International validation of a urinary biomarker panel for identification of active lupus nephritis in children.

Conventional markers of juvenile-onset systemic lupus erythematosus (JSLE) disease activity fail to adequately identify lupus nephritis (LN). While individual novel urine biomarkers are good at detecting LN flares, biomarker panels may improve diagnostic accuracy. The aim of this study was to assess the performance of a biomarker panel to identify active LN in two international JSLE cohorts.Novel urinary biomarkers, namely vascular cell adhesion molecule-1 (VCAM-1), monocyte chemoattractant protein 1 (MCP-1), lipocalin-like prostaglandin D synthase (LPGDS), transferrin (TF), ceruloplasmin, alpha-1-acid glycoprotein (AGP) and neutrophil gelatinase-associated lipocalin (NGAL), were quantified in a cross-sectional study that included participants of the UK JSLE Cohort Study (Cohort 1) and validated within the Einstein Lupus Cohort (Cohort 2). Binary logistic regression modelling and receiver operating characteristic curve analysis [area under the curve (AUC)] were used to identify and assess combinations of biomarkers for diagnostic accuracy.A total of 91 JSLE patients were recruited across both cohorts, of whom 31 (34 %) had active LN and 60 (66 %) had no LN. Urinary AGP, ceruloplasmin, VCAM-1, MCP-1 and LPGDS levels were significantly higher in those patients with active LN than in non-LN patients [all corrected p values (p c) < 0.05] across both cohorts. Urinary TF also differed between patient groups in Cohort 2 (p c = 0.001). Within Cohort 1, the optimal biomarker panel included AGP, ceruloplasmin, LPGDS and TF (AUC 0.920 for active LN identification). These results were validated in Cohort 2, with the same markers resulting in the optimal urine biomarker panel (AUC 0.991).In two international JSLE cohorts, urinary AGP, ceruloplasmin, LPGDS and TF demonstrate an 'excellent' ability for accurately identifying active LN in children

Defining remission in childhood-onset lupus: PReS-endorsed consensus definitions by an international task force

Objective: To derive childhood-onset SLE (cSLE) specific remission definitions for future treat-to-target (T2T) trials, observational studies, and clinical practice. // Methods: The cSLE International T2T Task Force conducted Delphi surveys exploring paediatric perspectives on adult-onset SLE remission targets. A modified nominal group technique was used to discuss, refine, and agree on the cSLE remission target criteria. // Results: The Task Force proposed two definitions of remission: ‘cSLE clinical remission on steroids (cCR)’ and ‘cSLE clinical remission off steroids (cCR-0)’. The common criteria are: (1) Clinical-SLEDAI-2 K = 0; (2) PGA score < 0.5 (0–3 scale); (4) stable antimalarials, immunosuppressive, and biologic therapy (changes due to side-effects, adherence, weight, or when building up to target dose allowed). Criterion (3) in cCR is the prednisolone dose ≤0.1 mg/kg/day (maximum 5 mg/day), whereas in cCR-0 it is zero. // Conclusions: cSLE definitions of remission have been proposed, maintaining sufficient alignment with the adult-SLE definition to facilitate life-course research

Defining remission in childhood-onset lupus:PReS-endorsed consensus definitions by an international task force

Objective: To derive childhood-onset SLE (cSLE) specific remission definitions for future treat-to-target (T2T) trials, observational studies, and clinical practice. Methods: The cSLE International T2T Task Force conducted Delphi surveys exploring paediatric perspectives on adult-onset SLE remission targets. A modified nominal group technique was used to discuss, refine, and agree on the cSLE remission target criteria.Results: The Task Force proposed two definitions of remission: ‘cSLE clinical remission on steroids (cCR)’ and ‘cSLE clinical remission off steroids (cCR-0)’. The common criteria are: (1) Clinical-SLEDAI-2 K = 0; (2) PGA score &lt; 0.5 (0–3 scale); (4) stable antimalarials, immunosuppressive, and biologic therapy (changes due to side-effects, adherence, weight, or when building up to target dose allowed). Criterion (3) in cCR is the prednisolone dose ≤0.1 mg/kg/day (maximum 5 mg/day), whereas in cCR-0 it is zero. Conclusions: cSLE definitions of remission have been proposed, maintaining sufficient alignment with the adult-SLE definition to facilitate life-course research.</p

PReS-endorsed international childhood lupus T2T task force definition of childhood lupus low disease activity state (cLLDAS)

ObjectiveTo achieve a consensus-based definition of Low Disease Activity (LDA) for use in cSLE trials.MethodsThe International cSLE T2T Task Force, comprising of paediatric rheumatologists/nephrologists, and adult rheumatologists undertook a series of Delphi surveys/consensus meetings to discuss, refine, and vote upon cSLE LDA criteria.ResultsThe Task Force agreed that LDA should be based upon the adult-SLE Lupus Low Disease Activity State definition (LLDAS), with modifications to make it applicable to cSLE (cLLDAS). They agreed upon five cLLDAS criteria: (1) SLE Disease Activity Index (SLEDAI)-2 K ≤4, with no activity in major organ systems; (2) no new features of lupus disease activity compared with the last assessment; (3) Physician Global Assessment score of ≤1 (0-3 scale); (4) prednisolone dose of ≤0.15 mg/kg/day, 7.5 mg/day/maximum; while on (5) stable antimalarials, immunosuppressives, and biologics.ConclusionsA cSLE-appropriate definition of cLLDAS has been generated, maintaining alignment with the adult-SLE definition to promote life-course research

FRI0164 BANFF INFLAMMATORY INDICES MAY BE SUPERIOR TO THE NIH SCORING IN PREDICTING CKD PROGRESSION IN LUPUS NEPHRITIS

Background:Chronic kidney disease/end stage renal disease (CKD/ESRD) from lupus nephritis (LN) is a major cause of morbidity and mortality. Advanced tubulointerstitial disease (TID) in LN is a better predicor of renal outcome than glomerular lesions. The current NIH classification is heavily weighted towards glomerular lesions and only provides a semiqualitative assessment of TID. In contrast, Banff classification of renal allograft pathology provides 6 reproducible scores for TID (inflammation, fibrosis, atrophy). Banff scoring may better predict CKD/ESRD in LN than NIH scoresObjectives:We compared Banff grading vs. NIH scoring as predictors of CKD progression at 5 years, defined as a decline in estimated glomerular filtration rate (eGFR) ≥30%, a strong risk factor for ESRD and mortalityMethods:We included patients with LN class III, IV, V on the index biopsy Jan 2005 and Dec 2018. H&amp;E/PAS stained slides were reviewed and scored by an experienced pathologist. Six TID Banff scores (0/1 vs. 2/3), NIH activity/chronicity (AI/CI) and NIH interstitial fibrosis/tubular atrophy (IF/TA), tubulointerstitial inflammation (TII) scores (none/mild vs. moderate/severe) were evaluated as predictors of CKD progression using survival analysesResults:Of the 125 patients, 46 had CKD progression and 20 subsequently developed ESRD. There were no differences between progressors and non-progressors in terms of baseline demographic, clinical data, LN class (Tab 1). Banff ti score (total inflammation) was associated with CKD progression in bivariate and time-dependent analyses. However, NIH TII score and corresponding Banff i score were not predictive (Tab 2, Fig 1). Overall NIH AI and CI were not predictive of CKD progression. Moderate/severe NIH IF/TA was associated with CKD progression as was Banff ci (interstitial fibrosis) score (Tab 2, Fig 2). Banff score for atrophy was not predictive. In a subset of 92 patients with baseline eGFR≥60ml/min/1.73m2only Banff ti score (but not i score or NIH TII, IF/TA) was predictive of CKD progression (Fig 1)Table 1.Baseline data in patients with/without CKD progressionProgressors1n=46Non-progressorsn=79pn (%) or median (IQR)Female36 (78)69 (87)0.18Age (years)26 (20-41)29 (21-43)0.53&lt;18 years7 (15)13 (16)0.86Race0.82 White4 (9)4 (5) Black18 (39)35 (44) Asian1 (2)1 (1) Unknown23 (50)39 (50)Diabetes5 (11)3 (4)0.12Hypertension33 (72)55 (70)0.8eGFR ml/min/1.73m296.1 (56.6-117.8)88.9 (47-117)0.51C3 mg/dL71 (52-88)67.5 (43-94)0.58C4 mg/dL12.65 (9-23)12 (7-20)0.48Anti-ds DNA titer IU108.7(36.6-194.9)151.3(39.2-200)0.57Total SLEDAI11 (8-16)12 (8-16)0.47Renal SLEDAI8 (4-12)8 (4-12)0.9LNProliferative GN2: III, IV18 (39)30 (38)0.15Nonproliferative GN: V9 (20)27 (34)Mixed GN: V and III/IV19 (41)22 (28)1Progressors: LN patients with eGFR decline ≥30% within 5 years.2GN: glomerulonephritisTable 2.NIH and Banff scores with/without progressorsProgressorsn=46Non-progressorsn=79pn (%) or median (IQR)NIHOverall AI1 (0-4)1 (0-3)0.61AI ≥ 111 (2)3 (3.8)0.62Overall CI3 (0-5)2 (0-3)0.33CI ≥ 324 (52)28 (35.4)0.07Moderate/severe TII7 (15.2)4 (5)0.05Moderate/severe IF/TA16 (35)15 (19)0.049BanffTubulitis: t00Interstitial inflammation: i 2/33 (6.5)5 (6.3)0.9Total inflammation: ti 2/316 (34.8)12 (15.2)0.01Tubular atrophy: ct 2/316 (34.8)16 (20.3)0.07Interstitial fibrosis: ci 2/317 (37)15 (19)0.03Inflammation in area of interstitial fibrosis and/or tubular atrophy: i-IFTA 2/3n=26*18 (69)n=51*25 (49)0.09* Biopsy number is smaller due to inability to apply score to biopsies without areas of fibrosis/tubular atrophyConclusion:Banff inflammation scores may be superior predictors of CKD/ESRD progression at 5 years, compared to the currently used NIH classification. Detection of inflammation by Banff scores may allow earlier interventions to prevent ESRDDisclosure of Interests:None declared</jats:sec

SAT0172 UTILIZATION OF HYDROXYCHLOROQUINE AND CORTICOSTEROIDS AMONG LUPUS PATIENTS WITH INCIDENT END-STAGE RENAL DISEASE (ESRD) ONSET: A LONGITUDINAL STUDY USING USRDS REGISTRY

Background:The development of ESRD due to lupus nephritis is one of the most common and serious complications of SLE. Mortality among SLE ESRD patients is 4-fold higher compared to lupus nephritis patients with preserved renal function1Mortality in SLE ESRD is also twice as high compared with non-SLE ESRD, even though SLE patients develop ESRD at a significantly younger age. In the absence of ESRD specific guidelines, medication utilization in SLE ESRD is unknown.Objectives:The objective of this study was to investigate the real-world current US-wide patterns of medication prescribing among lupus nephritis patients with new onset ESRD enrolled in the United States Renal Disease Systems (USRDS) registry. We specifically focused on HCQ and corticosteroids (CS) as the most used medications to treat SLE.Methods:Inclusion: USRDS patients 18 years and above with SLE as a primary cause of ESRD (International Classification of Diseases, 9thRevision (ICD9) diagnostic code 710.0, previously validated2). who developed ESRD between January 1st, 2006 and July 31, 2011 (to ensure at least 6 months of follow-up in the USRDS). Patients had to be enrolled in Medicare Part D (to capture pharmacy claims). The last follow-up date was defined as either the last date of continuous part D coverage or the end of the study period, Dec 31, 2013.Results:Of the 2579 patients included, 1708 (66%) were HCQ- at baseline, and 871 (34%) were HCQ+ at baseline. HCQ+ patients at baseline had a slightly lower duration of follow-up compared to HCQ- patients at baseline, median (IQR) of 2.32 (1.33, 3.97) years and 2.55 (1.44, 4.25) years, respectively, p= 0.02. During follow-up period, only 778 (30%) continued HCQ either intermittently or continuously to the last follow-up date, 1306 (51%) were never prescribed HCQ after baseline, and 495 (19%) discontinued HCQ before the last follow-up date. Of the 1801 patients who were either never prescribed or discontinued HCQ early after ESRD onset, 713 (40%) were prescribed CS to the end of the follow-up period: 55% were receiving a low dose &lt;10mg/daily, and 43 were receiving moderate dose (10-20mg daily)Conclusion:HCQ may be underprescribed and CS may be overprescribed in SLE ESRD. Changing the current prescribing practices may improve outcomes in SLE ESRDReferences:[1]Yap DY et al., NDT 2012.[2]Broder A et al., AC&amp;R 2016.Acknowledgments :The data reported here have been supplied by the United States Renal Data System (USRDS). The interpretation and reporting of these data are the responsibility of the author(s) and in no way should be seen as an official policy or interpretation of the U.S. government.Funding: :NIH/NIAMS K23 AR068441 (A Broder), NIH/NIAMS R01 AR 057327 and K24 AR 066109 (KH Costenbader)Disclosure of Interests: :Anna R. Broder: None declared, Wenzhu Mowrey: None declared, Anna Valle: None declared, Beatrice Goilav: None declared, Kazuki Yoshida: None declared, Karen Costenbader Grant/research support from: Merck, Consultant of: Astra-Zeneca</jats:sec

Systemic Lupus Erythematosus Activity and Hydroxychloroquine Use Before and After End-Stage Renal Disease

Abstract Background: SLE manifestations after ESRD may be underdiagnosed and undertreated, contributing to increased morbidity and mortality. Whether specific symptoms persist after ESRD or a shift towards new manifestations occurs has not been extensively studied, especially in the non-Caucasian patients in the United States. In addition, hydroxychloroquine (HCQ) prescribing patterns post-ESRD have not been described. The objective of this study was to assess lupus activity and HCQ prescribing before and after ESRD development. Knowledge gained from this study may aid in the identification of SLE manifestations and improve medication management post-ESRD. Methods: We performed a retrospective cohort study of SLE patients with incident ESRD between 2010 and 2017. SLE-related symptoms, serologic markers of disease activity, and medication use were collected from medical records before and after ESRD development.Results: Fifty-nine patients were included in the study. Twenty-five (43%) patients had at least one clinical (non-renal) SLE manifestation documented within 12 months before ESRD. Of them, 11/25 (44%) continued to experience lupus symptoms post-ESRD; 9 patients without clinical or serological activity pre-ESRD developed new symptoms of active SLE. At the last documented visit post-ESRD, 42/59 (71%) patients had one or more clinical or serological markers of lupus activity; only 17/59 (29%) patients achieved clinical and serological remission.Thirty-three of 59 (56%) patients had an active HCQ prescription at the time of ESRD. Twenty-six of the 42 (62%) patients with active SLE manifestations post-ESRD were on HCQ. Patients who continued HCQ post-ESRD were more likely to be followed by a rheumatologist (26 [87%] vs 17 [61%], p=0.024), had a higher frequency of documented arthritis (10 [32%] vs 1 [4%], p=0.005), CNS manifestations (6 [20%] vs 1 [4%], p=0.055), and concurrent immunosuppressive medication use (22 [71%] vs 12 [43%], p=0.029).Conclusions: Lupus activity may persist after the development of ESRD. New onset arthritis, lupus-related rash, CNS manifestations, low complement and elevated anti-dsDNA may develop. HCQ may be underutilized in patients with evidence of active disease pre- and post ESRD. Careful clinical and serological monitoring for signs of active disease and frequent rheumatology follow up is advised in SLE patients both, pre and post-ESRD.</jats:p