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Saudi Journal of Kidney Diseases and Transplantation
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ORIGINAL ARTICLE  
Year : 2013  |  Volume : 24  |  Issue : 4  |  Page : 743-750
Alveolar hemorrhage and kidney disease: Characteristics and therapy


1 Department of Nephrology, La Rabta Hospital, Tunis, Tunisia
2 Laboratory of Renal Pathology, LR001SP, Charles Nicole Hospital, Tunis, Tunisia

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Date of Web Publication24-Jun-2013
 

   Abstract 

Anti-neutrophil cytoplasmic antibody-associated vasculitis and Goodpasture's glomerular basement membrane disease are the most common causes of diffuse alveolar hemorrhage, a life-threatening disease. Systemic lupus erythematosus and the antiphospholipid syndrome are also causes of alveolar hemorrhage. We retrospectively reviewed 15 cases of diffuse alveolar hemorrhage (DAH) associated with renal diseases. Diagnosis of DAH was based on the presence of bloody bronchoalveolar lavage fluid. There were three men and 12 women, with a mean age of 50.5 years (extremes: 24-74 years). Proteinuria and hematuria were observed, respectively, in 15 and 14 cases. Six patients revealed arterial hypertension. Crescentic glomerulonephritis was diagnosed with kidney biopsies in ten cases. The etiology of renal disease was microscopic polyangiitis (MPA) in seven cases, Wegener disease in four cases, systemic lupus erythematous in one case, cryoglobulinemia in one case, myeloma in one case and propyl-thiouracil-induced MPA in one case. Hemoptysis occurred in 14 cases. The mean serum level of hemoglobin was 7.1 g/dL (5.1-10 g/dL). The mean serum creatinine concentration was 7.07 mg/dL (2.4-13.7 mg/dL). Gas exchange was severely compromised, with an oxygenation index <80 mmHg in 14 patients and <60 mmHg in seven patients. Bronchoalveolar lavage was performed in 11 cases, and had positive findings for hemorrhage in all. Methylprednisolone pulses and cyclophosphamide were used in 14 patients. Plasmapheresis was performed in three cases. One patient received cycles of Dexamethasome-Melphalan. Three patients died as a result of DAH. The mortality rate in our study was 20%.

How to cite this article:
Fatma LB, El Ati Z, Lamia R, Aich DB, Madiha K, Wided S, Maiz HB, Beji S, Karim Z, Moussa FB. Alveolar hemorrhage and kidney disease: Characteristics and therapy. Saudi J Kidney Dis Transpl 2013;24:743-50

How to cite this URL:
Fatma LB, El Ati Z, Lamia R, Aich DB, Madiha K, Wided S, Maiz HB, Beji S, Karim Z, Moussa FB. Alveolar hemorrhage and kidney disease: Characteristics and therapy. Saudi J Kidney Dis Transpl [serial online] 2013 [cited 2019 Oct 18];24:743-50. Available from: http://www.sjkdt.org/text.asp?2013/24/4/743/113868

   Introduction Top


Diffuse alveolar hemorrhage (DAH) is a clinical syndrome that can be life-threatening if if not diagnosed and treated in time. [1] In most cases, it occurs largely as a result of small-vessel vasculitis of the lungs. Antineutrophil cytoplasmic antibodies (ANCA) and Good-pasture's diseases are the most common causes of DAH, while other pathologies including systemic lupus erythematosus, antiphospholipid syndrome and multiple myeloma, are rare causes of this syndrome. Diagnosis of DAH is based on a combination of signs, symptoms, biological tests and histology. Hemoptysis, decreased hemoglobin levels and/or hematocrit, diffusion capacity for carbon monoxide (DLCO) of more than 30% and bronchoalveolar lavage (BAL)-positive findings of hemosiderin are relatively common features in DAH. [2] The aim of our study was to collect cases of patients with DAH and kidney disease, to describe their clinical, radiological and histological characteristics and approach for treatment.


   Patients and Methods Top


A group of 15 patients (12 females, three males) with DAH and renal disease were retrospectively identified from September 2007 to September 2010 in the Nephrology Department in La Rabta Hospital in Tunis, Tunisia. Their clinical presentations and laboratory, radiographic and pathologic findings and response to therapy were reviewed.

Characteristics of the patients were recorded from the medical files and the following items were analyzed: Demographic characteristics, pulmonary and renal tract involvement, etiologies of the DAH, response to therapy and outcome of patients.


   Results Top


There were 12 women and three men, with a mean age of 50.5 years (extreme: 24-74 years). Two patients had pulmonary fibrosis and one patient had diabetes. Proteinuria and hematuria were observed, respectively, in 15 and 14 cases. Six patients revealed arterial hypertension. Crescentic glomerulonephritis was diagnosed in ten cases. The mean serum creatinine concentration was 7.07 mg/dL (range from 2.4 to 13.7 mg/dL), requiring hemodialysis in ten cases. Thirteen patients had a kidney biopsy. Pauci-immune extracapillary glomerulonephritis with necrosis was diagnosed in ten cases. Only in our patient no. 7, kidney biopsy diagnosed pauci-immune extracapillary glomerulonephritis associated with IgG linear deposit.

Hemoptysis was present in 14 cases. The median serum level of hemoglobin was 7.1 g/dL (5.1-10 g/dL). Gas exchange was severely compromised, with an oxygenation index <80 mmHg in ten cases and <60 mmHg in seven cases. Thirteen patients presented with alveolar hemorrhage at disease onset. The two remaining patients revealed signs of DAH few days after starting the treatment.

BAL was performed in 11 cases. Evidence of microscopic alveolar hemorrhage was confirmed in BAL, defined as more than 20% siderophages and Gold score superior to 100; seven patients had more than 20% siderophages and 11 patients had Gold score superior to 100. The DLCO performed in only one case was positive. The remaining 14 patients did not have DLCO testing because they were too ill to cooperate. Our patients did not undergo transbronchial biopsies and hence no pulmonary histological reports were available.

Wegener's disease was diagnosed in four cases because of the presence of a pauci-immune extra-capillary glomerulonephritis with periglomerular granulomatous reaction; anti-PR3 type C-ANCA was found in all these cases, retro-orbital granulomatous mass and pansinusitis was seen in two cases and epistaxis with pulmonary nodules was seen in one case. The characteristics of our patients are summarized in [Table 1] and [Table 2] and [Figure 1] and [Figure 2].
Figure 1: Chest X-ray of patient no. 5, diffuse bilateral alveolar opacities.

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Figure 2: Chest computed tomography of patient no. 15, extensive and bilateral lesions.

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Table 1: Patients' characteristics of diffuse alveolar hemorrhage syndrome.

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Table 2: Study patients' characteristics of kidney involvement.

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All the patients received intravenous (i.v.) high-dose steroids. In addition, 14 patients received an i.v. pulse of cyclophosphamide. Two patients received ten cycles of plasmapheresis and one patient received seven cycles. In our study, the mean period of follow-up was 9.5 months (1-20 months). The renal function improved in only seven cases and the rest required chronic hemodialysis. Pulmonary involvement improved in 12 cases, and without relapse in 11 cases. Only one relapse of DAH was observed in patient no. 7 after 12 months of follow-up. This patient was maintained on chronic hemodialysis and required immunosuppression withdrawal because of the occurrence of a Kaposi sarcoma. Three patients died as a result of severe hypoxemia related to DAH, with a mortality rate of 20%.

Treatment and outcome of the patients are summarized in [Table 3].
Table 3: Treatment and outcome of the study patients.

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   Discussion Top


The pulmonary-renal syndrome is a combination of DAH and glomerulonephritis. [3] Our study described the clinical, radiographical characteristics, etiologies and outcome of a group of 15 patients with pulmonary-renal syndrome.

In earlier studies, the hemoptysis frequency ranged from 25% to 100%. [4] Definite diagnosis is based on the BAL findings. New infiltrates on chest X-rays accompanied by abrupt drop in Hb appear to be a more sensitive sign of DAH. However, radiographic findings range from diffuse alveolar infiltrates to lobar infiltrates, and are not specific. [5],[6] The classic sign of a raised DLCO on pulmonary function tests is useful and suggestive of DAH. [7],[8] However, this test has limited value in the acutely ill patients. In our study, the DLCO contributed to the diagnosis in only one case, and the rest were too ill to cooperate with this test. Evidence of microscopic alveolar hemorrhage was observed in all patients who underwent bronchoscopy.

In our study, DAH was clearly definite in only 11 cases who underwent BAL. In the other four cases, diagnosis of DAH was probable because of clinical, biologic and radiologic features. The many different forms of DAH can be classified into three large groups: Pauci-immune diseases, syndromes caused by immune deposits and a large miscellaneous group that includes drug reactions, infections and idiopathic diseases. [9]

Most studies on DAH emphasize that it is immunologically mediated and associated with MPA or rapidly progressive glomerulonephritis in patients with anti-MPO type P-ANCA; [10],[11] DAH occurs at a rate of 12-29% in MPA patients. [11],[12] In our study, DAH was associated with MPA in seven (49%) patients. Four more cases were due to Wegener's disease. [13],[14],[15]

Typical pulmonary lesions of DAH on chest X-ray include bilateral, reticular or nodular opacities. Chest computed tomography is required to accurately characterize the pattern and extent of pulmonary disease. [16],[17] In our study, the chest computed tomography was performed in only eight cases and showed extensive bilateral lesions in all cases. Typical lesions such as frosted glass were observed in seven cases.

DAH is a rare complication of systemic lupus erythematous, with a reported frequency ranging from 1% to 5.4% of lupus cohorts. [18],[19],[20],[21] However, it is often serious, requiring early, intensive therapy and is associated with high mortality, ranging from 23% to 92%. [22]

Propyl-thiouracil-induced P-ANCA vasculitis may be responsible for DAH in less than 1% of the patients receiving this drug. [23],[24],[25] Symptoms resolved completely after propyl-thiouracil withdrawal and steroid therapy. [24],[25]

In patients with evidence of DAH and renal involvement, kidney biopsy may be considered to identify the etiology and guide the therapy. [26] In this study, 13 patients of 15 patients had a kidney biopsy.

Similar to the literature, we used in our study methylprednisolone and cyclophosphamide pulses and plasmapheresis. Actually, the plasma exchanges are a component of regimens prescribed to treat systemic necrotizing vasculitis. [27] It can remove putative pathogenic auto-antibodies and circulating immune complexes from the blood of patients.

Recent reports have described the successful use of recombinant factor VIIa (rFVIIa) and intravenous immunoglobulin (IVIg) in severe DAH. [28],[29],[30]

Experience with more aggressive immunosuppression in severe diffuse alveolar hemorrhage-associated vasculitis, such as T-cell depletion or autologous stem cell transplantation, has been limited to a few centers. B-cell depletion with rituximab is currently attracting most attention with good success in refractory disease. [31]

DAH in multiple myeloma was reported in allogenic bone marrow transplantation, but rarely as an initial feature. [32] Alveolar capillary membrane lesions are related to the paraprotein-mediated mechanism (immunoglobulin A) sometimes associated with pulmonary hypertension. [33],[34] In our myeloma case, improvement of DAH was observed 15 days after initiation of dexamethasome and Alkylan treatment, with no relapse after nine months of follow-up.

DAH associated with kidney disease should be diagnosed promptly in all patients with falling red cell indices and new infiltrates on chest radiographs, even in the absence of hemoptysis or acute dyspnea. Bronchoscopy, imaging, spirometry, serology and histology are all appropriate to use for the diagnosis of DAH. The underlying kidney disease is variable and frequently related to immunologically mediated disease. Despite advances in treatment, DAH usually heralds severe vasculitis and mortality remains high. Early treatment with frequent i.v. pulse methylprednisolone and i.v. cyclophosphamide and/or plasma exchange should be instituted for a better outcome.

 
   References Top

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33.Russi E, Odermatt B, Joller-Jemelka HI, Spycher MA. Alveolar haemorrhage as a presenting feature of myeloma. Eur Respir J 1993;6:267-70.  Back to cited text no. 33
    
34.Schreiber J, Häntze S, Florschütz A, et al. A rare cause of diffuse pulmonary hemorrhage in a 45 year-old man. Internist (Berl) 2006;47: 944-51.  Back to cited text no. 34
    

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Correspondence Address:
Lilia Ben Fatma
Department of Nephrology, La Rabta Hospital, Jabbari, 2007, Tunis
Tunisia
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DOI: 10.4103/1319-2442.113868

PMID: 23816724

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