Rifampicin-induced non-responsiveness to corticosteroid treatment in nephrotic syndrome.

The nephrotic syndrome in childhood is usually of the minimal-change variety. At least 95% of children with this lesion respond to adequate corticosteroid treatment. Failure to respond is an indication for renal biopsy to exclude a more sinister glomerular lesion. We report the case of a boy whose failure to respond was not due to progressive glomerular disease but to a drug interaction. Case report A 6-year-old boy, son of an Irish mother and Pakistani father, presented to a local hospital with abdominal pain. He had microscopic haematuria but no proteinuria and the urine was sterile. An intravenous pyelogram and micturating cystogram were normal. The pain subsided spontaneously and no definite diagnosis was made. Six months later he was admitted to the Nottingham Children's Hospital with a four-day history of swelling of the limbs and abdomen. He was oedematous but normotensive. There was pronounced proteinuria and intermittent microscopic haematuria. The results of investigations were as follows: 24-hour urinary protein 1-1 g/l; serum albumin concentration 13 g/l; differential protein clearance 0-10, 0-11 (highly selective proteinuria 0-1); serum C3 1-78 g/l; serum C4 0-56 g/l; serum creatinine 40 jtmol/l (0 45 mg/100 ml); blood urea 4 mmol/l (24 mg/ 100 ml). Nephrotic syndrome was diagnosed. Spontaneous remission occurred over the next nine days. He was then inadvertently given BCG vaccination. Five days later the nephrotic syndrome relapsed. Treatment with prednisolone 2 mg/kg/day was started. To prevent possible dissemination of the vaccine rifampicin plus isoniazid were also given. Over the next four weeks there was no response: oedema and hypoalbuminaemia persisted. By then the dose of prednisolone had been increased to 3 mg/kg/day. A renal biopsy was indicated, but the patient had not become Cushingoid and so the possibility of a drug interaction was investigated. The plasma half life of prednisolone was found to be 1-29 hours. This was estimated by standard pharmacokinetic techniques' measuring the decline in prednisolone plasma concentration after an oral dose on an empty stomach of 10 mg prednisolone dissolved with 10 uCi tritiated prednisolone in 10 ml water. The prescribed corticosteroid was withheld on the day of the study. Rifampicin and isoniazid were then discontinued and treatment with prednisolone continued at the original dose of 2 mg/kg/day. Within 13 days the patient was in remission. Four weeks after discontinuing rifampicin the plasma half life of prednisolone had increased to 217 hours in agreement with mean data obtained in …