To describe the objectives, design and methods of the Spanish Multicentre Registry of Patients with ANCA-associated Vasculitis (RESER/NVAN), as well as its strengths and limitations. RESER/NVAN is a project promoted by the Spanish Society of Rheumatology, in collaboration with the Spanish Society of Nephrology, whose main objective is to estimate the incidence of ANCA-associated vasculitis in Spain.
MethodsRetrospective longitudinal observational study of ANCA-associated vasculitis patients ≥18 years of age diagnosed between 1 January 2015 and 31 March 2021. All patients in the reference area of each centre were included, with the reference area being the area that includes the population attended by the centre. Thirty-two centres distributed throughout the Spanish geography participated, and the administrative and/or clinical databases of each centre and those of the services that could be involved in the diagnosis and/or treatment of these patients were reviewed. Sociodemographic and anthropometric variables, lifestyle habits, comorbidities and variables characterising vasculitis were collected.
ConclusionsRESER/NVAN represents one of the largest cohorts of patients with ANCA-associated vasculitis in Spain. Despite its retrospective nature, the study provides comprehensive and reliable information on ANCA-associated vasculitis and is an excellent source of data for future analyses to increase knowledge of this disease.
Describir los objetivos y la metodología del Registro Multicéntrico de Pacientes con Vasculitis Asociada a ANCA en España (RESER/NVAN), así como sus fortalezas y limitaciones. RESER/NVAN es un proyecto promovido por la Sociedad Española de Reumatología, en colaboración con la Sociedad Española de Nefrología, cuyo objetivo principal es estimar la incidencia de vasculitis asociadas a ANCA en España.
MetodologíaEstudio observacional longitudinal con recogida retrospectiva de datos en el que se han incluido pacientes ≥18 años diagnosticados “de novo” de vasculitis asociada a ANCA en el periodo de tiempo que comprende desde el 1 de enero de 2015 hasta el 31 de marzo de 2021. Se incluyeron todos los pacientes del área de referencia de cada centro, considerando como área de referencia aquella que incluye la población atendida por el centro. Participaron 32 centros repartidos por toda la geografía española y se revisaron las bases de datos administrativas y/o clínicas de cada centro y las propias de los servicios que pudieran estar implicados en el diagnóstico y/o tratamiento de estos pacientes. Se recogieron variables sociodemográficas, antropométricas, hábitos de vida, comorbilidades y variables de caracterización de la vasculitis.
ConclusionesEl proyecto RESER/NVAN constituye una de las cohortes de pacientes con vasculitis asociadas a ANCA más grandes de España. A pesar de su naturaleza retrospectiva, esperamos que la información recogida de forma exhaustiva en el estudio nos permita tener una fuente de datos multicéntrica sobre la que realizar futuros análisis para generar mayor conocimiento sobre esta enfermedad.
According to the 2012 International Chapel Hill Consensus Conference, within antineutrophil cytoplasmic antibody-associated vasculitis (ANCA) the following entitites are included: granulomatosis with poliangeítis (previously Wegener) (GPA),
eosinophilic granulomatosis with polyangiitis (formerly Churg-Strauss) (EGPA) and microscopic polyangiitis (MPA) are systemic necrotising vasculitides that predominantly affect small vessels and are associated with high morbidity and mortality.1,2
Of the retrospective incidence estimates published in the literature for Spain, the study by Gonzalez-Gay et al. estimated the age-adjusted annual incidence (per million inhabitants) in the Lugo area during the period 1988–2001, with the following results: 2.95 (1.44–6.05) for GPA; 1.31 (0.87–1.96) for EGPA; and 7.91 (4.74–13.20) for MPA.3 On the Costa del Sol, the study by Romero-Gómez et al. the annual incidence (not adjusted for age) for the period 1994–2010 was estimated at 2.1 (0.8–3.4) for GPA; .6 (0–1.3) for EGPA; and 3.4 (1.7–5.1) for MPA.4 More recently, the study by Benavides-Villanueva et al. estimated an annual incidence in Cantabria for the period 2000–2023 of 5.9 (4–7.8) for MPA and 5.6 (3.9–7.3) for GPA.5 Other epidemiological studies, such as that by Draibe et al., reported seasonal variations in the incidence of ANCA-associated vasculitis with renal involvement in Catalonia, with a higher incidence during the winter months.6
However, we did not find any studies in the literature that cover broader areas of Spain and that would facilitate a more precise description of the epidemiology of these diseases in our region. This knowledge is fundamental for optimal planning of care for these patients.
This paper describes the methodology of the RESER/NVAN project, as well as its potential strengths and limitations. RESER/NVAN is a project promoted by the Spanish Society of Rheumatology (SER), in collaboration with the Spanish Society of Nephrology (SEN), the main objective of which is to estimate the incidence of ANCA-associated vasculitis in Spain.
The secondary objectives were to:
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Assess the variation of disease incidence by geographic area.
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Assess the complicance with ACR/EULAR 2022 classification criteria.
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Characterise the clinical manifestations of the disease at diagnosis and throughout its progression, as well as the phenotypic differences based on the ANCA subtype.
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Describe organ damage and analyse predictive factors for damage.
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Evaluate disease severity and prognosis at diagnosis in our setting using the Five Factor Score.
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Describe associated comorbidities in these patients, with particular emphasis on severe infection and cardiovascular disease.
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Evaluate the different treatments and dosages received by patients with ANCA-associated vasculitis, as well as associated adverse effects, with particular interest in the long-term safety of corticosteroids and biologic therapies.
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Evaluate disease status and degree of control at the end of follow-up.
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Evaluate the histopathological pattern of renal involvement.
Longitudinal observational study with retrospective data collection (obtained by reviewing the medical records of patients treated in the Rheumatology, Nephrology, Pulmonology, Otolaryngology [ENT], and Internal Medicine Departments).
Study population. Selection criteriaPatients aged ≥18 years, diagnosed de novo with ANCA-associated vasculitis (incident cases), as recorded in their medical records, between January 1, 2015, and March 31, 2021, regardless of the department in which they were treated.
All patients within each centre's catchment area were included, defined as the population served by the centre, regardless of the severity of the disease. Additionally, centres that are referral centres and receive patients with more severe diagnoses from larger areas included patients in the study, specifying that they did not belong to the centre's catchment area. These latter patients will not be considered for estimating the incidence of the primary endpoint.
Selection of participating centresAll hospitals with specialised rheumatology care were invited to participate through a public call via the SER's media outlets. Centres were selected based on a participation request submitted by those interested, detailing their capacity to identify all patients diagnosed with ANCA-associated vasculitis at the centre, collect data, and monitor them within the timeframes established in the study protocol. Given the low incidence of these vasculitis, priority was given to hospitals serving populations of at least 300,000 inhabitants (researchers at participating centres were asked to provide information on their catchment population). Finally, 32 centres distributed throughout Spain were selected (Table 1, Fig. 1).
List of participating centres in the RESER/NVAN study.
| AC | HOSPITAL |
|---|---|
| Andalusia | Hospital Universitario Virgen de Valme |
| Andalusia | Hospital Gral Juan Ramón Jiménez |
| Andalusia | Hospital Regional Universitario de Málaga |
| Andalusia | Hospital Universitario Reina Sofía |
| Andalusia | Hospital Virgen Macarena |
| Balearic Islands | Hospital Son Llatzer |
| Canary Islands | Hospital Universitario de Canarias |
| Canary Islands | Complejo Hospitalario Universitario Insular - Materno Infantil (CHUIMI) |
| Canary Islands | Hospital Universitario de Gran Canaria Dr. Negrín |
| Canary Islands | Hospital Universitario Nuestra Sra. De la Candelaria |
| Cantabria | Hospital Universitario Marqués de Valdecilla |
| Catalonia | Hospital del Mar- Parc de Salut del Mar |
| Catalonia | Hospital Universitario de Bellvitge |
| Catalonia | Hospital Universitario Parc Taulí |
| Catalonia | Hospital Universitario de Granollers |
| Catalonia | Hospital de la Santa Creu i Sant Pau |
| Catalonia | Fundación Puigvert |
| Community of Valencia | Hospital General Universitario Dr. Balmis |
| Community of Valencia | Hospital Universitario Dr. Peset |
| Community of Valencia | Hospital General de Valencia |
| Euskadi | Hospital de Basurto |
| Euskadi | Hospital Universitario de Donostia |
| Galicia | Complejo Hospitalario Universitario de A Coruña (CHUAC) |
| Galicia | Complejo Hospitalario Universitario de Vigo (CHUVI) |
| Galicia | Complexo Hospitalario Universitario de Pontevedra (CHUP) |
| Madrid | Hospital Universitario 12 de Octubre |
| Madrid | Hospital Universitario Ramón y Cajal |
| Madrid | Hospital Universitario Gregorio Marañón |
| Madrid | Hospital Universitario La Princesa |
| Madrid | Hospital Universitario Puerta de Hierro Majadahonda |
| Madrid | Hospital Universitario La Paz |
| Murcia | Hospital Universitario Virgen de la Arrixaca |
Due to the multidisciplinary nature of care for patients with ANCA-associated vasculitis, in addition to the Rheumatology Department, the research team at those centres that wished, included members from all the involved specialties (Nephrology, Pulmonology, ENT, and Internal Medicine).
Study developmentThe administrative and/or clinical databases of each centre, as well as those of the departments that might be involved in the diagnosis and/or treatment of these patients, were reviewed to locate all patients diagnosed with ANCA-associated vasculitis between January 1, 2015, and March 31, 2021.
Once all patients were located, all the detailed information in the variables and measurements section was collected in an electronic data collection form (eCRD) designed specifically for this study.
Given the retrospective longitudinal design, the following points in time were established for reviewing the information:
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On diagnosis
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Two months after diagnosis
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Six months after diagnosis
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One year after diagnosis
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Two years after diagnosis
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Five years after diagnosis
For operational reasons, September 30, 2022, was considered the cutoff date for monitoring each patient's progress. This ensured that the information collected from all patients reflected their progress for at least one year from their diagnosis.
The study was conducted in accordance with Good Clinical Practice guidelines and the principles of the Declaration of Helsinki in its latest revision, and was approved by the Ethics Committee for Medicinal Products Research (CEIm) of Galicia (Code 2022/269), as well as by the CEIm of each participating centre that requested it.
In accordance with the "Memorandum of Collaboration between the Ethics Committees for Medicinal Products Research for the Evaluation and Management of Observational Studies with Medicinal Products," informed consent was not obtained from the subjects.
Variables and measurementsThe information collected in the study included sociodemographic, anthropometric, lifestyle, comorbidity, medication, and infection variables in the month prior to the onset of vasculitis, interstitial lung disease, and vasculitis characterisation variables:
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Sociodemographic, anthropometric, and lifestyle variables: age, sex, height, weight, smoking status, alcohol consumption, cocaine use.
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Comorbidities prior to the onset of vasculitis and at the end of follow-up: hypertension, diabetes, dyslipidemia, cardiovascular disease, respiratory disease, other autoimmune diseases, chronic kidney disease, neoplasms, hypothyroidismmorbilidades.
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Suspected medication as a trigger for vasculitis.
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Infections in the month prior to the onset of vasculitis as a possible trigger.
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Interstitial lung disease: pattern of involvement, imaging studies, treatment.
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Characterisation Variables of ANCA-Associated Vasculitis (Appendix B, Supplementary Table S1)7,8,9,10,11,12,13,14
Due to the study's primary objective, sample size estimation was not necessary, as calculating incidence required including all patients from participating centres diagnosed with ANCA-associated vasculitis who met the selection criteria within the established time period.
Statistical analysisIncidence was calculated as the ratio of new cases registered during the established period to the susceptible population (general population ≥18 years) in each hospital's catchment area, expressed per million inhabitants. The age and sex distribution of the susceptible population in each area was estimated using data provided by the National Institute of Statistics for each province. Ninety-five per cent confidence intervals (CIs) for incidence rates were estimated assuming a Poisson distribution.
Continuous data was described as mean and standard deviation (mean ± SD) or median [25th–75th percentile] depending on whether their distribution was normal, and categorical variables as absolute frequencies and percentages
Means of continuous variables with a normal distribution were compared using the Student's t-test. If the distribution was not normal, they were analysed using the Kruskal–Wallis test. Categorical variables were compared using the chi-square test.
Statistical significance was defined as p < .05.
Quality controlOnline monitoring was performed on 100% of the included patients, with particular attention to those variables considered most relevant to the study objectives.
In addition to the monitoring process, procedures were standardised. On the one hand, a RESERN/VAN investigator's manual was developed, defining the variables, explaining the data collection periods, and providing instructions on using the eCRD. This manual was available to all researchers participating in the study. Furthermore, a standardisation meeting was held before the start of the study, attended by all selected centres, where the objectives, procedures, and how to conduct the study were explained.
DiscussionThis study describes the objectives and methodology of the Multicentre Register of Patients with ANCA-Associated Vasculitis in Spain (RESER/NVAN). The RESER/NVAN project was undertaken due to the absence of updated and representative data for the whole of Spain on the incidence of ANCA-associated vasculitis. Its main objective was to be able to provide a precise description of the epidemiology of these diseases.
Although the Gonzalez-Gay et al.3 study had estimated the incidence of these diseases in the area of Lugo in the 1988–2001 period, as had the Romero-Gómez et al.4 study in the Costa del Sol area in the 1994–2010 period and the Benavides-Villanueva et al.5 study in Cantabria in the 2000-2023 period, no larger areas of Spain were found to be covered in recent studies in the literature.
StrengthsThe main study strength is the large number of centres which participated, leading to a larger national cohort of patients with ANCA-associated vasculitis.
Furthermore, centres distributed throughout Spain were selected, thus achieving a more representative distribution across the country. Centre selection was carried out through a competitive process, which assessed their suitability for meeting the study's objectives and procedures based on information provided in a feasibility questionnaire. One of the main requirements was that they provide accurate population data for their catchment area.
Another strength to highlight is the comprehensive collection of a large number of variables, both general and specific to the characteristics of vasculitis. This provides a multicentre data source for future analyses.
Finally, the analysed period included part of the SARS-CoV-2 pandemic.
LimitationsThe main limitation of the study stems from its retrospective design, which may lead to information bias, as some of the study variables may not be systematically recorded in medical records. To address this limitation, an eCRD was designed using the most specific and common variables for this type of pathology, minimising data loss.
Another potential limitation of the study is the possibility of underestimating the incidence if not all patients with these pathologies were included. Furthermore, vasculitis is a rare disease, making its incidence difficult to determine precisely. To minimise this problem, centres capable of identifying these patients by consulting their service records or central databases were selected. Despite these measures, patients diagnosed and treated in the private healthcare system or other areas may have been missed. However, these pathologies require hospital diagnosis and treatment, reducing the likelihood that patients would not be in contact with public hospitals in their catchment area and, therefore would not be included in the incidence estimate.
ConclusionsThe RESER/NVAN project is one of the largest cohorts of patients with ANCA-associated vasculitis in Spain. Despite its retrospective nature, the extended time period analysed, extending it to almost the present day, and the geographical distribution of the centres will allow us to obtain more up-to-date and representative information for the country as a whole. This, in turn, will allow us to generate greater knowledge about the clinical characteristics and management of this disease.
CRediT authorship contribution statementSusana Romero-Yuste and Manuel Macía contributed equally to this work and share first authorship.
FundingThe RESER/NVAN study was funded by AstraZeneca and CSL Vifor. AstraZeneca and CSL Vifor did not influence the design, analysis, or interpretation of the results, which were carried out with strict independence from the funding industry.
Appendix A:RESER/NVAN project collaboration groupCristina Valero Martínez (Servicio de Reumatología), Rosario García de Vicuña (Servicio de Reumatología), Carolina Cisneros (Servicio de Neumología), Santos Castañeda (Servicio de Reumatología), Antonio Fernández Perpén (Servicio de Nefrología) (Hospital Universitario La Princesa, Madrid); Martí Aguilar (Servicio de Reumatología), Juliana Bordignon Draibe (Servicio de Nefrología) (Hospital Universitario de Bellvitge, Barcelona); Jesús Cerdeña (Servicio de Reumatología), Fayna González Cabrera (Servicio de Nefrología), Silvia Marrero Robayna (Servicio de Nefrología), Alicia Puente Puente (Servicio de Medicina Interna), Antonia de la Ascensión Álvarez Omar (Servicio de Medicina Interna) (Hospital Universitario de Gran Canaria Dr. Negrín, Gran Canaria); Patricia Moya Alvarado (Servicio de Reumatología), Ivan Castellvi (Servicio de Reumatología), Hèctor Corominas (Servicio de Reumatología), Diego Castillo (Servicio de Reumatología), Irene Silva (Servicio de Reumatología) (Hospital de la Santa Creu i Sant Pau, Barcelona), Monserrat Díaz Encarnación (Servicio de Nefrología), Helena Marco Rusiñol (Servicio de Nefrología), Xoana Barros Freira (Servicio de Nefrología) (Fundación Puigvert, Barcelona); Beatriz González Álvarez (Servicio de Reumatología), Cristina Córdoba Martín (Servicio de Reumatología) Mª José Reguera Carmona (Servicio de Nefrología), Mónica Delgado Sánchez (Servicio de Reumatología), Alejandro Alonso Bethencourt (Servicio de Nefrología) (Hospital Universitario Nuestra Señora de la Candelaria, Santa Cruz de Tenerife); Javier García González (Servicio de Reumatología), Enrique Morales Ruiz (Servicio de Nefrología), Eugenia Enríquez Merayo (Servicio de Reumatología), Isabel Hernandez Rodríguez (Servicio de Reumatología), Raquel Zas Vaamonde (Servicio de Reumatología), Natalia Molina Esteban (Servicio de Reumatología) (Hospital Universitario 12 de Octubre, Madrid); Fco. Javier Novoa Medina (Servicio de Reumatología), Germán Pérez Suárez (Servicio de Nefrología), Carlos Jorge Ripper (Servicio de Medicina Interna) (Hospital Universitario Insular de Gran Canaria, Las Palmas); Mercedes Freire González (Servicio de Reumatología) Marta da Cunha Naveira (Servicio de Nefrología), Guillermo González Arribas (Servicio de Reumatología), Clara Ventín Rodríguez (Servicio de Reumatología) (Complexo Hospitalario Universitario A Coruña, A Coruña); Vanesa Calvo (Servicio de Reumatología), Fabricio Benavides Villanueva (Servicio de Reumatología), Diana Prieto (Servicio de Reumatología), Luis Martín Penagos (Servicio de Nefrología), Ricardo Blanco (Servicio de Reumatología) (Hospital Universitario Marqués de Valdecilla, Santander); Gema Bonilla Hernán (Servicio de Reumatología), Maria Maldonado Martín (Servicio de Nefrología), Diana Peiteado Lopez (Servicio de Reumatología), Cristina Vega (Servicio de Nefrología), Begoña Rivas (Servicio de Nefrología), Pilar Nozal Aranda (Servicio de Inmunología), Ana Noblejas (Servicio de Medicina Interna), Irene Monjo Henry (Servicio de Reumatología), Luis Gómez Carrera (Servicio de Neumología) (Hospital Universitario La Paz, Madrid); Pablo Rodríguez Merlos (Servicio de Reumatología), Belén Serrano Benavente (Servicio de Reumatología), Julia Martínez Barrio (Servicio de Reumatología) (Hospital General Universitario Gregorio Marañón, Madrid); Evelin Cecilia Cervantes Pérez (Servicio de Reumatología), Enrique Peláez Pérez (Servicio de Nefrología), Luz Cuiña Barja (Servicio de Nefrología) (Complexo Hospitalario Universitario de Pontevedra, Pontevedra); Joaquín Belzunegui Otano (Servicio de Reumatología), Nerea Alcorta Lorenzo (Servicio de Reumatología) (Hospital Universitario de Donostia, San Sebastián); Francisco José De La Prada Álvarez (Servicio de Nefrología), Francisco Javier Toyos Saenz De Miera (Servicio de Reumatología), José Javier Pérez Venegas (Servicio de Reumatología), Fabiola Alonso García (Servicio de Nefrología), Mercedes Salgueira Lazo (Servicio de Nefrología), Rocío Molas (Servicio de Reumatología) (Hospital Universitario Virgen Macarena, Sevilla); Alberto Ruiz Román (Servicio de Reumatología), María Teresa Mora Mora (Servicio de Nefrología) (Hospital Universitario Juan Ramón Jiménez, Huelva); Nuria Lozano Rivas (Servicio de Reumatología), Carlos Marras Fernández (Servicio de Reumatología), Javier José Martínez Ferrín (Servicio de Reumatología), Jennifer Esther Ruiz Sara (Servicio de Reumatología), Ma Mercedes Piqueras García (Servicio de Reumatología), Ángela Egea Fuentes (Servicio de Reumatología), Ana Cristina Castillo González (Servicio de Reumatología), Fernando Hadad Arrascue (Servicio de Nefrología), Pedro Ortuño Lopez (Servicio de Nefrología) (Hospital Clínico Universitario Virgen de la Arrixaca, Murcia); Alida Taberner (Servicio de Reumatología), Juan Jose Alegre Sancho (Servicio de Reumatología), Ana Isabel Ávila Bernabeu (Servicio de Nefrología), Pablo Andujar Brazal (Servicio de Reumatología) (Hospital Universitari Doctor Peset, Valencia); Patricia Delgado Mallén (Servicio de Nefrología), Hiurma Sánchez Pérez (Servicio de Reumatología), Antonio Aznar Esquivel (Servicio de Reumatología), Esmeralda Delgado Frías (Servicio de Reumatología), Mª Ángeles Cobo Caso (Servicio de Nefrología), Rosa Miquel Rodríguez (Servicio de Nefrología), Sara Estupiñán Torres (Servicio de Nefrología) (Hospital Universitario de Canarias, Tenerife); Mª Ángeles Blazquez Cañamero (Servicio de Reumatología), Sandra Garrote Corral (Servicio de Reumatología), Ma Jesús García Villanueva (Servicio de Reumatología), Javier Villacorta Pérez (Servicio de Nefrología), Andrés González García (Servicio de Medicina Interna) (Hospital Universitario Ramón y Cajal, Madrid); Maria Machattou (Servicio de Reumatología) Pablo Navarro Palomo (Servicio de Reumatología), Blanca García Magallón (Servicio de Reumatología), Ana Huerta Arroyo (Servicio de Nefrología), Susana Mellor Pita (Servicio de Medicina Interna) (Hospital Universitario Puerta de Hierro Majadahonda, Madrid); Samuel Hernández Baldizon (Servicio de Reumatología), Mª Victoria Íñigo (Servicio de Nefrología), Antonio Juan Mas (Servicio de Reumatología), Inmaculada Ros Vilamajo (Servicio de Reumatología), Lilian López (Servicio de Reumatología), Regina Faré García (Servicio de Reumatología) (Hospital Son Llàtzer, Palma de Mallorca); Irene Carrión Barberá (Servicio de Reumatología), Tarek Carlos Salman Montes (Servicio de Reumatología), Ana Pros Simon (Servicio de Reumatología), Eva Rodríguez García (Servicio de Nefrología), Iago López (Servicio de Reumatología), María Lee Alcober (Servicio de Reumatología) (Hospital del Mar, Barcelona); Elisabet Perea Martínez (Servicio de Reumatología), Gloria Ros Soto (Servicio de Nefrología), Marta González Moreno (Servicio de Neumología), Mariano Andrés Collado (Servicio de Reumatología), Raquel García Sevilla (Servicio de Neumología), Miguel Perdiguero (Servicio de Nefrología), Paloma Vela (Servicio de Reumatología), Rocío Caño (Servicio de Reumatología), Silvia Gómez Sabater (Servicio de Reumatología) (Hospital General Universitario Dr. Balmis de Alicante, Alicante); Carlos Galisteo Lencastre Da Veiga (Servicio de Reumatología), Silvia Garcia (Servicio de Reumatología), Joan Calvet Fontova (Servicio de Reumatología) (Hospital Universitari Parc Tauli Sabadell, Sabadell); Idoia Acosta Hernández (Servicio de Nefrología), Andrea Buján López (Servicio de Nefrología), Mª Esther Ruíz Lucea (Servicio de Reumatología), Ana Rosa Intxaurbe Pellejero (Servicio de Reumatología), Natalia Rivera García (Servicio de Reumatología), Carmen Lucía García Gómez (Servicio de Reumatología) (Hospital Universitario Basurto, Bilbao); Remedios Toledo Rojas (Servicio de Nefrología), Carlos Romero Gómez (Servicio de Medicina Interna), Natalia Mena Vázquez (Servicio de Reumatología), Sara Manrique Arija (Servicio de Reumatología), Iván Pérez de Pedro (Servicio de Medicina Interna) Pilar Hidalgo Guzmán (Servicio de Nefrología), María del Mar Ayala Gutiérrez (Servicio de Medicina Interna), Halbert Hernández Negrin (Servicio de Reumatología) (Hospital Regional Universitario de Málaga, Málaga); Cristina Campos Fernandez (Servicio de Reumatología), Amalia Rueda Cid (Servicio de Reumatología), Jorge Juan Fragio Gil (Servicio de Reumatología), Pablo Martínez Calabuig (Servicio de Reumatología) (Hospital General Universitario de Valencia, Valencia); Jordi Camins Fàbregas (Servicio de Reumatología), Vera Ortiz Santamaría (Servicio de Reumatología) (Hospital General de Granollers, Barcelona); Rafaela Ortega Castro (Servicio de Reumatología), Alejandro Escudero Contreras (Servicio de Reumatología), Jerusalem Calvo Gutierrez (Servicio de Reumatología), Clementina López Medina (Servicio de Reumatología), Mª Carmen Ábalos (Servicio de Reumatología), Santiago Dans (Servicio de Reumatología) (Hospital Universitario Reina Sofía, Córdoba); Rafael Benito Melero González (Servicio de Reumatología), Jeanette Fernández Cusicanqui (Servicio de Nefrología), Almudena Barros Barros (Servicio de Reumatología), Francisco Fernandez Fleming (Servicio de Nefrología), Mercedes Moreiras Plaza (Servicio de Nefrología), Ana Fijó Prieto (Servicio de Nefrología) (Complexo Hospitalario Universitario de Vigo, Vigo); Sergio Rodríguez Montero (Servicio de Reumatología), Mª Nazaret Roldán Ruiz (Servicio de Reumatología), Celia Azabal Pérez (Servicio de Reumatología), Rosalia Martínez Pérez (Servicio de Reumatología), Mario León García (Servicio de Reumatología), Ana Moreno Giraldo (Servicio de Reumatología), Mª Esther Sánchez García (Servicio de Medicina Interna) (Hospital Universitario Virgen de Valme, Sevilla).
The authors have no conflict of interests to declare.
The following are Supplementary data to this article:
