Fibrillary glomerulonephritis presenting as rapidly progressive glomerulonephritis

Fibrillary glomerulonephritis (GN) is an uncommon cause of rapidly progressive kidney failure. We report a case of rapidly progressive kidney failure with kidney biopsy showing crescentic GN on light microscopy and immunofluorescence showing linear/globular glomerular basement membrane (GBM) staining for immunoglobulin G and C3, consistent with anti-GBM disease. However, electron microscopy showed fibrillary deposits in the GBM, suggesting a diagnosis of fibrillary GN. As exemplified by this case, it is important to consider fibrillary GN in the differential diagnosis of crescentic GN with linear immunoglobulin G deposits within the GBM. Electron microscopy is crucial to make this diagnosis.     

D-penicillamine therapy associated with rapidly progressive glomerulonephritis.

A 55-year-old woman with advanced rheumatoid arthritis developed rapidly progressive glomerulonephritis with epithelial crescents and pulmonary hemorrhage following treatment with D-penicillamine. D-penicillamine was then withdrawn and a pulse therapy with methylprednisolone halted the progression of kidney and lung damage. We review the other cases previously reported and discuss pathogenesis and treatment of this rare condition.     

Steroid pulse therapy in rapidly progressive glomerulonephritis]

In an attempt to clarify the indication and efficacy of the methylprednisolone pulse therapy (1000 mg x 3 times) for rapidly progressive glomerulonephritis (RPGN), 3 patients with the disease were carefully followed and the clinical course during and after the treatment were precisely analysed. According to the declination rate of reciprocals of serum creatinine (1/Cr), one patient were divided into the acute type (-1.00 x 10(-2) dl/mg/day or less) and the others into the subacute type (more than -1.00 x 10(-2) dl/mg/day). In the patient of acute type, renal biopsy revealed cellular crescent formation in 93.8% of glomeruli observed. One course of the pulse therapy resulted in a decrease in Cr from 3.0 mg/dl to 1.3 mg/dl and transformation of cellular crescents to fibrocellular or fibrous crescents. In the other two patients of subacute type, crescents were observed in 72.7% and 72.0% of glomeruli observed, and 87.5% and 38.9% of them were composed of cellular crescents respectively. Initial courses of the pulse therapy resulted in decreases of Cr from 3.5 mg/dl to 2.4 mg/dl and from 3.0 mg/dl to 1.4 mg/dl respectively. Additional courses, given because of insufficient reduction of Cr in the former, induced a further lowering to 1.3 mg/dl, and because of re-elevation of Cr to 2.2 mg/dl and remaining of cellular crescents in 20% in the latter, induced a decrease of Cr to 1.5 mg/dl and disappearance of cellular crescents.(ABSTRACT TRUNCATED AT 250 WORDS)     

Post-reperfusion rapidly progressive glomerulonephritis in post-transplant IgA nephropathy

Rapidly progressive glomerulonephritis (RPGN) is a rare occurrence in IgA nephropathy (IgAN) in renal transplant patients on immunosuppressive therapy. RPGN post ischemia-reperfusion has not been previously reported. We report a 62 year old male patient on azathioprine therapy, 9 years after left cadaveric renal transplantation due to end stage renal disease of unknown etiology, who presented with progressive deterioration in renal function and hematuria. Renal biopsy was consistent with IgAN. Duplex and CT scan demonstrated a decreased renal graft perfusion, due to severe atherosclerosis and stenosis of iliac arteries. The patient underwent left axilo-femoral bypass graft surgery with improvement in kidney graft perfusion and function. However, few weeks later, patient presented with pulmonary edema and advanced renal failure and he was initiated on hemodialysis. Repeated renal biopsy demonstrated crescentic GN. To the best of our knowledge, this is the first report of RPGN following reversal of ischemia and reperfusion. There was no evidence for atherembolic disease which is not uncommon after vascular surgery and it has been reported to be rarely associated to crescentic GN. Theoretical explanations for exacerbation of IgAN to crescentic GN, following successful reperfusion, could be enhancement of capillary damage, inflammation and oxidative stress. Putative mechanisms for these phenomena may be interaction of reperfusion-induced hyperfiltration, high intraglomerular capillary pressure, oxidative stress, increased polymorphonucler cells infiltration and inflammation; the presence of IgA immune deposits and azathioprine metabolites, both can also be associated to enhancement of oxidative stress.     

A clinical and immunopathologic dissection of rapidly progressive glomerulonephritis.

This contribution seeks to illustrate the immunopathogenetic complexities of the syndrome of rapidly progressive glomerulonephritis. As with most of the clinical syndromes of glomerular disease, rapidly progressive glomerulonephritis may be dissected into a number of categories based upon combinations of clinical, morphologic and immunologic observations. It has been demonstrated that such observations have an important bearing on the natural history, prognosis and treatment of this syndrome. Much remains to be learned, particularly with respect to etiological factors, the genesis of extracapillary proliferation and the means of modifying or preventing these diseases.     

Long-term treatment and prognosis of rapidly progressive glomerulonephritis

Short-term prognosis of rapidly progressive glomerulonephritis (RPGN) has improved since immunosuppressive therapy was introduced. The long-term course of the disease was investigated in 46 consecutive and unselected patients over a period of 15 years (1970-1986) with a mean observation time of five years (+/- 45 months). Most of the 46 patients had idiopathic RPGN (61%). Initially, hemodialysis needed 25 of the 46 patients (54%). Immunosuppressive therapy (plasma exchange, methylprednisolone pulses, steroids, cyclophosphamide, azathioprine) was administered in 36 of the 46 patients (78%). A remission was achieved in only 19 of the 36 patients who received immunosuppression (53%) and no spontaneous improvement was seen. Factors indicating poor prognosis were initial high serum creatinine, high percentage of crescents in glomeruli, glomerular sclerosis, and immunohistologic staining of the IgG at the tubuli. In 11 patients with remission, immunosuppression was discontinued and 6 had a relapse. Long-term immunosuppression was given to 8 patients with remission. Their renal function was not normal (creatinine 240 +/- 77 mumol/l), but none had a relapse (p = 0.01). It is concluded that the treatment of RPGN requires long-term attendance and repeated immunosuppression comparable to a systemic immune disease.     

Methylprednisolone therapy for acute crescentic rapidly progressive glomerulonephritis

In the last 10 years we have evaluated 63 patients with acute crescentic rapidly progressive glomerulonephritis (AC-RPGN), 46 of whom received pulse methylprednisolone (PM). The groups consisted of patients with no immune deposits, immune complexes, vasculitis, and antiglomerular basement membrane (anti-GBM) disease. Seventy-nine percent of non-anti-GBM patients improved versus 25% of unpulsed, p less than 0.005; 70% stopped dialysis (D) versus none of unpulsed, p less than 0.009; creatinine decreased from 8.6 before to 2.7 mg/dl after PM, p less than 0.05. Percent crescents and oligoanuria did not influence PM results, but did with conventional therapy (prednisone, cytotoxics, anticoagulants, supportive treatment). Seventeen percent of anti-GBM patients improved, none stopped D. In anti-GBM patients, serum creatinine less than 6 mg/dl was associated with a favorable response to PM, p = 0.045. Twenty-one percent of responding patients lost function at 19.8 months. The long-term response for non-anti-GBM patients was 62%. Patients with low chronicity on biopsy had shorter duration of disease (p = 0.006) and 92% initial, 85% long-term improvement; those with high chronicity had an immediate 71%, and 36% long-term response rate, p less than 0.02. Thus, PM is effective and appears superior to conventional therapy in treatment of non-anti-GBM AC-RPGN.     

Pauci-immune rapidly progressive glomerulonephritis after nephrectomy in a renal donor

Idiopathic rapidly progressive glomerulonephritis (RPGN) is a clinicopathologic syndrome in which glomerular damage is accompanied by a rapid and progressive decline in renal function, usually resulting in irreversible renal failure in weeks or months. We report the occurrence of pauci-immune RPGN, more specifically microscopic polyarteritis nodosa (PAN), in a 60-year-old woman 15 months after donor nephrectomy, and 3 months after documentation of intact, residual renal function. The transplanted kidney continues to function well in the recipient, 6 years posttransplantation, and 4.5 years beyond destruction of the donor's contralateral kidney by RPGN. The donor underwent cadaveric renal transplantation after 2 years on dialysis, and at the 3-year mark has intact renal function. These intriguing observations strongly argue that host environmental factors, rather than intrarenal factors, play a major causative role in the pathogenesis of RPGN.     

Autoantibodies to GBM and neutrophil cytoplasm in rapidly progressive glomerulonephritis

The incidence of autoantibodies to glomerular basement membrane (AGBMA) and neutrophil cytoplasmic antigens (ANCA) in the initial sera of 889 consecutive patients with a suspected diagnosis of rapidly progressive glomerulonephritis, was determined by prospective study. Forty-seven (5%) were positive for AGBMA alone, 246 (28%) were positive for ANCA alone, 576 (65%) had neither autoantibodies while 20 (2%) had both. Clinical and pathological data collected from patients with both autoantibodies suggested the coexistence of anti-glomerular basement membrane disease and systemic vasculitis. Together, assays for AGBMA and ANCA are important in the diagnosis and management of rapidly progressive glomerulonephritis and may help its further classification.     

T-cells and macrophages in rapidly progressive glomerulonephritis: clinicopathologic correlations

We phenotyped with monoclonal antibodies (MAb) the cellular infiltrates in kidneys of patients with rapidly progressive glomerulonephritis (RPGN) responsive (R) or nonresponsive (NR) to pulse methylprednisolone therapy (PM)-eight anti-GBM, six no immune deposits, three immune complex, two vasculitis, and one proliferative GN. There were glomerular, periglomerular, crescentic, and interstitial T and T-cell subsets. Few interstitial and no glomerular B and NK cells were observed. TH cells were much more common than TS. Phenotypes were quantitatively evaluated in 221 nephritic and 32 control glomeruli. T and/or TH cells were positively correlated with M phi, r = 0.30 to 0.74, P less than 0.05 to 0.0005. Although differences in phenotypes were observed, these differences were insufficient to distinguish between subtypes. Analysis of R and NR revealed no relationship to percent crescents, entry serum creatinine, oliguria, or need for dialysis. NR was related to presence of anti-GBM disease, P = 0.001, as was ability to stop dialysis, 0 of 7 GBM versus 9 of 10 other, P less than 0.001. Mild infiltrates of lymphocytes and M phi correlated with R, P less than or equal to 0.02. R had fewer numbers of TH and M phi in glomeruli, P = 0.0001, in crescents, P less than 0.02, and total TH and M phi compared to NR, P less than 0.001. Crescentic and total TH/S ratios were lower in NR than R, P less than 0.05. These findings demonstrate that components of the cell-mediated immune (CMI) system are present by MAb analysis, that subtypes cannot be differentiated by CMI constitution, and R to PM is related to intensity and composition of CMI involvement. Independence of the CMI system relative to anti-GBM disease remains to be clarified.     

The use of heparin in the treatment of idiopathic rapidly progressive glomerulonephritis.

14 cases of idiopathic rapidly progressive glomerulonephritis (I. R. P. G. N.) treated by heparin between 1968 and 1974 were collected by the authors. Extra-capillary crescents (E. C. C.) occurred in 75 to 100% of glomeruli in ten patients and in 50 to 75% in four. Gross proteinuria, hematuria and renal failure were always present. 9 patients were admitted with primary oligo-anuric renal failure. 11 patients were treated by repeated hemodialysis before and during anticoagulant treatment. Heparin was given by intra-venous injection every 3 hours for one to two months with Howell times range from 150 to 200% of control. Heparin was the only treatment in 6 cases, and was given with dipyridamole in 4, with prednisone in 3 and with azathioprine in one case. 5 severe or fatal hemorragic complications were observed. The clinical course was usually unfavorable with 5 early deaths, 3 provisional steady-states with 2 late deaths. Six patients were treated by periodic hemodialysis. Repeat kidney biopsies were obtained in 8 patients. The findings suggest that heparin affects mainly the E. C. C. and fibrinoid deposits but not glomerular sclerosis. The inefficiency of all current treatments of primary oligo-anuric IRPGN is stressed. In patients with better initial renal function choice between anticoagulant and/or immuno-depressive drugs must be scrutinized in individual cases bearing in mind potential iatrogenic complications. In equivocal cases, patients should be referred to the chronic hemodialysis and/or transplantation program.