Background: Lupus nephritis (LN) is a significant cause of morbidity and mortality. One of the primary objectives in managing lupus nephritis is to prevent relapses. Relapses are correlated with increased hospitalizations, poor renal outcomes, morbidity and mortality. In this context, recognizing predictors of renal relapse is crucial to guide managing patients with LN.

Objectives: We aim to investigate the incidence, predictive factors and outcomes related to renal relapse.

Methods: All patients with biopsy-proven LN (ISN/RPS 2003), with complete clinical data and a follow-up period of at least one year, were included in our study. Demographic, clinical and laboratory data were obtained from the existing database and revised, especially for the renal parameters. Induction and maintenance therapies were also recorded. Complete response (CR) was determined at the 6th and 12th months. CR was defined as urine protein-creatinine ratio (UPCR) <0.5 g/g. Renal relapse was defined as a UPCR >1 g/g in patients with baseline proteinuria <0.5 g/g or an increase in UPCR by ≥1 g/g in patients with baseline proteinuria >0.5 g/ g and/or an increase serum creatinine. DORIS complete remission was described as a clinical SLEDAI=0, no serological activity, and no treatment with glucocorticoids or immunosuppressive (IS). LLDAS was defined as a SLEDAI ≤ 4 with no activity in major organ systems, a daily prednisolone dose ≤ 7.5 mg/day, and allowing for maintenance IS. We defined patients who devoleped renal involvement more than five year after SLE diagnosis as delayed LN. Flares, death, chronic kidney disease (CKD), permanent dialysis and transplantation were also recorded. The association of clinical characteristics of the cohort with renal flares and outcome was investigated.

Results: Of 252 patients, 72 had relapsed. The mean number of relapses was 0.4±0.8. The number of patients who relapsed once was 72, the number of patients who relapsed twice was 27, the number of patients who relapsed three times was 9, and the number of patients who relapsed four times was 2. Age at diagnosis with systemic lupus erythematosus (SLE) and LN was younger in relapsers (30±10,8; 23,7± 9,4; p<0.001) (31,7± 11,1; 25,8± 9,4; p<0.001). Delayed LN diagnosis was more common in relapsers (23 (12,8); 17 (23,6); p:0.034). eGFR at first renal presentation was lower in the non-relapse group (92,2± 37,8; 104,5± 34,1; p:0.029). No difference was detected in other clinical and laboratory characteristics and induction treatments. In relapsers, the frequency of azathioprine as maintenance treatment was higher than MMF (32(44,4); 19 (26,4); p<0.001). Relapsers showed a higher rate of CKD (13 (7,2); 18 (25); p<0.001), hemodialysis (3 (1,7); 9 (12,5); p<0.001), and transplantation (2 (1,1); 5 (6,9); p:0.011) and had a lower DORIS complete remission (22 (12,2); 2 (2,8) and DORIS clinical remission (119 (66,1); 33 (45,8); p:0.003). Hospitalization (1,2± 0,6; 2,1± 1,2; p<0.001), infection (45 (25); 31 (43,1); p0.005), damage (125 (69,4); 60 (83,3); p:0.024), cumulative cyclophosphamide (5,6± 4,8; 9,1± 7,8; p:0.001) and steroid dose (23,6± 12,3; 32,7±13,5; p<0.001) were higher in the relapse group. Multivariate analysis demonstrated that younger age at SLE diagnosis (OR: 0,941; CI: 0,911-0,971; p<0.001) increased relapse, whereas DORIS complete remission after first renal presentation (OR:0,099; CI: 0,013-0,752; p:0.025) decreased relapse (Table 1).

Conclusion: Predicting relapse is essential to prevent relapse and relapse-related renal damage. A study showed that repeated relapses were associated with progression to CKD and poorer patient survival [1]. Parikh et al [2] found that spending more than 30% of the time in renal flare was predictive of the development of CKD. In our cohort, patients with relapses were younger at diagnosis. No difference was found in induction treatments for the first renal presentation, but relapses were more frequent under azathioprine treatment than under MMF. When predictors of relapse were evaluated, younger age at diagnosis of SLE and failure to achieve complete DORIS remission were found to be risk factors for relapse. CKD, infection, and hospitalization were found to be more frequent in patients with relapse, emphasizing the importance of preventing relapse.

REFERENCES: [1] Perez-Arias AA, Márquez-Macedo SE, Pena-Vizcarra OR, Zavala-Miranda MF, Romero-Díaz J, Morales-Buenrostro LE, et al. The influence of repeated flares in response to therapy and prognosis in lupus nephritis. Nephrology Dialysis Transplantation. 2023 Apr 1;38(4):884–93.

[2] Parikh S V., Nagaraja HN, Hebert L, Rovin BH. Renal flare as a predictor of incident and progressive CKD in patients with lupus nephritis. Clinical Journal of the American Society of Nephrology. 2014;9(2):279–84.

Acknowledgements: NIL.

Disclosure of Interests: None declared.

© The Authors 2025. This abstract is an open access article published in Annals of Rheumatic Diseases under the CC BY-NC-ND license ( http://creativecommons.org/licenses/by-nc-nd/4.0/ ). Neither EULAR nor the publisher make any representation as to the accuracy of the content. The authors are solely responsible for the content in their abstract including accuracy of the facts, statements, results, conclusion, citing resources etc.