Acute Interstitial Nephritis Induced by Clozapine

Abstract

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.

Involvement of Extracellular Vesicles in the Proinflammatory Response to Clozapine: Implications for Clozapine-Induced Agranulocytosis

“…Together, these findings support the working model that innate immune activation, a hypothesized prerequisite to IDR progression, is unique to clozapine, while lymphopenia occurs via an independent mechanism that is conserved among analogues. Clozapine-altered chemistry parameters (e.g., ALT, BUN) may be relevant for other adverse effects including liver injury (Wu Chou et al, 2014;Oates et al, 2018;Gunther and Dopheide, 2023) and acute interstitial nephritis (Davis and Kelly, 2019;McLoughlin et al, 2022;Vantipalli et al, 2022), and these IDRs may share early mechanisms. Indeed, with repeat clozapine dosing, increased hepatic covalent binding (Gardner et al, 2005;Ip and Uetrecht, 2008) and inflammatory changes in the liver (Jia et al, 2014;Zlatkovic et al, 2014;Sernoskie et al, 2023) and the kidney (Mohammed et al, 2020) have been observed.…”

Clozapine-Induced Granulomatous Interstitial Nephritis: A Case Report

“…The median age of the patients varies from 25 to 40 years of age [4,5]. The disease is more common in women as compared to men [3,6]. A few cases have also been reported in older individuals and in male patients [7].…”

“…Prednisone has also been studied as a mainstay of treatment with prednisone taper providing an adequate response in most of the patients [3]. In rare cases, the kidney function might not completely normalize [6].…”

“…Granulomatous interstitial nephritis is a relatively rare condition detected in about 0.5 to 0.9% of all renal biopsies and accounts for 6% of patients diagnosed with tubulointerstitial nephritis [1,2]. Clozapine-induced granulomatous interstitial nephritis is a relatively rare phenomenon that has not been extensively reported in the literature [3]. We present a case of a 56-year-old female who presented with syncope and worsening renal function.…”

Rethinking Clozapine: Lights and Shadows of a Revolutionary Drug

“…On the other hand, urinary retention and urinary incontinence are rare adverse effects [214], while sporadic cases of acute interstitial nephritis have been reported. Indeed, one of the most recent reports in the literature described the case of a 50-year-old schizoaffective man who developed acute interstitial nephritis induced by Clozapine, 300 mg daily, and recovered after the drug's interruption [215].…”