Increased incidence of anti-glomerular basement membrane antibody (anti-GBM) nephritis in the Mersey Region, September 1984-October 1985

We report an increase in the incidence of anti-glomerular basement membrane antibody nephritis in the Mersey Region over the 13 months from September 1984 to October 1985. During this period anti-glomerular basement membrane antibody nephritis was diagnosed in 10 patients: seven cases occurred between 1 June and 31 October 1985. We could identify no common infective agent or history of toxic exposure. Although outbreaks of parvovirus infection were reported in the region during this period, no patient had serological evidence of recent infection with parvo- or other virus. The only atypical feature was the high incidence of allergic rash which was seen in four of six patients treated with antibiotics before admission. Only two patients recovered sufficient renal function to make dialysis unnecessary. Both had a longer duration of prodromal symptoms, lower levels of circulating anti-glomerular basement membrane antibody antibodies and histological evidence of less aggressive disease.     

Pulmonary hemorrhage and glomerulonephritis in the absence of anti-glomerular basement membrane antibody

We have described a case of pulmonary hemorrhage and idiopathic crescentic glomerulonephritis unrelated to anti-glomerular basement membrane antibodies and/or immune complexes. Although pulmonary hemorrhage was controlled dramatically with high doses of corticosteroids, renal function declined rapidly.     

Goodpasture's syndrome in childhood: Treatment with plasmapheresis and immunosuppression

Goodpasture's syndrome rarely affects children. Therefore, we present our experience in a young boy whose pulmonary hemorrhage was dramatically resolved by three plasma exchanges. We believe the hemorrhage was caused primarily by acute capillaritis. He received cytoxan and steroids and a series of plasma exchanges which removed/suppressed his anti-glomerular basement membrane (anti-GBM) antibody production. However, after a year, his renal function did not return, and he required renal transplantation and continues to do well.     

Plasmapheresis in the treatment of rapidly progressive glomerulonephritis.

The present study was carried out to examine the efficacy of plasma exchange in patients with rapidly progressive glomerulonephritis (RPGN). Seventeen patients with RPGN were treated with plasmapheresis as adjunct to immunosuppressive therapy. Of these, 4 had antiglomerular basement membrane (GBM) antibody-mediated glomerulonephritis (GN), 8 had immune-complex GN (5 SLE, 2 HSP, 1 cryoblobulinemia), 5 had pauci-immune GN (3 peripheral antineutrophil cytoplasmic antibody [P-ANCA], 1 cytoplasmic antineutrophil cytoplasmic antibody [C-ANCA], 1 other). Treatment of 10 of these patients with plasmapheresis within the first month of disease onset resulted in a stable renal function for a period extending from 1 to 3 years, except in 2 patients who had high baseline levels of serum creatinine. In the remaining patients, 2 were treated with hemodialysis 6 years later at the end of follow-up. We conclude that plasmapheresis, when used in combination with immunosuppressive drugs, is beneficial, leading to improved renal function.     

Therapeutic plasma exchange for the treatment of rapidly progressive glomerulonephritis.

Therapeutic plasma exchange (TPE) has been widely accepted as a successful means of removing the antiglomerular basement membrane (anti-GBM) antibodies that result in the rapidly progressive glomerulonephritis (RPGN) of Goodpasture's syndrome. TPE has also been investigated as a means of removing the immune complexes associated with the glomerulonephritides of systemic lupus erythematosus, IgA nephropathy, Henoch Sch?nlein purpura, and cryoglobulinemia. Recently, an antineutrophil cytoplasmic antibody (ANCA) has been implicated in the pathogenesis of RPGN associated with such diseases such as Wegener's granulomatosis and periarteritis nodosa. ANCA has also been found in many cases of RPGN formally considered to be idiopathic. The identification of this autoantibody has given new credence to the possibility that TPE may be beneficial in the treatment of these diseases. This article reviews the data regarding the use of TPE for RPGN.     

Clinical and morphological aspects of the management of crescentic anti-glomerular basement membrane antibody (anti-GBM) nephritis/Goodpasture's syndrome

Twenty-two patients with crescentic anti-GBM nephritis or Goodpasture's syndrome with renal impairment were reviewed. All patients were treated with a combination of plasma exchange and immunosuppression. Sixteen patients (73 per cent) showed improvement in renal function (greater than 30 per cent reduction in serum creatinine level) apparently in response to treatment, and nine patients (41 per cent) made long-term recoveries in renal function. The most important features carrying a bad prognosis were total anuria, and/or a very high percentage of glomeruli showing crescents (greater than 85 per cent) in the initial renal biopsy. Some patients with other so-called 'bad' prognostic features, including severely impaired renal function at presentation, oliguria and the need to institute dialysis had unexpected marked improvement in renal function and/or recovered renal function in the long term provided treatment with plasma exchange was begun promptly and maintained for a sufficient period to allow resolution of the disease process. Renal biopsies at the beginning and later proved to be an extremely valuable guide for the progress and outcome of the disease.     

Clinical and Morphological Aspects of the Managment of Crescentic Anti-glomerular Basement Membrane Antibody (Anti-GBM) Nephritis/Goodpasture's Syndrome

Twenty-two patients with crescentic anti-GBM nephritis or Goodpasture'ssyndrome with renal impairment were reviewed. All patients weretreated with a combination of plasma exchange and immunosuppression. Sixteen patients (73 per cent) showed improvement in renal function(> 30 per cent reduction in serum creatinine level) apparentlyin response to treatment, and nine patients (41 per cent) madelong-term recoveries in renal function. The most important features carrying a bad prognosis were totalanuria, and/or a very high percentage of glomeruli showing crescents(> 85 per cent) in the initial renal biopsy. Some patientswith other so-called ‘bad’ prognostic features,including severely impaired renal function at presentation,oliguria and the need to institute dialysis had unexpected markedimprovement in renal function and/or recovered renal functionin the long term provided treatment with plasma exchange wasbegun promptly and maintained for a sufficient period to allowresolution of the disease process. Renal biopsies at the beginning and later proved to be an extremelyvaluable guide to the progress and outcome of the disease.     

Drug associated acute interstitial nephritis: clinical and pathological features and the response to high dose steroid therapy

Nine episodes of drug associated acute interstitial nephritis, in seven patients, were treated between 1972 and 1980. The drugs implicated were cotrimoxazole (three times), ampicillin, Magnapen (ampicillin and flucloxacillin), penicillin, gentamicin, paracetamol and bendrofluazide. The time from exposure to the onset of symptoms ranged from one to 30 days. Presentation was with acute renal failure, which was non-oliguric in five cases, accompanied by rash (four), fever (four), and loin pain (two). Renal biopsy was carried out in all cases, and showed a characteristic interstitial infiltrate comprising substantial numbers of lymphocytes and plasma cells, with a variable number of neutrophils, eosinophils and histiocytes. Immunofluorescence was negative in all four cases studied in the acute phase, and showed scattered deposits of IgG, IgM, IgA and C3 on the tubular basement membrane in one patient during recovery. Significant proteinuria and an abnormal urine deposit were present in all cases, and seven of nine had radiological evidence of enlarged kidneys. Seven episodes were treated with high doses of methyl prednisolone and in all there was a response with a diuresis or spontaneous fall in serum creatinine within 72 hrs, and recovery of virtually normal renal function. Of two cases who did not initially receive steroids, one improved more slowly and one developed chronic renal impairment.     

Immunotherapy in renal diseases

Immunotherapy has been used for the treatment of renal diseases for a long time, and there has been significant progress in such treatment. This review focuses on the use of immunotherapy for the treatment of glomerular diseases. The use of immunosuppression in the treatment of minimal change disease, membranous nephropathy, primary focal segmental glomerulosclerosis, lupus nephritis, immunoglobulin-A nephropathy, antineutrophil cytoplasmic antibody-associated disease, and anti-glomerular basement membrane disease is discussed.     

Mercuric chloride induced autoimmune disease in Brown-Norway rats: sequential search for anti-basement membrane antibodies and circulating immune complexes

Mercuric chloride induces in the Brown-Norway rat a biphasic autoimmune disease characterized initially by linear IgG deposits along the glomerular basement membrane followed later by granular IgG deposition. In the present study, anti-glomerular basement membrane antibodies and immune complex-like material were sequentially assessed in serial serum samples. Both were transiently found at the same period. Glomerular linear IgG deposits were present on day 11 but circulating anti-glomerular basement membrane antibodies were only found later on day 16. Circulating immune complexes were first detectable on day 8 before the earliest granular IgG deposits were first observed in the spleen vessels on day 16. The disappearance of circulating anti-glomerular basement membrane antibodies and of circulating immune complexes, although HgCl2 injections were pursued, is in agreement with the self-limited character of mercuric chloride induced autoimmune disease and suggests the induction of immunosuppressive mechanisms.     

非典型抗肾小球基底膜病研究进展

抗肾小球基底膜病是一种发病率较低,但伴有严重临床症状的自身免疫性疾病。随着诊断技术的发展,临床中发现,部分患者的临床表现及实验室检查结果与典型抗肾小球基底膜病有许多不同之处。此类抗肾小球基底膜病患者发病机制不明,临床表现不典型,给临床诊断带来了一些困难,目前的治疗方法也无统一标准。本文将对非典型抗肾小球基底膜病研究进展作一综述。     

强化血浆置换联合肾上腺皮质激素治疗急进性肾小球肾炎的疗效

[目的]探讨强化血浆置换联合肾上腺皮质激素治疗急进性肾小球肾炎(RPGN)的临床疗效.[方法]采用强化血浆置换联合肾上腺皮质激素治疗59例RPGN患者,对患者的治疗效果进行分析.[结果]患者平均进行强化血浆置换(13.2±2.6)次,平均住院时间(72.8±11.0)d,血尿消失时间(27.4±11.6)d,浮肿消退时间(15.8±5.1)d,血压恢复时间(14.7±4.2)d.治疗4周后、治疗8周后患者血清白蛋白(ALB)、肾小球滤过率(eGFR)、24 h尿量均较治疗前显著提高,且差异具有显著性(P<0.05),尿蛋白、血肌酐(SCr)、抗肾小球底膜抗体测定值较治疗前均显著降低(P<0.05).59例患者中痊愈为25.42%(15/59),好转为57.63%(34/59),无效占16.95%(10/59),治疗至出院时评估为无效的10例患者均在本院门诊血液透析中心进行血液透析治疗.[结论]强化血浆置换联合肾上腺皮质激素治疗RPGN具有较好的疗效,临床上应该尽早对患者进行血浆置换治疗.     

Analyses of registry data of patients with anti-GBM and antineutrophil cytoplasmatic antibody-associated (ANCA) vasculitis treated with or without therapeutic apheresis

Therapeutic apheresis (TA) as a treatment for antibody-associated vasculitis (AAV) was questioned by the PEXIVAS although the MEPEX study favored TA.The aim of this study was to evaluate the efficacy of TA to improve renal function in patients consecutively included in the WAA-apheresis registry versus patients not treated with TA.Materials and methodsIncluded were 192 patients that suffered from anti-glomerular basement membrane disease (anti-GBM, n = 28) and antineutrophil cytoplasmic antibody-associated vasculitis of MPO or PR3 origin. Of these 119 had performed TA and the other 73 had not performed TA for theses diagnoses (CTRL).ResultsElderly had an increased risk to die within 12 months (p = 0.002). All 28 anti-GBM had renal involvement, 21 dialysis dependent. At 3 month nine (36 %) did not need dialysis. Baseline data regarding renal function of AAV patients, subtype MPO and PR3, were worse in the TA groups than in CTRL. Recovery out of dialysis was better for the PR3-TA group compared with 1) the controls of MEPEX (RR 0.59, CI 0.43−0.80) and 2) the MPO-TA patients (RR 0.28, CI 0.12−0.68). The MPO-TA recovered similarly as the MEPEX-CTRL. Renal function improved most for TA-patients from baseline during the first 3 months (MPO-TA and PR3-TA) and stabilized thereafter and less for MPO-CTRL and PR3-CTRL.ConclusionPR3-TA patients seem to have best chances to get out of dialysis. PR3-TA and MPO-TA improved residual renal function better than CTRL. The present study recommends reconsiderations to use TA for AAV especially those with PR3-vasculitis with severe renal vasculitis.     

Endocarditis-associated rapidly progressive glomerulonephritis mimicking vasculitis: a diagnostic and treatment challenge

BackgroundInfective endocarditis (IE)-associated rapidly progressive glomerulonephritis (RPGN) is rarely reported. Sporadic case reports have noted the diagnostic and therapeutic challenge in IE-associated glomerulonephritis because it may masquerade as idiopathic vasculitis.MethodsPatients with clinical diagnosis of IE-related RPGN in a tertiary hospital in China between January 2004 and May 2021 were identified and retrospectively reviewed.ResultsTwenty-four patients with IE-associated RPGN were identified. All patients presented with fever and multiorgan system involvement on top of heart and kidneys, spleen (79%, 19/24), skin (63%, 15/24), lung (33%, 8/24) and nervous system (17%, 4/24). Six of the 24 patients (25%) were initially suspected to have ANCA-associated or IgA vasculitis. Forty-five percent of patients are seropositive for ANCA. Renal histology showed mesangial and/or endocapillary hypercellularity with extensive crescents in most patients. C3-dominant deposition was the predominant pattern on immunofluorescence and pauci-immune necrotising crescentic glomerulonephritis was observed in one case. All patients received antibiotics with or without surgery. Six patients received immunosuppressive therapy before antibiotics due to misdiagnosis and seven patients received immunosuppressive therapy after antibiotics due to persistence of renal failure. Three of the 24 patients died due to severe infection. All the surviving patients had partial or complete recovery of renal function.ConclusionIE-associated RPGN is rare and the differential diagnosis from idiopathic vasculitis can be challenging due to overlaps in clinical manifestations, ANCA positivity and absence of typical presentations of IE. The prognosis is generally good if antibiotics and surgery are not delayed. The decision on introducing immunoruppressive treatment should be made carefully on a case by case basis when kidney function does not improve appropriately after proper anti-infective therapy.

Key messages

• Infective endocarditis associated RPGN is rare and differentiating it from idiopathic vasculitis can be challenging due to overlap in clinical manifestations, ANCA positivity and occasional absence of typical manifestations of infective endocarditis.
• Kidney function usually responds to antibiotic therapy alone.
• Immunosuppressive therapy may be beneficial in carefully selected patients whose kidney function does not improve with antibiotics alone.

     

New strategies for plasma exchange in systemic vasculitis

The use of plasma exchange in the treatment of systemic vasculitis has been controversial and poorly defined. Since the discovery of anti-neutrophil cytoplasm antibodies (ANCA) and the demonstration of their specificity for systemic vasculitis, there has been a reassessment of the use of plasma exchange along the same lines as its use in anti-glomerular basement membrane disease. ANCA has also contributed to the diagnosis and classification of rapidly progressive glomerulonephritis, in which there is now firmer evidence to support the use of plasma exchange. Current work into the immunoregulation of ANCA by idiotype/anti-idiotype interactions is leading to new approaches to therapy and plasma exchange alone appears capable of inducing prolonged remission in some patients with vasculitis, possibly through an effect on these interactions.     

The partial recovery of kidney function in chronic uremia patients during hemodialysis treatment

Out of 432 patients placed on the treatment with hemodialysis (HD) for terminal renal failure (TRF) at the All-Union Nephrologic Center from January 1, 1978 to December 31, 1987, 17 patients manifested partial recovery of renal function, which enabled dialysis treatment to be discontinued for a time. Among the 17 patients with noticeable improvement of renal function, 8 presented with lupoid rapid-progressing glomerulonephritis (RPGN), 2 with RPGN associated with hemorrhagic vasculitis, 1 with idiopathic RPGN, 4 with chronic glomerulonephritis (CGN), 1 with chronic pyelonephritis, and 1 with polycystic kidneys. In 11 patients with RPGN, the rate of renal failure progression, expressed by the regression coefficient, was much higher among those in whom HD treatment was discontinued that in the group of patients without renal function recovery. In the 4 patients with CGN, renal function was recovered after the correction of marked disorders of purine metabolism, whereas in the 1 patient with chronic pyelonephritis and in the 1 with polycystic kidneys after urinary infection elimination. According to the ultrasonography data, out of the 17 patients with partial recovery of renal function, the size of the kidneys turned out normal in 14 patients.     

"Triple-positive" renal limited vasculitis presenting with rapidly progressive glomerulonephritis: A case report

Rationale: Coexistence of anti-glomerular basement membrane (anti-GBM) disease with anti-neutrophil cytoplasmic antibody (ANCA) in a case of glomerulonephritis is often identified as a "double-positive" disease. Interestingly, the majority of "double positive" ANCA is myeloperoxidase (MPO)-ANCA and some of the MPO-ANCA positive cases showed intrarenal arteritis, suggesting an ANCA-associated kidney lesion. Proteinase 3-ANCA positive diseases are also rarely reported. Patients positive for all three antibodies, i.e., triple-positive patients, are extremely rare.Patient's Concern: A 53 year-old female presented with anasarca and oliguria of 2 months' duration. Diagnosis: Pauci-immune type renal limited crescentic glomerulonephritis positive for MPO-ANCA, proteinase 3-ANCA, and anti-GBM antibody (triple-positive). Interventions: Intravenous high dose cyclophosphamide, oral azathioprine, intravenous methylprednisolone, and plasma exchange as per British Health Professionals in Rheumatology Guidelines. Outcomes: After one-month follow-up, anasarca and proteinuria were lessened, serum creatinine was normalized, titers of MPO-ANCA levels were decreased, and anti-GBM antibody levels were normalized. Lessons: Triple-positive renal limited vasculitis is rare and response to combined immunosuppressive therapy and plasma exchange can contribute to successful remission.     

Profile of crescentic glomerulonephritis in Natal--a clinicopathological assessment

Crescentic glomerulonephritis is invariably associated with a fulminant syndrome of rapidly progressive renal failure which generally progresses to end-stage renal failure within weeks or months of onset. A widely differing aetiological background has been reported from Western countries. Work from the African continent is sparse. In a study from the province of Natal in South Africa between 1981 and 1987, 27 cases of crescentic nephritis were identified from a total of 458 patients who underwent renal biopsy at King Edward VIII and Addington hospitals. Poststreptococcal nephritis was the commonest aetiological factor (n = 8). There were six black patients in this group. Nine patients were classified as idiopathic and of these five were black. Four patients (one black) had antiglomerular basement membrane disease. Of the 24 patients subjected to variable combinations of immunosuppression, antiplatelet agents, dialysis and plasmapheresis, 11 improved, observed over four months to four years. Oliguria and severe renal failure at presentation signified a poor prognosis.     

Partial characterization of antigenic streptococcal plasma membrane components in acute glomerulonephritis

Fluorescein-labeled immunoglobulin G (IgG) fractions of serum from patients with acute poststreptococcal glomerulonephritis stained parts of the glomerular basement membrane and mesangium of kidney tissue obtained from the same patients during the early phase of the disease. Renal tissue obtained from normal individuals and from patients with other kidney diseases failed to stain with these IgG fractions. Preabsorption of the serum fractions with various freezethawed bacteria demonstrated that only certain group A streptococci abolished the staining capacity. Fractionation of the streptococci into cellular constituents indicated that it was predominantly the plasma membrane fraction which blocked the immune staining. Spectrofluorometry using alkali-solubilized renal tissue confirmed these observations in a quantitative manner. By sucrose density-gradient ultracentrifugation of the plasma membrane two possible antigens were isolated. One was soluble in phosphate-buffered saline and the other was insoluble. The soluble component was a lipoprotein with a molecular weight of approximately 120,000.     

急进性肾炎的诊治进展

急进性肾小球肾炎(rapidly progressive glomerulonephritis,RPGN)以急性肾炎综合征伴肾功能急剧恶化为临床特征,病理为新月体肾炎.早期诊断主要依靠血清免疫学检查及尽早肾活检.早期治疗应根据病理类型及患者情况采用个体化的治疗方案,包括强化治疗和免疫抑制治疗.