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THU0299 Factors Associated with Long-Term Renal Function Deterioration in Lupus Nephritis Treated Initially with Combined Prednisolone and Mycophenolate Mofetil (MMF) or Tacrolimus (TAC)
  1. C. C. Mok1,
  2. S. Ying2,
  3. P. T. Chan1,
  4. C. H. To1
  1. 1Medicine, Tuen Mun Hospital
  2. 2Medicine, Princess Margaret Hospital, HK, Hong Kong

Abstract

Objectives To study the risk factors for renal function decline in patients with lupus nephritis treated initially with combined steroid and MMF or Tac.

Methods Data were extracted from a randomized controlled trial of the efficacy of MMF vs Tac for induction treatment of lupus nephritis. All patients recruited were treated with high-dose prednisolone (0.6mg/kg/day for 6-8 weeks and tapered) with either MMF (2-3g/day) or Tac (0.1-0.06mg/kg/day) for 6 months. Patients with good clinical response were shifted to azathioprine (AZA) (2mg/kg/day) and continued on low dose prednisolone (<10mg/day) for maintenance. Rescue therapies were given to patients who did not have response to treatment at the discretion of the attending physicians. Factors associated with renal function decline at 5 years were studied by Cox regression analyses.

Results 150 patients (92% women) with biopsy confirmed active lupus nephritis were studied (ISN/RPS class III 17%; IVG 31%; IVS 12%; III/IV+V 21%; pure V 20%). The mean age was 35.5±12.8 years and SLE duration was 50.2±62 months at the time of renal biopsy. 102 (68%) patients had first time glomerulonephritis while the others had relapsed disease. The mean histological activity and chronicity score was 8.2±3.4 and 2.6±1.6, respectively. 59(39%) patients were hypertensive, 62(41%) had active urinary casts and 112(75%) had microscopic hematuria at presentation. The mean creatinine clearance (CrCl) was 79.0±30.8 ml/min and 67% patients had CrCl less than 90ml/min. At 6 months, 61% patients achieved good clinical response, 25% had partial response but 15% patients had no response (NR) (urine P/Cr improvement <50% or >3.0 or deterioration in CrCl (>20%) ± persistently active urinary sediments and lupus serology). Rescue regimens for NR patients included: oral or intravenous pulse cyclophosphamide (68%), Tac or MMF (14%) and MMF + Tac combination (18%). 128(85%) patients received AZA (83.1±23mg/day) for maintenance therapy. After a mean follow-up of 56±28 months, 27(18%) patients had loss of CrCl by >=30% and 17 (11%) patients developed stage 4/5 chronic kidney disease (CKD) (CrCl <30ml/min). The cumulative risk of loss of CrCl by >=30% or stage 4/5 CKD was 3% at 12 months, 7.7% at 24 months, 8.4% at 36 months, 13.6% at 48 months and 17.3% at 60 months. Cox regression revealed histological activity score (HR 0.78[0.65-0.94]; p=0.007), chronicity score (1.46[1.06-2.01]; p=0.02), non-response at 6 months (HR 3.87[1.34-11.2]; p=0.01), class V histology (HR 0.35[0.16-0.74]; p=0.006) and number of renal flares (HR 1.59[1.01-2.49; p=0.04] were independent risk factors for CrCl loss by 30% of stage 4/5 CKD, after adjustment for age, sex, SLE duration, first-time renal disease, proteinuria and CrCl at presentation and the treatment arm during induction phase (MMF or Tac).

Conclusions Combined prednisolone with MMF or Tac is equally effective for the initial treatment of active lupus nephritis. No response at 6 months, proliferative types of lupus nephritis, lower activity but higher chronicity score on renal biopsy and the number of renal flares are predictive of renal function decline at 5 years.

Disclosure of Interest None Declared

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