Cyclophosphamide pulse therapy in advanced progressive IgA nephropathy

For advanced progressive primary IgA nephropathy (IgAN) no established therapy exists. We conducted a prospective, uncontrolled trial to evaluate the effect of intravenous cyclophosphamide pulse (CyP) therapy on the course of advanced progressive IgAN. Twenty-one patients (mean age 52 +/- 10 years; male/female 20/1) with biopsy-proven IgAN without crescentic extracapillary proliferation and a serum creatinine of more than 2.0 mg/dl and/or an increase more than 25% in the previous 3 months were included. Patients were treated with CyP (750 mg/m(2 )body surface area) every 4 weeks for 6 months and low dose oral prednisolone. The loss of renal function per year was significantly reduced from 16% before therapy to 4% after therapy (p < 0.001). A further increase >25% of serum creatinine after therapy was observed in 8 patients after 0.7 years (range 0.3-3.0 years), and 3 of these patients developed end-stage renal disease. Proteinuria decreased significantly during CyP therapy. A low nadir of white blood cell and platelet count was associated with a better renal outcome (p = 0.025). In conclusion, CyP therapy and low dose oral prednisolone is effective in preserving renal function in a subgroup of patients with advanced progressive IgAN.     

The indication of steroid pulse therapy and apheresis therapy for multiple sclerosis

We discuss steroid pulse therapy and apheresis therapy indicated for the treatment of multiple sclerosis (MS). In the basic treatment course for MS, steroid pulse therapy is a first-line treatment for relapsing-remitting multiple sclerosis (RR-MS) in the course of the exacerbation, and apheresis therapy is performed in refractory cases. Treatment strategies for chronic progressive MS are not to be established. Steroid pulse therapy has been established as a treatment for MS in the active phase through randomized controlled trials (RCT). Apheresis therapy includes plasmapheresis and cytapheresis, and plasmapheresis includes plasma exchange (PE) and immunoadsorption plasmapheresis (IAPP). PE and IAPP are performed for MS treatment. PE has been established as a useful treatment for active phase MS. The efficacy of IAPP has been frequently reported, but no reports have been based on RCT. We also summarize the indications, methods, and adverse reactions of steroid pulse therapy and apheresis therapy.     

IgA nephropathy

Summary Seventy-five biopsy samples from patients with chronic renal disorders were examined by the usual techniques of light microscopy and immunofluorescence; in fifteen patients IgA nephropathy was found. These patients were young adults; the onset of the disease was characterized by macrohematuria, and recurrent episodes of hematuria were observed. Histological examination revealed proliferative endothelio-mesangial glomerulonephritis at various stages of development with focal or diffuse patterns; immunofluorescence revealed constant and intense positive reactions for IgA mainly in association with C3. It is assumed that there is a relationship connecting the more advanced histological changes, a more severe clinical course and the presence of IgM deposits.     

The effects of cytotoxic therapy in progressive IgA nephropathy

Background: IgA nephropathy (IgAN) is not always benign, and some patients at high risk of end-stage renal disease (ESRD) experience a rapid decline in renal function. This study retrospectively examined the beneficial effects of cytotoxic therapy. Methods: We identified 102 patients with progressive IgAN despite optimal conservative management. Of these, 31 who received cytotoxic therapy and 55 who were managed conservatively were included. Results: Median eGFR and urinary protein-to-creatinine ratio (uPCR) at baseline did not differ between the groups (p?=?0.475 and 0.259, respectively). Median GFR slope was also similar (p?=?0.896). Cumulative renal survival was better in the cytotoxic therapy group than in the control group (p?=?0.009). Cytotoxic therapy was associated with lower risk of progression to ESRD, independent of eGFR, uPCR, GFR slope and kidney histologic findings (HR 0.13, 95% CI 0.03–0.66). In the cytotoxic therapy group, the median GFR slope decreased from ?7.8 (?10.5, ?5.0) mL/min/1.73 m² per year to ?3.4 (?5.1, ?1.8) mL/min/1.73 m² per year after treatment (p?Conclusions: Cytotoxic therapy attenuated the rate of GFR decline and was associated with a favorable renal outcome in patients with progressive IgAN.

• Key messages

• Cytotoxic therapy was associated with a favorable renal outcome in IgA nephropathy patients whose glomerular filtration rate progressively declined despite optimal conservative management.

• Cytotoxic therapy significantly attenuated the rate of glomerular filtration rate decline as well as the amount of proteinuria in patients with progressive IgA nephropathy.

• Adverse events following cytotoxic therapy were comparable to conservative management.

     

膜型IgA肾病

肾病是我国常见的肾小球疾病，病理类型很多，但膜型ＩｇＡ肾病极罕见。本文报告３例膜型ＩｇＡ肾病。病理特点是系膜增生的同时，肾小球毛细血管基底膜增厚，并有钉突形成。患者有大量蛋白尿。系膜区有大量ＩｇＡ沉积，毛细血管基底膜外侧有ＩｇＧ沉积。超微结构显示在系膜区及基底膜上皮细胞下均有电子致密物。本文通过免疫荧光和免疫电镜的研究认为，膜型ＩｇＡ肾病是膜型肾小球肾炎与系膜增生型ＩｇＡ肾病的相互重叠。     

Experimental IgA nephropathy

An animal model for IgA immune complex nephritis was developed. IgA immune complexes formed in vitro with an IgA anti-dinitrophenyl (DNP) derived from MOPC-315 plasmacytoma, and dinitrophenylated bovine serum albumin (DNP-BSA) produced mild focal glomerulonephritis in mice. Similar, but more severe pathological changes were produced with complexes formed in vivo either in normal mice or MOPC-315 tumor-bearing mice. In contrast to the focal nature of the PAS-positive glomerular lesions observed by light microscopy, immunofluorescent examination revealed IgA deposits in all glomeruli. This discrepancy between immunofluorescent and histopathologic findings as well as the distribution of the immune complexes within the affected glomeruli, are some of the features which bear resemblance between this experimental model and human IgA nephropathy. Fixation of complements by DNP-BSA-IgA immune complexes, formed in vitro or in vivo, was shown to occur in the glomeruli of mice with IgA immune complex nephropathy. The pattern of C3 glomerular deposits was similar to that of IgA. However, complement proved to be nonessential for complex deposition. This conclusion is based on the observation that decomplemented mice, although showing no deposition of C3 in their glomerulus, developed glomerular immunohistological changes similar to those observed in experimental mice that were not decomplemented. Polymeric IgA was observed to be critical for renal deposition of complexes and induction of nephritic histological changes. In contrast, monomeric IgA immune complexes failed to produce glomerular deposits. This finding raises the possibility that secretory IgA, which is predominantly polymeric, may play a role in human IgA-associated glomerulonephritis.     

扁桃体切除术联合药物治疗IgA肾病Meta分析

目的评价扁桃体切除术联合药物（tonsillectomy combined with medication therapy, TCMT）治疗IgA肾病的疗效。方法检索Embase、PubMed、中国生物医学文献数据库（CBM）、中国期刊网（CNKI）等数据库公开发表的关于TCMT治疗IgAN的研究文献,末次检索时间为2016年3月31日。纳入以扁桃体切除术联合药物治疗为干预措施治疗IgA肾病的随机对照试验和前瞻性对照试验,并对纳入文献质量进行评价,采用Stata13.0软件进行meta分析。结果共纳入6篇文献,3篇为前瞻性对照研究,3篇为随机对照研究。①总体疗效：符合标准的文献3篇,总样本量224例,其中TCMT组134例,药物治疗组90例,meta分析示两组疗效差异有统计学意义（OR=2.68,95%CI=1.47~4.90,P=0.001）。②尿蛋白缓解率：符合标准的文献5篇,总样本量326例,其中TCMT组167例,药物治疗组159例,meta分析示两组疗效差异有统计学意义（OR=4.38,95%CI=2.67~7.20,P<0.001）。③尿红细胞缓解率：符合标准的文献5篇,总样本量326例,其中TCMT组167例,药物治疗组159例,meta分析示两组疗效差异有统计学意义（OR=3.90,95%CI=1.38~11.07,P=0.01）。结论从现有的临床证据看,扁桃体切除术联合药物治疗可显著提高总体疗效、尿蛋白缓解率及尿红细胞缓解率,疗效优于单用药物治疗。     

骨化三醇联合厄贝沙坦治疗IgA肾病的临床观察

目的:观察1,25-二羟维生素D3(骨化三醇)联合厄贝沙坦治疗IgA 肾病的疗效及安全性.方法:将45 例IgA 肾病随机分为骨化三醇(VD3)组、厄贝沙坦(ARB)组和联合治疗(ARB+VD3)组,观察8 周.检测治疗前后尿蛋白、肾功能、血钙.结果:治疗后ARB 组尿蛋白较基线下降(P ＜ 0.05);联合治疗组尿蛋白较基线明显下降(P ＜ 0.01),较之ARB 组及VD3 组其下降更为明显,差异有统计学意义(均P ＜ 0.05).所有患者均无明显不良反应,未发生高钙血症.结论:骨化三醇联合厄贝沙坦可以有效降低IgA 肾病患者尿蛋白,疗效优于单独用药,且无明显不良反应.     

Transglutaminase is essential for IgA nephropathy development acting through IgA receptors

IgA nephropathy (IgAN) is a common cause of renal failure worldwide. Treatment is limited because of a complex pathogenesis, including unknown factors favoring IgA1 deposition in the glomerular mesangium. IgA receptor abnormalities are implicated, including circulating IgA-soluble CD89 (sCD89) complexes and overexpression of the mesangial IgA1 receptor, TfR1 (transferrin receptor 1). Herein, we show that although mice expressing both human IgA1 and CD89 displayed circulating and mesangial deposits of IgA1-sCD89 complexes resulting in kidney inflammation, hematuria, and proteinuria, mice expressing IgA1 only displayed endocapillary IgA1 deposition but neither mesangial injury nor kidney dysfunction. sCD89 injection into IgA1-expressing mouse recipients induced mesangial IgA1 deposits. sCD89 was also detected in patient and mouse mesangium. IgA1 deposition involved a direct binding of sCD89 to mesangial TfR1 resulting in TfR1 up-regulation. sCD89-TfR1 interaction induced mesangial surface expression of TGase2 (transglutaminase 2), which in turn up-regulated TfR1 expression. In the absence of TGase2, IgA1-sCD89 deposits were dramatically impaired. These data reveal a cooperation between IgA1, sCD89, TfR1, and TGase2 on mesangial cells needed for disease development. They demonstrate that TGase2 is responsible for a pathogenic amplification loop facilitating IgA1-sCD89 deposition and mesangial cell activation, thus identifying TGase2 as a target for therapeutic intervention in this disease.     

IgA肾病相关生物标志物的临床价值探讨

IgA肾病(IgA nephropathy,IgAN)是免疫病理诊断名称,其包括一类病理类型不同、预后差异较大的疾病。该病在我国很常见,约占肾穿刺诊断肾病的42%。因而,如何提高对该病的认识,以早期诊断、早期预防,具有重要的意义。     

IgA nephropathy: challenges and opportunities

Immunoglobulin A (IgA) nephropathy poses many challenges to investigators and physicians in its etiology, pathogenesis, prevention, and treatment. But at the same time, opportunities abound for new tests and treatments that may eventually lead to control of this common form of chronic kidney disease.     

ACEI/ARB therapy for IgA nephropathy: a meta analysis of randomised controlled trials

Background: Published reports examining the efficacy of RAS blockers: angiotensin converting‐enzyme inhibitor (ACEI) and angiotensin II receptor blocker (ARB) agents for preserving renal function in IgA nephropathy (IgAN) have yielded conflicting results. To evaluate systematically the effects of ACEI/ARB agents on IgAN, we conducted a meta analysis of published randomised controlled trials (RCTs). Methods: MEDLINE, EMBASE, the Cochrane Library and article reference lists were searched for RCTs that compared ACEI/ARB with placebo and any other antihypertensive agents or non‐immunosuppressive agents for treating IgAN. The quality of the studies was evaluated with the method of intention to treat analysis and allocation concealment, as well as with the Jadad method. Meta analyses were performed on the outcomes of proteinuria and renal function in patients with IgAN. Results: Eleven RCTs involving 585 patients were included in the review. Seven trials used placebo/no treatment as controls. Four trials used other antihypertensive agents as controls. Overall, ACEI/ARB agents had statistically significant effects on protecting renal function(p < 0.00001) and reduction of proteinuria (p < 0.00001) when compared with control group. Tests for heterogeneity showed no difference in effect among the studies. Systolic and diastolic blood pressure, glomerular filtration rate (GFR), age, did not influence treatment response. ACEI/ARB agents were well tolerated. Conclusions: The current cumulative evidence suggests that ACEI/ARB agents had statistically significant effects on protecting renal function and reduction of proteinuria in patients with IgAN when compared with control groups. ACEI/ ARB agents are a promising medication and should be investigated further.     

A retrospective study of pulse steroid therapy for acute respiratory failure associated with tuberculosis

BackgroundTuberculosis can cause acute respiratory failure, which is associated with a high mortality rate, even in patients receiving effective anti-tuberculosis therapy. We retrospectively analyzed patients with acute respiratory failure associated with tuberculosis who underwent pulse steroid therapy to describe the clinical characteristics and effectiveness of pulse steroid therapy in this condition.MethodsThe medical records of patients admitted to our hospital for culture-proven tuberculosis treatment from April 1, 2017, to March 31, 2022, who received pulse steroid therapy for acute respiratory failure associated with tuberculosis were reviewed.ResultsIn total, 10 patients were included in this study. Chest computed tomography (CT) revealed diffuse ground-glass opacities and consolidation in these patients. Overall, 70% of the patients (7/10) showed an adjudicated response to pulse steroid therapy, with improved respiratory condition and radiological findings. Three patients died without response to pulse steroid therapy. One patient died of pancreatic cancer after recovering from respiratory failure. The remaining six patients were discharged without supplemental oxygen and completed anti-tuberculosis therapy.ConclusionsPulse steroid therapy can lead to dramatic improvements in some patients with acute respiratory failure associated with tuberculosis.     

羟氯喹联合治疗对IgA肾病残余蛋白尿的影响

目的 探讨羟氯喹(HCQ)联合肾素-血管紧张素系统抑制剂、激素和/或免疫抑制剂对IgA肾病患者残余蛋白尿的影响.方法 纳入2018年9月至2020年8月四川省人民医院活检为IgA肾病的门诊患者,HCQ联合治疗组28例和对照组46例,均随访6个月.比较两组患者随访期间残余蛋白尿下降率以及残余蛋白尿有效下降率的累积频率等....     

Pulmonary capillaritis in IgA nephropathy

Pulmonary capillaritis presenting as diffuse alveolar hemorrhage is a rare manifestation in patients with IgA nephropathy. A 20-year-old male with hemodialysis dependent, end-stage renal failure presented with recurrent hemoptysis and respiratory failure. A histologic diagnosis of pulmonary capillaritis was established by transbronchial lung biopsy. He was successfully treated with intravenous methylprednisone and plasma exchange followed by oral prednisone and cyclophosphamide. This report highlights the independent renal and pulmonary manifestations of IgA nephropathy and the management of the resultant diffuse alveolar hemorrhage with aggressive immunosuppression.     

Genetic studies of IgA nephropathy

IgA nephropathy is the commonest form of glomerulonephritis worldwide, but we still know relatively little about its pathogenesis. Potentially, genetic studies might provide new insights and suggest novel therapeutic approaches to this important cause of chronic kidney disease. Two approaches that are likely to yield new information are analysis of multiply affected pedigrees and large-scale, well-controlled association studies.