A Case of Clozapine Induced Acute Renal Failure
The adverse reaction to clozapine occurred in a 38-year-old Korean male patient with treatment-resistant bipolar I disorder. He was diagnosed with bipolar I disorder at around the age of 19 and had been treated with many different antipsychotics over the past 20 years. His last medication before clozapine was lithium, valproate and risperidone which brought his mood symptom into remission. However, during his outpatient clinic follow-up, he continuously complained of hand tremor and eventually lithium was stopped. Then his mood became elated and he had to be hospitalized for the treatment of his manic episode. After being hospitalized, he received higher dosages of valproate and risperidone, but his manic symptom showed no improvement even after a month. Finally, medication change to clozapine was decided. Anti-manic effect of clozapine monotherapy has been confirmed by several clinical trials (Kimmel et al., 1994; Frye et al., 1998; Suppes et al., 1999). When 22 patients with bipolar disorder were treated to clozapine monotherapy, 77.3% showed response. 60 patients diagnosed with treatment resistant bipolar disorders and schizoaffective disorders were treated with clozapine monotherapy and the response rate was 60% after 6 months and 83% after 2 years. Therefore, we decided this patient should be treated with clozapine monotherapy, as it was a case of treatment resistant bipolar I disorder patient. Clozapine was started from 12.5 mg and were increased up to 200 mg in 14 days. On the 14th day, the patient developed hyperthermia (39.2℃) which was subsided after 6 days. On the 19th day, he suddenly gained 8 kgs of weight, and developed generalized edema and urinary difficulty. On laboratory results, he showed signs of acute renal failure: CBC results showed no eosinophilia but WBC was checked 15300/uL, and routine chemistry showed BUN 32.3 mg/dL, creatinine 4.1 mg/dL, ESR 35 mm/h and CRP 29.74 mg/dL. Protein 2+, blood 3+, RBC and WBC were found in urine analysis.\nNo specific finding was found in EKG and echocardiography. Abdomen CT showed diffuse bowel wall thickening with some distension, minimal enterocolitis and diffuse swelling of both kidneys which were evidences for ARF. Chest X-ray showed atelectasis and pleural effusion at both of his lower lungs.\nImmune antibody test showed no evidence systemic disease, and the blood and urine culture were negative. Renal biopsy was not performed due to patient's refusal. The only medication that was recently changed was clozapine, and lithium and valproate level were all within therapeutic range. Under the impression of acute renal failure due to clozapine, clozapine was stopped and the patient received hemodialysis 6 times a week. In 10 days, the patient could self-urinate and laboratory results showed normalized kidney function with BUN 20.7 mg/dL and creatinine 1.2 mg/dL. Even though renal biopsy couldn't be performed due to patient's refusal, diagnosis of acute renal failure induced by clozapine could be made under clinical circumstances.