Histological differences in new-onset IgA nephropathy between children and adults.

BACKGROUND: It is suggested that IgA nephropathy (IgAN) manifests differently in children vs adults on the basis of biopsy findings. However, this has been difficult to establish owing to the uncertainty of the timing of disease onset in adult IgAN. We addressed this question by comparing both histology and leucocyte accumulation in biopsies of recently diagnosed childhood and adult IgAN. METHODS: Biopsies taken within 2 years from the onset of renal abnormalities in 33 childhood (10 +/- 3 years of age) and 38 adult (35 +/- 6 years) cases of IgAN were examined for histological changes (cellularity in mesangial, endocapillary and extracapillary areas, matrix expansion, adhesions/crescents and interstitial damage), glomerular deposition of immunoglobulin and complement, and the presence of macrophages, activated macrophages and T cells by immunohistochemistry. RESULTS: Glomerular hypercellularity owing to increased cells in mesangial area was prominent in paediatric IgAN and significantly greater than in adult IgAN. In contrast, glomerular matrix expansion, crescent formation and interstitial damage were more severe in adults compared to paediatric IgAN. Indeed, glomerular hypercellularity correlated with proteinuria in paediatric but not in adult IgAN, whereas glomerular matrix correlated with proteinuria and renal function in adult but not in paediatric IgAN. The degree of C3c deposition was significantly greater in paediatric IgAN, while deposition of fibrinogen was greater in adult IgAN. Glomerular and interstitial CD68+ macrophages and a subset of sialoadhesin (Sn)+ activated macrophages were identified in both paediatric and adult IgAN, being significantly greater in number in adult IgAN. Glomerular leucocyte infiltration correlated with proteinuria while interstitial leucocyte infiltration correlated with interstitial damage in both groups. However, only the subset of Sn+ macrophages gave a significant correlation with renal function, glomerular hypercellularity and glomerular matrix. CONCLUSIONS: This study has demonstrated significant differences in the early glomerular lesions of IgAN in children vs adults. Furthermore, Sn+ activated macrophages are implicated in the pathogenesis of IgAN in both patient groups. The prognostic significance of these findings warrants further study.     

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

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

Does thin basement membrane disease prolong the urinaryabnormality in minimal change IgA nephropathy?

Background. The renal prognosis of minimal change IgA nephropathy (MC IgAN) is generally a favorable one. It can also be associated with thin basement membrane disease (TBMD). However, occasionally, a persistent urinary abnormality is observed in some MC IgAN patients. This study was conducted to determine whether the complications of TBMD lead to a prolongation of the urinary abnormality in MC IgAN. Methods. We examined serial biopsy specimens from 991 adult patients (aged 16 years and older) with MC IgAN, 481 patients with TBMD, and 266 patients with MC IgAN + TBMD. The characteristics and duration of the urinary abnormality were compared among the three groups using the Kaplan-Meier method. Results. No significant difference was found in the prolongation of urinary abnormality between the MC IgAN and MC IgAN + TBMD groups. The reasons were twofold: The urinary abnormality in TBMD disappeared at an early stage (P < 0.01), and the complication rate of TBMD diffuse type (which sometimes has prolonged urinary abnormality) with MC IgAN was very low in comparison with that in TBMD diffuse type alone (P < 0.0001). Aging and hypertension were identified as factors inducing prolonged urinary abnormality in MC IgAN and TBMD. Conclusion. TBMD excluding the diffuse type, did not have an effect on the abnormal urinalysis of MC IgAN in the clinical course. Received: October 23, 1998 / Accepted: March 2, 1999     

Glomerular changes in microscopic haematuria, studied by quantitative immunoelectron microscopy and in situ zymography.

BACKGROUND:Haematuria of glomerular origin, even if mild, implies the development of defects in the glomerular basement membrane (GBM). In diseases where there is no infiltration of leukocytes into the glomerulus-such as thin basement membrane disease (TBMD) and histologically mild cases of IgA nephropathy (IgAN)-the mechanism by which such defects form is unclear. METHODS:Frozen renal tissue from 18 cases of TBMD, 18 of mild IgAN and 18 cases with no detectable abnormality were studied: (i) by quantitative in situ zymography, to estimate the activity of glomerular collagenases; and (ii) by quantitative immunoelectron microscopy to estimate the amount of major basement membrane proteins per unit length and per unit area of glomerular basement membrane. RESULTS:Cases of IgAN showed considerably more glomerular collagenase activity than normal (P=0.001). Thin basement membrane disease showed no difference in collagenase activity. A count of LCA-positive cells in glomeruli confirmed that the IgAN cases did not show glomerular leukocyte infiltration. Conversely, cases of IgAN showed no difference in GBM composition from normal, nor was any difference in GBM thickness detected in this group. However, cases of TBMD showed considerably less laminin (P=0.0008), fibronectin (P=0.002) and type VI collagen (P=0.0005) per unit length of basement membrane. Collagen IV showed a smaller reduction per unit length (P=0.01), but unlike the other protein studies it appeared to be present in higher concentration per unit area (P=0.03), suggesting that it is more 'compact' in TBMD disease. CONCLUSIONS:Two distinct mechanisms of haematuria seem to be involved in these two conditions. In IgAN there is increased activity of enzymes that can degrade GBM, probably reflecting mesangial cell activation. In TBMD an abnormal composition of the thinned GBM is confirmed. When considered with published reports of genetic abnormalities in TBMD, these results raise the possibility of an abnormal interaction between collagen IV and laminin.     

Quantitative analysis of glomerular type IV collagen alpha3-5 chain expression in children with thin basement membrane disease

Thin basement membrane disease (TBMD) and Alport syndrome, two forms of childhood nephritis, have generally been considered to be hereditary diseases. In Alport syndrome, several reports have demonstrated pathogenic mutations of the genes encoding type IV collagen alpha3, 4 and/or 5 chain [alpha3, 4 and/or 5(IV)]. Previous immunohistochemical studies indicated that these antigens were absent from the glomerular basement membrane (GBM) in Alport syndrome, whilst a normal labeling pattern was maintained in TBMD. In order to understand the role of the alpha3, 4 and/or 5(IV) antigens in TBMD, we used confocal laser scanning microscopy (CLSM) to examine cryosections of renal biopsies from 12 children with TBMD and 11 control children with IgA nephropathy (IgAN) without proteinuria. All tissue sections were stained with a mixture of FITC-conjugated rat monoclonal antibodies directed against human alpha3(IV), alpha4(IV) or alpha5(IV) and a Texas red-conjugated rat monoclonal antibody raised against human alpha2(IV). CLSM was performed and quantitative analysis of the ratio of the staining signal for alpha3(IV), alpha4(IV) or alpha5(IV) to alpha2(IV) [alpha3(IV), alpha4(IV) or alpha5(IV)/alpha2(IV)] along the GBM was determined. The average number of pixels for alpha3(IV), alpha4(IV) or alpha5(IV)/alpha2(IV) was 3.52 +/- 1.49, 3.54 +/- 1.25 and 1.09 +/- 0.49 in TBMD and 3.62 +/- 1.46, 3.99 +/- 1.53 and 1.77 +/- 0.47 in control subjects, respectively. Statistical analysis indicated that alpha5(IV)/alpha2(IV) ratio was significantly lower (p < 0.01) in children with TBMD compared to controls. These findings raise the possibility that TBMD might be caused by an abnormality of the alpha5(IV) antigen along the GBM.     

Hematuria and proteinuria in a mass school urine screening test

A total of 1,044 school children identified with hematuria and/or proteinuria during a mass school urine screening test were referred to pediatric nephrologists at 13 hospitals in Korea. These children had isolated hematuria (IH) (60.1%), isolated proteinuria (IP) (26.4%: transient, 19.6%; orthostatic, 4.9%; persistent, 1.9%) or combined hematuria and proteinuria (CHP) (13.5%). The patients history, physical examination, laboratory tests, kidney ultrasound and Doppler ultrasonography were obtained. Renal biopsies were performed on 113 children who showed severe proteinuria, hypertension, abnormal renal function, family history of chronic renal disease, systemic diseases or persistent hematuria and/or proteinuria for more than 12 months. IgA nephropathy (IgAN), thin basement membrane nephropathy (TBMN), membranoproliferative glomerulonephritis (MPGN), focal segmental glomerulosclerosis (FSGS), other GN, Alport syndrome and lupus nephritis were detected. IgAN and TBMN were the most common causes in the CHP group and IH group, respectively. Abnormal findings on the renal ultrasound with or without Doppler ultrasonography were noted in 147 cases (suspected nutcracker phenomenon, 65; increased parenchymal echogenicity, 40; hydronephrosis, 15). This study showed that the use of a mass school urine screening program can detect chronic renal disease in its early stage and recommends that more attention should be paid to identifying those children with CHP and massive proteinuria. A school urine screening program can detect chronic renal disease in its early stage. When mass screening is used, the initial aggressive diagnostic procedures such as renal biopsy are not needed. In addition, a regular follow-up for those children with IH and IP is certainly warranted.     

Partial depletion of macrophages by ED7 reduces renal injury in Adriamycin nephropathy

BACKGROUND: Because macrophages are considered to be possible effectors of disease in Adriamycin (ADR) nephrosis, we hypothesized that depletion of macrophages might protect against the initiation of renal injury. In the present study, a monoclonal antibody (ED7) directed against CD11b/CD18 integrin, which is expressed by macrophages, was used to investigate the pathogenetic effects of macrophages in ADR nephropathy. METHODS: Male Wistar rats were treated with ED7 antibody, starting 1 day prior to ADR (7.5 mg/kg) treatment, or 7 days post-ADR when overt proteinuria was established. RESULTS: Circulating ED7-positive cells were reduced by approximately 30% in rats with ADR nephrosis by the ED7 antibody, while the number of macrophages in the renal cortex of ADR rats was reduced by nearly 50% with the ED7 treatment, whether administered before or after ADR. Creatinine clearance was significantly ameliorated by ED7 when commenced pre-ADR (P < 0.05), but not when commenced post-ADR (P = NS) in comparison to untreated ADR rats. However, proteinuria was not alleviated by either ED7 treatment. Morphometric analysis showed less glomerular sclerosis when ED7 was commenced pre-ADR compared with ADR alone (P < 0.01), but not when commenced post-ADR (P = NS). Tubular atrophy was reduced by ED7 when it was commenced pre-ADR (tubular cell height and tubular diameter: P < 0.01 and P < 0.001, respectively), as was interstitial expansion (P < 0.01) compared with ADR alone. Cortical macrophage infiltration was reduced by 50% compared with ADR alone by the ED7 commenced before or after ADR. The number of cortical CD4+ T cells fell with ED7 starting pre-ADR, but not with the ED7 treatment commencing after ADR. CONCLUSION: Partial macrophage depletion starting before but not after ADR protected both renal function and structure in this model of chronic proteinuric renal disease.     

A comparison of the clinical and laboratory features of thin basement membrane disease (TBMD) and IgA glomerulonephritis (IgA GN).

AIM: The aim of this study was to determine the clinical and laboratory characteristics that distinguished thin basement membrane disease (TBMD) from IgA glomerulonephritis (IgA GN) at presentation and at follow-up. PATIENTS AND METHODS: Seventy-one patients with TBMD and 31 with IgA GN were studied. Males accounted for 11/71 (15%) patients with TBMD, and 20/31 (65%) of those with IgA GN (p < 0.001). RESULTS: At presentation, patients with TBMD had hematuria (42%) or proteinuria (42%), and sometimes both (24%), while those with IgA GN usually had both hematuria and proteinuria (71%, p < 0.0001). Furthermore, patients with IgA GN were more likely to have higher urinary RBC counts (p < 0.001), and more proteinuria (p < 0.001) than those with TBMD. An elevated serum creatinine or blood pressure did not distinguish between TBMD and IgA GN at presentation. At review, fewer individuals with IgA GN had elevated levels of urinary RBC and protein, and the proportions were not different from those in patients with TBMD. This was presumably because the acute episode had resolved. CONCLUSION: The outcome was worse in patients with IgA GN, with 8/31 (26%) having an elevated serum creatinine and 3/31 (10%) with end-stage renal failure, compared with an elevated serum creatinine in 3/61 (5%) patients with TBMD (p < 0.02) and no patients with renal failure (p < 0.05).     

Recurrence of IgA nephropathy 17 months after renal transplantation in the allograft transmitted thin basement membrane disease (TBMD) from donor

Recurrence of IgA nephropathy (IgAN) following renal transplantation has been described in 40-50% of such patients and it usually has a good outcome. We present the case of a 20-yr-old woman with IgAN who developed end-stage renal failure in 1995. In November 1996, she received a kidney from a living-related donor and was treated with tacrolimus, azathioprine and steroids. Zero- and one-hour biopsies were performed, which revealed minor glomerular abnormalities in light microscopy, thin basement membrane disease (TBMD) in electron microscopy. Eight months later she developed microscopic hematuria and proteinuria; however, the graft function was normal. Renal biopsy revealed an IgAN that is thought to be due to recurrence of the original disease.     

Frequency of renal diseases and clinical indication for renal biopsy in children (Report of the Italian National Registry of Renal Biopsies in Children)

Background. Children's renal biopsy data were gathered for 3 consecutive years (1992-1994) by the Group of Renal Immunopathology of the Italian Society of Pediatric Nephrology, which opened a paediatric section of the Italian Registry of Renal Biopsies. Materials. The Registry recorded the histological diagnosis and the clinical data at renal biopsy of 432 children ⩽15 years old (mean age 8.96±3.7 years). Results. The most common glomerulonephritis (GN) at renal biopsy was idiopathic IgAGN (18.8%) and the most frequent secondary GN was Henoch-Schonlein purpura (HSP) nephritis (11.6%). Minimal-change disease (MCD) accounted for 11.6%, focal and segmental sclerosis (FSG) 8.5%, mesangial proliferative GN (MPGN) 9.5%, membranoproliferative GN 5.5%, and thin-membrane disease 5%. Lupus nephritis was diagnosed in 5% and Alport's GN in 3.9% of the cases. The annual incidence of primary GN in Italian children was 11.1 cases per million children population (p.m.c.p.), IgAN accounting for 3.1 cases, MCD 2.3, and HSP nephritis 1.9 cases p.m.c.p. respectively. Italian children underwent renal biopsy because of isolated microscopic haematuria in 19.3% of the cases, non-nephrotic proteinuria with or without microscopic haematuria in 31.2%, and nephrotic-range proteinuria in 34.2%, less frequently (15.3%) because of acute or chronic renal failure. Children with persistent isolated microscopic haematuria had most frequently IgAN (34.9%) or thin-membrane disease (25.3%), while those with non-nephrotic proteinuria had IgAN (30.4%) and HSP nephritis (23%). In cases with nephrotic proteinuria renal biopsy showed MCD in 34.5% of the cases, FSG in 16.9%, and MPGN in 12.2%. When renal biopsy was performed in chronic renal failure chronic interstitial renal disease was detected in 62.5% of the cases. Conclusions. This National Registry provides data on the indications for performing renal biopsy in Italian children and on the frequency and annual incidence of histological lesions detected. IgAN, primary or related to HSP, was the most common nephritis in Italian children undergoing renal biopsy.     

Tubular and interstitial expression of ICAM-1 as a marker of renal injury in IgA nephropathy

BACKGROUND: The upregulated renal expression of intercellular adhesion molecule 1 (ICAM-1) is associated with glomerular and interstitial infiltration of leukocytes. AIM: To test the hypothesis that renal expression of ICAM-1 may be predictive in the highly variable IgA nephropathy (IgAN). METHODS: ICAM-1 (CD54) in tubular epithelium and interstitial leukocytes, macrophages (CD14), and T cells (CD3) were assessed using avidin-biotin-peroxidase in renal biopsy specimens from 45 patients with IgAN and from 29 patients with no glomerulonephritis. RESULTS: In IgAN, tubular ICAM-1+ was seen in 25 of 45 (55%) biopsy specimens, associated with glomerular hypercellularity, glomerulosclerosis involving less than 50% of the glomerular area, interstitial cellular infiltration, tubular atrophy, and proteinuria (U = 44, p = 0.005). Interstitial ICAM-1+ leukocytes were correlated with glomerulosclerosis involving less and more than 50% of the glomerular area, tubular atrophy, interstitial fibrosis, and serum creatinine concentration (r = 0.6343, p < 0.001). In patients with an increase of 50% in the serum creatinine concentration, interstitial ICAM-1+ leukocytes and CD14+ and CD3+ cells were significantly more numerous than in patients with a stable creatinine concentration. In patients with no glomerulonephritis, tubular ICAM-1+ was seen in 7 of 29 (24%) biopsy specimens, inversely correlated with the number of normal glomeruli and associated with glomerulosclerosis covering more than 50% of the glomerular area, tubular atrophy, and creatinine. CONCLUSIONS: Tubular and interstitial expression of ICAM-1 can be a marker of tubulointerstitial disturbance in IgAN. Interstitial ICAM-1 may be an adverse predictor of disease progression.     

Use of mizoribine as a rescue drug for steroid-resistant pediatric IgA nephropathy

Recent clinical trials have shown a beneficial effect of mizoribine (Miz), an immunosuppressive drug, in the treatment of new-onset pediatric IgA nephropathy (IgAN). In this study, we evaluated the efficacy of Miz treatment in three children with established steroid-resistant IgAN. The patients had IgAN featuring persistent proteinuria and diffuse mesangial proliferation and had failed to respond to 2 years of treatment with prednisolone. Based upon the second biopsy results, patients were given methylprednisolone (mPSL) pulse therapy that induced a transient reduction in proteinuria, which was reversed when the mPSL dose was tapered. Miz therapy was then instigated in place of pulse mPSL. All three patients showed a substantial reduction in proteinuria and resolution of hematuria within 5 months. A follow-up biopsy in two of the patients showed a substantial reduction in the severity of glomerular lesions and a decrease in the number of activated macrophages. In conclusion, Miz therapy was found to be a safe and effective therapy in three cases of steroid-resistant pediatric IgAN. The ability of Miz to reduce the number of activated macrophages may be an important mechanism by which this drug ameliorated renal disease in these patients.     

IgA肾病患者血与尿血管内皮生长因子水平变化的临床意义

目的 :探讨IgA肾病患者血、尿血管内皮生长因子 (VEGF)水平的临床意义。 方法 :IgA肾病患者2 0例和健康对照 14例 ,留取空腹血清和晨起清洁中段尿 ,采用抗体夹心ELISA方法测定血、尿VEGF水平。详细收集IgA肾病患者的血压、肾功能、2 4h尿蛋白定量和血尿程度等资料 ,与血、尿VEGF对比分析其临床意义。结果 :IgA肾病患者血、尿VEGF水平均高于健康对照组 (P <0 .0 1或P <0 .0 5 ) ;IgA肾病患者血、尿VEGF水平与 2 4h尿蛋白定量呈正相关 (P <0 .0 1或P <0 .0 5 ) ,2 4h尿蛋白定量 <1.5g的患者血、尿VEGF水平明显低于尿蛋白定量 >1.5 g的患者 (P <0 .0 1或P <0 .0 5 ) ;与患者血尿程度、血压无相关性。结论 :IgA肾病患者血、尿VEGF水平与IgA肾病尿蛋白排出量呈正相关     

尿巨噬细胞移动抑制因子与IgA肾病的相关性

目的：探讨尿巨噬细胞移动抑制因子（MIF）水平与IgA肾病（IgAN）患者病情进展之间的关系。方法：用酶免疫方法（EIA）测定35例IgAN患者尿MIF浓度,并与肾脏病理分级、24h尿蛋白（TUP）、内生肌酐清除率（Ccr）、血尿等进行分组分析,以10例健康体检者作对照组。结果：IgAN患者尿MIF浓度较健康人明显增高,差异有统计学意义（P〈0．01）,且随着病理分级增加而逐渐增高,各组间差异有统计学意义（均P〈0．01）,尿MIF水平与24h蛋白尿水平显著相关（r=0．787,P〈0．01）,与Ccr、血尿无显著相关;随着病情控制,治疗后尿MIF较治疗前显著下降,差异有统计学意义（P〈0．01）。结论：IgAN尿MIF浓度明显增高,与病情严重程度相关,对于患者病情的判断有一定价值。     

Altered P-selectin and CD44 expression in the renal tissues and peripheral blood of children with IgA nephropathy

Objective  To understand the role of P-selectin (CD62P) and CD44 in mediating immune inflammation in the nephrotic process of children with IgA nephropathy (IgAN), cooperative expression of CD62P and CD44 in peripheral blood and renal tissues of IgAN children was investigated and its association with changes of histopathologic, serologic, and urinary properties was tested. Material and methods  Forty-six IgAN children were divided into three groups according to pathologic grades and clinical features. Fifteen blood samples from normal children and four normal renal biopsy specimens were used as controls. Plasma level of CD62P was detected by double antibody sandwich immunoradiometric assay; ELISA was used to determine serum level of CD44. Expression of CD62P and CD44 in renal tissues was determined by immunohistochemistry. Results  Cooperative expression of CD62P and CD44 was detected in renal tissues and peripheral blood of IgAN children. Altered expression of CD62P and CD44 in peripheral blood significantly correlated not only with hematuria, proteinuria, serum cholesterol, and albumin, and with urine NAG and β₂-MG, but also with degree of tubulointerstitial injury in IgAN children. Conclusion  The evidence supported CD62P and CD44 as initial and promoting factors mediating immune inflammation in the nephrotic process in IgAN children. The cooperative expression profiles of CD62P and CD44 in renal tissues and peripheral blood combined with serologic and urinary predictors may be important in diagnosis of progression in children with IgAN.     

尿N-乙酰-β-D氨基葡萄糖苷酶在IgA肾病肾小管间质损伤中的评估价值

目的评估尿N-乙酰-β-D氨基葡萄糖苷酶在IgA肾病肾小管间质损伤中的价值。方法回顾性分析2014年2月至2018年6月于本院行肾穿刺活检确诊为IgA肾病的患者82例,分为NAG正常组(NAG<12 U/L,14例)、NAG升高组(NAG>12 U/L,68例);分析两组患者间临床与病理指标的差异,并评估NAG与肾小管间质病变的相关关系。结果NAG正常组的NAG、血肌酐、胱抑素-C、尿微量白蛋白的统计量显著低于NAG升高组(P<0.05),NAG正常组的eGFR的统计量显著高于NAG升高组(P<0.05),病理改变中,NAG正常组的肾小球系膜细胞增殖、肾间质炎症细胞浸润、肾间质纤维化、肾小管萎缩积分显著低于NAG升高组,进一步logistic回归分析显示微量白蛋白、eGFR、系膜增殖、肾小管间质的病理改变为影响NAG水平的独立危险因素。结论尿NAG水平与患者eGFR、mALB以及小管间质病变密切相关,可以作为评估和监测IgAN的小管间质病变程度的临床指标。     

IgA肾病治疗的思考

IgA肾病是我国最常见的原发性肾小球疾病。主要以IgA免疫球蛋白沉积于肾小球为病理特征;以血尿、蛋白尿、高血压和肾功能损害为主要临床表现。每次血尿和(或)蛋白尿发作是肾小球损伤的标志,如不有效进行干预,可逐渐出现肾功能损害。控制血尿和(或)蛋白尿,降低尿检异常发生的频率,是治疗原发性IgA肾病及防止肾脏慢性化损伤的关键。ACEI/ARB在减少IgA肾病患者的蛋白尿、保护残存肾功能、延缓其进展为终末期肾病等方面优于其他降压药。IgA肾病如有较多新月体形成、明显血尿和蛋白尿,可考虑使用糖皮质激素和(或)与免疫抑制剂。由于IgA肾病是一个慢性化过程,长期随访对改善该病的预后显得尤为重要。     

Analysis of 4931 renal biopsy data in central China from 1994 to 2014

The purpose of this study is to investigate the changing spectrum and clinicopathologic correlation of biopsy-proven renal diseases in central China. We retrospectively analyzed data of 4931 patients who underwent renal biopsy in ten hospitals between September 1994 and December 2014. Among them, 81.55% were primary glomerular diseases (GD), and 13.02% were secondary GD. IgA nephropathy (IgAN) was the most common primary GD (43.45%), followed by focal glomerulonephritis (16.79%), mesangial proliferative glomerulonephritis (MsPGN, 14.35%), and membranous nephropathy (MN, 13.28%). IgAN was leading primary GD in patients under 60 years old, while MN was the leading one over 60 years old. The most frequent secondary GD was lupus nephritis (LN) (47.35%). The prevalence of IgAN, MN and minimal change disease was found to increase significantly (p?<?0.001, p?<?0.001, and p?<?0.01, respectively), while that of MsPGN, membranoproliferative glomerulonephritis and LN decreased significantly (p?<?0.001, p?<?0.001, and p?<?0.05, respectively). The main indication for renal biopsy was proteinuria and hematuria (49.03%), followed by nephrotic syndrome (NS, 20.36%). IgAN was the most common cause in patients with proteinuria and hematuria, chronic-progressive kidney injury, hematuria and acute kidney injury; and MN was the leading cause of NS. Primary GD remained the predominant renal disease in central China. IgAN and LN were the most prevalent histopathologic lesions of primary and secondary GD, respectively. The spectrum of biopsy-proven renal disease had a great change in the past two decades. Proteinuria and hematuria was the main indication for renal biopsy.     

Clinicopathological correlations in nephrotic children with IgA nephropathy

Background. The prognostic significance of nephrotic syndrome (NS) in children with IgA nephropathy (IgAN) is unclear. Methods. NS was found in eight children with IgAN (mean onset age, 9.3 years). The clinicopathological findings of these eight children were investigated. Results. Five patients presented with macroscopic hematuria, while the remaining three were discovered in a school urinary screening program or by chance urinalysis. Six patients developed NS at the onset, and two developed NS later in the course of IgAN. All patients were treated with corticosteroids. At the end of follow-up, heavy proteinuria persisted in four children, one of whom had renal dysfunction at the onset of NS and developed end-stage renal failure, and two of whom developed NS after the onset of IgAN. Proteinuria decreased to less than 1 g/day 3 months after NS in four patients, two of whom showed disappearance of proteinuria afterward. Renal biopsy specimens revealed mesangial proliferation and crescent formation in all patients. The degree of persisting proteinuria was correlated with the presence of glomerular sclerosis, fibrous crescents, tubulo-interstitial changes on light microscopy, and depositions of C3 on immunofluorescence microscopy. Conclusions. Children who developed NS after the onset of IgAN developed renal dysfunction; the prognosis of those who showed chronic histopathological changes on renal biopsy specimens was poor, even in these young children. Received: April 17, 2000 / Accepted: July 4, 2000     

Significance of CD25 positive cells and macrophages in noncrescentic IgA nephropathy

The aim of this study was to determine whether infiltration by CD25 positive cells, macrophages, and activated macrophages in the kidney is predictive of chronic histological injury and renal prognosis in adults with noncrescentic IgA nephropathy. Renal biopsies of 36 patients with noncrescentic IgA nephropathy were examined by immunohistochemistry for glomerular and interstitial CD4, CD8, and CD25 positive cells, monocytes/macrophage (Mac387), and activated macrophages (27E10). Renal injury (glomerulosclerosis, mesangial cell hypercellularity, tubular atrophy, and interstitial fibrosis) at the time of biopsy and renal prognosis (follow-up creatinine and creatinine clearance) were assessed. The mean follow-up period was 22.5 +/- 16.5 months. The number of interstitial CD8 positive cells was the best predictor of renal injury at the time of biopsy, and was positively correlated with glomerulosclerosis (p = 0.04), tubular atrophy (p = 0.04), and interstitial fibrosis (p = 0.01) but not with mesangial cell hypercellularity. The number of interstitial Mac387 and 27E10 positive cells were the best predictors of renal prognosis (r2 = 0.33 and 0.34 respectively, both p < 0.01). These data suggest the presence of CD8 cells and macrophages in the kidney at the time of biopsy could potentially serve as pathological markers to identify patients with IgA nephropathy, which may warrant more aggressive medical therapy.