Pulmonary renal syndrome: A 4-year, single-center experience

doi:10.1053/ajkd.2002.29876

American Journal of Kidney Diseases

Volume 39, Issue 1, January 2002, Pages 42-47

https://doi.org/10.1053/ajkd.2002.29876 Get rights and content

Abstract

Pulmonary renal syndrome (PRS), defined as a combination of diffuse pulmonary hemorrhage and glomerulonephritis (GN), represents a severe syndrome for which minimal outcome data are available in the literature. We present a retrospective study of 14 consecutive patients from 1996 to 2000. Mean patient age was 65 ± 2.1 (SEM) years, and 7 patients were women. At presentation, Po₂ on air was 6.0 ± 0.5 kPa, and creatinine level was 554 ± 70 μmol/L. Thirteen patients had systemic vasculitis, and 1 patient had systemic lupus erythematosus (SLE). Five patients were cytoplasmic antineutrophil cytoplasmic autoantibody (C-ANCA) positive, and 7 patients were perinuclear ANCA (P-ANCA) positive; 2 of the latter patients also were positive for anti-glomerular basement membrane antibodies. Renal biopsy was performed in 10 patients. Histological examination showed membranous GN in the patient with SLE and segmental necrotizing crescentic GN in the other 9 patients examined. Twelve of 14 patients were initially dialysis dependent, and 8 of 14 patients required ventilatory support. All patients were treated with corticosteroids, 8 of 14 patients were administered intravenous methylprednisolone, 13 of 14 patients were administered daily cyclophosphamide, and 12 of 14 patients underwent plasma exchange. Patients were followed up for 22 ± 9 months. Early reduction in cyclophosphamide dosage was required in 9 patients for neutropenia. Seven patients were alive at the end of follow-up, but 5 patients (36%) died in the first month. Of the survivors, 85% and 67% were alive after 1 and 2 years of completed follow-up: 83% and 75% of these survivors were dialysis independent, respectively. Five relapses were seen in 4 patients. One patient died of progressive pulmonary fibrosis. Sepsis was a major factor in 6 of 7 deaths. This patient group was older than those previously reported. Findings confirm previous suggestions that PRS requiring intensive care treatment has high mortality, and early survivors have good 1- and 2-year outcomes. Cyclophosphamide-associated neutropenia and infection were frequent contributors to death, and less toxic alternatives may improve outcome in PRS. © 2002 by the National Kidney Foundation, Inc.

Section snippets

Methods

Fourteen consecutive cases of PRS managed at a single center between 1996 and 2000 were studied. Thirteen of these were de novo presentations of PRS at this institution; the care of the other patient had been transferred from another center. Criteria for inclusion were diffuse pulmonary hemorrhage, GN with deteriorating renal function, and hypoxia (Po₂ < 8.0 kPa). Diffuse pulmonary hemorrhage was defined as the presence of diffuse, bilateral, parenchymal infiltrates on chest radiograph,

Results

Mean patient age was 65 ± 2.1 (SEM) years, and seven patients were women. The mean duration of the prodromal illness, characterized by lethargy, weight loss, and arthralgia, was 2.9 ± 0.4 (SEM) months. Two patients had previous diagnoses of cryptogenic fibrosing alveolitis (CFA), and one patient, mixed connective tissue disease. One of the two patients with CFA was ANCA positive, with myeloperoxidase (MPO)-ANCA specificity. Two patients had a history of nephrotic syndrome. One of these

Discussion

A firm diagnosis of PRS is best established by using a combination of clinical presentation, serological results, and histological results, although obtaining material for the latter may present practical difficulties in a critical care setting. Confirmation of diffuse lung hemorrhage by bronchoscopy often was helpful, and others also have used bronchoalveolar lavage in this setting. The occurrence of prodromal illness of significant duration in most cases indicates a need and opportunity for

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The presentation, etiologies, pathophysiology, and treatment of pulmonary renal syndrome: A review of the literature
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Pulmonary renal syndrome (PRS) is a constellation of different disorders that cause both rapidly progressive glomerulonephritis and diffuse alveolar hemorrhage. While antineutrophil cytoplasmic antibody associated vasculitis and anti-glomerular basement membrane disease are the predominant causes of PRS, numerous other mechanisms have been shown to cause this syndrome, including thrombotic microangiopathies, drug exposures, and infections, among others. This syndrome has high morbidity and mortality, and early diagnosis and treatment is imperative to improve outcomes. Treatment generally involves glucocorticoids and immunosuppressive agents, but treatment targeted to the underlying disorder can improve outcomes and mitigate side effects. Familiarity with the wide range of possible causes of PRS can aid the clinician in workup, diagnosis and early initiation of treatment. This review provides a summary of the clinical presentation, etiologies, pathophysiology, and treatment of PRS.
Combination treatment with rituximab, low-dose cyclophosphamide and plasma exchange for severe antineutrophil cytoplasmic antibody-associated vasculitis
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Antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis can present with life-threatening lung-kidney syndromes. However, many controlled treatment trials excluded patients with diffuse alveolar hemorrhage or severely impaired glomerular filtration rates, and so the optimum treatment in these cases is unclear. In this retrospective cohort study, we report the outcomes of 64 patients with life-threatening disease treated with a combination regimen of rituximab, low-dose intravenous cyclophosphamide, oral glucocorticoids, and plasma exchange. At entry, the median estimated glomerular filtration rate was 9 mL/min, 47% of patients required dialysis, and 52% had diffuse alveolar hemorrhage. All patients received a minimum of seven plasma exchanges, and the median cumulative doses of rituximab, cyclophosphamide, and glucocorticoid were 2, 3, and 2.6 g, respectively, at six months. A total of 94% of patients had achieved disease remission (version 3 Birmingham Vasculitis Activity Score of 0) at this time point, and 67% of patients who required dialysis recovered independent kidney function. During long-term follow-up (median duration 46 months), overall patient survival was 85%, and 69% of patients remained free from end-stage kidney disease, which compares favorably to a historic cohort with severe disease treated with a conventional induction regimen. Combination treatment was associated with prolonged B cell depletion and low rates of relapse; 87% of patients were in continuous remission at month 36. The serious infection rate during total follow-up was 0.28 infections/patient/year, suggesting that combination treatment is not associated with an enduring risk of infection. Thus, we suggest that combination immunosuppressive therapy may permit glucocorticoid avoidance and provide rapid and prolonged disease control in patients with severe ANCA-associated vasculitis.
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Citation Excerpt :
Fifteen articles were further included after reviewing the reference lists of selected papers. In total, 90 [2–7,9,14–96] references were included (Supplementary Table 1) following the flow chart materialized in Fig. 1. Among these 90 references, 39 were from Europe, 25 from North America, 22 from Asia, 2 from Oceania and 2 from Africa, involving 336, 86, 107, 7 and 2 patients, respectively, for a total of 538 DPP.
Double-positive patients (DPP) exhibiting anti-glomerular basement membrane (GBM) and anti-neutrophil cytoplasmic antibodies (ANCAs) belong to an entity that is newly and poorly described, mainly in short series. We aimed to better characterize the epidemiological features, clinical presentation and therapeutic outcomes of these patients through a systematic review.
We performed a systematic review of English-, German-, Spanish- and French-written publications from February 1987 to March 2020 reporting cases of DPP using the following databases: PubMed, Scielo, ScienceDirect, Google Scholar, The Cochrane Library, Open Grey, The Grey Literature Report, Clinicaltrials.gov and International Clinical Trial Registry Platform of the World Health Organization.
In total, 538 DPP were identified from 90 articles. Their clinical presentations were often severe, and the majority exhibited acute kidney failure (91.8%) with a median initial serum creatinine level of 873 μmol/L; 50.7% had alveolar haemorrhage. Other manifestations were present in 30.3% of DPP, mainly ear, nose, throat and articular manifestations. ANCAs were predominantly directed against MPO (n = 377/523; 72.1%) compared to PR3 (n = 107/523; 20.5%), with rare cases of triple positivity (n = 15/538; 2.9%). Although most patients received initial immunosuppressive therapy (n = 285/317; 89.9%), the one-year overall, renal and relapse-free survival rates were 64.8%, 38.7% and 71.1%, respectively.
DPP are associated with the characteristics of two eponymous vasculitis types, responsible for a poor overall and renal prognosis. Thus, simultaneous testing of both antibodies and systematic renal biopsy should be recommended in every patient with rapidly progressive glomerulonephritis to recognize this difficult-to-treat and rare disease.
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^*: Address reprint requests to Hugh Gallagher, MBBS, SW Thames Renal Unit, St Helier Hospital, Wrythe Lane, Carshalton, Surrey SM5 1AA, UK. E-mail: [email protected]

^**: 0272-6386/02/3901-0006$35.00/0

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Original InvestigationsPulmonary renal syndrome: A 4-year, single-center experience*,**

Abstract

Section snippets

Methods

Results

Discussion

Chest

Kidney Int

Semin Arthritis Rheum

Kidney Int

The significance of certain pulmonary lesions in relation to the aetiology of pneumonia

Am J Med Sci

Goodpasture's syndrome (pulmonary haemorrhage associated with glomerulonephritis

Aust Ann Med

The role of antiglomerular basement membrane antibody in the pathogenesis of human glomerulonephritis

J Exp Med

Pulmonary-renal syndrome

Semin Respir Crit Care Med

Circulating autoantibodies as serological markers in the differential diagnosis of pulmonary renal syndrome

J Intern Med

The syndrome of lung hemorrhage and nephritis is usually an ANCA-associated condition

Arch Intern Med

Pulmonary hemorrhage in systemic lupus erythematosus

Medicine

Original Investigations
Pulmonary renal syndrome: A 4-year, single-center experience*,**