Risk of chronic kidney disease in 260 patients with lupus nephritis-analysis of a nationwide multicentre cohort with up to 35 years of follow-up.

OBJECTIVES: To compare proliferative (PLN) and membranous (MLN) lupus nephritis (LN) regarding clinical and laboratory presentation and long-term outcomes; To investigate predictors of progression to chronic kidney disease (CKD). METHODS: Multicentre observational study, with retrospective analysis of a prospective cohort, using data from the Rheumatic Diseases Portuguese Registry-Reuma.pt. Patients with biopsy-proven PLN, MLN and mixed LN were included. Cox regression survival analysis was used to investigate predictors of CKD. RESULTS: 260 patients were included. Median follow-up was 8 years (IQR 11; minimum 1, maximum 35 years). MLN patients presented with significantly lower serum creatinine (0.70 (IQR 0.20; minimum 0.50, maximum 1.30) mg/dl vs 0.80 (IQR 0.31; minimum 0.26, maximum 2.60) in PLN, p= 0.003). Proteinuria levels did not differ between groups (p= 0.641). Levels of complement were reduced in PLN but nearly normal in MLN patients, and there were fewer patients with positive anti-dsDNA antibodies in the MLN group (p< 0.001). One year after the beginning of treatment, 62% of the patients achieved EULAR/ERA-EDTA complete response, with further 5% achieving partial response. Patients with lower proteinuria at diagnosis were more likely to achieve a complete renal response at one year, however, proteinuria at diagnosis or at one year did not predict long term CKD. Estimated glomerular filtration rate (eGFR) ≤75 mL/min/1.73 m2 at one year was the strongest predictor of progression to CKD (HR 23 [95% CI 8-62], p< 0.001). Other possible predictors included the use of azathioprine for induction of remission, older age at diagnosis and male sex. CONCLUSION: Proteinuria levels did not predict LN histologic class in our cohort. eGFR cutoff of 75 mL/min/1.73 m2 after one year of treatment was strongly predictive of progression to CKD.

10-year experience of early arthritis clinic at a tertiary rheumatology center: achievements and challenges.

OBJECTIVES: To characterize patients evaluated in our Early Arthritis Clinic (EAC) in the first ten years; to assess diagnostic delay and its underlying causes; and to evaluate the level of agreement between the referring physician and the rheumatologist regarding the presence of referral criteria. METHODS: Cross-sectional study including patients attending EAC between 2012 and 2021. Demographic data, provenience, final diagnosis, referral criteria and time related to diagnosis delay were retrieved from clinical files and the Portuguese Registry of Rheumatic Patients (reuma.pt). Characteristics of the patients and the time variables were analysed with descriptive statistical analysis. The agreement between the referring physician and rheumatologist regarding the referral criteria was evaluated using Cohen's Kappa. RESULTS: A total of 440 patients (68.9% females, mean age of 54±16.7 years) were referred, mostly from primary care (71.6%). Inflammatory Rheumatic Disease was diagnosed in 65.7% of the patients, with 58.9% classified as early arthritis. The median time from onset of symptoms to referral for EAC was 76 days (IQR 33.5-144.0); the median time from referral to the first EAC was 34 (IQR 19.0-46.0) days, and the median time from onset of symptoms to first EAC was 114.5 (IQR 66.8-190.3) days (16.3 weeks). Only about 10% were observed by a Rheumatologist before six weeks after symptom onset. The level of agreement between the referring physician and the rheumatologist was slight to fair to clinical criteria and moderate to substantial to laboratory criteria. CONCLUSIONS: A significant delay still is observed in patients with early arthritis suspicion, being the time from onset of symptoms to referral is the most relevant. A low agreement between referral and Rheumatologists suggests that non-rheumatologists education/training is needed. Identifying the barriers that prevent the adequate referral of patients is necessary to define strategies to improve it.

Neurophysiological and psychosocial mechanisms of fibromyalgia: A comprehensive review and call for an integrative model.

Research into the neurobiological and psychosocial mechanisms involved in fibromyalgia has progressed remarkably in recent years. Despite this, current accounts of fibromyalgia fail to capture the complex, dynamic, and mutual crosstalk between neurophysiological and psychosocial domains. We conducted a comprehensive review of the existing literature in order to: a) synthesize current knowledge on fibromyalgia; b) explore and highlight multi-level links and pathways between different systems; and c) build bridges connecting disparate perspectives. An extensive panel of international experts in neurophysiological and psychosocial aspects of fibromyalgia discussed the collected evidence and progressively refined and conceptualized its interpretation. This work constitutes an essential step towards the development of a model capable of integrating the main factors implicated in fibromyalgia into a single, unified construct which appears indispensable to foster the understanding, assessment, and intervention for fibromyalgia.

2022 EULAR recommendations for screening and prophylaxis of chronic and opportunistic infections in adults with autoimmune inflammatory rheumatic diseases.

OBJECTIVES: To develop EULAR recommendations for screening and prophylaxis of chronic and opportunistic infections in patients with autoimmune inflammatory rheumatic diseases (AIIRD). METHODS: An international Task Force (TF) (22 members/15 countries) formulated recommendations, supported by systematic literature review findings. Level of evidence and grade of recommendation were assigned for each recommendation. Level of agreement was provided anonymously by each TF member. RESULTS: Four overarching principles (OAP) and eight recommendations were developed. The OAPs highlight the need for infections to be discussed with patients and with other medical specialties, in accordance with national regulations. In addition to biologic/targeted synthetic disease-modifying antirheumatic drugs (DMARDs) for which screening for latent tuberculosis (TB) should be performed, screening could be considered also before conventional synthetic DMARDs, glucocorticoids and immunosuppressants. Interferon gamma release assay should be preferred over tuberculin skin test, where available. Hepatitis B (HBV) antiviral treatment should be guided by HBV status defined prior to starting antirheumatic drugs. All patients positive for hepatitis-C-RNA should be referred for antiviral treatment. Also, patients who are non-immune to varicella zoster virus should be informed about the availability of postexposure prophylaxis should they have contact with this pathogen. Prophylaxis against Pneumocystis jirovecii seems to be beneficial in patients treated with daily doses >15-30 mg of prednisolone or equivalent for >2-4 weeks. CONCLUSIONS: These recommendations provide guidance on the screening and prevention of chronic and opportunistic infections. Their adoption in clinical practice is recommended to standardise and optimise care to reduce the burden of opportunistic infections in people living with AIIRD.

Emotion regulation and the salience network: a hypothetical integrative model of fibromyalgia.

Fibromyalgia is characterized by widespread pain, fatigue, sleep disturbances and other symptoms, and has a substantial socioeconomic impact. Current biomedical and psychosocial treatments are unsatisfactory for many patients, and treatment progress has been hindered by the lack of a clear understanding of the pathogenesis of fibromyalgia. We present here a model of fibromyalgia that integrates current psychosocial and neurophysiological observations. We propose that an imbalance in emotion regulation, reflected by an overactive 'threat' system and underactive 'soothing' system, might keep the 'salience network' (also known as the midcingulo-insular network) in continuous alert mode, and this hyperactivation, in conjunction with other mechanisms, contributes to fibromyalgia. This proposed integrative model, which we term the Fibromyalgia: Imbalance of Threat and Soothing Systems (FITSS) model, should be viewed as a working hypothesis with limited supporting evidence available. We hope, however, that this model will shed new light on existing psychosocial and biological observations, and inspire future research to address the many gaps in our knowledge about fibromyalgia, ultimately stimulating the development of novel therapeutic interventions.

Normal percentile reference curves for skin ultrasound thickness and stiffness at Rodnan sites.

OBJECTIVES: Our primary objective was to establish preliminary normal reference curves for ultrasound-dermal thickness and skin stiffness in the 17 Rodnan skin sites, considering the effect of gender and age on these measures. As an exploratory objective, we investigated the effect of body mass index and the menopause on skin ultrasound measures. METHODS: A cross-sectional study was conducted involving 140 healthy volunteers, aged 20-79 years. Recruitment was stratified by gender and age (10-year categories). Ultrasound-dermal thickness and skin stiffness were assessed by high-frequency ultrasound and shear-wave elastography, respectively, at the 17 Rodnan skin sites. Outcomes were evaluated through a mixed linear model, univariate and multivariate regressions. Normal reference curves were derived for both ultrasound measures in each skin site. An online calculator of the percentiles of skin ultrasound measures was developed. RESULTS: Ultrasound-dermal thickness and stiffness measures were higher in men than women in all Rodnan skin sites (except in chest for ultrasound-dermal thickness). Age had also a significant impact in both ultrasound measures, but only in some skin sites. Gender and age percentile curves (97.5th, 95th, 75th, 50th, 25th, 5th, 2.5th) were plotted for each of the measures in each skin site. CONCLUSIONS: Gender and age are strongly associated with skin ultrasound parameters, imposing the need for gender-specific and age-specific reference values. Normal reference percentile curves are provided as a basis for future cooperative work to strengthen its evidence basis, representativeness and refinement regarding potentially influential factors.

Predictors of hospitalization in patients with systemic lupus erythematosus: a 10-year cohort study.

INTRODUCTION/OBJECTIVES: Recognising systemic lupus erythematosus (SLE) patients at higher risk for hospitalization, aiming at developing tailored management strategies, may help minimize admissions and improve long-term health outcomes. Our study aimed to identify predictors for hospitalization in patients with SLE. METHOD: Cohort study of SLE patients followed in a referral centre. All hospitalizations from study baseline up to 120 months were identified, and the primary indication for admission was categorized as follows: (1) SLE disease activity; (2); infection; and (3) other conditions. Demographic, clinical, and laboratory parameters at baseline were sought as predictors of hospitalization for (i) any cause, (ii) disease activity, and (iii) infection using survival analysis with Kaplan-Meier curves and log-rank tests. Potential predictors were further tested using multivariate Cox proportional hazards regression models. RESULTS: We included 398 patients (median follow-up: 120 months). The incidence rate of hospitalization was 17.7 per 100 patient-years. The most frequent indications for hospitalization were SLE disease activity (29.4%) and infection (23.4%). In multivariate analysis, male gender, age > 50 years, antiphospholipid antibodies positivity (aPL), SLEDAI-2 K > 5, organ damage, and prednisone daily dose (PDN) predicted hospitalization for any cause. SLEDAI-2 K > 5, aPL, PDN, and IS medication predicted hospitalization for active SLE. Male gender, prior biopsy-proven lupus nephritis, aPL, organ damage, and ongoing treatment with high-risk IS predicted hospitalization for infection. Treatment with antimalarials was associated with a lower risk of hospitalization for any cause and for infection. CONCLUSIONS: Positive aPL identifies SLE patients presenting a higher risk of hospitalization, while medication with antimalarials was associated with a lower risk. Key Points • Positive aPL is predictive of hospitalization for any medical condition, disease activity, and infection • Organ damage is predictive of hospitalization for any condition and infection • Antimalarials are predictive of a lower risk of hospitalization for any condition and infection.

The safety of glucocorticoids in the treatment of inflammatory rheumatic disease: new evidence.

PURPOSE OF REVIEW: Glucocorticoids justifiably remain a cornerstone in the treatment of many inflammatory rheumatic diseases but many are opposed to their use because of the side effects, most of them known to be dose-dependent. Most concerns regarding glucocorticoids stem from observational studies which are affected by several forms of bias, mainly confounding by indication, that may result in overestimation of harm. Solid evidence regarding the safety of low-dose glucocorticoids remains remarkably scarce. RECENT FINDINGS: Several observational studies showed heterogeneous results and two 6-month trials showed no increase of harm. The GLORIA trial of 5 mg/day prednisolone vs. placebo in patients aged 65+ is the first randomized control trial with glucocorticoids safety as coprimary outcome. The benefits of glucocorticoids in terms of symptoms and structural damage were confirmed, but the proportion of patients with at least one adverse event of special interest (serious or glucocorticoids-related) was increased by 24%, mostly due to nonsevere infections. SUMMARY: Based on current evidence the benefit-risk balance of low-dose glucocorticoids in rheumatoid arthritis, and probably in other rheumatic diseases is generally favourable. Physicians should be aware of the risks and mitigate them, but avoid the negative effects of unfounded fear.

Antimalarial treatment and minimizing prednisolone are associated with lower risk of infection in SLE: a 24-month prospective cohort study.

INTRODUCTION/OBJECTIVES: Infections are a major cause of morbidity and death in systemic lupus erythematosus (SLE). Perfecting the understanding of contributors to infection burden in SLE is pivotal to improve management and outcomes. This study aims to identify clinical predictors of infection in SLE. METHOD: We conducted a prospective cohort study at a referral SLE clinic. Infections were identified at each visit and categorized as (a) any type, (b) serious, (c) non-serious, and (d) bacterial. Survival analysis followed by multivariate Cox regression with an estimation of hazard ratios (HR) with 95% confidence intervals (95%CI) was performed. RESULTS: We included 259 patients during a mean follow-up of 23.3 ± 5.7 months. The incidence rate of infection of any type was 59.3 cases per 100 patient-years. Multivariate Cox models showed that (a) prednisolone ≥ 7.5 mg/day (HR = 1.95, 95%CI 1.26-3.03) and female gender (HR = 2.08, 95%CI 1.12-3.86) were associated with higher risk of infection of any type; (b) prednisolone ≥ 10 mg/day was associated with higher (HR = 4.32, 95%CI 1.39-13.40), and antimalarials with lower risk (HR = 0.18, 95%CI 0.06-0.51) of serious infection; (c) female gender (HR = 1.92, 95%CI 1.04-3.57) and prednisolone ≥ 7.5 mg/day (HR = 1.89, 95%CI 1.21-2.96) were associated with higher risk of non-serious infection; (d) antimalarials were associated with lower (HR = 0.49, 95%CI 0.26-0.93) and female gender (HR = 5.12; 95%CI 1.62-16.18) with higher risk of bacterial infection. CONCLUSIONS: The risk of infection was higher in females in this young, well-controlled, low-comorbidity SLE cohort. Antimalarials were associated with lower and prednisolone ≥ 7.5 mg with higher risk of infection. Key Points • Lupus patients treated with prednisolone ≥ 7.5 mg/day were 89% more likely to present infections. • Lupus patients receiving prednisolone ≥ 10 mg/day were four times more likely to present serious infections. • Lupus patients receiving antimalarials were 82% less likely to present serious infections.

Acute Pulmonary Edema During a Cesarean Delivery After an Adverse Drug Event.

Acute pulmonary edema (APEd) is rare in pregnancy and in the postpartum period. An intermediate type of APEd characterized as a transudate with a protein concentration between that of cardiogenic and noncardiogenic APEd has been described in the literature. This transudate might actually be the result of capillary pressure having increased to a point of high-permeability edema and/or alveolar hemorrhage. Clinically, the presentation would be a dramatic form of APEd - flash pulmonary edema - characterized by a rapid accumulation of fluid within the lung's interstitial and alveolar spaces as a result of suddenly elevated cardiac filling pressures. Here, we present a case of a healthy pregnant woman who underwent cesarean delivery and developed a constellation of signs and symptoms, suggestive of an APEd, after a supratherapeutic bolus of phenylephrine. During the diagnostic excursion, bilateral parenchymal infiltrations suggestive of hemorrhage were observed on a computed tomography scan. This case highlights the high morbidity associated with adverse drug events and the imperative to prevent them. It also underscores the critical need for careful management of volume shifts and hemodynamics in full-term pregnancies.

Outcomes of COVID-19 in patients with primary systemic vasculitis or polymyalgia rheumatica from the COVID-19 Global Rheumatology Alliance physician registry: a retrospective cohort study.

BACKGROUND: Patients with primary systemic vasculitis or polymyalgia rheumatica might be at a high risk for poor COVID-19 outcomes due to the treatments used, the potential organ damage cause by primary systemic vasculitis, and the demographic factors associated with these conditions. We therefore aimed to investigate factors associated with COVID-19 outcomes in patients with primary systemic vasculitis or polymyalgia rheumatica. METHODS: In this retrospective cohort study, adult patients (aged ≥18 years) diagnosed with COVID-19 between March 12, 2020, and April 12, 2021, who had a history of primary systemic vasculitis (antineutrophil cytoplasmic antibody [ANCA]-associated vasculitis, giant cell arteritis, Behçet's syndrome, or other vasculitis) or polymyalgia rheumatica, and were reported to the COVID-19 Global Rheumatology Alliance registry were included. To assess COVID-19 outcomes in patients, we used an ordinal COVID-19 severity scale, defined as: (1) no hospitalisation; (2) hospitalisation without supplemental oxygen; (3) hospitalisation with any supplemental oxygen or ventilation; or (4) death. Multivariable ordinal logistic regression analyses were used to estimate odds ratios (ORs), adjusting for age, sex, time period, number of comorbidities, smoking status, obesity, glucocorticoid use, disease activity, region, and medication category. Analyses were also stratified by type of rheumatic disease. FINDINGS: Of 1202 eligible patients identified in the registry, 733 (61·0%) were women and 469 (39·0%) were men, and their mean age was 63·8 years (SD 17·1). A total of 374 (31·1%) patients had polymyalgia rheumatica, 353 (29·4%) had ANCA-associated vasculitis, 183 (15·2%) had giant cell arteritis, 112 (9·3%) had Behçet's syndrome, and 180 (15·0%) had other vasculitis. Of 1020 (84·9%) patients with outcome data, 512 (50·2%) were not hospitalised, 114 (11·2%) were hospitalised and did not receive supplemental oxygen, 239 (23·4%) were hospitalised and received ventilation or supplemental oxygen, and 155 (15·2%) died. A higher odds of poor COVID-19 outcomes were observed in patients who were older (per each additional decade of life OR 1·44 [95% CI 1·31-1·57]), were male compared with female (1·38 [1·05-1·80]), had more comorbidities (per each additional comorbidity 1·39 [1·23-1·58]), were taking 10 mg/day or more of prednisolone compared with none (2·14 [1·50-3·04]), or had moderate, or high or severe disease activity compared with those who had disease remission or low disease activity (2·12 [1·49-3·02]). Risk factors varied among different disease subtypes. INTERPRETATION: Among patients with primary systemic vasculitis and polymyalgia rheumatica, severe COVID-19 outcomes were associated with variable and largely unmodifiable risk factors, such as age, sex, and number of comorbidities, as well as treatments, including high-dose glucocorticoids. Our results could be used to inform mitigation strategies for patients with these diseases. FUNDING: American College of Rheumatology and the European Alliance of Associations for Rheumatology.

Patient-Physician discordance in assessment of disease activity in Rheumatoid Arthritis patients.

BACKGROUND: In rheumatoid arthritis (RA), global disease activity is commonly evaluated, from the patient's and the physician's perspective, through a 100mm visual analogue scale (VAS) and plays an important role in the assessment of diseases activity and treatment decisions. Our aim was to determine patient-physician discordance in the assessment of disease activity and to explore its determinants. METHODS: Cross sectional study including RA patients (ACR/EULAR 2010 classification criteria). The discrepancy between patients-physicians (∆PPhGA) was defined as PGA minus PhGA, and a difference > |20mm| was considered as "discordant". Correlation between ∆PPhGA and other variables was assessed through Pearson's correlation and comparison between groups through t-test. Variables with p < 0.05 or considered clinically relevant were included in multivariable linear regression analysis to identify determinants for ∆PPhGA. A p < 0.05 was considered statistically significant. RESULTS: In total, 467 patients with RA were included (81.2% female; mean age 63.9% ± 12.2 years). PGA and PhGA were discordant in 61.7% of the cases. The proportion of concordance increased (p < 0.01) when considering only patients in remission (DAS 28 3V < 2.6). In multivariable analysis (R2adjusted=0.27), VAS-pain-patient (ß 0.74, 95% CI 0.62-0.88, p=0.00) and TJC (ß 0.16, 95% CI 0.45-0.48, p=0.02) remained associated with a higher ∆PPhGA. CONCLUSION: Our study confirmed that a significant discrepancy between patients and physicians in the assessment of global disease activity is frequent in clinical practice, and is probably due to valorization of different parameters by the two groups.

SARS-CoV-2 outbreak in immune-mediated inflammatory diseases: the Euro-COVIMID multicentre cross-sectional study.

BACKGROUND: The COVID-19 pandemic has raised numerous questions among patients with immune-mediated inflammatory diseases regarding potential reciprocal effects of COVID-19 and their underlying disease, and potential effects of immunomodulatory therapy on outcomes related to COVID-19. The seroprevalence of SARS-CoV-2 and factors associated with symptomatic COVID-19 in patients with immune-mediated inflammatory diseases are still unclear. The Euro-COVIMID study aimed to determine the serological and clinical prevalence of COVID-19 among patients with immune-mediated inflammatory diseases, as well as factors associated with COVID-19 occurrence and the impact of the pandemic in its management. METHODS: In this multicentre cross-sectional study, patients aged 18 years or older with a clinical diagnosis of rheumatoid arthritis, axial spondyloarthritis, systemic lupus erythematosus, Sjögren's syndrome, or giant cell arteritis were recruited from six tertiary referral centres in France, Germany, Italy, Portugal, Spain, and the UK. Demographics, comorbidities, treatments, and recent disease flares, as well as information on COVID-19 symptoms, were collected through a questionnaire completed by participants. SARS-CoV-2 serology was systematically tested. The main outcome was the serological and clinical prevalence of COVID-19. Factors associated with symptomatic COVID-19 were assessed by multivariable logistic regression, and incidence of recent disease flares, changes in treatments for underlying disease, and the reasons for treatment changes were also assessed. This study is registered with ClinicalTrials.gov, NCT04397237. FINDINGS: Between June 7 and Dec 8, 2020, 3136 patients with an immune-mediated inflammatory disease answered the questionnaire. 3028 patients (median age 58 years [IQR 46-67]; 2239 [73·9%] women and 789 [26·1%] men) with symptomatic COVID-19, serological data, or both were included in analyses. SARS-CoV-2 antibodies were detected in 166 (5·5% [95% CI 4·7-6·4]) of 3018 patients who had serology tests. Symptomatic COVID-19 occurred in 122 (4·0% [95% CI 3·4-4·8]) of 3028 patients, of whom 24 (19·7%) were admitted to hospital and four (3·3%) died. Factors associated with symptomatic COVID-19 were higher concentrations of C-reactive protein (odds ratio 1·18, 95% CI 1·05-1·33; p=0·0063), and higher numbers of recent disease flares (1·27, 1·02-1·58; p=0·030), whereas use of biological therapy was associated with reduced risk (0·51, 0·32-0·82; p=0·0057). At least one disease flare occurred in 654 (21·6%) of 3028 patients. Over the study period, 519 (20·6%) of 2514 patients had treatment changes, of which 125 (24·1%) were due to the pandemic. INTERPRETATION: This study provides key insights into the epidemiology and risk factors of COVID-19 among patients with immune-mediated inflammatory diseases. Overall, immunosuppressants do not seem to be deleterious in this scenario, and the control of inflammatory activity seems to be key when facing the pandemic. FUNDING: Pfizer, Sanofi, Amgen, Galapagos, and Lilly.

Investigating the Usefulness of European Society of Cardiology Guidelines for Hospitalization in Acute Pericarditis at a Single Tertiary Center.

Background The European Society of Cardiology (ESC) guidelines for the diagnosis and management of pericardial diseases identify predictive factors of poor prognosis and advise either in favor or against hospitalization accordingly. We aim to evaluate the adequacy of hospitalization criteria in a cohort of patients presenting to the emergency department (ED) with acute pericarditis. Methods Retrospective analysis of patients admitted to ED with acute pericarditis, from 2009 to 2019. During ED stay, all patients were evaluated by a cardiologist who decided if the patient was to be discharged or hospitalized. Hospitalized and discharged patients were compared regarding the primary outcome, defined by a composite of: the need for pericardiocentesis and/or cardiac surgery, pericarditis recurrence, and all-cause death. The clinical decision was then counterpoised with ESC guidelines. Results A total of 192 patients were included in the analysis (median age 44.5 years old, 83.3% male) of which 87 (45.5%) were hospitalized. A total of 25% registered the primary outcome, mainly due to acute pericarditis recurrence, occurring in 21.9%. Predictors of recurrence were: glucocorticoid therapy (Odds Ratio [OR]=11.93, 95% Confidence Inirtval [CI] 3.13-45.5, p<0.001), fever at admission (OR=2.67, 95% CI 1.29-5.49, p=0.008), immunosuppression (OR=4.03, 95% CI 1.280-12.659, p=0.017) and increased cardiothoracic index (OR 3.85, CI 95% 1.67-8.86, p=0.002). Regarding hospitalisation/discharge decision, the ESC guidelines were respected in 73.4% of the cases. However, no significant difference in the primary outcome was noted whether the ESC guidelines were respected or not (27.5% vs. 24.3%, p=0.707). Conclusions Discrepancy between current guidelines and the clinical decision did not translate into a different outcome.

Early predictors of renal outcome in patients with proliferative lupus nephritis: a 36-month cohort study.

OBJECTIVES: To identify predictors of complete renal response (CRR) and renal flares in SLE patients with active proliferative LN. METHODS: This was a retrospective cohort study over 36 months including patients with biopsy-proven proliferative LN (class III/IV), from two European tertiary centres. CRR and renal flare were defined as proteinuria <0.5 g/day with normal renal function and proteinuria >1 g/day after CRR attainment, respectively. Demographic, clinical and analytic parameters were evaluated as early predictors of renal outcome, using survival analysis. Candidate variables were tested as predictors for CRR at time 0, 3 and 6 months after starting induction treatment. Potential predictors for renal flare were evaluated at time of reaching CRR. Variables with P < 0.10 on univariate analysis with log-rank tests were further tested with multivariate Cox proportional hazards regression models. RESULTS: We included 104 patients [81.7% female, mean (s.d.) age at baseline 32.0 (13.3) years]. Over follow-up, 91.7% reached CRR, within a median time of 6.0 months. Proteinuria <2 g/day at baseline [hazard ratio (HR) = 1.80, 95% CI 1.16, 2.79, P < 0.01] and 3 months (HR = 2.32, 95% CI 1.24, 4.32, P < 0.01) after starting induction therapy were independent predictors of CRR. Renal flares occurred in 18.4% of patients reaching CRR, after a mean time of 16.5 (8.6) months. Age up to 25 years at time of LN diagnosis (HR = 5.41, 95% CI 1.72, 16.97, P < 0.01) and positive anti-RNP (HR = 3.52, 95% CI 1.21, 10.20, P = 0.02) were independent predictors of renal flares. CONCLUSION: In patients with SLE and proliferative LN, factors assessed at baseline and 3 months from starting induction treatment can predict CRR and renal flares once CRR is achieved.