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Saudi Journal of Kidney Diseases and Transplantation
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CASE REPORT  
Year : 2021  |  Volume : 32  |  Issue : 1  |  Page : 227-231
Anti-glomerular Basement Membrane Disease with Atypical Associations


1 Department of Nephrology, Apollo Hospital, Jubillee Hills, Hyderabad, Telangana, India
2 Department of Pathology, Apollo Hospital, Jubillee Hills, Hyderabad, Telangana, India

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Date of Web Publication16-Jun-2021
 

   Abstract 


Anti-glomerular basement membrane (anti-GBM) disease is a systemic autoimmune disorder characterized by circulating immunoglobulin (Ig) G antibodies to carboxy-terminal, noncollagenous 1 domain of type IV collagen of GBM. Patients typically present with rapidly progressive glomerulonephritis and pulmonary hemorrhage. Anti-GBM disease has been reported to coexist with pauci-immune antineutrophil cytoplasmic autoantibody-positive glomerulonephritis and membranous glomerulopathy. The presentation of anti-GBM disease with thrombotic microangiopathy (TMA) and IgA nephropathy has been rarely described. We herein report two cases of anti-GBM antibody disease, both with crescentic glomerulonephritis and peripheral linear deposits of IgG, one case with clinical and histological findings of associated TMA and other with findings of extensive mesangial IgA deposits. Both the patients were treated with corticosteroid, intravenous cyclophosphamide, and plasma exchange but had poor renal recovery. Association of anti-GBM disease with TMA or IgA nephropathy could open up new pathogenetic mechanism and may help us to prognosticate anti-GBM disease.

How to cite this article:
Malviya PB, Modigonda S, Maitra S, Gowrishankar S. Anti-glomerular Basement Membrane Disease with Atypical Associations. Saudi J Kidney Dis Transpl 2021;32:227-31

How to cite this URL:
Malviya PB, Modigonda S, Maitra S, Gowrishankar S. Anti-glomerular Basement Membrane Disease with Atypical Associations. Saudi J Kidney Dis Transpl [serial online] 2021 [cited 2021 Dec 8];32:227-31. Available from: https://www.sjkdt.org/text.asp?2021/32/1/227/318529



   Introduction Top


Classical Goodpasture’s disease is a relatively rare monophasic illness with pulmonary hemorrhage and crescentic glomerulonephritis. The disease is caused by autoimmunity to the noncollagenous 1 domain of the tissue-specific basement membrane (type IV) collagen chains which are present in kidney and alveolar basement membrane.[1] The pathologic finding of linear staining of immunoglobulins along the glomerular capillary wall by direct immunofluorescence is indicative of anti-glomerular basement membrane (anti-GBM) glomerulonephritis and this is predominantly immunoglobulin G (IgG).[2] Antibodies of anti-GBM are detected in approximately 95% of patients by immunoassays using various forms of purified or recombinant substrates. It has a specificity of >95% and sensitivity of >90%.[2] Anti-GBM antibodies have been identified to coexist in a proportion of patients with antineutrophil cytoplasmic autoantibody (ANCA) associated vasculitis usually peri-nuclear antineutrophil cytoplasmic antibodies (pANCA) and infrequently with membranous nephropathy.[2] We report a rare case of each of anti-GBM disease with coexisting IgA nephropathy and thrombotic microangiopathy (TMA). Very few cases of association with IgA or TMA have been reported in the literature so far.


   Case Reports Top


Written informed consents for the publication of the cases were obtained from the patients.

Case 1 (anti-GBM with TMA)

A 53-year-old male was admitted to our institutionin September 2017 with the presenting complaints of burning micturition, bilateral swelling of legs, facial puffiness, and reduced urine output for 10 days. There was a history of pedal edema and decreased urine output which significantly worsened over the period of 10 days for which he was evaluated outside. Urine examination revealed 1+ albumin, plenty of red blood cells (RBC); serum creatinine of 13.7 mg/dL; ultrasonography (USG) of kidneys, ureters and bladder (KUB) -right kidney: 12.7 cm, left kidney: 10.8 cm. Patient urine output dropped further and he became anuric and he was initiated on dialysis. After admission to this institute, he had one episode of seizure for which he was started on injection levetiracetam. He denied any history of cough, hemoptysis, breath-lessness, fever, skin rash, or joint pain. There was no history of diabetes, hypertension and similar complaints in the past. There was no family history of renal disease. The patient was comfortable at rest, physical and systemic examination was unremarkable except for pallor, bilateral pitting pedal edema, and an elevated blood pressure of 170/100 mm Hg. Fundoscopy was normal; two-dimensional echo showed ejection fraction of 63%, no evidence of left ventricular hypertrophy. CT head was done which was normal. His hemoglobin was 7.3 g/dL and serum creatinine at the time of admission was 6.8 mg/dL. Serum C3 was 0.573 and C4 was 0.207 (within normal limits). Antibody profile was negative for antinuclear antibody, anti-double-stranded DNA, pANCA, and cytoplasmic ANCA (cANCA). The patient had progressive drop in platelet count from 98,000 to 54,000 during the hospital stay with raised actate dehydrogenase 859 and schistocytes of 4%–5%. The quantitative assay of anti-GBM antibody was strongly positive. Serology for human immunodeficiency virus (HIV), hepatitis B virus (HBV), and hepatitis C virus (HCV) was negative. The patient underwent hemodialysis (HD) with alternate sessions of plasma exchange (10 sessions) in view of anti-GBM with suspected TMA. He received three doses of pulse methylprednisolone 500 mg, one dose IV cyclophosphamide 500 mg followed by oral corticosteroid 60 mg/day. His platelet count gradually improved and he underwent renal biopsy.

Renal biopsy was done on day 10 after admission which showed four glomeruli all with fibrocellular crescents and peripheral linear deposits of IgG consistent with anti-GBM antibody disease [Figure 1]. There were associated vessel changes of a TMA with fibrinoid deposits and fragmented RBCs in the wall and intimal myxoid changes ([Figure 1] inset). There was tubular atrophy and interstitial fibrosis over 30% of the cortex sampled.
Figure 1: Twofibrocellular crescents with rupture of the glomerular basement membrane (Jones silver methanamine, ×400). Inset showing features of thrombotic microangiopathy with fibrinoid deposits and fragmented RBC in the wall and intimal myxoid changes of arteriole (H and E, ×400).

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Case 2 (anti-GBM with IgA nephropathy)

A 29-year-old male was admitted in May 2018 with the presenting complaints of burning micturition, bilateral swelling of legs, facial puffiness, and reduced urine output for 15 days. He had a history of low grade intermittent fever not associated with chills and rigors since one month. Patient had history of pedal edema and decreased urine output which significantly worsened over the period and he was anuric three days before presenting to our institution. He also gives history of intermittent headache since 15 days. He denied any history of cough, hemoptysis, breathlessness, skin rash, or joint pain. There was no family history of renal disease. The patient was comfortable at rest, and physical examination showed hypertension and bilateral pitting pedal edema. His cardiovascular, abdominal, and respiratory system examinations were normal. Urine examination revealed 3+ albumin, 10–15 RBC; serum creatinine of 12.7 mg/dL; USG KUB: right kidney – 11.7 cm, left kidney – 11.8 cm. His hemoglobin was 11 g/dL and electrolytes were normal. Serology for HIV, HBV and HCV was negative. Serum C3 was 0.683 and C4 was 0.319 (within normal reference range). Antibody profile was negative for anti-nuclear antibodies, anti-dsDNA, pANCA, and cANCA. His anti-GBM titer was strongly positive (4+). The patient underwent HD with alternate sessions of plasma exchange (12 sessions) in view of anti-GBM disease. He received three doses of pulse methylprednisolone 500 mg, one dose of IV cyclophosphamide 500 mg followed by oral corticosteroid 60 mg/day.

Renal biopsy was done on day 3 of admission which showed features of crescentic glomerulonephritis with 100% crescents and peripheral linear deposits of IgG. The underlying tuft showed mesangial and endo-capillary hypercellularity with significant mesangial deposits of IgA suggestive of an associated IgA nephropathy (M1, E1, S0, and T1). Tubular injury, moderate tubular atrophy (40%), and moderate interstitial inflammation were seen. The blood vessels were unremarkable [Figure 2] and [Figure 3].
Figure 2: Two glomeruli showing fibrocellular crescents (PAS, ×400).

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Figure 3: Immunofluorescence showing linear deposits of IgG and granular deposits of IgA in mesangium.

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   Discussion Top


Anti-GBM disease is a systemic autoimmune disorder characterized by circulating IgG antibodies to type IV collagen of GBM. Patients typically present with rapidly progressive glomerulonephritis and pulmonary hemorrhage. The most common association of anti-GBM has been seen with ANCA (double positivity). It had been seen that patients of double positivity have better patient survival but no change in renal survival.[3] Our patients had no clinical/serological evidence of ANCA-associated vasculitis.

We have discussed here two rare case reports of anti-GBM disease one which is associated with TMA and other with IgA nephropathy. TMA is characterized by a clinical presentation with thrombocytopenia, microangiopathic hemolytic anemia, and organ injury.[4] According to current understanding TMA is classified into primary (hereditary and acquired), secondary and infection-associated TMA.[5] TMA can also in association with IgA nephropathy, ANCA-associated vasculitis, membranous nephropathy, FSGS and MPGN or C3 gomerulonenephritis,[6] but its association with anti-GBM disease is rare. Momose et al[7] reported a case of fibrillary glomerulo-nephritis where there was associated TMA and anti-GBM disease. This patient received 36 sessions of plasma exchange with poor renal recovery. Another case report by Gowrishankar et al[8] had shown anti-GBM disease with TMA and bilateral lung opacities but the biopsy, in this case, did not show crescents and it progressed to end-stage renal disease. Our patient had clinical, serological, and histopathological evidence of TMA with anti-GBM disease. The patient received 12 sessions of plasma exchange, IV cortico-steroids, IV cyclophosphamide and HD. Patient was dialysis dependent at one month follow up.

IgA nephropathy is the most common mesangioproliferative glomerulonephritis with abnormal O-glycosylation of the IgA1 hinge region being the key pathogenic factor. A number of diseases having association with IgA nephropathy have been described.[9] Patients of IgA nephropathy usually present with a history of upper respiratory tract infection and microscopic or macroscopic hematuria Liver disease or inflammatory bowel disease are often associated with IgA nephropathy. About 10%–15% of patients of anti-GBM have deposition of IgA or IgM or rarely IgM alone.[10] Previous case reports of anti-GBM disease with IgA deposition in kidneys suggest two possibilities. Firstly, IgA can be the direct causative factor for anti-GBM, or it can have casual association with anti-GBM disease. Linear deposition of IgA along the glomerular basement membrane has been reported in anti-GBM disease[11],[12] but deposition in the mesangium, as in our case suggests underlying IgA nephropathy.[13],[14] Previous authors have speculated that IgA deposition in the glomeruli may expose cryptic antigens of the GBM and trigger the release of inflammatory mediators leading to anti-GBM disease.[14] A case report by Ge et al[13] described anti-GBM with granular IgA deposits in mesangium with reversible posterior leukoencephalopathy syndrome. Despite adequate immunosuppression, and plasma exchange this patient did not improve as also seen in our case. This patient went for transplant and post-transplant biopsy at five month shown no recurrence.

In both our cases, it is possible that the kidneys were affected by dual pathology in the form of anti-GBM antibody disease superimposed with TMA in one and associated with background IgA nephropathy in other. The biopsy picture in both our cases had revealed these associations and brought it to our clinical attention. Despite adequate immunosuppression and plasma exchange in both, the outcome was poor. Similar findings were observed in previous case reports suggesting anti-GBM disease with associated TMA or IgA nephropathy may have poor prognosis.

Conflict of interest: None declared.



 
   References Top

1.
Turner N, Cui Z. Oxford Textbook of Clinical Nephrology. 4th ed. Oxford, United Kingdom: Oxford University Press; 2016. p. 599.  Back to cited text no. 1
    
2.
Turner N, Cui Z. Oxford Textbook of Clinical Nephrology. 4th ed. Oxford, United Kingdom: Oxford University Press; 2016. p. 600-4.  Back to cited text no. 2
    
3.
File I, Pucsok K, Trinn C, Ujhelyi L, Balla J, Mátyus J. Clinical consequence and significance of anti-neutrophil cytoplasmic antibody positivity in anti-glomerular basement membrane disease. Orv Hetil 2013;154:1696-701.  Back to cited text no. 3
    
4.
Moake JL. Thrombotic microangiopathies. N Engl J Med 2002;347:589-600.  Back to cited text no. 4
    
5.
Brocklebank V, Wood KM, Kavanagh D. Thrombotic microangiopathy and the kidney. Clin J Am Soc Nephrol 2018;13:300-17.  Back to cited text no. 5
    
6.
Manenti L, Gnappi E, Vaglio A, et al. Atypical haemolytic uraemic syndrome with underlying glomerulopathies. A case series and a review of the literature. Nephrol Dial Transplant 2013;28:2246-59.  Back to cited text no. 6
    
7.
Momose A, Nakajima T, Chiba S, et al. A case of fibrillary glomerulonephritis associated with thrombotic microangiopathy and anti-glomerular basement membrane antibody. Nephron Extra 2015;5:30-8.  Back to cited text no. 7
    
8.
Gowrishankar S, Patro A, Maitra S. Anti-GBM antibody disease sans crescents with thrombotic microangiopathy. NDT Plus 2009;2:282-4.  Back to cited text no. 8
    
9.
Johnson RJ, Feehally J, Floege J. IgA nephropathy and Henoch-Schönlein nephritis. In: Comprehensive Clinical Nephrology. 5th ed. Philadelphia: Saunders; 2014. p. 270.  Back to cited text no. 9
    
10.
Johnson RJ, Feehally J, Floege J. IgA nephropathy and Henoch-Schönlein nephritis. In: Comprehensive Clinical Nephrology. 5th ed. Philadelphia: Saunders; 2014. p. 281.  Back to cited text no. 10
    
11.
Moulis G, Huart A, Guitard J, Fortenfant F, Chauveau D. IgA-mediated anti-glomerular basement membrane disease: An uncommon mechanism of Goodpasture’s syndrome. Clin Kidney J 2012;5:545-8.  Back to cited text no. 11
    
12.
Ke CL, Wen YK, Chen ML. IgA variant of anti-glomerular basement membrane glome-rulonephritis associated with pulmonary hemorrhage and microangiopathic hemolytic anemia. Ren Fail 2012;34:657-60.  Back to cited text no. 12
    
13.
Ge YT, Liao JL, Liang W, Xiong ZY. Anti-glomerular basement membrane disease combined with IGA nephropathy complicated with reversible posterior leukoencephalopathy syndrome: An unusual case. Am J Case Rep 2015;16:849-53.  Back to cited text no. 13
    
14.
Annamalai I, Chandramohan G, Srinivasa Prasad ND, Fernando E, Sujith S. Rapidly progressive glomerulonephritis due to anti-glomerular basement membrane disease accompanied by IgA nephropathy: An unusual association. Saudi J Kidney Dis Transpl 2017;28:1404-7.  Back to cited text no. 14
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Correspondence Address:
Prashant Bharat Malviya
Department of Nephrology, Apollo Hospital, Jubillee Hills, Hyderabad, Telangana
India
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DOI: 10.4103/1319-2442.318529

PMID: 34145136

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