deep venous thrombosis ( dvt ) is a complication well - known to be associated with nephrotic syndrome . in patients with nephrotic syndrome ,
dvt is reported to be observed mostly in the lower extremities , renal veins , and pulmonary arteries [ 1 , 2 , 3 ] . however , there are no reports of dvt developing in the upper extremities of patients with nephrotic syndrome .
we herein report a case in which dvt developed in the left arm during treatment of nephrotic syndrome due to idiopathic membranous nephropathy .
a 56-year - old male was admitted to our hospital in may 2012 for evaluation of nephrotic syndrome .
he had neither a personal nor family history of notable illness such as thrombotic diseases . one month previously , he had presented with bilateral leg edema .
two weeks before admission , he had been diagnosed with massive proteinuria with hypoalbuminemia in another clinic .
physical examination on admission revealed the following : height 168 cm , weight 61.6 kg , blood pressure 124/75 mm hg , pulse rate 80 beats / min with a regular rhythm , and temperature 36.4c .
urinary protein excretion was 11.8 g/24 h. blood analysis , biochemical and serological examination showed a white blood cell count of 7.7  10/l , hemoglobin 15.4 g / dl , platelet count 315  10/l , total protein 3.7 g / dl , albumin 0.8 g / dl , urea nitrogen 15 mg / dl , creatinine 0.96 mg / dl , uric acid 5.8 mg / dl , total cholesterol 460 mg / dl , hemoglobin a1c 5.7% , igg 213 mg / dl , iga 320 mg / dl , and igm 57 mg / dl .
antinuclear antibody , rheumatoid factor activity , hepatitis b and c , and human immunodeficiency virus were all negative .
there was a marked elevation in fibrinogen ( 658.9 mg / dl ) and d - dimer ( 3.1 g / ml ) , and a decrease in antithrombin iii activity ( 66.3% ) .
prothrombin time , prothrombin time - international normalized ratio , and activated partial thromboplastin time were all normal . a fecal occult blood test , computed tomography ( ct ) through the chest and abdomen , and upper endoscopy did not suggest the presence of malignancy .
because our patient initially refused renal biopsy , he was empirically treated with 40 mg / day of prednisolone from the third day after admission , together with continuous intravenous infusion of heparin for prophylaxis of thrombotic complications .
however , he presented no clinical improvement and then received a percutaneous renal biopsy on day 34 .
the specimen consisted of 18 glomeruli showing diffuse and irregular thickening of the glomerular basement membrane with deposition of igg4 , compatible to idiopathic membranous nephropathy stage ii . during prednisolone treatment , he developed a gradually progressive swelling of the upper and lower left arm .
levofloxacin was administrated because phlegmon in the upper extremity was considered , but the swelling worsened .
contrast - enhanced ct on day 54 showed obstructions of the left internal jugular vein and the left subclavian vein by large thrombi ( fig .
the blood levels of protein c , protein s , and 2-glycoprotein i were within the normal ranges .
in addition to the heparin infusion , oral warfarin was added , with prothrombin time - international normalized ratio monitoring between 2 and 3 .
edema of the patient 's left upper limbs gradually improved and disappeared within 1 month .
a contrast ct 89 days after discharge confirmed a significant reduction of thrombi ( fig .
his nephrotic syndrome was in remission , and no further thrombotic symptoms have been seen to date .
the major types of thrombotic complications in nephrotic syndrome cases are dvt , pulmonary embolism , and renal vein thrombosis [ 1 , 3 ] . sometimes the inferior vena cava , and , rarely , the portal , splenic , and superior mesenteric vein can be affected [ 2 , 5 , 6 ] . additionally , a pediatric case of nephrotic syndrome exhibiting thrombosis of the internal jugular vein accompanied by neck pain has been reported .
however , there have been no reports of adult nephrotic cases with thrombosis of the internal jugular vein or of nephrotic cases with thrombosis of the subclavian vein .
upper - extremity dvt is a rarer manifestation of venous thromboembolic disease than that in the lower extremities . in recent years ,
that manifestation has become more commonly recognized because of the increased use of central venous catheters , artificial heart pacemakers , and defibrillators .
mechanical stenosis and venous obstruction by those devices , pulmonary cancer , or thoracic outlet syndrome induce the formation of thrombi in the brachial , axillary , subclavian , and internal jugular vein , or the superior vena cava , resulting in dvt in the upper extremities [ 8 , 9 ] .
furthermore , left innominate vein stenosis due to extrinsic compression by the sternum and arch vessels can cause venous stasis in the upper extremities .
secondary pathogenesis by mechanical stenosis and venous obstruction described above is associated with more than 80% of the cases with upper - extremity dvt .
the rest , which accounts for less than 20% of the cases , is caused by arm exercise or idiopathic conditions . in our case
, there were no clinical symptoms or imaging findings suggestive of structural abnormalities in the venous system of the upper extremities or the neck .
in addition , there was no episode of arm exercise during the hospitalization . in adult cases of nephrotic syndrome ,
most of the venous thromboses occur within 6 months after the diagnosis of nephrotic syndrome , especially in association with the increase of urinary protein and decrease of serum albumin . in the present case ,
dvt occurred approximately 2 months after the diagnosis of nephrotic syndrome when marked proteinuria and hypoalbuminemia had persisted because of poor effects of corticosteroid therapy . in addition , dvt in our case improved alongside the improvement of the nephrotic syndrome after the administration of cyclosporine .
therefore , we believe that the most probable cause of upper - extremity dvt in this case was associated with nephrotic syndrome , which is hardly ever the case , as described above . furthermore , the 2-month duration of oral corticosteroid therapy , which is also an important factor for venous thrombosis , presumably had some influence on dvt in this case .
we consider that rest during hospitalization , especially after renal biopsy , also might have advanced the likelihood of thrombosis .
the first - line therapy of upper - extremity dvt is anticoagulation by heparin or warfarin when dvt involves the axillary or more proximal veins . in the present case ,
the swelling of the upper limb was successfully improved along with a reduction of thrombus size after the administration of warfarin and heparin without causing pulmonary embolism , which is a life - threatening complication of upper - extremity dvt .
in addition to the effectiveness of anticoagulation therapy , the remission of nephrotic syndrome and the tapering of prednisolone might have contributed to the improvement of upper - extremity dvt by reducing the thrombophilic state . in conclusion , to the best of our knowledge , this is the first case report of upper - extremity dvt associated with nephrotic syndrome .
it is necessary to consider upper - extremity dvt when upper - extremity edema is observed in patients with nephrotic syndrome .
the detailed mechanisms of upper - extremity dvt in association with nephrotic syndrome need to be elucidated .
 deep venous thrombosis ( dvt ) in the upper extremities is a rare but important clinical illness , which leads to severe complications such as pulmonary embolism . unlike dvt in the lower extremities , which is mainly induced by a hypercoagulable state , dvt in the upper extremities 
 is usually caused by mechanical obstruction or anatomical stenosis in the venous system . 
 we herein report a case in which dvt developed in the left upper limb during treatment of nephrotic syndrome . 
 this is the first case report of upper - extremity dvt in association with nephrotic syndrome in the literature . 
 our patient was a 56-year - old male with nephrotic syndrome due to idiopathic membranous nephropathy who was treated with 40 mg / day of prednisolone . during corticosteroid therapy 
 , he developed a swelling of the left upper limb . 
 computed tomography revealed thrombi in the left internal jugular vein and the left subclavian vein without anatomical abnormalities in his venous system . 
 thus , he was diagnosed with dvt of the upper extremities . after the initiation of warfarin treatment and subsequent regression of nephrotic syndrome , the swelling disappeared and the thrombi significantly diminished . 
 dvt should be considered when upper - extremity edema is observed in patients with nephrotic syndrome . 
Introduction
Case Report
Discussion
Disclosure Statement