Tacrolimus versus Cyclophosphamide in Steroid-Dependent or Steroid-Resistant Focal Segmental Glomerulosclerosis: A Randomized Controlled Trial

Abstract

Background: The efficacy and safety of tacrolimus (TAC) and cyclophosphamide (CTX) were prospectively examined in steroid-dependent or steroid-resistant primary focal segmental glomerulosclerosis (FSGS). Methods: Patients with biopsy-proven FSGS were enrolled and randomly divided into two groups: CTX and TAC. Patients treated with CTX (0.5–0.75 g/m²·month, i.v.) received prednisone at 0.8 mg/kg·day, while patients treated with TAC (0.1 mg/kg·day) received prednisone at 0.5 mg/kg·day. The plasma concentration of TAC was monitored and maintained at 5–10 ng/ml. After a 6-month treatment the patients were evaluated. Patients with complete remission (CR) and partial remission (PR) continued the treatment for 12 months with the dose tapered, whereas the patients with no response were excluded from the study and underwent an alternative treatment. Results: A total of 33 patients were recruited and 27 completed the 12-month follow-up. The TAC-treated patients (n = 15) showed a quick remission. The initial remission time averaged 1.23 ± 0.21 versus 2.21 ± 0.77 months in the CTX group (n = 18), but no significant difference was achieved (p > 0.05). At 6 months, the two groups showed a similar outcome. Ten patients from each group showed remission (7 CR and 3 PR). At 12 months, the CTX group had 9 CR and 3 PR while the TAC group had 6 CR and 5 PR. Remission rates in TAC tended to be higher than that in CTX, but there was no difference. CTX patients had a high prevalence of infections (50.0 vs. 13.3% in TAC, p < 0.05). In contrast, TAC-treated patients showed a high incidence of hyperglycemia (26.7 vs. 0.0% in CTX, p < 0.05). Conclusion: These results suggest that CTX and TAC had a similar efficacy in steroid-dependent and steroid-resistant FSGS as manifested by reduced proteinuria, improved serum albumin level and renal function.

The Evidence-Based Approach to Adult-Onset Idiopathic Nephrotic Syndrome

“…Additional data published after the KDIGO guidelines support this notion. A small, single-center study of adults with idiopathic FSGS compared intravenous monthly cyclophosphamide to tacrolimus for 6 months, with both groups receiving steroids ( 51 ). There were no significant differences between the groups, but both groups had improved proteinuria and serum albumin with stable GFR.…”

Advanced therapeutics in focal and segmental glomerulosclerosis

“…Our study showed that intravenous pulsed CTX therapy in addition to steroid achieved satisfactory clinical effects in steroiddependent and SR-FSGS (55.6% achieved remission at 6 months and 66.7% at 12 months). 9 Therefore, CTX therapy is still an appropriate choice for patients with primary FSGS, even in some refractory cases, and may be considered as first-line immunosuppressive agent due to its high effectto-cost ratio.…”

Optimal management of primary focal segmental glomerulosclerosis in adults

“…43,44 A Chinese trial compared the association of tacrolimus with prednisone to the association of IV cyclophosphamide with prednisone given to 33 adults with steroid-dependent or steroid-resistant FSGS: they reported 6-and 12-month cumulative remission rates of 67% and 73%, respectively, in the tacrolimus-prednisone group compared with 56% and 67%, respectively, in the cyclophosphamide-prednisone group. 44 Two alternative treatments may be proposed as secondline therapies, although few data are available on their efficacy: they are alkylating agents and monoclonal antibodies against CD20. Alkylating agents, given as oral cyclophosphamide, are associated with higher remission rates and a longer time of remission than calcineurin inhibitors.…”

“…27,49 Remission rates, in studies where tacrolimus has been given to patients who are dependent on or resistant to corticoids, were between 48% and 100%. 37,44,[50][51][52] Any difference between cyclosporine and tacrolimus regarding nephrotoxicity has not been proven. Side effects include tremor, arterial hypertension, and diabetes mellitus.…”