Clozapine-Induced Acute Interstitial Nephritis: A Systematic Review.J Clin Psychopharmacol 2026 May 20. [Online ahead of print]JC
BACKGROUND
Clozapine, an atypical antipsychotic used primarily for treatment-resistant schizophrenia, has been associated with a wide range of side effects, including the rare but serious complication of acute interstitial nephritis (AIN). This systematic review aimed to summarise published cases of clozapine-induced AIN, focusing on clinical presentations, diagnostic findings, treatment approaches, and patient outcomes to improve awareness and management of this adverse reaction.
METHODS
A systematic search of the databases Medline, Embase, Cochrane Library, and PsycINFO was conducted according to PRISMA guidelines. Two independent reviewers assessed each study for eligibility and study quality, and extracted the data.
RESULTS
A total of 13 cases were included in the final analysis. The mean treatment duration of clozapine before AIN onset was 34.8 days. Doses of clozapine ranged from 100 mg to 700 mg daily, with a mean dose of 281.8 mg. Seven cases were noted to be treated concomitantly with sodium valproate. Symptomatology was diverse, and the most common symptom described was fever (8/13 cases). Clozapine was discontinued in all cases. All cases subsequently had resolution of their physical symptoms, and renal function improved in 92% of cases, however one patient developed permanent chronic kidney disease. Other than clozapine cessation, additional treatments utilized included oral corticosteroid therapy, intravenous corticosteroid therapy, and intravenous fluids. Three cases required short-term dialysis therapy. There were no patients requiring long-term dialysis or other renal replacement therapies, and there were no deaths.
CONCLUSIONS
Clozapine-induced AIN is a rare, idiosyncratic adverse reaction with diverse presentations. Prompt recognition and intervention are essential to prevent long-term renal damage. Routine renal function monitoring during clozapine therapy, akin to agranulocytosis screening, could be considered to facilitate early detection and management of this complication.
