Background/Purpose:

To study the factors associated with renal remission, relapse and renal function decline in patients with lupus nephritis treated with combined steroid and MMF or Tac.

Methods:

Data were extracted from a RCT of the efficacy of MMF vs Tac for induction treatment of lupus nephritis.  All patients recruited were treated with high-dose prednisolone 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) for maintenance.  Rescue therapies were given to patients who did not respond to induction.  Factors associated with complete renal response (CR), relapse and renal function decline at 5 years were studied by regression analyses.

Results:

150 patients (92% women) with lupus nephritis were studied (Class III±V 36%; IVG/S±V 46; pure V 19%; age 35.5±12.8 years; SLE duration 50.2±62 months).  At baseline, 59(39%) patients were hypertensive and 67% patients had CrCl <90ml/min.  At 6m, 61% patients achieved CR, 24% had partial response (PR) but 15% patients had no response (NR).  Logistic regression revealed that the baseline urine P/Cr ratio (OR 0.75[0.57-0.99]; p=0.04) and the presence of membranous feature on renal histology (OR 0.25[0.07-0.91]; p=0.04) were independently associated with CR at 6m.  AZA maintenance was given to 59 (78%) MMF-treated (dose 82.5±24 mg/day) and 60 (81%) TAC-treated patients (dose 86.5±21 mg/day; p=0.32).  Patients with NR were re-induced with CYC (N=20), low-dose combination of MMF and TAC (N=5), cross-over to TAC or MMF (N=6).  After a follow-up of 60.8±26 months, proteinuric and nephritic renal flares occurred in 24% and 18% of patients treated initially with MMF and 35% and 27% in those treated with TAC, respectively.  In patients who achieved CR or PR after initial treatment, Cox regression showed that the female sex (HR 10.9[1.19-101]; p=0.04), positive anti-dsDNA at month 6 (HR 4.95[1.64-14.9]; p=0.005) and the use of ACE inhibitor after 6 month (HR 8.86[1.28-61.2]; p=0.03) were independently associated with renal flares (proteinuric or nephritic).  The cumulative incidence of a composite outcome of decline of CrCl by ≥30%, development of CKD stage 4/5 or death at 5 years was 21% in patients treated with MMF and 22% in those treated with TAC.  Factors significantly associated with this outcome were first time lupus nephritis (HR 0.21[0.05-0.82]; p=0.03), creatinine clearance (CrCl) at 6 month (HR 0.97[0.95-0.99]; p=0.005) and the use of AZA maintenance (HR 0.23[0.49-4.30]; p=0.046).  Repeat renal biopsy in 23 patients with renal flares showed that the increase in chronicity score was similar between the MMF (1.3±3.0) and TAC (1.8±2.0) groups of patients (p=0.42).

Conclusion:

Tac is non-inferior to MMF for induction therapy of lupus nephritis.  More proteinuria at baseline and the presence of histological membranous features are unfavorably associated with good renal response after induction treatment.  Female patients and persistent elevation of anti-dsDNA after induction therapy are associated with renal flares.  Lower creatinine clearance at 6 months and the absence of AZA maintenance are associated with renal function deterioration after 5 years.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/factors-associated-with-renal-remission-relapse-and-long-term-renal-function-decline-in-lupus-nephritis-treated-with-combined-prednisolone-and-mycophenolate-mofetil-mmf-or-tacrolimus-tac/