Urinary excretion of frusemide and its metabolites in a diabetic nephropathy patient

For many years the metabolism of frusemide was a highly controversial subject [1, 2]. We reported that in kidney transplantation patients to whom large doses of frusemide was given, a considerable amount of the metabolites of frusemide proposed, i.e. glucuronidated frusemide (G) and 4-chloro-5sulfamoylanthranilic acid (CSA), was excreted in their urine [3]. The importance of the dosage history on the appearance of CSA in the urine was emphasized. We have received some inquiries as to whether the above findings were specific only to kidney transplantation patients or not. In order to clarify this point, we present here a case who suffered from chronic renal failure due to diabetic nephropathy and was administered large dose of frusemide. Unchanged frusemide, G and CSA were determined by the HPLC methods as previously reported [3]. The case was a 69 year-old male. He had been suffering from diabetes mellitus since 1970 and from liver cirrhosis since 1984. He had been under insulin therapy since 1983 after sulfonylurea therapy for 3 years. The patient was admitted to Osaka University Hospital in March 1986 because of oliguria and dyspnea. On admission, marked ascites was noted. Laboratory data revealed azotemia (blood urea nitrogen 123 mg/dl, creatinine 4.2 mg/dl) and liver dysfunction (GOT53U/1, y-GTP171U/1, ALP 510 U/l, total bilirubin 2.1 mg/dl). Large doses of frusemide (100-500mg i.v. daily) were administered to the patient for more than three weeks. A summary of the data for five consecutive days is shown in Table 1. A considerable amount of CSA (2.78-26.55 mg/day) was excreted in the urine. A positive correlation (r=0.955, P<0.02) was found between the 24 h excretion of unchanged frusemide and sodium excretion. Although the number of the Table 1. Summary of patient data for 5 consecutive days