Clinical and histopathological characteristics of biopsy-proven renal diseases in Croatia

There is little data on the spectrum of renal diseases in children in Croatia. The Croatian Society for Pediatric Nephrology has established the Registry of Biopsy-Proven Renal Diseases in an attempt to address this issue nationwide. Here we report preliminary results of a retrospective analysis of clinical and histopathological data of 565 children aged < or =17 years presenting to 9 hospitals in Croatia from 1991 to 2004, in whom kidney biopsy was performed. The most common indication for renal biopsy was nephrotic syndrome (39.1%), followed by asymptomatic proteinuria/hematuria (22.0%) and acute nephritic syndrome (17.0%). All biopsies were analysed by light-, immunofluorescent and electron microscopy. The majority of children, 552 out of 565 (92.4%), had glomerulonephritis (GN). Tubulointerstitial nephritis was found in 16 (2.8%), congenital renal parenchyma anomalies in 14 (2.5%) and vascular disease in 11 (1.9%) cases. One (0.2%) child had sarcoidosis with nephrocalcinosis. The sample was non-diagnostic in 1 (0.2%) case. Among children with GN, primary GN accounted for 70.9%, secondary GN for 16.1% and hereditary GN for 13.0% cases. The most frequent primary GN forms were focal segmental glomerulosclerosis (FSGS) (24.6%), mesangial proliferative glomerulonephritis (MEPGN) (19.2%) and IgA nephropathy (18.1%). Acute GN in resolution was found in 11.1% and minimal changes GN in 6.8% of cases. Most children with secondary GN had nephritis of Henoch-Sch?nlein purpura (HSP) (54.7%) and nephritis of systemic lupus erythematosus (SLE) (40.5%), while among hereditary GN Alport syndrome was most common (80.9%). In the group of children with primary GN who presented with nephrotic syndrome, most common forms were FSGS (38.5%) and MEPGN (24.0%). Minimal changes GN accounted for only 10.9% of cases. IgA nephropathy, primary or related to HSP (20.0%), FSGS (16.1%), MEPGN (12.6%) and Alport syndrome (9.7%) were the most common biopsy-proven renal diseases in Croatian children. The analysis provided data on the frequency of histological renal lesions in children in Croatia. The higher frequency of FSGS and MEPGN among Croatian children in comparison with other countries deserves further evaluation.     

Childhood nephrotic syndrome: change in pattern and response to steroids

BACKGROUND: In our center, childhood nephrotic syndrome (NS) had been reported for over a decade to be steroid sensitive contrary to reports in other parts of Nigeria. The purpose of this study was to determine if there are changes in presentation and response to steroids, with reviews of the literature on NS. METHODS: Analysis of 28 patients seen at the University of Port Harcourt Teaching Hospital, Nigeria, from 1999-2004 with the diagnosis of NS was performed. RESULTS: There were 14 girls and 14 boys with NS. The peak age was 1-4 years. Twenty (71.4%) children had idiopathic nephrotic syndrome (INS). Four had chronic renal failure, one had sickle cell disease (HbSS), two were positive to human immunodeficiency virus (HIV) 1 and 2, and one had pulmonary tuberculosis. Anemia was found in 13 patients, while 17 had Plasmodium falciparum. Plasmodium malariae and hepatitis-B surface antigen were not isolated. Renal biopsy was performed in four patients and revealed minimal-change disease in one child, focal segmental glomerulosclerosis in two and no conclusive result in one patient. Oral prednisolone was used in INS. After one month of therapy, 16 of 20 responded, of which 12 (75%) were <5 years. The NS relapsed in 15 of 16 steroid-sensitive patients. Cyclophosphamide and levamisole were used in four and one patients with FRNS, respectively. Four (14.3%) patients died; all were secondary NS. CONCLUSION: INS remains common in our center, and the majority respond to steroid therapy     

An analysis of 4,514 cases of renal biopsy in Korea

To evaluate the distribution and changing patterns of renal diseases in Korea, a total of 4,514 cases of renal biopsy collected over a 23-year period between 1973 and 1995 were reviewed. Of 4,200 cases excluding 314 unsatisfactory biopsies, adult cases comprised 59.5% and pediatric cases, 40.5%. The male to female ratio was 1.5:1 in adults and 2.2:1 in children. Glomerulonephritis (GN) comprised 80.0% of the total. The most common primary GN in adults was minimal change disease (MCD) (26.6%), followed by IgA nephropathy (IgAN) (22.1%), membranous GN (MGN) (11.8%), and membranoproliferative GN (MPGN) (5.9%). In children, the primary GN incidence rates were MCD (24.8%), IgAN (10.3%), poststreptococcal (including postinfectious) GN (PSGN) (8.6%), and focal segmental glomerulosclerosis (FSGS) (4.0%). The most common secondary GN in adults was lupus nephritis and in children Henoch-Schonlein purpura nephritis. The most common cause of nephrotic syndrome was MCD in both adults and children, followed by MGN and FSGS. The elderly, aged sixty years and older, comprised 2.7% of cases and recorded equal numbers of MCD and MGN. The proportion of the biopsies found to be seropositive for HBs antigen was 27.9%, and these showed either MGN or MPGN pattern. Repeat biopsy was performed in 168 patients, due to previous biopsy failure in 15.5%. When the primary GN cases were analyzed at 5-year intervals, the prevalence of PSGN, which was greater than 25% during the 1973-1982 period, decreased abruptly in children thereafter, whereas the prevalence of FSGS increased slowly since the 1988-1992 period in both adults and children. The decrease of PSGN and the increase of FSGS suggest a role for socioeconomic and environmental factors in Korea.     

Electron microscopic findings suggestive of focal and segmental glomerulosclerosis in patients with steroid-resistant nephrotic syndrome

Distinction between minimal change disease and unsampled Focal Segmental Glomerulosclerosis is a challenging concept in kidney biopsy of patients with nephrotic syndrome with minimal histopathological findings. This study was performed to compare electron microscopic findings in patients with steroid-resistant nephrotic syndrome with minimal histopathological abnormalities and cases with Focal Segmental Glomerulosclerosis. This Cohort study was conducted in Cancer Institute, Imam Khomeini Hospital Complex, Tehran, Iran. Twenty patients with steroid-resistant nephrotic syndrome and minimal changes on the light microscopic study were selected as case group. Similarly, 20 patients with Focal Segmental Glomerulosclerosis were selected as the control group. Ultrastructural findings were re-evaluated and scored qualitatively (0–3+). In patients with minimal changes on light microscopic evaluation, clinical course of the disease was followed after 5 years. Mean ages of the patients (8 women and 12 men) in case and control groups were 12.9 and 15.9 years, respectively (p > 0.05). There was no significant difference in number of examined glomeruli and sampling from cortico–medullary junction area between the groups. The mean percentage of sclerotic glomeruli in control group was 15.4%. Tubular atrophy and interstitial fibrosis were more frequent in control patients. Podocyte proliferation, GBM duplication (involving more than 10% of capillary walls), and moderate to severe multifocal expansion of mesangial matrix were significantly more obvious in FSGS patient samples (p < 0.05). No statistically significant difference was found in severity of cytoplasmic vacuolization, GBM wrinkling and splitting between the groups. Most of (80%) the patients with minimal changes improved during the 5-year follow-up. Generally, we concluded that Podocyte proliferation, GBM remodeling, and moderate to severe mesangial matrix expansion are the most reliable findings on electron microscopic examination in favor of FSGS.     

Diagnosis of congenital and infantile nephrotic syndromes in renal biopsies in Minas Gerais,Brazil: Six case reports

Congenital or infantile nephrotic syndromes (CNS/INS) correspond to a heterogeneous group of rare diseases in which glomerular renal dysfunction and proteinuria are prominent. The aim of this study is to present six cases of possible CNS/INS with diagnoses based on clinical findings and especially histological, ultrastructural, and immunohistochemical characteristics of renal biopsies. Four cases are presented with diffuse mesangial sclerosis, one of them possibly part of Denys–Drash syndrome and two cases with CNS probably of the Finnish type in patients between 3 months old and 13 years old. The study focuses on the late evolution of Denys–Drash syndrome to end-stage renal disease in a 13-year-old patient and the diagnosis of diffuse mesangial sclerosis in an 8-year-old patient. Thus, it contributes to a better epidemiological characterization of these syndromes, demonstrating cases of CNS/INS in infrequent age groups.     

Focal segmental glomerulosclerosis in childhood: histology,glomerular morphometry,electron microscopy and immunofluorescence findings in biopsies performed early in the course of the disease

The histological evolution of Focal Segmental Glomerulosclerosis (FSGS) is poorly documented due to variation in the time at which the biopsy is taken. We looked at patients presenting with steroid resistant nephrotic syndrome (SRNS) in which the first biopsy was performed within 3 months of presentation. FSGS lesion was demonstrable in 68.5% of cases in the first biopsy. Glomerular size was increased in 86% of patients indicating that is an early event in the course of the disease. The group was heterogenous with respect of mesangial cellularity, mesangial matrix, position of FSGS lesion in the glomeruli, glomerular size, lamina densa thickness and immunofluorescence findings. No association of morphological features was seen permitting subclassification of this group on morphological grounds. Thus, both the FSGS lesion and glomerular enlargement occur early in the evolution of idiopathic FSGS presenting with SRNS.     

Nonlupus nephritides in patients with systemic lupus erythematosus: a comprehensive clinicopathologic study and review of the literature.

Renal biopsy specimens from patients with systemic lupus erythematosus (SLE) rarely show changes that are pathogenetically and morphologically unrelated to SLE. The morphology and behavior of these nonlupus nephritides are not well known. Two hundred fifty-two renal biopsies performed on 224 patients with SLE collected from 3,036 native kidney biopsies performed between 1975 and 1998 were reviewed, and those that showed nonlupus nephritides (index biopsies) were selected for studies. Thirteen biopsy specimens with nonlupus nephritides were identified in 13 patients, who belonged to 3 clinically distinct groups. Group I included 6 patients in whom SLE was diagnosed at the time of index biopsies. The index biopsies in these patients showed focal segmental glomerusclerosis (FSGS; 3 cases), Immunoglobulin (Ig) M nephropathy (1 case), and thin basement membrane disease (1 case). The diagnostic features for FSGS included segmental sclerosis involving at least 1 glomerulus, absence of lupus nephritis or other conditions that may cause nonspecific segmental sclerosis of glomeruli such as ischemia or nephrosclerosis, and nephrotic-range proteinuria. There was uniform, global, diffuse and marked thinning of the glomerular basement membrane in the case of thin basement membrane disease. Group II included 3 patients in whom SLE was diagnosed 2 to 9 years before the time of index biopsies and SLE was active at the time of biopsy. The index biopsies in these patients showed FSGS (2 cases) and hypertensive nephrosclerosis (1 case). Group III included 4 patients in whom SLE was diagnosed 5 to 36 years before the time of index biopsies and SLE was inactive at the time of biopsy. The index biopsies in these patients showed 1 case each of amyloidosis, FSGS, hypertensive nephrosclerosis, and allergic acute tubulointerstitial nephritis. Previous renal biopsies, performed in 5 patients, showed IgM nephropathy (1 case), diffuse proliferative lupus GN (1 case), focal proliferative lupus GN (1 case), and mesangial proliferative lupus GN (2 cases). Follow-up biopsies, performed in 3 patients, confirmed the diagnosis of FSGS (2 cases) and hypertensive nephrosclerosis (1 case) noted in the index biopsies. Nonlupus nephritides may occasionally be encountered in SLE patients, regardless of clinical or serologic disease activity. These renal lesions display a broad morphologic spectrum in which FSGS seems most frequent. Renal biopsy plays a crucial role in identifying these lesions, which may have prognostic and therapeutic implications distinct from those of lupus nephritis.     

Immunopathology of early and clinically silent lupus nephropathy.

Detailed immunopathologic studies of early or silent renal alterations in systemic lupus erythematosus have been sparse. The renal biopsies of 16 lupus patients with normal renal function, including 8 with hematuria and/or proteinuria of recent onset, and 8 without clinically detectable renal disease were investigated by light, immunofluorescence, and electron microscopy. Immunoglobulins, complement components, and electron-dense deposits were detected in glomeruli of all patients, regardless of morphologic appearance or lack of clinical evidence of renal involvement. Features of membranous glomerulonepritis were observed in 4 patients with substantial proteinuria. In the remaining 12 patients, including 3 with hematuria and 4 with slight proteinuria, either minimal glomerular alterations or features of mesangial proliferative glomerulonephritis were seen. Transformation of the original disease was demonstrated in 3 of 3 patients rebiopsied within 2 years. The significance of these findings is discussed in relation to a) the spectrum of clinical and immunopathologic alterations in lupus nephritis and b) transformation of the original disease.     

Circulating heavy IgM in IgM nephropathy.

IgM nephropathy (IgMN) causes nephrotic syndrome and is characterized by IgM mesangial deposits. It is speculated that these deposits are derived from circulating IgM aggregates or immune complexes, either of which would have a molecular weight heavier than that of normal IgM. To test this hypothesis the sera of 11 patients with IgMN, five patients with nephrotic syndrome of other etiologies, and 13 normal controls were analysed for such heavy IgM. The serum samples were passed over a Biogel A5M molecular sieve column and the fractions were tested for IgM concentration by enzyme linked immunosorbent assay (ELISA). The column effluent from the void volume to the IgM peak was divided into four equal regions, and the average IgM concentrations in each region were compared. The IgMN group had significantly higher IgM concentrations than normal controls in the heaviest region (0.81 +/- 0.84 vs. 0.32 +/- 0.17 micrograms/ml; P = 0.01) and in the lightest region (95.8 +/- 59.5 vs. 46.3 +/- 41.2 micrograms/ml; P = 0.02). Although the IgMN group appeared to have about double the IgM levels of the nephrotic control group in all four regions, this was only significant in the lightest (19S) region. In serum samples from two IgMN patient methods known to break antigen antibody bonds eliminated the heavy IgM; in one case we used gel filtration in potassium thiocyanate and in another ultracentrifugation at pH 2.8. In addition, the heavy IgM in this second patient exhibited complement fixation activity in a sandwich ELISA for IgM-C3 complexes. We conclude that IgMN patients have circulating heavy IgM, which by preliminary studies probably consists of complement fixing IgM immune complexes.     

Nephrotic syndrome with mesangial-cell proliferation in children--a distinct entity?

Various morphologic patterns have been identified in renal biopsies of children with the idiopathic nephrotic syndrome. Children with focal segmental glomerulosclerosis have clinicopathologic features sufficiently distinct to warrant a separate subclassification. "Immunoglobulin M (IgM) nephropathy" and other morphologic patterns are less well defined. The clinicopathologic characteristics of eight patients with the nephrotic syndrome, increased mesangial cellularity on renal biopsy, and hematuria (mesangioproliferative nephropathy) were evaluated. Response to standardized prednisone therapy was poor. Of the seven children followed for 7-29 months, only two were in remission at the time of writing, and each of these had had one prior relapse. The eighth patient was lost to follow-up after one month. Although the number of patients studied was small, there was a strong correlation between degree of mesangial-cell proliferation and failure of primary treatment. As concepts of the pathogenesis of idiopathic nephrotic syndrome in children continue to evolve, the mesangioproliferative lesion should be recognized and marked for further study.     

Mesangial alterations in steroid-responsive minimal change nephrotic syndrome

Summary Renal biopsies from 25 children with steroid-sensitive minimal change nephrotic syndrome were evaluated retrospectively to determine whether there is any relation between the morphological changes and the frequency of relapses. Biopsy material was examined by light-, immunofluorescence-, and electron microscopy, and by morphometric methods. The patients were divided in a group of 15 children with frequent relapses (FR) and another group of 10 children with an absence of, or only infrequent, relapses (NR/IR). Semiquantitative evaluation of biopsy specimens disclosed no significant differences between groups, but morphometric measurements performed on toluidine stained semithin sections showed a significant increase of mesangial nuclei in FR compared with NR/IR (P<0.01). Furthermore, the mean area of mesangial nuclei was decreased and the relative frequency of smaller nuclear profiles was higher in patients with FR compared to NR/IR (p<0.01). These findings suggest mesangial cell activation in FR which may be related to a longer course of the disease prior to renal biopsy (mean 4.0 years in FR vs. 1.4 years in NR/IR). In our opinion, morphometric assessment of discrete mesangial alterations is a promising method for exploring clinicopathological correlations in minimal change nephrotic syndrome.Presented in part at the 5th International Symposium of Pediatric Nephrology, Philadelphia, USA, October 6–10, 1980     

不同病理类型局灶节段性肾小球硬化症的临床病理分析

目的探讨不同病理类型局灶节段性肾小球硬化症（FSGS）的临床病理特征及其与临床表现的关系。方法对北京大学第一医院2000年1月—2005年12月收集的102例特发性FSGS进行回顾性病理阅片及分型,并对其活动性及慢性化病理改变进行定量评估,分析不同病理类型FSGS的病理变化及其临床表现的特征。结果102例FSGS中,非特殊型占55．9％,门部型占6．9％,细胞型占25．5％,顶端型占4．8％,塌陷型占6．9％。细胞型和顶端型FSGS的尿蛋白水平较非特殊型明显增高,塌陷型和顶端型FSGS的肾病综合征比例较其他三型明显升高（x^2=12．23,P＜0．05）,细胞型和塌陷型FSGS的病理活动性积分较其他3型明显增高（P＜0．05）;门部型FSGS的病程较其他4组患者明显增高,其病理慢性化积分较顶端型和非特殊型明显增高（P＜0．05）;顶端型FSGS的病理总积分最少,明显低于细胞型和塌陷型（P＜0．05）;其慢性化积分较非特殊型和门部型明显降低（P＜0．05）。结论非特殊型FSGS是特发性FSGS的主要病理类型;塌陷型和细胞型FSGS是病变处于活动性阶段的病理类型,门部型FSGS为病理改变呈慢性化的病理类型,顶端型FSGS是病理改变最轻的病理类型。     

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.     

Ezrin--a useful factor in the prognosis of nephrotic syndrome in children: an immunohistochemical approach

BACKGROUND: Minimal change disease (MCD) and diffuse mesangial proliferation (DMP) are the most common pathomorphological forms of nephrotic syndrome glomerulopathies in children. The clinical course of DMP can be characterised by either DMP-sensitivity (DMP-S) or DMP-resistance (DMP-R) to steroids, resulting in an unfavourable course of the glomerulopathy. Although the clinical processes of DMP-S and DMP-R are initially identical, resistance to steroids may be foreseen by the immunohistochemical expression of cytoskeleton-associated proteins in podocytes. AIMS: To estimate the immunohistochemical expression of ezrin in children with MCD, DMP and focal segmental glomerulosclerosis (FSGS) and to evaluate its usefulness in predicting resistance to steroids. MATERIALS AND METHODS: Renal biopsy specimens of patients with MCD (n = 15), DMP (n = 16) and FSGS (n = 6) were taken. The control tissue consisted of normal-appearing cortex taken from kidneys resected for localised neoplasms (n = 6). The indirect immunohistochemical protocol for the use of a monoclonal antibody directed against ezrin was used. RESULTS: The immunohistochemical expression of ezrin in cases progressively reduced from MCD to DMP-S to DMP-R to FSGS. Except for DMP-R and FSGS (p>0.05), the difference in ezrin expression in podocytes was significant. CONCLUSION: Ezrin can be a potent marker of podocyte injury (podocytopathy) and may help in the histological qualification of MCD, DMP and FSGS. The increased permeability of the filtration barrier in steroid-resistant and proteinuric glomerulopathies may be a consequence of subcellular changes in podocyte-associated proteins following decreased expression of ezrin.     

Focal segmental glomerulosclerosis: a diagnostic problem

Focal segmental glomerulosclerosis (FSGS) is an important clinical problem as it leads to end-stage renal disease. Clinicians have long been able to treat patients with FSGS. Therefore, the demands the clinicians make on pathomorphologists, which include the diagnosis of FSGS at a possibly early stage, are justifiable. However, early diagnosis of FSGS is difficult. The analysis involved 150 cases of FSGS diagnosed between 2003 and 2008. These constitute 14.53% of renal biopsy material of that period. The test material comes from 138 adults and 12 children. The adult group mostly included patients with albuminuria (58 patients) and nephrotic syndrome (36 patients). Smaller groups included patients with albuminuria and hypertension, erythrocyturia and albuminuria, isolated erythrocyturia. The children group mostly included patients with the nephrotic syndrome. Individual patients suffered from isolated albuminuria and erythrocyturia. In both groups, FSGS NOS lesions prevailed. However, FSGS hilar and FSGS tip lesions, as well as completely sclerotized glomeruli were also present. Diverse symptoms of diseases may pose specific difficulties in clinical diagnosis. Similarly, determination of FSGS lesion type may be difficult due to simultaneous presence of different subtypes in the same punctate.     

Long-term outcome of kidney transplantation in adult recipients with focal segmental glomerulosclerosis

Focal segmental glomerulosclerosis (FSGS) is an important cause of nephrotic syndrome and end-stage renal disease. FSGS recurrence after renal transplantation has a potentially detrimental course leading to the loss of renal function. In order to establish FSGS recurrence rates and evaluate the course of the disease on living-related-donor renal transplantation in ethnic Korean adults (> or = 18 years), we reviewed our experiences of 27 kidney transplantations with FSGS over the last 15 years. Of the 27 renal allografts, 13 were found to have recurrent FSGS by graft biopsy. In comparison with background data upon patients with and without recurrence of FSGS, the donor age of patients with recurrent FSGS was significantly higher than that of those without recurrence (median, 39 years vs 26, p < 0.05). In terms of, age at transplantation, length of dialysis period, and mode of dialysis no differences were found between recurrent and nonrecurrent cases. The graft survival rate of recipients from a kidney donor of age less than 40 years was significantly higher than that of recipients from a kidney donor of age more than 40 years, at 5 and 10 years, respectively (87% vs 33%, 41% vs 0%, p < 0.05). The association between clinical variables and recurrence was assessed by multiple logistic regression analysis, and donor age was found to be a risk factor of FSGS recurrence (p<0.05). Variables such as HLA-mismatch numbers and immunosuppression were not found to be associated. In conclusion, the recurrence rate of FSGS in adult recipients with FSGS was 48% and patients that received kidney from an older donor appear to be at higher risk of developing recurrence. The use of a renal graft from a younger donor is considered advisable for adult recipients with FSGS.     

Cyclosporin a treatment in children with minimal change nephrotic syndrome and focal segmental glomerulosclerosis

Summary In a pilot study 23 children with nephrotic syndrome were treated with cyclosporin A (Cs) for 6–45 months. 8 children suffered from steroid dependent minimal change nephrotic syndrome (MCNS) and had experienced at least one course with cytotoxic drugs, but had relapsed thereafter. 2 children had diabetes mellitus type I with nephrotic syndrome and 13 children had steroid resistant focal segmental glomerulosclerosis (FSGS). Cs was started with 100 mg/m2/day in two doses and increased stepwise to obtain a Cs whole blood trough level of 200–400 ng/ml. In steroid dependent MCNS treatment with Cs reduced relapse rate significantly, and prednisone therapy could be stopped completely. After discontinuation of Cs, relapses reoccurred as frequently as before. Renal function remained unimpaired despite repeated Cs treatment courses up to 38 months. In cases of nephrotic syndrome with diabetes type I Cs treatment led to complete remission without changing the insulin requirement. However, after discontinuation of Cs relapses reoccurred. In steroid resistant FSGS 6 children benefited from Cs treatment: 4 went into complete remission, 2 into partial remission. The 2 children with complete remission relapsed but remained Cs responsive. The remaining 7 children with FSGS did not respond to Cs but continued the course of their disease, with two patients rapidly progressing to terminal renal failure. Side-effects of Cs treatment were mild. It is concluded that Cs is an effective agent in steroid dependent MCNS and can be used as an alternative drug in specific cases like steroid toxicity or diabetes mellitus. In steroid resistant FSGS a trial with Cs seems to be warranted since some cases do respond favorably. To avoid nephrotoxicity treatment with Cs should always be monitored closely by determination of blood levels and renal function.Abbreviations MCNS minimal change nephrotic syndrome - FSGS focal segmental glomerulosclerosis - Cs Cyclosporin A     

Renal lesions in AIDS: a biopsy and autopsy study.

We studied renal lesions at biopsy (20 cases) and at autopsy (21 cases) among patients with the acquired immune deficiency syndrome (AIDS). Nephrotic syndrome with concomitant renal insufficiency was most common indication for biopsy. 85 percent of biopsies showed features of HIV associated nephropathy (HIVAN) which include: Focal segmental glomerulosclerosis (FSGS), glomerular collapse and mesangial hyperplasia. These glomerular changes were always accompanied by tubular microcysts and ultrastructurally, tubuloreticular inclusions (TRI) within the glomerular endothelium were often noted. Changes of HIVAN were also seen in two cases who were HIV negative at the time of biopsy but were positive on repeat testing. Minimal change disease, mesangiocapillary glomerulonephritis and diffuse proliferative lupus nephritis were other biopsy lesions. Autopsy findings were HIVAN (33 percent), tubular necrosis and opportunistic infections. We conclude that HIVAN is a distinct clinicopathologic entity that may sometimes be the first manifestation of the underlying disease state.     

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。     

Ultrastructural Changes Suggestive of Focal Segmental Glomerulosclerosis in Atypical Minimal Change Nephrotic Syndrome

In an attempt to recognize early stages of focal segmental glomerulosclerosis (FSGS) in patients with a clinical course suggesting a diagnosis other than minimal change disease (MCD) and normal histology, or minor, nondiagnostic changes on light microscopy (LM), we used a protocol for systematic and extensive electron microscopy (EM) examination of kidney biopsies obtained from such patients. By this method ultrastructural pathology was found in 8 patients. These changes were localized, involving only portions of single glomerular segments. The findings included mild to moderate increase of the mesangial matrix, focal wrinkling of the capillary basement membrane, and early obliteration of the normal architecture of individual capillary loops, as well as electron-dense deposits in a mesangial and subendothelial distribution. Of these 8 patients, 2 are at present in remission without therapy (in 1, following therapy with cyclophosphamide); 3 are in remission on steroid therapy; 1 developed massive proteinuria during pregnancy, after a spontaneous remission lasting almost 2 years; 1 patient advanced to terminal renal failure 3 1/2 years after biopsy; and 1 died of sepsis 1 month after biopsy. We believe that the ultrastructural changes found may represent early or mild FSGS and that the protocol described can add valuable information in clinically worrisome patients in whom renal histology appears normal.