THU0299 Factors Associated with Long-Term Renal Function Deterioration in Lupus Nephritis Treated Initially with Combined Prednisolone and Mycophenolate Mofetil (MMF) or Tacrolimus (TAC)
Authors: C. C. Mok, S. Ying, P. T. Chan, C. H. To
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Objectives</h3> To study the risk factors for renal function decline in patients with lupus nephritis treated initially with combined steroid and MMF or Tac. <h3>Methods</h3> 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 (&lt;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. <h3>Results</h3> 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 &lt;50% or &gt;3.0 or deterioration in CrCl (&gt;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 &gt;=30% and 17 (11%) patients developed stage 4/5 chronic kidney disease (CKD) (CrCl &lt;30ml/min). The cumulative risk of loss of CrCl by &gt;=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). <h3>Conclusions</h3> 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. <h3>Disclosure of Interest</h3> None Declared