FRI0375 Delayed lupus nephritis in the course of systemic lupus erythematosus predicts a poorer renal response to induction therapy, renal flares, and worse long-term renal outcomes: a multicenter, retrospective cohort study
Authors: M. Nakano, K. Kubo, Y. Shirota, Y. Iwasaki, N. Tanaka, Y. Takahashi, S. Tateishi, H. Yamashita, M. Miyazaki, H. Sato, T. Igari, H. Kanda, H. Kaneko, T. Ishii, K. Fujio, A. Mimori
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Background</h3> Some prognostic factors for lupus nephritis (LN) have been mentioned such as nephrotic syndrome, class 4 and chronicity on histology. In a previous single-centre study, we reported a potentially poorer renal response to induction therapy in LN that developed later after SLE onset (delayed, D-LN) compared with LN manifesting at SLE onset (early, E-LN)<sup> 1)</sup>. However, our study was limited by a small sample size and lack of long-term observation. <h3>Objectives</h3> This multicenter study aimed to validate whether D-LN was a useful predictor of a poor response to induction therapy with more detailed clinical and pathological parameters. Furthermore, we investigated whether D-LN was also a predictor of flares and long-term renal outcomes in addition to the established prognostic factors. <h3>Methods</h3> We retrospectively examined 215 biopsy-proven LN patients (136 E-LN, 79 D-LN) who attended 3 hospitals above between 1997 and 2014 and who were observed for 3–20 (median: 10.8) years from LN onset. We compared baseline clinical, pathological features and treatment options at LN onset between E-LN and D-LN. Then we compared the cumulative complete response (CR) rates, renal/extra-renal relapse rates, and the rates of renal insufficiency between the two groups. Renal insufficiency was defined as follows:<sup>1</sup> serum creatinine (SCr) doubling or ESRD for severe insufficiency, and<sup>2</sup> SCr increasing by 1.5 times and also &gt;1.0 (female) or &gt;1.2 mg/dl (male) for mild insufficiency. Moreover, we evaluated predictors of the response, flares and long-term renal outcomes with multivariate analysis. <h3>Results</h3> Anti-Sm/RNP antibodies and mixed proliferative and membranous nephritis (class 3+5 or 4+5) were significantly more prevalent in D-LN than E-LN (48.1 vs. 32.4%, 68.8 vs. 40.4%, 40.5 vs. 18.4%, respectively). Log-rank test showed that significantly lower cumulative CR rates over 3 years (65.8 <i>vs.</i> 83.1% at 12 months, 83.5 <i>vs.</i> 92.6% at 36 months, p<i>&lt;0.01</i>) and significantly higher relapse rates (both renal and extra-renal) over 20 years in D-LN than E-LN. Mild renal insufficiency was significantly more likely to occur in D-LN over 20 years (21.5<i> vs.</i> 12.5%, p<i>=0.04</i>). We performed multivariate Cox regression analysis for the response, flare, and renal outcomes including significant variables on univariate analysis. As independent predictors of CR, D-LN, nephrotic syndrome and chronicity index were identified. As those of renal flares, D-LN was detected. Although D-LN was not associated with severe renal insufficiency, D-LN was identified as an independent predictor of mild renal insufficiency as well as some other factors (table 1). <h3>Conclusions</h3> D-LN might be a novel predictor of a poorer treatment response, renal flares and long-term renal outcomes independent of the established prognostic factors. The distinct differences in the autoantibody profiles between E-LN and D-LN groups suggest that D-LN patients might reflect a refractory SLE subset with a specific immunological profile. <h3>Reference</h3> [1] Nakano M, et al. Different responses to induction therapy in two onset categories of lupus nephritis.EULAR2017THU 0251. <h3>Acknowledgements</h3> None <h3>Disclosure of Interest</h3> None declared