The optimal management of asymptomatic serological reactivation (ASR) in lupus nephritis (LN) patients remained undefined. This project aims to investigate the impact of pre-emptive treatment on disease relapse in LN patients who experienced ASR.

LN patients who presented with ASR [defined as 1) increase in anti-dsDNA >100 IU/mL , with or without drop in serum complement; or 2) increase in anti-dsDNA to higher than the normal range and >2 times of the preceding value, with or without drop in serum complement; and 3) Absence of renal or systemic manifestations of SLE) will be randomized to receive pre-emptive increase in immunosuppression or had their current immunosuppressive therapies unchanged.

Patients will be followed at 4-, 12-, 24-wk and then every 12 weeks up to 24 months to monitor for renal or extra-renal relapses. Bloods and urine will be collected for measurement of renal and serological parameters, and also B cell signatures.

Primary outcomes: Renal Flare (denoted as proteinuria >1g/D; presence of urinary RBC >30 hpf/RBC casts, or increase in SCr >15% and positive anti-dsDNA)

Secondary outcomes:

• Safety & tolerability of pre-emptive increase of immunosuppressive treatments
• Extra-renal flares
• Renal function at 24 months
• Changes in serological parameters](streamdown:incomplete-link)

Inclusion Criteria:

• Patients with biopsy-proven lupus nephritis who experienced an episode of Asymptomatic Serological Flare (ASF) as defined by:

  1. Increase in anti-dsDNA to >100 IU/mL, with or without drop in serum complement levels OR

  2. Increase in anti-dsDNA to higher than the normal range and more than two times of the preceding value, with or without drop in serum complement levels

     AND

  3. Absence of renal or systemic manifestation of SLE.

Exclusion Criteria:

1. Patients who cannot provide informed consent.
2. Patients whom the clinicians opined to have excessively high risk of infection or malignancy.
3. Patients who are pregnant or lactating.