a 61-year - old man came to the hospital complaining of bilateral flank pain . left
flank pain began approximately a month earlier , followed by right flank pain 4 days later .
the patient also complained of dyspnea on exertion , urinary frequency , and foamy urine .
he was diagnosed with hypertension 15 years prior and had taken traditional korean herbal medicines , such as acanthopanax , phellinus , licorice root , and steamed red ginseng .
one week before coming to our hospital , he visited a local ophthalmologic clinic for bilateral floater symptoms and was diagnosed with anterior uveitis and treated with systemic and topical steroids .
laboratory tests conducted at the hospital showed a blood urea nitrogen of 26 mg / dl ( the upper limit of normal ) , a serum creatinine of 2.3 mg / dl , and an estimated glomerular filtration rate ( gfr ) of 30.9 ml / min ( normal , 80 to 120 ml / min ) .
a kidney biopsy specimen revealed diffuse interstitial infiltration of lymphocytes and eosinophils and mild tubular atrophy with focal fibrosis of the interstitium ( fig .
systemic administration of prednisolone 1 mg / kg / day was started and slowly tapered ; furosemide and carvedilol were added for blood pressure control .
the patient 's visual acuity was 20 / 20 in the right eye and 20 / 25 in the left eye .
a slit lamp examination showed a mild degree ( 1 + to 2 + ) of inflammatory cells in the anterior chamber of both eyes ; however , synechia of the iris was not observed .
based on these findings , a diagnosis of tinu syndrome was made , and the patient was treated with a topical steroid ( pred forte ; allergan , irvine , ca , usa ) for anterior uveitis .
tinu syndrome is reportedly three times more common in women than in men , with a median age at onset of 15 years ( range , 9 to 74 years ) .
although diagnosis of tinu syndrome is uncommon after 61 years of age , we experienced a patient with such a case . generally , renal involvement in tinu is mild ; however , in our patient the grf decreased to well below the normal range .
failure to detect the disease earlier may have been the possible cause of the renal impairment .
several medications , such as antibiotics and non - steroidal anti - inflammatory drugs , have been reported as a cause of tinu syndrome . using traditional korean medicines for 9 years
tinu is an uncommon disease and is primarily a diagnosis by exclusion ; symptoms are associated with both uveitis and interstitial nephritis .
general symptoms with tinu include fever ( 53% ) , weight loss ( 47% ) , general weakness and malaise ( 44% ) , and anorexia ( 28% ) .
ocular effects seen with uveitis are limited to the anterior chamber in approximately 80% of cases ; both eyes are affected in 77% of cases .
posterior uveitis can sometimes be seen . in most cases ( 65% ) , nephritis precedes uveitis ; however , in 21% of cases , uveitis is present before nephritis , and in 15% the two conditions occur simultaneously .
symptoms associated with nephritis are typical of acute interstitial nephritis , such as flank pain , pyuria ( mainly sterile ) , hematuria , and proteinuria ( which is less severe than seen with nephrotic syndrome )
an association with human leukocyte antigens has been mentioned in some reports , as well as sensitization of common antigens located both in the eye and the kidney as possible pathologic processes of tinu .
in addition to hypersensitivity reactions , the causative drug may act as a hapten , inducing cytokine production or vasculitis .
another possible etiology is cross reactivity of active transporters that are inhibited by carbonic anhydrase inhibitors in both the renal tubule and ciliary epithelium .
eosinophilia , elevated c - reactive protein , elevated erythrocyte sedimentation rate , normocytic normochromic anemia , and abnormal liver function tests are among the possible findings .
in addition , anti - neutrophil cytoplasmic antibody , anti - nuclear antibody , and rheumatoid factor may be positive , and complement levels may be decreased . in the present case ,
all laboratory findings were within the normal range except for kidney function . in the absence of proteinuria and pyuria , detection of beta-2 microglobulin in the urine
the degree of proximal or distal tubular dysfunction may not be directly proportional to the decrease in gfr .
tubulointerstitial edema and infiltration can be observed in kidney biopsy under a light microscopy , while the glomerulus and blood vessels are relatively normal ; this is consistent with the present case .
infiltration with lymphocytes , plasma cells , and histiocytes may be observed , and in 34% of cases , eosinophils .
immunofluorescent findings are negative for antibody or complement in 86% of cases ; similarly , no antibodies or complements were detected in our patient .
the differential diagnosis of tinu includes sarcoidosis , sjogren 's syndrome , behcet 's disease , wegener 's granulomatosis , systemic lupus erythematosis , hyperthyroidism , primary hyperparathyroidism , and infectious diseases ( e.g. , tuberculosis , brucellosis , toxoplasmosis , and herpes ) .
tinu is often not recognized and affected patients often fail to seek medical care , making the prevalence of the disease appear less than in actuality .
topical steroids are commonly recommended as the treatment of choice of anterior uveitis . during the initial attack
, topical steroids are usually sufficient to control the inflammation . based on published case reports , ocular symptoms resolved in 3 months in 44% of cases while symptoms persisted for more than 3 months in 14% of cases
if the inflammation is not controlled with steroids or if steroid use is contraindicated or not tolerated , immunosuppressive agents such as azathioprine or methotrexate may be considered .
a diagnosis of tinu should be considered in patients with idiopathic uveitis presenting with renal disease even in elderly patients .
as tinu is diagnosed by exclusion , a kidney biopsy and a thorough ophthalmologic examination are needed .
once the diagnosis of tinu is made , immediate steroid therapy is necessary together with a collaborative approach to treatment by an internist and an ophthalmologist .
 tubulointerstitial nephritis and uveitis ( tinu ) syndrome is a rare disease entity usually occurring in children . in the present study 
 a case of tinu syndrome in an elderly patient is described and relevant literature is reviewed . a 61-year - old man presented with bilateral flank pain , urinary frequency , and foamy urine . 
 a kidney ultrasonography revealed an increase in kidney parenchyma echogenicity . following a kidney biopsy , 
 the patient was diagnosed with acute tubulointerstitial nephritis . 
 an ophthalmology examination initially performed for floater symptoms , revealed anterior uveitis in both eyes . 
 acute tubulointerstitial nephritis and anterior uveitis in both eyes responded to treatment with oral prednisolone , furosemide , carvedilol , and a topical steroid . 
 tinu syndrome can occur in the elderly and should be part of the differential diagnosis when seeing a patient who has uveitis in association with renal disease ; any therapy should be managed by both an internist and an ophthalmologist . 
Case Report
Discussion