P222
LONG-TERM OUTCOME OF NEPHROTIC SYNDROME SECONDARY TO
PRIMARY FOCAL SEGMENTAL GLOMERULOSCLEROSIS TREATED WITH
TACROLIMUS MONO-THERAPY.
T Connor, J Levy, R Tarzi, C Pusey, J Galliford, T Cairns, and M Griffith
West London Renal & Transplant Centre, Hammersmith Hospital, London, UK
Background: Focal segmental glomerulosclerosis (FSGS) is a significant cause of end-stage
renal failure in developed countries. Patients with nephrotic syndrome have a worse prognosis.
Steroids are an effective treatment in some patients, but side effects are significant especially
with prolonged therapy. Tacrolimus (tac) is also an effective treatment for the nephrotic
syndrome in FSGS, but long-term therapy is often necessary, and there are concerns about
toxicity. This study reports on the long-term outcome of patients treated with tac monotherapy.
Methods: Retrospective review of all patients with nephrotic syndrome secondary to primary
FSGS treated with tac for at least 12 months. All patients received standard therapy with
maximum tolerated ACE inhibitors +/- ARBs. Complete remission (CR) was defined as normal
serum albumin with PCR <50; partial remission (PR) as proteinuria ≤50% baseline.
Results: 1. Demographics: 17 patients with nephrotic syndrome due to primary FSGS were
treated with Tac. The mean age was 43 years (19-73 years), and 11 were male. Ethnicity: 7
Caucasian, 2 African-Caribbean, 8 Asian. 7/17 patients had received previous immune
suppression (6 steroids, 1 cyclosporin A). Mean albumin was 16 (9-29) g/L and mean
creatinine 111 (57 – 312) umol/L at presentation.
2. Remission: All patients achieved partial remission at a mean 69 days (12-363), while 16/17
achieved complete remission at a mean 145 days (12-651). Interestingly, the 7 patients with
histological ‘tip’ lesions went into CR sooner at a mean 78 days (20-250).
Patients were treated with tac for an average of 36 (12-53) months. Although the mean
creatinine at the end of treatment was similar at 93 (54-176) umol/L, there were variations in
individual patients (Fig 1). None required cessation of tac due to deterioration of function.
350
Figure 1: Trend in serum
creatinine (umol/L) in 17
patients with primary FSGS
treated
with
long-term
tacrolimus over 51 months
follow-up.
300
250
200
150
100
50
0
0
1
3
6
9 12 15 18 21 24 27 30 33 36 39 42 45 48 51
3. Relapse: 5/17 patients had a relapse of nephrotic syndrome while taking tac at 24 (6-39)
months, 2/5 following poor compliance. Tac was withdrawn in 3/17 patients in remission after
a mean 35 (28-41) months. 2/3 relapsed at 13 and 31 months after ceasing therapy. Of note 3
patients had 4 successful pregnancies without relapse of their nephrotic syndrome while
maintained on tac.
4. Side effects: There were no admissions for infection. Tac was stopped in 1 patient after the
discovery of metastatic colon cancer (aged 77, after 4 years of treatment).
Conclusions: Most patients on long-term tac for primary FSGS exhibit a stable GFR. Close
monitoring of renal function and tac levels is essential. Tac is usually well tolerated even in the
elderly, and can facilitate successful pregnancy in some patients. Randomised trials are
required to compare tac with other standard therapies.