Tacrolimus Therapy in Adults With Steroid- and Cyclophosphamide-Resistant Nephrotic Syndrome and Normal or Mildly Reduced GFR

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.

Factors

Histopathologic types: minimal change nephropathy (n = 6), FSGS (n = 8), and mesangioproliferative glomerulonephritis (n = 5).

Outcomes

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.

Index Words: Tacrolimus, intravenous cyclophosphamide, steroid resistance, idiopathic nephrotic syndrome