Simultaneous allergic interstitial nephritis and cardiomyopathy in a patient on clozapine

Sir,

Clozapine is an atypical anti-psychotic, currently indicated for patients with schizophrenia who are non-responsive to, or intolerant of, other neuroleptics. Apart from striking sedation and lowered seizure threshold, the most serious side effect is agranulocytosis. It is also rarely associated with myocarditis, cardiomyopathy and allergic interstitial nephritis [1–4]. We report a case of concomitant allergic interstitial nephritis and cardiomyopathy in a patient recently started on clozapine.

A healthy 26-year-old man with bipolar-type schizoaffective disorder presented with bizarre, threatening behaviour and paranoid hallucinations. He was started on valproic acid, lithium, risperidone and clonazepam. Minimal improvement was noted, and after 8 weeks he was gradually switched from risperidone to 125 mg of clozapine. At this point all his blood work was normal and he had good exercise tolerance. After 2 weeks of initiating clozapine, he was transferred to our hospital for a fever of 104.2 F. On admission he was found to be hypertensive (BP 167/107) and tachycardiac. His physical exam was unremarkable, without any signs of fluid overload. He had an elevated serum creatinine (1.5 mg/dl) and WBC (13 000/mm³) with peripheral eosinophilia (820/mm³). His urinalysis showed 2+ protein, 5–10 white cell casts and >50 WBC with significant eosinophiluria. Chest X-ray and urine, blood and CSF cultures were negative. All medications were stopped, and he was given intravenous hydration. Intravenous steroids were started for presumed clozapine-induced interstitial nephritis. On Day 6, his creatinine peaked to 5 mg/dl. He maintained good urine output throughout his stay. A renal biopsy was scheduled but was cancelled because of subsequent complicated course and improving renal function thereafter.

On Day 8 he developed dyspnea and bilateral inspiratory rales. He denied chest pain. Chest X-ray and CT-scan were consistent with pulmonary oedema. His pro-BNP was 27 727 pg/ml. EKG and cardiac enzymes remained normal and viral titers were negative. He was started on intravenous diuretics. An echocardiogram showed moderate global left ventricular dysfunction with an EF of 40% and left ventricular diastolic internal dimension of 5 cm. Next day, he was intubated for respiratory distress from CHF and was transferred to ICU. His respiratory status gradually improved with diuresis and he was extubated after 3 days. Beta-blockers, hydralazine and nitrates were initiated for CHF. At discharge, his eosinophilia resolved, creatinine was 1.36 mg/dl and pro-BNP was 812 pg/ml. Two weeks later, an echocardiogram showed some recovery (EF 50%).

The patient's previous tolerance of all other medications, the chronological onset of his symptoms after initiating clozapine and the fact that there was no previous cardiac history suggest that this case most likely represents clozapine-induced acute interstitial nephritis and cardiomyopathy. While dilated cardiomyopathy is more common with clozapine, a third of patients develop non-dilated cardiomyopathy [5], as seen in our patient. Both the processes are probably related to IgE-mediated hypersensitivity reaction, and hence the simultaneous occurrence is not surprising [1,3,5]. To the best of our knowledge, this is the first case of simultaneous clozapine-induced interstitial nephritis and cardiomyopathy. Clozapine maybe associated with fatal complications in healthy young adults and it is imperative that physicians are aware of these potentially lethal side effects.

Conflict of interest statement. None declared.