Predictors and clinical significance of lupus low disease activity state 12 months after lupus nephritis

Abstract

<p><strong>Background</strong> Lupus nephritis (LN) is a significant comorbidity that affects around 50% of patients with systemic lupus erythematosus (SLE). Complete or partial renal response 12 months after LN is a recommended treatment target. Low disease activity in extra-renal domains by achieving LLDAS may also contribute to one of the critical treatment goals in LN patients ^[1]. However, the predictors of LLDAS in LN patients and the renal-specific benefits of LLDAS were also not fully understood.</p><p><strong>Objectives</strong> To investigate the predictors of LLDAS at 12 months post-LN and the clinical usefulness of achieving this state in LN patients.</p><p><strong>Methods</strong> Patients with biopsy-proven LN during 2010-2020 were included. Baseline demographics, blood parameters and urinalysis results were recorded. Patients were then followed up every 4 months to repeat blood tests and urinalysis. Renal response and LLDAS were assessed at 12 months post-LN, and any future relapses were recorded. Complete renal response (CRR) was defined as proteinuria ≤0.5g/day with normal estimate glomerular filtration rate (eGFR); partial renal response (PRR) was defined as a reduction in proteinuria by ≥50% with near normal eGFR. LLDAS was attained by meeting: (1) SLE Disease Activity Index ≤4 with no major organ activity; (2) no new lupus disease; (3) physician global assessment ≤1; (4) prednisolone dose ≤7.5mg; (5) standard maintenance immunosuppressants ^[1]. Relapse was a biopsy-proven LN after an initial treatment response of proteinuria reduction of ≥50% or to subnephrotic range. We assessed the predictors of LLDAS at 12 months post-LN and performed time-to-relapse survival analysis.</p><p><strong>Results</strong> 143 LN patients were included with a median follow-up duration of 10.4 years. At 12 months, 57 (40%), 14 (10%) and 69 (48%) patients achieved CRR, PRR and LLDAS, respectively. Among 136 patients who achieved treatment response, 30 (22%) patients developed LN relapse after a median of 2.98 years. LN at age greater than 30 or the presence anti-smith autoantibodies had significantly lower odds of reaching LLDAS at 12 months after LN, with odds ratio of 0.35 (<em>p</em> = 0.047) and 0.30 (<em>p</em> = 0.043) respectively (Table 1). Patients reaching CRR/PRR and LLDAS both had a significantly lower chance of relapse with <em>p</em> = 0.014 and <em>p</em> = 0.002 respectively (Figure 1).</p>