Association of crescentic glomerulonephritis with membranous glomerulonephropathy: a report of three cases

Association of membranous glomerulonephropathy with crescentic glomerulonephritis is apparently extremely rare. We report three patients who had this combination. One patient had biopsy-proven membranous glomerulonephropathy thirteen months prior to sudden and rapid decline in renal function necessitating hemodialysis. A repeat renal biopsy showed a superimposed crescentic nephritis and antiglomerular (GBM) antibodies were demonstrable in the serum. A second patient had proteinuria of unknown duration and then developed renal failure. Renal biopsy showed crescentic nephritis with a fine granular glomerular immunofluorescence for IgG typical of membranous glomerulonephropathy. Anti-GBM antibodies were present in this patient's serum. The third patient presented with acute renal failure of moderate severity. A renal biopsy revealed crescentic nephritis, granular deposits of immunoglobulins, and epimembranous electron-dense deposits typical of membranous glomerulonephropathy. Although his creatinine clearance improved spontaneously, nephrotic syndrome has persisted and a repeat renal biopsy showed a progression of the membranous glomerulonephropathy with the disappearance of the crescentic lesions. The reason for this peculiar association of membranous glomerulonephropathy and crescentic glomerulonephritis is unclear. It is possible that deposition of immune-complexes along glomerular basement membrane may render the glomerulus more susceptible to additional injury from a variety of other agents. Alternatively, depostis formed in one disease could initiate release of normal or altered basement membrane material and lead to formation of anti-GBM antibodies and subsequent development.     

A pediatric case of myeloperoxidase-antineutrophil cytoplasmic (ANCA)-related crescentic glomerulonephritis associated with propylthiouracil treatment for Graves' disease

We treated a 13-year-old girl who developed myeloperoxidase-antineutrophil cytoplasmic antibody (MPO-ANCA)-related crescentic glomerulonephritis (GN) during propylthiouracil (PTU) treatment for Graves' disease. MPO-ANCA-related crescentic GN during PTU therapy has been described previously in only one recent report of 2 children. We report this case here and describe 15 (13 adult cases) more patients with MPO-ANCA-related GN associated with PTU found in a literature review. The mean age at onset was 41.3 years, and the length of PTU administration ranged from 2 weeks to 6 years (mean 3.5 years). Clinical signs and symptoms were hematuria (100%), proteinuria (100%), arthralgia (7 of 16 cases; 43.8%), fever (4 cases; 20.0%), purpura (2 cases; 12.5%), skin ulcer (1 case; 6.3%) and dyspnea (1 case; 6.3%). These patients were treated with steroid (15 cases; 93.8%), cyclophosphamide (8 cases; 50.0%), steroid pulse therapy (4 cases; 25.0%), or plasma exchange (1 case; 6.3%), or were not treated (1 case; 6.3%). Most patients revealed crescentic GN (15 cases; 93.8%) on renal biopsy, while one exhibited mesangial proliferative GN (6.3%). For 2 of the 16 patients (12.5%) irreversible renal dysfunction persisted and hemodialysis was started. Patients with Graves' disease treated with PTU should be observed carefully by urinalysis and monitoring of the serum creatinine level.     

Plasma exchanges in the treatment of rapidly progressive glomerulonephritis associated with chronic dental infection

A patient is described in whom rapidly progressive, crescentic (in 80% of the glomeruli) glomerulonephritis was associated with chronic dental infection. Eradication of the infection as the sole form of therapy failed to arrest the rapidly advancing renal failure. Institution of plasma exchanges and immunosuppression was accompanied by an abrupt reversal of the renal function and a remission, which until now has lasted for two years.     

The amyloid beta protein induces oxidative damage of mitochondrial DNA

A 55-year-old man was admitted to our hospital with of hemoptysis, progression of anemia and renal failure in February, 1996. Idiopathic interstitial pneumonia had been diagnosed and he had been followed at a regional hospital since 1988. On the third day after admission, he suffered from sudden and massive hemoptysis. Goodpasture's syndrome was diagnosed because anti-GBM antibody was detected in serum. A high titer of MPO-ANCA was also recognized simultaneously. Steroid pulse therapy, immunosuppressive therapy, and plasmapheresis were begun, but he died on the 28th hospital day because of severe hypoxemia and multi-organ failure. Histological examination after autopsy revealed crescentic glomerulonephritis with linear deposition of IgG in the glomerular capillary wall, and interstitial pneumonia accompanied by massive alveolar hemorrhage. It was suggested that in this patient, not only anti-GBM antibody but also circulating MPO-ANCA might have participated in the progression of the crescentic glomerulonephritis and alveolar hemorrhage observed in Goodpasture's syndrome.     

Goodpasture syndrome involving overlap with Wegener's granulomatosis and anti-glomerular basement membrane disease

A 68-year-old Caucasian woman presented to the hospital with nodular pulmonary infiltrates and acute renal failure. Wegener's granulomatosis was initially considered to be most likely because of the presence of increased serum levels of c-anti-neutrophil cytoplasmic antibodies (c-ANCA). A consultation through the Internet after a renal biopsy demonstrated crescentic, necrotizing glomerulonephritis and linear deposits of immunoglobulin G (IgG) and complement C3, typical of anti-glomerular basement membrane (GBM) disease. Hemodialysis was instituted; however, the patient suddenly developed a massive cerebral hemorrhage and died before full therapy could take effect. Postmortem analysis of the patient's sera revealed high titers of IgG against the alpha 3 NC1 domain of type IV collagen. Serologic evidence of both p-ANCA and anti-GBM antibodies are becoming more frequently recognized in the setting of rapidly progressive glomerulonephritis. The patient reported here had the unusual combination of c-ANCA antibodies with anti-GBM disease, and this association raises complex questions regarding the pathogenesis of this type of renal injury.     

Necrotizing crescentic glomerulonephritis without significant immune deposits: a clinical and serological study

To determine the spectrum of systemic diseases associated with pauci-immune necrotizing crescentic glomerulonephritis, we have analysed extra-renal manifestations, occurrence of extra-glomerular vasculitis and incidence and specificity of antinuclear cytoplasmic antibodies (ANCA) in 40 patients selected only on renal histological criteria. Extra-renal symptoms were unexpectedly observed in all patients but one, and were suggestive of vasculitis in 24. Extra-glomerular vasculitis was seen in 18 kidney biopsies and four biopsies from other organs. Among the 33 patients with suspected or established vasculitis, 13 had presumed or biopsy-proven Wegener's granulomatosis, three had a macroscopic form of polyarteritis nodosa and 17 could not be adequately classified. An additional patient had clinical signs of Wegener's granulomatosis without clinical and histological evidence of vasculitis. ANCAs were detected in 28 of 33 and 25 of 34 sera tested by immunofluorescence and enzyme-linked immunoassay, respectively: 19 contained anti-myeloperoxidase antibodies and six had anti-proteinase 3 activity. Anti-myeloperoxidase and anti-proteinase 3 antibodies were present in all clinical subgroups but with various frequencies: anti-myeloperoxidase antibodies were more common (six of 12) than anti-proteinase 3 (four of 12) in patients with suspected or histologically proven Wegener's granulomatosis. Anti-proteinase 3 antibodies were 3- to 4-fold more common in patients with Wegener's granulomatosis than in those with systemic vasculitis of other causes (one of 12) or necrotizing crescentic glomerulonephritis without evidence of extra-renal vasculitis (one of 10). These results strongly suggest that pauci-immune necrotizing crescentic glomerulonephritis belongs to the broad spectrum of necrotizing vasculitides affecting glomerular capillaries. This study shows substantial improvement in renal prognosis and life expectancy with aggressive immunosuppressive therapy despite the older age of the patients, dissemination of the vasculitic process and often delayed diagnosis.     

Myocardial DNA strand breaks are detected in biopsy tissues from patients with dilated cardiomyopathy

A 68-year-old woman was admitted to Kinki University Hospital because of progressive renal failure. She had been well until two months before admission. Laboratory data were as follows: serum creatinine 4.1 mg/dl, BUN 69 mg/dl, MPO-ANCA 33 EU, anti-glomerular basement membrane antibodies (AGBMA) 118 U. Histological findings showed cellular and fibrocellular crescents in many glomeruli. Therefore, we diagnosed rapidly progressive glomerulonephritis (RPGN) due to MPO-ANCA and anti-GBM associated renal disease. The patient was started on prednisolone and double filtration plasmapheresis (DFPP) therapy. Subsequently, the values of MPO-ANCA and AGBMA decreased. However, the patient's condition suddenly worsened and she died of interstitial pneumonia. Autopsy examination revealed crescentic glomerulonephritis and alveolar hemorrhage with linear deposition of IgG along the glomerular and alveolar capillary walls by immunofluorescence studies. We considered this to be a rare case of Goodpasture's syndrome associated with not only anti-GBM antibodies, but also MPO-ANCA.     

Therapy of rapidly progressive glomerulonephritis with immunosuppressive agents

Rapidly progressive glomerulonephritis is a kidney disease leading to sudden and definitive damages of the renal parenchyma and progressive impairment of its function until the complete failure. Histological findings of the changes are characterized with dominant glomerular lesions with crescentic formations. Early and intensive immunosuppressive therapy with pulse doses of steroids (Solumedrol 1.5 to 2.5 g), followed by Prednisolone 1 mg/kg every other day and cytostatic drugs (cyclophosphamide 1-2 mg-kg/every other day) discontinues the processes of specific and non-specific inflammation in the kidney and could enable regeneration of the kidney tissues with favorable outcome of the disease. Immunosuppressive therapy should be gradually lowered after two months, and applied for at least three to six months.     

Involvement of neutrophil elastase in crescentic glomerulonephritis

To elucidate the role of neutrophils in the tissue damage of crescentic glomerulonephritis (GN), we examined neutrophils infiltrated in renal tissues and the localization of neutrophil elastase (NE), as a neutrophil-derived tissue destructive mediator, using an immunohistochemical technique with antibodies specific for neutrophils and neutrophil elastase; the enzyme histochemical technique (chloroesterase staining) also was used to detect neutrophils. In normal controls, neutrophil infiltration was scarce, and NE was localized in neutrophil cytoplasm. Neutrophils were abundant in crescentic GN and infiltrated in the glomerulus and interstitium; the infiltrating neutrophils were often aggregated. NE was localized in the cytoplasm of neutrophils and also appeared extracellularly (in granular or diffuse patterns) in glomerular necrotizing lesions, crescents, ruptured portions of Bowman's capsules, and in periglomerular and perivascular sites of the interstitium. Moreover, urinary concentration of NE measured by enzyme-linked immunosorbent assay (ELISA) in crescentic GN patients was significantly higher than in normals (93.6 +/- 13.3 v 1.4 +/- 0.5 microg/g x Cr, respectively; P < .001). These data suggest that NE plays a significant role in renal tissue damage, especially in the formation of glomerular necrotizing and crescentic lesions and in periglomerular interstitial lesions of crescentic GN.     

Transfection of the gene for B7-1 but not B7-2 can induce immunity to murine malignant mesothelioma

A 56-year-old female with rheumatoid arthritis was admitted because of bilateral hip pain. In a few months of her hospitalization, a relatively abrupt renal dysfunction was emerged besides complement breakdown, and renal biopsy revealed crescentic glomerulonephritis. Immunofluorescence study showed peripheral granular deposits of IgG, IgM, and C3 in the glomeruli. Cresents were predominantly composed of macrophages and glomerular epithelial cells. Amyloid nephropathy, renal vasuculitis, and association of other collagen vascular diseases were negligible for the causative factor. It was suggested that immune complexes were formed in the glomeruli, in which both humoral and cellular immune responses were to be induced, that brought cescents formation in the lesions. Crescentic glomerulonephritis in patients with rheumatoid arthritis is rare and a possible pathogenetic mechanisms involved in the development of renal dysfunction are discussed with the special reference to immune complex-induced inflammation.     

Histopathologic comparison of conventional radial keratotomy and minimally invasive radial keratotomy in rabbits

CLINICAL OBSERVATIONS: Three patients with previous pulmonary infections were recently admitted with rapidly progressive renal failure. Renal biopsy showed crescentic glomerulonephritis with deposits of IgA, C3c and C3d. Serology disclosed P-ANCA with high-titer anti-myeloperoxidase antibodies. Two out of three patients became dialysis dependent despite immunosuppression with methylprednisolone and cyclophosphamide. Renal function improved in both patients after 2 weeks and 9 months, respectively, permitting termination of hemodialysis. All patients benefited from immunosuppressive treatment which is currently still being continued. CONCLUSION: The data suggest that early immunosuppression is beneficial in patients presenting with crescentic rapidly progressive IgA GN and anti-myeloperoxidase antibodies, which may represent a novel subset of crescentic IgA GN associated with high-titer anti-myeloperoxidase antibodies constituting an overlap group between microscopic polyangiitis and IgA GN.     

Unsatisfactory results of a first-generation modular femoral stem implanted without cement. A 4- to 9-year follow-up study

In a attempt to clarify the effects of methylprednisolone pulse therapy on the insidious (subacute) type of crescentic glomerulonephritis with slow, but steady deterioration of renal function and poor response to treatment, we analyzed the clinical course of 24 patients (male:female = 15:9) with a mean age of 48.5 years. They fulfilled the following criteria: 1) crescents were observed in more than 50% of the glomeruli, 2) the increment of serum creatinine (Cr) could be determined sequentially on three or more occasions before treatment, and reciprocals of serum Cr declined with slopes of less than 1.0 x 10(-2) dl/mg/day, 3) corticosteroids and/or immunosuppressants were administered. The patients were divided into two groups: pulse therapy group (P) (15 patients), to which methylprednisolone 500 or 1,000 mg a day was administered intravenously for three consecutive days, and a conventional therapy group (C) (9 patients). There were no differences between groups P and C in clinical parameters, including sex, age, underlying diseases, urinary protein, blood pressure, serum Cr and slope of 1/Cr before treatment, and pathological findings, including percentages of glomeruli with crescents and degree of interstitial lesions. However, improvement of serum Cr, which was defined as a decline to the normal range or less than half of the pretreatment level, was observed in 9 (60%) in group P vs. only 1 (11%) in group C (p < 0.05). Re-biopsies were performed after treatment in 6 patients of group P with an improvement of serum Cr, and showed a decrease in the rate of crescent formation and almost complete loss of cellular crescents. At 1, 2 and 3 years follow-up, the renal survival rates were 86, 70 and 53%, respectively, in group P vs. 67, 14 and 14% respectively, in group C (p < 0.05). No serious side effects were observed in group P. These results suggest that methylprednisolone pulse therapy may be very effective for the insidious type of crescentic glomerulonephritis.     

A case of ANCA-associated rapidly progressive glomerulonephritis with oral aphtha and erythema nodosum

We reported a case of a 22-year old female with a microscopic form of polyarteritis nodosa (PN) who initially manifested Beh?et's disease-like symptoms, such as fever, arthralgia, oral aphtha and erythema nodosum, and rapidly progressive glomerulonephritis (RPGN). On admission, her urinalysis showed active nephritic syndrome and her renal function rapidly deteriorated; serum creatinine levels elevated from 1.2 to 3.9 mg/dl within 2 weeks. Skin biopsy specimens from erythema showed panniculitis. Accordingly, she was treated with daily 30 mg of oral prednisolone and three-day intravenous pulse therapy of 1000 mg of methylprednisolone twice. After treatment, skin eruption and oral aphtha disappeared, and the serum creatinine level improved to 1.2 mg/dl. Percutaneous renal biopsy performed on the 28th day showed focal necrotizing glomerulonephritis and hyalinosis of small arteries. Immunofluorescence studies showed only trace stainings for IgG, IgA and beta lc. Electron microscopic findings revealed fusion of the foot process and swelling of endothelial cells, but no dense deposits. Anti-neutrophil cytoplasmic antibody (ANCA) was positive for IgG class with a 40-fold titer by indirect immunofluorescence test and showed a cytoplasmic pattern combined with high urinary IL-8 level (280.1 pg/ml). We diagnosed this case as a microscopic form of PN. ANCA titer and urinary IL-8 correlated positively with the disease activity, and were finally below 8-fold and 58.6 pg/ml, respectively after resolution of RPGN for 42 months. In this case, ANCA was useful not only for differential diagnosis of the patients with systemic vasculitis and crescentic glomerulonephritis, but also for evaluation of the disease activity.     

Hypocomplementemic membranoproliferative glomerulonephritis in a child with ulcerative colitis (author's transl)

A 5 1/2 year old girl with hypocomplementemic membranoproliferative glomerulonephritis suffered from severe nephrotic syndrome. Despite intensive treatment with corticosteroids and immunosuppressive drugs the clinical state deteriorated. Three years after clinical onset of the disease the girl entered our regular hemodialysis program because of terminal renal insufficiency. After two weeks of intermittent hemodialysis she presented intestinal bleeding, which could not be stopped. One week later complete ileus developed and the child died. Before the onset of melaena no occult blood or mucus could be detected in the faeces. The autopsy revealed a severe ulcerative colitis with pseudopolyposis of the whole colon. In serum specimens still available colonic antigen could be detected by means of immunodiffusion using a rabbit antiserum against fetal colonic extract. Immunofluorescence studies showed granular deposits of immunoglobulins and complement along the glomerular capillary walls suggesting an immunogenesis of the glomerulonephritis by circulating immune complexes. The possibility of an interrelationship in the pathogenesis of both diseases is discussed. It should not be excluded that immune complexes formed in excess of colonic antigen have caused or perpetuated chronic glomerulonephritis.     

Sclerosing tufted angioma. Apropos of 4 cases involving lower limbs

Autoantibodies to MPO are associated with various forms of systemic vasculitis, including the renal limited form described as idiopathic crescentic glomerulonephritis. In vitro the antibodies are able to further activate primed neutrophils to the production of reactive oxygen species and the release of lysosomal enzymes. In vivo experimental studies in which an autoimmune response to MPO was induced in rats have demonstrated the in vivo potential of the autoantibodies to aggravate subclinical inflammatory lesions. In the right context, vasculitis and glomerulonephritis can ensue. Further studies are being directed to the precise characterization of autoimmune responses in order to obtain clues for the etiopathogenesis of the associated diseases.     

Synthesis and binding-analysis of 5E-[19-(2-bromoacetoxy)methyl]25-hydroxyvitamin D3 and 5E-25-hydroxyvitamin D3-19-methyl[(4-azido-2-nitro)phenyl]glycinate: novel C19-modified affinity and photoaffinity analogs of 25-hydroxyvitamin D3

In addition to fibrillary glomerulonephritis (FGN), Congo red negative mesangial fibrils may commonly be seen in sclerosing glomerular diseases. Rarely, these nonspecific mesangial fibrils (NMF) may mimic fibrils in FGN and cause a differential diagnostic pitfall. Following an interesting case of sclerosing crescentic glomerulonephritis with abundant NMF (which is presented in some detail) we have reviewed our renal biopsy files for a period of two and a half years and found additional 16 cases where the presence of NMF warranted studies to exclude FGN and other diseases with fibrillary deposits. The immunofluorescence pattern characteristically seen in FGN was not present in any of these cases. Our data confirm that mesangial fibrillary material seen ultrastructurally in sclerosing glomeruli with negative or nonspecific immunofluorescence (IF) represents a nonspecific reaction of the mesangial matrix to chronic glomerular injury. The presence of NMF should not lead to the erroneous diagnosis of FGN. Negative or nonspecific immunofluoresence, localization to the mesangium in a usually segmental fashion, and the more bundle-like than random arrangement of fibrils are helpful diagnostic hints in differentiating NMF from fibrils in FGN.     

The simulation and calculation of the fatigue of the lower complete denture in function by means of the finite element analysis

A 54-year-old man, who had been diagnosed as having MPO-ANCA-related glomerulonephritis in 1993, developed severe anemia and was admitted to our hospital on October, 1997. Endoscopic examination of the upper gastrointestinal tract revealed melena due to duodenal ulcer (Dieulafoy type). The level of ANCA titer was elevated considerably (640 EU), but otherwise there was no evidence of systemic vasculitis activation such as fever, arthralgia, skin eruption, renal insufficiency, and rise in C reactive protein. A renal biopsy showed neither crescentic formation nor necrosis of glomerulus. Subsequently he developed hematochezia and renal dysfunction rapidly progressed thereafter. Angiographical examination of superior mesenteric artery revealed that the bleeding was responsible for the lesion of the small intestine, probably the ileum. In spite of TAE (transarterial embolization) he had recurrence of severe hematochezia three days later. Partial ileotomy was performed and progression of the anemia was stopped. Multiple ulcer was found in the resected ileum. The small arteries in the submucosa at the ulceration showed fibrinoid necrosis of the vessel walls. These findings suggested that ANCA-related vasculitis had relapsed. The patient received methylprednisolone pulse therapy, followed by oral administration of prednisolone after the operation. Both serum levels of creatinine and MPO-ANCA gradually decreased after the initiation of treatment. However, 24 days later, he suddenly manifested severe abdominal pain, and was diagnosed as having perforation of the stomach or duodenum. Due to supportive therapy and reduction of the steroid dose, peritonitis subsided, but symptoms caused by systemic vasculitis developed. Later raised the dose of steroid suppressed the activity of systemic vasculitis. In this case, elevation of the ANCA titer demonstrated recurrence of MPO-ANCA-related vasculitis as gastrointestinal bleeding.     

Immunohistochemical and electrophysiological evidence for omega-conotoxin-sensitive calcium channels in unmyelinated C-fibres of biopsied human sural nerve

Two cases of glomerulonephritis associated with colonization of cerebrospinal fluid shunts inserted for the treatment of hydrocephalus (shunt nephritis) are described and additional 113 cases reported in world literature, are reviewed. Both of our patients were affected by two episodes of shunt nephritis. Complete clinical remission of renal disease followed antibiotic treatment in one patient, and shunt replacement combined with antibiotic therapy in the other. In the 115 cases of shunt nephritis reported to date, the causative organisms, clinical features, pathogenesis, renal histology, treatment, and outcome are discussed in detail. The importance of regular observation for early recognition of this reversible form of glomerulonephritis, is emphasized.     

Expression of types I, II, and III TGF-beta receptors in human glomerulonephritis

Protein and mRNA expression of transforming growth factor-beta (TGF-beta) receptor type I (TbetaRI), type II (TbetaRII), and type III (TbetaRIII) were studied in serial sections of kidney samples obtained from patients with glomerulonephritis. In minimal change disease, weak expression of TbetaRI and TbetaRII was observed mainly in glomerular endothelial cells, peritubular capillaries, and interstitial arteriolar endothelial cells, whereas TbetaRIII expression was found mainly in the interstitium. Expression of all three TGF-beta receptors (TbetaR) was increased remarkably in glomerular and Bowman's capsular cells comprising the tuft adhesions to Bowman's capsules in glomerulonephritis with increased matrix accumulation, including IgA nephropathy, lupus nephritis, focal and segmental glomerulosclerosis, myeloperoxidase-antineutrophil cytoplasmic antibody-associated crescentic glomerulonephritis, and membranoproliferative glomerulonephritis. Increased expression of the three TbetaR was also seen in glomerular epithelial cells in the vicinity of glomerulosclerotic lesions, in crescent cells, and in some tubules and infiltrative mononuclear cells found in the periglomerular and tubulointerstitial lesions with increased matrix deposition. In contrast, no remarkable TbetaRII expression was noted in mesangial proliferative lesions in IgA nephropathy, lupus nephritis, and membranoproliferative glomerulonephritis. These data suggest that distinctive modulation of TbetaR expression may be involved in the development of adhesive, sclerotic, and proliferative renal lesions in human glomerulonephritis.