levetiracetam is an anti - epileptic drug used for the treatment of partial and generalized seizures .
we report the case of a 69-year - old woman with previously normal renal function who developed acute granulomatous interstitial nephritis ( gin ) requiring dialysis following levetiracetam consumption .
a 69-year - old woman with a background of early stage chronic lymphocytic leukaemia ( cll ) was noted to have episodes of phrase repetition and instances of memory loss over 1 year .
a magnetic resonance imaging showed mild deep white matter small vessel ischaemic changes with a small old infarct of the right caudate nucleus .
six weeks later , she developed generalized erythematous macular rash ( figure 1a ) and was admitted to hospital for wet dressings .
a skin biopsy confirmed a lichenoid drug reaction and serological markers of vasculitis were negative . at this time , the patient had normal renal function as assessed by a serum creatinine of 49 mmol / l ( 0.55 mg / dl ) and the absence of pyuria , haematuria ( by urinary microscopy ) or albuminuria on a spot urine assessment .
carbamazepine was discontinued and the patient was commenced on levetiracetam 500 mg twice a day and discharged home .
( a ) rash representative of that affecting the entire body after commencement of carbamazepine .
( b ) renal biopsy [ haematoxylin and eosin ( h&e ) stain 250 ] showing diffuse active non - caseating granulomatous tubulointerstitial nephritis .
( c ) h&e stain ( 400 ) demonstrating areas of gin with lymphohistiocytic infiltrate and giant cells .
fourteen days following commencement of levetiracetam , she presented with a 2-day history of severe oral mucositis and feeling generally unwell . on examination , she was afebrile and her blood pressure was 120/65 mmhg .
urinalysis demonstrated + 1 protein only . initial laboratory evaluation revealed a serum urea of 37.1 mmol / l ( 103 mg / dl ) , creatinine of 393
mmol / l ( 4.44 mg / dl ) and an elevated leucocyte count of 26.3  10/l ( 26.3  10/l ) , which were predominantly lymphocytes .
urine microscopy showed > 100  10 leucocytes per litre and < 10  10 erythrocytes per litre .
the urinary albumin : creatinine ratio was 47.6 mg / mmol ( 421.7 mg / g ) . a serological vasculitic screen was negative  in particular , the anti - nuclear anibody , extractable nuclear antibodies , double - stranded dna antibody , anti - neutrophil cytoplasmic antibody and rheumatoid factor were all negative .
computed tomography ( ct ) of the urinary tract showed large kidneys ( left measuring 13.5 cm and right 12.4 cm ) with no hydronephrosis or hydroureter .
fluid overload , worsening azotaemia and metabolic acidosis required treatment with the commencement of haemodialysis via temporary venous catheter .
the renal biopsy contained cortex and medulla with eight glomeruli , two of which were globally sclerosed .
there was a diffuse active inflammation of the tubulointerstitium with non - necrotizing lymphohistiocytic giant cell granulomas as well as associated tubule destruction ( figure 1b and c ) .
ziehl neelsen , auramine and periodic acid - schiff stains were negative for mycobacterium and fungi .
there was no evidence of glomerulonephritis by routine light microscopic , immunofluorescence or electron microscopic examination .
she was initially treated with intravenous methylprednisolone daily ( 500 mg for 3 days ) and the levetiracetam was replaced by sodium valproate 500 mg twice a day .
other more common causes of granulomatous interstitial disease were considered including tuberculosis , which was excluded with a negative urine culture and polymerase chain reaction ( pcr ) .
sarcoidosis was also excluded with a ct scan of the chest and abdomen that did not reveal hilar lymphadenopathy or other features suggestive of sarcoidosis and a normal serum angiotensin - converting enzyme 35
the oral mucositis was secondary to herpes simplex virus as demonstrated on pcr of a swab of an oral lesion and was treated with acyclovir ( dose adjusted for renal impairment , 250 mg intravenously for 3 days ) .
g / l ( 540 mg / dl ) , igm < 10 mg / l ( 10 mg / dl ) , iga = 480 mg / l ( 48 mg / dl ) ] secondary to cll and was given intravenous gammaglobulin ( 24 g daily over 3 days ) .
she had three haemodialysis treatments over 6 days and rapidly recovered renal function with increasing urine output and improved biochemistry ( figure 2 ) .
she had a course of oral prednisone commencing at 50 mg daily ( 1 mg / kg / day ) that was withdrawn gradually over 3 months .
her renal function normalized and her current serum creatinine is 70 mmol / l ( 0.80 mg / dl ) .
renal toxicity secondary to levetiracetam has not previously been reported in adults although there is a single paediatric case report .
the most common side effects of levetiracetam in adults are somnolence , asthenia and dizziness .
it has high oral bioavailability and is excreted predominantly in the urine ( 93% after 48 h ) .
adjustment of the dose is required in renal impairment as its elimination is directly dependent on creatinine clearance . although tubulointerstitial nephritis is relatively common , gin is rare , accounting for 1% of diagnoses in native renal biopsies [ 4 , 5 ] .
the most common causes of gin are sarcoidosis , drugs and infection , particularly tuberculosis .
drugs implicated in cases of gin are varied and include non - steroidal anti - inflammatory drugs , phenytoin , nitrofurantoin and vancomycin .
gin has been seen as a consequence of cll with one case reporting leukaemic cells infiltrating the renal tissue with surrounding t cells and granuloma formation .
this patient had renal failure requiring haemodialysis and a diagnosis of gin confirmed by renal biopsy .
the outcome of patients with gin is generally favourable   but some patients with an insidious presentation may progress to end - stage renal failure .
steroids have been used at varying dosages but due to the infrequency of the disease , there are no defined treatment guidelines .
 granulomatous interstitial nephritis ( gin ) is an uncommon cause of renal failure , which may be caused by drugs . 
 levetiracetam is an increasingly used anti - epileptic medication that is not known to cause renal toxicity in adults . to our knowledge 
 , levetiracetam has not previously been reported as a cause of gin . 
 we report the case of a 69-year - old woman who developed haemodialysis - requiring acute renal failure after commencement of treatment with levetiracetam , which was shown to be gin by renal biopsy . 
 she made a complete recovery with cessation of levetiracetam and treatment with steroids . 
Introduction
Case report
Discussion