FRI0246 CELLULAR/FIBROCELLULAR CRESCENT IS A 52-WEEK AND LONG-TERM POOR PROGNOSTIC FACTOR OF ACTIVE LUPUS NEPHRITIS
Authors: Aya Nawata, Kazuhisa Nakano, Shingo Nakayamada, Yoshiya Tanaka
Journal: Annals of the Rheumatic Diseases (2019)

<h3>Background</h3> Lupus nephritis (LN) is one of the most serious manifestation of systemic lupus erythematosus (SLE), associated with poor prognosis. LN exhibits a variety of histological findings including both inflammatory lesions such as crescent formation and immune complex (IC) deposition lesions. In current INS/RPS 2003 classification, all of them are classified as class III, IV and V. Recently, in the 2016 update of Oxford classification of IgA nephropathy, crescent formation (C) was added as an independent prognostic factor. Further examination of pathological and clinical prognostic factors for LN is required. <h3>Objectives</h3> To identify renal remission rate and clinico-pathological characteristics associated with renal non-remission at 52 weeks (52w) in LN patients <h3>Methods</h3> A single center retrospective study. We enrolled Japanese 152 patients of LN class III, IV, and V those who could observe for 52 w out of 274 SLE cases performed renal biopsy in our department between 1995 to 2017. After 52w after biopsy, they were classified as complete remission (CR), partial remission (PR) and non-remission (NR) according to ACR and LUNAR remission criteria by estimated glomerular filtration rate (eGRF) or serum creatinine (sCre) and proteinuria. Overall renal remission is defined as RR (CR + PR). The primary endpoint was the RR achieving rate, and the secondary endpoints were the baseline histological and clinical factors related to NR. Clinical factors: albumin (alb), IgG, C3, C4, CH50, anti-nuclear antibodies (Abs), anti- dsDNA Abs, anti-Sm Abs, anti-RNP Abs in the sera, complete blood count, urinalysis, presence of comorbidities (antiphospholipid antibody syndrome, hypertension), disease activity score (SLEDAI and BILAG score) and therapeutic drug [prednisolone (PSL), intravenous cyclophosphamide (IVCY), etc]. Histological factors: endocapillary proliferation, cellular/fibrocellular crescents, wire-loop lesion, hyaline thrombi, karyorrhexis, tuft necrosis, segmental sclerosis, global sclerosis, interstitial inflammation and vascular lesion. <h3>Results</h3> Baseline data: mean age 39 years, 135 females, 18 men, histrogical class III, 53 cases, IV: 58 cases, pure V: 12 cases, III/IV + V: 30 cases. At 52w after biopsy, SLEDAI (16 → 2), BILAG (17 → 2) score is significantly decreased. Dose of PSL was reduced(48 → 9 mg). At 52w, all cases were classified as RR (125 cases, 82%) and NR (27 cases, 18%) by ACR/LUNAR remission criteria. Surprisingly, all cases of pure V reached remission. Class III or IV LN (RR 114 cases; 91% vs NR 27 cases; 100%, p = 0.01) and cellular/fibrocellular crescent formation (RR 51 cases; 40% vs NR 18 cases; 66% p = 0.01) were significantly higher in NR. Clinically, long disease duration (p = 0.02), coexisting hypertension (RR 7 cases; 6% vs NR 9; 33%, p &lt;0.01) and TMA (RR 1 case;0.7%, NR 2 cases;7%, p = 0.02), baseline urine protein (RR 1.5g vs NR 2.2g, p&lt;0.01), baseline low WBC (p = 0.03), baseline low IgG (p = 0.02) were detected. About therapeutic drugs, IVCY significantly improved remission rate (RR 84 cases 68% vs. NR 9 cases 41%, p = 0.03). After long-term observation, 52w NR was significantly lower eGFR level (RR 81 vs NR 50, p &lt;0.01, median observation period of 138 months). 3 cases developed ESRD and all of those cases show crescent formation. <h3>Conclusion</h3> As histological factors contributing to 52w-NR, class III or IV and crescent formation were detected. This result suggested that the therapeutic response was relatively better in cases with IC deposition lesions than those with inflammatory lesions. In LN, more-detailed pathological classification which could extract crescent formation might be required. <h3> Disclosure of Interests: </h3> Aya Nawata: None declared, Kazuhisa Nakano: None declared, Shingo Nakayamada Grant/research support from: Mitsubishi-Tanabe, Takeda, Novartis and MSD, Speakers bureau: Bristol-Myers, Sanofi, Abbvie, Eisai, Eli Lilly, Chugai, Asahi-kasei and Pfizer, Yoshiya Tanaka Grant/research support from: Abbvie, Astellas, Bristol-Myers Squibb, Chugai, Daiichi-Sankyo, Eisai, Mitsubishi-Tanabe, MSD, Ono, Taisho-Toyama, Takeda, Speakers bureau: Abbvie, Asahi-kasei, Astellas, Bristol-Myers Squibb, Chugai, Daiichi-Sankyo, Eli Lilly, Eisai, Glaxo-Smithkline, Janssen, Mitsubishi-Tanabe, Novartis, Pfizer Japan Inc, Sanofi, Takeda, UCB, YL Biologics