Background/Purpose Renal relapses are part of the natural history of lupus nephritis (LN) and represent a significant challenge not only because they are associated with an increased risk of decline in renal function, but also there is a cumulative toxicity of immunosuppressive treatments. In this retrospective study, we aimed to review renal flare frequency and management in a large single centre cohort of adult LN patients. 

Methods Patients with biopsy proven LN were identified from our electronic database. LN classes based on glomerular pathology were defined according to the ISN/RPS classification. Clinical and laboratory data were obtained from electronic records of patients. Complete remission (CR) was defined as proteinuria <0.5g/day, whilst partial remission (PR) was defined as >50% reduction in baseline proteinuria achieving <2g/day. We defined proteinuric flares as proteinuria >1g/day in patients with CR, and doubling of proteinuria in cases of PR.

Results 104 (87%) of 119 SLE patients with biopsy proven LN achieved either CR (n=84, 81%) or PR (n=20, 19%). 34 (33%) had at least one flare (27 had preceding CR and 7 had PR); among those 8 had >2 flares (19%). 21 patients (64%) had class 3 or 4 LN, 7 (21%) class 5 LN, 4 (12%) class 2 LN and 1 (3%) focal segmental glomerulosclerosis. The median time between remission and relapse was 29 months (IQR, 16-66) in CR, and 13 months (IQR, 3-32) in PR (p=0.089). The maintenance immunosuppressive drug at time of flare was Mycophenolate Mofetil (MMF, n=13, 42%) or Azathioprine (AZA, n=10, 32%).  15 (48%) had Angiotensin blockers (ATB), and 22 (71%) were on low dose Corticosteroids (CS) (<10mg/day). Non-adherence to treatment at time of relapse was documented in 7 cases (22%). At the time of flare, the median proteinuria was 1.7g (IQR, 1.3-3.2) in CR, and 2.5g (IQR, 1.4-3.8) in PR. 14 (41%) had raised Creatinine, 14 had raised dsDNA (47%), 18 had low complements (56%) at flare. To treat relapse, 13 patients (45%) started a new immunosuppressive drug (Cyclophosphamide n=6, MMF n=5, Rituximab n=1 or AZA n=1), 3 (10%) had immunosuppressive drug dose escalation, 4 (14%) were treated with CS alone, and 6 (21%) were treated with ATB. After treatment, proteinuric outcome was available for 24 patients: 16 patients (67%) achieved CR, 6 (25%) reached PR, whilst 2 (8%) did not go into remission. 5 patients (15%) reached stage 5 chronic kidney disease after the flare. 

Conclusion LN renal flares are common. Our study shows that a third of LN patients develop at least one relapse after reaching remission, usually within 3 years. The length of time to flare tends to be shorter in cases of preceding PR than in CR. Lack of adherence to long term immunosuppression was identified as a significant factor in LN flare (22% cohort). Patients with LN in remission require close follow-up.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/renal-relapses-are-common-in-lupus-nephritis/