The temporal relationship between urinary C5b-9 and C3dg and clinical parameters in human membranous nephropathy

We have previously reported that urinary excretion of the complementactivation products C3dg and C5b–9 in human membranousnephropathy (MN) correlated with clinical outcome in a cross-sectionalanalysis. We report here the results of a retrospective longitudinalstudy of the temporal relationship between urinary C3dg andC5b–9 excretion and clinical parameters. A group of 23adult patients with biopsyproven MN were studied over a meantime period per patient of 3.5 years. Freshly voided urine sampleswere collected regularly; C3dg and C5b–9 were measuredby ELISA (mean number of samples per patient=13). During the period of the study, nine patients with decliningrenal function (group A) were treated with a standard steroidregimen. Serum creatinine had improved or stabilized in sevenof these patients at the end of treatment. All nine patientswere excreting C3dg and C5b–9 before treatment. Six otherpatients with declining renal function (group B) were not treatedwith steroids because of clinical contraindications. Serum creatininecontinued to increase during the study in four of these sixpatients. C3dg and C5b–9 were present in the urine samplesof these six patients on the majority of dates tested. Eight patients maintained stable renal function during the study(group C), either normal (6 patients) or impaired (2 patients).Of these patients, six were consistently negative for urinaryC3dg and C5b–9 despite persistent proteinuria, and onepatient who was initially positive became negative within 15months, and remained negative for the rest of the study period.One patient was positive on one of 12 occasions tested. Theseresults suggest that urinary complement activation productsindicate ongoing active glomerular damage and may prove to beimportant determinants for the introduction and monitoring oftherapy.     

The pathogenetic significance of C5b-9 in IgA nephropathy

Renal biopsies from 20 patients with IgAN were retrospectivelystudied using monoclonal antibodies against T cells, monocytes/macrophages(MM), HLA-DR-related antigen and the C5b-9 neoantigen. GlomerularC5b-9 deposits were mainly found in the mesangial areas andshowed an association with IgA (P<0.005) and C3 deposits(P<0.001). Interstitial T cells and MM were highly correlatedwith the interstitial DR+ve cells (P<0.001 and P<0.0005respectively). Tubular C5b-9 deposition was observed on thetubular basement membranes and related to the numbers of interstitialT cells (P<0.005), MM (P<0.005) and DR+ve cells (P<0.01)as well as to the tubular DR expression (P <0.025). The severityof tubular atrophy and interstitial fibrosis showed a positivecorrelation with the interstitial T cells, MM and DR+ve cells,as well as with the intensity of tubular C5b-9 deposition (P<0.05and P<0.05 respectively). Plasma creatinine on presentationwas correlated with the numbers of interstitial T cells (P<0.05),MM (P<0.01), interstitial DR+ve cells (P<0.005), and tubularC5b-9 deposits (P<0.005). No correlation between glomerularT cells, MM, and C5b-9 deposits with plasma creatinine was seen.During follow-up, renal function deteriorated in those patientswith the more extensive tubular C5b-9 deposits In conclusion, glomerular C5b-9 deposition seems to be secondaryto the IgA and C3 deposition. In contrast, tubular C5b-9 isrelated to the numbers of interstitial T cells and MM. Activatedinterstitial mononuclear cells may lead to the tubular depositionof C5b-9, which eventually might contribute to the developmentof tubulointerstitial lesions (TIL) and renal function impairment     

血清抗核抗体阳性的不典型膜性肾病与狼疮膜性肾病及特发性膜性肾病的临床病理比较

目的 探讨血清抗核抗体（ANA）阳性的不典型膜性肾病（AMN）与狼疮膜性肾病（LMN）、特发性膜性肾病（IMN）的关系，寻找对诊断LMN具有较高预测价值的临床和病理学指标。 方法 2003年1月至2006年12月期间在北京协和医院住院并行肾活检，临床、病理资料保存完整的患者为对象。分组：AMN组（n = 28）：血清ANA滴度≥1∶80，少于4条美国风湿病学会（ARA）修订的系统性红斑狼疮分类标准，病理呈肾小球基底膜病变伴系膜增生和（或）免疫荧光C1q阳性；IMN组（n = 100）；LMN组（n = 45）。回顾性分析各组病例的临床表现、病理学特点。应用免疫组化法，对各组部分病例肾活检组织行IgG亚型染色，半定量分析染色强度。对各组部分病例肾活检组织行免疫荧光双染色（IgG-TRITC，C3-FITC），用激光扫描共聚焦显微镜观察肾小球沉积的IgG和C3的空间分布。 结果 (1)AMN组起病年龄（38±17）岁，女∶男比为2.5∶1，介于LMN和IMN之间。3组起病年龄差异有统计学意义（P < 0.01），AMN组女∶男比高于IMN组（P = 0.017）。AMN组血液系统异常、血抗SSA抗体阳性百分比较高（21.4%、40.7%）。(2)AMN组系膜增生、系膜区及内皮下电子致密物出现的百分比高于IMN组（P < 0.01）。(3)AMN和LMN组肾小球IgG3沉积占优势的百分比分别为78.9%、73.9%；IMN组IgG4沉积占优势的百分比为61.1%，差异均有统计学意义（IMN组与AMN、LMN组比较, P < 0.01）。(4)IMN组常出现IgG和C3在上皮下的共沉积现象，而在AMN和LMN组中少见。(5)在鉴别LMN和IMN的指标中，敏感性较高的有肾小球IgG4不占优势（91.3%）；特异性较高的有内皮下电子致密物（100.0%）、血抗SSA抗体（95.5%）、肾小球IgG3占优势（94.4%）。 结论 AMN的临床表现与IMN类似，而各项病理学特点，尤其是肾小球IgG亚型沉积特点与LMN更为接近。它有可能是狼疮肾炎中较为隐匿的一个亚型。     

特发性膜性肾病的免疫抑制剂治疗

特发性膜性肾病(IMN)多以大量蛋白尿、低蛋白血症、浮肿、高脂血症等肾病综合征表现起病,是我国原发性肾小球肾炎中常见类型。个体预后差异较大。免疫抑制剂是治疗IMN中主要药物之一。糖皮质激素、烷化剂(环磷酰胺/苯丁酸氮芥)、钙调磷酸酶抑制剂(环孢素/他克莫司)、雷公藤等免疫抑制剂在治疗IMN具有重要地位。最近研究显示新型免疫抑制剂如利妥昔单抗、吗替麦考酚酯、来氟米特、促肾上腺皮质激素等在治疗IMN中也具有一定前景。     

Urinary excretion of cytokines and complement SC5b-9 in idiopathic membranous glomerulonephritis

Idiopathic membranous glomerulonephritis (iMGN) has previouslybeen shown to be associated with urinary excretion of terminalcomplement complexes while increased urinary levels of cytokineshave been reported in mesangial proliferative glomerulonephritis.In the present cross-sectional study urinary excretion of IL-1ßTNF-, IL-6;, and soluble C5b-9 (SC5b-9) was examined for 23patients with iMGN, 16 patients with diabetic nephropathy (DNP),and 17 healthy subjects. IL-1ß excretion (pg/mg crea)was significantly higher in iMGN patients (375, range 162–11000) than in DNP patients (39, range 22–59, P<0.001)or healthy controls (151, range 23–481, P<0.00l). TNF-excretion rate (pg/mg crea) was clearly higher (38, range 21–700)in iMGN patients than in DNP patients (14, range 8–52,P< 0.001) or healthy subjects (11, range 7–26, P<0.001).Median IL-6 excretion (pg/mg crea) was only marginally higherin iMGN patients (73, range 0–850) than in healthy subjects(64, range 3–158, P=0.02) but significantly higher thanin DNP patients (29, range 17–47, P<0.001). No significantcorrelation with corresponding serum values was observed forurinary IL-6 or TNF- excretion. Urinary IL-1/ß andTNF- correlated with decreased renal function. Five of 23 patientsshowed progression of iMGN over a follow-up of 6 months. Theexcretion of all cytokines, TNF- in particular, was significantlyhigher in patients with a progressive disease than in the otherpatients. High TNF- excretion (>57 pg/mg crea) was detectedin 4/5 patients with progression but in none of the stable patients(P<0.001). Seventy-seven per cent of the iMGN patients and94% of DNP patients, but none of the healthy subjects had detectableSC5b-9 excretion. In DNP patients the urinary SC5b-9 levelscorrelated with proteinuria whereas in iMGN the SC5b-9 excretioncould not be accounted for by proteinuria alone. Urinary excretionof SC5b-9 correlated with decreased renal function and had arelationship to urinary IL-1/ß and TNF- excretionin iMGN patients. Moreover the median excretion rate of SC5b-9was higher in patients with than in those without progressionof iMGN. The results suggest that increased urinary IL-1ß,TNF-, and SC5b-9 excretion are detected in patients having iMGN.They may be indicators of a progressive renal disease in iMGN.     

Efficacy of cyclosporin in difficult-to-treat idiopathic membranous nephropathy

SUMMARY: Poor tolerance and the potential long-term toxicity have limited the widespread use of corticosteroids and cytotoxic drugs in the treatment of idiopathic membranous nephropathy (IMN). Cyclosporin A (CyA) has been proven to be a less toxic alternative, but its efficacy needs further confirmation. Cyclosporin A (2–3mg/kg per day) in combination with low-dose methylprednisolone (4mg/day) was given to 28 nephrotic patients with IMN who had failed to respond, or tolerate, or to complete treatments with steroids and/or cytotoxic drugs. the mean duration of treatment was 11 ± 7 months. Seven patients (25%) showed a complete remission of proteinuria, 17 (60%) a partial one, and four (15%) did not respond at all. the average time to achieve optimal remission was 4.2 ± 1.4 weeks following the initiation of therapy. In those who responded completely or partially, plasma creatinine (Per) did not change significantly from pre CyA levels during follow up (1.0 ± 0.3 vs 1.2 ± 0.3mg/dL, P =NS). the remaining four patients who had renal insufficiency already before CyA (mean Per: 2.1 ± 0.8mg/dL), showed a rapid deterioration of renal function after the initiation of CyA (mean Per: 3.1 ± 1.5 mg/dL, P <0.01), and as a consequence, the drug was discontinued. A mul-tivariate analysis on the clinical and histological features demonstrated that the degree of renal function impairment ( P <0.02), the percentage of obsolete glomeruli ( P <0.01), and the severity of interstitial fibrosis ( P <0.005) independently predicted the response to therapy. Low dose CyA is an effective and safe alternative treatment for patients with IMN and normal renal function. However, the drug should be given with caution to patients with established renal insufficiency.     

Relationship between interstitial infiltrates and steroid responsiveness of proteinuria in membranous nephropathy

Mononuclear inflammatory cells were retrospectively analysedusing monoclonal antibodies in the interstitium and glomeruliof 16 renal biopsy specimens from patients with nephrotic syndromedue to idio-pathic membranous nephropathy (IMN). The aim ofthe study was to determine the composition of the infiltrateand to assess the ability to predict the response of proteinuriato corticosteroids. All patients had received prednisolone asa sole treatment. Nine patients had shown a complete or partialremission of proteinuria (group A) and seven did not respondat all (group B). Both groups were matched for age and degreeof proteinuria; also both groups had normal renal function atthe time of biopsy. Very few intraglomerular leukocytes, mostlymonocytes/ macrophages (MM) were found. The majority of interstitialcells were T lymphocytes and MM. CD4+ve T helper/inducer cellspredominated among the interstitial T cell population and Bcells were a minor component. No significant differences werefound between the two groups regarding the types of the intraglomerularcells. However, interstitial T-cells, CD4 + ve T helper/inducercells, CD8+ve T cytotoxic/suppressor cells and MM were significantlyhigher in group A than in group B. Also HLA-DR expressing interstitialcells were much in excess in group A. In addition patients with complete remission of proteinuriahad higher numbers of interstitial cells compared to those withpartial response. There was no correlation between the numbersof types of intraglomerular and interstitial cells and the degreeof proteinuria at presentation. Also no association was foundbetween intraglomerular or interstitial cell population andsubsequent relapse of proteinuria. In conclusion, interstitial but not intraglomerular mononuclearcells seem to determine the initial response of proteinuriato corticosteroids in patients with IMN.     

Plasma total homocysteine concentration in nephrotic patients with idiopathic membranous nephropathy.

BACKGROUND: The atherothrombotic risk pattern of the nephrotic syndrome resembles that of hyperhomocysteinemia. However, the effect of nephrotic range proteinuria on homocysteine metabolism has never been studied. METHODS: The study included 11 male nephrotic patients with idiopathic membranous nephropathy who underwent a treatment trial with adrenocorticotrophic hormone and 11 male non-nephrotic, renal function-matched control subjects. The nephrotic patients were studied before and after the treatment, which induced a marked reduction in urinary protein excretion and a moderate improvement in renal function in all cases. RESULTS: Plasma total homocysteine (tHcy) concentration did not change significantly during treatment, whereas the nephrotic patients had significantly lower tHcy than the non-nephrotic patients (14.2 +/- 3.4 micromol/l vs 19.0 +/- 5.4 micromol/l). tHcy correlated significantly with serum concentrations of creatinine (r = 0.53, P < 0.05) and albumin (r = 0.43, P < 0.05), glomerular filtration rates (GFRs) (iohexol clearances) (r = -0.42, P < 0.05) and urinary albumin excretion (r = -0.47, P < 0.05). CONCLUSION: The expected tHcy-lowering effect of improved renal function may have masked a tHcy-elevating effect due to reduced proteinuria leading to no net change in tHcy during treatment. The notion of an increase in tHcy associated with remission of the nephrotic syndrome is in accordance with the significantly lower tHcy in the nephrotic renal patients compared with the non-nephrotic renal function-matched patients, and the relationships between tHcy and serum albumin concentrations as well as urinary albumin excretion. Thus, the results of this small study suggest that nephrotic range proteinuria directs homocysteine metabolism towards a decrease in tHcy. However, the findings need to be confirmed in larger patient populations and in different varieties of the nephrotic syndrome.     

Immunosuppressive therapy with cyclophosphamide and prednisolone in severe idiopathic membranous nephropathy

In idiopathic membranous nephropathy (IMN) immunosuppressivetherapy should be reserved for patients with potential riskfactors at baseline or who show a progressive course. Cyclophosphamidepulse therapy (CPT) in IMN is not yet widely tested. We carriedout a trial of CPT combined with conventional treatment in agroup of patients with IMN at a greater risk. The study group consisted of 36 nephrotic adult IMN patients(M, 26; F, 10) with various combinations of risk factors. Meanproteinuria was 11.3 g/day, 47.% patients were hypertensive,78% had tubular changes, and 36% had focal glomerulosclerosis.They were treated with CPT and/or conventional low-dose cyclophosphamideand prednisolone. Median duration of immunosuppression was 14months and median total cumulative dose of cyclophosphamide172mg/kg body weight. At 6 months (6m) remission was achieved in 44% cases and atthe 36th month in 73%. None of the patients developed moderateor severe renal failure. Side-effects were minimal. Multivariateanalysis of baseline data and the changing course of the diseaseduring therapy showed that tubular changes (P = 0.0025), creatinineclearance at baseline (P = 0.04) and at 6m (P = 0.02), and proteinuriaat 6m (P<0.0001) significantly influenced the therapeuticeffect. We conclude that cyclophosphamide (including pulse) and prednisolonecan bring significant remission and maintain renal functionin IMN with potential risk factors.     

Association of serum mannose-binding lectin,anti-phospholipase A2 receptor antibody and renal outcomes in idiopathic membranous nephropathy and atypical membranous nephropathy: a single center retrospective cohort study

ObjectivesIdiopathic membranous nephropathy (iMN) is a major cause of nephrotic syndrome. Atypical membranous nephropathy (aMN) is a new type of nephropathy in China, characterized by a ‘full-house’ on immunofluorescent examination, that is IgG, IgA, IgM, C3, C1q positive, but without clinical evidence of a secondary cause. Phospholipase A2 receptor (PLA2R) was the major target antigens in iMN patients. Activation of the mannose-binding lectin (MBL) pathway plays a vital role in the development of MN. Our objective was to investigate the role of PLA2R and MBL in the pathogenesis of iMN and aMN.MethodsWe conducted a retrospective observational study using propensity score matching by age, gender, and eGFR. All clinical, laboratory data, and follow-up data of the patients were collected. Serum levels of anti-PLA2R antibodies and MBL were tested.ResultsFinally, 30 iMN patients and 30 aMN patients were included, and 20 healthy controls were retrospectively collected in this study. The 24 h proteinuria level was higher and serum albumin was lower in anti-PLA2R (+) patients than in anti-PLA2R (−) patients in both iMN and aMN groups. In aMN patients, MBL levels were significantly higher in anti-PLA2R (+) patients than in anti-PLA2R (−) patients (p = .045). The serum level of anti-PLA2R positively correlated with no-remission in both iMN and aMN groups.ConclusionsThe complement lectin pathway has an association with the development of MN, especially in patients with positive anti-PLA2R antibodies. Serum MBL cannot differentiate between the two diseases. Serum MBL levels are not associated with clinical manifestations, nor with prognosis.     

Renal C3 synthesis in idiopathic membranous nephropathy: correlation to urinary C5b-9 excretion

Renal C3 synthesis in idiopathic membranous nephropathy: Correlation to urinary C5b-9 excretion. BACKGROUND: Complement activation plays a central pathogenetic role in idiopathic membranous nephropathy (IMN). Urinary excretion of C5b-9 correlates to the immunologic activity of this disease. Recently, renal cortical C3 gene expression has been described in several nephropathies. METHODS: The aim of this study was to investigate the renal C3 gene expression by in situ hybridization in IMN and to correlate it with histopathologic, pathophysiologic, and immunologic (urinary C5b-9) indices of disease activity. RESULTS: C3 was expressed in 77% of 22 renal biopsies of IMN patients, mainly at the cortical tubular and glomerular parietal epithelial cell levels. C3 protein synthesis by tubular cells was demonstrated by immunofluorescence. The intensity of C3 gene expression by both glomerular and tubulointerstitial compartments correlated with the glomerular stage of disease (P = 0. 0023 and P = 0.0214, respectively). Although no correlation was found with proteinuria, serum creatinine at renal biopsy time was strongly associated with renal C3 expression. IMN patients showed a trend of increased urinary C5b-9 levels, which correlated to C3 at the tubulointerstitial level (P = 0.0143). CONCLUSION: Renal C3 production, mainly at the tubular level, may be induced by urinary excretion of C5b-9 in IMN and may have a pathogenetic role in the tubulointerstitial damage that can be associated with this disease.     

特发性膜性肾病血栓栓塞并发症的预防与治疗

特发性膜性肾病(IMN)最常见的并发症为静脉血栓和栓塞症,其可对机体造成不同程度的损伤,加剧患者的病情进展,影响预后,严重时甚至可造成患者死亡。但至今为止尚无指导临床用药的可靠实验室指标,也无统一的诊疗规范或措施。本文根据国内、外最新研究进展及相关指南,从预防及治疗的角度,探讨临床上对IMN并发静脉血栓或栓塞的干预方法,并对IMN并发静脉血栓或栓塞治疗过程的监测指标做一概述。     

Urinary C3dg and C5b-9 indicate active immune disease in human membranous nephropathy.

We have measured complement activation markers, C3dg and C5b-9 in plasma and urine from patients with idiopathic membranous nephropathy and IgA nephropathy. There was no significant difference in levels of plasma C5b-9 between the patient groups. However, high plasma concentrations of C3dg were associated significantly with IgA nephropathy with 45% of patients having levels over 25 U/ml (P less than 0.001). High concentrations of urinary C3dg and C5b-9 were associated significantly with membranous nephropathy (43% and 43% of the patient group, respectively) compared to patients with IgA nephropathy (10% and 0%, respectively, P less than 0.001). In a retrospective analysis of 31 patients with membranous nephropathy, 66% of patients with high initial urinary C5b-9 showed an unstable clinical course compared to 18% of patients with initially absent or low C5b-9 (P less than 0.001). We suggest that high urinary C5b-9 identifies those patients with a membranous lesion which retains an active immunological component contributing to the pathology of progressive glomerular damage.     

低剂量利妥昔单抗治疗难治性特发性膜性肾病的临床疗效分析

目的 探讨低剂量利妥昔单抗(rituximab,RTX)治疗难治性特发性膜性肾病(idio-pathic membranous nephropathy,I N)的有效性及安全性.方法 回顾性收集2017年1月至2018年12月诊断的难治性IMN且抗磷脂酶A2受体(PLA2R)抗体阳性病例32例,接受低剂量RTX治疗方案...     

氯沙坦对特发性膜性肾病患者尿蛋白谱的影响

目的观察氯沙坦对特发性膜性肾病(idiopathic membranous nephropathy,IMN)患者尿蛋白谱的影响,以期阐明其部分治疗机制。方法将79例IMN患者随机分为观察组(42例)及对照组(37例),所有患者在纳入实验前均常规治疗1个月。观察组在常规治疗基础上服用氯沙坦(100mg/d)治疗3个月,对照组继续给予常规治疗3个月。治疗前后分别进行尿β2-微球蛋白肌酐比值(urinaryβ2-microglobulin to creatinine ratio,β2-MG/Cr)、视黄醇结合蛋白肌酐比值(retinol binding protein to creatinine ratio,RBP/Cr)、蛋白肌酐比值(urinary protein to creatinine ratio,PRO/Cr),足细胞顶端膜性蛋白肌酐比值(Podocalyxin to creatinine ratio,PCX/Cr)、白蛋白肌酐比值(albumin to creatinine ratio,Alb/Cr)、免疫球蛋白G肌酐比值(immunoglobulin G to creatinine ratio,IgG/Cr)测定,然后对治疗前后结果进行分析评价。结果观察组氯沙坦治疗后尿PCX/Cr、Alb/Cr、PRO/Cr较治疗前有明显降低(P0.01),但尿β2-MG/Cr、RBP/Cr、IgG/Cr治疗前后比较无明显差异(P0.05);对照组尿PRO/Cr、ALB/Cr治疗后有所下降(P0.05),其余比值治疗前后无明显差异(P0.05)。观察组治疗后较对照组治疗后尿PCX/Cr、ALB/Cr、PRO/Cr有所降低(P0.05),β2-MG/Cr、RBP/Cr、IgG/Cr无明显差异(P0.05)。结论氯沙坦可明显减少IMN患者尿蛋白排泄,其机制可能与肾小球基底膜电荷屏障的修复有关,对肾小球基底膜的结构损伤无修复作用,也未发现对损伤肾小管明显的保护作用。     

Elevated urinary excretion of the C5b-9 complex in membranous nephropathy.

In experimental membranous nephropathy, antibody binding to glomerular epithelial cell membrane antigens results in complement activation and formation of complement C5b-9 membrane attack complexes in glomeruli. During active disease, the C5b-9 complexes are shed into the urine. To test the hypothesis that a similar mechanism might be operative in human membranous nephropathy, we measured urinary excretion of C5b-9 and C5 in 146 proteinuric patients with biopsy-proven glomerular diseases or diabetes mellitus. Urinary excretion of C5b-9 relative to C5 excretion was higher in 40 patients with membranous nephropathy than in 106 patients with proteinuria due to non-membranous glomerulonephritis when analyzed by covariance analysis (P less than 0.0002). Urinary C5b-9 excretion was higher in membranous nephropathy than in membranoproliferative glomerulonephritis (N = 13, P less than 0.05), minimal change-focal sclerosis (N = 33, P less than 0.001), mesangial proliferative glomerulonephritis (N = 9, P less than 0.02) and IgA nephropathy (N = 7, P less than 0.025). Urinary C5b-9 excretion was also higher in patients with lupus nephritis (N = 18, P less than 0.02) compared to those with non-membranous glomerulonephritis. The lupus patients with the highest excretion had clinical or pathological features of membranous nephropathy. Nine patients with membranous nephropathy and elevated urinary C5b-9 excretion had a shorter duration of disease (P less than 0.05), lower serum creatinine levels (P less than 0.05) and more proteinuria (P less than 0.02) than the 31 membranous nephropathy patients with normal values.(ABSTRACT TRUNCATED AT 250 WORDS)     

Benefit and cost from the long-term use of cyclosporine-A in idiopathic membranous nephropathy

Aim: Idiopathic membranous nephropathy (IMN), the most common cause of nephrotic syndrome in adults, is usually treated by cyclosporin A (CsA). Estimation of the effectiveness of long‐term use of CsA in the remission and relapse rate of nephrotic syndrome along with histological changes in repeat renal biopsies was the aim of the study. Methods: Thirty‐two nephrotic patients with well‐preserved renal function treated by prednisolone and CsA were studied. A repeat biopsy was performed in 18 patients with remission of nephrotic syndrome, after 24 months of treatment, to estimate the activity of the disease and features of CsA toxicity. Results: Complete remission of nephrotic syndrome was observed in 18 (56%) and partial remission in 10 patients (31%) after 12 months of treatment (total 87%). Relapses were observed in 39% and 60% of patients with complete and partial remission, respectively, and multiple relapses in 25% of patients, who showed gradual unresponsiveness to CsA and decline of renal function. Progression of stage of the disease and more severe glomerulosclerosis and tubulointerstitial injury were recognized in 55% and 61% of patients respectively. Features of CsA nephrotoxicity were not observed. The severity of histological changes was related to the time elapsed from the first biopsy (r = 0.452, P < 0.05). Conclusion: Low doses of CsA with prednisolone induce remission of nephrotic syndrome in most idiopathic membranous nephropathy patients. Although typical features of CsA nephrotoxicity are not observed, significant deterioration of histological lesions occurs with time, even in patients with remission. Long‐term use of CsA should be examined with caution.     

血清磷脂酶A2受体抗体预测利妥昔单抗治疗特发性膜性肾病疗效价值的初探

目的 探索血清磷脂酶A2受体抗体预测利妥昔单抗治疗特发性膜性肾病疗效的预测价值.方法 纳入2017年8月1日至2020年5月31日新疆维吾尔自治区人民医院首次确诊或长期随访使用利妥昔单抗治疗的特发性膜性肾病的患者120例,依据血清磷脂酶A2受体抗体情况将患者分为阳性组和阴性组,进行组间资料比较,用Kaplan-Meie...     

Clinical course and outcome of idiopathic membranous nephropathy in Japanese children

We retrospectively studied 12 Japanese children (8 boys, 4 girls) with idiopathic membranous nephropathy (IMN), aged 2.9–15.8 (mean 7.7) years at onset. All patients were identified through either screening or a routine urinalysis; proteinuria was present in all, haematuria, which was macroscopic in 4, in 11. Three had nephrotic syndrome (NS) at or soon after onset. Stages on electron microscopy, performed in 10 patients, were I in 3, II in 5 and III in 2. Steroids alone or with cyclophosphamide were administered to 5 patients, including the 3 patients showing NS. Complete remission of proteinuria occurred in 8 patients 0.3–1.6 (mean 0.6) years after onset, and proteinuria did not recur. After a follow-up of 1.6–11.6 (mean 5.9) years, these 8 patients were in complete remission and the remaining 4 had only mild proteinuria; none had hypertension or impaired renal function. Thus, we infer that IMN in Japanese children may have a better course and outcome than IMN in non-Japanese children. Based on a comparative study of Japanese (previously reported cases added to ours) and non-Japanese (mostly Caucasian) children with IMN, this was confirmed: it is possible that steroid therapy in Japanese patients is more effective in inducing remission of NS and preserving renal function.