Urine protein patterns can serve as diagnostic tools in patients with IgA nephropathy

BACKGROUND: IgA nephropathy (IgAN) is the most common chronic glomerular disease in adults. End-stage renal disease (ESRD) develops in about 30% of the patients. Early intervention and consequent therapy may prevent or at least delay the development of ESRD in these patients. Up to now, the diagnosis could only be achieved with a renal biopsy. METHODS: The urine of 45 patients with IgAN was collected and screened for protein/polypeptide patterns with a novel high throughput method, capillary electrophoreses on-line coupled to a mass spectrometer (CE-MS). CE-MS allows the fast and accurate evaluation of up to 2000 polypeptides in one urine sample. The results in IgAN were compared to findings in 13 patients with membranous nephropathy (MN) and 57 healthy individuals. RESULTS: In the patients with IgAN, even when urinary protein excretion was within the normal range of regular tests, the polypeptide pattern in urine differed significantly from that of healthy controls and patients with MN, indicating a specific "IgAN" pattern of polypeptide excretion. Classification regarding discrimination of IgAN from healthy controls and from MN had a sensitivity of 100% and 77%, respectively. Specificity was 90% and 100%, respectively. Compared to patterns established earlier in patients with minimal change disease (MCD), focal segmental glomerulosclerosis (FSGS), or diabetic nephropathy (DN), sensitivity and specificity were 100%. Treatment of the patients was associated with changes of the pattern, possibly indicating a therapeutic effect. CONCLUSION: Proteomic analysis with CE-MS coupling permits fast and accurate identification and differentiation of polypeptide patterns in the urine of patients with IgAN, allowing differentiation from healthy controls and, probably, other renal diseases.     

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.     

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.     

Do current recommendations for kidney biopsy in nephrotic syndrome need modifications?

The current recommendations of kidney biopsy in childhood idiopathic nephrotic syndrome (CINS) were put forward to minimize unnecessary kidney biopsies in underlying minimal change disease (MCD). However, there remains a diversity of opinion about the criteria for biopsying children with idiopathic nephrotic syndrome. This study was conducted to prospectively study their usefulness in avoiding biopsies in MCD and to evaluate further modifications for minimizing biopsies in CINS. Of 400 consecutive CINS patients, 222 patients were subjected to kidney biopsy according to the current recommendations. The histopathology spectrum of these selectively biopsied children revealed focal segmental glomerulosclerosis (FSGS) in 39%, MCD in 34.2%, membranoproliferative glomerulonephritis (MPGN) in 16.2%, mesangioproliferative glomerulonephritis (MesPGN) in 7.6%, membranous nephropathy (MN) in 1.8%, and diffuse mesangial sclerosis (DMS) in 0.9%. We observed that despite the current recommendations and efforts to minimize biopsy, 34% of children had MCD on histopathology. Two or more clinical (hematuria and hypertension) or biochemical (renal insufficiency) parameters were present in all children with MPGN. Low C3 was present only in children with MPGN. All the steroid responders were found to have MCD, FSGS, or MesPGN on biopsy. Cyclophosphamide response correlated better with steroid responsiveness (P=0.02) than with histo- pathology (P=0.80) in MCD, FSGS, and MesPGN. Based on these observations, we suggest some modifications in current recommendations for kidney biopsy to minimize biopsying children with MCD. These are (1) biopsies in children (age 1–16 years) should be restricted (a) to a subgroup with two or more clinical and biochemical parameters and (b) in steroid non-responders, (2) the decision to administer cyclophosphamide should be based on steroid response pattern without requiring a prior routine biopsy. Received: 16 July 1999 / Revised: 20 November 2001 / Accepted: 24 November 2001     

豫琼两地原发性肾小球疾病病理类型的变迁对比及临床分析

目的 回顾性分析豫北地区及海南两地近12年原发性肾小球疾病疾病谱的构成演变特点及其意义.方法 分别收集2008年1月至2019年12月于新乡医学院第一附属医院及海南医学院第一附属医院经临床及肾活检诊断为原发性肾小球疾病3985例患者的临床及病理资料,并对其进行对比分析,根据年份分为2008年至2011年、2012年至2...     

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。     

Characteristics of patients with coexisting IgA nephropathy and membranous nephropathy

Background: Coexistence of IgA nephropathy (IgAN) and membranous nephropathy (MN) in the same patient is rare. Few studies have reported the clinical and pathological features of patients with combined IgAN and MN (IgAN–MN).

Methods: The clinico-pathological features, levels of galactose-deficient IgA1 (Gd-IgA1) and autoantibodies against M-type transmembrane phospholipase A₂ receptor (anti-PLA₂R) in sera were compared among IgAN–MN, IgAN, and MN patients.

Results: Twenty-six patients with biopsy-proven IgAN–MN were enrolled. The mean age at biopsy was 43.6?±?15.9?years, and 65.4% were male. Proteinuria and estimated glomerular filtration rate (eGFR) levels in patients with IgAN–MN were similar to that of MN patients. Compared with the IgAN patients, IgAN–MN patients showed a higher median proteinuria level (4.3 vs. 1.2?g/day, p?2, p?p?=?.801). Percentage of IgAN–MN patients with detectable serum levels of anti-PLA₂R was lower than that of MN patients (38.5% vs. 68.6%, p?=?.011).

Conclusions: IgAN–MN patients display similar clinical features to MN patients and milder pathological lesions than IgAN patients. IgAN–MN patients have similar levels of Gd-IgA1 to those of IgAN patients, and a lower proportion of anti-PLA₂R than MN patients.     

Characterization of kidney lesions in Indian adults: towards a renal biopsy registry

BACKGROUND: In the absence of a renal biopsy registry, there is a paucity of data on the renal disease pattern seen in India. This study reviews the changing pattern of renal disease seen at a single center over the last 30 yrs. METHODS: Histopathological data of 5415 adequate native kidney biopsies performed on consecutive adult Indian patients presenting to our hospital from 1986-2002 were analyzed. This pathological demography classified according to the modified World Health Organization (WHO) classification was compared to the earlier published cohort collected from 1971-1985 (n=2827) to ascertain the changing trends. RESULTS: The indications for renal biopsy were comparable between the cohorts and included nephrotic syndrome (65%), nephritic syndrome (13%) and chronic renal failure (10.2%). Primary glomerular disease accounted for 71% of all biopsies. Non-immunoglobulin A (IgA) mesangio proliferative glomerulonephritis as a group was the predominant pathology (20.2%), followed by idiopathic focal segmental glomerulosclerosis (FSGS) (17%), minimal change disease (MCD) (11.6%), membranous glomerulopathy (MN) (9.8%), IgA nephropathy (8.6%) and membranoproliferative glomerulonephritis (MPGN) (3.7%). Of the patients with secondary kidney diseases, lupus nephritis (6.5%), diabetic nephropathy (2.5%), interstitial nephropathy (2.5%) and benign nephrosclerosis (2.2%) were notable. During the 31 yrs of the study period, there was a steady increase in FSGS prevalence (p<0.001), MN (p<0.0001), and post infectious glomerulonephritis (PIGN) (p<0.001). A reduction in the frequency of MPGN (p<0.001) and MCD (p<0.001) was observed. CONCLUSIONS: This is the largest series of renal biopsy data from India; and therefore, could reflect the demographic picture of renal diseases in this country. It discusses evolving patterns over 30 yrs and highlights differences with the developed world. This report represents the basis for the future of a renal biopsy registry in India.     

The Czech registry of renal biopsies. Occurrence of renal diseases in the years 1994-2000.

BACKGROUND: This report describes data collected by the Czech Registry of Renal Biopsies (CRRB). METHODS: Twenty-eight centres provided data on all biopsies of native kidneys performed in the Czech Republic (population 10.3 million) over the period 1994-2000. Data on serum creatinine concentration (sCr), 24 h proteinuria, haematuria, serum albumin level, arterial hypertension, diabetes mellitus, histological diagnosis and complications after renal biopsy were collected. RESULTS: Altogether 4004 biopsies in 3874 patients were performed (males 57.9%, children < or = 15 years 17.7%, elderly >60 years 14.3%). Microhaematuria was present in 65.9%, macrohaematuria in 9.2%, nephrotic proteinuria (> or = 3.5 g/24 h) in 39.3%, and low-grade proteinuria (<3.5 g/24 h) in 41.4%. Among adults, hypertension was present in 45.2%, mild renal insufficiency in 23% (sCr 111-200 micromol/l) and advanced renal insufficiency in 13.7% (sCr 201-400), while 11.5% of patients had sCr >400 micromol/l. The most frequent renal diseases were primary (59.8%) and secondary (25.4%) glomerulonephritis (GN). Tubulointerstitial nephritis (TIN) was observed in 4.4% and hypertensive nephroangiosclerosis in 3.4%. The samples were non-diagnostic in 4.6%. Among primary GNs, the most frequent diagnoses were: IgA nephropathy (IgAN) 34.5%, minimal change disease (MCD) 12.4%, non-IgA mesangioproliferative GN (MesGN) 11.3%, focal segmental glomerulosclerosis (FSGS) 10.8% and membranous GN (MGN) 9.3%. Among secondary GNs, systemic lupus erythematosus (SLE) represented 23.0%, necrotizing vasculitis (NV) 15.5%, Henoch-Schonlein purpura 5.7%, thin basement membrane glomerulopathy (TBN) 19.3%, Alport syndrome 6.9%, renal amyloidosis 9.9% and myeloma kidney 2.9%. Among children, the most common were IgAN (19.2%), MCD (17.6%) and TBM glomerulopathy (12.3%), while among the elderly the most common were MGN (11.0%), NV (10.7%) and amyloidosis (9.6%). The most common in patients with nephrotic proteinuria were MCD (50.5%) among children, but IgAN (24.6%) in adults aged 16-60 years and MGN (16.8%) among the elderly. IgAN (21.3%) and FSGS (8.3%) were the most common diagnoses among patients with mild renal insufficiency, but TIN (11.6%) and NV (11.3%) were the most common in more advanced renal insufficiency. Since 1999, diabetic patients represented 12.2% of adults, with mean proteinuria 8.9 g/24 h; diabetic glomerulosclerosis was found in 42.4% (with microhaematuria present in 66%) and non-diabetic renal diseases in 47.5% (IgAN in 17.5%, MGN and NAS in 11.1% and NV in 9.5%). The mean annual incidence (per million population) was: primary GN 32.4, secondary GN 13.8, IgAN 11.2, MCD 4.0, MesGN 3.7, FSGS 3.5, SLE 3.2, MGN 3.0, TBM 2.7, TIN 2.4 and NV 2.1. Ultrasound needle guidance was used in 56%, preferably in children (79%). The frequency of serious complications (gross haematuria, symptomatic haematoma, blood transfusion) remained at 3%. CONCLUSION: The CRRB provides important data on the epidemiology of GN based on a whole country population.     

Reduced podocin expression in minimal change disease and focal segmental glomerulosclerosis is related to the level of proteinuria

Background

Glomerular podocyte molecules are involved in the pathogenesis of congenital nephrotic syndrome. However, their role in primary nephrotic syndrome is not clear. This study investigated the expression of nephrin, podocin and synaptopodin in primary nephrotic syndrome.

Methods

Eighty-seven patients with primary nephrotic syndrome including minimal change disease (MCD), focal segmental glomerulosclerosis (FSGS), membranous nephropathy (MN) and membranoproliferative glomerulonephritis Type I (MPGN) were included in the study. Glomerular expression of nephrin, podocin and synaptopodin was studied in renal biopsies by immunofluorescence and immunohistochemistry. Correlation of expression with clinical and biochemical parameters was performed.

Results

The pattern of expression for all podocyte proteins in controls was uniform fine granular along the capillary walls towards the visceral epithelial cell aspect. Glomerular expression of nephrin was present in all renal biopsies and was similar to that in controls. Glomerular synaptopodin expression was seen in all MN and MPGN patients, while it was seen in 74 % (17/23) MCD and 93.5 % (29/31) FSGS. Reduced synaptopodin expression showed no correlation with clinical and biochemical factors. Podocin expression was present in 5/23 MCD (22 %), 3/31 FSGS (9.6 %), 13/17 MN (76.4 %) and 13/16 MPGN (81 %) patients. The reduced expression of podocin significantly correlated with the degree of proteinuria (p = 0.032). No correlation with age, gender and serum creatinine level was observed.

Conclusion

Reduction of glomerular podocin expression found in MCD and FSGS is related to the amount of proteinuria. Our findings suggest that alteration in podocyte phenotype may not be a primary event and may reflect the degree of podocyte injury in primary nephrotic syndrome.     

Impact of Immunofluorescence on the Histological Pattern of Pediatric Kidney Biopsies from Northern Pakistan

Abstract

Kidney biopsy is an investigation for diagnosis and prognosis of a variety of nephritides. It also influences therapeutic options. Immunofluorescence (IMF) greatly adds in identifying the pathologies which may not be obvious on light microscopy (L/M), such as IgM, IgA nephropathy, pauci-immune glomerulonephritis, and anti-glomerular basement membrane disease. We present here data of 170 pediatric kidney biopsies from July 2005 to December 2009 from Department of Nephrology and Hypertension, Lady Reading Hospital, Peshawar, Pakistan. The study was undertaken to see whether IMF would alter the histological pattern of pediatric kidney biopsies and to compare these data with an earlier data from our department of 415 pediatric kidney biopsies done over 7-year period from 1998 to 2005, which were analyzed with L/M alone. Out of 170 kidney biopsies using L/M and IMF, IgM turns out to be most common pattern (20%), followed by minimal change disease (MCD) (17.05%), focal and segmental glomerulosclerosis (FSGS) (15.88%), chronic sclerosing glomerulonephritis (Chr. sclerosing GN) (12.35%), mesangio proliferative glomerulonephritis (MPGN) (7.65%), mesangio capillary glomerulonephritis (MCGN) (6.47%), membranous glomerulonephritis (Mem. GN) (5.29%), IgA nephropathy (5.29%), cresentic glomerulonephritis (Cres. GN) (3.53%), lupus nephritis (2.96%), and others (3.53%). Comparing these results of 170 cases with 415 renal biopsies without IMF, IgM dominated the histological pattern in IMF group whereas MCD followed by FSGS and MPGN were prominent in group without IMF. Therefore, variation in the overall histological pattern with IMF technique proved statistically significant (p < 0.0001). Addition of IMF has altered the frequency of MCD, a change from 24% (100/415) to 17% (29/170), FSGS from 18.3% (76/415) to 15.88% (27/170), and MPGN from 17.35% (72/415) to 7.65% (13/170).     

间质纤维化评分在不同病理类型所致的肾病综合征患者中的临床意义及其与肾脏预后的关系

目的 分析间质纤维化评分在不同病理类型所致的肾病综合征患者中的临床意义及其与肾脏预后的关系.方法 选取2016年5月至2018年9月本院收治的298例肾病综合征患者,包括经活检证实的微小病变肾病(MCD)患者92例、局灶节段性肾小球硬化(FSGS)患者114例、膜性肾病(MN)患者56例和IgA肾病(IgAN)患者36...     

Japan Renal Biopsy Registry: the first nationwide, web-based, and prospective registry system of renal biopsies in Japan

Background

The Committee for the Standardization of Renal Pathological Diagnosis and the Working Group for Renal Biopsy Database of the Japanese Society of Nephrology started the first nationwide, web-based, and prospective registry system, the Japan Renal Biopsy Registry (J-RBR), to record the pathological, clinical, and laboratory data of renal biopsies in 2007.

Methods

The patient data including age, gender, laboratory data, and clinical and pathological diagnoses were recorded on the web page of the J-RBR, which utilizes the system of the Internet Data and Information Center for Medical Research in the University Hospital Medical Information Network. We analyzed the clinical and pathological diagnoses registered on the J-RBR in 2007 and 2008.

Results

Data were collected from 818 patients from 18 centers in 2007 and 1582 patients from 23 centers in 2008, including the affiliated hospitals. Renal biopsies were obtained from 726 native kidneys (88.8%) and 92 renal grafts (11.2%) in 2007, and 1400 native kidneys (88.5%) and 182 renal grafts (11.5%) in 2008. The most common clinical diagnosis was chronic nephritic syndrome (47.4%), followed by nephrotic syndrome (16.8%) and renal transplantation (11.2%) in 2007. A similar frequency of the clinical diagnoses was recognized in 2008. Of the native kidneys, the most frequent pathological diagnosis as classified by pathogenesis was immunoglobulin (Ig) A nephropathy (IgAN) both in 2007 (32.9%) and 2008 (30.2%). Among the primary glomerular diseases (except IgAN), membranous nephropathy (MN) was the most common disease both in 2007 (31.4%) and 2008 (25.7%).

Conclusions

In a cross-sectional study, the J-RBR has shown IgAN to be the most common disease in renal biopsies in 2007 and 2008, consistent with previous Japanese studies. MN predominated in the primary glomerular diseases (except for IgAN). The frequency of the disease and the clinical and demographic correlations should be investigated in further analyses by the J-RBR.     

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.

     

呈局灶节段性肾小球硬化的IgA肾病临床病理特点

目的探讨呈局灶节段性肾小球硬化（FSGS）的IgA肾病（IgAN）的临床和病理特点。方法选取我院1988年1月至2002年2月经肾活检确诊为IgAN的患者587例，其中呈FSGS85例，呈弥漫性系膜增生性肾小球肾炎（MsPGN）162例，呈弥漫性系膜增生性肾小球肾炎伴局灶节段性肾小球硬化（MsPGN伴FSGS）185例，比较3种类型IgAN临床和病理资料。结果FSGS型IgAN占同期所有IgAN的14．5％，临床类型以大量蛋白尿型为主，占37．64％。肾小球球囊黏连发生率高达74．12％，小管间质纤维化发生率97．65％，病理分级以LeeⅣ～Ⅴ级为主，免疫病理以IgA—MG型为主，与MsPGN伴FSGS型和MsPGN型的IgAN相比，FSGS型IgAN病程较长，高血压、肾功能不全发生率较高（P〈0．05），而血尿的发生率与后两者无明显区别。结论呈FSGS型IgAN大量蛋白尿、高血压、肾功能不全的发生率高，病变较重，预后较差。     

Primary glomerular diseases in Brazil (1979-1999): is the frequency of focal and segmental glomerulosclerosis increasing?

AIMS: Different patterns of glomerulonephritis (GN) are reported from all over the world and the occurrence of primary GN is changing in the course of time. We report the frequencies of primary GN in a major teaching hospital in Brazil, from 1979-1999. METHODS: The case files of renal biopsies of primary GN were reviewed. The included patients were > 14 years of age, with native kidneys, and the specimens were examined with at least light and immunofluorescence microscopy. We excluded biopsy results of patients with any kind of known secondary glomerular involvement. Differences in proportions of diagnoses between the periods over time were evaluated using Chi-square test for trend. RESULTS: We considered 943 patients for the analysis. Focal and segmental glomerulosclerosis (FSGS) was the most common lesion (n = 279), followed by membranous GN (n = 140), membranoproliferative type I GN (n = 109) and IgA nephropathy (n = 109). FSGS (32.1%) was the most frequent diagnosis among nephrotic patients whereas IgAN (29.4%) predominated in non-nephrotic ones. The occurrence of FSGS increased from the earlier to the later periods: 22.3% (1979-1983), 23.7% (1984-1988), 35.7% (1989-1993), 33.9% (1994-1999), p < 0.05. The increase in frequency of FSGS was proportionally higher in non-nephrotic patients and FSGS became as common as IgA nephropathy in this group (31.6% and 28.0%, respectively) from 1994-1999. CONCLUSIONS: FSGS was the most common pattern of primary glomerulonephritis and its relative frequency seems to be increasing in biopsied patients over time. The reasons for this behavior are unclear and warrant further investigations.     

儿童隐匿性肾炎的临床和病理研究

目的：探讨儿童隐匿性肾炎的临床和肾组织病理改变特点及其关系。方法：回顾性分析肾活检的323例隐匿性肾炎患儿的临床和肾组织病理改变情况。结果：323例隐匿性肾炎患儿中，单纯性血尿229例，单纯性蛋白尿19例，血尿伴蛋白尿75例。肾组织病理改变类型包括：轻微病变103例（31，89％）、基本正常74例（22．91％）、IgA肾病（IgAN）73例（22．60％）、薄基底膜病（TBMN）27例（8．36％）、系膜增生性肾炎（MsPGN）18例（5．57％）、局灶增生性肾炎（FPGN）10例（3．10％）、膜性肾病（MN）8例（2，48％）、局灶节段肾小球硬化（舢）8例（2．48％）、微小病变（MCD）1例（0，31％）、IgM肾病（IgMN）1例（0．31％）。单纯性血尿组中肾组织结构基本正常的比例较血尿伴蛋白尿组明显偏高（P〈0，01）；血尿伴蛋白尿组中IgAN的比例高于单纯性血尿组和单纯性蛋白尿组（分别P〈0．01、P〈0．05）。IgAN的Lee分级：单纯性血尿组中Ⅰ、Ⅱ级85．00％，Ⅲ级及以上15．00％；血尿伴蛋白尿组中Ⅰ、Ⅱ级58．10％，Ⅲ级及以上41．90％，明显高于单纯性血尿组（x^2=6．47，P〈0．05）。结论：儿童隐匿性肾炎的病理以轻微病变、基本正常、IgAN为常见表现，血尿伴蛋白尿患儿病变较单纯性血尿患儿为重。     

Focal segmental glomerulosclerosis plays a major role in the progression of IgA nephropathy. I. Immunohistochemical studies

IgA nephropathy (IgAN) often shows lesions morphologically identical with those of focal segmental glomerulosclerosis (FSGS). In order to determine the possible role of FSGS in IgAN lesions, we measured glomerular capsular adhesions, often the first step toward FSGS, in biopsies from 127 patients with IgAN, 100 with lupus nephritis, and 26 with primary FSGS. Capsular adhesions with no lesions in the underlying tuft, consistent with podocyte abnormality or loss, were found regularly in FSGS and IgAN, but infrequently in lupus. Fifteen biopsies of patients with IgAN were studied immunohistochemically using markers for podocytes, Bowman's parietal epithelial cells, proliferating cells, and macrophages. Cytokeratins CK-8 and C2562 differentiated normal podocytes (negative) from parietal epithelial cells (variably positive). There was focal loss of the podocyte markers synaptopodin, glomerular epithelial protein 1 (GLEPP-1), nephrin, and vascular endothelial growth factor (VEGF), particularly at sites of capsular adhesions in otherwise histologically normal glomeruli. Cells displaying the parietal epithelial cell markers PAX2 (paired box gene 2) and the cytokeratins were also positive for the proliferating cell marker, proliferating cell nuclear antigen. These cells gathered at sites of adhesion, and in response to active lesions in the tuft, grew inward along the adhesion onto the tuft, forming a monolayer positive for parietal markers and the podocyte marker Wilms tumor protein-1 (WT-1). These cells deposited a layer of collagen over the sclerosing tuft. Thus, all biopsies of patients with IgAN had changes basically identical to those classically described in FSGS. Hence, our study strongly suggests that podocytopathy of a type similar to that in primary FSGS occurs frequently in IgAN.     

肾病综合征患者肾组织podocin的表达

目的 观察不同病理类型&#65380; 不同激素反应性肾病综合征(NS)患者肾小球足细胞中podocin的表达和分布特征&#65377;方法 肾组织作冰冻切片免疫荧光双染色, 以激光共聚焦显微镜采集图像&#65377;与定位标志Ⅳ型胶原α3链比较&#65377; 受检NS患者21例, 其中局灶节段性肾小球硬化(FSGS)12例(难治性7例, 非难治性5例)&#65380; 微小病变(MCD)5例&#65380; 膜性肾病(MN)4例;正常肾组织对照3例&#65377;采用LSM 510图像处理系统进行处理&#65377;荧光强度以吸光度表示&#65377; 结果 (1)podocin在正常肾组织沿肾小球基底膜呈连续&#65380; 线形分布&#65377;部分FSGS患者podocin的分布呈点状&#65380; 短线条状, 少数患者未见podocin沉积&#65377;(2)FSGS患者肾小球中podocin表达量(80.5±33.5)与对照正常肾组织(138.4±38.1)比较,显著减少(P=0.0211), 其中难治性FSGS(67.2±30.5)与正常肾组织的差异有统计学意义(P=0.0131); 非难治性FSGS患者(99.0±31.0)与正常肾组织的差异无统计学意义(P=0.1585)&#65377;(3)MCD(112.1±47.6)&#65380; MN(92.5±34.8)患者podocin的表达量亦降低,与正常肾组织比较,无统计学意义(P=0.4497, P=0.1570)&#65377;(4)不同病理类型各组NS患者肾小球中podocin表达量的差异均无统计学意义(P > 0.05)&#65377;结论 FSGS的NS患者肾小球中podocin的表达减少, 难治性FSGS患者尤为明显, 部分FSGS患者podocin分布发生改变&#65377;podocin的检测可能在FSGS激素疗效评价方面有一定价值&#65377;     

Human cytomegalovirus in immunoglobulin A nephropathy: detection by polymerase chain reaction.

Human cytomegalovirus (HCMV) has been suspected to participate in the pathogenesis of IgA nephropathy (IgAN). However, with regard to the presence of HCMV in the renal tissue of IgAN, conflicting results have been reported using a variety of different techniques. Renal biopsies of 29 patients with IgAN, of 7 with focal segmental glomerulosclerosis (FSGS) and of 11 normal kidneys were analyzed for the presence of HCMV-DNA using the polymerase chain reaction. HCMV-DNA was detected by hybridization with digoxigenin-labelled probes in 14 of 19 analyzed frozen renal biopsies from patients with IgAN. However, only 1 of 17 renal biopsies of IgAN embedded in paraffin was positive for HCMV-DNA. Furthermore, HCMV-DNA was detected in 4 of 18 frozen normal kidneys but in none of the tissues from patients with FSGS. The present results provide further evidence of an association between the presence of HCMV in renal tissue and IgAN.