leads to immune complex formation in glomeruli, complement activation, and injury induced by both circulating inflammatory and resident glomerular effector cells. Th17 cells can also induce glomerular injury directly. In this review, information derived from studies in vitro, well characterized experimental models, and humans summarize and update likely pathogenic mechanisms involved in human diseases presenting as nephritis (postinfectious GN, IgA nephropathy, antiglomerular basement membrane and antineutrophil cytoplasmic antibody-mediated crescentic GN, lupus nephritis, type I membranoproliferative GN), and nephrotic syndrome (minimal change/FSGS, membranous nephropathy, and C3 glomerulopathies). Advances in understanding the immunopathogenesis of each of these entities offer many opportunities for future therapeutic interventions.     

老年肾脏病患者临床及病理特征分析

目的分析老年(年龄≥60岁)肾脏病患者临床及肾脏病理特点。 方法收集2010年1月至2016年12月在我科行肾穿刺活检的老年患者742例,对其性别、年龄、原发性疾病、肾脏病理类型及肾穿刺后并发症进行回顾性分析。以卡方检验比较老年患者与青年患者肾活检并发症的发生率,数据采用SPSS 19.0统计学软件处理。 结果①742例老年患者,年龄60～88岁,平均年龄(72.7±11.3)岁;60～74岁637(85.8%),75～88岁105例(14.2%)。男性426例(57.4%)。②患高血压者331例(44.6%);贫血272例(36.7%);高尿酸血症199例(26.8%);低蛋白血症257例(34.6%)。CKD1～5期比例分别为27.4%、33.8%、29.8%、7.1%、1.9%。③与同期行肾活检年龄≤60岁患者比较,老年患者肾穿刺术后肾周大血肿、需要输血、需行肾动脉栓塞等严重出血并发症的风险无统计学差异(χ² ＝0.457、0.108、0.199,P>0.05)。④742例老年患者中,原发性肾小球疾病390例(52.6%),继发性肾小球疾病268例(36.1%),肾小管间质疾病72例(9.7%),其他12例(1.6%)。原发性肾脏疾病以膜性肾病和系膜增生性肾小球肾炎最为常见,分别为30.4%和17.3%;继发性肾脏病中糖尿病肾病占21.3%、高血压肾损害和肿瘤相关性肾损害分别为12.3%和11.9%。 结论老年肾脏病患者高血压、贫血、高尿酸血症发生率高。原发性肾脏病以膜性肾病为多见,继发性肾脏病以糖尿病肾病、肿瘤相关肾损害最为常见。对于老年肾脏病患者均应结合临床,筛查继发病因。对于无肾穿禁忌证的老年肾脏病患者,应积极行肾活检应明确病理类型指导治疗、判断预后。     

Polymorphs infiltrate glomeruli in mesangial IgA glomerulonephritis

During episodes of macroscopic hematuria, patients with IgA nephropathy commonly have polymorphonuclear neutrophils (PMNs) as well as fibrin and mononuclear cells in glomerular capillaries. We quantitated PMN and macrophage infiltration in glomeruli of 54 patients with IgA nephropathy in whom renal biopsies were obtained within 30 days of macroscopic hematuria. Control biopsies (N = 22) were from patients with IgA nephropathy and urinary erythrocyte counts below 50,000/ml. PMN monocyte/macrophages were quantitated using the monoclonal antibodies FMC10 and HAM56, respectively. In patients with heavy hematuria, 45.9 +/- 3.4% (mean +/- SE) of glomeruli were positive for PMNs (control 10.5 +/- 2.8%, P = 0.001) with a mean PMN count/glomerulus of 1.10 +/- 0.20 (control 0.13 +/- 0.03, P = less than 0.001). 65.6 +/- 9.7%. Of the glomeruli were positive for monocytes in the heavy hematuria group (control 40.0 +/- 8.4, P less than 0.05) with the mean monocyte count per glomerulus being 1.6 +/- 0.2 (control 0.6 +/- 0.1, P less than 0.01). We conclude that, in the acute phase of mesangial IgA nephropathy, PMN and monocytes are present and presumably participate in glomerular injury.     

Staphylococcus aureus cell envelope antigen is a new candidate for the induction of IgA nephropathy

BACKGROUND: IgA nephropathy is the most common form of glomerulonephritis worldwide. We previously reported a novel form of glomerulonephritis with glomerular IgA deposits following methicillin-resistant Staphylococcus aureus (S. aureus) infection. We investigated the role of S. aureus related antigens in the immunopathogenesis of IgA nephropathy by producing several monoclonal antibodies against S. aureus surface antigens and determining the epitopes of deposited antigens in patients with IgA nephropathy. METHODS: Cell membrane proteins were isolated from cultured S. aureus. Mouse monoclonal antibodies against these proteins were generated, and their target epitopes were determined by antibody affinity chromatography and amino acid sequence analysis, and by monoclonal antibody screening of Escherichia coli clones transfected with plasmids from the Lambda S. aureus Genomic Library. Renal biopsy specimens from 116 patients with IgA nephropathy and 122 patients with other forms of renal disease were examined for glomerular antigen depositions by immunofluorescence microscopy. RESULTS:. The major antigen recognized by monoclonal antibodies against S. aureus cell membrane was identified as the S. aureus cell envelope antigen designated 'probable adhesin' (ACCESSION AP003131-77, Protein ID; BAB41819.1). In 68.1% (79/116) of renal biopsy specimens from patients with IgA nephropathy, S. aureus cell envelope antigen was localized in the glomeruli, and the data confirmed that S. aureus cell envelope antigen was co-localized with IgA antibody in the glomeruli. No deposition of this antigen was detected in the glomeruli of patients with non-immune complex deposit forms of glomerulonephritis. CONCLUSION: S. aureus cell envelope antigen is a new candidate for the induction of IgA nephropathy.     

Glomerular expression of biglycan and decorin and urinary levels of decorin in primary glomerular disease

AIMS: Recent studies have suggested that small leucine-rich proteoglycans (SLRP) of the extracellular matrix play a major role in modulating the activity of growth factors and in regulating the deposition of collagens. In this study, the expression of the SLRPs biglycan and decorin in the glomeruli of patients with primary glomerular disease (minimal change disease, IgA nephropathy, and membranous nephropathy) and urine immunoreactive levels examined. METHODS: Renal biopsy specimens were obtained from patients with minimal change disease, IgA nephropathy and membranous nephropathy. Immunohistochemical staining was performed on fresh-frozen samples using anti-biglycan and anti-decorin antibodies. Examination of urine proteoglycan excretion from a total of 26 patients and 8 normal volunteers was performed by indirect ELISA. RESULTS: In normal kidney samples, biglycan and decorin expression was found predominantly in the intrarenal arteries and tubulointerstitium, with only minimal expression in the glomeruli. Glomerular expression of these proteoglycans in glomerular disease was unchanged in all of the 4 patients examined with minimal change disease. In the case of IgA nephropathy or membranous nephropathy, some of the patients showed minimally increased immunostaining of either biglycan or decorin, but there were no signs of simultaneous upregulation of both proteoglycans. To further examine the changes in proteoglycan expression, ELISA was performed on urine samples. Urine biglycan levels were below detection levels, but high values of urine decorin immunoreactivity were found in the patients with glomerular disease. A significant negative correlation was found between urine decorin and creatinine clearance. CONCLUSION: These results suggest that distinct changes in the expression of the SLRPs biglycan and decorin may be seen in patients with primary glomerular disease. Moreover, the negative relationship between urine decorin levels and renal function supports the hypothesis that decorin may be involved in the pathophysiology of renal dysfunction in humans.     

Renal allograft glomerulopathy and the value of immunohistochemistry

Studies of late renal allograft biopsies focus on chronic damage investigated by light microscopy (LM). We evaluated the use of immunohistochemistry (IH) as applied in the routine study of transplant glomerulopathies. Among renal transplants in 1985 - 1997, 129 were identified where a graft biopsy had been obtained 6 months or more after transplantation, studied by LM and IH and the original renal disease was known. IH results were evaluated in relation to glomerular LM findings and the original diagnosis. The risk of graft loss in relation to recurrent and de novo glomerulopathy was evaluated. By LM, 69 biopsies (53%) showed glomerulopathy, mesangial sclerosis only in 26, proliferative changes in 15, membranous in 15 and combined membranous and proliferative in 13. By IH, 46 biopsies (36%) stained positive with IgM and/or complement only and 24 with immune complexes including IgA and/or IgG. Seven biopsies (5.4%) showed glomerular disease by IH in spite of normal LM. Recurrence was diagnosed in 22 grafts; 12 had IgA nephropathy, 3 had SLE, 6 other immune complex nephritides and 1 systemic vasculitis. Twenty-eight biopsies (22%) with proliferative and/or membranous glomerulopathy lacked clear connection to the original renal disorder. More than half of these had deposits of IgM and C3 only. The further graft survival was significantly reduced in the presence of de novo glomerulopathy by LM, relative risk 2.0 (confidence interval 1.1 - 3.8) in a Cox-proportional hazards analysis also including serum creatinine and Banff chronic allograft nephropathy (CAN) grade, p = 0.03. In conclusion, transplant glomerulopathy should be separated from recurrence. De novo glomerulopathy is frequent and ominous.     

Enhanced expression of the CD71 mesangial IgA1 receptor in Berger disease and Henoch-Schönlein nephritis: association between CD71 expression and IgA deposits

ABSTRACT. IgA nephropathy (IgA-N) that comprises Berger disease and Henoch-Sch?nlein Purpura (HSP) nephritis is defined by mesangial IgA deposits. Recently, this group has characterized a new receptor for IgA, the transferrin receptor (CD71), expressed on mesangial cells. To assess whether CD71 was involved in the pathogenesis of IgA-N, its expression was analyzed together with IgA deposits on 16 kidney biopsies from 16 patients with Berger disease (n = 4) or HSP (n = 12). These biopsies were compared with 17 kidney biopsies of a group of 15 patients (control group) with other glomerulonephritis, including systemic lupus erythematosus, poststreptococcal acute glomerulonephritis, membranoproliferative glomerulonephritis, steroid-sensitive minimal change nephrotic syndrome, steroid-resistant idiopathic nephrotic syndrome with focal and segmental glomerulosclerosis, and persistent and isolated proteinuria with minimal change on kidney biopsy. In this control group, IgA deposits could be observed in eight kidney biopsies of seven patients. These biopsies were also compared with normal kidney specimens (normal group). In normal kidney, it was found that CD71 was linearly expressed on tubular epithelium but was either not expressed or very dimly in glomeruli. In contrast, CD71 was strongly expressed in 105 of the 107 glomeruli of the kidney biopsies from the IgA-N group. For the control group, it was found that expression of CD71 in glomeruli was correlated to the presence of IgA deposits. Indeed, among the 87 glomeruli of nine kidney biopsies (eight patients) without IgA fixation, 78 exhibited no CD71 expression and nine exhibited a very dim one. On the other hand, all 49 glomeruli of the eight kidney biopsies (seven patients) in which IgA deposits were detected exhibited CD71 expression (P < 10(-4)). Performance of dual-labeling studies with confocal microscopy on kidney biopsies of IgA-N patients demonstrated that most of the IgA deposits co-localized with CD71. It was also demonstrated that the intensity of the expression of CD71 was not linked to the intensity of clinical or biologic findings but to the intensity of cellular proliferation in both IgA-N and control groups. These results show that mesangial CD71 expression is not specific to IgA-N. However, the association between IgA deposits and CD71 expression and their co-localization in the mesangium provide strong evidence that CD71 is a major IgA receptor on mesangial cells.