Evaluation of Ki-67, CD68 and Bcl-2 staining, dialysis and mortality in crescentic glomerulonephritis / Evaluación de tinción de Ki-67, CD68 y Bcl-2, diálisis y mortalidad en glomerulonefritis de crescéntica

ABSTRACT Introduction: Immunohistochemical staining of Ki-67, CD68 and Bcl-2 have been studied in glomerulonephritis. We aimed to assess these immunohistochemical staining features, hemodialysis initiation and 60 month mortality ratesin crescentic glomerulonephritis. Methods: In this retrospective study, patients, with a previous diagnosisof crescentic glomerulonephritis weredivided into two groups: Hemodialysis Initiated and Not Initiated groups. Kidney biopsy specimens'Ki-67, CD68 and Bcl-2 staining scores were defined as below 5% "0", 5-10% "+1", 11-20% "+2", over 20% "+3". Patients demographic, laboratory data, status ofhemodialysis initiation, and mortality wereobtained from medical records and immunohistochemical staining scores were compared between groups. Estimated glomerular filtration rates (eGFR) were assessed at 0, 6, and 12 months, except patients' ongoing hemodialysis. Results: A total of 56 patients were diagnosed as crescentic glomerulonephritis. Pauci-immune crescentic glomerulonephritis (58.9%) was the most common etiology. Hemodialysis was initiated in 36 patients. Mean age, baseline creatinine, urea, C-reactive protein levels were significantly higher and, hemoglobin and proteinuria levels were significantly lower in the Hemodialysis Initiated group. Immunohistochemical staining scores were not significantlydifferentbetween groups. In Hemodialysis Initiated group, 8.33% of patients were recovered from hemodialysis. Mortality rates were 44,4% and 10% in patients in the group of hemodialysis initiated and not initiated group respectively. When we combine the hemodialysis not initiated patients and patients recovered from hemodialysis;median eGFR atbaseline, 6th and 12th month were32.9, 43.9, and 58.0 mL/min/1.73m2, respectively (p=0.016). Conclusion: Hemodialysis initiation was associated with high mortality. Degree of immunohistochemical staining was similar in both groups. Increment in eGFR was documented in first year in patients, other than the ones on still on hemodialysis.

RESUMEN Introducción: Se ha estudiado la tinción inmunohistoquímica de Ki-67, CD68 y Bcl-2 en glomerulonefritis. Objetivo: Evaluar estas características de tinción inmunohistoquímica, el inicio de la hemodiálisis y la tasa de mortalidad a los 60 meses en la glomerulonefritis crescéntica. Material y métodos: En este estudio retrospectivo, los pacientes, con diagnóstico previo de glomerulonefritis crescéntica se dividieron en dos grupos: Hemodiálisis iniciada y no iniciada.La puntuación de tinción Ki-67, CD68 y Bcl-2 de las muestras de biopsia de riñón se definió del siguiente modo: por debajo del 5% "0", 5-10% "+1", 11-20% "+2", más del 20% "+3".Se compararon los siguientes datos en los pacientes: demografía, resultados de laboratorio, de iniciación de la hemodiálisis y la mortalidad obtenida de los registros médicos y las puntuaciones de tinción inmunohistoquímica entre los grupos.La Tasa de filtrado glomerular estimada(TFGe) fue evaluada a los 0, 6 y 12 meses,excepto en los pacientes en hemodiálisis en curso. Resultados: Un total de 56 pacientes fueron diagnosticados con glomerulonefritis crescéntica. La glomerulonefritis crescénticapauciinmune(58,9%) fue la etiología más común. Se inició hemodiálisis en 36 pacientes.La edad media, los niveles basales de creatinina, urea y proteína C reactiva fueron significativamente más altos, y los niveles de hemoglobina y proteinuria fueron significativamente más bajos en el grupo de Hemodiálisis Iniciada. Las puntuaciones de tinción inmunohistoquímica no fueron significativas entre los grupos. En el grupo de Hemodiálisis Iniciada 8,33% de los pacientes recuperó función renal y salió de diálisis. La tasa de mortalidad en el grupo de Hemodiálisis no Iniciada fue del 10,0% y en el grupo que inicio HD del 44%. Cuando combinamos los pacientes Hemodiálisis no Iniciada y los pacientes recuperados de hemodiálisis la mediana de TGFe en la línea de base, 6º y 12º mes fue 32,9, 43,9 y 58,0 mL/minuto/1,73m2, respectivamente (p<0,016). Conclusión: El inicio de la hemodiálisis se asoció con una alta mortalidad. El grado de tinción inmunohistoquímica fue similar en ambos grupos. El incremento de la TFGe se documentó en el primer año en pacientes distintos de los que aún estaban en hemodiálisis.

Updates on the role of T lymphocytes in crescentic glomerulonephritis / 国际儿科学杂志

The formation of crescent is a typical pathological change characterized by a rapid deterioration of renal function.T lymphocytes are involved in the formation of crescent and the pathological progression of crescent nephritis.CD4 + and CD8 + cells in T lymphocyte subsets, and T cell costimulatory factors mediate immune responses in different ways.They participate in the occurrence, development and fibrosis of crescent, or delay their deterioration.In order to provide a new target for clinical treatment of crescent nephritis, we review the mechanism of T lymphocytes in the formation and development of crescentic body.

A study of clinicopathological features and outcomes of crescentic glomerulonephritis

Background: Crescentic Glomerulonephritis (CrGN) is characterized by rapidly progressive renal failure. Most of the literatures have defined >50% crescents in biopsy as CrGN. Only very few studies have included the presence of <50% crescents as CrGN.Methods: To assess the clinico-pathological features and outcome of CrGN with >10% crescents on renal biopsy and comparing them splitting our diagnosis into Immune Complex Mediated CrGN (ICCGN) and non-immune complex mediated CrGN (NICCGN) groups.Results: ICCGN was the commonest group. When compared to ICCGN group, NICCGN patients were older, anuric, had more glomerular necrosis and severe IFTA in biopsy at presentation, more became dialysis dependent at index visit discharge. When patients with >50% crescents in both the groups were compared similar results were seen except that infective complications and proliferative lesions were more in ICCGN. When patients with <50% crescents in both the groups were compared similar findings were seen except that no difference was seen in clinical features and dialysis dependency between them.Conclusions: Oliguria at presentation, Hb <9 g/dl, index visit eGFR<15 ml/min, crescents >60%, moderate to severe IFTA are the independent risk factors for dialysis dependency at index visit discharge.

Association between neutrophil-lymphocyte & platelet lymphocyte ratios with prognosis & mortality in rapidly progressive glomerulonephritis

Background & objectives: Rapidly progressive glomerulonephritis (RPGN) is a clinical syndrome manifested by features of nephritic syndrome and progressive loss of renal function over a short time. The objective of this study was to investigate the relationship between neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR) and prognostic factors and pathological findings of renal biopsy in RPGN. Methods: Consecutive newly diagnosed RPGN patients who had follow up for at least six months were retrospectively analyzed. The estimated glomerular filtration rate (eGFR) was calculated. Albumin, C-reactive protein (CRP) levels and CRP/albumin ratio were also calculated. Results: Fifty four patients were included in the study. The mean age was 48.92±20.12 years. Clinicopathological diagnosis was pauci-immune glomerulonephritis (GN) in 40 while two had postinfectious GN, six systemic lupus erythematosus, three IgA nephropathy, two Henoch-Schönlein purpura and one membranoproliferative GN. The mean NLR was 7.02±6.34 and mean PLR was 273.90±39.15. Positive correlations between NLR and CRP levels (P=0.009, r=0.511) and CRP/albumin ratios (P=0.005, r=0.542) were observed. PLR and CRP/albumin ratios (P=0.041, r=0.412) were correlated positively. The per cent of fibrocellular crescents was negatively correlated with NLR (P=0.019, r=?0.291), and positively correlated with the lymphocyte count (P=0.05, r=0.256). In secondary crescentic subgroup, the per cent of fibrinoid necrosis had a positive correlation with PLR (P=0.013, r=0.642). Both NLR (P=0.036) and PLR (P=0.051) detected at the first month of the treatment period, were observed to be significantly correlated with mortality. Interpretation & conclusions: This study showed that NLR could predict mortality in patients with RPGN; correlated with systemic inflammation; showed a negative correlation with the per cent of fibrocellular crescents and could be regarded as a measure of glomerular inflammatory state. Moreover, PLR may be considered to be an indicator of disease severity in acute phase of crescentic GN.

Concurrent Anti-glomerular Basement Membrane Nephritis and IgA Nephropathy

Anti–glomerular basement membrane (GBM) nephritis is characterized by circulating anti-GBM antibodies and crescentic glomerulonephritis (GN) with deposition of IgG along the GBM. In a limited number of cases, glomerular immune complexes have been identified in anti-GBM nephritis. A 38-year-old female presented azotemia, hematuria, and proteinuria without any pulmonary symptoms. A renal biopsy showed crescentic GN with linear IgG deposition along the GBM and mesangial IgA deposition. The patient was diagnosed as concurrent anti-GBM nephritis and IgA nephropathy. Therapies with pulse methylprednisolone and cyclophosphamide administration were effective. Concurrent cases of both anti-GBM nephritis and IgA nephropathy are rare among cases of anti-GBM diseases with deposition of immune complexes. This rare case of concurrent anti-GBM nephritis and IgA nephropathy with literature review is noteworthy.

Progress in diagnosis and treatment of pediatric microscopic polyangiitis / 中华实用儿科临床杂志

Microscopic polyangiitis (MPA) is an anti-neutrophil cytoplasmic antibody (ANCA) associated systemic small vessel vasculitis and is uncommon in children.Pathologically characterized by paucity immune deposition,fibroid necrosis and crescent formation in glomeruli.MPA is a multi-organ involvement disease.Renal is the mostly involved and commonly manifested as aggressive glomerulonephritis.Lung is the most common involved extrarenal organ.Most MPA patients have positive myeloperoxidase-ANCA and positive perinuclear-ANCA.The onset of MPA is usually obscure,which makes early diagnosis difficult.Detection of ANCA is performed in order to discriminate suspected MPA patients earlier.Confirmed diagnosis relies on pathology.Early standardized treatment is a key factor in prognosis.Standard inductive treatment is currently the combination of corticosteroids with the cytotoxic agent cyclophosphamide.Azathioprine is suggested as the first-choice medication in maintenance therapy.Bio-agents,such as Rituximab,have shown good curative effect both in the inductive treatment and maintenance therapy.

Cocaine/levamisole-induced systemic vasculitis with retiform purpura and pauci-immune glomerulonephritis

Levamisole has been increasingly used as an adulterant of cocaine in recent years, emerging as a public health challenge worldwide. Levamisole-associated toxicity manifests clinically as a systemic vasculitis, consisting of cutaneous, hematological, and renal lesions, among others. Purpura retiform, cutaneous necrosis, intravascular thrombosis, neutropenia, and less commonly crescentic nephritis have been described in association with anti-neutrophil cytoplasmic antibodies (ANCAs) and other autoantibodies. Here we report the case of a 49-year-old male who was a chronic cocaine user, and who presented spontaneous weight loss, arthralgia, and 3 weeks before admission purpuric skin lesions in the earlobes and in the anterior thighs. His laboratory tests on admission showed serum creatinine of 4.56 mg/dL, white blood count 3,800/μL, hemoglobin 7.3 g/dL, urinalysis with 51 white blood cells/μL and 960 red blood cells/μL, and urine protein-to-creatinine ratio 1.20. Serum ANCA testing was positive (>1:320), as well as serum anti-myeloperoxidase and anti-proteinase 3 antibodies. Urine toxicology screen was positive for cocaine and levamisole, with 62.8% of cocaine, 32.2% of levamisole, and 5% of an unidentified substance. Skin and renal biopsies were diagnostic for leukocytoclastic vasculitis and pauci-immune crescentic glomerulonephritis, respectively. The patient showed a good clinical response to cocaine abstinence, and use of corticosteroids and intravenous cyclophosphamide. Last serum creatinine was 1.97 mg/dL, white blood cell count 7,420/μL, and hemoglobin level 10.8 g/dL. In levamisole-induced systemic vasculitis, the early institution of cocaine abstinence, concomitant with the use of immunosuppressive drugs in severe cases, may prevent permanent end organ damage and associate with better clinical outcomes.

Relationship between serum AECA and clinical signatures of ANCA negative pauci-immune deposition type crescentic glomerulonephritis patients / 中国免疫学杂志

Objective:To investigate the expression of anti-endothelial cell antibodies(AECA) in patients serum with anti-neutrophil cytoplasmic antibody( ANCA) negative pauci-immune deposition type crescentic glomerulonephritis and its relationship with clinical signatures. Methods:We selected 94 pauci-immune deposition type crescentic glomerulonephritis patients from 2010 to 2015 treated in our hospital,45 of which with ANCA-negative( observation group) and 49 cases of ANCA-positive patients ( control group) , AECA levels of each groups serum were detected by Western blot test. Results: The average age of the observation group and Bermingham vasculitis activity score(BVAS) respectively (41. 08 +9. 43) years old and (15. 03 +3. 82),significantly lower than the control group (P<0. 05);the observation group had fever,joint pain accounted for 26. 67% and 13. 33%,significantly lower than the control group ( P<0. 05 );the observation group of nephrotic syndrome accounted for 48. 89%, higher than the control group ( P<0. 05);observation group positive rate of serum AECA was 46. 67%,significantly lower than the control group 81. 63% (P<0. 05);the observation group IgG-AECA identified 7 proteins,while the control group had identified 11 proteins,of which the observation group the positive rate of anti 90 kD antibody was 13. 33%( 6/45 ) , significantly lower than the control group 51. 02%( 25/49 ) ( P<0. 05 );observation group of anti 76 kD antibody positive patients had rash ratio of 100%, significantly higher than negative patients ( P<0. 05),anti 200 kD antibody positive the BVAS score of the patients was (18. 02 + 2. 51),which was significantly higher than that of the negative patients ( P < 0. 05 ) . Conclusion: The different level of AECA in ANCA negative pauci-immune crescentic glomerulonephritis patients may be associated with certain clinical manifestations;clinical manifestations differences between the ANCA negative and positive patients may be associated with different expression of the AECA related,the detail need a further study.

Membranous glomerulonephritis combined with anti-neutrophil cytoplasm antibody-associated crescentic glomerulonephritis / 第二军医大学学报

Objective To study the clinicopathological features of membranous nephropathy(MN) with ANCA-associated crescentic glomerulonephritis (ANCA-associated CGN). Methods 79 cases diagnosed as MN with ANCA associated CGN were selected from the whole English and Chinese literatures and a similar case was from our hospital. Total 80 casess were included in this study to summarize the clinicopathological features, treatment and prognosis. Results 44 male and 36 female patients were included. The average age was 56. 8±13. 1 years and the average disease onset period was 3. 2±3. 6 months. In 95% cases, MN and ANCA associated CGN occurred simultaneously. 93. 8% patients presented renal dysfunction onset of the disease, the common clinical manifestation were nephrotic syndrome with rapidly progressive glomerulonephritis. All patients were serum ANCA positive and 88. 2% cases were MPO-ANCA positive. The average 24h proteinuria was 5. 27±4. 3g and SCr was 420. 7±307μmol/L. Renal biopsy showed crescent formation and GBM thicken. Immunofluorescence showed IgG and C3 deposits were positive. Prednisone combined with CTX could improve the prognosis. 62. 7% cases reached relieve remission. Conclusions The coexistence of ANCA associated CGN and MN was rare. The pathogenesis of this condition is still unclear. Immunosuppressive therapy might improve the outcome.

A Case of Crescentic Glomerulonephritis and Marginal Zone B-cell Lymphoma / 대한내과학회지

Secondary rapidly progressive glomerulonephritis (RPGN) can be caused by many diseases and conditions, including vasculitis, systemic rheumatic diseases, infections, drugs and malignancies. Among the secondary RPGNs, malignancy-associated RPGN is extremely rare and causes renal function deterioration within several weeks to months. Thus, timely immunosuppressant therapy can improve renal outcome. Herein, we describe a case of RPGN detected simultaneously with marginal zone B-cell lymphoma. An 82-year-old male patient, who presented generalized edema and oliguria, was diagnosed with crescentic glomerulonephritis and marginal B-cell lymphoma. After the patient was given methylprednisolone pulse therapy, renal function was restored and hemodialysis was successfully discontinued without complications.

A Case of Crescentic Glomerulonephritis and Marginal Zone B-cell Lymphoma / 대한내과학회지

Secondary rapidly progressive glomerulonephritis (RPGN) can be caused by many diseases and conditions, including vasculitis, systemic rheumatic diseases, infections, drugs and malignancies. Among the secondary RPGNs, malignancy-associated RPGN is extremely rare and causes renal function deterioration within several weeks to months. Thus, timely immunosuppressant therapy can improve renal outcome. Herein, we describe a case of RPGN detected simultaneously with marginal zone B-cell lymphoma. An 82-year-old male patient, who presented generalized edema and oliguria, was diagnosed with crescentic glomerulonephritis and marginal B-cell lymphoma. After the patient was given methylprednisolone pulse therapy, renal function was restored and hemodialysis was successfully discontinued without complications.

Meningitis granulomatosa, glomerulonefritis rápidamente progresiva y vasculitis / Granulomatous meningitis, crescentic glomerulonephritis and vasculitis

El compromiso meníngeo es una manifestación infrecuente de la granulomatosis de Wegener. Puede manifestarse como cefalea con hiperproteinorraquia y engrosamiento de la duramadre con aspecto granulomatoso, que se observa en la resonancia magnética. Presentamos un varón de 57 años con granulomatosis de Wegener que debutó con compromiso de vías aéreas superiores, oídos, órbitas y meningitis granulomatosa asintomática y que posteriormente evolucionó con mononeuritis múltiple y glomerulonefritis crescéntica ANCA positiva. La presencia de ANCA y el compromiso sistémico (vías aéreas superiores, oído, órbitas, nervios periféricos, duramadre y glomerulonefritis rápidamente progresiva) permitieron en este caso llegar a un diagnóstico de certeza e iniciar el tratamiento inmunosupresor combinado (corticoides y ciclofosfamida). Evolucionó con remisión clínica y serológica (negativización de ANCA), pero persistiendo leve deterioro secuelar auditivo y de la función renal, sin recidiva de la enfermedad de base.

Meningeal involvement is an infrequent manifestation of Wegener's granulomatosis. Clinical manifestations can be headache with high protein level in the cerebrospinal fluid and an enhanced MRI signal of granulomatous thickening of the duramater in the brain. We report a 57 year-old male with Wegener granulomatosis with onset manifestations of asymptomatic granulomatous meningitis, upper respiratory tract, ears and orbits involvement. He progressively developed ANCA positive multiple mononeuritis and crescentic glomerulonephritis. The diagnostic confirmation of Wegener's granulomatosis based on a positive ANCA test and on the evidence of systemic disease (crescentic glomerulonephritis and involvement of the upper respiratory tract, ears, orbits, peripheral nerves and duramater) allowed a prompt initiation of aggressive immunosuppressive treatment with systemic cyclophosphamide and high - dosis corticosteroids. The patient entered into a sustained clinical remission with mild residual neurosensorial hearing loss and renal failure.

Crescentic glomerulonephritis: A clinical and histomorphological analysis of 46 cases.

Background: Crescentic glomerulonephritis (CrGN), defined as crescents involving more than 50% of the glomeruli, includes pauci-immune, immune complex-mediated and anti-glomerular basement membrane disease. Objectives: The present study was aimed at evaluating the various clinical, biochemical and histological parameters in CrGN with respect to these categories and clinical outcome. Materials and Methods: Renal biopsies diagnosed as CrGN between Jan 2008 and Feb 2010 were included. Clinical and laboratory parameters were retrieved along with the therapeutic approach and clinical outcome, wherever available. Renal biopsy slides were evaluated for various glomerular, tubulo-interstitial and arteriolar features. Appropriate statistical tests were applied for significance. Results: A total of 46 cases of CrGN were included; majority (71.7%) of cases were pauci-immune (PI) while 28.3% were immune complex-mediated (IC). Among clinical features, gender ratio was significantly different between PI and IC groups (P = 0.006). The various histological parameters, including proportion of cellular crescents, tuft necrosis and Bowman's capsule rupture, were similar in both the groups. Four unusual associations, including idiopathic membranoproliferative glomerulonephritis (MPGN), multibacillary leprosy, acute lymphoblastic leukemia and C1q nephropathy were detected. Adequate follow-up information was available in 21 (46%) of the patients. Of these, 11 (52.4%) were dialysis-dependent at the last follow-up. Adult patients required renal replacement therapy more frequently than pediatric cases (P = 0.05). Presence of arteriolar fibrinoid necrosis also showed association with poor clinical outcome (P = 0.05). Conclusions: Crescentic glomerulonephritis remains one of the main causes of acute renal failure with histological diagnosis. Immunohistologic examination is essential for accurate classification into one of the three categories. This condition should be considered in rare causal associations like leprosy or MPGN with renal failure, to allow for timely performed renal biopsy and appropriate aggressive therapy.

Podocyte Expression of Osteopontin and FSP-1/S100A4 in Human Crescentic Glomerulonephritis

BACKGROUND: Osteopontin (OPN) is a cytokine associated with a cell-matrix via integrins. Fibroblast specific protein-1 (FSP-1), known as S100A4, has been implicated in cell migration by non-muscle myosin. We investigated whether the role of OPN and FSP-1/S100A4 expression in their contribution to the podocyte phenotype change to form podocyte bridge and cellular crescent. METHODS: Glomerular expression of OPN and FSP-1/S100A4 in renal biopsies of 16 patients with crescentic glomerulonephritis (CrGN) and 13 normal renal biopsies were studied by immunohistochemistry. RESULTS: The expression of OPN and FSP-1/S100A4 was increased in the podocytes of glomeruli, with and without crescents, in patients with CrGN. Neither OPN nor FSP-1/S100A4 was expressed in glomeruli from the normal controls (p<0.01). A significant positive correlation was found between the expression of OPN in glomerular tufts and cellular crescents, and the expression of OPN and FSP-1/S100A4 in glomerular tufts (p<0.05). CONCLUSIONS: The results suggest that OPN plays a role in early podocyte attachment to Bowman's capsule, and FSP-1/S100A4 potentiate podocyte contribution to cellular crescent formation by inducing cellular migration and growth.

ANCA-related crescentic glomerulonephritis in a patient with systemic sclerosis / 대한내과학회지

The renal manifestations of systemic sclerosis include proteinuria, hypertension, azotemia, and renal crisis. Two types of scleroderma renal crisis (SRC) are recognized. Typical SRC is a syndrome consisting of acute-onset malignant hypertension accompanied by rapidly progressive renal failure, hypertensive retinopathy, and elevated plasma renin activity. The other type is normotensive renal failure, which is generally accompanied by antineutrophil cytoplasmic autoantibody (ANCA)-positive crescentic glomerulonephritis. A 51-year-old woman with scleroderma without marked dermatological change developed ANCA-related renal failure. She had neither malignant hypertension nor an elevated plasma rennin concentration. Renal biopsy showed crescentic glomerulonephritis (pauci-immune type), and the myeloperoxidase-specific ANCA (MPO-ANCA) titer was elevated at 1015 AAU. She was cured using steroid pulse therapy, combined with an angiotensin-converting-enzyme inhibitor and angiotensin-II receptor blocker

Granulomatose de Wegener: apresentação clínica e tratamento / Wegener´S Granulomatosis: clinical features and management

Granulomatose de Wegener (GW) é uma vasculite necrotizante granulomatosa sistêmica de pequenos vasos, que acomete principalmente o trato respiratório superior e rins. É enfermidade rara, tem altas taxas de morbidade e mortalidade, e pacientes com comprometimento renal têm pior evolução. Relatamos um caso desta relativamente rara enfermidade com o objetivo de revisar, na literatura, as opções terapêuticas, discutir o tratamento instituídoe suas complicações e enfatizar sua apresentação clínica. Paciente do sexo masculino, 69 anos, com quadro de rinossinusite crônica, epistaxe e ulceração de mucosa nasal acompanhadas de lesões purpúreas, hematúria, e insuficiência renal avançada de um mês de evolução apresentou ANCA-c positivo(até diluição de 1:640) e histologia renal com glomerulonefrite crescêntica esclerosante. Foi instituído tratamento agressivo com pulsoterapia(metilprednisolona), seguida de corticoterapia oral, porém, o paciente evoluiu para óbito com 15 dias do tratamento devido a choque séptico. Aapresentação clínica do paciente está de acordo com os relatos prévios da literatura, entretanto, o tratamento instituído foi diferente do recomendado: pulso de ciclofosfamida (CFA) e corticóide. Entretanto, questiona-se: a imunossupressão com CFA era a melhor opção terapêutica, diante da gravidade do processo infeccioso?

Wegener Granulomatosis (WG) is a rare disorder characterized by vasculitis of small arteries, arterioles and capillaries, necrotizing granulomatous lesionsof both upper and lower respiratory tract and glomerulonephritis. The entity carries high morbidity and mortality rates; renal involvement aggravates itsprognosis. A case of this relatively rare disease is reported aiming to review the literature regarding the therapeutic alternatives and discuss our treatmentchoice and the drug-associated complications emphasizing the clinical picture of the patient. A 69 year old man with chronic sinusitis, epistaxis, nasalulcerations, purpura, hematuria, and advanced renal insufficiency for one month, showed high c-ANCA level (positive until 1/640) and focal segmental glomerulonephritis with crescent formation and necrosis on renal histology. The patient was aggressively treated with methylprednisolone followed by oral corticosteroids. Despite 15 day therapy he died from septic shock. The patient’s clinical presentation agreed with the one found in previous studies, but the treatment chosen was different from the most frequent recommendation: cyclophosphamide and corticosteroids. Based on the course of the patient, a questions remains unanswered: would it be immunosuppressive therapy with cyclophosphamide the best choice in face of a severe infectious disease?

A Case of ANCA-positive Crescentic Glomerulonephritis after Propylthiouracil Treatment in Graves' Disease / 대한신장학회잡지

Propylthiouracil (PTU) therapy is commonly used in the treatment of Graves' disease, but often accompanies several side effects, including a mild increase in liver enzymes, leukopenia, skin rash, and arthralgia. ANCA-positive vasculitis and crescentic glomerulonephritis have been rarely reported in patients suffering from (with) Graves' disease and treated with PTU. We experienced a rare case of ANCA-positive crescentic glomerulonephritis presenting rapid progressive renal failure in a 30-year-old woman, suffering from Graves' disease and treated with PTU for 6 years. She was admitted with dyspnea for 1 day and fever, gross hematuria, arthralgia and sore throat for several days. Her chest X-ray revealed moderate cardiomegaly, bilateral pulmonary edema, and bilateral pleural effusion. She had a palpable, firm, diffuse goiter. Anti-myeloperoxidase (anti-MPO) antibody and anti-protease 3 (anti-PR3) antibody were both positive by ELISA. A percutaneous renal biopsy showed crescentic golmerulonephritis showing active cellular crescent formation with some inflammatory cell infiltration and mesangial cell proliferation. Cellular crescents were present in 2 of 3 glomeruli. Immunofluorescence stain showed weak granular deposits of IgG, IgM and C3 in the mesangium and capillary wall. ANCA-positive crescentic glomerulonephritis associated with PTU was diagnosed. The patient was started on intravenous methylprednisolone 250 mg 2 times daily, and then oral prednisolone 100 mg every other day and PTU was discontinued. Her renal function was recovered gradually and anti-MPO antibody and anti-PR3 antibody subsequently fell. Second biopsy, 7 months after first biopsy, showed focal global glomerulosclerosis. 16 months after first biopsy. she had stable renal function with mild renal insufficiency and euthyroid state.

A Case of ANCA-associated Pauci-immune Crescentic Glomerulonephritis in Juvenile Rheumatoid Arthritis

Juvenile rheumatoid arthritis(JRA) is the most common major connective tissue disease in children. Renal involvement in JRA is rare. Among the renal lesions that have been reported in JRA, amyloidosis and drug-induced nephropathy are the most common. Crescentic glomerulonephritis in JRA has rarely been reported. We report a case of ANCA-associated pauci-immune crescentic glomerulonephritis in JRA. The patient was a 15-year old boy with a 3-year history of JRA. He presented with gross hematuria, proteinuria, positive p-ANCA and elevation of BUN and creatinine. Pathologic findings revealed focal necrotizing and crescentic glomerulonephritis. There were no significant immunoglobulin or complement deposits. His renal function recovered after intravenous methylprednisolone pulse therapy and oral steroid use. In Korea, this is the first reported case of pauci-immune crescentic glomerulonephritis in JRA.

Histopathologic Studies on Crescentic Glomerulonephritis / 대한신장학회잡지

BACKGROUND: Crescentic glomerulonephritis is expressed pathologically by crescent formation in Bowman's capsule and clinically by rapidly progressive loss of renal function. The pathologic experience of crescentic glomerulonephritis in one institution was analyzed here. METHODS: We classified 25 cases of crescentic glomerulonephritis patients into 4 categories and reviewed the cases pathologically and clinically. RESULTS: We found no case with group I (anti- GBM disease), 8 cases in group II (immune complex glomerulonephritis) including 3 patients with IgA nephropathy, 2 patients with Henoch-Sch nlein purpura and 3 patients with APSGN, 12 cases in group III (ANCA-associated glomerulonephritis) including 7 patients with microscopic polyangitis, 4 patients with Wegener's granulmatosis and 1 patient with ANCA GN, and 5 cases in group IV (idiopathic crescentic glomerulonephritis). The mean ages of patients with group II, III, and IV were 32.0, 59.3 and 39.0 years old, respectively, and mean serum creatinine levels at the time of biopsy were measured as 9.1, 5.2, 8.8 mg/dL in each group. On light microscopic findings, the frequency of crescents in glomeruli was 64.4% in group II, 43.7% in group III, and 51.2% in group IV. The score of infiltration into tubules of inflammatory cells was 0.8 in group II, 0.4 in group III, and 0.6 in group IV and the score of fibrosis in interstitium was 1.0 in group II, 0.8 in group III and 1.2 in group IV. The score of atherosclerosis in arteries was 1.4, 0.9 and 1.6 in each group. CONCLUSION: We conclude that the precise diagnosis and classification of crescentic glomerulonephritis by an early renal biopsy and clinical assessments are important in the management of rapidly progressive (crescentic) glomerulonephritis. Since the number of the cases was not so enough, we could not analyze the statistical significance between morphologic differences of each group of crescentic glomerulonephritis, but if more cases were collected, acknowledgements of differences and prognostic factors in pathologic findings could be possible.

ANCA-neagtive pauci-immune crescentic glomerulonephritis / 中国实用内科杂志

Objectives To study the clinical and pathological features of patients with ANCA-negative pauci-immune crescentic glomerulonephritis.Methods ANCA was detected and the clinical and pathological features were analyzed in 33 patients with pauci-immune crescentic glomerulonephritis.Results Of the 33 patients with pauci-immune crescentic glomerulonephritis, 15(45%) were ANCA negative, which accounted for 15% of the patients with crescentic glomerulonephritis. Of the 15 patients with negative ANCA,9 had multi-system involvement and 6 were clinically limited to kidney only. Renal biopsies showed small vessel vasculitis in 2 patients. After intensive immunosuppressive therapy, one out of thirteen patients was cured,six achieved clinical remission,while the other 6 became dialysis dependent.Conclusions The clinical and pathological features of the patients with ANCA-negative pauci-immune crescentic glomerulonephritis are similar to those with ANCA-positive,while the ages of these patients are younger and the prognosis poorer.