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Saudi Journal of Kidney Diseases and Transplantation
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CASE REPORT Table of Contents   
Year : 2010  |  Volume : 21  |  Issue : 2  |  Page : 332-336
Dilated cardiomyopathy in a patient with antibody-negative Goodpasture's syndrome and pulmonary relapse


1 Department of Nephrology, Selcuk University, Meram School of Medicine, Meram, Konya, Turkey
2 Department of Internal Medicine, Selcuk University, Meram School of Medicine, Meram, Konya, Turkey

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Date of Web Publication9-Mar-2010
 

   Abstract 

The Goodpasture's syndrome, also konwn as anti-GBM disease, is an uncommon disease, responsible for 20% of all cases of rapidly progressive glomerulonephritis. Anti-GBM antibodies are directed against non-collagenous domain (NC-1) of the alpha-3 chain of type IV collagen. When conventional ELISA assays are used, these antibodies can be detected in almost all the patients. Nevertheless, some reports have described antibody-negative relapsing disease. Some aggravating factors, namely, smoking, pulmonary infection and hypervolemia, may expose embedded antigenic target and may be responsible for the relapse. In addition, these antibody­negative relapses also respond to standard treatment, which comprises of plasma exchange, pulse steroids and cyclophosphamide. Herein, we report a patient who presented at the Selcuk Univer­sity Meram School of Medicine, Meram, Konya, Turkey, with the pulmonary-renal syndrome. He was also found to have idiopathic dilated cardiomyopathy (DCM). To our knowledge, this is the first report describing co-existence of DCM and anti-GBM disease. There is growing evidence showing strong relation of both DCM and anti-GBM disease with HLA. Although not proven, this might have occurred in our patient. In our opinion, volume overload was facilitated by anuria and DCM and led to an antibody-negative pulmonary relapse. The relapse was treated just as the first episode and the patient improved satisfactorily.

How to cite this article:
Solak Y, Selcuk NY, Polat I, Atalay H, Turkmen K. Dilated cardiomyopathy in a patient with antibody-negative Goodpasture's syndrome and pulmonary relapse. Saudi J Kidney Dis Transpl 2010;21:332-6

How to cite this URL:
Solak Y, Selcuk NY, Polat I, Atalay H, Turkmen K. Dilated cardiomyopathy in a patient with antibody-negative Goodpasture's syndrome and pulmonary relapse. Saudi J Kidney Dis Transpl [serial online] 2010 [cited 2020 Dec 4];21:332-6. Available from: https://www.sjkdt.org/text.asp?2010/21/2/332/60196

   Introduction Top


The Goodpasture's syndrome, also known as anti-GBM disease, is an uncommon disease, responsible for 20% of all cases of rapidly pro­gressive glomerulonephritis. [1] The anti-GBM antibodies are directed against the non-colla­genous domain (NC-1) of the alpha-3 chain of type IV collagen and is responsible for the pulmonary-renal clinical picture. In almost all patients with the anti-GBM disease, circulating anti-GBM antibodies can be detected by ELISA. [2] However, antibody-negative relapses have been described. Herein, we present a young male who had dilated cardiomyopathy (DCM) and anti-GBM disease concomitantly, and developed an antibody-negative pulmonary relapse.


   Case Report Top


An 18-year-old male patient presented with complaints of shortness of breath, blood-tinged sputum and pretibial edema. He had been hos­pitalized in another center for 10 days and was referred to our hospital for the pulmonary com­plaints. He had a flu-like disease 15 days prior to the first hospitalization. Following this, he developed dyspnea and occasional hemoptysis. He had been anuric and on hemodialysis (HD) since the first hospitalization.

At initial evaluation, physical examination revealed a malnourished young man in mode­rate distress. The blood pressure was 140/80 mmHg, heart rate was 106 beats/min and he was afebrile. Breath sounds were diminished globally and there were crackles at both lung bases. An S-3 gallop was audible and there was a soft 1-2/6 murmur at the mitral region. He had +2 pedal edema.

At admission, results of blood biochemistry and complete blood count studies were as fo­llows: blood urea, 113 mg/dL (N=17-43); serum creatinine, 6.3 mg/dL (0.7-1.2); sodium, 134 mEq/L; potassium, 4.45 mEq/L; calcium, 8.7 mg/dL (N=8.9-10.3); phosphorus, 5.5 mg/dL (N=2.4-4.7); albumin, 2.9 mg/dL; CRP, 47 mg/dL (0-10); total white blood cell (WBC), 9.000/mm 3 ; hemoglobin, 8.9 g/dl and platelet count of 344.000/mm 3 . The INR and aPTT were 1.59 (N=1-1.5) and 115.4 seconds (N=26­40 secs), respectively.

Chest X-ray revealed patchy alveolar infil­trates throughout the middle and lower zones of both lungs [Figure 1]. Abdominal ultrasound showed bilateral normal-sized kidneys with increased echogenicity. Thoracic computed to­mography (CT) scan showed extensive air­space disease compatible with alveolar hemo­rrhage [Figure 2].

With initial diagnosis of active pulmonary­renal syndrome, the patient was admitted to the medical intensive care unit and adminis­tered HD with ultrafiltration. After obtaining blood samples for ANCA, anti-GBM antibody and other serologic markers, the patient was administered plasma exchange therapy (PET) with fresh frozen plasma (FFP) (total of 14 sessions) with the possibility that he might have the Goodpasture's syndrome. He was also given three pulses of methylprednisolone (500 mg each) and a single dose of 250 mg of cy­clophosphamide, as infusion. A renal biopsy was performed and the result, which showed linear IgG and C3 staining of glomerular ca­pillaries, was consistent with anti- GBM disease.

Anti-GBM antibody, which was studied with ELISA, was found to be positive. Since he had an S-> gallop on auscultation, and was easily becoming volume overloaded despite meticu­lous fluid restriction and adequate ultraliltra­tion, an echocardiogram was performed. Echo­cardiography revealed an ejection fraction of 25%, left ventricular wall-motion abnormali­ties, dilated left atrium and ventricle, and peri­cardial effusion. Myocardial perfusion scinti­graphy with Tc-99 m and MIBI showed nor­mal myocardial perfusion thereby excluding ischemic cardiomyopathy. Cardiac magnetic re­sonance indicated findings of DC M.

Our study patient had never used alcohol and was not a smoker either. He had no family history of DCM and no hypertension before the current illness. I-le also had no myocarditis, collagen vascular disease or high-output states to account for the development of DCM. We planned to perform an endomyocardial biopsy, which the patient refused. A diagnosis of idio­pathic DCM was eventually made.

During the hospitalization, the clinical condi­tion of the patient improved and oral mainte­nance immunosuppression with prednisolone 0.8 mg/kg body-weight and 25 mpg cyclophos­phamide was commenced. Approximately 45 days after completion of the last session of plasmapheresis, the patient developed sudden onset of dyspnea and hemoptysis. Chest X-ray revealed extensive patchy alveolar infiltrates. Anti-GBM antibodies were again negative. Bearing in mind that relapse of pulmonary manifestations of antibody-negative anti-GBM disease was possible, we placed the patient on PET with FFP and administered three-day pulse prednisolone treatment. After 10 sessions of PET, the patient's condition improved and he was discharged on oral prednisolone, amlodi­pine, trimethoprim-sulpliamethoxaole, erythro­poietin and calcitriol.


   Discussion Top


Anti-GBM disease is defined as the triad of glomerulonephritis, pulmonary hemorrhage, and anti-GBM antibody formation. Despite this triad of clinical findings, patients with anti-GBMdisease may present with a spectrum of condi­tions ranging from pulmonary hemorrhage with minimal or no renal involvement, to Bill-blown renal failure with limited or no pulmonary in­volvement. [3]

Anti-GBM disease exemplifies the classic case of pathogenic antibody-mediated disease. The culprit is anti-GBM antibodies, which are di­rected against non-collagenous domain (NC-1) ol'the alpha-3 chain of type IV collagen. [4] Anti­GBM disease has been strongly associated with HLA DR2 which is present in 80% of the cases. [5]

DCM accounts for approximately 25% of all cases of congestive heart failure. [6] Ischemic and hypertensive cardiomyopathies are the leading underlying causes. A number of environmental exposures (mainly alcohol abuse), myocarditis, collagen vascular diseases, high output states, some drugs and heavy metals also cause DCM. There are now abundant gene linkage studies and multiple genes have been identified. [7] Cer­tain specific human leukocyte class-II antigens (particularly DR4) are associated with DCM. The hallmarks of'DCM are enlargement ol'one or both of the ventricles and systolic dysfunc­tion. [8] The most typical symptoms include dysp­nea, fatigue and volume gain.

To our knowledge, this is the first report of co-existence of DCM with anti-GBM disease. The importance of DCM being a complication of anti-GBM disease in our patient, is that vo­lume overload made the patient prone to al­veolar hemorrhage. Some factors can play a role as a trigger in a patient who already has anti-GBM antibodies. Among them are smo­king, pulmonary infection, hypervolemia, hydro­carbons, urinary infection and lithotripsy. [9] Al­though not convincingly proved, smoking in­duces damage of the basement membrane with subsequent denudation of certain epitope of the alpha-3 (IV) collagen chain and antibody production. [10] We believe that hypervolemia and pulmonary edema may play a similar role in terms of triggering pulmonary hemorrhage. When we consider the relatively rare relapse rate of anti-GBM disease after effective treat­ment, preventing pulmonary hemorrhage which is triggered by aforementioned conditions is of particular importance and a delicate fluid re­gime in oligo-anuric patients who are under­going HD should be an integral part of treat­ment. Several serologic studies in recent years, have documented a strong association of anti­GBM disease with the MHC class-II gene, HLA DR2. [4] Also, there is mounting, evidence with respect to the relationship between DCM and HLA antigens. Although unable to prove, the co-existence of these two distinct entities in the same patient may be explained by the presence of a HLA gene polymorphism, which is responsible for susceptibility to both diseases.

After having responded to immunosuppre­ssive therapy at first presentation, our patient developed a pulmonary relapse and again, anti­GBM antibody was not detected by ELISA. Disease activity usually burns out once the patient develops advanced kidney failure and is started on HD, even without immunosuppre­ssive therapy. [11] Thus, relapses are unusual in patients who are successfully treated or trans­planted, despite the presence of the continuous antigenic target. [12]

Our patient's pulmonary relapse occured 45 days after completion of immunsuppressive treatment. Unlike the classical knowledge, he experienced severe alveolar hemorrhage des­pite presence of advanced renal failure (he had been undergoing HD for approximately four months at that time) and absence of any pre­cipitating, events, except for volume overload. He did not have any detectable anti-GBM antibodies either. There are few reports in the literature about relapse of antibody-negative anti-GBM disease. [13] Precipitating, factors trigger disease activity by exposing pulmonary or re­nal target antigen and achieve this by increa­sing anti-GBM antibody titers. However, this was not the case in our patient.

Linear deposition of immunoglobulin along the GBM in the setting of crescentic nephritis confirms the diagnosis. However, renal biopsy is not always feasible when the patients pre­sent with catastrophic pulmonary hemorrhage. Rapid diagnosis of anti-GBM disease is in­creasingly reliant on ELISA techniques to de­tect circulating, anti-GBM antibodies. False-positive and false-negative results occasionally may occur using this method. [13] Using a highly sensitive method of detecting circulating, anti­GBM antibodies with biosensor techniques, Salama AD et al [13] showed that such antibodies can be detected despite negative ELISA and Western blot results. Since we do not have this technique like many other laboratories, we could not show whether our antibody nega­tivity was false negative or not. However, cli­nicians dealing, with patients with anti-GBM disease should be aware of the possibility of antibody-negative relapses (if studied by ELISA) and should not hesitate to implement PET along with immunosuppression.

 
   References Top

1.Savage C, Pusey C, Bowman C, et al. Antiglo­merular basement membrane antibody media­ted disease in the british Isles 1980-4. BMJ 1986;292:301-4.  Back to cited text no. 1      
2.Pusey CD. Anti-glomerular basement membrane disease. Kidney Int 2003;64(4):1535-50.  Back to cited text no. 2      
3.Levy JB, Turner AN, Rees AJ, Pusey CD. Long-term outcome of anti-glomerular basement membrane antibody disease treated with plasma exchange and immunosuppression. Ann Intern Med 2001;134:1033-42.  Back to cited text no. 3  [PUBMED]    
4.Turner N, Mason PJ, Brown R. et al. Mole­cular cloning of the human Goodpasture antigen demonstrates it to be the alpha 3 chain of type IV collagen. J Clin Invest 1992;89:592-601.  Back to cited text no. 4      
5.Rees AJ, Peters DK, Compston DA, Batchelor JR. Strong association between HLA-DRW2 and antibody-mediated Goodpasture's syndrome. Lancet 1978;1:966-8.  Back to cited text no. 5  [PUBMED]    
6.Braunwald E, Bristow MR. Congestive heart failure: Fifty years of progress. Circulation 2000;102:14-23.  Back to cited text no. 6      
7.Burkett EL, Hershberger RE. Clinical and ge­netic issues in familial dilated cardiomyopathy. J Am Coll Cardiol 2005;45:969-81.  Back to cited text no. 7  [PUBMED]    
8.Mann DL. Bristow MR. Mechanisms and models in heart failure: The biomechanical model and beyond. Circulation 2005;111:2837-49.  Back to cited text no. 8      
9.Schwartz EE, Teplick JO, Onesti 0, Schwartz AB. Pulmonary hemorrhage in renal disease: Goodpasture's syndrome and other causes. Radiology 1977;122:39-46.  Back to cited text no. 9      
10.Borza DB, Neilson EG, Hudson BG. Patho­genesis of Goodpasture syndrome: A molecular perspective. Semen Nephrol 2003;23: 522-31.  Back to cited text no. 10      
11.Wilson CB. Dixon FJ. Anti-_glomerular base­ment membrane antibody-induced eIOI11CrUlo­nephritis. Kidney II1t 19733:74-89.  Back to cited text no. 11      
12.Ooi JD, Holdsworth SR, Kitching AR. Ad­vances in the Pathogenesis of Goodpasture's Disease: From epitopes to autoantibodics to effector T cells. J Autoimmun 2008:3 1(3 ):295-300.  Back to cited text no. 12      
13.Salama AD, Dougan T. Levy JB. et al. Good-pasture's disease in the absence of circulating anti-glomerutar basement membrane antibodies as detected by standard techniques. Am .1 Kidney Dis 2002;39:1 162-7.  Back to cited text no. 13      

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Correspondence Address:
Yalcin Solak
Department of Nephrology, Selcuk University, Meram School of Medicine, Meram, Konya
Turkey
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