kimura disease ( kd ) presents as a subcutaneous mass , most frequently occurring in the head and neck regions .
the histological characteristics of the disease are hyperplastic lymphoid tissue that contains well - developed lymphoid follicles , marked infiltration of eosinophils , vascular proliferation , and fibrosis .
however , treatments with steroid and immunosuppressive agents were also reported to produce beneficial effects , although discontinuation of steroid often results in recurrence of the masses . in patients with renal manifestations
we herein report the case of secondary membranous nephropathy ( mn ) associated with kd which recovered after surgical resection of the mass .
a 33-year - old woman presented with a soft - tissue mass in her left axillary area .
a percutaneous biopsy was performed , and histological findings showed atypical lymphoid hyperplasia with many eosinophilic infiltrations , which are consistent with kd ( fig .
one year after the diagnosis of kd , a 6-cm , left scapulo - anterior pseudoaneurysm was noted ( fig .
1 ) , which required a stent - graft insertion . following the graft insertion , the size of pseudoaneurysm decreased .
treatment with prednisolone was continued for 1 year , and eosinophilia gradually improved to<500/mm within this period .
one and half year after the diagnosis of kd , the patient presented with a month - long history of foamy urine and a weight gain of 5  kg ; pitting edema of both lower extremities was also observed . upon admission ,
the patient s blood pressure was 98/61  mmhg , white blood cell ( wbc ) count was 7,200/mm ( with 33.8% eosinophils ) , and hemoglobin and platelet levels were 14.5  g / dl and 287,000/mm , respectively .
serum blood urea nitrogen and creatinine levels were within the normal range , with a creatinine clearance rate of 120  ml / min/1.73  m. other laboratory assessments showed normal electrolyte , low serum albumin ( 1.3  g / dl ) , and high cholesterol ( 521  mg / dl ) levels ; complement proteins
( c3 and c4 ) and immunoglobulins ( ig ) a , g , and m were within normal limits .
the patient s virology profile was negative for hepatitis b and c , and her immunologic status was negative for anti - double - stranded dna , antistreptococcal antibodies , cryoglobulins , and rheumatoid factor .
urinalysis was 4 + positive for protein , with five to six red blood cells and five to nine wbcs per high - power field .
the random , spot urinary protein - to - creatinine ratio ( upcr ) was 16.6  g / g , and urine protein electrophoresis showed nonspecific proteinuria .
a light microscopic examination of renal biopsy specimens showed diffuse thickening of the capillary walls , focal , mild hypercellular mesangial cells , and normal - sized glomeruli .
an electron microscopic examination revealed electron - dense deposits in some subepithelial areas and diffuse foot process effacement .
an immunofluorescence microscopic examination revealed granular deposits of igm , igg , c3 , and c1q in the mesangium ( fig .
angiotensin receptor blocker or angiotensin - converting enzyme inhibitor was considered the first - choice treatment .
however , the patient s blood pressure was too low to add antihypertensive drugs to the treatment protocol .
g / g / d to 2.0  g / g / d ) over a 6-month period upon treatment with cyclosporine ( 3.5  mg / kg / d ) and prednisolone ( dose tapered from 0.5  mg / kg / d to 0.17  mg / kg / d within 6 months ) .
however , 1.5 years from the onset of nephrotic syndrome , the patient s random upcr and serum creatinine level increased to 31.0  g / g and 2.11  mg / dl , respectively .
fractional sodium excretion was calculated to be 1.23% . moreover , at the same time , the left subclavian mass had enlarged from an initial 5.8  cm3.6  cm to 7.2  cm7.2  cm , causing occlusion of the left axillary artery .
therefore , surgical resection was necessary , and pathological reports of the excised specimen were consistent with kd .
fortunately , after the mass excision , the azotemia normalized from a serum creatinine level of 2.11  mg / dl to 1.11  mg / dl , and proteinuria resolved from a random upcr of 31.0  g / g to 6.9  g / g within 1 month . after 3 months of follow up , the patient s serum creatinine level was 0.68  mg / dl , and the random upcr was 2.78  g / g ( fig .
kd often follows a benign , chronic course but does not generally resolve spontaneously and shows frequent relapses .
although most patients do not have systemic symptoms , 1216% of these patients have nephropathy that often presents as nephrotic syndrome .
although the pathogenesis of renal involvement and vasculitis in kd is unclear , several immunopathogenetic features have been suggested .
katagiri et al   showed that elevated tumor necrosis factor- , interleukin ( il)-4 , il-5 , and il-13 are found in the peripheral blood cells of kd patients , as well as in the lesion tissue .
this observation supports the fact that t - helper 2 ( th2 ) cytokines play a part in the development of kd .
in addition , lu et al   reported a case of kd secondary to chronic renal graft failure .
because chronic graft rejection is considered to be induced by th2 cell - produced ils , th2 cytokines and overgrowth of the cd4 th2 may play an important role in kd .
many treatment methods were proposed for kd , including corticosteroid , cyclosporine , surgical excision , and radiotherapy ( rt ) .
this implies that t - cell- mediated pathogenesis maybe involved in kd since corticosteroids are known to regulate t - cell proliferation and lymphokine production .
however , recurrence upon termination of steroid therapy was reported in 1540% of the patients .
katagiri et al   reported on the effectiveness of cyclosporine ( 4  mg / kg / d for 3 months followed by 3.5  mg / kg / d for 6 months ) in treating kd .
a previous study showed that rt is more effective than local excision and steroid therapy for the treatment of kd . with the 65-month median follow - up duration
, local control was achieved in nine ( 64.3% ) of the 14 patients in the rt group and in two ( 22.2% ) of the nine patients in the non - rt group . for local mass control ,
however , the role of surgical resection in controlling renal manifestations in patients with kd has not yet been clarified .
this case showed that surgical resection resulted in reversal of not only azotemia but also proteinuria .
a similar reversal case was reported previously with regard to castleman s disease . a patient with a mixed type of localized castleman s disease complicated with nephrotic syndrome underwent removal of two mesenteric lymphoid masses .
after the surgical resection , the proteinuria gradually decreased and disappeared . in patients with castleman s disease having renal complications , immunosuppressants such as prednisolone and azathioprine
are often used , similar to the treatment for kd . however , surgical resection is helpful to reverse the renal function .
both kd and castleman s disease cases imply that some unknown circulating mediators secreted by the primary tumor may cause renal dysfunction .
it has long been postulated that some circulating humoral factors might cause proteinuria in minimal change nephrotic syndrome ( mcns ) and focal segmental glomerulosclerosis ( fsgs ) .
a t - cell - derived humoral factor might induce damages to the glomerular permeability barrier in mcns .
hemopexin is one of the proposed molecules , which can cause proteinuria and glomerular alterations characteristic of mcns . in cases with fsgs ,
post - transplant recurrence of proteinuria and its response to plasmapheresis suggest the role of some plasma factors .
soluble urokinase receptor is detected in the plasma of patients with recurrent fsgs , and this can induce foot process effacement , proteinuria , and fsgs - like glomerulopathy . in our patient ,
surgical mass reduction induced reversal of not only proteinuria but also the serum creatinine level .
although the patient s serum creatinine level gradually increased over a 2-year period , the estimated glomerular filtration rate was fully normalized after surgical mass reduction .
this suggests that renal dysfunction in this patient is possibly caused by a reversible mechanism .
we can postulate that unknown circulating factors secreted by the angiolymphoid hyperplastic mass persistently restrict glomerular filtration possibly without evident chronic damage . because proteinuria slowly improved compared with the serum creatinine level ,
some humoral factors might have induced structural change to the glomerular permeability barrier so that it took more time to recover .
we described the first official case of secondary mn in a kd patient in korea .
this suggests that surgical resection could be preferentially be considered prior to medical treatment in kd patients with renal complications .
 kimura disease ( kd ) is an eosinophilic , granulomatous , benign , chronic inflammatory disease with an unknown etiology . 
 a 33-year - old woman visited our hospital because of a palpable , left subclavian mass , a left scapulo - anterior pseudoaneurysm , and nephrotic syndrome . 
 her subclavian lymph node biopsy examination result was consistent with kd , and results of a renal biopsy indicated secondary membranous nephropathy . 
 after renal histological examination confirmed nephropathy , treatment with prednisolone and cyclosporine was initiated , which was maintained for over 1 year . 
 however , this therapy only provided a transient improvement in proteinuria . 
 one year after commencing the treatment , both proteinuria and azotemia aggravated as the left axillary mass doubled in size . 
 finally , the mass was surgically excised , following which the azotemia rapidly normalized and proteinuria resolved within 1 month . 
 this case shows that tumor resection in a patient with kd with secondary nephropathy may resolve secondary renal manifestations . 
 furthermore , reversible renal dysfunction may be caused by unknown secreted molecules . 
Introduction
Case report
Discussion
Conflict of interest