Tacrolimus Therapy in Adults With Steroid- and Cyclophosphamide-Resistant Nephrotic Syndrome and Normal or Mildly Reduced GFR
Received 6 October 2008; accepted 28 February 2009. published online 01 May 2009.
Background
In a proportion of adults with steroid-resistant nephrotic syndrome (SRNS), intravenous cyclophosphamide therapy fails. Tacrolimus may be a promising alternative to cyclophosphamide for such patients.
Study Design
Prospective observational study.
Setting & Participants
19 adults with SRNS (6 with minimal change nephropathy, 8 with focal segmental glomerulosclerosis [FSGS], and 5 with mesangioproliferative glomerulonephritis) that did not respond to intravenous cyclophosphamide therapy were studied from January 2003 to September 2006. Oral tacrolimus was administered (target trough levels, 5 to 10 ng/mL) for 24 weeks, then reduced doses were given (target trough level, 3 to 6 ng/mL) for another 24 weeks.
Measurements: outcome variables included complete remission (decrease in daily proteinuria to protein ≤ 0.3 g/d), partial remission (decrease in daily proteinuria to protein < 3.5 g/d but > 0.3 g/d), relapse (increase in daily proteinuria to protein ≥ 3.5 g/d in patients who had partial or complete remission), change in kidney function, and tacrolimus dosing and serum levels.
Results
17 patients completed at least 24 weeks of tacrolimus therapy. Complete remission was achieved in 11 patients (64.7%), and partial remission was achieved in 3 (17.6%). Complete or partial remission was achieved in 5 of 5 patients with minimal change nephropathy, 4 of 7 patients with FSGS, and 5 of 5 patients with mesangioproliferative glomerulonephritis. Primary resistance to tacrolimus was seen in 3 patients (17.6%), all with FSGS. Mean times to achieve partial and complete remission were 5.6 ± 1.4 and 8.0 ± 5.1 weeks, respectively. In patients who achieved complete or partial remission, 35.7% experienced relapse during follow-up (mean, 37.6 ± 13.4 months). Two patients had doubling of serum creatinine levels, both with FSGS.
Limitations
Observational study.
Conclusions
Tacrolimus rapidly and effectively induced remission of SRNS in Chinese adults with disease refractory to treatment with intravenous cyclophosphamide. Treatment may be less effective in patients with FSGS.
Kidney Disease Center, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, Zhejiang Province, People's Republic of China
Address correspondence to Jianghua Chen, MD, Kidney Disease Center, The First Affiliated Hospital, College of Medicine, Zhejiang University, #79 Qingchun Rd, Hangzhou, Zhejiang Province, PR China, 310003
ABSTRACT