The spectrum of children's kidney diseases—9925 renal biopsy-proven cases from a single center of China between 2004 and 2017

Objective To analyze the spectrum of children's kidney pathology by renal biopsy. Methods The clinical and pathological data of the cases in Jinling Hospital involving the patients younger than 18 years old who received renal biopsy from April 1st, 2004 to December 31th, 2017 were retrospectively collected, and compared with the renal pathological data of 1611 children aged 0-18 years from June 1982 to March 2004. Results This study included 9925 cases of kidney diseases proven by renal biopsy. The ratio of male to female was 1.79∶1. Primary glomerulonephritis (PGN) accounted for 66.14%, and secondary glomerulonephritis (SGN) accounted for 28.00%. Top five of the PGN were IgA nephropathy (IgAN, 19.11%), mesangial proliferative glomerulonephritis (MsPGN, 16.07%), minimal change disease (MCD, 14.20%), focal segmental glomerulosclerosis (FSGS, 6.19%) and membranous nephropathy (MN, 4.70%) in whole children, IgAN (13.12%), MsPGN (11.20%), MCD(10.63%), FSGS (4.55%) and MN (2.54%) in males, and IgAN (5.99%), MsPGN (4.87%), MCD (3.57%), MN (2.16%) and FSGS (1.63%) in females. Top three of the SGN were Henoch-Schonlein purpura nephritis (HSPN, 17.74%), lupus nephritis (LN, 8.23%) and vasculitis nephropathy (1.82%). The male was in a dominant position in all kinds of pathologic types than female except LN. HSPN was the most frequent type in adolescents between 6-13 years old. LN was the commonest one in 14-18-year-old girls, while IgAN was the the most common in 14-18-year-old boys. Post infective nephritis was the most popular in 12-14-year-old teenagers. It was also found that MN ascended in female. When compared with the data before 2004, HSPN and LN accounted for a greater proportion in SGN, post infective nephritis displayed a smaller proportion. Conclusions PGN is the mainly kind of glomerular disease as before, and immune disorder related to glomerular diseases increase and post infective nephritis decreases in proportion. This study provides the reference and epidemic data for diagnosis, treatment and prevention of children's renal diseases.     

Regional distribution of sulfatide in human kidney, and anti-sulfatide antibodies in sera from patients with nephritis detected by TLC immunostaining]

Glycolipids were isolated from lipid extract of human kidney. The major neutral glycolipids have been identified as ceramide monohexoside (CMH), ceramide dihexoside (CDH), ceramide trihexoside (CTH), and globoside. As the major acidic glycolipids, Gal Cer sulfate (sulfatide), Lac Cer sulfate, GM3, sialosyl paragloboside, GD3, and disialosyl paragloboside were identified and the most abundant component was sulfatide. Sulfatide was 2 times more concentrated in medulla compared to cortex. In addition, the localization of sulfatide antigen was determined in renal sections by immunoperoxidase staining method. Strong positive staining with sulfatide was observed in distal tubules, limbs of Henle's loop and collecting tubules of normal tissue, whereas glomeruli were negative of staining. However, positive results of glomerular epithelial cells occurred in FSGS and IgA nephropathy so far. Acidic fraction of lipid extract were chromatographed and then tested for antigen by immunostaining. Sera from patients with nephritis contain antibodies to the sulfatides of human kidney as determined by the direct binding of antibody to thin-layer chromatograms. These results suggest that sulfatide antigen may play important role in the occurrence and aggravation of glomerular diseases.     

Investigation of CD68 positive monocytes/macrophage(CD68+ Mo/M phi) in urine and infiltrated tissue of various kidney diseases in children

In order to investigate the participation of monocytes/macrophages(Mo/M phi) in the progression of various kidney diseases of children, Mo/M phi in urine and that infiltrating renal tissue were both measured as the number of CD68 positive Mo/M phi (CD68+ Mo/M phi), using anti-CD68 antibody. The number of CD68+ Mo/M phi infiltrating in one glomerulus was significantly higher in Henoch-Sch?nlein purpura nephritis(HSPN) (p < 0.01) in comparison with that in minimal change nephrotic syndrome(MCNS) (p < 0.01), and a high tendency was found in IgA nephropathy (IgAN), proliferative glomerulonephritis (non-IgAN), focal segmental glomerulosclerosis(FSGS) and membranoproliferative glomerulonephritis (MPGN), respectively. The number of CD68+ Mo/M phi infiltrating one mm2 of tubulo-interstitium area was significantly higher in HSPN(p < 0.05), FSGS(p < 0.01), Alport's syndrome(p < 0.01), respectively, than that in MCNS. The number of CD68+ Mo/M phi in one milliliter of urine correlated significantly with both that infiltrating the glomerulus and the tubulo-interstitium(both p < 0.01). Moreover the number of urine CD68+ Mo/M phi in a clinically active stage was significantly higher than that in an inactive stage in the AGN(p < 0.05), IgAN(p < 0.05), HSPN(p < 0.05), non-IgAN(p < 0.01) and MPGN groups(p < 0.05), respectively. From these results, 1) It was suggested that the Mo/M phi infiltrating renal tissue participated in the development of various kidney diseases. 2) It was predicted that CD68+ Mo/M phi in urine reflected both the number of Mo/M phi infiltrating the glomerulus and that in the tubulo-interstitium. 3) It was suggested that the number of CD68+ Mo/M phi in urine indicated clinical activity in proliferative glomerulonephritis groups of children.     

四川地区肾活检2330例临床病理分析

目的：探讨四川地区肾穿刺活检病理类型的分布特点以及疾病谱的变迁。方法回顾性分析2330例肾活检患者的临床病理资料,分析本地区肾脏疾病的临床病理特征。结果2330例肾活检患者中,男女比例为1∶1.15,发病高峰年龄为20~40岁。2330例患者中,原发性肾小球疾病1896例（占81.37%）,常见的病理类型依次为 IgA 肾病820例（占35.19%）、系膜增生性肾小球肾炎372例（占15.97%）、膜性肾病298例（占12.79%）、微小病变肾病200例（占8.58%）和局灶节段性肾小球硬化症78例（占3.35%）;继发性肾小球疾病367例（占15.75%）,以狼疮性肾炎最常见（134例,占5.88%）,其次为紫癜性肾炎127例（占5.45%）、糖尿病肾脏疾病35例（占1.5%）和淀粉样变性肾病20例（占0.86%）;肾小管间质疾病50例（占2.15%）;遗传性肾病17例（占0.73%）。2330例肾脏疾病患者的临床表现依次为肾病综合征1015例（占43.56%）、慢性肾炎综合征681例（占29.22%）、急性肾炎综合征392例（占16.82%）、隐匿性肾小球肾炎121例（占5.29%）、慢性肾衰竭72例（占3.09%）、急性肾衰竭47例（占2.02%）。近年来,膜性肾病构成比呈逐渐增加趋势。结论本地区肾脏疾病多见于青壮年,以原发性肾小球疾病最常见,其中 IgA 肾病和系膜增生性肾小球肾炎是最多见的病理类型,膜性肾病的检出率有增高趋势。继发性肾小球疾病以狼疮肾炎和紫癜性肾炎最常见。     

Alport综合征患者肾组织层粘连蛋白α2链异常分布

目的 观察Alport综合征(AS)患者肾组织层粘连蛋白α2链、α5链和γ1链的分布。方法 采用免疫荧光方法,运用普通荧光和激光共聚焦扫描显微镜观察抗层粘连蛋白α2链、α5链和γ1链单克隆抗体在肾组织中的沉积情况。肾组织标本来自11例AS患者,其中男8例,女3例,年龄11~52岁。10例患者符合X伴性显性遗传(XLAS),1例女性患者符合显性遗传。8例男性XLAS患者肾小球基底膜(GBM)、远端肾小管基底膜均无Ⅳ型胶原α3、5链沉积,表皮基底膜(EBM)无α5(Ⅳ)链沉积;2例女性XLAS患者肾组织α3、5(Ⅳ)链和EBM α5(Ⅳ)链均呈不连续表达,另1例女性患者则同正常肾组织。正常人肾组织标本作为正常对照,9例IgA肾病(IgAN)、6例局灶节段硬化性肾小球病(FSGS)、5例薄基膜病(TBMD)和6例肾小球轻微病变(GML)患者作为疾病对照。结果 正常人肾组织层粘连蛋白α2链主要沉积于肾小球系膜区,层连蛋白α5、γ1链沉积于GBM、所有肾小管基底膜和入球小动脉基底膜。10例XLAS和1例显性遗传AS患者肾组织除了肾小球系膜区外,层粘连蛋白α2链在GBM上亦出现表达。IgAN、TBMD和FSGS患者层粘连蛋白α2链仅在肾小球系膜区沉积。层粘连蛋白α5、γ1链在AS患者和其他肾脏病组织沉积同正常肾组织。结论 层粘连蛋白α2链在AS患者GBM出现异位表达,为继Ⅳ型胶原α链异常之后发现的又一AS基底膜成分的异常,其对于AS可能具有重要的诊断价值。     

Serum hepatocyte growth factor levels in patients with renal diseases.

The serum levels of hepatocyte growth factor (HGF) were determined in patients with various renal diseases. In patients with acute-phase acute renal failure (ARF) and chronic tubulointerstitial nephritis (chronic TIN), the serum HGF levels were 0.55 +/- 0.24 and 0.44 +/- 0.37 ng/ml (mean +/- SD), respectively, and were significantly higher than that in the control group (0.12 +/- 0.12 ng/ml). The serum HGF level tended to be high also in patients with active-phase steroid-sensitive nephrotic syndrome (SSNS). The serum levels of HGF were not elevated in patients with IgA nephropathy (IgAN), Henoch-Sch?nlein purpura nephritis (HSPN), membranoproliferative glomerulonephritis (MPGN), poststreptococcal acute glomerulonephritis (PSAGN), unilateral renal atrophy, unilateral nephrectomy, or proximal tubular dysfunction. These observations suggest that glomerular disorders cause no apparent elevation of the serum HGF level, and that elevation of the serum HGF level may be associated with tubulointerstitial damage in renal diseases.     

Evaluation of IgA1 O-glycosylation in Henoch-Schönlein Purpura Nephritis Using Mass Spectrometry

BackgroundGlomerular deposition of IgA1 is a common feature of Henoch-Schönlein purpura nephritis (HSPN) and is indistinguishable from that seen in IgA nephropathy (IgAN). Serum IgA1 is abnormally O-glycosylated in IgA nephropathy, which may contribute to the development of glomerular injury. Abnormal O-glycosylated IgA1 was also detected in HSPN using lectin enzyme-linked immunosorbent assay; however, this method cannot provide the exact structural information of O-glycans. Mass spectrometry is an effective means of quantification of O-glycans, and there is no report to evaluate IgA1 O-glycans in HSPN using mass spectrometry.Materials and MethodsWe investigated O-glycosylation profile in serum IgA1 from 7 HSPN recipients, 26 IgAN recipients, 25 recipients with other kidney diseases (OKDs), and 26 normal healthy donors using mass spectrometry.ResultsOf the 14 GalNac-Gal combinations detected using mass spectrometry, the percentage of the only 6GalNAc-2Gal combination was significantly different between HSPN and IgAN. The percentage of GalNAc 3 in HSPN recipients was significantly higher than that in OKDs recipients and healthy donors (P = .0027 and P < .0001, respectively). Inversely, the percentage of GalNAc 5 in HSPN recipients was significantly lower than that in OKDs recipients and healthy donors (P = .0008, P < .0001, respectively). Moreover, the Gal content and the Gal/GalNAc ratio of HSPN recipients were significantly lower than OKDs recipients and healthy donors.ConclusionsExamination of Henoch-Schönlein purpura recipients revealed that the number of GalNAc fell and the Gal attachment to GalNAc was reduced compared to other kidney diseases and healthy donors. The IgA1 O-glycosylation profile of HSPN was very similar to that of IgAN.     

Spectrum of biopsy-proven kidney diseases in northwest China: a review of 30 years of experiences

Purpose

Large-scale, contemporary studies assessing the spectrum of kidney diseases in northwest China are lacking. Therefore, we aimed to assess the profile of 30-year temporal changes in biopsy-proven kidney diseases in northwest China.

Methods

This cross-sectional study included all patients with a native kidney biopsy specimen in the First Affiliated Hospital of Xi'an Jiaotong University between 1989 and 2018. Data on demographic characteristics and pathological diagnosis were extracted from medical records and pathological reports. Changing patterns of kidney diseases over the study period and disease distributions in different gender and age groups were examined.

Results

This study included 13,620 patients with a mean age of 38.5?±?16.5 years and included 58.2% of men. Primary glomerulonephritis (PGN), second glomerulonephritis (SGN), tubulointerstitial disease, and other renal diseases accounted for 79.1, 18.3, 2.4, and 0.2% of all kidney diseases, respectively. In PGN, IgA nephropathy (IgAN) (25.1%) was the most common type, followed by non-IgA mesangial proliferative glomerulonephritis (MsPGN) (24.9%) and membranous nephropathy (MN) (17.4%). The frequency of MN dramatically increased (p?<?0.001) over the course of the study. Lupus nephritis (6.2%) and Henoch-Schönlein purpura nephritis (HSPN) (4.9%) were leading SGN diagnosis. The frequencies of IgAN, non-IgA MsPGN, and HSPN declined, while those of ANCA/pauci-immune glomerulonephritis and diabetic nephropathy significantly increased.

Conclusion

PGN continues to be the predominant kidney disease in northwest China, and IgAN is the most common type. The frequencies of MN and diabetic nephropathy significantly increased. These findings might be explained by behavioral and environmental exposures and provide implications on future hypothesis-driven research.

     

Glomerular deposition of cross-linked fibrin in human kidney diseases

The immunofluorescent localization of cross-linked fibrin (XFb) in kidneys from 87 patients with renal diseases was evaluated using a monoclonal antibody that discriminates XFb from fibrinogen and its derivatives. Glomerular deposition of XFb, along the endothelial surface and in the mesangium, was frequently observed in patients with IgA nephropathy, Henoch-Sch?nlein purpura nephritis (HSPN), lupus nephritis, and hemolytic uremic syndrome (HUS), which was confirmed by immunoelectron microscopy. Dual-label immunofluorescent studies showed that XFb was deposited in limited areas among the sites reactive with anti-fibrinogen antibodies; XFb was not present in the crescents, Bowman's capsule or interstitium. The localization of XFb was generally discordant with that of the platelet membrane antigen and von Willebrand factor (factor VIII-related) antigen. Subendothelial co-deposition of XFb and immunoglobulins (IgA with or without IgG) occasionally accompanying C3 was found in the glomeruli of some of the patients with IgA nephropathy and HSPN. The distribution of XFb observed by immunoelectron microscopy was similar to that of electron dense deposits. The glomerular population of monocytes/macrophages in patients with XFb deposition was similar to that of those without deposition. Urinary XFb derivatives were detected by the latex agglutination test in three of the 16 patients with glomerular XFb deposition, and in two of the 18 patients without it. These data indicate that the coagulation system is activated in the kidney of patients with IgA nephropathy, HSPN, lupus nephritis and HUS, and support the concept that glomerular fibrin deposition is associated with endothelial/subendothelial and mesangial injury. The activation of the coagulation system in IgA nephropathy and HSPN seems to be mediated by immune complexes rather than monocytes/macrophages. Determination of urinary XFb derivatives is not helpful for assessing glomerular XFb deposition.     

Peripheral blood IgA bearing cells in children with Henoch-Sch?nlein purpura nephritis and IgA nephropathy. Relationship between IgA bearing cells and clinico-pathological findings or T alpha 4 cells]

It has been reported that patients with Henoch-Sch?nlein purpura nephritis (HSPN) and IgA nephropathy (IgAN) showed an familial increase of IgA bearing peripheral blood lymphocyte. To elucidate the relationship between IgA bearing cells and clinico-pathological findings or T cell subsets, especially IgA specific helper T cells (T alpha 4 cells), 20 patients with HSPN and 33 patients with IgAN were studied. The results demonstrated as follows; 1) IgA bearing cells were significantly increased in patients with both HSPN and IgAN (p < 0.001). 2) The increase of IgA bearing cells was well correlated to the degree of patients' proteinuria and hematuria (p < 0.05), and also correlated with the severity of patients' renal pathological findings in both diseases. 3) With relation to the T cell subsets in patients with both diseases, only the CD4+ Leu8- cells (helper T cells) and T alpha 4 cells were significantly increased, in addition, positive correlation between IgA bearing cells and CD4+ Leu8- cells or T alpha 4 cells was observed. 4) The increase of IgA bearing cells seemed to be transient in HSPN, but remained elevated in IgAN. In conclusion, it was indicated that patients with HSPN and IgAN could have IgA related immunological abnormalities, which may be reflected in the increase of IgA bearing cells and T alpha 4 cells. It was also suggested that determination of IgA bearing cells could be a useful parameter which may be reflected in the disease activity of HSPN and IgAN.     

No evidence for pathogenic role of IgE in Henoch-Schoenlein purpura nephritis

Background. The incidence of increased plasma IgE levels was reported to be significantly higher in Henoch-Schoenlein purpura nephritis (HSPN) than in IgA nephropathy (IgAN), and IgE deposits were demonstrated on epidermal Langerhans cells and dermal mast cells in four of six patients with HSPN in two European studies. We designed this study to investigate whether levels of clinical and biological markers of atopy in children with HSPN were significantly higher than those in children with IgAN, non-IgA glomerulonephritis (non-IgAGN), or microhematuria. Methods. The incidence of atopic disease, increased IgE levels, and positive radioallergosorbent test (RAST) results was investigated in 28 children with HSPN, 26 with IgAN, 28 with non-IgAGN, and 30 with microhematuria, all aged 8–16 years. All patients except for those in the microhematuria group, had proteinuria greater than100 mg/dl and had had a kidney biopsy. Results. The incidence of atopic disease, increased IgE levels, and positive RAST results in children with HSPN did not differ from findings in children with IgAN, non-IgAGN, or microhematuria. Conclusion. Our results in Japanese children do not support the idea (suggested by the two European studies) that IgE may play an important role in the pathogenesis of HSPN. Received: February 9, 1998 / Accepted: July 3, 1998     

Studies on Hanganutziu-Deicher antibodies in renal diseases]

H-D antibodies which were known as antibodies detectable in patients with serum sickness have recently been detected in renal diseases. We attempted to detect IgG, IgA and IgM antibodies to N-glycolyl GM3, among other H-D antibodies, by ELISA in various renal diseases and found increased IgM antibody in mesangial proliferative glomerulonephritis, membranoproliferative glomerulonephritis, IgA nephropathy, minimal change nephrotic syndrome and Henoch-Sch?nlein purpura nephritis (HSPN), elevated IgA antibody in IgA nephropathy and HSPN and raised IgG antibody in IgA nephropathy. In 2 cases of IgA nephropathy, there was noted a good correlation between clinical course and anti-N-glycolyl GM3 antibody titers. Measurement by ELISA of IgG antibody to cytomegalovirus (CMV) seemed as one of immune pathogenetic factors of IgA nephropathy showed a high positive rate for this antibody of IgA nephropathy patients and a positive correlation between the antibody and anti-N-glycolyl GM3 antibody. The key molecule of H-D antigens is N-glycolyl neuraminic acid (NGNA) and this sialic acid does not normally exist in humans. One can surmise, therefore, that in those renal diseases in which there was noted an elevation of anti-N-glycolyl GM3 antibody, this antigen is formed or generated by some unknown mechanism. In other words, it may be that humans are not entirely negative for H-D antigens but have a minimum inherent antigenicity and a potential capacity to synthesize these antigens.(ABSTRACT TRUNCATED AT 250 WORDS)     

IgA肾病520例临床病理分析

目的研究IgA肾病(IgAN)的临床和病理特点及其相互关系。方法对1992年11月～2003年6月温州医学院附属第一医院肾内科病理室肾活检诊断的原发性IgAN520例进行临床与病理分型关系的分析。结果520例IgAN临床表现以无症状性尿检异常最常见,占346例(66.5%),其次是慢性肾炎和肾病综合征,分别占77例(14.8%)和66例(12.7%)。病理类型以局灶节段硬化性肾小球肾炎最常见,占186例(35.8%),其次是系膜增生性肾小球肾炎、轻微病变肾小球肾炎和局灶节段增生性肾小球肾炎,分别为116例(22.3%)、104例(20%)和63例(12.1%)。结论IgAN的临床病理表现多样化并具有一定特点。临床表现最常见为无症状性尿检异常,在病理上最常见的是局灶性肾小球病变类型。     

Detection of urinary macrophages expressing the CD16 (Fc gamma RIII) molecule: a novel marker of acute inflammatory glomerular injury

BACKGROUND: The CD16 antigen is the Fc gamma receptor III. CD14+CD16+ cells are proinflammatory monocytes/macrophages (Mo/M phi) that constitute a minor population in the peripheral blood of healthy individuals. Little is known about the expression of CD16 antigen on Mo/M phi in glomerulonephritis. METHODS: Flow cytometric analyses were performed on urine and blood samples obtained from 209 patients with various renal diseases. Patients variously suffered from rapidly progressive crescentic glomerulonephritis (RPGN), membranoproliferative glomerulonephritis (MPGN), postinfectious acute glomerulonephritis (AGN), Henoch-Sch?nlein purpura nephritis (HSPN), IgA nephropathy (IgAN), membranous nephropathy (MN), minimal change nephrotic syndrome (MCNS), lupus nephritis (LN), acute interstitial nephritis, hereditary nephropathy, idiopathic renal hematuria (IRH), and renal stone. RESULTS: The CD16+ M phi population of cells was present in the urine of hematuria-positive patients with proliferative glomerulonephritis, including AGN, IgAN, RPGN, MPGN, and LN with acute inflammatory lesions, such as endocapillary proliferation, tuft necrosis, and cellular crescents. In contrast, the urinary CD16+ M phi population was negligible in hematuria-positive patients with nonproliferative renal disease, including hereditary nephropathy, IRH, and renal stone and also in patients with proliferative glomerulonephritis lacking acute inflammatory lesions. Total urinary M phi of these patients were much less than those of patients having proliferative glomerulonephritis with acute inflammatory lesions. Transient expansion of the CD16+ M phi population in urine was observed during the acute exacerbation of urinary abnormalities, whereas the disappearance of CD16+ M phi closely preceded the amelioration of urinary abnormalities in patients with proliferative glomerulonephritis. In 38 of the 98 patients positive for CD16+ M phi population in urine, the CD16+ Mo population was negligible in peripheral blood. Immunohistochemically, CD16+ M phi were present in the glomeruli of active proliferative glomerulonephritis, whereas such cells were absent in inactive proliferative glomerulonephritis or nonproliferative glomerular diseases. CONCLUSION: CD16+ M phi may be effector cells involved in the acute inflammation common to all types of proliferative glomerulonephritis. Furthermore, the detection of CD16+ M phi in urine, as well as urinary M phi counts, may serve as a useful indicator of the active stage of proliferative glomerulonephritis.     

Monocyte infiltration and cross-linked fibrin deposition in IgA nephritis and Henoch-Schoenlein purpura nephritis

To clarify the role of immune cell infiltration and fibrin deposition in glomerular injury, renal biopsy specimens taken from patients with primary IgA nephritis and Henoch-Sch?nlein purpura nephritis (HSPN) were evaluated using monoclonal antibodies specific to mononuclear cell surfaces and cross-linked fibrin (XFb). Monocytes/macrophages were the predominant cell type infiltrating glomeruli in IgA nephritis and HSPN. The intraglomerular monocyte population in both diseases was significantly higher than that in normals, mesangial proliferative (non-IgA) glomerulonephritis or minimal change nephrotic syndrome. In IgA nephritis, there was a clear correlation between glomerular monocyte accumulation and the degree of proteinuria. Although the monocyte influx tended to decline with time in HSPN, it remained unchanged in IgA nephritis. XFb deposition was found in the glomeruli of 27 out of 48 patients with IgA nephritis, and in 15 out of 20 with HSPN. The degree of XFb deposition in IgA nephritis correlated significantly with the degree of mesangial proliferation. These findings indicate a close relationship of monocyte/macrophage infiltration and XFb deposition with glomerular injury in IgA nephritis.     

Antimouse laminin antibodies in IgA nephropathy and various glomerular diseases.

IgG, IgA and IgM class antibodies to mouse laminin and human fibronectin in sera from patients with various glomerular diseases (50 cases of IgA nephropathy, 5 cases of minimal-change nephrotic syndrome; 6 cases of membranous nephropathy, 5 cases of systemic lupus erythematosus, 2 cases of Henoch-Sch?nlein purpura, 3 cases of poststreptococcal nephritis and 4 cases of preeclampsia) and from 30 normal controls were tested using a solid-phase enzyme-linked immunosorbent assay method. IgA antimouse laminin antibody titers in sera from IgA nephropathy patients were significantly higher (p less than 0.05) than in controls. There were no statistical differences in IgA antimouse laminin antibody titers between patients with other glomerular diseases and normal controls. IgM antimouse laminin antibody was significantly raised (p less than 0.01) in sera from patients with preeclampsia. The reaction of mouse laminin with the IgA nephropathy and preeclampsia sera on each of the IgA and IgM assay systems was inhibited by the antigen at up to 5 micrograms/ml. However, it was not inhibited by anti-C3d, anti-C1q, anti-J chain and antisecretory component sera or saccharides. The reaction of mouse laminin with an exceptionally high-titer IgA antimouse laminin antibody serum from a normal control on the IgA assay system was clearly inhibited by 1 mM of melibiose, which contains alpha-galactosyl residues. The same concentration of melibiose, however, did not inhibit the reaction of mouse laminin with IgA nephropathy sera on the same assay system. Treatment of mouse laminin with alpha-galactosidase did not alter any binding from IgA nephropathy sera but binding was lost from an exceptionally high-titer normal control serum. There were no correlations between serum IgA level and IgA antimouse laminin antibody titer in sera from IgA nephropathy patients. Immunoblot techniques revealed the presence of antibody in sera from IgA nephropathy patients reacting with both subunits A and B of laminin, somewhat stronger with laminin A. None of the sera tested contained antifibronectin antibodies. These results indicate that the IgA antimouse laminin antibody is a specific antibody in IgA nephropathy and might play a role in the pathogenesis of the nephritis since mouse laminin and human mesangial laminin present a common epitope.     

白细胞介素1受体拮抗剂等位基因与紫癜性肾炎和IgA肾病的相关联系

目的 为了进一步阐明紫癜性肾炎(HSPN)及IgA肾病(IgAN)二者在发病机理上可能存在的联系。方法 用PCR方法对43例HSPN,97例IgAN患者和98名正常人IL-l受体拮抗剂(IL-lra)基因数目可变的串联重复(VNTR)多态性进行了分析。结果 HSPN患者白细胞介素l受体拮抗剂等位基因(IL IRN 2)的携带率明显高于正常人(P<0.02)和IgAN患者(P<0.05)。在IgAN患者中表现为反复发作性肉眼血尿者其IL IRN 2等位基因的携带率明显高于其它临床类型IgAN患者(P<0.o1),而与HSPN无显著性差异(P>0.05)。结论 HSPN患者IL-lra基因特定的遗传背景在其发病机理中可能起一定作用。IgAN患者中表现为反复发作性肉眼血尿者较其它临床类型IgAN患者与HSPN有更多的相似之处,而ILlRN 2等位基因高携带率可能是二者发病机理的共同点之一。     

In situ evaluation of podocin in normal and glomerular diseases

BACKGROUND: Mutations of the NPHS2 gene are responsible for autosomal-recessive steroid-resistant nephrotic syndrome. Its product, podocin, faces the slit diaphragm area with its two ends in the cytoplasm of foot processes. METHODS: We generated rabbit polyclonal antibodies against conjugated peptides from human podocin N- and C-termini, and studied podocin and synaptopodin using kidney tissues of normal humans and those with glomerular diseases. RESULTS: Antipodocin antibodies detected the original 42 kD fragment and an extra smaller fragment by Western blot analysis using human isolated mature glomeruli. RNA analysis showed two bands, the original and the other of a decreased length. Immunohistochemically, podocin was detected in a linear pattern along the glomerular capillary loop. Antipodocin antibody (C-terminal) stained the smooth muscles of renal arterioles and aorta. Among 42 patients, podocin was normally expressed in glomeruli in purpura nephritis, IgA nephropathy (IgAN), and minimal-change disease (MCD), while it was either decreased or absent in most subjects with focal segmental glomerulosclerosis (FSGS). The expression of synaptopodin was similar to that of podocin, although some discrepancy existed. CONCLUSION: Although indirect, our data suggest the existence of a vascular isoform of podocin with a different molecular mass. We propose that examination of podocin expression may help differentiate MCD from FSGS.     

What is the difference between IgA nephropathy and Henoch-Schönlein purpura nephritis?

Henoch-Sch?nlein purpura nephritis (HSPN) and IgA nephropathy (IgAN) are considered to be related diseases since both can be encountered consecutively in the same patient, they have been described in twins, and bear identical pathological and biological abnormalities. Apart from the presence of extrarenal clinical signs found only in HSPN, other differences are noticed between the two diseases. The peak age ranges between 15 and 30 years for a diagnosis of IgAN, whereas HSPN is mainly seen in childhood. Nephritic and/or nephrotic syndromes are more often seen at presentation in HSPN. In contrast to IgAN, HSPN has been described in association with hypersensitivity. Endocapillary and extracapillary inflammations as well as fibrin deposits in the glomerulus are more frequent in HSPN. No major biological differences have been found between the two illnesses, except for a larger size of circulating IgA-containing complexes (IgA-CC) and a greater incidence of increased plasma IgE levels in HSPN. As tissue infiltration by leukocytes is a major feature of HSPN vasculitis, a possible role of a more potent activation of the latter cells by IgA-CC and/or circulating chemokines in HSPN should be considered. Further studies are required to elucidate this possible mechanism as well as the role of hypersensitivity in HSPN.