the main clinical presentation of renal amyloidosis is massive proteinuria , often in the nephrotic range , and it is important for clinicians to suspect amyloidosis in the course of the investigation of proteinuria . however , some cases with renal amyloidosis are characterized by progressive renal dysfunction rather than proteinuria ; a proteinuria - absent case has even been reported ( 1 ) . because its clinical manifestation varies , probably according to the site and degree of amyloid deposition ( 2 ) , renal amyloidosis has the potential to be clinically misdiagnosed in patients without a large amount of proteinuria . we herein report a case of biopsy - proven systemic amyloid light - chain ( al ) amyloidosis who had mild proteinuria and severe renal dysfunction and was initially suspected of having interstitial nephritis caused by sjgren 's syndrome . a 70-year - old japanese woman visited our department with a complaint of leg edema . she had no history of hypertension or diabetic mellitus , but she had experienced a transient cardiac failure episode four months prior that could not be further investigated . when she had received left femoral head replacement surgery for the fracture three months prior , anemia and an elevated serum creatinine level of 1.89 mg / dl had been noted . she was positive for antinuclear antibody and had slight hypocomplementemia , so she was referred to the division of rheumatology at our hospital . she did not meet the criteria of systemic lupus international collaborating clinics ( slicc ) classification for diagnosing systemic lupus erythematosus ( 3 ) . she had a complaint of dry eye but did not have dry mouth symptoms . since she did not show any symptoms or laboratory data suggestive of other autoimmune diseases , such as rheumatoid arthritis , dermatomyelitis , or scleroderma , the finding of positive anti - ss - a antibody in association with a positive gum test and schirmer 's tear test prompted a diagnosis of primary sjgren 's syndrome . her serum creatinine level had increased to 4.53 mg / dl , so she was admitted to the division of nephrology for further investigation . on admission , her height was 154.0 cm , weight 44.9 kg , blood pressure of 124/70 mmhg , pulse rate of 74/min , and body temperature 36.5c . a physical examination revealed no remarkable findings except for mild pitting edema in both legs . a urine examination showed 2 + protein , 1 + occult blood in the dip stick , and 0.4 g of protein in 24-hour urine collection . the levels of urinary low - molecular - weight proteins ( alpha 1-microglobulin and beta 2-microglobulin ) were markedly elevated , and urinary n - acethyl--d - glucosaminidase ( nag ) was slightly elevated , indicating the presence of tubulointerstitial damage . anti - neutrophil cytoplasmic antibody was negative , and serum immunoelectrophoresis , used in the diagnostic evaluation for al amyloidosis , showed no monoclonal components . therefore , we strongly suspected interstitial nephritis due to sjgren 's syndrome as a possible cause of the rapid deterioration of the renal function . gfr : glomerular filtration rate , mpo - anca : myeloperoxidase - anti - neutrophil cytoplasmic antibody , pr3-anca : proteinase 3-anti - neutrophil cytoplasmic 
 antibody the values in parentheses show the normal range . renal biopsy performed a week after admission showed 7 globally sclerosed glomeruli out of 20 , 2 glomeruli with mild mesangial expansion , and the remaining 11 glomeruli had massive nodular lesions at the vascular pole , extending to the mesangial areas with weak positive periodic acid - schiff ( pas ) staining ( fig . the arteries and arterioles were replaced with weakly pas - positive deposits throughout the layers , and their lumen were severely stenosed or occluded ( fig . tubular atrophy and interstitial fibrosis with mononuclear cell infiltration were found in about 70% of tubulointerstitial areas , with the occasional presence of tubulitis ( fig . congo - red staining showed positivity in the areas corresponding to weakly pas - positive deposits ( fig . iga , igg , c1q , and c3 were negative , but igm was positive at the nodular regions of glomeruli . kappa light chain was negative , but lambda light chain was strongly positive in the arterial walls and the glomeruli ( fig . a : periodic acid - schiff ( pas ) staining shows massive nodular lesions at the vascular pole of glomeruli extending to the mesangial areas with weakly positive pas staining . the arteries and arterioles were replaced with weakly pas - positive materials throughout the layers , and the lumen was severely stenosed or occluded . atrophic tubules and interstitial fibrosis were present , with moderate mononuclear cell infiltration and slight tubulitis ( original magnification , 200 ) . b : congo - red staining shows positivity in weakly pas - positive lesions in glomeruli , arterioles , and small arteries , as well as in some interstitial areas ( original magnification , 200 ) . c : immunofluorescence for lambda shows positivity on massive nodular lesions at the vascular pole of the glomerulus extending to the mesangial area and small arteries . g : glomerulus , v : vasculature ( original magnification , 200 ) d : electron microscopy shows amyloid deposition at the mesangial area ( * ) , with randomly disposed amyloid fibrils on higher magnification ( inset , bar=0.5 m ) . repeated immunofixation electrophoresis using concentrated urine and serum immunofixation turned out to be positive for bence jones lambda - type monoclonal proteins . the serum kappa / lambda free light chains ratio was 0.18 , indicating elevated lambda light chain . gastroduodenal biopsy could not prove amyloid deposition , probably because the biopsy specimens did not contain the muscular layer . 2a ) and granular sparkling sign of the thickened ventricular septum ( 16 mm ) with severely impaired systolic / diastolic function on cardiac ultrasonography ( fig . in addition , abdominal wall fat aspiration was positive for direct fast scarlet staining in the small artery walls ( fig . given that the renal function continued to deteriorate , hemodialysis was introduced seven weeks after admission . chemotherapy with melphalan and dexamethason was initiated . the kappa / lambda ratio normalized to 0.57 , but her renal function did not improve , and she ultimately began maintenance hemodialysis . b : echocardiogram showing thickened ventricular walls and a thickened ventricular septum with nonhomogenous granular sparking echoes . lv : left ventricle , rv : right ventricle , la : left atrium , ao : aortic outflow direct fast scarlet staining shows positivity in the small artery walls in abdominal wall fat tissue ( original magnification , 200 ) . the major renal histopathological findings of sjgren 's syndrome are acute or chronic tubulointerstitial nephritis , with chronic tubulointerstitial nephritis the most common presentation associated with urine - concentration and urine - acidification defects ( 5 ) . our case had no episodes of nocturia implicating urine - concentration impairment , and her renal failure was so severe that the existence of a urine - acidification defect could not be evaluated . however , the extremely high levels of urinary low - molecular - weight proteins with mild proteinuria ( 0.4 - 0.5 g / day ) and microscopic hematuria in our case strongly indicated that the major damaged site was the tubulointerstitial area . low concentrations of lambda - type monoclonal proteins in this patient may be the reason why serum immunoelectrophoresis did not show monoclonal components before renal biopsy . however , it is unknown whether or not this relates to primary sjgren 's syndrome or the 4% plasma cells in the bone marrow . roughly 97 - 100% of al and aa renal amyloidosis patients have glomerular amyloid deposition ( 6 - 9 ) . several reports have shown that massive or global deposition of amyloid in the glomeruli was associated with the level of proteinuria ( 2,6,7 ) . another report on aa amyloidosis showed that the distribution pattern of glomerular amyloid deposits was closely associated with the level of proteinuria ; mesangiocapillary deposition tends to have massive proteinuria whereas hilar deposition has a lower proteinuria level ( 10 ) . ( 11 ) suggested a good correlation between glomerular amyloid distribution patterns and chemical types of amyloidosis . in the mesangial nodular pattern , deposited amyloid was almost invariably aa protein , whereas cases with mesangio - capillary and epimembranous patterns cases were al amyloidosis - predominant . unlike in the present case , the hilar pattern is often seen in patients with aa amyloidosis . amyloid deposition is not limited to the glomeruli but also occurs in the vasculature and the interstitial area of the kidney . as such , an impaired renal function is often associated with a mild degree of proteinuria . a previous case with vascular - limited al amyloid deposition similarly , predominant aa amyloid deposition in the vasculature with vascular - pole - limited deposition in the glomeruli was associated with a low proteinuria level , and the impairment of the kidney function was the initial clinical clue of renal involvement ( 10 ) . kidney dysfunction was reported to be associated with inflammatory cell infiltration and tubular casts ( 2 ) , tubular atrophy , and arteriolar amyloid deposition ( 10 ) . reported that cases with severe vascular amyloidosis presented with a high degree of inflammatory cell infiltration , as the proximity of vascular amyloid deposits to the capillaries tends to cause inflammatory reactions ( 7 ) . dominant sites of amyloid deposition other than the glomeruli are often described in aa amyloidosis . cases with aa amyloidosis had high grades of tubulointerstitial and vascular damage ( 13 ) . amyloid deposition was limited around vessels and absent in the glomeruli in 28.9% of aa amyloidosis patients ( 14 ) . reported that there were no differences in the distribution of amyloid depositions between al and aa types ( 6 ) . some chemicophysical properties of the amyloid fibrils have been suggested to be associated with the distribution patterns within the renal compartments , but the precise mechanism has not been established ( 6 ) . in our case , vascular depositions of al amyloid , including glomerular hilar depositions extending to mesangial areas , were the dominant feature , accompanied by severe tubulointerstitial damage . the findings did not support tubulointerstitial nephritis caused by sjgren 's syndrome or light - chain cast nephropathy . ischemic changes due to progressive amyloid deposition in the vasculatures may be the major cause of the deterioration of the renal function in our case . there have been several reports concerning the coexistence of primary sjgren 's syndrome and amyloidosis . however , most of them were nodular amyloidosis , mostly localized to the dermis ( 15 ) or lung ( 16 ) . to the best of our knowledge , there has been only one report of a concomitant diagnosis of sjgren 's syndrome and systemic al amyloidosis ( 17 ) . unfortunately , the lack of lacrimal or salivary gland biopsy could not preclude the possibility of the involvement of amyloid deposition in the targeted tissues in our case . in summary , we herein reported a case of systemic al amyloidosis with renal involvement , predominantly in the vasculatures , that had been strongly suspected of being interstitial nephritis due to sjgren 's syndrome before a pathological examination by renal biopsy . clinicians should take into account the possibility of renal amyloidosis , even if patients show a clinical presentation of interstitial nephritis without massive proteinuria .
we report a 70-year - old woman with sjgren 's syndrome who had severe renal dysfunction with mild proteinuria and elevated urinary low - molecular - weight proteins . based on these clinical presentations , interstitial nephritis due to sjgren 's syndrome 
 was strongly suspected . 
 unexpectedly , renal pathology revealed amyloid light - chain ( al ) lambda - type depositions predominantly in the vasculatures with severe tubulointerstitial damage . 
 concentrated urine immunofixation was positive for bence jones lambda - type monoclonal proteins . given the involvement in other organs , systemic al amyloidosis was diagnosed . 
 the patient underwent chemotherapy , but hemodialysis was ultimately instituted . 
 it should be remembered that renal amyloidosis occurs as a clinical presentation of interstitial nephritis .