Tacrolimus as rescue therapy for adult-onset refractory minimal change nephrotic syndrome with reversible acute renal failure

Abstract

Some adult patients with minimal change nephrotic syndrome (MCNS) who are refractory to steroid treatment or combination with immunosuppressive drug developed reversible acute renal failure (ARF) due to persistent severe hypoalbuminemia and proteinuria. It is a challenge to find rescue therapies that are effective and safe in treating such difficult patients. In this prospective observational study, 13 patients with adult-onset MCNS, all unresponsive to treatment with a steroid or a steroid with other immunosuppressive drugs, were studied from January 2005 to February 2009. All patients developed ARF before enrollment. Oral tacrolimus (TAC) was started at 1 mg/day (target trough levels of 3-6 ng/mL) before serum creatinine (SCr) decreased to ≤133 μmol/L, and then increased doses were given (target trough level of 5-10 ng/mL) when SCr decreased to ≤133 μmol/L. Primary outcome variables were remission, and recovery from ARF. Secondary outcome variables were time to recovery from ARF, time to remission, relapse rate, changes in SCr and estimated glomerular filtration rate (eGFR). One patient discontinued TAC due to deterioration of ARF, and 12 patients recovered from ARF. The mean time to recovery from ARF was 15.8 ± 4.4 days. Nine patients (69.2%) experienced complete remission (CR) and two patients (15.4%) experienced partial remission (PR). The mean time to PR and CR was 4.8 ± 2.7 and 9.4 ± 2.3 weeks, respectively. After a mean follow-up of 69.6 months, 36.4% (4/11) of patients who had remission experienced relapses. One patient who was resistant to TAC therapy had a doubling of serum creatinine concentration during follow-up. TAC may be a suitable therapeutic option for treatment of adult-onset refractory MCNS with reversible ARF.