原发性IgA肾病与非IgA系膜增生性肾小球肾炎的临床病理分析

目的 比较原发性IgA肾病与非IgA系膜增生性肾小球肾炎（non-IgA mesangial proliferative glomerulonephritis,non-IgA MsPGN）的临床及肾脏病理改变特点.方法 选择我科经肾活检确诊的原发性IgA肾病患者（A组）和non-IgA MsPGN患者（B组）进行临床与病理资料对比分析.结果 A、B组的性别、前驱上呼吸道感染诱因、起病时伴发高血压、镜下血尿、血肌酐无统计学差异（P＞0.05）.B组较A组起病年龄小,起病时伴发肉眼血尿比率低,肾病综合征发生率高,血IgG水平低,差异均有统计学意义（P＜0.05）.A组肾小球、肾小管间质、肾小动脉病理改变发生率高于B组（P＜0.05）,IgM、C3沉积、系膜区电子致密物沉积、大块状致密物、足细胞微绒毛化、肾小球基底膜分层发生率均较B组高（P＜0.01）.结论 IgA肾病与non-IgA MsPGN在临床表现、病理改变上存在明显差异,IgA肾病较non-IgA MsPGN病理损伤重.     

Discriminant analysis of clinical markers before renal biopsy in patients with IgA nephropathy

Discriminant analysis of clinical markers before renal biopsy in patients with IgA nephropathy is described. Sixty eight patients with IgA nephropathy (IgA nephropathy group) and 66 patients with other chronic glomerulonephritis (non-IgA nephropathy group) were examined. The discriminant analysis was applied to separate those two groups by using twenty clinical parameters as well as binding capacity of serum IgA to the glomeruli of renal specimens. Binding of serum IgA of patients to the glomeruli obtained from patients with IgA nephropathy was performed using avidin-biotin immunofluorescence. Among twenty clinical markers, the levels of serum IgA and creatinine, and degree of microhematuria in IgA nephropathy group were significantly higher than those in non-IgA nephropathy group Furthermore, the positive incidence of serum IgA binding of IgA nephropathy group was significantly higher than that of serum IgA binding of non-IgA nephropathy group. The correct classification rate were 79.10% using five clinical markers including serum IgA, microhematuria, serum C4, quantitation of proteinuria and degree of proteinuria. It is indicated that the levels of serum IgA and the binding of serum IgA to the glomeruli were considered to be major markers for clinical diagnosis of patients with IgA nephropathy It was concluded that the discriminant analysis before renal biopsy was useful for diagnosis of IgA nephropathy.     

Clinical-pathologic features and outcomes of IgA nephropathy patients with IgM deposition

Objective To determine the correlation of IgM deposition with clinic-pathological features and outcomes of IgA nephropathy patients. Methods A total of 1060 patients, who were diagnosed as IgA nephropathy by renal biopsies between 2001 and 2007 in Guangxing Hospital were enrolled. According to immunofluorescent test, patients were divided into patients with mesangial IgM deposition and patients without IgM deposition. Renal survival curves were assessed by Kaplan-Meier method. The effect of IgM deposition on outcomes of IgA nephropathy patients was examined by univariate and multivariable Cox proportional-hazards regression. Results Among 1060 IgA nephropathy patients, there were 750 patients with IgM deposition and 310 patients without IgM deposition. (1) Urinary protein and uric acid in patients with IgM deposition were significantly higher than those in patients without IgM deposition (all P＜0.05). Other clinical indicators shown no statistical difference (all P＞0.05). Moreover, IgM deposition patients had higher serum IgA, serum IgG and serum IgM (all P＜0.05). (2) In pathological indicators, IgM deposition patients had more segmented sclerosis or adhesions (S1 of Oxford classification), activity lesions as inflammatory cell infiltration and mesangial proliferation, and chronic pathological changes as tubular atrophy, segmented glomerular damage than patients without IgM deposition (all P＜0.05). (3) All patients were followed-up for a median of 89.7(61.8, 113.4) months, Kaplan-Meier analysis revealed that kidney survival rate was significantly lower in IgM deposition patients compared with patients without IgM deposition (Log-rank χ2=4.95, P=0.026). In a univariate Cox hazards regression mode, IgM deposition was a risk factor for poor prognosis of IgA nephropathy patients (HR=1.597, 95%CI 1.053-2.422, P=0.027). However, in a multivariable Cox analysis, IgM deposition shown no influence on outcomes of IgA nephropathy patients (HR=1.409, 95%CI 0.921-2.156, P=0.114). Conclusions IgA nephropathy patients with IgM deposition have higher urinary protein, and more serious pathological damage and immune fluorescence deposition. IgM deposition affects renal survival of IgA nephropathy, while IgM deposition is not an independent risk factor for prognosis of IgA nephropathy.     

Increased immunoglobulin-secreting cells in the blood of patients with active idiopathic IgA nephropathy

Peripheral blood lymphocytes from 33 patients with idiopathic IgA nephropathy (IgAN) and 15 healthy controls were stimulated in vitro by Protein A from Staphylococcus Cowan I; immunoglobulin (Ig) production was measured by a reverse hemolytic plaque assay to evaluate the quantity of cells secreting Ig. In addition, serum Ig levels, circulating IgG, IgA and IgM immune complexes (ICs) and the Fc and C3b receptor mediated phagocytosis of peripheral monocytes were measured. The laboratory findings in different phases of the disease were compared. The mean level of IgA-plaque forming cells (IgA PFC) in IgAN patients with normal renal function was significantly higher (p less than 0.001) than the mean control value. In contrast, they were reduced significantly in those patients who were subjected to periodic hemodialysis (p less than 0.001). Disease activity produced a significant increase in IgG PFC and IgA PFC, high IgG and IgM serum levels, high circulating IgG ICs, and low C3b-mediated phagocytic function of the peripheral macrophages. These findings demonstrate that IgAN is associated with an increased number of IgG and IgA-secreting cells in the peripheral blood of patients during the active phase of the disease and that the concurrent presence of high levels of circulating Ig ICs may be responsible for the gross hematuria, as their deposition in the glomeruli could activate the complement system.     

Retroviral envelope glycoprotein (gp 70) is not a prerequisite for pathogenesis of primary immunoglobulin A nephropathy in ddY mice.

Deposition of a major retroviral envelope glycoprotein, gp 70, in renal glomeruli of ddY mice, an animal model for primary IgA nephropathy, was examined by immunofluorescence. The positive staining of gp 70 was not observed in glomeruli of our substrain of ddY mice at any ages examined using two different anti-gp 70 antisera and three different staining conditions, whereas deposition of IgA, IgG and IgM was manifest in mice aged over 40 weeks. As a control, NZB x NZW F1 mice from 4 months of age onwards showed severe glomerular deposition of gp 70, in keeping with previous reports. Thus, it appears that gp 70 deposition may not be sine qua non for the pathogenesis of IgA nephropathy of all substrains of ddY mice.     

Glomerular deposition of mannose-binding lectin in human glomerulonephritis.

BACKGROUND: Mannose-binding lectin (MBL), a member of the collectin family, binds to various oligosaccharides and activates the classical pathway of complement independent from C1q. At present it is unknown whether this so-called lectin pathway of complement activation plays a role in the pathogenesis of human glomerulonephritis. METHODS: Direct immunofluorescence of 84 renal biopsies using an MBL-specific monoclonal antibody and antibodies directed against IgG, IgA, IgM, C1q, C3, and terminal complement complex (TCC) was performed. Serum MBL levels of 50 patients were determined by enzyme-linked immunosorbent assay. RESULTS: MBL was detected in the glomeruli of patients with lupus nephropathy (15 of 16), membranous nephropathy (10/15), membranoproliferative glomerulonephritis type I (5/6) and anti-GBM nephritis (2/4). MBL deposition paralleled that of immunoglobulins, C1q, C3, and TCC but was less intense as compared to C1q. Focal segmental deposits of MBL were present in focal segmental glomerulosclerosis (4/6), IgA nephropathy (3/11), amyloidosis AL (1/4), and advanced renal fibrosis (2/2). Here MBL staining was identical to IgM and C3 and considered an unspecific entrapment of MBL in sclerotic lesions in these cases. No significant difference in MBL serum levels was observed between normal controls and patients with lupus nephritis, membranous nephropathy, membranoproliferative glomerulonephritis, focal segmental sclerosis, minimal change disease or IgA nephropathy. In patients suffering from membranous nephropathy with (n=10) or without (n=5) glomerular MBL deposits serum creatinine, C3, C4, serum protein, and proteinuria were not statistically different. CONCLUSION: MBL is present in the glomeruli of patients with glomerulonephritis involving deposition of IgG and activation of the classical pathway of complement. We propose that MBL binds to agalactosyl oligosaccharides of IgG that terminate in N-acetylglucosamine. The extent to which the lectin pathway of complement contributes to overall complement activation in the glomeruli remains unknown, but is likely to be marginal.     

Effect of immunoglobulin depositions of glomerular sialic acids in patients with IgA nephropathy

A study of double immunofluorescence-staining of immunoglobulins and sialic acids in the glomeruli from patients with IgA nephropathy is described. Renal biopsy specimens from patients with IgA nephropathy were stained with rhodamine-labeled antihuman IgA, IgG or IgM antisera and then stained with FITC-labeled Limulus polyphemus (LPA), Tricum vulgaris (WGA) or antihuman C3 antisera. Marked positive stainings of IgA and C3 and positive binding of LPA or WGA were observed in the glomerular mesangial areas from patients with IgA nephropathy. LPA or WGA were not bound with glomerular capillary walls from patients with moderate and advanced stages of IgA nephropathy, although depositions of IgA and C3 were markedly observed in such walls. There was a significant inverse correlation between the deposition of IgA and the binding of LPA or WGA in glomerular capillary walls obtained from these patients with IgA nephropathy. The levels of proteinuria from patients with moderate and advanced stages of IgA nephropathy were significantly higher than those with minimal and slight stages of such disease. It is suggested that the decrease of sialic acids in glomerular capillary walls might be due to a deposition of IgA in some patients with IgA nephropathy. It is concluded that high levels of proteinuria might be due to the decrease of sialic acids in glomerular capillary walls from patients with moderate and advanced stages of IgA nephropathy.     

Serum levels of soluble Fas and disease activity in patients with IgA nephropathy

Using a sandwich ELISA, we studied 48 patients with IgA nephropathy and 10 patients with diffuse mesangial proliferative glomerulonephritis without IgA deposition (non-IgA PGN) to determine if levels of serum soluble Fas (s-Fas) might reflect the disease activity. The levels of serum s-Fas in patients with the advanced stage of IgA nephropathy were significantly higher than those in patients with the mild stage of the disease, in non-IgA PGN or in healthy controls. The results showed that advanced stage IgA nephropathy patients who showed heavy proteinuria and the presence of urinary casts revealed high levels of serum s-Fas. It was thus suggested that the measurement of serum s-Fas is useful in evaluating the degree of renal injury in patients with IgA nephropathy.     

Anti -PLA2R autoantibodies in serum and IgG subclass deposits on glomeruli in undetermined atypical membranous nephropathy

ObjectiveTo investigate the characteristic of autoantibodies of M – type phospholipase A2 receptor (PLA2R) in serum and the glomerular IgG subclass deposits in undetermined atypical membranous nephropathy (MN) patients. MethodsFrom Feb 2004 to Nov 2011, 53 cases diagnosed as MN by kidney puncture biopsy in our hospital were included into the study. There were 20 undetermined atypical membranous nephropathy (UAMN), 20 idiopathic membranous nephropathy (IMN) and 13 secondary membranous nephropathy (SMN) which were composed of lupus membranous nephropathy (LMN) and HBV related membranous nephropathy (HBV-MN). Clinlical and pathological characteristics were analyzed. The autoantibodies of PLA2R in serum were detected and the glomerular IgG subclass deposits were observed. Results(1) The average age underwent renal biopsy was (37.9±3.8) years of UAMN, (50.1±3.0) years of IMN and (49.5±4.5) years of SMN. The difference in onset average age at disease was significant between UAMN and IMN (P＝0.0178). The female/male ratio (F/M) in UAMN, IMN and SMN was 0.8∶1, 0.7∶1 and 0.6∶1(P＞0.05). (2) Compared with SMN, the level of 24-hours urinary protein excretion (3.47 g vs 7.89 g, P＝0.023), the ratio of amount urinary protein patients (50.0% vs 84.6%, P＝0.043), the level of serum IgG [(8.40±3.58) g/L vs (10.09±4.69) g/L, P＝0.025] and the positive rate of ANA in serum (10.0% vs 53.8%, P＝0.006) in UAMN were all much lower. There were no significant statistical differences in serum albumin, serum creatinine, eGFR, positive rate of HBsAg, HBeAg or HCV, as well as the ratio of hypo - albuminemia and nephritic syndrome among the three groups. (3) IF positive rate of IgA, IgM and C1q in UAMN were all significantly higher than that in IMN (P＜0.01). There were no significant differences in IF positive rate of IgA, IgM, C1q, IgG and C3 between UAMN and SMN. The IF strength of IgA, IgG, IgM, C3 and C1q in UAMN showed no significant differences between UAMN and SMN. (4) The serum autoantibodies of PLA2R were only detected in 10 cases of IMN group (50%) with all the other cases negative. This detection rate of serum autoantibodies of PLA2R showed significant statistical differences among the three groups (P＜0.01), but no differences between UAMN and SMN (the detection rate in both groups were 0%). (5) IgG1 deposits was the dominant IgG on the glomeruli in UAMN group (40%), as well as in SMN group (76.9%). IgG4 deposits was the dominant IgG on the glomeruli in IMN group (60%). The positive rate of IgG1 and IgG3 in UAMN showed no significant statistical differences when compared with IMN or SMN. The positive rate of IgG2 in UAMN was significantly lower than in SMN（30.0% vs 69.2%, P＜0.05). The positive rate of IgG4 in UAMN was significantly lower than in IMN (20% vs 60%, P＜0.05). The positive rate of IgG1, IgG2 and IgG3 in SMN were all significantly higher than in IMN. ConclusionsNone of the UAMN group had autoantibodies of PLA2R in serum, and IgG1 deposits was the dominant IgG subclass on the glomeruli which indicated the similarity with the SMN group. At the same time, UAMN was significantly different from SMN in clinical manifestations.     

IgA nephropathy. Evaluation of prognostic factors in patients with moderate disease

Previous studies of IgA nephropathy have demonstrated a number of prognostically significant clinical and pathological factors in groups of patients with the full histological spectrum of the disease. Whether these factors can be applied to a group of IgA nephropathy patients with disease of moderate degree is unknown. Forty patients (9 females, 31 males) with grade III IgA nephropathy (no more than 10% obsolete glomeruli and little or no interstitial fibrosis) were evaluated with respect to age, sex, degree of proteinuria, history of recurrent gross hematuria, hypertension, extent and type of segmental glomerulosclerosis, demonstration of IgG and/or IgM in deposits, presence of peripheral capillary deposits, whether or not there were crescents, and extent of vascular sclerosis. The mean age was 29.6 +/- (SD) 13.1 years. Sixteen patients presented with recurrent gross hematuria, and 24 had microscopic hematuria and proteinuria as the initial manifestation. Hypertension was seen in 5 patients. The mean serum creatinine concentration was 1.09 +/- 0.47 mg/dl (96.4 +/- 41.5 mumol/l), and the mean 24-hour urinary protein was 1.5 +/- 1.3 g. Nine patients had proteinuria greater than or equal to 2.0 g/24 h. Thirty-two patients demonstrated segmental glomerulosclerosis in their biopsies, 13 of which had more than 10% of the glomeruli involved. Seven patients developed established renal failure (Cr greater than or equal to 2.0 mg/dl; 176.8 mumol/l). The 60-and 100-month renal survival rates were 96 and 52%. Life table analysis disclosed that only the degree of proteinuria (greater than or equal to 2.0 g/24 h; p less than 0.05) and the extent of segmental glomerulosclerosis (p less than 0.025) were of prognostic significance.(ABSTRACT TRUNCATED AT 250 WORDS)     

IgG, IgA and IgM rheumatoid factors in patients with glomerulonephritis

Rheumatoid factors (RF), autoantibodies to IgG, have been postulated to have some pathogenetic role in the development of some types of glomerulonephritis. A simple and sensitive solid-phase fluorescence immunoassay was employed to determine whether IgG, IgA and IgM RF were detectable in sera from patients with various types of glomerulonephritis, rheumatoid arthritis (RA) and those with various streptococcal infections. IgG, IgA and IgM RF were significantly increased in the majority of patients with RA, lupus nephritis (SLE), acute poststreptococcal glomerulonephritis (APSGN) and various streptococcal infections. The titers of IgG and IgA RF were significantly higher in patients with APSGN than in those with simple pharyngitis. IgM RF was increated in patients with IgA nephropathy (IgA-N) and in those with membranoproliferative glomerulonephritis type I (MPGN). No significantly high RF was observed in membranous nephropathy (MN) or chronic mesangial proliferative glomerulonephritis without IgA deposition (PGN). It is suggested that some autologous immune mechanisms may be involved in the pathogenesis of some types of glomerulonephritis.     

Characteristics of immunoglobulin A nephropathy with mesangial immunoglobulin G and immunoglobulin M deposition

Aim: There are immunoglobulin (Ig)A nephropathy (IgAN) cases showing mesangial IgG and/or IgM deposition, however, their characteristics have remained unknown. Methods: Three hundred and eighty‐four IgAN patients were divided according to the existence of mesangial IgG and/or IgM deposition: IgA deposition only (A group, n = 77); IgA and IgM deposition (AM group, n = 114); IgA and IgG deposition (AG group, n = 36); and IgA, IgG and IgM deposition (AGM group, n = 157). Clinical and histological findings, and outcomes were examined and compared among these four groups. Results: At the time of renal biopsy, serum creatinine was significantly higher in the A and AM group, however, creatinine clearance did not differ among the four groups. The ratio of glomerular obsolescence was significantly higher in the AM group than in the A and AGM group, and the ratio of glomerular tuft adhesion was significantly higher in the AM, AG and AGM group than in the A group. However, the other clinical and histological findings, electron microscopic findings and renal survivals did not differ among the four groups. Proteinuria was independently associated with an increase in risk of doubling of creatinine (P = 0.005), however, IgG and IgM depositions were not by multivariate Cox regression. Conclusion: The presence of other Ig classes, besides IgA deposits, was found to be associated with glomerular obsolescence and tuft adhesions, however, without any effect on renal survival in IgAN.     

IgA-containing immune complexes in the urine of IgA nephropathy patients.

BACKGROUND: Sera of IgA nephropathy (IgAN) patients contain high levels of circulating immune complexes composed of IgA1 molecules with aberrantly glycosylated hinge-region O-linked oligosaccharides and IgG or IgA1 antibodies with anti-glycan or anti-hinge-region peptide specificities. Due to damaged sieving properties of the glomerular capillary wall in IgAN, these immune complexes may appear in the urine. METHODS: We collected urine samples from 29 patients with biopsy-proven IgAN (Group I), 27 proteinuric patients with non-IgA nephropathies (Group II) and 28 healthy volunteers (Group III). The levels of urinary IgA and IgG and IgA-IgG-containing immune complexes were measured by ELISA and standardized for urinary creatinine concentrations. RESULTS: The urinary IgA and IgG levels were significantly higher in Groups I and II than in Group III. Although the excretion of IgA as a fraction of total urinary protein was not significantly greater in IgAN patients than in patients with other renal diseases, the excretion of aberrantly glycosylated IgA1 was observed by western blot in 68% of the IgAN patients but in none of the healthy controls. The urinary levels of IgA-IgG immune complexes were significantly higher in Group I than in Groups II (P < 0.01) and III (P < 0.05). There was no significant difference in the levels between Groups II and III. These immune complexes had a molecular mass between 650-850 kDa, as shown by size-exclusion chromatography. CONCLUSION: The amounts of urinary IgA-IgG-containing immune complexes were significantly higher in patients with IgAN than in patients with non-IgA nephropathies or healthy controls.     

Defective in vivo Fc- and C3b-receptor function in IgA nephropathy

Reticuloendothelial function was assessed in 17 patients with IgA nephropathy, using 99Tc-labeled autologous erythrocytes coated with either C3B or IgG. Results were compared with clearances in 14 normal control subjects and with a group of 14 patients with idiopathic mesangial proliferative glomerulonephritis without IgA deposition. The half-life of IgG-coated red cells in the IgA group was 69.8 +/- 32.5 minutes (control 42.2 +/- 9.0 minutes, P = 0.001). The half-life in the non-IgA mesangial proliferative group, 77.9 +/- 31.3 minutes, was not significantly different from that of the IgA patients. Clearance of C3b-coated cells, expressed as the percentage of cells cleared at 30 minutes, was 7.1% +/- 2.6% in the IgA patients, compared with 16.0% +/- 3.2% in control subjects (P less than 0.001) and 13.8% +/- 7.5% in the non-IgA mesangial proliferative group (NS). No statistical correlation was found between clearance results in individual patients and age, sex, weight, serum creatinine, or the severity of disease on clinical and pathological criteria. The severity of the defect in Fc- and C3b-receptor dependent clearances were not statistically correlated in individual patients.     

Serum IgA/C3 ratio may predict diagnosis and prognostic grading in patients with IgA nephropathy

Recently, the authors reported that the ratio of serum IgA to C3 (serum IgA/C3 ratio) is a good marker to distinguish patients with IgA nephropathy from non-IgA nephropathy patients together with serum IgA levels using an international reference preparation (IFCC/CRM470). In this study, the authors investigated whether the serum IgA/C3 ratio might be an indicator of prognostic grading in patients with IgA nephropathy. Two hundred and thirteen patients with IgA nephropathy and 96 other glomerular diseases including diffuse or focal mesangial proliferative glomerulonephritis without mesangial IgA deposition (non-IgA PGN), membranous nephropathy and thin basement membrane syndrome were examined. The levels of serum IgA and C3 in these patients were adjusted by the specified formula to those using international standard serum (IFCC/CRM470) in this study. The results of this study showed the highest levels of IgA/C3 ratio in patients with IgA nephropathy. The serum IgA/C3 ratio appears to gradually increase according to the prognostic grading of this disease. Therefore, measurement of the serum IgA/C3 ratio may be useful for prediction of diagnosis and prognostic grading in patients with IgA nephropathy.     

Participation of complement components in glomerular deposition in IgA nephropathy

To clarify the role of complement components in glomerular deposition in IgA nephropathy, clinicopathological and immunohistological studies were performed on 299 patients (171 males and 128 females; age, 9-71 years). Glomerular IgA deposition with IgG and/or IgM was observed more frequently in patients with Clq and/or C4 than in those with only C3 deposition (P less than 0.001). Patients with glomerular deposition of Clq and/or C4 showed more severe proteinuria (1 g/24 hr less than), a lower glomerular filtration rate (GFR), a higher incidence of duplication of capillary walls and more severe proliferation of mesangial cells and an increase in mesangial matrix (P less than 0.05), as compared to those without both Clq and C4. Patients with glomerular C3 deposition had significantly lower serum CH50 levels at the time of renal biopsy (P less than 0.02) and a significantly higher incidence of sclerotic lesions (P less than 0.05). Patients with C3 deposition in the mesangium and peripheral capillaries had significantly higher serum IgA levels (P less than 0.02), a significantly higher incidence of adhesion (P less than 0.01), duplication and endocapillary proliferation (P less than 0.05) and a more severe increase in mesangial cells (P less than 0.01) than those with C3 deposition only in the mesangium. The above findings demonstrate that analysis of the complement system in glomeruli is important for the evaluation of glomerular damage, clinical findings and prognosis.     

Clinico-pathological characterization and outcome of primary focal segmental glomerular sclerosis with deposition of IgM

Objective To explore the clinico-pathological features and outcomes of primary focal segmental glomerular sclerosis with IgM deposition. Methods One hundred and two patients with primary focal segmental glomerular sclerosis (pFSGS) in Hangzhou hospital of traditional Chinese medicine between 1996 and 2012 were retrospectively studied. The patients were divided into IgM deposition group (n=66) with IgM deposition in glomeruli and none-IgM deposition group (n=36)without IgM deposition. Baseline and clinical characteristics of all FSGS patients were assessed and outcomes were reviewed. The survival rates of the patients were analyzed using theKaplan-Meiermethod. Results (1) There were not difference in age, sex ratio, incidence of microscopic hematuria, hypertension, renal insufficiency, eGFR, Ccr and Scr between two groups. However, proteinuria, incidence of nephrotic syndrome, urine microalbumin, urine NAG, serum cholesterol, serum high-density lipoprotein, and serum IgM in IgM deposition group were significantly higher than those in none-IgM deposition group (P＜0.05), serum albumin and serum IgA in IgM deposition group were significantly lower than those in none-IgM deposition group (P＜0.05). (2) The IgM deposition group had a significantly higher incidence of glomerular deposition of IgA, IgG, C3, C1q and fibrinogen than none-IgM deposition group (P＜0.05). The score of mesangial matrix proliferation in the IgM deposition group was lower than that in none-IgM deposition group (P＜0.05). (3) fifty-four patients (35 patients in IgM deposition group and 19 patients in none-IgM deposition group） were followed-up for a median of 64.6 (22.8, 103.8) months. Progression to renal failure was observed in 5 patients of IgM deposition group and none in none-IgM deposition group. Compared with the none-IgM deposition, the survival rates in the IgM deposition group were statistically lower (P＜0.05).Conclusions PFSGS patients with IgM deposition were severer in proteinuria, higher incidence ofIgA, IgG, C3, C1q and fibrinogen deposition in glomeruli and worse outcome than those without IgM deposition.     

A comparative immunologic study of IgA nephropathy

A conglutinin binding assay has been used to detect circulating immune complexes (CIC) containing IgA, IgG, or IgM in sera from patients with IgA nephropathy. IgA class CIC were detected in 40.7% of patient. IgG class CIC were detected only in patients with glomercular IgG deposits. IgM class CIC were detected more often in patients with glomerular IgM deposits than in patients without glomerular IgM deposits. These results demonstrate an association between the immunoglobulin in CIC and those in glomerular deposits. CIC were not detected in sera from most patients with IgA nephropathy by a Clq binding assay, however, since this assay does not detect IgA class CIC. Immunoelectronmicroscopic studies of IgA nephropathy have shown that C3 deposits are localized to the same areas as IgA deposits. In conclusion, we suggest that mesangial IgA deposits are composed of immune complexes and may be derived from CIC.     

Effects of angiotensin-converting enzyme inhibitor, angiotensin II receptor antagonist and calcium antagonist on urinary podocytes in patients with IgA nephropathy

The urinary podocyte is postulated to be a marker for estimation of the severity of active glomerular injury and a predictor of disease progression in children with glomerulonephritis. Non-dihydropyridine calcium antagonist, including verapamil, reduce proteinuria to an extent similar to that of the angiotensin-converting enzyme inhibitor (ACEI), including trandolapril, but to a greater extent than other antihypertensives. Angiotensin (Ang) II receptor antagonists, including candesartan cilexetil, show potent and long-term preventive effects against the progression of renal injury. The aim of the present study is to assess whether verapamil, trandolapril and candesartan cilexetil affect proteinuria and urinary podocytes in patients with IgA nephropathy. Thirty-two normotensive patients aged 18-54 years with biopsy-proven IgA nephropathy, nonnephrotic proteinuria (1-3 g/day), and normal renal function (creatinine clearance >80 ml/min) were studied. Twenty patients with diffuse mesangial proliferative glomerulonephritis (non-IgA PGN) and 20 healthy controls were also included in this study. The number of urinary podocytes in patients with advanced IgA nephropathy (n = 16) was significantly higher than that in patients with the disease in the mild stage (n = 16) (p < 0.01) or in patients with non-IgA PGN (p < 0.01). Urinary podocytes were not detected in healthy controls. The 32 patients with IgA nephropathy were randomly divided into four treatment groups: those treated with verapamil (120 mg/day, n = 8); those treated with trandolapril (2 mg/day, n = 8); those treated with candesartan cilexetil (8 mg/day, n = 8), and those given a placebo (n = 8). Treatment continued for 3 months. Antiproteinuric response in the trandolapril group was similar to that in the candesartan cilexetil group (-38 vs. -40%). The action of trandolapril or candesartan cilexetil was greater than that of verapamil (p < 0.01). Reduction in the number of urinary podocytes from baseline was significantly greater in patients treated with trandolapril or candesartan cilexetil than in patients treated with verapamil (p < 0.01). However, there was no difference between patients treated with trandolapril and those treated with candesartan cilexetil. Proteinuria and urinary podocytes were unaffected in the placebo group. These data suggest that urinary podocytes may be a marker of disease activity in adult patients with IgA nephropathy and that trandolapril and candesartan cilexetil are more effective than verapamil in reducing the number of podocytes.     

Minimal change nephrotic syndrome with predominant mesangial IgA deposits: clinicopathological study

It has been reported that minimal change nephrotic syndrome (MCNS) shows no deposit of immunoglobulins or complement components in the glomeruli. We found 6 patients with IgA deposits in the glomeruli among 101 patients with MCNS, and examined the clinicopathological features of these cases. In all cases, light microscopy showed minor glomerular abnormalities. However, immunohistochemical study demonstrated marked IgA deposits in the glomerular mesangium. IgM was detected in 5 cases, IgG in 2, C3 in 2, and Clq in 1. On electron microscopy, small mesangial deposits were found in all cases and foot process effacement was partially demonstrated. There were no abnormalities in the glomerular basement membrane. The renal functions were within normal ranges in all 6 cases. In three cases, biopsies were performed within a month after the initiation of profuse proteinuria. In the other three cases, frequent relapses had been observed for 6 to 15 years before the biopsies. However, all patients ultimately revealed complete remission with corticosteroid treatment. Serum IgA levels were within normal range in examined 4 cases. Hematuria was negative in all of them. The clinical findings seem to be identical to MCNS rather than IgA nephropathy, and IgA deposits may have no pathogenetic significance, although the pattern of deposition looks quite similar to that of IgA nephropathy. These results indicate that the renal lesions in the 6 patients may belong to the subtype of MCNS, rather than IgA nephropathy.