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Background: Lupus nephritis (LN) is a serious manifestation of systemic lupus erythematosus (SLE). About 14-33% of LN fail to respond to standard treatment 1, 2. In this study, we evaluated the treatment outcomes of LN who failed to respond to standard first-line immunosuppressives and identified the clinical characteristics of 'difficult-to-treat' (DTT LN). Objectives: 1)To evaluate the prevalence and demographic characteristics of patients with DTT LN. 2)To explore the factors determining DTT LN. 3)To compare the mortality and renal outcomes between DTT LN patients and responsive forms of lupus nephritis. Methods: The department renal biopsy registered was screened to identify individuals who had atleast one biopsy between 2004 and 2023. Records of all who underwent a renal biopsy were reviewed. Those with LN class III, IV, and V LN at the first biopsy were included. Demographic, clinical, laboratory and histopathological features were recorded. Any patient with partial or non-remission at 6 or 12 months of induction therapy requiring more than one induction therapy, or a relapse within two years after achieving complete remission were classified as 'difficult to treat' LN. The predictors of DTT LN were assessed using binary logistic regression. The outcome including worsening creatinine, end-stage renal disease(ESRD) or death at the last available follow up was considered and compared between the two groups. Results: We identified 379 SLE (94.7% women) with biopsy-proven LN with complete records who had at least 2-year follow-up. The age (median, IQR) was 30 (24-38) years, with a median duration of disease of 72 (36-108) months at the onset of LN. Median SLEDAI-2K at the time of first renal biopsy was 12 (8-16). Among the first kidney biopsies, 147 (38.8%) were class III, 153 (40.4%) were class IV, 56 (14.8%) were pure class V and 23 (6.1%) were class III/IV + V. One hundred and twenty-three of 379 (32.45%) were identified as difficult-to-treat(DTT). Among these, 53/123 (43.08%) received two induction agents, 38/123 (30.89%) received three induction, and 9/123 (7.3%) received >3 induction. Among various first induction regimens used in DTT patients, 69 (56%) received high dose cyclophosphamide (mNIH), 35 (28%) received low dose cyclophosphamide (ELNT) and 19 (15%) received mycophenolate mofetil. Most of the second-line induction agents used were MMF or rituximab. Rates of complete remission to first, second and third induction regimen among DTT were 31%, 26% and 3% respectively. SLEDAI-2K, SLICC ACR damage index, hypertension, acute kidney injury were significantly associated with DTT LN (Table 1). Several histopathological features had higher odds in the DTT group(table 2). On multivariate logistic regression, only SLEDAI 2K and hypoalbuminemia at the time of first biopsy remained as independent predictors of DTT LN(Table 2). In the overall cohort mortality was 17 (4.5%) and 13 (3.4%) patients progressed to ESRD. ESRD (8.9% vs 0.8%) and death(11.4% vs 1.2%) were significantly higher in DTT group. Conclusion: Approximately 1/3rd of patients in our cohort did not respond to first line induction agent. Among these 38.21% responded completely to second or third inductions, 48.78% failed to achieve remission even with repeat induction. Presence of high SLEDAI-2K and hypoalbuminemia at initial diagnosis predicts difficult-to-treat LN. REFERENCES: 1 Kronbichler A, Brezina B, Gauckler P, Quintana LF, Jayne DRW. Refractory lupus nephritis: When, why and how to treat. Autoimmun Rev. 2019;18:510-18. 2 Yo JH, Barbour TD, Nicholls K. Management of refractory lupus nephritis: challenges and solutions. Open Access Rheumatol. 2019;11:179-88. Acknowledgements: NIL. Disclosure of Interests: None declared.
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