Crescentic fibrillary glomerulonephritis associated with hepatitis C viral infection

Fibrillary glomerulonephritis (FGN) is a pathological diagnosis that is rarely associated with systemic disorders. In this case report, we describe a woman who presented with FGN of the crescentic type in association with hepatitis C viral infection. The existing literature on the association between these 2 disorders is reviewed, and postulated therapy is presented.     

Crescentic glomerulonephritis associated with thrombotic microangiopathy

A 71-year-old woman was examined at the department of urology in our hospital, with the chief complaint of macrohematuria. She was diagnosed as having bladder cancer and was hospitalized. After three courses of chemotherapy with cisplatin and epirubicin hydrochloride, total bladder resection and ileostomy were performed. Although the operation was curative, the hematuria persisted. Her renal function rapidly deteriorated. Hemolytic anemia and thrombocytopenia were found, and schistocytes were detected in a peripheral blood smear. Seizures occurred in the patient's clinical course. A diagnosis of thrombotic microangiopathy (TMA) was made. The patient died despite receiving treatment. An autopsy was performed, and the renal microscopic findings showed crescentic glomerulonephritis (Cres GN). We present a rare case of Cres GN associated with TMA. Received: December 13, 2000 / Accepted: October 31, 2001     

Crescentic glomerulonephritis associated with totally implantable central venous catheter-related Staphylococcus epidermidis infection

A 59-year-old woman was admitted to our hospital for treatment of acute renal insufficiency. She had been under home intravenous hyperalimentation therapy through a totally implantable central venous catheter for 2 years because of post-radiation enteritis. Clinical examination on admission revealed severe renal insufficiency complicated with hypocomplementemia, marked proteinuria and hematuria. Chest roentgenography demonstrated moderate pulmonary congestion. Hemodialysis was initiated and her pulmonary congestion improved. On the 14th and 21st hospital day, blood culture revealed Staphylococcus epidermidis colonization. Cefazolin was administered and C-reactive protein decreased, however, renal insufficiency and hypocomplementemia did not improve. To investigate the genesis of renal insufficiency, renal biopsy was performed. Light microscopic findings of the kidney revealed severe crescentic glomerulonephritis complicated with moderate tubulointerstitial damage. Immunofluorescence-microscopic findings of the kidney revealed positive IgG, IgM, C3 deposition along the capillary lumen. From these laboratory findings and the clinical course, we diagnosed her renal disease as crescentic glomerulonephritis induced by catheter-related bloodstream infection, and the central venous catheter was removed. After removal, urinary output and hypocomplementemia remarkably improved, however, unfortunately, her renal dysfunction did not improve and maintenance hemodialysis needed to be continued. Although her renal disease was not caused by ventriculo-atrial shunt but by central venous catheter-related bloodstream infection, we supposed that the pathogenesis was a closely similar entity to shunt nephritis.     

Crescentic glomerulonephritis associated with renal cell carcinoma.

Various glomerular lesions are described in association with malignancy. We report a rare case of crescentic glomerulonephritis occurring in association with renal cell carcinoma. A granular deposition of immune complexes and complement strongly suggests a tumor associated immune complex glomerulonephritis.     

Crescentic glomerulonephritis

Crescentic glomerulonephritis are characterised by a crescent shaped cellular proliferation that may lead to glomerular destruction. Over 50% of at least 10 analysed glomeruli should be affected. The search for immune deposits by immunofluorescence is an important diagnostic step. Patients present with rapidly progressive glomerulonephritis (RPGN): renal failure, proteinuria and haematuria. Extra-renal symptoms may help diagnosis. Diseases are classified in three groups according to immunofluorescence studies. Group I is characterised by linear deposits along the glomerular basement membrane (GBM) with anti-GBM auto-antibodies responsible for Goodpasture's disease. Group II put together various diseases with immune complex deposits. In group III, no significant immune deposits are found. Those "pauci-immune" glomerulonephritis are secondary to anti-neutrophil cytoplasmic antibodies (ANCA) positive systemic vasculitis, mainly Wegener's granulomatosis and microscopic polyangiitis. Primary glomerulonephritis may also be associated with crescent formation. Treatment is urgently required. Diagnosis is suspected in the context of extra-renal symptoms or immunological abnormalities, and confirmed by a kidney biopsy, that also helps to define prognosis. Apart from some group II glomerulonephritis, the induction treatment is often an association of steroids and cyclophosphamide, with plasma exchange in case of Goodpasture's disease. After remission, a maintenance treatment is required for ANCA-positive vasculitis to prevent relapses. The high rate of opportunistic infections and cancer give the rational for searching less aggressive therapeutic options.     

Crescentic glomerulonephritis associated with renal cell carcinoma after cancer immunotherapy

A 59 year-old woman showed rapidly progressive glomerulonephritis during immunotherapy for metastatic renal cell carcinoma. She received unilateral nephrectomy and cytotoxic T lymphocyte (CTL) therapy for the treatment of retroperitoneal lymph node metastasis of renal cell carcinoma. With CTL therapy, her retroperitoneal lymph node mass decreased in size. One year after the third round of CTL therapy, her serum creatinine was increased and massive proteinuria occurred. Her renal biopsy specimen revealed necrotizing and crescentic glomerulonephritis with immune complex deposition. Her retroperitoneal lymph node mass continued to decrease in size. Consequently, for the purpose of avoiding interfering with the CTL therapy, we performed double filtration plasmapheresis (DFPP) monotherapy for removal of immune complexes without using immunosuppressive drugs or prednisolone. After 24 sessions of DFPP, her serum IgG was reduced from 3,942 mg/dL to 2,400 mg/dL, and proteinuria (from 9.0 g/day to 0.9 g/day) and renal function (serum creatinine; from 5.6 mg/dL to 2.2 mg/dL) also improved. However, 3 months after the final DFPP, she expired due to perforation of the colon. The autopsy sample of the kidney showed that most of the glomeruli were obsolescent, but immunoglobulin depositions were reduced and necrotizing lesions were diminished. In the patients with RPGN associated with renal cell carcinoma, renal functional recovery has not been observed upon immunosuppressive treatment. Consequently, plasmapheresis is considered to be one of the effective and safe methods for patients with this association. We also discuss previous reports of RPGN associated with renal cell carcinoma, or RPGN after cancer immunotherapy.     

Crescentic lupus glomerulonephritis

Crescentic lupus glomerulonephritis (greater than or equal to 50% crescents) occurred in 16% of systemic lupus erythematosus (SLE) patients biopsied over a 32-month period. All had underlying WHO class IV lupus nephritis. These patients more frequently manifested with acute renal failure usually of the non-oliguric type, had heavier proteinuria and lower serum albumin, but were otherwise indistinguishable from non-crescentic WHO class IV lupus nephritis in their other renal and extrarenal manifestations or in their serological findings. Crescentic lupus glomerulonephritis may occur in patients at first presentation with SLE, or develop in patients after prolonged follow-up initially for lupus nephritis of WHO class IV or other classes. Combined methylprednisolone pulse therapy, immunosuppressives, antiplatelet agents with or without anticoagulant produced good initial responses. Prognosis was unfavorable for inadequately treated patients or for patients with persistent nephrotic syndrome and crescents.     

Crescentic glomerulonephritis in children

Data on patients with crescentic glomerulonephritis (>50% glomeruli with crescents), referred to the Hospital for Sick Children during the past 13 years, were reviewed. Thirty patients (13 male, 17 female) aged 3.7–15.7 years (mean 9.5) were evaluated. Initial clinical features included: oedema (24/30), hypertension (19/30), gross haematuria (15/30), oliguria (15/30) and a decreased glomerular filtration rate (GFR<30 ml/min per 1.73 m²) (22/30). Henoch-Schönlein purpura was present in 9 patients, microscopic polyarteritis in 3, polyarteritis nodosa in 1, Wegener's granulomatosis in 1, systemic lupus erythematosus in 1, post-streptococcal glomerulonephritis in 2, mesangiocapillary glomerulonephritis in 7, anti-glomerular basement membrane glomerulonephritis in 2, and 4 were idiopathic. In 10 patients 50%–79% of glomeruli were affected by crescentic changes (group 1) and in the remaining 20, 80% or more (group 2). The crescents were cellular, fibrocellular or fibrous, and the degree of sclerosis was assessed. Patients in both groups were treated with plasma exchange, corticosteroids, anticoagulants, cyclophosphamide and azathioprine in different combinations. On follow-up, 3 patients were dead, 1 was lost to follow-up, 12 were on dialysis/transplant programmes, 4 had a GFR of less than 30 and 10 a GFR of more than 30 ml/min per 1.73 m². In our experience, 50% progressed to end-stage renal failure. The interval between disease onset and start of treatment was a prognostic factor for outcome. Fibrous crescents were associated with a worse outcome than fibrocellular crescents (P<0.05). Outcome was not, however, related to the percentage of glomeruli affected (P>0.05). Although the effectiveness of the individual components of the treatment regimens used was difficult to assess, one-third of patients at the latest follow-up had a GFR of more than 30 ml/min per 1.73 m².     

Crescentic glomerulonephritis associated with infective endocarditis: renal recovery after immediate surgical intervention

A 57-year-old man was referred to our hospital because of acute cardiac failure and acute renal insufficiency. Laboratory data showed elevation of serum immune complex levels and antineutrophil cytoplasmic antibody (ANCA) titers, with cytoplasmic pattern (C-ANCA) on indirect immunofluorescence (IIF), and proteinase 3 specificity (PR3-ANCA) on solid-phase enzyme-linked immunosorbent assay (ELISA). Hemodialysis therapy was initiated, and this relieved the symptoms of cardiac failure. Echocardiography revealed three-grade aortic insufficiency and two large floating vegetations on the aortic valve. Considering the risk of embolism, we immediately performed aortic valve replacement and surgically removed the vegetations, subsequently giving antibiotic therapy. Six weeks after the operation, the patient's renal function showed marked improvement and the serological abnormalities, except for ANCA titers, had normalized, resulting in no need for dialysis. A renal biopsy specimen revealed diffuse proliferative glomerulonephritis (GN) with crescents including more than 50% of glomeruli, and granular deposits of IgM, C3, and C1q on immunofluorescence. ANCA titers remained high, but the patient's renal function has been stable, indicating a discrepancy between ANCA titers and his clinical course. In this patient, treatment by immediate surgical intervention, performed during the acute phase with active GN and highly reduced renal function, led to dramatic renal recovery. This case suggests that surgical removal of vegetations in the early stage of crescentic GN may result in a good renal outcome in patients with rapidly progressive GN associated with endocarditis. Although it has been suggested that ANCA may have some relationship to GN in endocarditis, in this patient, its pathogenetic significance is questionable. Received: March 10, 2000 / Accepted: May 23, 2000     

Crescentic glomerulonephritis associated with rifampicin in a patient co-infected with tuberculosis and human immunodeficiency virus

A 73-year-old man presented with acute renal failure after 3-month standard antituberculosis therapy with rifampicin for pulmonary tuberculosis. Previously undiagnosed human immunodeficiency virus (HIV) infection was found at the same time. A kidney biopsy showed crescentic glomerulonephritis and tubulointerstitial nephritis. Furthermore, endothelial tubuloreticular inclusions were seen on electron microscopy. Rifampicin was stopped because it was considered as the most possible cause responsible for the rapidly progressive glomerulonephritis (RPGN). Immunosuppressive therapy was not carried out because of the risk of aggravation of underlying infectious diseases including tuberculosis and HIV. Fortunately, renal function recovered 1 month after discontinuation of rifampicin. This case presented a clinical challenge in the differential diagnosis of the cause for RPGN in such a complex condition and the therapeutic dilemma regarding the use of immunosuppressive drugs.     

Crescentic and necrotizing glomerulonephritis with C3 deposition

Case 1: A 38-year-old female with a history of tonsillitis and sinusitis was admitted to our hospital because of lung edema. On admission, her serum creatinine increased to 5.57 mg/dL. Hypocomplementemia was not found. ASO and MPO-ANCA were 24 U/mL and 12 EU, respectively. She underwent emergency hemodialysis. Renal biopsy showed global sclerosis and fibrocellular crescentic formation, and marked angionecrosis was noted by light microscopy. Granular deposition of C3, IgG and IgM was seen along the capillary walls on immunofluorescence study. Glomerular intramembranous deposits were scattered on electron microscopy. She was treated with intravenous methylprednisolone pulse therapy, and following oral prednisolone administration was decreased gradually. No therapeutic effects were observed, and intermittent hemodialysis was continued and became maintenance hemodialysis therapy. Case 2: A 28-year-old female suffering from both pharyngitis and acute renal failure with systemic edema was admitted to our hospital. On admission, her serum creatinine and ASO were 4.31 mg/dL and 239 U/mL, respectively. MPO-ANCA was negative and CH50 was normal. Hemodialysis was initiated on the 6th hospital day. In renal biopsy, most glomeruli showed cellular crescentic formation, and marked angionecrosis was noted by light microscopy. Global sclerosis was not found in this case. Granular deposition of C3 resembling a starry sky pattern was seen along the capillary walls on immunofluorescence study. Electron microscopy revealed scattered glomerular subepithelial deposits. She was treated with intravenous methylprednisolone pulse therapy and then oral prednisolone administration. Because of the gradual improvement in renal function, hemodialysis was terminated after 53 sessions, however, the patient's chronic renal failure has persisted to date. In these two cases, the pathological findings supported the diagnosis of severe acute post-infectious glomerulonephritis with the characteristic crescentic and necrotizing glomerulonephritis with C3 deposition.     

Crescentic glomerulonephritis in a child with infective endocarditis

Renal manifestations associated with infective endocarditis (IE) may present with different clinical patterns, and the most common renal histopathological finding is diffuse proliferative and exudative type of glomerulonephritis, leading to hematuria and/or proteinuria. Renal failure due to crescentic glomerulonephritis (CGN) in children with IE is a very rare condition. We report here a 6-year-old boy, who had a history of cardiac surgery for pulmonary atresia and ventricular septal defect, presenting with the clinical findings of IE and hematuria associated with renal failure due to CGN. He was treated with a combination of intravenous (IV) methylprednisolone pulses and appropriate antibiotics, but also received one dose of IV cyclophosphamide. Complete serological, biochemical, and clinical improvement was achieved after 2 months of follow-up. Antibiotic therapy is the essential part of the treatment of IE-associated glomerulonephritis; however, this case also highlights the importance of aggressive immunosuppressive therapy to suppress the immunological process related with infection in this life-threatening condition leading to renal failure.     

Crescentic involved glomerulonephritis in infective endocarditis

The author has analysed the renal alterations in 8 patients, each of whom died of renal failure. Extracapillary crescents had developed in more than 50% of the glomeruli in all of them. Renal symptoms followed those of endocarditis after two weeks. Proteinuria, haematuria and impairment of renal functional parameters featured the clinical course of the disease. From the haemoculture, bacteria (in 6 cases) and fungus (in one case) were isolated. Haemoculture was negative in one case. The obtained serum complement values, intraglomerular immunoglobulin and/or complement depositions, electron-dense deposits along the glomerular basement membrane and within the mesangium all proved the presence of an immunocomplex mechanism. The rapid course leading to renal failure can be explained by the abundant crescent formation.     

Crescentic glomerulonephritis in a patient with heterozygous Fabry's disease

A 58-year-old woman who suffered from a heterozygous Fabry's disease and immune complex crescentic glomerulonephritis (GN) is reviewed. The diagnosis was made on the basis of the pathologic findings and peripheral leukocyte alpha-galactosidase activity. Light microscopy revealed a vacuolization of epithelial cells and electron microscopy showed myelin figures in the cytoplasm of visceral epithelial cells typical of Fabry's disease at the first renal biopsy. During the following 4 months she developed progressive renal failure and a second renal biopsy disclosed the formation of cellular crescents in 7 of 11 glomeruli observed. A rare case of combined Fabry's disease and crescentic glomerulonephritis is discussed.     

Crescentic glomerulonephritis in hyper IgD syndrome

 The hyperimmunoglobulinemia D syndrome (HIDS) is a well-defined entity resembling familial Mediterranean fever. HIDS is a systemic inflammatory disease associated with stimulation of T-cell-mediated immunity. These patients are at low risk for amyloidosis and are not known to develop nephropathy. We report a boy of Mediterranean ancestry who exhibited typical HIDS and end-stage renal failure. Kidney biopsy revealed pauci-immune crescentic glomerulonephritis (cGN). We hypothesized that the glomerular involvement was secondary to the cytokine network activation observed in HIDS. Thus, cGN should be considered as part of the syndrome, and kidney biopsy should be performed early in the course of the renal disease in patients with HIDS. Received: 2 February 1998 / Revised: 30 June 1998 / Accepted: 2 July 1998