Daily dose of metformin caused acute kidney injury with lactic acidosis: a case report.

BACKGROUND: Metformin-induced lactic acidosis with acute kidney injury is rare but well known. Here we report a case of a Japanese patient taking metformin who experienced severe acute renal failure accompanied with significantly elevated metformin plasma concentrations and signs of lactic acidosis. CASE PRESENTATION: A 60-year-old Japanese man with type II diabetes, who was taking metformin (500 mg three times a day) along with several other medications, visited the emergency department with dizziness, malaise, and oliguria. The initial laboratory test results showed elevated levels of serum creatinine and blood urea nitrogen, although his renal function was normal approximately 2 weeks earlier. His lactate level was raised (4.27 mmol/L), and he was diagnosed with lactic acidosis. Considering the low creatinine clearance and elevated urinary albumin/serum creatinine ratio, urinary N-acetyl-ß-D-glucosaminidase level, and ß2-microglobulin level, the patient was further diagnosed with AKI (in other words, acute tubular necrosis). A renal biopsy performed on day 3 after admission revealed renal tubular epithelium necrosis, supporting this diagnosis. The patient underwent intermittent hemodialysis until he was discharged on day 13. The metformin concentrations on days 3, 5, and 7 were 8.95, 2.58, and 0.16 µg/mL, respectively, which is significantly higher than the maximal steady-state concentration of metformin at the recommended dosage (approximately 1 µg/mL). The calculated pharmacokinetic parameters of metformin suggested poor renal excretion and a low distribution volume at higher metformin levels. Other possible acute kidney injury-causing factors included dehydration, alcohol consumption, and the use of an angiotensin receptor blocker or SGLT2 inhibitor. CONCLUSIONS: This is the first reported case of acute kidney injury possibly caused by high levels of metformin with lactic acidosis in a patient treated with the recommended metformin dose. Thus, the development of metformin-induced acute kidney injury should be considered for patients with several acute kidney injury risk factors who are taking metformin.

Efficacy and Safety of Enzalutamide in a Real-World Cohort of Japanese Patients With Castration-resistant Prostate Cancer.

BACKGROUND/AIM: It has been reported that some adverse events (AEs) of enzalutamide (ENZ) occur more frequently in Japanese patients with castration-resistant prostate cancer (CRPC) due to higher steady-state trough plasma concentrations of ENZ (CSS, ENZ) and its active metabolite (NDE), (CSS, NDE). Thus, we investigated the efficacy, safety, and pharmacokinetics of ENZ in Japanese patients with CRPC. PATIENTS AND METHODS: Fourteen patients were administered ENZ at a standard dose (160 mg/day) or reduced doses (80 or 120 mg/day). Prostate-specific antigen (PSA), AEs, CSS, ENZ, and CSS, NDE were examined. RESULTS: A maximum PSA decrement of ≥50% from baseline was achieved in 92% of patients. AEs were few (>20%) and mild. No differences in CSS, ENZ and CSS, NDE between other ethnic groups in previous literature and our subjects was observed. CONCLUSION: ENZ shows adequate efficacy and safety in Japanese patients with CRPC, even if administered at reduced doses in real-world conditions.