Organizing Pneumonia in A Patient Double-Positive for ANCA and Anti-GBM Antibodies: A Case Report / 中国医学科学杂志(英文版)

Both anti-glomerular basement membrane (GBM) disease and the anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) are common causes of pulmonary-renal syndrome. Organizing pneumonia (OP), a special pattern of interstitial lung disease, is extremely rare either in AAV or anti-GBM disease. We report an old woman presented with OP on a background of co-presentation with both ANCA and anti-GBM antibodies.

Reporte de un caso de glomerulonefritis rápidamente progresiva por anticuerpos antimembrana basal glomerular / Case report of rapidly progressive glomerulonephritis due to anti-glomerular basement membrane antibodies

RESUMEN Una vez más en medicina interna no podemos, aún, prescindir de los métodos invasivos para alcanzar un diagnóstico. Los avances diarios en el hallazgo de nuevas herramientas paraclínicas no permiten reemplazar aquellos métodos de certeza como la anatomía patológica. El caso presentado es una muestra de ello. Se trata de una mujer de 27 años de edad, con antecedente de tiroiditis de Hashimoto que consulta por presentar severo deterioro de la función renal asociado a oligoanuria. Realizamos una revisión del tratamiento de las glomerulonefritis rápidamente progresivas por anticuerpos antimembrana basal glomerular, serológicamente negativas.

ABSTRACT Once again in internal medicine we cannot do a diagnosis without invasive methods. Daily advances in the finding of new paraclinical tools do not allow the replacement of certain methods such as pathological anatomy. The case presented is a sample of this. This is a 27-year-old woman with a history of Hashimoto's thyroiditis who consults for presenting severe impairment of kidney function associated with oligoanuria. We performed a review of the treatment of the rapidly progressive glomerulonephritis for serologically negative anti-GBM antibodies.

Síndrome de Goodpasture atípico como reto diagnóstico / Atypical Goodpasture syndrome as diagnostic challenge

Resumen La enfermedad de Goodpasture es una entidad clínica con una base fisiopatológica inmunológica como punto de partida, en la que la unión al dominio terminal NC1 afecta principalmente en la zona glomerular y pulmonar, con lo que su diagnóstico está orientado hacia estas insuficiencias orgánicas; su incidencia varía de 0.5 a 1 casos por millón de habitantes, por lo que se considera una enfermedad poco frecuente y de mortalidad elevada debido a las complicaciones derivadas del mecanismo inmunológico. La manifestación pulmonar de manera aislada representa un porcentaje aún menor; la hemoptisis es, incluso en 66% de los casos, la forma más frecuente de expresión clínica. El pronóstico de estos pacientes se asocia con la forma de manifestación de la enfermedad y la calidad en la atención recibida. El diagnóstico definitivo se realiza mediante toma de biopsia; sin embargo, la existencia de anticuerpos anti-MBG (antimembrana basal glomerular) mediante la prueba ELISA puede manejarse en el diagnóstico con buena sensibilidad.

Abstract Goodpasture's disease is a clinical entity with an immunological pathophysiological basis, where the union to terminal NC1 domain mainly affects glomerular and lungs; thus, its diagnosis is oriented to such organ failure; its incidence varies from 0.5 to 1 cases per million population, for this reason it is considered a rare disease with high mortality due to complications from immune mechanism. Isolated lung presentation accounts for an even fewer percentage; in two thirds of cases hemoptysis is the most common clinical expression of the disease. Prognosis of these patients is associated to the presentation of the disease and the quality of care provided during the same. The definitive diagnosis is made by biopsy; however, the presence of antiGBM antibodies (glomerular basement membrane) by ELISA can be handled in the diagnosis with good sensitivity.

A Case of Goodpasture's Syndrome Combined with Crohn's Disease / 결핵및호흡기질환

A 29-year-old male patient was admitted due to his general weakness and poor oral intake for several months. He was diagnosed as having Crohn disease 16 years ago and total colectomy was performed 10 years ago. On the 3rd day after admission, gross hematuria and sudden hemoptysis combined with diffuse infiltration were noted on chest X-ray. His symptoms and the diffusely increased lung opacities improved with administering high-dose steroid therapy. Later, anti-GBM antibody was found to be positive on the laboratory findings. We report here on a rare case of Goodpsture syndrome combined with prolonged Crohn disease along with a review of literature.

Adenovirus-mediated Gene Therapy of Uteroglobin Protects the Experimental Glomerulonephritis in Mice / 대한신장학회잡지

PURPOSE: Uteroglobin (UG), steroid inducible cytokine-like protein, has potent anti-inflammatory and immunomodulatory action. It is secreted by the mucosal epithelia of virtually all mammals. The aims of this study were to investigate the efficacy of recombinant adenovirus carrying uteroglobin (AdCMV-UG) in prevention and treatment of glomerulonephritis (GN) in mice. METHODS: The AdCMV-UG was created by inserting the uteroglobin cDNA into the pAdTrack- CMV vector and was transfected into the 293 cells through liposome mediated vehicles. AdCMV-UG was injected direct to the both kidneys of 20 mice. In control groups (disease controls), 13 mice received adenoviral vector with GFP and another 11 mice received PBS only. After 5days of viral injection, GN was induced by repetitive intravenous injection of 3.0 mg rabbit anti-GBM Ab to the pretreated mice (C57/B6). Histological and biochemical changes were evaluated 7 and 14 days after injection of anti-GBM Ab. RESULTS: UG was expressed in the renal tissues and mesangial cells infected with the infection of AdCMV-UG. Pretreatment with AdCMV-UG attenuated the cellular crescent formation 7 days after induction of GN when compared to AdCMV-GFP, PBS only. We also observed reduced mesangial matrix expansion in mice treated with adenovirus carrying UG. Proteinuria was significantly reduced in the mice treated with adenovirus carrying UG when compared with disease control mice (AdCMV-UG 102.2+/-20.97, AdCMV-GFP 170.6+/-41.77, and PBS 169.8+/-55.67, respectively p<0.05 mg/mg). However, at 14 days after anti-GBM Ab injection (total 19 days), there was no significant difference in the amounts of prot einuria and morphologic findings between pretreated and disease control groups. CONCLUSION: Adenoviral mediated gene transfer is an effective way of gene delivery. Locally expressed uteroglobin attenuated the severity of glomerulonephritis induced by anti-GBM antibody, although it was transient. Gene therapy using uteroglobin may be constituted for the treatment of human diseases such as chronic GN.

Prevention and Treatment of Experimental Glomerulonephritis Using Recombinant Uteroglobin / 대한신장학회잡지

Glomerulonephritis(GN) is characterized by cognate immune responses against self or non-self antigen. It is suggested that the crescentic GN is a manifestation of cell-mediated immune response akin to delayed type hypersensitivity. Uteroglobin(UG) is a steroid-dependent, immunomodulatory, and cytokine-like protein. It was reported that UG prevented fibronectin(Fn) deposition in the glomeruli of normal mice to form Fn-UG heterodimers that competed with Fn self-aggregation. We hypothesized that UG would prevent the development of experimental GN induced by anti-glomerular basement membrane globulin(anti-GBM Ab) in mice through immunomodulatory properties. GN was induced by intravenous injection of 4.5 mg rabbit anti-GBM Ab to mice(C57BL/6). Renal injury was evaluated at 7, 14, and 21 days thereafter. UG-treated mice(n=10) were received for 3 days(0.5 mg/mouse/day) beginning 1 hour after anti-GBM Ab injection. Also, disease-control mice(n=10) were received PBS for 3 days after anti-GBM Ab. Proteinuria was significantly reduced in the mice treated with UG when compared with the disease-control mice after 7 and 14 days of anti-GBM Ab injection. The amount of proteinuria was similar between UG treated and normal control mice. The mesangial matrix expansion and cellular crescent were markedly attenuated by the injection of UG. The proliferative responses of mesangial cells(C57BL/6) to LPS were blunted with the addition of UG in dose-dependent manner. In this study, we revealed the preventive effects of UG in the experimental model of glomerulonephritis. This result in turn could provide the basis for the treatment of human disease such as chronic glomerulonephritis.

Effects of FK506 on anti-glomerular basement membrane nephritis in rats / 中国病理生理杂志

AIM: To investigate the effects of FK506 on anti-glomerular basement membrane(GBM) nephritis in rats. METHODS: Anti-GBM nephritis model was elaborated by rabbit anti-rat GBM antibody injection in SD rats in this study. The rats were divided into three groups: FK506 treated group(0 5 mg?kg -1 ?d -1 , sc), untreated nephritis control group and normal control group. FK506 was administered daily six hours after injection of anti-GBM IgG. All the rats were observed urinary protein at the 4th day, the 14th day and the 21st day. At the same time, the kidney specimens were collected, and T cell transforming function was also monitored. RESULTS: Rats injected with rabbit anti-GBM Ab developed heavy proteinuria by 4 days, and serum creatinine and serum urea appeared which kept on the rising. Glmerular hypercellularity, crescents, and protein casts were observed in nephritic rats. By electron microscopy, the thickening of GBM and loss of foot processes were seen. T cell transforming function was higher than normal. But, all pathological changes obviously turned for the better in FK506 treated group. CONCLUSION: FK506 could inhibit the progression of rat anti-GBM nephritis.

A Case of Anti-Glomerular Basement Membrane Antibody Associated Crescentic Glomerulonephritis with Positive Antineutrophilic Cytoplasmic Antibody / 대한신장학회잡지

A 63-year-old woman presented to the hospital with gross hematuria and acute renal failure. Kidney function deteriorated rapidly and progressively. A renal biopsy revealed segmental or circumferential crescents associated with linear deposits of immunoglobulin G, typical of anti-glomerular basement membrane disease. Both c-ANCA and anti-GBM antibody were detected in serum. She was treated with hemodialysis, plasmapheresis, high dose steroid and cyclophosphamide. However, she died 7 weeks after treatment because of pneumonia, without recovery of renal function. Serologic positivity of both ANCA and anti-GBM antibody are becoming more frequently recognized in rapidly progressive glomerulonephritis. The influence of c-ANCA on the clinical course of anti-GBM glomerulonephritis remains to be determined.

Sequential Changes of Extracellular Matrix mRNA in Anti-GBM Antibody Induced Crescentic Glomerulonephritis in the Rabbit

Progressive renal fibrosis is considered to be the final common pathway leading to chronic renal insufficiency, however, the mechanism regarding renal fibrosis in renal injury is not well understood. Recently, several kinds of cytokines have been known to be related to fibrosis after renal injury. The interaction between elements regulating fibrogenesis would be better understood by looking at the effect of TGF-beta1 on the synthesis and accumulation of extracellular matrix, especially collagenous proteins. Crescentic glomerulonephritis (CGN) was induced in New Zealand White rabbits by administration of guinea pig anti-GBM IgG after sensitization with guinea pig IgG; and their kidneys were analyzed for the development of crescents and fibrosis through sequential renal biopsies. Serum creatinine levels in a time course progressively increased until day 15. We semi-quantitatively assayed the levels of the expression of alpha1(I) collagen mRNA and TGF-beta1 mRNA factored for GAPDH mRNA using RT-PCR. We observed a progressive interstitial fibrosis and the expression of collagen I both in the cortex and medulla. The effect of repeated renal biopsy itself on pathology and on the expression of alpha1(I) collagen mRNA and TGF-beta1 mRNA in a time course were not significant, but a very mild increase of the expression of alpha1(I) collagen mRNA was noted at day 15. Histology showed a progressive crescent formation and interstitial fibrosis in a time course that roughly paralleled the expression of alpha1(I) collagen mRNA in both cortex and medulla. TGF-beta1 mRNA was hardly expressed at day 0 in cortex as well as in medulla. It was elevated from day 1, peaked at day 7, and then decreased. In medulla, TGF-beta1 mRNA was noticeably expressed at day 1, peaked at day 4, and then decreased. The expression of alpha1(I) collagen mRNA was seen even before inducing CGN. It was gradually and continuously increased until day 15 both in cortex and medulla. These results suggest that the expression of TGF-beta1 mRNA precedes that of alpha1(I) collagen mRNA in the early stage of CGN and has a central role for provoking the accumulation the collagen I, the most representative interstitial extracellular matrix, in the rabbit model CGN induced by anti-GBM antibody. We conclude that the measurement of the expression of TGF-beta1 mRNA and/or alpha1(I) collagen mRNA in a biopsy sample can be a useful predictor for renal outcome.

Sequential Studies of Glomerular Crescent Formation in Rabbits with Anti-Glomerular Basement Membrane(GBM) Antibody Induced Glomerulonephritis(GN)

To investigate the mechanism of crescent formation, sequential pathologic changes from the New Zealand White rabbits with anti-GBM antibody induced GN by administration of guinea pig anti-GBM IgG were studied by light (LM), immunofluorescent (IF) and electron (EM) microscopy. Although no glomerular changes were observed in LM, swelling of the endothelial cells and the epithelial cells were noted in EM by day 2. By day 7, early and cellular crescents were evident. Proteinaceous materials and fibrins were noted in the glomerular capillary lumina (GCL) and Bowman's space (BS) associated with segmental hypercellularity. The GBM damage became progressively severe, followed by focal detachment of the visceral epithelial cells from the GBM. At day 14, fibrin strands, mononuclear cells and collagen fibrils were present between the proliferating extracapillary cells. At day 31, fibrocellular crescents were predominated. Elongated spindle cells, morphologically resembling myofibroblasts, were noted near the Bowman's capsule (BC). A degree of tubular atrophy, interstitial fibrosis, and inflammatory infiltrates increased as it did with fibrous organization of crescent. Intense linear IF staining for IgG and C3 were seen throughout the experiments along the GBM. In conclusion, the progression of crescent from an early "proteinaceous" stage through cellular, fibrocellular and fibrous stages was well documented in this study. Inflammatory cells and coagulation mechanism may activate the initiation of the GBM damage at the early stage. Activated periglomerular mononuclear cells may also cause disruption of BC which facilitates entry of activated periglomerular cells and fibroblasts into BS leading to progressive fibrous crescent formation.

Protective effects and mechanisms of tetramethypyrazine on accelerated anti-GBM antibody nephritis in rats / 中国药理学通报

AIM To investigate the protective effects and mechanisms of TMP on accelerated anti-glomerulus basement membrane(GBM) antibody nephritis of rats. METHODS Model of accelerated anti-GBM nephritis was established in rats and TMP was administrated 120 mg?kg -1 ?d -1 by ip since the day before the model established, consecutively for 15 days. Content of 24h urine protein was detected after model established and rats were killed on d 7 and d 14. Contents of blood urine nitrogen (BUN) and serum creatinine (SCr) were detected. Renal cortex cytoplasm and mitochondria were produced and change of content of lipid peroxidation products malondialdehyde(MDA), activities of glutathione peroxidase(GSH-Px) and catalase(CAT) and superoxide dismutase(SOD) were investigated. RESULTS Compared with model group, TMP group showed significant inhibition in changes of proteinuria and BUN, SCr(P