idiopathic demyelinating polyneuropathies are not common in the context of acute kidney injury ( aki ) .
poems syndrome ( polyneuropathy , organomegaly , endocrinopathy , monoclonal gammopathy , and skin changes ) is a rare disease characterized by the presence of proliferation of plasma cells with mainly lambda - chain restriction and diverse systemic symptoms occurring over several years , meaning that patients typically visit several clinical departments before obtaining the final diagnosis1 ) . kidney dysfunction is not included in the diagnostic criteria of poems syndrome , but aki can be present with other systemic symptoms2 ) .
a 52-year - old korean man was admitted to this hospital because of abdominal distension and diarrhea .
he had been well until 4 years ago , when he was diagnosed with cerebral infarct at another hospital .
he was a businessman who rarely drank alcohol and had no previous history of medication .
when he was transferred to our hospital 2 years ago , he had the symptom of mild tingling sensation in the left hand .
one and a half years ago , paresthesia of right arm and intermittent difficulties with handwriting developed .
brain magnetic resonance imaging ( mri ) with mr angiography showed neither infarct nor vascular stenosis .
nine months ago , after undergoing health checkups , he was referred to the nephrology , endocrinology , and ophthalmology clinics because of high scr ( 1.52mg / dl ) , elevated thyroid stimulating hormone , and papilledema in both eyes , respectively .
since then , he suffered from gradually increasing paresthesia of both feet , progressing to both ankles and to both lower legs .
he did not feel muscle weakness , but had some difficulties maintaining balance while walking as well as morning stiffness of both arms .
nerve conduction studies showed absent bilateral tibial nerve responses , slow motor responses on bilateral peroneal nerves , decreased sensory responses on bilateral sural nerves on the lower extremities , and slow motor and sensory nerve conduction velocities over the right median nerve .
on cutaneous examination , red papules with diameters of 2 to 6 mm , which developed in the previous year , were scattered on the truncal areas .
hypertrichosis with hyperpigmentation was observed in both hands and lower arms and finger clubbing was present .
the pathologic diagnosis of the papules was glomerular hemangioma . computed tomography ( ct ) of the chest and abdomen
ct of abdomen showed multiple small lymph node enlargements around the aorta as well as a small amount of ascites .
a diagnosis of chronic inflammatory demyelinating polyneuropathy was made and therapy with oral prednisolone was initiated . during the next 2 months , weakness in the patient 's legs increased and he developed a limping gait
. he could not walk on his toes and heels and his perception of vibration decreased in both knees .
the test results for syphilis , hepatitis b and c , and hiv were negative .
tests for autoantibodies such as rheumatoid factor , anti - nuclear antibody , anti - ganglioside antibody , and anti - myelin - associated glycoprotein antibody , were all negative .
tests for vasculitis and anti - phospholipid syndrome were also negative . the levels of serum complements c3 , c4 and immunoglobulins ig g , a , and m were within normal limits .
a small m - peak was noted ( 0.1 g / dl ) in serum protein electrophoresis ( pep ) and no light chain was detected in urine pep .
six months before admission , he was referred to the oncologist for this finding and monoclonal gammopathy of undetermined significance ( mgus ) was a plausible diagnosis .
three months after steroid pulse therapy , his muscle weakness and gait improved , but burning paresthesia persisted .
after 4 months , the steroid dose had been tapered and stopped . after stopping steroid treatment , he noted rapid progression of muscle weakness ( he could not stand from the floor ) and difficulties with walking and balancing .
although his appetite markedly decreased , his body weight increased by 5 kg and leg edema and abdominal girth increased .
he had not taken any nephrotoxic agents including nonsteroidal anti - inflammatory drugs ( nsaids ) .
laboratory results showed an increase in scr to 3.21mg / dl and fena and feurea was 0.24% and 12.3% , respectively .
as abdominal distension increased with ascites he needed therapeutic paracentesis every 4 to 5 days .
light microscopic examination revealed renal cortex and medulla containing about 33 glomeruli , one of which was globally sclerotic .
most glomeruli showed increase in size and cellularity with mild to moderate endocapillary proliferations with diffuse double contours of capillary walls .
there were diffuse interstitial edema and mild interstitial lymphocytes infiltrations with focal tubular atrophy containing hyaline casts destructing of tubular cells .
immunofluorescence study did not show any immunoglobulin or complement deposition or staining for kappa and lambda light chain .
electron microscopic examination revealed that most glomerular capillary lumina were compromised with diffuse duplications of capillary walls and subendothelial widenings with flocculent materials and mesangial interposition .
visceral epithelial cells showed hyperplasia and focal effacement of foot process about 20% of external capillary surfaces .
bone marrow biopsy showed normal bone marrow cellularity ( 60% ) and a normal ratio of the plasma cells ( 2.3% ) .
megakaryocyte hyperplasia was observed and a lymphoid follicle was seen in the bone marrow biopsy .
immunohistochemical staining showed that the majority of plasma cells were positive for lambda light chain ( fig .
the patient 's diagnosis was almost certainly poems syndrome accompanied by recurrent aki ; however , an additional major criterion was required . upon retrospective review of his previous chest and abdomen
ct , we found osteosclerotic bone lesions in thoracic vertebral bones in the chest ct scan ( fig .
3 ) . therefore , poems syndrome was diagnosed based on polyneuropathy , monoclonal plasma cell disorder with iga lambda , sclerotic bone lesion , extravascular volume overload , endocrinopathy , hepatomegaly and skin changes , consistent with proposed diagnostic criteria .
once the diagnosis of poems had been established , the patient was treated with a 28 days cycle of bortezomib and dexamethasone combination followed by autologous hematopoietic stem cell transplantation ( hsct ) at another hospital .
two months after the procedure , the patient showed a notable clinical improvement including polyneuropathy , normal scr ( 0.80mg / dl ) and mobilization was possible with the aid of a walker .
poems syndrome is a rare paraneoplastic syndrome resulting from a proliferative monoclonal plasma cell disorder1 ) .
the diagnosis of poems syndrome must include two mandatory major criteria of ( 1 ) demyelinating polyneuropathy and ( 2 ) monoclonal plasma cell - proliferation ( almost always  type ) .
in addition , one other major criterion must be present ( any one of the following three features : osteosclerotic bone lesions [ almost always present ] , elevated levels of vascular endothelial growth factor [ vegf ] , or castleman disease ) .
in addition , at least one of the following seven minor criteria should be met : organomegaly , extravascular volume overload , endocrinopathy ( excluding diabetes mellitus or hypothyroidism ) , typical skin changes , papilledema , or thrombocytosis , polycythemia1 ) . making a diagnosis can be a challenge as the syndrome is rare and can be mistaken for other neurologic disorders .
the most prominent symptom of this patient was his progressive sensory neuropathy , followed by the development of motor weakness over a period of 4 years .
possible differential diagnoses of polyneuropathy and kidney injury include nutritional deficiency such as pyridoxine or thiamine , human immunodeficiency virus - related neuropathy , amyloid , vasculitis , and paraneoplastic syndrome3 ) .
his laboratory results for viruses and vasculitis revealed no positive findings and his aki had no definite cause .
during the clinical course of this patient , there was no event of renal ischemia caused by nephrotoxic drugs or other systemic hemodynamic change . in the kidney , continuous endothelial injury caused mesangial interposition , mesangial proliferation and finally mesangial sclerosis .
in addition to the glomerular change , ischemic damage caused by obliteration of arterioles and small arteries was proposed to induce recurrent acute kidney injury2 ) .
vegf is a potent microvascular permeability - enhancing mediator and a selective mitogen for vascular endothelial cell8 ) .
therefore , the vegf produced by plasma cells leads to a decrease in intravascular volume by increasing vascular permeability , which may contribute to prerenal aki5 ) .
we might discern from this case that serum and urine pep should be obtained in patients with polyneuropathy and unexplained kidney injury to detect monoclonal gammopathy . however , serum and urine pep of this patient were normal 8 and 6 months ago ( table 1 ) . in poems syndrome ,
the median percent of plasma cells in the bone marrow is less than 5% , which is reflected by the small amount of m - protein , and serum pep often can not detect the m - peak1 ) .
instead , serum and urine ife should be performed to identify the isotype , as these techniques are three times more sensitive in detecting monoclonal immunoglobulin than serum pep4 ) . in kidney biopsy ,
immunofluorescence staining showed no deposition of -light chain and electron microscopy showed no electron - dense deposits .
these are quite different findings from other plasma cell disorders that showed kidney damage with deposition of a monoclonal immunoglobulin4 ) .
instead , renal pathology of this patient showed extensive endothelial cell injury and evidence of increased extravascular permeability .
secretion of vegf from the monoclonal plasma cells in patients with poems syndrome has been suspected to trigger these changes25 ) , but the mechanism remains unknown and must be investigated6 ) .
in contrast to the pathologic lesions , proteinuria was absent and microscopic hematuria was minimal in this patient , which may reflect a relatively intact glomerular basement membrane structure and podocyte functions .
treatment of poems syndrome is directed to target the underlying monoclonal plasma cell disease7 ) and therapeutic strategies for the treatment of multiple myeloma have been reported to show successful patient and renal outcomes and an improvement in morbidities related to treatment67 ) .
as this patient showed bone marrow involvement , he received systemic chemotherapy and had autologous blood stem cell transplantation .
 poems syndrome is a rare paraneoplastic syndrome and there are few reports of polyneuropathy and monoclonal gammopathy associated with kidney dysfunction . here 
 , we report a case of poems syndrome with recurrent acute kidney injury ( aki ) . a 52-year - old man presented with bilateral aggravating paresthesia and latermotor weakness of the lower extremities accompanied by repeated elevation of serum creatinine . 
 the patient was finally diagnosed with poems syndrome on the basis of fulfilling the two mandatory major criteria ( polyneuropathy and monoclonal gammopathy ) , one other major criterion ( sclerotic bone lesion ) , and several minor criteria . 
 a renal biopsy was performed to clarify the cause of aki and showed membranoproliferative glomerulonephritis - like lesions with mesangiolysis and endothelial cell injury . 
 this case illustrates that renal manifestations , not included in the diagnostic criteria for poems , can be apparent before various other systemic symptoms . 