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takayasu 's arteritis ( ta ) is an autoimmune disease that accompanies the active inflammation of relatively large - sized vessels like the aorta and its primary branches .
most of the glomerulonephropathies associated with ta show the histological feature of mesangial proliferation , such as membranoproliferative glomerulonephritis , immunoglobulin a ( iga ) nephropathy , focal segmental glomerulosclerosis   and crescentic glomerulonephritis .
membranous glomerulonephropathy ( mg ) is a non - mesangial proliferative glomerulonephropathy , and its association with ta is extremely rare . to our best knowledge , only two case reports have described the association of mg with ta previously [ 6 , 7 ] .
those two patients , however , also showed the feature of systemic lupus erythematosus ( sle ) .
herein , we report a case of mg with undiagnosed ta at the time of kidney biopsy .
this is the first case report that describes a patient who presented as mg associated with ta , but not complicated by sle .
a 54-year - old man with hyperlipidemia developed chance proteinuria during routine medical checkup . within the next 4 months ,
edema in his lower limbs worsened with progression of hypoalbuminemia and increment in urinary protein excretion .
he was referred to the nephrology department of our facility for the evaluation of proteinuria .
five years previously , he felt discomfort and coldness in his left hand and noted difficulty in detecting the peripheral pulse of the left radial artery .
further medical evaluation revealed left subclavian artery stenosis and he underwent percutaneous angioplasty with stent placement .
this episode suggests the possibility of ta , however , the diagnosis was not made at that time . upon admission ,
his temperature was 36.8c , blood pressure 130/81 mm hg ( right arm ) and 128/83 mm hg ( left arm ) , and pulse 70 beats per minute with regular rhythm .
the peripheral arteries ( brachial , radial , popliteal and dorsal pedal ) were palpable without laterality .
laboratory data was as follows : wbc 13,300/l , hb 14.7 g / dl , platelets 36.2  10/l , bun 7 mg / dl , creatinine 0.6 mg / dl , total protein 6.1 g / dl ( -1 4.7% , -2 15.5% ,  15.7% ,  22.7% without monoclonal peak ) , albumin 1.85 g / dl , ldl - cholesterol 160 mg / dl , fasting plasma glucose 96 mg / dl , hemoglobin a1c 5.4% , c - reactive protein ( crp ) 1.23 mg / dl ( normal 0.000.25 ) , erythrocyte sedimentation rate 34 mm / h , immunoglobulin g ( igg ) 870 mg / dl , iga 110 mg / dl , immunoglobulin m ( igm ) 35 mg / dl , c3 178.6 mg / dl ( normal 65.0135.0 ) , and c4 46.1 mg / dl ( normal 13.035.0 ) .
serology for antistreptolysin - o , hepatitis b , hepatitis c , anti - nuclear antibody , anti - double - stranded dna antibody , and mpo and pr3 anti - neutrophil cytoplasmic antibody was negative .
plasma renin activity was 2.6 ng / ml / h ( normal 0.35.4 ng / ml / h ) and plasma aldosterone concentration was 17 pg / ml ( normal 36240 ) . urinalysis demonstrated protein ( 4 + ) without hematuria .
2 ) ; a total of 19 glomeruli were obtained from two pieces of specimen .
the thickness of the glomerular basement membrane ( gbm ) was almost normal and typical spike formation or bubble - like appearance was not obvious .
hyalinosis and moderate thickening of the vessel wall was noted in the intralobular arteries and arterioles .
inflammatory changes on the vascular walls were not apparent . under immunofluorescence microscopy , igg was found in a granular pattern along the gbm .
analysis of igg subclass revealed strong deposition of igg1 and igg4 as well as mild deposition of igg2 .
staining for iga , igm , c3 , c4 , c1q and fibrinogen were negative . under electron
microscopy , foot process effacement and extensive subepithelial electron dense deposits with the projection of basement membrane between adjacent immune deposits were broadly observed .
malignancy survey including chest x - ray , ct scan , testing the stool for blood , upper gastrointestinal endoscopy , measurement of tumor markers ( cea , ca19 - 9 , psa ) demonstrated no significant abnormality .
the patient 's previous medical history of left subclavian artery stenosis strongly implied the presence of ta .
after kidney biopsy , enhanced ct scan showed extensive thickening and enhancement of the vascular wall from the ascending portion to the abdominal aorta , resulting in narrowed and tortuous lumen .
involvement of the brachiocephalic trunk and bilateral vertebral arteries was detected , however , the bilateral renal arteries were unaffected .
considering the previous episode of subclavian artery stenosis , this patient met at least 3 of 6 american college of rheumatology criteria ( decreased brachial artery pulse , blood pressure difference > 10 mm hg and arteriogram abnormality ) for the classification of ta .
ta was diagnosed and oral prednisolone ( psl ) was initiated at a dose of 40 mg / day .
three month later , the urinary protein to creatinine ratio became < 0.15 g / gcr .
enhanced ct scan 1 year later showed improvement of wall thickening in the entire aorta .
psl was gradually tapered to 5 mg daily and he remains free from relapse of both mg and ta ( fig .
ta is characterized by the active inflammation of relatively large - sized vessels like aorta and its primary branches .
kimura et al .   demonstrated the association of hla - b52 and hla - b39.2 with ta in the japanese population .
major histocompatibility class i chain - related a , th17 cells , nk cells or inflammatory cytokines like vegf and il-6 have been clarified to be involved in the pathogenesis of ta , however , the exact pathogenesis remains to be elucidated .
renal complication in ta is conventionally divided into two categories : renovascular disease and glomerular disease .
renal artery stenosis can occur as a consequence of arterial wall thickening due to atherosclerosis secondary to prolonged inflammation .
decreased blood supply into the kidney sometimes results in inappropriate activation of the renin - angiotensin aldosterone system , leading to uncontrollable hypertension .
in the present case , abdominal three - dimensional ct angiography showed no significant stenosis in the bilateral renal arteries , and none of the kidneys were atrophic ( fig .
histologically , narrowing of the lumen of the arterioles and intralobular arteries was mild , and in the vascular walls inflammatory changes were not evident .
two out of 19 observable glomeruli were globally sclerosed , however , the other glomeruli were relatively swollen rather than collapsed , indicating that the blood supply into the patient 's kidneys was maintained .
his blood pressure was within normal range , and plasma renin activity and plasma aldosterone concentration was not elevated .
with respect to glomerulonephropathy associated with ta , only a few clinical reports are currently available [ 2 , 3 , 4 , 5 , 6 , 7 ] .
de pablo et al .   performed retrospective pathological kidney investigation in 25 autopsy cases of ta .
their study showed that 10 out of 25 cases ( 40% ) had diffuse mesangial proliferative glomerulonephritis , while 4 ( 16% ) cases had other forms of glomerulonephritis ( focal segmental glomerulosclerosis , global and focal glomerulosclerosis , segmental necrotizing glomerulonephritis and amyloidosis ) . to date
, only two case reports have described mg associated with ta [ 6 , 7 ] .
notably , the patients in these reports were also complicated by sle   or lupus - like glomerulonephropathy   ( table 1 ) .
complication of ta by sle is also rare , only approximately 20 cases having been reported to date .
the patient with both ta and sle reported by kitazawa et al .   showed intramembranous microspheres and epithelial cytoplasmic processes on the gbm , the findings of so - called podocytic infolding glomerulopathy ( pig ) .
pig is a relatively new disease entity proposed in 2008 and sometimes associated with lupus nephritis class v . in the present case ,
although the criteria for sle have not been met so far in the present case , the possibility of the development of sle in the future should be kept in mind . in japan , approximately 80% of mg in adults are reported to be 
idiopathic , whereas 20% of them have secondary causes ( hepatitis b virus infection , autoimmune disease like sle , malignancies , certain medications , igg4-related disease , hematopoietic cell transplantation and graft - versus - host disease ) .
it is usually difficult to determine a direct causal relationship between mg and assumed secondary causes .
beck et al .   demonstrated that antibodies against phospholipase a2 receptor are detectable in patients with idiopathic mg , but not in patients with secondary form or in healthy individuals .
measurement for antibodies against phospholipase a2 receptor seems useful to determine whether mg is idiopathic or not , however , this procedure remains highly experimental and currently unavailable in routine clinical practice in japan .
several immunohistochemical analyses for the deposition of igg subclasses in glomerular disease have been performed . in mg ,
predominance of igg1 and igg4 suggests the idiopathic form , whereas predominance of igg1 and igg2 suggests the malignancy - associated form and predominance of igg1 and igg3 lupus nephritis . in the present case , analysis of igg subclass revealed ( 2 + ) positivity for igg1 and igg4 and ( 1 + ) positivity for igg2 along the gbm with granular pattern .
general physical examination , measurement of tumor markers , enhanced ct , test for stool blood and endoscopic survey showed no evidence of underlying malignancy . in terms of igg subclass analysis ,
however , it has been reported that igg subclass analysis does not have sufficient specificity for discriminating the idiopathic from the secondary form of mg . in the present case ,
he had a history of left subclavian artery stenosis 5 years before , implying that ta had preceded the onset of mg at least 5 years .
considering the chronology of onset of ta and mg , and the fact that proteinuria had completely disappeared after the remission of ta by steroid therapy , ta might be the secondary cause of mg in the present case . in conclusion , to our best knowledge , this is the first case report that describes mg associated with ta not complicated by sle .
although mesangial proliferative glomerulonephropathy has been predominantly reported , mg , a non - mesangial proliferative glomerulonephropathy , could be manifested with ta .
since information is extremely limited , further reports are needed to shed light on glomerular disease associated with ta .
glomerulonephropathy is a rare complication of takayasu 's arteritis ( ta ) . to date , most glomerulonephropathies associated with ta show the histological feature of mesangial proliferation . 
 membranous glomerulonephropathy ( mg ) is a form of glomerulonephropathy in which the mesangial proliferation is not conspicuous and its association with ta is extremely rare . 
 a 54-year - old man was referred to our hospital due to progressive edema in the lower limbs and nephrotic range proteinuria . 
 five years previously , he underwent percutaneous angioplasty for left subclavian artery stenosis . kidney biopsy revealed stage ii mg . 
 general examination including enhanced ct scan confirmed the presence of ta . 
 he started oral prednisolone therapy at a dose of 40 mg daily . the c - reactive protein level normalized 7 days after the prednisolone therapy . 
 three months later , proteinuria had remitted . though the true relationship between mg and ta was not revealed in present case , considering the fact that complete remission of nephrotic syndrome occurred following the improvement of c - reactive protein level in response to steroid therapy 
 , ta might be the secondary cause of mg . to our best knowledge , only two case reports described the association of mg and ta previously . 
 those two patients , however , also demonstrated the feature of systemic lupus erythematosus in addition to ta . 
 this is the first case report that describes a patient who presented as mg associated with ta , but not complicated by systemic lupus erythematosus .