Effect of prolonged tacrolimus treatment in idiopathic membranous nephropathy with nephrotic syndrome

Pharmacology. 2013;91(5-6):259-66. doi: 10.1159/000348570. Epub 2013 May 7.


Objective: Tacrolimus has been used for idiopathic membranous nephropathy (IMN) therapy, but most patients who achieved remission showed a high relapse rate when tacrolimus was withdrawn after 6-12 months of therapy. We proposed that a prolonged therapeutic course should help reduce the relapse rate.

Methods: A total of 42 patients with nephrotic syndrome caused by IMN were randomly divided into short-term (n = 20) and long-term (n = 22) groups. All patients received initial treatment with tacrolimus and prednisone for 6 months, and afterward only the long-term patient group was tapered with low-dose tacrolimus until 24 months.

Results: Over 85% of the patients achieved proteinuria reduction, serum albumin improvement and serum lipid recovery; the probability of remission in both groups was over 80% at 6 months. The remission rate was steady at over 80% after 12 and 24 months in the long-term group, but only 50 and 45%, respectively, in the short-term group. Nine patients (45%) relapsed in the short-term group after tacrolimus withdrawal, while not a single patient suffered recurrence in the long-term group. The concentration of tacrolimus remained similar between the two groups at 5-8 ng/ml during the initial 6 months, and was significantly decreased at 12 months compared to 6 months (p < 0.05), along with reduction of oral administration in the long-term group.

Conclusion: Combined therapy of tacrolimus with prednisone can relieve IMN significantly; prolonged tacrolimus treatment at a low blood concentration can alleviate the illness persistently, with a low recurrence rate and gratifying safety.

Publication types

  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Drug Therapy, Combination
  • Female
  • Glomerulonephritis, Membranous / complications
  • Glomerulonephritis, Membranous / drug therapy*
  • Glomerulonephritis, Membranous / metabolism
  • Humans
  • Immunosuppressive Agents / administration & dosage*
  • Immunosuppressive Agents / blood
  • Immunosuppressive Agents / pharmacokinetics
  • Male
  • Middle Aged
  • Nephrotic Syndrome / drug therapy*
  • Nephrotic Syndrome / etiology
  • Nephrotic Syndrome / metabolism
  • Prednisone / administration & dosage*
  • Proteinuria / drug therapy
  • Proteinuria / metabolism
  • Serum Albumin / analysis
  • Tacrolimus / administration & dosage*
  • Tacrolimus / blood
  • Tacrolimus / pharmacokinetics
  • Treatment Outcome


  • Immunosuppressive Agents
  • Serum Albumin
  • Prednisone
  • Tacrolimus