Outcomes of tacrolimus therapy in adults with refractory membranous nephrotic syndrome: a prospective, multicenter clinical trial.

Abstract

INTRODUCTION:

The treatment of adult refractory idiopathic membranous nephropathy with steroid and other immunosuppressant-resistant nephrotic syndrome can be a significant challenge. The authors investigated the efficacy and safety of tacrolimus (TAC) as a promising regimen.

METHODS:

A prospective, multicenter trial was conducted in 9 nephrology centers from 2006 to 2008. Fourteen patients were enrolled. In conjunction with prednisone, TAC was started at 0.05 mg/kg/d, titrated to achieve a trough blood level of 5 to 10 ng/mL for the first 6 months, then reduced to 4 to 6 ng/mL for the subsequent 6 months. The primary endpoints included complete or partial remission. Secondary endpoints included relapse, change of clinical parameters and adverse events.

RESULTS:

After 12 months, complete remission was achieved in 35.7% of patients and partial remission in 42.9%, yielding a response rate of 78.6%. Proteinuria, serum albumin, cholesterol, triglyceride and low-density lipoprotein were improved significantly (P < 0.001, P < 0.001, P = 0.002, P = 0.01, P = 0.004, respectively). Proteinuria and serum albumin were significantly improved (42.0% ± 13.2%, P = 0.02; 15.2% ± 4.5%, P = 0.01, respectively) even after the first month of treatment. One patient relapsed during the subsequent 6 months of follow-up. Adverse events included 2 cases of infection and 1 case each of hyperglycemia, hand tremor, sudden death (nondrug related) and diarrhea.

CONCLUSIONS:

TAC plus prednisone may be an alternative therapeutic option for steroid and general immunosuppressant-resistant membranous nephrotic syndrome patients, with a favorable safety profile. However, given the limitation of a small number of patients in this trial, further study with a larger number and longer follow-up is needed.

• Authors: Wei Chen, Qinghua Liu, Yunhua Liao, Zhenhua Yang, Jian Chen, Junzhou Fu, Jinli Zhang, Yaozhong Kong, Ping Fu, Tanqi Lou, Zhengrong Liu, Yulian Ji, Zhibin Li, Xueqing Yu
• Journal: The American journal of the medical sciences (Am J Med Sci) Vol. 345 Issue 2 Pg. 81-7 (Feb 2013) ISSN: 1538-2990 [Electronic] United States
• PMID: 22627258 (Publication Type: Clinical Trial, Journal Article, Multicenter Study, Research Support, Non-U.S. Gov't)

Chemical References

• Immunosuppressive Agents
• Prednisone
• Tacrolimus

Topics

• Adult
• Drug Therapy, Combination
• Female
• Follow-Up Studies
• Humans
• Immunosuppressive Agents (administration & dosage)
• Male
• Middle Aged
• Nephrotic Syndrome (blood, drug therapy, immunology)
• Prednisone (administration & dosage)
• Prospective Studies
• Tacrolimus (administration & dosage)
• Treatment Outcome