IgA-associated glomerulonephritis with membranoproliferative glomerulonephritis-like pattern in two children

In this article, we report two patients with IgA-associated glomerulonephritis with a membranoproliferative glomerulonephritis (MPGN) -like pattern. Both patients had nephrotic syndrome at onset. One patient was treated with high-dose alternate-day prednisolone (PSL), and the other with indomethacin and low-dose PSL. One lost the urinary abnormalities 3 years after starting treatment. The other lost the nephrotic state and hematuria over a 5-year period, but proteinuria persisted until the last follow-up. Both patients had diffuse proliferative changes with mesangial interposition and subendothelial deposits, associated with strongly positive deposits of C3 and IgA along the capillary walls of the glomeruli. These two patients showed histological changes compatible with type-I MPGN, but the pattern of IgA deposits was not typical of idiopathic MPGN or IgA nephropathy. We assume this is a rare form of MPGN, not associated with liver disease or other systemic diseases.     

A case of immunotactoid glomerulopathy with IgA2, kappa deposition ameliorated by steroid therapy

We report a case of idiopathic immunotactoid glomerulopathy with IgA2, kappa light chain deposition, ameliorated by steroid therapy. A 28-year-old male patient was admitted to our hospital due to exacerbation of nephrotic syndrome. The onset of his renal disease was at 24 years of age and the renal biopsy revealed membranoproliferative glomerulonephritis with moderate-degree deposition of IgA, IgG, IgM, C3 and C1q. Prednisolone therapy was started at the dose of 50 mg/day and effective for nephrotic syndrome and renal dysfunction. Two years later, the proteinuria and microscopic hematuria gradually exacerbated during reduction of prednisolone. The second renal biopsy showed mesangioproliferative glomerulonephritis with predominant deposition of IgA and C3. The glomerular proliferative changes were successfully suppressed by steroid treatment. On electron microscopy, a microtubular deposit with an average width of 40 nm and double-tracked appearance was observed in the mesangial and subendothelial areas. Immunohistochemical examination revealed that the deposit was predominantly composed of IgA2 subclass and kappa light chain. Selective deposition of IgA2 subclass and kappa light chain indicated that the glomerular lesion should be induced by monoclonal immunoglobulin, although it could not be detected in the serum and urine clinically. Immunoglobulin subclass staining of renal biopsy specimens provides an important clue for understanding the pathogenesis of immunotactoid glomerulopathy or fibrillary glomerulonephritis.     

Mesangial immunoglobulin A deposits in minimal change nephrotic syndrome: a report of an older patient and review of the literature

A 57-year-old patient with a history of monoclonal immunoglobulin A (IgA) gammopathy developed idiopathic nephrotic syndrome. Renal biopsy showed minimal glomerular changes with predominant glomerular mesangial IgA. The association of glomerular mesangial IgA with otherwise typical minimal change nephrotic syndrome has been noted before, and the literature concerning this combination of findings is reviewed. The patient herein described represents one of the two oldest patients yet reported with this syndrome and raises questions about the relationship between minimal change disease and IgA nephropathy. Severe proteinuria (and even the nephrotic syndrome) is not necessarily the harbinger of a poor prognosis in IgA nephropathy if the glomerular morphology is otherwise consistent with minimal change nephrotic syndrome. Such patients should be treated in a fashion similar to those with minimal change nephrotic syndrome. The significance of the IgA gammopathy in the pathogenesis of this case is unknown.     

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.     

A case of IgA nephritis showing diffuse podocytic detachment from the glomerular basement membrane.

We report the case of a 15-year-old Japanese female with severe mesangial proliferative IgA glomerulonephritis who showed a dramatic response to cocktail therapy for nephrotic syndrome. She had suddenly developed massive proteinuria and microscopic hematuria. The first renal biopsy at one month after onset revealed severe mesangial hypercellularity and podocytic detachment from the glomerular basement membrane (GBM). The cocktail therapy resulted in a decrease of proteinuria clinically, and a second biopsy demonstrated repair of the podocytic detachment. We suggest that the massive proteinuria in this case was due to destruction of the size barrier by detachment of podocytes from the GBM, and the repair of the podocytic covering on the GBM was accelerated by the cocktail therapy.     

Clinico-pathological evaluation of mesangial IgA deposition of minimal change with nephrotic syndrome

The case of IgA glomerulonephritis that shows minimal change with nephrotic syndrome is unusual. Thirteen patients of mesangial IgA deposition of minimal change with nephrotic syndrome (IgAMCNS) are discussed in comparison with twenty patients of non IgA deposition of minimal change with nephrotic syndrome (MCNS). On a common basis of hematuria, two groups are undistinguished. On a reaction pattern to steroid treatment, the former is based on IgA nephritis and the latter is based on minimal change with nephrotic syndrome. There is no difference in light microscopical findings between the two groups. Electron microscopically, the former suggests IgA nephritis and the latter suggests minimal change with nephrotic syndrome. In immunofluorescence, the former group is rare to show typical IgA glomerulonephritis. In conclusion, IgAMCNS is considered to be nephrotic syndrome with asymptomatic IgA deposit in mesangium.     

Secondary IgA nephropathy presenting as nephrotic syndrome with glomerular crescentic changes and acute renal failure in a patient with autoimmune hepatitis

Patients with end-stage liver disease are prone to hemodynamic and immunologic renal injury, the latter at times manifesting as glomerulonephritis. Elevated serum immunoglobulin A (IgA) levels and mesangial IgG-IgA deposits are common in these patients, but are often clinically silent. We report a patient with autoimmune hepatitis and secondary IgA nephropathy (IgAN) who presented with nephrotic syndrome, acute renal failure (ARF), with 30% of the renal glomeruli having undergone crescentic change, and with IgA2 deposits in the glomerular mesangium. This article discusses secondary IgAN pathogenesis and its therapeutic management.     

Primary glomerulonephritis in Hong Kong

The clinical presentation and natural history of 428 patients with biopsyproven primary glomerulonephritis were reviewed. Minimal change glomerulonephritis presented with the nephrotic syndrome and followed a benign course. Membranous glomerulonephritis took a slow downhill course. HBs antigenaemia was present in 30% of patients with membranous glomerulonephritis. Mesangiocapillary glomerulonephritis often presented with mixed nephritic-nephrotic syndrome and had a bad prognosis. No type II variant was detected. Mesangial IgA glomerulonephritis commonly presented with abnormal urinary sediments although 2.5% of adults presenting with the nephrotic syndrome without glomerular insufficiency had mesangial IgA disease. Mesangial IgA glomerulonephritis was an important cause of end-stage renal failure in Hong Kong.     

IgA nephropathy in two adolescent sisters heterozygous for Fabry disease

We report a 16-year-old girl and her one-year-younger sister, both heterozygous for the c.34del24 mutation of the GLA (alpha-galactosidase A) gene, which they inherited from their father who is affected by Fabry disease (FD). Both girls presented with macrohematuria and rapidly progressing proteinuria. Urine analysis revealed glomerular hematuria and a nephrotic range of proteinuria suggesting a concomitant glomerulonephritis. Light microscopy of kidney biopsy was characteristic of IgA nephropathy (IgA deposits in mesangial areas and glomerular capillary loops, and mesangial hypercellularity), whereas electron microscopy showed changes typical of Fabry disease (multiple osmiophilic inclusions in the subendothelial and mesangial areas). These two cases and similar reports in the literature suggest that IgA nephropathy in FD is not merely coincidental.     

Mesangial IgA deposition in minimal change nephrotic syndrome: coincidence of different entities or variant of minimal change disease?

BACKGROUND: Mesangial deposition of IgA (MCA) is a very rare finding in minimal change disease and has previously been considered a pure coincidence. In the U.S. and Europe only anecdotal case reports exist. To date, there has been no consensus on nomenclature and categorization of this entity. We describe 2 cases of MCA with analogue histological findings but relevant differences in clinical presentation, and we discuss the clinical implications of mesangial IgA deposition in minimal change nephrotic syndrome. PATIENTS: A 47-year-old female was admitted to hospital with nephrotic syndrome, microscopic hematuria, arterial hypertension and slight impairment of renal function 3 weeks after an unspecific upper airway infection. A 42-year-old male presented with nephrotic syndrome, microscopic hematuria, normotension and normal renal function. Both of the nephrotic syndromes were steroid-responsive and steroid-dependent. FINDINGS: The clinical presentation of the male patient was consistent with the features of minimal change glomerulopathy, whereas the female patient combined signs of minimal change disease and IgA nephropathy. Light microscopy revealed mesangial IgA immune deposits and slight mesangial hypercellularity. Electron microscopic studies of MCA patients disclose diffuse effacement of glomerular foot processes. CONCLUSION: Our cases and a review of the literature indicate that the histological diagnosis of MCA may comprise different pathogenetic entities. From the clinical point of view, MCA has to be regarded as a minimal change nephrotic syndrome with symptomatic or asymptomatic mesangial IgA deposition. IgA deposition constitutes a risk factor for impairment of renal function and indicates a frequently relapsing course.     

Development of chronic renal failure in adult pure mesangial glomerulonephritis

Mesangial glomerulonephritis is uncommon histopathological pattern as a part of primary glomerular diseases. 64 (6.6%) patients of 968 non-transplant renal biopsies done at our department presented pure mesangial glomerulonephritis, without evidence of IgA nephropathy or systemic disorders. 22/64 (34.7%) of the patients presented with nephrotic syndrome, 12 were male, 10 female, aged 33.32 +/- 3.14. All of them were treated with steroids, 3/22 revealed complete remission, 4/22 partial remission and 6/22 did not respond to steroids, and later combined therapy with cyclophosphamide and cyclosporine. They developed end-stage renal failure within 4-8 years. 42/64 (65.3%) patients, 26 male, 16 female, aged 32.29 +/- 1.74 presented with erythruria and non-nephrotic proteinuria. Because of the absence of nephrotic syndrome only anti-hypertensive treatment was performed in this group of patients if necessary. One patient died because of hypertension complication (intracranial hemorrhage), two developed end-stage renal failure follow-up of 12 and 6 years.     

DEVELOPMENT OF CHRONIC RENAL FAILURE IN ADULT PURE MESANGIAL GLOMERULONEPHRITIS

Mesangial glomerulonephritis is uncommon histopathological pattern as a part of primary glomerular diseases. 64 (6.6%) patients of 968 non-transplant renal biopsies done at our department presented pure mesangial glomerulonephritis, without evidence of IgA nephropathy or systemic disorders. 22/64 (34.7%) of the patients presented with nephrotic syndrome, 12 were male, 10 female, aged 33.32 ± 3.14. All of them were treated with steroids, 3/22 revealed complete remission, 4/22 partial remission and 6/22 did not respond to steroids, and later combined therapy with cyclophosphamide and cyclosporine. They developed end-stage renal failure within 4–8 years. 42/64 (65.3%) patients, 26 male, 16 female, aged 32.29 ± 1.74 presented with erythruria and non-nephrotic proteinuria. Because of the absence of nephrotic syndrome only anti-hypertensive treatment was performed in this group of patients if necessary. One patient died because of hypertension complication (intracranial hemorrhage), two developed end-stage renal failure follow-up of 12 and 6 years.     

Clinicopathological study of patients presenting hematuria and proteinuria by renal biopsy

We performed 308 series renal biopsies during 4 years (1985-1989) and 289 cases were examined by light microscopic, electron microscopic, or immunofluorescent study. Clinically, chronic nephritic syndrome was most frequent (55.4%), followed by nephrotic syndrome (15.1%), and recurrent or persistent hematuria (12.8%). Pathologically, IgA nephropathy was most popular (39.3%), followed by normal glomerulus (9.1%), and thin basement membrane disease (8.7%). Glomerulonephritis clinically recognized with recurrent or persistent hematuria, hardly showing proteinuria, in 81.6% of the cases, consisted of normal glomerulus, or thin basement membrane disease by electron microscopic and immunofluorescent examinations. The remainder (18.4%) was with IgA nephropathy, which was histologically mild. On the other hand, cases of chronic nephritic syndrome (latent type) with persistent proteinuria and hematuria were with glomerulonephritis of various types including IgA nephropathy in 78.8% of the total cases. Therefore, proteinuria is an important sign of glomerulonephritis. In investigation in different age groups, IgA nephropathy was seen in about 40% of both pediatric and adult cases, whereas minor glomerular abnormalities and thin basement membrane disease were more frequent in pediatric cases. Tubulo-interstitial lesions and glomerular lesions in vascular or metabolic diseases were recognized more in adults than in children. Membranous glomerulonephritis (17 cases including 4 pediatric cases), complicated with malignant tumors such as bladder or rectal cancers and hepatoma was found in 3 aged patients. Examination for malignant tumor would be necessary for aged patients with membranous glomerulonephritis. As for the prognosis of IgA nephropathy, because histological changes of IgA nephropathy varied widely from very mild state to severe state, the prognosis is not always good.(ABSTRACT TRUNCATED AT 250 WORDS)     

肾活检患者451例临床与病理构成对比分析

目的 分析珠海地区肾脏疾病的病理及临床特点.方法 回顾性分析我院451例肾活检患者的临床及病理资料,探讨其病因、临床特点及病理类型的关系.结果 451例肾活检患者中,男、女高峰发病年龄为19～37岁,分别占59%及65%.原发性肾小球疾病共369例（占81.81%）,临床类型排在前3位的依次为无症状血尿、蛋白尿149例（占40.38%）、慢性肾小球肾炎104例（占28.18%）、肾病综合征76例（占20.60%）,病理类型排在前3位的依次为IgA肾病251例（占68.02%）、系膜增生性肾小球肾炎（MsPGN）33例（占8.94%）、微小病变型肾病（MCD）24例（占6.50%）;继发性肾小球疾病69例（占15.30%）,临床类型排在前3位的依次为狼疮肾炎26例（占37.68%）、乙型肝炎相关性肾小球肾炎24例（占34.78%）、紫癜肾炎9例（占13.04%）.结论 原发性肾小球疾病是目前最主要的肾小球疾病,IgA肾病在原发性肾脏疾病中发病率最高,继发性肾小球疾病中狼疮肾炎排在首位.     

Epidemiology of idiopathic glomerular disease: a prospective study

In this study incidence rates of idiopathic glomerular disease in 1.5 X 10(6) Dutch adults between 16 and 65 years of age were determined, as well as the prevalence of these diseases in terms of indication for renal biopsy. The study was conducted between 1978 and 1985; indications for renal biopsy in decreasing hierarchical order were recently discovered uremia, nephrotic syndrome, chronic hematuria of less than two years duration with or without proteinuria or disturbed renal function, and chronic proteinuria of less than two years duration, of unknown origin. The main findings are fourfold. The incidence of IgA nephropathy and thin glomerular basal membrane lesions was high, 19 and 13 per 10(6) adults respectively, and the prevalence in patients biopsied because of non-azotemic chronic hematuria was 31% and 22%, respectively. In the normotensive non-azotemic adults biopsied because of chronic, mild proteinuria the prevalence of focal segmental glomerular sclerosis and vascular hyalinosis was both 41%. Of the patients biopsied because of nephrotic syndrome the prevalence of membranoproliferative glomerulonephritis (5%) was low, as was the incidence (less than 2 per 10(6) adults per year). Finally, the prevalence of diffuse sclerosing glomerulonephritis was 25% in patients biopsied because of uremia. This study is useful for the differential diagnosis of idiopathic glomerular disease.     

Sequential occurrence of IgA nephropathy and Henoch-Schönlein purpura: support for common pathogenesis

We report a patient who developed Henoch-Schönlein purpura (HSP) 13 years after he presented with IgA nephropathy (IgAN). In both HSP and IgAN renal biopsy most commonly reveals focal proliferative glomerulonephritis on light microscopy and immunofluorescence displays mesangial IgA deposits. In addition, patients with HSP or IgAN have elevated serum IgA levels, circulating IgA immune complexes, IgA-bearing lymphocytes, immunoglobulin-producing cells, and binding of IgG to glomerular components of similar molecular weight. The occurrence of both diseases in the same patient or the same families and the presence of immune abnormalities compatible with HSP or IgAN in relatives of patients with these diseases suggest a common pathogenesis.     

Familial IgA nephropathy associated with bilateral sensorineural deafness.

Alport's syndrome is the most frequent disorder with familial nephritis and deafness, but other types of nephropathy have been occasionally associated with hereditary hearing loss. The familial occurrence of IgA nephropathy has been well documented. We report a family with hereditary, bilateral, sensorineural deafness spanning four generations. Three of five members with deafness had microscopic hematuria. Renal histology of the two deaf members undergoing biopsy showed mesangial glomerulonephritis with mesangial IgA deposits, without ultrastructural abnormalities of the glomerular basement membranes. Familial nephritis with deafness should not be equated with the diagnosis of Alport's syndrome.     

Lessons learned from the Japanese nephritis screening study

A program of urine screening for asymptomatic hematuria and proteinuria in school children has been conducted since 1973 by the Ministry of Education in Japan with great success in the early detection of asymptomatic renal disease. In order to know whether this nationwide program during 13 years has contributed to understanding of the epidemiology of chronic glomerular disease in Japan, a multicenter survey of the patients was conducted. Between 70% and 80% of IgA and non-IgA mesangial proliferative glomerulonephritis and 65%–80% of membranoproliferative glomerulonephritis (MPGN) were detected by mass urine screening at school. Severe glomerular lesions were more frequently observed in children with chance proteinuria and hematuria, as well as IgA and non-IgA mesangial proliferative glomerulonephritis with significant proteinuria. Mild glomerular change was more frequent in patients with MPGN, IgA and non-IgA mesangial proliferative nephritis with minimal proteinuria who were detected by our screening program, rather than those seen with some of the nephritic signs and symptoms at diagnosis. The above evidence suggests that a screening program may open the way for the early management of these diseases, especially where treatment is alrealy established.     

IgA肾病肾病综合征的临床和病理研究

目的：了解IgA肾病肾病综合征的临床和病理的特点及其与预后的关系。方法：观察72例经肾活检确诊为IgA肾病表现为肾病综合征的患的临床表现、实验室检查、病理改变、免疫组化、组织学定量分析及其与转归的关系。结果：患常见表现有高血压、肉眼和镜下血尿、贫血、氮质血症,病理改变多样;治疗后有22例完全缓解,15例部分缓解,16例呈持续性非肾病性蛋白尿,8例呈持续肾病性蛋白尿,10例发展为肾功能衰竭;其转归或激素敏感性与临床表现、蛋白尿选择性、小球病理形态、区膜区增宽和免疫沉着、小管间质病变及肾间质T淋巴和单核细胞分布显相关。结论：IgA肾病肾病综合征可有不同预后,其预后与临床表现、实验室发现、病理特点和免疫发病机理有关。     

Monocyte infiltration and cross-linked fibrin deposition in IgA nephritis and Henoch-Schoenlein purpura nephritis

To clarify the role of immune cell infiltration and fibrin deposition in glomerular injury, renal biopsy specimens taken from patients with primary IgA nephritis and Henoch-Sch?nlein purpura nephritis (HSPN) were evaluated using monoclonal antibodies specific to mononuclear cell surfaces and cross-linked fibrin (XFb). Monocytes/macrophages were the predominant cell type infiltrating glomeruli in IgA nephritis and HSPN. The intraglomerular monocyte population in both diseases was significantly higher than that in normals, mesangial proliferative (non-IgA) glomerulonephritis or minimal change nephrotic syndrome. In IgA nephritis, there was a clear correlation between glomerular monocyte accumulation and the degree of proteinuria. Although the monocyte influx tended to decline with time in HSPN, it remained unchanged in IgA nephritis. XFb deposition was found in the glomeruli of 27 out of 48 patients with IgA nephritis, and in 15 out of 20 with HSPN. The degree of XFb deposition in IgA nephritis correlated significantly with the degree of mesangial proliferation. These findings indicate a close relationship of monocyte/macrophage infiltration and XFb deposition with glomerular injury in IgA nephritis.