Superimposition of poststreptococcal acute glomerulonephritis on the course of IgA nephropathy

A 17-year-old male with poststreptococcal acute glomerulonephritis (PSAGN) superimposed on the course of IgA nephropathy is presented. The histological findings of the first renal biopsy showed mild IgA nephropathy with a mesangial deposition of IgA and C3. Eighteen months later, acute nephritic syndrome with hypocomplementemia and rising antihyaluronidase titer occurred 10 days following the onset of an upper respiratory infection. The second renal biopsy revealed severe diffuse endocapillary proliferative and exudative glomerulonephritis with cellular crescents in 70% of the glomeruli. Immunofluorescence showed granular staining of C3 alone along the capillary walls. The pre-existing IgA deposits had disappeared. Typical 'humps' were observed by electron microscopy. The symptoms were gradually resolved by intensive steroid and anticoagulant therapy. Five months after the episode of acute nephritic syndrome, the patient was clear of symptoms except for mild proteinuria and hematuria. The third renal biopsy at that time showed morphologic changes similar to those of the first renal biopsy with mild mesangial IgA deposits.     

Long-standing spontaneous clinical remission and glomerular improvement in primary IgA nephropathy (Berger's disease)

Of the 244 cases of IgA nephropathy diagnosed at Necker Hospital before 1981, 9 patients (3.7%) developed spontaneous clinical remission of long duration. Three of these 9 patients presented with gross hematuria, while in the others the disease was discovered by the finding of proteinuria at routine urinalysis. During the disease course 5 patients had recurrent episodes of gross hematuria, lasting several years in 4. At the time of the first biopsy all patients had hematuria and permanent proteinuria. In 1 patient, renal biopsy showed only an increase in mesangial matrix while in the others segmentary lesions were observed, affecting less than 30% of the glomeruli in 6. Diffuse mesangial deposits of IgA were present in all. During the follow-up, proteinuria and microscopic hematuria gradually decreased and completely disappeared within 4-14 years after the onset of the disease. A repeat biopsy performed during remission in 4 patients showed, in 3, an improvement of glomerular lesions and a significant decrease in IgA mesangial deposits in parallel with clinical recovery. As in other types of 'primary' glomerulonephritis, these data indicate that the initial disorder in IgA nephropathy may be spontaneously reversible even after a long course of the disease.     

IgA nephropathy in patients with familial Mediterranean fever

Two patients with a long-standing history of familial Mediterranean fever were found to have both microscopic hematuria and proteinuria during the acute attacks. Kidney biopsies from both patients revealed diffuse mesangial proliferative glomerulonephritis with intense mesangial IgA and C3 deposits and no evidence of amyloidosis. To our knowledge these are the first 2 cases documenting the presence of mesangial IgA nephropathy in patients with familial Mediterranean fever.     

Combined membranous nephropathy and IgA nephropathy

IgA nephropathy (IgAN) and membranous nephropathy (MN) are both common renal biopsy findings that rarely have been described together in the same patient. The significance of this finding is not clear. We present the clinical and pathological data of four patients with combined MN-IgAN and discuss possible pathogenetic mechanisms. By definition, all cases showed immunodominant mesangial deposits of IgA (+/-C3) and subepithelial capillary wall deposits of IgG (+/-C3) by immunofluorescence microscopy, confirmed by electron microscopy. There were three men and one woman, whose ages ranged from 41 to 67 years (average, 51.7 years). All four presented with microscopic hematuria and proteinuria, three in the nephrotic range. Renal function was normal in three individuals, and one subject had mild renal insufficiency accompanied by long-standing hypertension. Two other patients had newly uncovered hypertension. Complement levels were normal in all subjects. One patient had a positive antinuclear antibody (ANA) test, but none had other serologic or clinical features diagnostic of lupus. None of the four individuals had any other predisposing factors for either MN or IgAN, including hepatitis B infection. All four patients had stable renal function at last determination (average follow-up, 24 months; range, 4 to 34 months), with markedly reduced proteinuria in three individuals and persistent heavy proteinuria in one. A review of the literature indicates that combined MN-IgAN is most often characterized by heavy proteinuria and stable renal function. Some cases may be related to hepatitis B infection, but in most instances the cause is unknown. The combination of these two pathological processes does not result in a particularly deleterious clinical outcome for patients.     

Active and chronic phases of Berger's disease (IgA nephropathy)

Berger's disease, or IgA nephropathy, is generally considered as pursuing a chronic course, often with recurrent attacks of gross hematuria or persistent microscopic hematuria. However, little attention has been paid to the acute changes that may accompany this nephropathy, and there are few reports of follow-up renal biopsy studies in these patients. We have had the opportunity to study two patients with Berger's disease (IgA nephropathy) in whom initial and follow-up renal biopsy studies were available. Both of these patients presented clinically with gross hematuria and moderately heavy proteinuria. In both cases, the initial renal biopsy disclosed diffuse mesangial proliferation associated with crescent formation, while follow-up biopsy disclosed only mild mesangial proliferation and no crescents. In one case electron microscopy revealed prominent subendothelial and small mesangial deposits in the initial biopsy, which became almost solely large mesangial in the second biopsy. The other case demonstrated only mesangial deposits in both biopsies.     

A pediatric occurrence of crescentic glomerulonephritis associated with antineutrophil cytoplasmic antibodies and mesangial IgA deposits

Antineutrophil cytoplasmic antibody-(ANCA) associated glomerulonephritis usually shows histopathologic features of pauciimmune crescentic glomerulonephritis and occurs late in life. We report a 14-year-old Japanese girl presenting with proteinuria, hematuria and mildly elevated serum creatinine. A renal biopsy specimen demonstrated crescentic glomerulonephritis, immunofluorescence showed mesangial IgA staining. Electron microscopic examination disclosed paramesangial deposits. Serum ANCA against myeloperoxidase (MPO) were detected at high titers. Myeloperoxidase-ANCA-related nephritis accompanied by IgA nephropathy is considered rare in childhood and teen years. Yet, if ANCA assays and detailed electron microscopic examination of renal specimens were performed routinely in patients with rapidly progressive glomerulonephritis, the diagnosis might be more frequent in young patients.     

Henoch-Sch?nlein purpura and IgA nephropathy in father and son

Considerable controversy exists as to whether Henoch-Sch?nlein purpura and Iga nephropathy are different clinical manifestations of the same disease or if, on the contrary, they are separate entities. We report on the development of Henoch-Sch?nlein purpura and IgA nephropathy in 2 members of the same family. Patient 1, a 63-year-old man, presented with purpura in the legs, abdominal pain, hematuria, renal failure and proteinuria. A biopsy of a purpuric skin lesion showed small-vessel vasculitis, and a renal biopsy showed diffuse proliferative glomerulonephritis with prominent IgA deposits, thus making the diagnosis of Henoch-Sch?nlein purpura. Serum IgA was increased. Patient 2, the 30-year-old son of patient 1, underwent renal biopsy for the investigation of microscopic hematuria and proteinuria. There was no history of skin rash, and serum creatinine was normal. A renal biopsy showed expansion of the mesangial matrix and marked IgA deposition. HLA typing confirmed that they shared a haplotype. HLA B35 or DR4 were absent. These results demonstrate that Henoch-Sch?nlein purpura and IgA nephropathy can possibly be genetically related and therefore support the notion that these two diseases probably share a common pathogenesis.     

少量蛋白尿IgA肾病患者镜下血尿与病理指标的相关性分析

目的探索少量蛋白尿IgA肾病(IgAN)患者镜下血尿发生与病理指标的相关性。 方法回顾性分析2007年1月1日至2012年12月31日在解放军总医院经肾穿刺活检首次诊断的原发性IgAN、尿蛋白<0.5 g/24 h且无肉眼血尿患者。采集患者肾穿刺活检前1周内的血压、尿蛋白定量、尿红细胞形态及计数、肾功能等指标。肾活检后的病理指标按照IgAN牛津分型更新版评价,采用Poisson回归分析镜下血尿水平与病理指标的相关性。 结果共纳入尿蛋白<0.5 g/24 h的IgAN患者88例,其中无镜下血尿组22例,非满视野镜下血尿组58例,满视野镜下血尿组8例。Poisson回归分析显示在校正患者的尿蛋白和肾功能(eGFR)水平后,新月体形成(OR 6.55,95%CI 2.68～15.98)和系膜细胞增殖(OR 4.92,95%CI 1.75～13.83)与IgAN患者镜下血尿水平相关,系膜细胞增殖病变与节段硬化或球囊粘连病变存在交互作用(OR 3.82,95%CI 1.30～11.25)。 结论在蛋白尿少于0.5 g/d的IgAN患者中,患者镜下血尿水平相关的病理因素主要是增殖性病变,包括系膜细胞增殖和新月体形成。系膜细胞增殖病变合并节段硬化和(或)球囊粘连病变,与镜下血尿水平的相关性显著增加。     

Treatment of IgA nephropathy

IgA nephropathy (IgAN) is an important cause of progressive kidney disease with 25-30% of patients developing end-stage renal disease within 20 years of diagnosis. There is still no treatment to modify mesangial IgA deposition and available treatments are those extrapolated from the management of other patterns of chronic glomerulonephritis. There remains no consensus on the use of immunosuppressive agents for treatment of progressive IgAN and this is compounded by the relative lack in IgAN of randomized controlled trials relevant to current clinical practice. Patients with recurrent macroscopic hematuria or isolated microscopic hematuria and proteinuria <1 g/24 h require no specific treatment. Those with nephrotic syndrome and minimal change on renal biopsy should be managed as for minimal change nephropathy. There is no evidence to support the use of corticosteroids for nephrotic IgAN outside this group of patients. Patients presenting with acute renal failure require evaluation to distinguish acute tubular necrosis, which requires supportive therapy only, from crescentic IgAN, for which treatment with cyclophosphamide and corticosteroids in a regimen similar to that for renal small vessel vasculitis is indicated in the absence of significant chronic histologic injury. Patients at greatest risk of progressive renal impairment are those with hypertension, proteinuria >1 g/24 h, and reduced glomerular filtration rate at diagnosis. All such patients should be treated to a blood pressure of 125/75 mm Hg with dual blockade of the renin-angiotensin system with angiotensin-converting enzyme inhibition and angiotensin receptor blockade. At present, there is insufficient evidence for the additional use of immunosuppressive agents, antiplatelet agents, or anticoagulants.     

IgA nephropathy presenting clinical features of poststreptococcal glomerulonephritis

IgA nephropathy and poststreptococcal glomerulonephritis are common forms of primary glomerulonephritis in children. This paper reports a 5-year-old Omani boy who had a chance occurrence of these two different glomerular diseases. Our patient presented with clinical features of poststreptococcal glomerulonephritis and then developed recurrent macroscopic hematuria, polyarthritis, bloody diarrhea, and erythematous swelling of the penis. Renal biopsy revealed diffuse mesangial hypercellularity, with focal glomerular sclerosis, fibrous crescents, and mesangial IgA and C3 deposits, consistent with IgA nephropathy. The clinical features and differential diagnosis are outlined.     

Clinical and histological improvement with long-term, low-dose cyclosporin A in a patient with severe IgA nephropathy

We report the case of an 11-year-old girl with nephrotic syndrome with massive proteinuria and microscopic hematuria. Her first renal biopsy specimen (June 1997) showed diffuse/segmental mesangial proliferative glomerulonephritis with capillary wall thickening, crescent, and sclerosis by light microscopy, as well as diffuse/global moderate deposition of IgA, C₃, and fibrinogen predominantly in the mesangium, and partly along the capillary wall, by immunofluorescent microscopy. After the patient failed to show remission with the usual dose of prednisolone and azathioprine, cyclosporin A was administered, in addition to dipyridamole, warfarin, and prednisolone (on alternative days). In consequence, the proteinuria had completely disappeared after 6 weeks of this regimen and microscopic hematuria had disappeared after 8 months of the regimen. A second renal biopsy was performed in August 1998. The epithelial proliferation and crescent seen in the first biopsy specimen had disappeared, and only mesangial proliferation and sclerosis persisted, without histological evidence of cyclosporin-induced nephrotoxicity. A third renal biopsy was performed in March, 2000. IgA deposition in glomeruli had disappeared in this biopsy specimen. Low-dose cyclosporin A therapy resulted in dramatic improvements in both clinical manifestations and renal histological findings, without detrimental effects on renal function. Received: September 4, 2000 / Accepted: December 22, 2000     

IgA nephropathy in a patient with polycythemia vera. Clinical manifestation of chronic renal failure and heavy proteinuria

IgA nephropathy (IgAN) is one of the most frequent forms of glomerulonephritis (GN). However, its association with polycythemia vera (PV) has rarely been described. We report a case of IgAN combined with PV. The patient was a 46-year-old male with chronic renal failure, heavy proteinuria and erythrocytosis. He also presented hypertension and hematuria as well as splenomegaly, high arterial oxygen saturation and elevated leukocyte alkaline phosphatase activity. Possible causes of secondary erythrocytosis were ruled out. The renal biopsy revealed mesangial proliferative GN with predominant IgA deposition in mesangium. He was diagnosed as having IgAN and PV concomitantly. After administration of hydroxyurea, enalapril and felodipine, blood cell count and blood pressure normalized, while azotemia persisted. There was also a partial remission of the heavy proteinuria. We describe a case of IgAN associated with PV, and possible pathophysiologic relationships between two diseases are discussed with review of the literature.     

IgA肾病诊疗进展

IgA肾病是全球最常见的原发性肾小球肾炎,亚洲人群中发病率高于其他人种。IgA肾病是目前导致终末期肾病的重要原因之一。临床上以血尿为特点,常伴随蛋白尿、高血压。其病理表现主要为IgA免疫复合物在肾小球系膜区的沉积、系膜细胞增生、毛细血管内皮细胞增生等。其发病机制可能为血液循环中半乳糖缺乏的IgA1增多,在內外界环境刺激下,产生过多的、能沉积于肾小球系膜区的免疫复合物。目前,对IgA肾病的诊断主要依靠病理检查。治疗方面,以肾素-血管紧张素系统阻断剂、控制血压为基础,恰当联合免疫抑制剂、细胞毒性药物、鱼油等或能延缓IgA肾病的进展。本文的目的是对IgA肾病的诊疗现状进行总结和分析,为临床工作及进一步科研提供指导和参考。     

Mesangial IgA deposits in two patients with AIDS-related complex

Two patients with AIDS-related complex who presented with renal failure and microscopic hematuria were found to have mesangial deposits of IgA at renal biopsy. Though such glomerular deposits have not yet been reported in patients with HIV infection, their occurrence is most likely not coincidental. Indeed, there are striking similar abnormalities in patients with primary IgA nephropathy and in those infected with HIV. A careful screening for microscopic hematuria may lead to disclose further cases of mesangial IgA deposits in patients with HIV infection.     

Henoch-Schönlein syndrome and IgA nephropathy: A case report suggesting a common pathogenesis

An 8-year-old Caucasian male presented with two episodes of gross hematuria but was otherwise asymptomatic. Serum IgA levels were markedly elevated and a renal biopsy showed mesangial proliferative glomerulonephritis with immunofluorescent and electron microscopy findings consistent with IgA nephropathy (IgAN). Two years later he developed abdominal pain, rectal bleeding, gross hematuria and a classic purpuric rash of Henoch-Schönlein syndrome (HSS). Serum IgA levels continued to be elevated and 3 years later in follow-up he is clinically well. These observations support the concept that HSS and IgAN are variants of the same process. The reverse situation has been reported in a 15-year-old female who developed HSS at 4 years of age and IgAN at age 15 years.     

强直性脊柱炎肾损害的临床病理特点

目的探讨强直性脊柱炎（AS）合并肾损害的临床及病理特点。方法回顾性分析18例经肾脏活体组织检查的AS患者的临床及肾脏病理表现。结果18例患者中,9例呈隐匿性肾小球肾炎表现,5例呈慢性肾小球肾炎表现,1例呈肾病综合征表现,3例为慢性肾功能不全;4例血压增高,14例血压正常。24h尿蛋白定量平均为（1．17±1．39）g。15例肾功能正常,3例肾功能异常患者血肌酐平均为（153．2±36．8）umol／L。8例患者血清IgA水平升高,10例c反应蛋白升高,13例红细胞沉降率（EsR）增快,且血清IgA水平和C反应蛋白呈正相关（r=0．707,P=0．001）,血清IgA水平和ESR呈正相关（r=0．858,P〈0．001）。病理检查结果发现15例为IgA肾病（其中10例为轻度系膜增生性肾炎,1例为轻度系膜增生性肾炎并慢性肾小管间质肾病,2例为局灶增生性肾炎,1例为局灶增生坏死性肾炎,1例为局灶节段性肾小球硬化症）,1例为膜性肾病,1例为局灶增生性肾炎伴慢性肾小管间质肾病,1例为慢性。肾小管间质肾病。有慢性肾小管间质肾病者均有服中药史。结论AS相关性肾损伤的病理改变多样,但主要为IgA肾病,也可表现为膜性肾病、局灶增生性肾炎和慢性肾小管间质。肾病,其肾损伤可能与AS疾病本身和（或）治疗用药相关。     

Glomerular pathology of allograft kidneys in Hong Kong

AIMS: Our goal was to define the spectrum of glomerular diseases in allograft kidneys and to correlate them with clinical parameters. METHODS: Eight hundred ninety-one renal graft biopsies and 43 graft nephrectomies from 1980 to 2004 were obtained from 442 allografts transplanted to 425 patients. RESULTS: Glomerular diseases were diagnosed in 33% of kidney grafts. Indications for biopsy were baseline assessment (23 biopsies, 2.5%); renal dysfunction (790 biopsies, 88.7%); proteinuria (154 biopsies, 17.3%); hematuria (11 biopsies, 1.2%); and study protocol (four biopsies, 0.4%). The median time to take a biopsy was less than 8 months posttransplant. The mean time posttransplant when the biopsy diagnosis was made was 70 months for IgA nephropathy (IgAN); 66 months for transplant glomerulopathy (TG); 65 months for focal segmental glomerulosclerosis (FSG); 55 months for mesangiocapillary glomerulonephritis (MCGN); 45 months for membranous glomerulonephritis (GN); 49 months for mesangial proliferative GN; and 101 months for diabetic nephropathy. Recurrent glomerular disease was documented in 31 (7.0%) grafts. Specific glomerular diseases were diagnosed by biopsies in 106 (89.1%) of 119 proteinuric allografts. CONCLUSIONS: Glomerulopathy was common in allografted kidneys. IgAN, TG, FSG, mesangial proliferative GN, and membranous GN were the majority. A higher proportion of grafts from donors related to the recipients than from unrelated donors showed IgAN (P < .05), suggesting that genetic factors might play a role in the pathogenesis of IgAN. Recurrence of glomerulopathy underlying ESRD was frequent for IgAN, FSG, and MCGN, but this was rarely seen in membranous GN.     

Acute renal failure in IgA nephropathy: aggravation by gross hematuria due to anticoagulant treatment

IgA nephropathy is one of the most common forms of glomerulonephritis. Macroscopic or microscopic hematuria with mild proteinuria are the main symptoms. Without complicating factors, IgA nephropathy has a favourable long-term prognosis. We report a case of reversible acute renal failure (ARF) as a complication of mild IgA nephropathy while oral anticoagulants were administered. Diagnosis was based on a renal biopsy showing marked granular mesangial IgA-deposition. In addition, numerous tubules were extended and completely obstructed by red blood cell casts. After hemodialysis treatment and parallel anti-inflammatory steroids and after stopping anticoagulation, renal function gradually improved up to complete remission. This report indicates that anticoagulatory treatment may have negative effects on the long-term prognosis of IgA nephropathy with respect to development of ARF or tubulo-interstitial inflammation.     

Clinicopathological features of paediatric renal biopsies in Shanghai over a 31 year period

Aim: To identify the variations in paediatric renal biopsy pathology and clinicopathological features during the past 31 years. Methods: A retrospective analysis of paediatric renal biopsies performed at a single institution in Shanghai from January 1979 to December 2009 was conducted. Results: The major pathologies included minor glomerular abnormalities (MGA, 26.1%), IgA nephropathy (IgAN, 17%) and mesangial proliferative glomerulonephritis (MsPGN) without IgA deposition (11.3%). The major clinical presentations included nephrotic syndrome (NS, 39.4%), haematuria with proteinuria (24.4%) and persistent microscopic haematuria (15.1%). MGA accounted for 46.9% of the cases in NS. IgAN and HSN accounted for 24% and 28.9% of patients with concomitant haematuria and proteinuria, and thin basement membrane nephropathy accounted for 51.2% of cases with persistent microscopic haematuria. The frequency of IgAN (78.6%) was much higher than that of TBMN (29.0%) in patients with persistent microscopic haematuria with abnormal urinary albumin. Conclusion: Minor glomerular abnormalities and IgAN were the major renal diseases in our study population, and the focus of our paediatric nephrologists. The high proportion of TBMN suggested that there should be limited use of renal biopsy for patients with persistent microscopic haematuria and renal biopsy should be performed in the presence of proteinuria or abnormal levels of urinary albumin.     

儿童隐匿性肾炎的临床和病理研究

目的：探讨儿童隐匿性肾炎的临床和肾组织病理改变特点及其关系。方法：回顾性分析肾活检的323例隐匿性肾炎患儿的临床和肾组织病理改变情况。结果：323例隐匿性肾炎患儿中，单纯性血尿229例，单纯性蛋白尿19例，血尿伴蛋白尿75例。肾组织病理改变类型包括：轻微病变103例（31，89％）、基本正常74例（22．91％）、IgA肾病（IgAN）73例（22．60％）、薄基底膜病（TBMN）27例（8．36％）、系膜增生性肾炎（MsPGN）18例（5．57％）、局灶增生性肾炎（FPGN）10例（3．10％）、膜性肾病（MN）8例（2，48％）、局灶节段肾小球硬化（舢）8例（2．48％）、微小病变（MCD）1例（0，31％）、IgM肾病（IgMN）1例（0．31％）。单纯性血尿组中肾组织结构基本正常的比例较血尿伴蛋白尿组明显偏高（P〈0，01）；血尿伴蛋白尿组中IgAN的比例高于单纯性血尿组和单纯性蛋白尿组（分别P〈0．01、P〈0．05）。IgAN的Lee分级：单纯性血尿组中Ⅰ、Ⅱ级85．00％，Ⅲ级及以上15．00％；血尿伴蛋白尿组中Ⅰ、Ⅱ级58．10％，Ⅲ级及以上41．90％，明显高于单纯性血尿组（x^2=6．47，P〈0．05）。结论：儿童隐匿性肾炎的病理以轻微病变、基本正常、IgAN为常见表现，血尿伴蛋白尿患儿病变较单纯性血尿患儿为重。