Clozapine-associated renal failure: A case report and literature review

Davis, Erica; Kelly, Deanna L.

doi:10.9740/mhc.2019.05.124

Cited by 9 publications

(7 citation statements)

References 15 publications

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“…Three cases described clozapine rechallenge, either during the same admission or 4 years later in 1 case. In all these 3 cases, clozapine-associated renal insufficiency reoccurred, necessitating clozapine discontinuation 28 . In our patient, there may be rather temporal discrepancy between the initiation of clozapine and the development of acute kidney injury as described in the literature review.…”

Section: Discussionmentioning

confidence: 52%

“…In all these 3 cases, clozapine-associated renal insufficiency reoccurred, necessitating clozapine discontinuation. 28 In our patient, there may be rather temporal discrepancy between the initiation of clozapine and the development of acute kidney injury as described in the literature review. In addition, lack of information about urinalysis, which suggests nephritis more than histological confirmation, raised less possibility of clozapine-induced interstitial nephritis.…”

Section: Discussionmentioning

confidence: 60%

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Clozapine-Induced Fever and Plasma Cytokine Changes in a Patient With Schizophrenia

Nakamura¹,

Nagamine²

2022

Clin Neuropharm

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IntroductionClozapine-induced fever is frequently documented in the early stages of administration. Fever during clozapine treatment often presents a clinical challenge, because there are no established guideline to decide when fever is the adverse effect. Although the etiology of clozapine-induced fevers remains unknown, evidence has suggested that fever may develop secondarily to a generalized inflammatory response as a manifestation of the immune-modulating effects of clozapine.Case PresentationWe presented a 59-year-old male patient with a treatment-resistant schizophrenia, who was introduced clozapine for the first time. He became febrile on day 14 at 75 mg/d. He was diagnosed clozapine-induced fever, which was improved by dose reduction on day 27 at 25 mg/d. However, we noticed significant high levels of blood urea nitrogen and serum creatinine on day 29, which resulted in withdrawal of clozapine. Also, we found continuous eosinophilia on day 33. After we provided conservative therapy with appropriate intravenous fluids, his kidney function and eosinophilic counts returned to normal on day 59 and day 53, respectively. The time-sequential changes of levels of interleukin 6 and tumor necrosis factor α suggested that the upregulated cytokines play a role on clozapine-induced fever and subsequent eosinophilia under severe renal failure condition.ConclusionsTo our knowledge, this is the first case presentation of clozapine-induced fever discussing the mechanism, differential diagnosis, and decision making of clozapine treatment focusing on plasma cytokines. If once fever occurs, an extensive medical workup for the fever and a careful systemic medical management should be promptly proceeded to avoid clozapine-associated severe complications.

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Section: Discussionmentioning

confidence: 52%

Section: Discussionmentioning

confidence: 60%

Clozapine-Induced Fever and Plasma Cytokine Changes in a Patient With Schizophrenia

Nakamura¹,

Nagamine²

2022

Clin Neuropharm

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“…A few patients had exposure to the antibiotics because of suspicion of infection, which may have perpetuated the AIN caused by clozapine, although there is no conclusive evidence [ 13 ]. Few patients never regained the baseline kidney function after developing AKI with clozapine [ 6 , 7 , 12 , 15 , 16 ]. About half of the patients in the cases reported were treated with steroids and only three patients needed dialysis which was outlined in Table 3 .…”

Section: Discussionmentioning

confidence: 99%

“…Tubular inflammation with cellular infiltrates and interstitial edema is the distinctive feature noted on the kidney biopsy and establishes the diagnosis.New onset proteinuria, hematuria, and AKI after initiat-ing treatment with clozapine and improvement in the kidney function parameters after cessation of treatment establish the casual relationship. To the best of our knowledge, clozapineinduced AIN has been reported only 16 times in the literature review[5][6][7][8][9][10][11][12][13][14][15][16][17][18][19][20]. The clinical characteristics, investigations, kidney injury outcomes have been summarized in Tables…”

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confidence: 99%

Acute Interstitial Nephritis Induced by Clozapine

Vantipalli

Roy

Koduri³

et al. 2022

J Med Cases

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Acute interstitial nephritis (AIN) classically presents as acute kidney injury most often induced by offending drugs. Less frequently it is secondary to infections, autoimmune disorders, or idiopathic conditions. Development of drug-related AIN is not dose dependent and a recurrence can occur with re-exposure to the drug. We present a 50-year-old male with treatment resistant schizoaffective disorder who developed clozapine-induced AIN, confirmed with kidney biopsy within 2 months of taking this medication. His kidney function improved with removal of the drug and treatment with steroids. However, his kidney function was again significantly impaired when rechallenged with even a lower dose of clozapine a year later. Kidney function returned to baseline after stopping clozapine. Monitoring of kidney function during clozapine therapy is essential to therapy. Prompt diagnosis is imperative as discontinuation of offending agent can prevent acute kidney injury.

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“…It is noted that our patient who had a past medical history of CKD was dosed with gentamicin upon initial fever of 103.1°F on Treatment day 3. Though gentamicin has known nephrotoxic effects and was thus discontinued to prevent further kidney toxicity, many case reports have suggested that clozapine may induce and/or exacerbate renal failure and nephritis [16][17][18][19]. While further research is necessary to quantify the precise risk of clozapine on the kidney function, prior to initiating a trial dose of clozapine, including a thorough history, measuring a patient's kidney function, or eGFR, and BUN/creatinine panel in addition to weekly monitoring of clozapine and ANC levels may reduce exacerbation of CKD.…”

Section: Discussionmentioning

confidence: 99%

Considerations of HLA, Renal Failure, Valproic Acid Use, and Current Treatment Guidelines in Clozapine-Induced Agranulocytosis

Sussman

Epifania

Eng

et al. 2021

Case Reports in Psychiatry

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Clozapine, the choice atypical antipsychotic for refractory schizophrenia, schizoaffective disorder, and bipolar disorder, has been shown to reduce positive and negative symptoms of schizophrenia. Clozapine, though beneficial in reducing the need for hospitalization, rehabilitation, and health care costs, is known as a drug of last resort due to its potential adverse event of clozapine-induced agranulocytosis, which holds a case fatality rate between 4.2 and 16%. Herein, we describe a female patient with longstanding schizoaffective disorder and chronic kidney disease who suffered from clozapine-induced agranulocytosis after failing two other atypical antipsychotics. Retrospective considerations of this case and management highlight risk factors such as HLA status, renal failure, and concurrent valproic acid use which presently do not have official screening, guidelines, or restrictions in place when prescribing clozapine. Additionally, there are no specific clozapine-induced agranulocytosis management recommendations such as G-CSF/filgrastim dose, timing of bone marrow aspirate and biopsy, and use of concomitant valproate. We propose that further comprehensive official screening, monitoring, and guidelines in the prescribing of clozapine, and further guidelines in the treatment of clozapine induced agranulocytosis, could increase the cost-effectiveness of clozapine treatment, and decrease the incidence, and morbidity of this feared adverse event.

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Clozapine-associated renal failure: A case report and literature review

Cited by 9 publications

References 15 publications

Clozapine-Induced Fever and Plasma Cytokine Changes in a Patient With Schizophrenia

Clozapine-Induced Fever and Plasma Cytokine Changes in a Patient With Schizophrenia

Acute Interstitial Nephritis Induced by Clozapine

Considerations of HLA, Renal Failure, Valproic Acid Use, and Current Treatment Guidelines in Clozapine-Induced Agranulocytosis

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