Concurrent antiglomerular basement membrane disease and immune complex glomerulonephritis

Antiglomerular basement membrane (GBM) disease is characteristically described with linear deposition of IgG along GBM. However, the concurrent glomerular immune complex deposition was not rare and might be contributed to the development of anti-GBM disease. In the current series, glomerular immune complexes were identified in 10 of 47 patients who presented with renal-biopsy-proven anti-GBM disease. Six of the 10 patients complicated with a well-documented glomerulonephritis, including two patients with membranous nephropathy, one patient with IgA nephropathy, one patient with membranoproliferative glomerulonephritis, one patient with Schonlein-Henoch nephritis, and one patient with hepatitis B virus associated membranous nephritis. The other four patients had immune complexes with IgG or IgM predominance deposited in glomerular mesangium without a well-documented glomerulonephritis. Clinical and pathological data of patients with immune complex deposition (n = 10) were compared with those of patients with anti-GBM disease alone (n = 37). There was no significant difference in age, gender, clinical and pathological manifestations, and renal outcome between the two groups. In general, the association of glomerular immune complexes did not lead to a benign prognosis. Plasma exchange and extensive immunosuppressive therapy should be carried out as soon as possible. The immune complexes deposited in glomeruli might participate in the initiation of anti-GBM disease.     

IgA deficiency with membranous glomerulonephritis: a case report and review

Selective immunoglobulin A (IgA) deficiency may result in a predisposition to recurrent sinopulmonary infection and allergic diseases. IgA deficiency may also play a role in the development of autoimmune disorders. Selective IgA deficiency associated with glomerulonephritis was rare, while the clinical presentation in IgA deficiency-associated glomerulonephritis was variable. We report an 83 year-old male with selective IgA deficiency associated with membranous glomerulonephritis. He presented with nephrotic syndrome. Percutaneous renal needle biopsy showed diffuse global thickening and rigidity of glomerular capillary walls, mildly diffuse segmental expansion of mesangial matrix, focal and cortical scar with segmental obsolescence of glomeruli. Heavy IgG and moderate C3 deposits were found on immunofluorescence. We also review the previous cases of IgA deficiency with glomerulonephritis. Several clues were rendered to establish the association between IgA deficiency and membranous glomerulonephritis.     

An unusual case of IgA-mediated anti-glomerular basement membrane disease

Anti-glomerular basement membrane (GBM) disease is mediated by circulating autoantibodies, principally IgG, targeted at the type IV collagen of GBM. The IgA variant of anti-GBM disease has rarely been described. We report a 65-year-old man with uremia, undergoing hemodialysis, who was referred because of hemoptysis. A chest X-ray showed diffuse infiltration in the right lung field. Laboratory data were remarkable for renal failure, anemia, and thrombocytopenia. Furthermore, laboratory evidence of microangiopathic hemolytic anemia was present. A kidney biopsy revealed diffuse crescentic glomerulonephritis. Circulating IgA anti-GBM antibody was found, as well as the presence of significant IgA deposition in a linear pattern along the GBM, suggesting an anti-GBM antibody-mediated disease. The patient was treated with plasmapheresis and pulse steroid therapy, which resulted in an immediate improvement in the pulmonary hemorrhage and hematological abnormalities. However, the patient did not regain renal function and remained on hemodialysis.     

Experimental autoimmune anti-glomerular basement membrane glomerulonephritis: a protective role for IFN-gamma

IL-12 and IFN-gamma play key roles in murine lupus and planted antigen models of glomerulonephritis. However, their roles in renal organ-specific autoimmunity are unknown. To establish the roles of endogenous IFN-gamma and IL-12 in experimental autoimmune anti-glomerular basement membrane (GBM) glomerulonephritis (EAG), EAG was induced in normal C57BL/6 mice (WT), IL-12p40-deficient (IL-12p40-/-) mice, and IFN-gamma-deficient (IFN-gamma-/-) mice by immunization with alpha3-alpha5(IV)NC1 heterodimers. At 13 wk, WT mice developed EAG with linear mouse anti-GBM antibody deposition, histologic injury, proteinuria, and mild tubulointerstitial disease. Compared with WT mice, IL-12p40-/- mice had decreased histologic injury and trends to decreased leukocyte infiltrates. In contrast, 40% (4 of 10) of IFN-gamma-/- mice developed significant crescent formation and focal or diffuse interstitial infiltrates (WT, 0 of 8). Compared with WT and/or IL-12p40-/- mice, IFN-gamma-/- mice developed increased injury: histologic injury, total glomerular cell numbers, leukocytes in glomeruli, and renal expression of P-selectin and intercellular adhesion molecule 1. All groups developed similar serum anti-alpha3-alpha5(IV)NC1 antibodies and glomerular Ig deposition, but IFN-gamma-/- mice had decreased anti-alpha3-alpha5(IV)NC1 IgG2a. Therefore, IFN-gamma-/- mice developed increased cellular reactants despite a potentially less damaging antibody response. Dermal delayed-type hypersensitivity was increased in alpha3-alpha5(IV)NC1 immunized IFN-gamma-/- mice and was suppressed by recombinant murine IFN-gamma. CD4+ cells from draining nodes of immunized IFN-gamma-/- mice showed increased proportions of proliferating CD4+ cells but similar numbers of apoptotic cells. These studies demonstrate that in renal organ-specific autoimmunity, IL-12 is pathogenetic but IFN-gamma is protective. They lend weight to the hypothesis that depending on the context/severity of the nephritogenic immune response IFN-gamma has different effects.     

Evolution of antiglomerular basement membrane glomerulonephritis into membranous glomerulonephritis

Antiglomerular basement membrane glomerulonephritis (anti-GBM GN) is a rare disease characterized by autoantibodies to the alpha 3 chain of type IV collagen in the GBM. It is also known as Goodpasture’s syndrome when associated with pulmonary hemorrhage due to autoantibodies to the alpha 3 chain of type IV collagen also present in pulmonary alveoli. Even more rare is the evolution of anti-GBM GN into membranous nephropathy (MN). We report the management of a 9-year-old Caucasian girl with anti-GBM GN that evolved into MN and briefly review the literature.     

Histamine ameliorates anti-glomerular basement membrane antibody-induced glomerulonephritis in rats

Anti-glomerular basement membrane (anti-GBM)-induced glomerulonephritis involves T-helper type 1 (Th1) responses leading to rapid crescent formation. As many inflammatory and immune responses in general are affected by histamine, we examined the effects of histaminergic ligands on immune renal injury in the rat. Female Wistar-Kyoto rats were injected intraperitoneally with an antibody against the GBMs. Histaminergic ligands were then injected twice daily for 5 days after which renal function was assessed by proteinuria. Treatment with histamine led to significant dose-dependent reductions in proteinuria compared to the control antibody-injected group and markedly decreased the number of crescentic glomeruli and macrophage infiltration of the glomeruli. Furthermore, histamine significantly decreased the plasma concentration of interleukin-12, a Th1-type cytokine compared to the antibody-injected control animals. Dimaprit, an H(2)/H(4) agonist, mimicked the effects of histamine on proteinuria and crescent formation. Clozapine, an H(4) agonist, tended to mimic the effects of histamine, whereas an H(1), mepyramine, or an H(2) antagonist, ranitidine, did not reverse the protective effect of histamine. We suggest that histamine may alleviate renal injury in anti-GBM glomerulonephritis by suppressing the immune response.     

An unusual case of anti-glomerular basement membrane disease presenting with nephrotic syndrome

Anti-glomerular basement membrane (anti-GBM) disease is a vasculitic disease characterized by acute kidney injury, oliguria, hematuria and proteinuria. Proteinuria is rarely in the nephrotic range. A case of anti-GBM disease with proteinuria of 22.5g/day is discussed. Immunofluorescence showed strong linear IgG deposits while electron microscopy showed widespread visceral epithelial cell foot cell process effacement. No electron dense immune complex-type deposits were identified. Pathology findings were not suggestive of simultaneous presentation of anti-GBM disease and other diseases associated with nephrotic range proteinuria. Anti-GBM disease should be considered in a comprehensive differential diagnosis of severe proteinuria.     

Familial Mediterranean fever and membranous glomerulonephritis: report of a case

Familial Mediterranean fever (FMF) is an autosomal recessive genetic disease characterized by recurrent attacks of fever and painful episodes of sterile polyserositis. Kidney involvement may occur as a result of secondary amyloidosis during the course of FMF. Previously, different types of glomerulopathies such as IgM and IgA nephropathy, crescentic glomerulonephritis, diffuse proliferative glomerulonephritis, minimal change disease, and membranoproliferative glomerulonephritis were rarely reported. We herein represent a first case of membranous glomerulonephritis who had complete remission with colchicine treatment in the course of familial Mediterranean fever.     

Ribbing disease: a case report and literature review

Ribbing disease (RD) is a rare bone dysplasia characterized by benign endosteal and periosteal new bone formation confined to the diaphysis of the long bones of the lower extremities in young adults. The etiology and optimal treatment for the disease are unknown. It is often initially diagnosed as a low-grade osteomyelitis or a bone-forming neoplasia. It may also be confused with other causes of increased bone density. The onset is usually after puberty and the most common presenting symptom is pain that does not resolve with medical treatment and sometimes is intolerable. We report the case of a 22-year old woman with clinical and radiological manifestations of RD. In spite of different medical treatment modalities, pain did not resolve and the patient consulted multiple physicians. Intramedullary reaming of the tibia was performed to relieve the severe pain. To the authors' knowledge, in this report we present a case of RD for the third time in the orthopaedic literature and also she is the second case in the English literature to undergo a definite surgical treatment modality as intramedullary reaming for the solution of her pain. Owing to the rarity of the disease we aimed to report the complete findings of our encounter with the disease and to emphasize the role of an orthopaedic surgeon in consultation and intervention for the treatment of intolerable pain which is the most important symptom of this disease.     

Lupus nephritis and thin glomerular basement membrane coexistence: case report and review of the literature

International Urology and Nephrology -     

Late presentation of Alport posttransplantation anti-glomerular basement membrane disease

We describe a female patient with Alport disease who developed antiglomerular basement membrane nephritis late after kidney transplantation during the treatment of an acute bacterial pyelonephritis and discuss the potential role of the infection as a trigger for the development of this nephritis.     

Advances in the genetics of anti-glomerular basement membrane disease

Anti-glomerular basement membrane (GBM) disease is a rare but lethal autoimmune disorder. Over the past few years, the nature of the autoantigen and its epitopes has been defined, as well as the possible pathogenic role played by environmental factors, and by cellular and humoral immunity. However, the majority of data on anti-GBM disease comes from studies conducted on animal models, since human studies are relatively scarce. Genetic studies have highlighted strong positive associations of anti-GBM disease with the HLA-DRB1*1501 allele. In addition, the disease has been associated with genes of the FCGR and KLK families. Important as they are, these findings have to be considered preliminary, if not contentious. Here, we provide an overview of recent discoveries in the genetics of anti-GBM disease that may help elucidate the disease pathogenesis while improving therapeutic approaches. We also discuss the limitations of such discoveries. Finally, we suggest that extensive collaboration between investigators and novel integrative approaches are essential to the progress of our understanding of the anti-GBM disease. We attempted to summarize the current knowledge on the pathogenesis of anti-GBM disease by providing different but complementary perspectives from previous reviews.     

Superimposed glomerular immune complexes in anti-glomerular basement membrane disease

The association of anti-glomerular basement membrane (GBM) antibody-mediated glomerulonephritis and glomerular immune complexes is common and probably arises from a number of mechanisms. In the series, glomerular immune complexes were identified in 6 of 17 patients who initially presented with anti-GBM disease. In four cases, glomerular immune complexes were noted in renal biopsies obtained at clinical presentation; in the other two, they were first demonstrated seven and 28 months after presentation, when circulating anti-GBM antibody levels were undetectable. Circulating immune complexes were detected in only two of six patients, either 28 months before or 17 months after the demonstration of the glomerular membranous lesion. The association of glomerular immune complexes and anti-GBM disease may be coincidental with immunologically-unrelated immune complexes localizing in the GBM for physico-chemical reasons; or the presence of glomerular-bound anti-GBM antibodies may predispose to the deposition of molecules with particular affinity for these antibodies. One patient with glomerular immune complexes used heroin, which may be associated with immune complex formation and the development of glomerulonephritis; and one patient was subsequently thought to have systemic lupus erythematosus (SLE). An antecedent infection was found in two of the four patients who had glomerular complexes at presentation, but in only three of 13 with uncomplicated anti-GBM disease. Three of 6 patients with superimposed glomerular complexes had a history of exposure to organic solvents before the onset of disease, while none in the group with anti-GBM disease alone had.     

Silica and glomerulonephritis: case report and review of the literature

A 54-year-old foundry worker with extensive silica exposure, but no pulmonary disease, developed the nephrotic syndrome and renal failure over a 3-month period. Renal biopsy demonstrated a proliferative glomerulonephritis; energy dispersive x-ray analysis detected silicon within the renal tubules. Measurements of respirable silica at the foundry revealed levels up to 2.5 times the current occupational standard. Similar glomerular disease has been reported in silica-exposed animals and workers with silicosis. This case suggests that clinicians should include silica exposure in the differential diagnosis of unexplained diffuse proliferative glomerulonephritis, renal disease may occur without clinically evident pulmonary disease in silica exposure, and silica-induced glomerulonephritis warrants further clinical and epidemiologic research.     

水痘带状疱疹病毒相关性肾小球肾炎及脑炎一例报告及文献复习

目的 介绍1例水痘带状疱疹病毒相关性肾小球肾炎及脑炎病例。 方法 分析患者临床和肾脏病理资料,并复习有关文献。 结果 男性15岁患者,水痘发病后5 d出现急性肾炎综合征、肾病综合征表现及肾功能损害,血清补体C3下降。肾组织光镜检查诊断为毛细血管内增生性肾小球肾炎,伴足细胞增生及重度肾小管损伤;免疫荧光检查显示“满堂亮”;电镜检查见到多部位电子致密物。另外,电镜及Mann染色光镜检查还见到病毒样颗粒或（和）包涵体。血清病毒学检查水痘带状疱疹病毒（VZV）IgM抗体阳性。肾组织免疫组化染色和原位杂交显示肾小球及肾小管上皮细胞内存在VZV抗原及转录产物RNA。病程中患者曾多次出现癫痫发作,头颅磁共振检查及脑电图表现符合病毒性脑炎继发癫痫。所以本病例水痘-带状疱疹病毒相关肾炎及脑炎诊断成立。 结论 通过血清病毒学及组织病毒学多项检查证实本例为水痘-带状疱疹病毒相关性肾炎及脑炎,是首例报道。