Journal of Medical Cases, ISSN 1923-4155 print, 1923-4163 online, Open Access
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Case Report

Volume 13, Number 7, July 2022, pages 322-329

Acute Interstitial Nephritis Induced by Clozapine


Figure 1.
Figure 1. Periodic acid-Schiff staining displaying moderate mononuclear inflammation (circle) with associated tubular atrophy (arrow).
Figure 2.
Figure 2. Hematoxylin and eosin staining demonstrating moderate mononuclear interstitial inflammation (square) with plasma cells and eosinophil (arrow).


Table 1. Laboratory Values During Hospitalizations
ParametersOn presentationReference range
HPF: high power field.
The first admission labs
  Sodium (mmol/L)141135 - 145
  Potassium (mmol/L)4.03.5 - 5.1
  Chloride (mmol/L)10898 - 106
  CO2 (mmol/L)2723 - 29
  Anion gap (mmol/L)108 - 14
  Blood urea nitrogen (BUN) (mg/dL)98 - 24
  Creatinine (Cr) (mg/dL)1.20.7 - 1.3
  Glomerular filtration rate (mL/min)60> 90
  White blood cells (× 103/mm3)6.54 - 10
  Hemoglobin (g/dL)15.614 - 16
  Platelets (× 103/mm3)152150 - 450
The second admission labs
  Sodium (mmol/L)137
  Potassium (mmol/L)3.5
  Chloride (mmol/L)104
  CO2 (mmol/L)20
  Blood urea nitrogen (BUN) (mg/dL)12
  Creatinine (Cr) (mg/dL)1.61
  Glomerular filtration rate (mL/min)44
  White blood cells (× 103/mm3)6.3
  Hemoglobin (g/dL)14.3
  Platelets (× 103/mm3)224
  Total creatinine phosphokinase (U/L)3235 - 232
  Thyroid-stimulating hormone (mIU/mL)0.90.5 - 4.5
  Serum lithium level (mmol/L)0.90.5 - 1.5
  Urine analysis
    Specific gravity1.010
    Leucocyte esteraseNegative
    White blood cells5/HPF
    Red blood cells14/HPF
The third admission labs
  Sodium (mmol/L)135
  Potassium (mmol/L)4.8
  Chloride (mmol/L)102
  CO2 (mmol/L)20
  Blood urea nitrogen (BUN) (mg/dL)19
  Creatinine (Cr) (mg/dL)2.1
  Glomerular filtration rate (mL/min)33
  White blood cells (× 103/mm3)4.7
  Hemoglobin (g/dL)11.7
  Platelets (× 103/mm3)144
  Urine analysis
    Specific gravity1.026
    Leucocyte esteraseNegative
    White blood cells21/HPF
    Red blood cells8/HPF


Table 2. Clinical Characteristics of AIN From Clozapine
AuthorAge/genderOther antipsychoticsAntibiotic useSymptom onsetFeverCRPSymptoms subsided after stopping clozapineClozapine doseEosinophilia
AIN: acute interstitial nephritis; CRP: C-reactive protein; BID: twice a day; F: female; M: male.
Bassetti et al, 2021 [5]54/FLurasidone, quetiapineYes2 daysYesNot mentionedYes50 mg dailyNot available
McLoughlin et al, 2019 [6]56/FMultiple typical and atypical antipsychoticsYes7 daysYesElevatedYes275 mg dailyPresent
Davis et al, 2019 [7]59/MLithium, fluoxetine, fluphenazine, quetiapine, amantadine, depakoteNo21 daysNoNot mentionedYes62.5 mg dailyPresent
Caetano et al, 2016 [8]25/MMultiple but names not mentionedNo20 daysNot mentionedElevatedYes300 mg dailyNot available
Chan et al, 2015 [9]29/FQuetiapine, sodium valproateYes7 daysYesNot mentionedYes700 mg dailyNot available
Parekh et al, 2014 [10]54/MValproateYes14 daysYesElevatedYes100 mg dailyNot available
An et al, 2013 [11]38/MLithium, valproate, risperidoneNo14 daysYesElevatedYes200 mg dailyNot elevated
Mohan et al, 2013 [12]53/FValproateYes12 daysYesNot mentionedYes200 mg dailyPresent
Kanofsky et al, 2011 [13]28/MLithium, valproate, haloperidol, perphenazine, benztropineYes12 daysYesNot mentionedYes125 mg dailyPresent
Hunter et al, 2009 [14]57/FLithium, valproate, olanzapine, levomepromazine, haloperidolYes2 daysYesElevatedYes12.5 BID (rechallenge)Not mentioned
Siddique et al, 2008 [15]26/MLithium, valproic acid. risperidone, clonazepamNo14 daysYesNot mentionedYes125 mg dailyPresent
Au et al, 2004 [16]33/MValproate, gabapentin, risperidoneYes2 weeksYesNot mentionedYes100 mg dailyPresent
Estebanez et al, 2002 [17]69/MValproateNo3 monthsUnable to obtainUnable to obtainYesUnable to obtainUnable to obtain
Fraser et al, 2000 [18]49/MFlupentixol, thioridazine, mianserinYes35 daysYesNot mentionedYes200 mg dailyNot present
Southall et al, 2000 [19]24/FNot mentionedNo8 daysYesElevatedYes300 mg dailyPresent
Elias et al, 1999 [20]38/FLithium, trifluoperazine, fluphenazine, venlafaxineNo11 daysNoNot mentionedYes125 mg BIDNot mentioned


Table 3. Kidney Function Parameters and Management of AIN From Clozapine
AuthorOnset of renal failureUrine eosinophilsHematuriaProteinuriaRenal imagingRenal biopsySteroidsDialysis needsResidual dysfunction
AIN: acute interstitial nephritis; CT: computed tomography; USS: ultrasound scan.
Bassetti et al, 2021 [5]18 daysNot availableNot availableNot availableNormal size and morphologyNot doneYesNoNone
McLoughlin et al, 2019 [6]Not mentioned in initial exposure, 2 days after rechallengeNot availablePresentNot availableBoth kidney 13.3 cm and mild prominences of both pelvisesAcute interstitial nephritis with 90% plasma cellsYesNoYes
Davis et al, 2019 [7]21 daysNot availableNot availablePresentNot mentionedNot doneNot usedNoYes
Caetano et al, 2016 [8]24 daysNot availableNot availableNot availableNormal kidneysNot doneNo mentionNoNo
Chan et al, 2015 [9]7 daysPresentPresentPresentNormal sized kidneysTubulointerstitial nephritis, eosinophil rich infiltrates with occasional granulomasNoNoNo
Parekh et al, 2014 [10]6 weeksNot availablePresentPresentBilaterally enlarged kidney and increased cortical echogenicityTubulointerstitial nephritisYesNoNo
An et al, 2013 [11]19 daysNot availablePresentPresentCT diffuse swelling of both kidneysNot doneNoYesNo
Mohan et al, 2013 [12]3 monthsNot availableNot availablePresentNot availableAIN with 50% interstitial scarringYesNoYes
Kanofsky et al, 2011 [13]13 daysNot performedNot availablePresentNot availableNot doneYesNoNo
Hunter et al, 2009 [14]1 month in initial exposure, 2 days after rechallengeNot mentionedYesYesNot availableNot doneNoNoNo
Siddique et al, 2008 [15]2 weeksPresentNot mentionedYesNot availableNot doneYesNoAt discharge 1.36
Au et al, 2004 [16]2 weeksNot mentionedYesYesUSS bilateral echogenicityNot doneNoNoAt discharge 4.1
Estebanez et al, 2002 [17]3 monthsUnable to obtainUnable to obtainYesUnable to obtainAcute interstitial nephritisYesNoUnable to obtain
Fraser et al, 2000 [18]42 daysNot mentionedNot mentionedNot mentionedNot mentionedFlorid interstitial nephritisYesYesNo
Southall et al, 2000 [19]8 daysNot mentionedYesYesNot mentionedNot doneNoNoNo
Elias et al, 1999 [20]11 daysNot mentionedNot mentionedNot mentionedNot mentionedMononuclear cell interstitial infiltrate, frequent eosinophils, prominent granulomatous componentNoYesNo