Serum uric acid is associated with damage in patients with systemic lupus erythematosus
Identifieur interne : 000690 ( Pmc/Corpus ); précédent : 000689; suivant : 000691Serum uric acid is associated with damage in patients with systemic lupus erythematosus
Auteurs : Claudia Elera-Fitzcarrald ; Cristina Reátegui-Sokolova ; Rocio Violeta Gamboa-Cardenas ; Mariela Medina ; Francisco Zevallos ; Victor Román Pimentel-Quiroz ; Jorge Mariano Cucho-Venegas ; José Alfaro-Lozano ; Zoila Rodriguez-Bellido ; Cesar Augusto Pastor-Asurza ; Risto Alfredo Perich-Campos ; Graciela S. Alarc N ; Manuel Francisco Ugarte-GilSource :
- Lupus Science & Medicine [ 2053-8790 ] ; 2020.
Abstract
Serum uric acid levels have been reported as predictors of cardiovascular, pulmonary, neurological and renal morbidity in patients with SLE. However, their role in cumulative global damage in these patients has not yet been determined.
To determine whether serum uric acid levels are associated with new damage in patients with SLE.
This is a longitudinal study of patients with SLE from the Almenara Lupus Cohort, which began in 2012. At each visit, demographic and clinical characteristics were evaluated, such as activity (Systemic Lupus Erythematosus Disease Activity Index-2K or SLEDAI-2K) and cumulative damage (Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index or SDI). Treatment (glucocorticoids, immunosuppressive drugs and antimalarials) was also recorded. Univariable and multivariable Cox regression models were used to determine the impact of serum uric acid levels on the risk of new damage.
We evaluated 237 patients, with a mean age (SD) at diagnosis of 35.9 (13.1) years; 220 patients (92.8%) were women, and the duration of the disease was 7.3 (6.6) years. The mean SLEDAI-2K and SDI scores were 5.1 (4.2) and 0.9 (1.3), respectively. Serum uric acid level was 4.5 (1.4) mg/dL. Follow-up time was 3.1 (1.3) years, and 112 (47.3%) patients accrued damage during follow-up. In univariable and multivariable analyses, serum uric acid levels were associated with new damage (HR=1.141 (95% CI 1.016 to 1.282), p=0.026; HR=1.189 (95% CI 1.025 to 1.378), p=0.022, respectively).
Higher serum uric acid levels are associated with global damage in patients with SLE.
Url:
DOI: 10.1136/lupus-2019-000366
PubMed: 32153795
PubMed Central: 7046960
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PMC:7046960Le document en format XML
<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">Serum uric acid is associated with damage in patients with systemic lupus erythematosus</title><author><name sortKey="Elera Fitzcarrald, Claudia" sort="Elera Fitzcarrald, Claudia" uniqKey="Elera Fitzcarrald C" first="Claudia" last="Elera-Fitzcarrald">Claudia Elera-Fitzcarrald</name><affiliation><nlm:aff id="aff1"><institution content-type="department">School of Medicine</institution>,<institution>Universidad Científica del Sur</institution>,<addr-line content-type="city">Lima</addr-line>,<country>Peru</country></nlm:aff></affiliation><affiliation><nlm:aff id="aff2"><institution content-type="department">Rheumatology</institution>,<institution>Hospital Nacional Guillermo Almenara Irigoyen, EsSalud</institution>,<addr-line content-type="city">Lima</addr-line>,<country>Peru</country></nlm:aff></affiliation></author><author><name sortKey="Reategui Sokolova, Cristina" sort="Reategui Sokolova, Cristina" uniqKey="Reategui Sokolova C" first="Cristina" last="Reátegui-Sokolova">Cristina Reátegui-Sokolova</name><affiliation><nlm:aff id="aff2"><institution content-type="department">Rheumatology</institution>,<institution>Hospital Nacional Guillermo Almenara Irigoyen, EsSalud</institution>,<addr-line content-type="city">Lima</addr-line>,<country>Peru</country></nlm:aff></affiliation><affiliation><nlm:aff id="aff3"><institution content-type="department">Unidad de Investigación para la Generación y Síntesis de Evidencias en Salud</institution>,<institution>Universidad San Ignancio de Loyola</institution>,<addr-line content-type="city">Lima</addr-line>,<country>Peru</country></nlm:aff></affiliation></author><author><name sortKey="Gamboa Cardenas, Rocio Violeta" sort="Gamboa Cardenas, Rocio Violeta" uniqKey="Gamboa Cardenas R" first="Rocio Violeta" last="Gamboa-Cardenas">Rocio Violeta Gamboa-Cardenas</name><affiliation><nlm:aff id="aff2"><institution content-type="department">Rheumatology</institution>,<institution>Hospital Nacional Guillermo Almenara Irigoyen, EsSalud</institution>,<addr-line content-type="city">Lima</addr-line>,<country>Peru</country></nlm:aff></affiliation></author><author><name sortKey="Medina, Mariela" sort="Medina, Mariela" uniqKey="Medina M" first="Mariela" last="Medina">Mariela Medina</name><affiliation><nlm:aff id="aff2"><institution content-type="department">Rheumatology</institution>,<institution>Hospital Nacional Guillermo Almenara Irigoyen, EsSalud</institution>,<addr-line content-type="city">Lima</addr-line>,<country>Peru</country></nlm:aff></affiliation></author><author><name sortKey="Zevallos, Francisco" sort="Zevallos, Francisco" uniqKey="Zevallos F" first="Francisco" last="Zevallos">Francisco Zevallos</name><affiliation><nlm:aff id="aff2"><institution content-type="department">Rheumatology</institution>,<institution>Hospital Nacional Guillermo Almenara Irigoyen, EsSalud</institution>,<addr-line content-type="city">Lima</addr-line>,<country>Peru</country></nlm:aff></affiliation></author><author><name sortKey="Pimentel Quiroz, Victor Roman" sort="Pimentel Quiroz, Victor Roman" uniqKey="Pimentel Quiroz V" first="Victor Román" last="Pimentel-Quiroz">Victor Román Pimentel-Quiroz</name><affiliation><nlm:aff id="aff2"><institution content-type="department">Rheumatology</institution>,<institution>Hospital Nacional Guillermo Almenara Irigoyen, EsSalud</institution>,<addr-line content-type="city">Lima</addr-line>,<country>Peru</country></nlm:aff></affiliation></author><author><name sortKey="Cucho Venegas, Jorge Mariano" sort="Cucho Venegas, Jorge Mariano" uniqKey="Cucho Venegas J" first="Jorge Mariano" last="Cucho-Venegas">Jorge Mariano Cucho-Venegas</name><affiliation><nlm:aff id="aff2"><institution content-type="department">Rheumatology</institution>,<institution>Hospital Nacional Guillermo Almenara Irigoyen, EsSalud</institution>,<addr-line content-type="city">Lima</addr-line>,<country>Peru</country></nlm:aff></affiliation></author><author><name sortKey="Alfaro Lozano, Jose" sort="Alfaro Lozano, Jose" uniqKey="Alfaro Lozano J" first="José" last="Alfaro-Lozano">José Alfaro-Lozano</name><affiliation><nlm:aff id="aff2"><institution content-type="department">Rheumatology</institution>,<institution>Hospital Nacional Guillermo Almenara Irigoyen, EsSalud</institution>,<addr-line content-type="city">Lima</addr-line>,<country>Peru</country></nlm:aff></affiliation></author><author><name sortKey="Rodriguez Bellido, Zoila" sort="Rodriguez Bellido, Zoila" uniqKey="Rodriguez Bellido Z" first="Zoila" last="Rodriguez-Bellido">Zoila Rodriguez-Bellido</name><affiliation><nlm:aff id="aff2"><institution content-type="department">Rheumatology</institution>,<institution>Hospital Nacional Guillermo Almenara Irigoyen, EsSalud</institution>,<addr-line content-type="city">Lima</addr-line>,<country>Peru</country></nlm:aff></affiliation><affiliation><nlm:aff id="aff4"><institution>Universidad Nacional Mayor de San Marcos</institution>,<addr-line content-type="city">Lima</addr-line>,<country>Peru</country></nlm:aff></affiliation></author><author><name sortKey="Pastor Asurza, Cesar Augusto" sort="Pastor Asurza, Cesar Augusto" uniqKey="Pastor Asurza C" first="Cesar Augusto" last="Pastor-Asurza">Cesar Augusto Pastor-Asurza</name><affiliation><nlm:aff id="aff2"><institution content-type="department">Rheumatology</institution>,<institution>Hospital Nacional Guillermo Almenara Irigoyen, EsSalud</institution>,<addr-line content-type="city">Lima</addr-line>,<country>Peru</country></nlm:aff></affiliation><affiliation><nlm:aff id="aff4"><institution>Universidad Nacional Mayor de San Marcos</institution>,<addr-line content-type="city">Lima</addr-line>,<country>Peru</country></nlm:aff></affiliation></author><author><name sortKey="Perich Campos, Risto Alfredo" sort="Perich Campos, Risto Alfredo" uniqKey="Perich Campos R" first="Risto Alfredo" last="Perich-Campos">Risto Alfredo Perich-Campos</name><affiliation><nlm:aff id="aff2"><institution content-type="department">Rheumatology</institution>,<institution>Hospital Nacional Guillermo Almenara Irigoyen, EsSalud</institution>,<addr-line content-type="city">Lima</addr-line>,<country>Peru</country></nlm:aff></affiliation><affiliation><nlm:aff id="aff4"><institution>Universidad Nacional Mayor de San Marcos</institution>,<addr-line content-type="city">Lima</addr-line>,<country>Peru</country></nlm:aff></affiliation></author><author><name sortKey="Alarc N, Graciela S" sort="Alarc N, Graciela S" uniqKey="Alarc N G" first="Graciela S" last="Alarc N">Graciela S. Alarc N</name><affiliation><nlm:aff id="aff5"><institution content-type="department">Department of Medicine, Division of Clinical Immunology and Rheumatology</institution>,<institution>School of Medicine, The University of Alabama</institution>,<addr-line content-type="city">Birmingham</addr-line>,<addr-line content-type="state">Alabama</addr-line>,<country>USA</country></nlm:aff></affiliation><affiliation><nlm:aff id="aff6"><institution content-type="department">Department of Medicine</institution>,<institution>Universidad Peruana Cayetana Heredia</institution>,<addr-line content-type="city">Lima</addr-line>,<country>Peru</country></nlm:aff></affiliation></author><author><name sortKey="Ugarte Gil, Manuel Francisco" sort="Ugarte Gil, Manuel Francisco" uniqKey="Ugarte Gil M" first="Manuel Francisco" last="Ugarte-Gil">Manuel Francisco Ugarte-Gil</name><affiliation><nlm:aff id="aff1"><institution content-type="department">School of Medicine</institution>,<institution>Universidad Científica del Sur</institution>,<addr-line content-type="city">Lima</addr-line>,<country>Peru</country></nlm:aff></affiliation><affiliation><nlm:aff id="aff2"><institution content-type="department">Rheumatology</institution>,<institution>Hospital Nacional Guillermo Almenara Irigoyen, EsSalud</institution>,<addr-line content-type="city">Lima</addr-line>,<country>Peru</country></nlm:aff></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">PMC</idno><idno type="pmid">32153795</idno><idno type="pmc">7046960</idno><idno type="url">http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7046960</idno><idno type="RBID">PMC:7046960</idno><idno type="doi">10.1136/lupus-2019-000366</idno><date when="2020">2020</date><idno type="wicri:Area/Pmc/Corpus">000690</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Corpus" wicri:corpus="PMC">000690</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">Serum uric acid is associated with damage in patients with systemic lupus erythematosus</title><author><name sortKey="Elera Fitzcarrald, Claudia" sort="Elera Fitzcarrald, Claudia" uniqKey="Elera Fitzcarrald C" first="Claudia" last="Elera-Fitzcarrald">Claudia Elera-Fitzcarrald</name><affiliation><nlm:aff id="aff1"><institution content-type="department">School of Medicine</institution>,<institution>Universidad Científica del Sur</institution>,<addr-line content-type="city">Lima</addr-line>,<country>Peru</country></nlm:aff></affiliation><affiliation><nlm:aff id="aff2"><institution content-type="department">Rheumatology</institution>,<institution>Hospital Nacional Guillermo Almenara Irigoyen, EsSalud</institution>,<addr-line content-type="city">Lima</addr-line>,<country>Peru</country></nlm:aff></affiliation></author><author><name sortKey="Reategui Sokolova, Cristina" sort="Reategui Sokolova, Cristina" uniqKey="Reategui Sokolova C" first="Cristina" last="Reátegui-Sokolova">Cristina Reátegui-Sokolova</name><affiliation><nlm:aff id="aff2"><institution content-type="department">Rheumatology</institution>,<institution>Hospital Nacional Guillermo Almenara Irigoyen, EsSalud</institution>,<addr-line content-type="city">Lima</addr-line>,<country>Peru</country></nlm:aff></affiliation><affiliation><nlm:aff id="aff3"><institution content-type="department">Unidad de Investigación para la Generación y Síntesis de Evidencias en Salud</institution>,<institution>Universidad San Ignancio de Loyola</institution>,<addr-line content-type="city">Lima</addr-line>,<country>Peru</country></nlm:aff></affiliation></author><author><name sortKey="Gamboa Cardenas, Rocio Violeta" sort="Gamboa Cardenas, Rocio Violeta" uniqKey="Gamboa Cardenas R" first="Rocio Violeta" last="Gamboa-Cardenas">Rocio Violeta Gamboa-Cardenas</name><affiliation><nlm:aff id="aff2"><institution content-type="department">Rheumatology</institution>,<institution>Hospital Nacional Guillermo Almenara Irigoyen, EsSalud</institution>,<addr-line content-type="city">Lima</addr-line>,<country>Peru</country></nlm:aff></affiliation></author><author><name sortKey="Medina, Mariela" sort="Medina, Mariela" uniqKey="Medina M" first="Mariela" last="Medina">Mariela Medina</name><affiliation><nlm:aff id="aff2"><institution content-type="department">Rheumatology</institution>,<institution>Hospital Nacional Guillermo Almenara Irigoyen, EsSalud</institution>,<addr-line content-type="city">Lima</addr-line>,<country>Peru</country></nlm:aff></affiliation></author><author><name sortKey="Zevallos, Francisco" sort="Zevallos, Francisco" uniqKey="Zevallos F" first="Francisco" last="Zevallos">Francisco Zevallos</name><affiliation><nlm:aff id="aff2"><institution content-type="department">Rheumatology</institution>,<institution>Hospital Nacional Guillermo Almenara Irigoyen, EsSalud</institution>,<addr-line content-type="city">Lima</addr-line>,<country>Peru</country></nlm:aff></affiliation></author><author><name sortKey="Pimentel Quiroz, Victor Roman" sort="Pimentel Quiroz, Victor Roman" uniqKey="Pimentel Quiroz V" first="Victor Román" last="Pimentel-Quiroz">Victor Román Pimentel-Quiroz</name><affiliation><nlm:aff id="aff2"><institution content-type="department">Rheumatology</institution>,<institution>Hospital Nacional Guillermo Almenara Irigoyen, EsSalud</institution>,<addr-line content-type="city">Lima</addr-line>,<country>Peru</country></nlm:aff></affiliation></author><author><name sortKey="Cucho Venegas, Jorge Mariano" sort="Cucho Venegas, Jorge Mariano" uniqKey="Cucho Venegas J" first="Jorge Mariano" last="Cucho-Venegas">Jorge Mariano Cucho-Venegas</name><affiliation><nlm:aff id="aff2"><institution content-type="department">Rheumatology</institution>,<institution>Hospital Nacional Guillermo Almenara Irigoyen, EsSalud</institution>,<addr-line content-type="city">Lima</addr-line>,<country>Peru</country></nlm:aff></affiliation></author><author><name sortKey="Alfaro Lozano, Jose" sort="Alfaro Lozano, Jose" uniqKey="Alfaro Lozano J" first="José" last="Alfaro-Lozano">José Alfaro-Lozano</name><affiliation><nlm:aff id="aff2"><institution content-type="department">Rheumatology</institution>,<institution>Hospital Nacional Guillermo Almenara Irigoyen, EsSalud</institution>,<addr-line content-type="city">Lima</addr-line>,<country>Peru</country></nlm:aff></affiliation></author><author><name sortKey="Rodriguez Bellido, Zoila" sort="Rodriguez Bellido, Zoila" uniqKey="Rodriguez Bellido Z" first="Zoila" last="Rodriguez-Bellido">Zoila Rodriguez-Bellido</name><affiliation><nlm:aff id="aff2"><institution content-type="department">Rheumatology</institution>,<institution>Hospital Nacional Guillermo Almenara Irigoyen, EsSalud</institution>,<addr-line content-type="city">Lima</addr-line>,<country>Peru</country></nlm:aff></affiliation><affiliation><nlm:aff id="aff4"><institution>Universidad Nacional Mayor de San Marcos</institution>,<addr-line content-type="city">Lima</addr-line>,<country>Peru</country></nlm:aff></affiliation></author><author><name sortKey="Pastor Asurza, Cesar Augusto" sort="Pastor Asurza, Cesar Augusto" uniqKey="Pastor Asurza C" first="Cesar Augusto" last="Pastor-Asurza">Cesar Augusto Pastor-Asurza</name><affiliation><nlm:aff id="aff2"><institution content-type="department">Rheumatology</institution>,<institution>Hospital Nacional Guillermo Almenara Irigoyen, EsSalud</institution>,<addr-line content-type="city">Lima</addr-line>,<country>Peru</country></nlm:aff></affiliation><affiliation><nlm:aff id="aff4"><institution>Universidad Nacional Mayor de San Marcos</institution>,<addr-line content-type="city">Lima</addr-line>,<country>Peru</country></nlm:aff></affiliation></author><author><name sortKey="Perich Campos, Risto Alfredo" sort="Perich Campos, Risto Alfredo" uniqKey="Perich Campos R" first="Risto Alfredo" last="Perich-Campos">Risto Alfredo Perich-Campos</name><affiliation><nlm:aff id="aff2"><institution content-type="department">Rheumatology</institution>,<institution>Hospital Nacional Guillermo Almenara Irigoyen, EsSalud</institution>,<addr-line content-type="city">Lima</addr-line>,<country>Peru</country></nlm:aff></affiliation><affiliation><nlm:aff id="aff4"><institution>Universidad Nacional Mayor de San Marcos</institution>,<addr-line content-type="city">Lima</addr-line>,<country>Peru</country></nlm:aff></affiliation></author><author><name sortKey="Alarc N, Graciela S" sort="Alarc N, Graciela S" uniqKey="Alarc N G" first="Graciela S" last="Alarc N">Graciela S. Alarc N</name><affiliation><nlm:aff id="aff5"><institution content-type="department">Department of Medicine, Division of Clinical Immunology and Rheumatology</institution>,<institution>School of Medicine, The University of Alabama</institution>,<addr-line content-type="city">Birmingham</addr-line>,<addr-line content-type="state">Alabama</addr-line>,<country>USA</country></nlm:aff></affiliation><affiliation><nlm:aff id="aff6"><institution content-type="department">Department of Medicine</institution>,<institution>Universidad Peruana Cayetana Heredia</institution>,<addr-line content-type="city">Lima</addr-line>,<country>Peru</country></nlm:aff></affiliation></author><author><name sortKey="Ugarte Gil, Manuel Francisco" sort="Ugarte Gil, Manuel Francisco" uniqKey="Ugarte Gil M" first="Manuel Francisco" last="Ugarte-Gil">Manuel Francisco Ugarte-Gil</name><affiliation><nlm:aff id="aff1"><institution content-type="department">School of Medicine</institution>,<institution>Universidad Científica del Sur</institution>,<addr-line content-type="city">Lima</addr-line>,<country>Peru</country></nlm:aff></affiliation><affiliation><nlm:aff id="aff2"><institution content-type="department">Rheumatology</institution>,<institution>Hospital Nacional Guillermo Almenara Irigoyen, EsSalud</institution>,<addr-line content-type="city">Lima</addr-line>,<country>Peru</country></nlm:aff></affiliation></author></analytic><series><title level="j">Lupus Science & Medicine</title><idno type="eISSN">2053-8790</idno><imprint><date when="2020">2020</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><sec><title>Introduction</title><p>Serum uric acid levels have been reported as predictors of cardiovascular, pulmonary, neurological and renal morbidity in patients with SLE. However, their role in cumulative global damage in these patients has not yet been determined.</p></sec><sec><title>Objective</title><p>To determine whether serum uric acid levels are associated with new damage in patients with SLE.</p></sec><sec><title>Methods</title><p>This is a longitudinal study of patients with SLE from the Almenara Lupus Cohort, which began in 2012. At each visit, demographic and clinical characteristics were evaluated, such as activity (Systemic Lupus Erythematosus Disease Activity Index-2K or SLEDAI-2K) and cumulative damage (Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index or SDI). Treatment (glucocorticoids, immunosuppressive drugs and antimalarials) was also recorded. Univariable and multivariable Cox regression models were used to determine the impact of serum uric acid levels on the risk of new damage.</p></sec><sec><title>Results</title><p>We evaluated 237 patients, with a mean age (SD) at diagnosis of 35.9 (13.1) years; 220 patients (92.8%) were women, and the duration of the disease was 7.3 (6.6) years. The mean SLEDAI-2K and SDI scores were 5.1 (4.2) and 0.9 (1.3), respectively. Serum uric acid level was 4.5 (1.4) mg/dL. Follow-up time was 3.1 (1.3) years, and 112 (47.3%) patients accrued damage during follow-up. In univariable and multivariable analyses, serum uric acid levels were associated with new damage (HR=1.141 (95% CI 1.016 to 1.282), p=0.026; HR=1.189 (95% CI 1.025 to 1.378), p=0.022, respectively).</p></sec><sec><title>Conclusion</title><p>Higher serum uric acid levels are associated with global damage in patients with SLE.</p></sec></div></front><back><div1 type="bibliography"><listBibl><biblStruct><analytic><author><name sortKey="Desideri, G" uniqKey="Desideri G">G Desideri</name></author><author><name sortKey="Castaldo, G" uniqKey="Castaldo G">G Castaldo</name></author><author><name sortKey="Lombardi, A" uniqKey="Lombardi A">A Lombardi</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Trevi O Becerra, A" uniqKey="Trevi O Becerra A">A Treviño-Becerra</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Stack, Ag" uniqKey="Stack A">AG Stack</name></author><author><name sortKey="Hanley, A" uniqKey="Hanley A">A 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<front><journal-meta><journal-id journal-id-type="nlm-ta">Lupus Sci Med</journal-id><journal-id journal-id-type="iso-abbrev">Lupus Sci Med</journal-id><journal-id journal-id-type="hwp">lupusscimed</journal-id><journal-id journal-id-type="publisher-id">lupus</journal-id><journal-title-group><journal-title>Lupus Science & Medicine</journal-title></journal-title-group><issn pub-type="epub">2053-8790</issn><publisher><publisher-name>BMJ Publishing Group</publisher-name><publisher-loc>BMA House, Tavistock Square, London, WC1H 9JR</publisher-loc></publisher></journal-meta><article-meta><article-id pub-id-type="pmid">32153795</article-id><article-id pub-id-type="pmc">7046960</article-id><article-id pub-id-type="publisher-id">lupus-2019-000366</article-id><article-id pub-id-type="doi">10.1136/lupus-2019-000366</article-id><article-categories><subj-group subj-group-type="heading"><subject>Epidemiology and Outcomes</subject></subj-group><subj-group subj-group-type="hwp-journal-coll"><subject>1506</subject><subject>2257</subject></subj-group><series-title>Original research</series-title></article-categories><title-group><article-title>Serum uric acid is associated with damage in patients with systemic lupus erythematosus</article-title></title-group><contrib-group><contrib id="author-48988542" contrib-type="author" corresp="yes"><contrib-id contrib-id-type="orcid" authenticated="false">http://orcid.org/0000-0001-7271-2523</contrib-id><name><surname>Elera-Fitzcarrald</surname><given-names>Claudia</given-names></name><xref ref-type="aff" rid="aff1">1</xref><xref ref-type="aff" rid="aff2">2</xref></contrib><contrib id="author-49233784" contrib-type="author"><name><surname>Reátegui-Sokolova</surname><given-names>Cristina</given-names></name><xref ref-type="aff" rid="aff2">2</xref><xref ref-type="aff" rid="aff3">3</xref></contrib><contrib id="author-35676905" contrib-type="author"><name><surname>Gamboa-Cardenas</surname><given-names>Rocio Violeta</given-names></name><xref ref-type="aff" rid="aff2">2</xref></contrib><contrib id="author-72918891" contrib-type="author"><name><surname>Medina</surname><given-names>Mariela</given-names></name><xref ref-type="aff" rid="aff2">2</xref></contrib><contrib id="author-35676917" contrib-type="author"><name><surname>Zevallos</surname><given-names>Francisco</given-names></name><xref ref-type="aff" rid="aff2">2</xref></contrib><contrib id="author-50407697" contrib-type="author"><contrib-id contrib-id-type="orcid" authenticated="false">http://orcid.org/0000-0002-3638-7054</contrib-id><name><surname>Pimentel-Quiroz</surname><given-names>Victor Román</given-names></name><xref ref-type="aff" rid="aff2">2</xref></contrib><contrib id="author-33701670" contrib-type="author"><name><surname>Cucho-Venegas</surname><given-names>Jorge Mariano</given-names></name><xref ref-type="aff" rid="aff2">2</xref></contrib><contrib id="author-72918990" contrib-type="author"><name><surname>Alfaro-Lozano</surname><given-names>José</given-names></name><xref ref-type="aff" rid="aff2">2</xref></contrib><contrib id="author-35676962" contrib-type="author"><name><surname>Rodriguez-Bellido</surname><given-names>Zoila</given-names></name><xref ref-type="aff" rid="aff2">2</xref><xref ref-type="aff" rid="aff4">4</xref></contrib><contrib id="author-34087453" contrib-type="author"><name><surname>Pastor-Asurza</surname><given-names>Cesar Augusto</given-names></name><xref ref-type="aff" rid="aff2">2</xref><xref ref-type="aff" rid="aff4">4</xref></contrib><contrib id="author-35676939" contrib-type="author"><name><surname>Perich-Campos</surname><given-names>Risto Alfredo</given-names></name><xref ref-type="aff" rid="aff2">2</xref><xref ref-type="aff" rid="aff4">4</xref></contrib><contrib id="author-36184450" contrib-type="author"><name><surname>Alarcón</surname><given-names>Graciela S</given-names></name><xref ref-type="aff" rid="aff5">5</xref><xref ref-type="aff" rid="aff6">6</xref></contrib><contrib id="author-34087246" contrib-type="author"><contrib-id contrib-id-type="orcid" authenticated="false">http://orcid.org/0000-0003-1728-1999</contrib-id><name><surname>Ugarte-Gil</surname><given-names>Manuel Francisco</given-names></name><xref ref-type="aff" rid="aff1">1</xref><xref ref-type="aff" rid="aff2">2</xref></contrib></contrib-group><aff id="aff1"><label>1</label><institution content-type="department">School of Medicine</institution>,<institution>Universidad Científica del Sur</institution>,<addr-line content-type="city">Lima</addr-line>,<country>Peru</country></aff><aff id="aff2"><label>2</label><institution content-type="department">Rheumatology</institution>,<institution>Hospital Nacional Guillermo Almenara Irigoyen, EsSalud</institution>,<addr-line content-type="city">Lima</addr-line>,<country>Peru</country></aff><aff id="aff3"><label>3</label><institution content-type="department">Unidad de Investigación para la Generación y Síntesis de Evidencias en Salud</institution>,<institution>Universidad San Ignancio de Loyola</institution>,<addr-line content-type="city">Lima</addr-line>,<country>Peru</country></aff><aff id="aff4"><label>4</label><institution>Universidad Nacional Mayor de San Marcos</institution>,<addr-line content-type="city">Lima</addr-line>,<country>Peru</country></aff><aff id="aff5"><label>5</label><institution content-type="department">Department of Medicine, Division of Clinical Immunology and Rheumatology</institution>,<institution>School of Medicine, The University of Alabama</institution>,<addr-line content-type="city">Birmingham</addr-line>,<addr-line content-type="state">Alabama</addr-line>,<country>USA</country></aff><aff id="aff6"><label>6</label><institution content-type="department">Department of Medicine</institution>,<institution>Universidad Peruana Cayetana Heredia</institution>,<addr-line content-type="city">Lima</addr-line>,<country>Peru</country></aff><author-notes><corresp><label>Correspondence to</label> Dr Claudia Elera-Fitzcarrald; <email>claudiaelerafitz@gmail.com</email></corresp></author-notes><pub-date pub-type="collection"><year>2020</year></pub-date><pub-date pub-type="epub"><day>5</day><month>2</month><year>2020</year></pub-date><volume>7</volume><issue>1</issue><elocation-id>e000366</elocation-id><history><date date-type="received"><day>09</day><month>10</month><year>2019</year></date><date date-type="rev-recd"><day>13</day><month>1</month><year>2020</year></date><date date-type="accepted"><day>22</day><month>1</month><year>2020</year></date></history><permissions><copyright-statement>© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.</copyright-statement><copyright-year>2020</copyright-year><license license-type="open-access"><ali:license_ref start_date="2020-02-05">http://creativecommons.org/licenses/by-nc/4.0/</ali:license_ref><license-p>This is an open access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited, appropriate credit is given, any changes made indicated, and the use is non-commercial. See: <ext-link ext-link-type="uri" xlink:href="http://creativecommons.org/licenses/by-nc/4.0/">http://creativecommons.org/licenses/by-nc/4.0/</ext-link>.</license-p></license></permissions><self-uri xlink:title="pdf" xlink:href="lupus-2019-000366.pdf"></self-uri><abstract><sec><title>Introduction</title><p>Serum uric acid levels have been reported as predictors of cardiovascular, pulmonary, neurological and renal morbidity in patients with SLE. However, their role in cumulative global damage in these patients has not yet been determined.</p></sec><sec><title>Objective</title><p>To determine whether serum uric acid levels are associated with new damage in patients with SLE.</p></sec><sec><title>Methods</title><p>This is a longitudinal study of patients with SLE from the Almenara Lupus Cohort, which began in 2012. At each visit, demographic and clinical characteristics were evaluated, such as activity (Systemic Lupus Erythematosus Disease Activity Index-2K or SLEDAI-2K) and cumulative damage (Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index or SDI). Treatment (glucocorticoids, immunosuppressive drugs and antimalarials) was also recorded. Univariable and multivariable Cox regression models were used to determine the impact of serum uric acid levels on the risk of new damage.</p></sec><sec><title>Results</title><p>We evaluated 237 patients, with a mean age (SD) at diagnosis of 35.9 (13.1) years; 220 patients (92.8%) were women, and the duration of the disease was 7.3 (6.6) years. The mean SLEDAI-2K and SDI scores were 5.1 (4.2) and 0.9 (1.3), respectively. Serum uric acid level was 4.5 (1.4) mg/dL. Follow-up time was 3.1 (1.3) years, and 112 (47.3%) patients accrued damage during follow-up. In univariable and multivariable analyses, serum uric acid levels were associated with new damage (HR=1.141 (95% CI 1.016 to 1.282), p=0.026; HR=1.189 (95% CI 1.025 to 1.378), p=0.022, respectively).</p></sec><sec><title>Conclusion</title><p>Higher serum uric acid levels are associated with global damage in patients with SLE.</p></sec></abstract><kwd-group><kwd>systemic lupus erythematosus</kwd><kwd>autoimmune diseases</kwd><kwd>autoimmunity</kwd></kwd-group><funding-group><award-group id="funding-1"><funding-source><institution-wrap><institution>Pan American League of Associations for Rheumatology (PANLAR)</institution></institution-wrap></funding-source><award-id>2015 PANLAR Prize</award-id></award-group><award-group id="funding-2"><funding-source><institution-wrap><institution>Institutional grant from EsSalud</institution></institution-wrap></funding-source><award-id>04-IETSI-ESALUD-2016</award-id><award-id>1483-GCGP-ESSALUD-2013</award-id><award-id>1733-GCGP-ESSALUD-2014</award-id><award-id>2015 Kaelin Prize</award-id></award-group></funding-group><custom-meta-group><custom-meta><meta-name>special-feature</meta-name><meta-value>unlocked</meta-value></custom-meta></custom-meta-group></article-meta></front><body><sec sec-type="intro" id="s1"><title>Introduction</title><p>In humans, uric acid is the final product of purine metabolism. At physiological pH, uric acid is found predominantly (98%–99%) as a deprotonated anion. The solubility of uric acid at normal physiological pH is generally given at 6.8 mg/dL, with reference ranges for uric acid of 3.5–7.2 mg/dL (210–430 µmol/L) and 2.6–6.0 mg/dL (155–360 µmol/L) in younger men and premenopausal women, respectively.<xref rid="R1" ref-type="bibr">1</xref> Hyperuricaemia is the result of increased production or decreased excretion of uric acid.<xref rid="R2" ref-type="bibr">2</xref> Uric acid levels have been associated with increased risk of heart mortality,<xref rid="R3" ref-type="bibr">3</xref> increased risk of kidney disease<xref rid="R4" ref-type="bibr">4</xref> and as a predictor of metabolic syndrome.<xref rid="R5" ref-type="bibr">5</xref></p><p>In patients with SLE, uric acid has been recognised as a potential marker of endothelial dysfunction and renal disease, as an association has been found between active lupus nephritis and hyperuricaemia,<xref rid="R6" ref-type="bibr">6</xref> as well as with cerebral infarction and peripheral neuropathy.<xref rid="R7" ref-type="bibr">7</xref> Likewise, uric acid levels are useful in predicting the future development of pulmonary hypertension in patients with SLE with normal basal systolic pulmonary artery pressure.<xref rid="R8" ref-type="bibr">8</xref> In addition, serum uric acid levels have been reported as predictor of increased risk of kidney damage.<xref rid="R9" ref-type="bibr">9</xref></p><p>Thus, the objective of this study was to determine whether serum uric acid levels are associated with the occurrence of new damage in patients with SLE.</p></sec><sec sec-type="methods" id="s2"><title>Methods</title><sec id="s2-1"><title>Patients</title><p>Starting in January 2012, all patients with SLE presenting to the Rheumatology Department of the Hospital Guillermo Almenara Irigoyen in Lima, Peru, have been invited to participate in the Almenara Lupus Cohort.</p><p>All patients met the 1997 American College of Rheumatology (ACR) criteria when entering the cohort. Patients with at least two visits were included. Demographic data included gender, age at diagnosis, socioeconomic status according to the Graffar method, and educational level defined as years of formal education. On the other hand, clinical variables included disease activity (evaluated using the Systemic Lupus Erythematosus Disease Activity Index-2K (SLEDAI-2K)),<xref rid="R10" ref-type="bibr">10</xref> damage (assessed using the Systemic Lupus International Collaborating Clinics/ACR Damage Index (SDI)),<xref rid="R11" ref-type="bibr">11</xref> disease duration and comorbidities using the Charlson Comorbidity Index.<xref rid="R12" ref-type="bibr">12</xref> Therapeutic variables included the use of glucocorticoids (current dose and time of exposure). Similarly, the use of immunosuppressive and antimalarial drugs was recorded as current, past or never administered. A past user was defined as those patients receiving treatment until the day before the assessment. All variables were assessed at baseline, with the exception of new damage, which was assessed at subsequent visits.</p></sec><sec id="s2-2"><title>Statistical analyses</title><p>Univariable and multivariable Cox regression models were performed to determine the impact of serum uric acid level on the risk of new damage. Multivariable models were adjusted for age at diagnosis, disease duration, socioeconomic status, educational level, SLEDAI-2K, SDI, comorbidities, and use of prednisone, immunosuppressive and antimalarial drugs. P<0.05 was considered significant in all analyses. All statistical analyses were performed using SPSS V.26.0.</p></sec></sec><sec sec-type="results" id="s3"><title>Results</title><p>Two hundred and thirty-seven patients with SLE were evaluated. The mean age (SD) at diagnosis was 35.9 (13.1) years, 220 patients (92.8%) were women, almost all were Mestizo (European and Native American ancestry), and the disease duration at baseline was 7.3 (6.6) years. The mean SLEDAI-2K and SDI scores were 5.1 (4.2) and 0.9 (1.3), respectively. Charlson Comorbidity Index score was 0.5 (0.9). Serum uric acid levels were 4.5 (1.4) mg/dL; 24 (10.1%) patients had uric acid levels above the normal limit. The current mean dose of prednisone was 7.1 (6.4) mg/day. Time of exposure to prednisone was 6.9 (6.2) years, and follow-up time was 3.1 (1.3) years. One hundred and twelve (47.3%) patients accumulated some type of damage during follow-up. Patient characteristics are shown in <xref rid="T1" ref-type="table">table 1</xref>.</p><table-wrap id="T1" orientation="portrait" position="float"><label>Table 1</label><caption><p>Characteristics of patients with SLE</p></caption><table frame="hsides" rules="groups"><thead><tr><td align="left" valign="bottom" rowspan="1" colspan="1"></td><td align="left" valign="bottom" rowspan="1" colspan="1">Mean or n</td><td align="left" valign="bottom" rowspan="1" colspan="1">SD or percentage</td></tr></thead><tbody><tr><td align="left" valign="top" rowspan="1" colspan="1">Age at diagnosis (years)</td><td align="char" char="." valign="top" rowspan="1" colspan="1">35.9</td><td align="char" char="." valign="top" rowspan="1" colspan="1">13.1</td></tr><tr><td align="left" valign="top" rowspan="1" colspan="1">Gender, male</td><td align="char" char="." valign="top" rowspan="1" colspan="1">17</td><td align="char" char="." valign="top" rowspan="1" colspan="1">7.2</td></tr><tr><td align="left" valign="top" rowspan="1" colspan="1">Socioeconomic status</td><td align="left" valign="top" rowspan="1" colspan="1"></td><td align="left" valign="top" rowspan="1" colspan="1"></td></tr><tr><td align="left" valign="top" rowspan="1" colspan="1"> High</td><td align="char" char="." valign="top" rowspan="1" colspan="1">46</td><td align="char" char="." valign="top" rowspan="1" colspan="1">19.4</td></tr><tr><td align="left" valign="top" rowspan="1" colspan="1"> Medium</td><td align="char" char="." valign="top" rowspan="1" colspan="1">96</td><td align="char" char="." valign="top" rowspan="1" colspan="1">40.5</td></tr><tr><td align="left" valign="top" rowspan="1" colspan="1"> Low</td><td align="char" char="." valign="top" rowspan="1" colspan="1">95</td><td align="char" char="." valign="top" rowspan="1" colspan="1">40.1</td></tr><tr><td align="left" valign="top" rowspan="1" colspan="1">Educational level (years)</td><td align="char" char="." valign="top" rowspan="1" colspan="1">13.1</td><td align="char" char="." valign="top" rowspan="1" colspan="1">3.2</td></tr><tr><td align="left" valign="top" rowspan="1" colspan="1">Disease duration (years)</td><td align="char" char="." valign="top" rowspan="1" colspan="1">7.4</td><td align="char" char="." valign="top" rowspan="1" colspan="1">6.7</td></tr><tr><td align="left" valign="top" rowspan="1" colspan="1">Uric acid level (mg/dL)</td><td align="char" char="." valign="top" rowspan="1" colspan="1">4.6</td><td align="char" char="." valign="top" rowspan="1" colspan="1">1.5</td></tr><tr><td align="left" valign="top" rowspan="1" colspan="1">SLEDAI-2K</td><td align="char" char="." valign="top" rowspan="1" colspan="1">5.2</td><td align="char" char="." valign="top" rowspan="1" colspan="1">4.3</td></tr><tr><td align="left" valign="top" rowspan="1" colspan="1">SDI</td><td align="char" char="." valign="top" rowspan="1" colspan="1">1.0</td><td align="char" char="." valign="top" rowspan="1" colspan="1">1.3</td></tr><tr><td align="left" valign="top" rowspan="1" colspan="1">Charlson Comorbidity Index</td><td align="char" char="." valign="top" rowspan="1" colspan="1">0.5</td><td align="char" char="." valign="top" rowspan="1" colspan="1">0.9</td></tr><tr><td align="left" valign="top" rowspan="1" colspan="1">Prednisone current dose (mg/day)</td><td align="char" char="." valign="top" rowspan="1" colspan="1">7.2</td><td align="char" char="." valign="top" rowspan="1" colspan="1">6.4</td></tr><tr><td align="left" valign="top" rowspan="1" colspan="1">Time of exposure to prednisone (years)</td><td align="char" char="." valign="top" rowspan="1" colspan="1">6.9</td><td align="char" char="." valign="top" rowspan="1" colspan="1">6.2</td></tr><tr><td align="left" valign="top" rowspan="1" colspan="1">Antimalarial use</td><td align="left" valign="top" rowspan="1" colspan="1"></td><td align="left" valign="top" rowspan="1" colspan="1"></td></tr><tr><td align="left" valign="top" rowspan="1" colspan="1"> Never</td><td align="char" char="." valign="top" rowspan="1" colspan="1">20</td><td align="char" char="." valign="top" rowspan="1" colspan="1">8.4</td></tr><tr><td align="left" valign="top" rowspan="1" colspan="1"> Past</td><td align="char" char="." valign="top" rowspan="1" colspan="1">28</td><td align="char" char="." valign="top" rowspan="1" colspan="1">11.8</td></tr><tr><td align="left" valign="top" rowspan="1" colspan="1"> Current</td><td align="char" char="." valign="top" rowspan="1" colspan="1">189</td><td align="char" char="." valign="top" rowspan="1" colspan="1">79.7</td></tr><tr><td align="left" valign="top" rowspan="1" colspan="1">Immunosuppressive drug use</td><td align="left" valign="top" rowspan="1" colspan="1"></td><td align="left" valign="top" rowspan="1" colspan="1"></td></tr><tr><td align="left" valign="top" rowspan="1" colspan="1"> Never</td><td align="char" char="." valign="top" rowspan="1" colspan="1">60</td><td align="char" char="." valign="top" rowspan="1" colspan="1">25.3</td></tr><tr><td align="left" valign="top" rowspan="1" colspan="1"> Past</td><td align="char" char="." valign="top" rowspan="1" colspan="1">60</td><td align="char" char="." valign="top" rowspan="1" colspan="1">25.3</td></tr><tr><td align="left" valign="top" rowspan="1" colspan="1"> Current</td><td align="char" char="." valign="top" rowspan="1" colspan="1">117</td><td align="char" char="." valign="top" rowspan="1" colspan="1">49.4</td></tr><tr><td align="left" valign="top" rowspan="1" colspan="1">Follow-up time</td><td align="char" char="." valign="top" rowspan="1" colspan="1">3.1</td><td align="char" char="." valign="top" rowspan="1" colspan="1">1.3</td></tr></tbody></table><table-wrap-foot><fn id="T1_FN1"><p>SDI, Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index; SLEDAI-2K, Systemic Lupus Erythematosus Disease Activity Index-2K.</p></fn></table-wrap-foot></table-wrap><p>Organ damage per domain is described in <xref rid="T2" ref-type="table">table 2</xref>.</p><table-wrap id="T2" orientation="portrait" position="float"><label>Table 2</label><caption><p>Damage per domain</p></caption><table frame="hsides" rules="groups"><thead><tr><td align="left" valign="bottom" rowspan="2" colspan="1"></td><td align="left" valign="bottom" rowspan="1" colspan="2">Not new damage</td><td align="left" valign="bottom" rowspan="1" colspan="2">New damage</td><td align="left" valign="bottom" rowspan="1" colspan="1">P value</td></tr><tr><td align="left" valign="bottom" rowspan="1" colspan="1">n (%)</td><td align="left" valign="bottom" rowspan="1" colspan="1">Uric acid, mean (SD)</td><td align="left" valign="bottom" rowspan="1" colspan="1">n (%)</td><td align="left" valign="bottom" rowspan="1" colspan="1">Uric acid, mean (SD)</td><td align="left" valign="bottom" rowspan="1" colspan="1"></td></tr></thead><tbody><tr><td align="left" valign="top" rowspan="1" colspan="1">Global score</td><td rowspan="1" align="char" char="." valign="top" colspan="1">125</td><td rowspan="1" align="char" char="." valign="top" colspan="1">4.37 (1.36)</td><td rowspan="1" align="char" char="." valign="top" colspan="1">112</td><td rowspan="1" align="char" char="." valign="top" colspan="1">4.83 (1.46)</td><td align="char" char="." rowspan="1" valign="top" colspan="1">0.014</td></tr><tr><td align="left" valign="top" rowspan="1" colspan="1">Domains</td><td align="left" valign="top" rowspan="1" colspan="1"></td><td align="left" valign="top" rowspan="1" colspan="1"></td><td align="left" valign="top" rowspan="1" colspan="1"></td><td align="left" valign="top" rowspan="1" colspan="1"></td><td align="left" valign="top" rowspan="1" colspan="1"></td></tr><tr><td align="left" valign="top" rowspan="1" colspan="1">Ocular</td><td rowspan="1" align="char" char="." valign="top" colspan="1">223</td><td rowspan="1" align="char" char="." valign="top" colspan="1">4.58 (1.48)</td><td rowspan="1" align="char" char="." valign="top" colspan="1">14</td><td rowspan="1" align="char" char="." valign="top" colspan="1">4.61 (1.27)</td><td align="char" char="." rowspan="1" valign="top" colspan="1">0.942</td></tr><tr><td align="left" valign="top" rowspan="1" colspan="1">Neuropsychiatric</td><td rowspan="1" align="char" char="." valign="top" colspan="1">197</td><td rowspan="1" align="char" char="." valign="top" colspan="1">4.63 (1.52)</td><td rowspan="1" align="char" char="." valign="top" colspan="1">40</td><td rowspan="1" align="char" char="." valign="top" colspan="1">4.38 (1.11)</td><td align="char" char="." rowspan="1" valign="top" colspan="1">0.323</td></tr><tr><td align="left" valign="top" rowspan="1" colspan="1">Renal</td><td rowspan="1" align="char" char="." valign="top" colspan="1">198</td><td rowspan="1" align="char" char="." valign="top" colspan="1">4.31 (1.21)</td><td rowspan="1" align="char" char="." valign="top" colspan="1">22</td><td rowspan="1" align="char" char="." valign="top" colspan="1">5.88 (1.57)</td><td align="char" char="." rowspan="1" valign="top" colspan="1"><0.001</td></tr><tr><td align="left" valign="top" rowspan="1" colspan="1">Lung</td><td rowspan="1" align="char" char="." valign="top" colspan="1">215</td><td rowspan="1" align="char" char="." valign="top" colspan="1">4.58 (1.44)</td><td rowspan="1" align="char" char="." valign="top" colspan="1">22</td><td rowspan="1" align="char" char="." valign="top" colspan="1">4.66 (1.71)</td><td align="char" char="." rowspan="1" valign="top" colspan="1">0.796</td></tr><tr><td align="left" valign="top" rowspan="1" colspan="1">Cardiac</td><td rowspan="1" align="char" char="." valign="top" colspan="1">233</td><td rowspan="1" align="char" char="." valign="top" colspan="1">4.61 (1.46)</td><td rowspan="1" align="char" char="." valign="top" colspan="1">4</td><td rowspan="1" align="char" char="." valign="top" colspan="1">3.43 (0.87)</td><td align="char" char="." rowspan="1" valign="top" colspan="1">0.109</td></tr><tr><td align="left" valign="top" rowspan="1" colspan="1">Peripheral vascular</td><td rowspan="1" align="char" char="." valign="top" colspan="1">235</td><td rowspan="1" align="char" char="." valign="top" colspan="1">4.59 (1.47)</td><td rowspan="1" align="char" char="." valign="top" colspan="1">2</td><td rowspan="1" align="char" char="." valign="top" colspan="1">3.75 (0.49)</td><td align="char" char="." rowspan="1" valign="top" colspan="1">0.418</td></tr><tr><td align="left" valign="top" rowspan="1" colspan="1">Gastrointestinal</td><td rowspan="1" align="char" char="." valign="top" colspan="1">231</td><td rowspan="1" align="char" char="." valign="top" colspan="1">4.61 (1.47)</td><td rowspan="1" align="char" char="." valign="top" colspan="1">6</td><td rowspan="1" align="char" char="." valign="top" colspan="1">3.53 (0.73)</td><td align="char" char="." rowspan="1" valign="top" colspan="1">0.074</td></tr><tr><td align="left" valign="top" rowspan="1" colspan="1">Musculoskeletal</td><td rowspan="1" align="char" char="." valign="top" colspan="1">200</td><td rowspan="1" align="char" char="." valign="top" colspan="1">4.51 (1.44)</td><td rowspan="1" align="char" char="." valign="top" colspan="1">37</td><td rowspan="1" align="char" char="." valign="top" colspan="1">4.98 (1.57)</td><td align="char" char="." rowspan="1" valign="top" colspan="1">0.078</td></tr><tr><td align="left" valign="top" rowspan="1" colspan="1">Cutaneous</td><td rowspan="1" align="char" char="." valign="top" colspan="1">236</td><td rowspan="1" align="char" char="." valign="top" colspan="1">4.59 (1.47)</td><td rowspan="1" align="char" char="." valign="top" colspan="1">1</td><td rowspan="1" align="char" char="." valign="top" colspan="1">4.80</td><td align="char" char="." rowspan="1" valign="top" colspan="1">0.884</td></tr><tr><td align="left" valign="top" rowspan="1" colspan="1">Gonadal</td><td rowspan="1" align="char" char="." valign="top" colspan="1">115</td><td rowspan="1" align="char" char="." valign="top" colspan="1">4.15 (1.10)</td><td rowspan="1" align="char" char="." valign="top" colspan="1">6</td><td rowspan="1" align="char" char="." valign="top" colspan="1">5.20 (0.78)</td><td align="char" char="." rowspan="1" valign="top" colspan="1">0.023</td></tr><tr><td align="left" valign="top" rowspan="1" colspan="1">Diabetes</td><td rowspan="1" align="char" char="." valign="top" colspan="1">223</td><td rowspan="1" align="char" char="." valign="top" colspan="1">4.56 (1.45)</td><td rowspan="1" align="char" char="." valign="top" colspan="1">3</td><td rowspan="1" align="char" char="." valign="top" colspan="1">4.40 (0.36)</td><td align="char" char="." rowspan="1" valign="top" colspan="1">0.852</td></tr><tr><td align="left" valign="top" rowspan="1" colspan="1">Cancer</td><td rowspan="1" align="char" char="." valign="top" colspan="1">233</td><td rowspan="1" align="char" char="." valign="top" colspan="1">4.57 (1.46)</td><td rowspan="1" align="char" char="." valign="top" colspan="1">4</td><td rowspan="1" align="char" char="." valign="top" colspan="1">5.43 (1.50)</td><td align="char" char="." rowspan="1" valign="top" colspan="1">0.248</td></tr></tbody></table></table-wrap><p>In univariable and multivariable analyses (adjusting for variables known to have an impact on damage accrual), serum uric acid levels were associated with new damage (HR=1.141 (95% CI 1.016 to 1.282), p=0.026; HR=1.189 (95% CI 1.025 to 1.378), p=0.022, respectively), as shown in <xref rid="T3" ref-type="table">table 3</xref>.</p><table-wrap id="T3" orientation="portrait" position="float"><label>Table 3</label><caption><p>Factors associated with the occurrence of new damage (univariable and multivariable analyses)</p></caption><table frame="hsides" rules="groups"><thead><tr><td align="left" valign="bottom" rowspan="1" colspan="1">Variables</td><td align="left" valign="bottom" rowspan="1" colspan="1">HR (95% CI)</td><td align="left" valign="bottom" rowspan="1" colspan="1">P value</td><td align="left" valign="bottom" rowspan="1" colspan="1">HR (95% CI)</td><td align="left" valign="bottom" rowspan="1" colspan="1">P value</td></tr></thead><tbody><tr><td align="left" valign="top" rowspan="1" colspan="1">Uric acid level (mg/dL)</td><td align="left" valign="top" rowspan="1" colspan="1">1.141 (1.016 to 1.282)</td><td align="char" char="." valign="top" rowspan="1" colspan="1">0.026</td><td align="left" valign="top" rowspan="1" colspan="1">1.197 (1.020 to 1.403)</td><td align="char" char="." valign="top" rowspan="1" colspan="1">0.028</td></tr><tr><td align="left" valign="top" rowspan="1" colspan="1">Age at diagnosis (years)</td><td align="left" valign="top" rowspan="1" colspan="1">1.023 (1.009 to 1.038)</td><td align="char" char="." valign="top" rowspan="1" colspan="1">0.001</td><td align="left" valign="top" rowspan="1" colspan="1">1.038 (1.018 to 1.058)</td><td align="char" char="." valign="top" rowspan="1" colspan="1"><0.001</td></tr><tr><td align="left" valign="top" rowspan="1" colspan="1">Gender (male)</td><td align="left" valign="top" rowspan="1" colspan="1">1.005 (0.489 to 2.065)</td><td align="char" char="." valign="top" rowspan="1" colspan="1">0.989</td><td align="left" valign="top" rowspan="1" colspan="1">1.027 (0.455 to 2.321)</td><td align="char" char="." valign="top" rowspan="1" colspan="1">0.949</td></tr><tr><td align="left" valign="top" rowspan="1" colspan="1">Socioeconomic status</td><td align="left" valign="top" rowspan="1" colspan="1"> </td><td align="left" valign="top" rowspan="1" colspan="1"></td><td align="left" valign="top" rowspan="1" colspan="1"> </td><td align="left" valign="top" rowspan="1" colspan="1"></td></tr><tr><td align="left" valign="top" rowspan="1" colspan="1"> High</td><td align="left" valign="top" rowspan="1" colspan="1">Ref</td><td align="left" valign="top" rowspan="1" colspan="1"></td><td align="left" valign="top" rowspan="1" colspan="1">Ref</td><td align="left" valign="top" rowspan="1" colspan="1"></td></tr><tr><td align="left" valign="top" rowspan="1" colspan="1"> Medium</td><td align="left" valign="top" rowspan="1" colspan="1">1.239 (0.745 to 2.061)</td><td align="char" char="." valign="top" rowspan="1" colspan="1">0.409</td><td align="left" valign="top" rowspan="1" colspan="1">0.461 (0.174 to 1.223)</td><td align="char" char="." valign="top" rowspan="1" colspan="1">0.120</td></tr><tr><td align="left" valign="top" rowspan="1" colspan="1"> Low</td><td align="left" valign="top" rowspan="1" colspan="1">1.422 (0.950 to 2.129)</td><td align="char" char="." valign="top" rowspan="1" colspan="1">0.087</td><td align="left" valign="top" rowspan="1" colspan="1">1.023 (0.579 to 1.805)</td><td align="char" char="." valign="top" rowspan="1" colspan="1">0.938</td></tr><tr><td align="left" valign="top" rowspan="1" colspan="1">Educational level (years)</td><td align="left" valign="top" rowspan="1" colspan="1">0.940 (0.889 to 0.993)</td><td align="char" char="." valign="top" rowspan="1" colspan="1">0.027</td><td align="left" valign="top" rowspan="1" colspan="1">0.885 (0.793 to 0.988)</td><td align="char" char="." valign="top" rowspan="1" colspan="1">0.029</td></tr><tr><td align="left" valign="top" rowspan="1" colspan="1">Disease duration (years)</td><td align="left" valign="top" rowspan="1" colspan="1">1.032 (1.008 to 1.055)</td><td align="char" char="." valign="top" rowspan="1" colspan="1">0.007</td><td align="left" valign="top" rowspan="1" colspan="1">1.056 (1.006 to 1.109)</td><td align="char" char="." valign="top" rowspan="1" colspan="1">0.029</td></tr><tr><td align="left" valign="top" rowspan="1" colspan="1">SLEDAI-2K</td><td align="left" valign="top" rowspan="1" colspan="1">1.040 (1.000 to 1.082)</td><td align="char" char="." valign="top" rowspan="1" colspan="1">0.051</td><td align="left" valign="top" rowspan="1" colspan="1">1.018 (0.971 to 1.068)</td><td align="char" char="." valign="top" rowspan="1" colspan="1">0.457</td></tr><tr><td align="left" valign="top" rowspan="1" colspan="1">SDI</td><td align="left" valign="top" rowspan="1" colspan="1">1.283 (1.147 to 1.435)</td><td align="char" char="." valign="top" rowspan="1" colspan="1"><0.001</td><td align="left" valign="top" rowspan="1" colspan="1">1.095 (0.836 to 1.208)</td><td align="char" char="." valign="top" rowspan="1" colspan="1">0.960</td></tr><tr><td align="left" valign="top" rowspan="1" colspan="1">Creatinine level (mg/dL)</td><td align="left" valign="top" rowspan="1" colspan="1">0.993 (0.882 to 1.118)</td><td align="char" char="." valign="top" rowspan="1" colspan="1">0.907</td><td align="left" valign="top" rowspan="1" colspan="1">0.979 (0.817 to 1.175)</td><td align="char" char="." valign="top" rowspan="1" colspan="1">0.823</td></tr><tr><td align="left" valign="top" rowspan="1" colspan="1">Charlson Comorbidity Index</td><td align="left" valign="top" rowspan="1" colspan="1">1.030 (0.854 to 1.243)</td><td align="char" char="." valign="top" rowspan="1" colspan="1">0.755</td><td align="left" valign="top" rowspan="1" colspan="1">0.853 (0.646 to 1.128)</td><td align="char" char="." valign="top" rowspan="1" colspan="1">0.265</td></tr><tr><td align="left" valign="top" rowspan="1" colspan="1">Prednisone current dose (mg/day)</td><td align="left" valign="top" rowspan="1" colspan="1">0.993 (0.964 to 1.023)</td><td align="char" char="." valign="top" rowspan="1" colspan="1">0.637</td><td align="left" valign="top" rowspan="1" colspan="1">1.000 (0.965 to 1.037)</td><td align="char" char="." valign="top" rowspan="1" colspan="1">0.994</td></tr><tr><td align="left" valign="top" rowspan="1" colspan="1">Time of exposure to prednisone (years)</td><td align="left" valign="top" rowspan="1" colspan="1">1.032 (1.006 to 1.058)</td><td align="char" char="." valign="top" rowspan="1" colspan="1">0.016</td><td align="left" valign="top" rowspan="1" colspan="1">1.001 (0.952 to 1.053)</td><td align="char" char="." valign="top" rowspan="1" colspan="1">0.957</td></tr><tr><td align="left" valign="top" rowspan="1" colspan="1">Antimalarial use</td><td align="left" valign="top" rowspan="1" colspan="1"> </td><td align="left" valign="top" rowspan="1" colspan="1"></td><td align="left" valign="top" rowspan="1" colspan="1"> </td><td align="left" valign="top" rowspan="1" colspan="1"></td></tr><tr><td align="left" valign="top" rowspan="1" colspan="1"> Never</td><td align="left" valign="top" rowspan="1" colspan="1">Ref</td><td align="left" valign="top" rowspan="1" colspan="1"></td><td align="left" valign="top" rowspan="1" colspan="1">Ref</td><td align="left" valign="top" rowspan="1" colspan="1"></td></tr><tr><td align="left" valign="top" rowspan="1" colspan="1"> Past</td><td align="left" valign="top" rowspan="1" colspan="1">0.970 (0.466 to 2.017)</td><td align="char" char="." valign="top" rowspan="1" colspan="1">0.934</td><td align="left" valign="top" rowspan="1" colspan="1">1.372 (0.584 to 3.226)</td><td align="char" char="." valign="top" rowspan="1" colspan="1">0.468</td></tr><tr><td align="left" valign="top" rowspan="1" colspan="1"> Current</td><td align="left" valign="top" rowspan="1" colspan="1">0.708 (0.409 to 1.225)</td><td align="char" char="." valign="top" rowspan="1" colspan="1">0.217</td><td align="left" valign="top" rowspan="1" colspan="1">1.106 (0.587 to 2082)</td><td align="char" char="." valign="top" rowspan="1" colspan="1">0.756</td></tr><tr><td align="left" valign="top" rowspan="1" colspan="1">Immunosuppressive drug use</td><td align="left" valign="top" rowspan="1" colspan="1"> </td><td align="left" valign="top" rowspan="1" colspan="1"></td><td align="left" valign="top" rowspan="1" colspan="1"> </td><td align="left" valign="top" rowspan="1" colspan="1"></td></tr><tr><td align="left" valign="top" rowspan="1" colspan="1"> Never</td><td align="left" valign="top" rowspan="1" colspan="1">Ref</td><td align="left" valign="top" rowspan="1" colspan="1"></td><td align="left" valign="top" rowspan="1" colspan="1">Ref</td><td align="left" valign="top" rowspan="1" colspan="1"></td></tr><tr><td align="left" valign="top" rowspan="1" colspan="1"> Past</td><td align="left" valign="top" rowspan="1" colspan="1">1.021 (0.597 to 1.744)</td><td align="char" char="." valign="top" rowspan="1" colspan="1">0.940</td><td align="left" valign="top" rowspan="1" colspan="1">1.191 (0.654 to 2.170)</td><td align="char" char="." valign="top" rowspan="1" colspan="1">0.568</td></tr><tr><td align="left" valign="top" rowspan="1" colspan="1"> Current</td><td align="left" valign="top" rowspan="1" colspan="1">1.420 (0.916 to 2.202)</td><td align="char" char="." valign="top" rowspan="1" colspan="1">0.117</td><td align="left" valign="top" rowspan="1" colspan="1">1.649 (0.997 to 2.728)</td><td align="char" char="." valign="top" rowspan="1" colspan="1">0.051</td></tr></tbody></table><table-wrap-foot><fn id="T3_FN1"><p>Ref, reference; SDI, Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index; SLEDAI-2K, Systemic Lupus Erythematosus Disease Activity Index-2K.</p></fn></table-wrap-foot></table-wrap></sec><sec sec-type="discussion" id="s4"><title>Discussion</title><p>The association between uric acid levels and damage accrual in patients with SLE was evaluated, and serum uric acid level was found to be associated with the development of new damage in these patients. Previous studies have found an association between hyperuricaemia and hypertension,<xref rid="R13" ref-type="bibr">13</xref> metabolic syndrome<xref rid="R14" ref-type="bibr">14</xref> and renal disease,<xref rid="R2" ref-type="bibr">2</xref> as well as with organ failure or damage,<xref rid="R15" ref-type="bibr">15</xref> especially renal.<xref rid="R16" ref-type="bibr">16</xref></p><p>In several autoimmune diseases, high serum uric acid levels play an important role in the development and risk of certain comorbidities; for example, in rheumatoid arthritis, uric acid is a cardiovascular risk factor reflected in the increased thickness of the carotid artery.<xref rid="R17" ref-type="bibr">17</xref> On the other hand, in systemic sclerosis, Gigante <italic>et al</italic><xref rid="R18" ref-type="bibr">18</xref> found that serum uric acid levels were higher in those with more microvascular damage as compared with those with less microvascular damage.</p><p>Taraborelli <italic>et al</italic><xref rid="R19" ref-type="bibr">19</xref> examined the effect of disease duration of 511 patients with SLE on damage; this study showed that, at 1 year of follow-up, about 40% of patients had some damage: usually mild or moderate. The prevalence of damage progressively increased over time, starting from a mean SDI score of 0.6 (SD: 0.89) at 1 year to 0.9 (SD: 1.19) at 5 years and 3.7 (SD: 1.5) at 35 years of follow-up. Bruce <italic>et al</italic><xref rid="R20" ref-type="bibr">20</xref> found that increasing age had a significant influence on the probability of damage accrual, and is also the case for ethnicity. For example, compared with Caucasians from Europe or Canada, US patients of African ancestry had a higher risk of evolving from no damage to damage and also of progressing from baseline damage to higher damage,<xref rid="R20" ref-type="bibr">20</xref> and the case is the same for Hispanic patients.<xref rid="R21" ref-type="bibr">21</xref> Moreover, Shaharir <italic>et al</italic><xref rid="R22" ref-type="bibr">22</xref> investigated the associated factors of disease damage among patients with lupus nephritis and found that higher daily prednisolone dose predicted disease damage.</p><p>In SLE, serum uric acid levels have been reported to be associated with several impairments, including renal, cardiovascular, pulmonary and neurological, which when analysed together may explain the impact on damage. Yang <italic>et al</italic><xref rid="R23" ref-type="bibr">23</xref> found that serum uric acid level was associated with the development of lupus nephritis and previously we have reported that serum uric acid level predicts increased kidney damage.<xref rid="R9" ref-type="bibr">9</xref> In the same way, Ugolini-Lopes <italic>et al</italic><xref rid="R24" ref-type="bibr">24</xref> found that serum uric acid levels <6.05 mg/dL at 12 months of follow-up were a predictor of good long-term renal outcome in lupus nephritis. Likewise, in the study by Sabio <italic>et al</italic>,<xref rid="R25" ref-type="bibr">25</xref> patients with hyperuricaemia presented a worse cardiovascular risk profile that included hypertension, obesity, high cholesterol levels, renal damage and metabolic syndrome; in addition, serum uric acid levels correlated with high levels of erythrocyte sedimentation rate, C reactive protein, fibrinogen and homocysteine. Similarly, Castillo-Martínez <italic>et al</italic><xref rid="R8" ref-type="bibr">8</xref> demonstrated that serum uric acid levels greater than 7 mg/dL would increase the risk of developing pulmonary hypertension by 8.5 times.<xref rid="R8" ref-type="bibr">8</xref> Similar findings have been reported by Kim <italic>et al</italic>,<xref rid="R26" ref-type="bibr">26</xref> where a value greater than 6.5 mg/dL of uric acid would be reasonably accurate in predicting the presence of pulmonary hypertension. In addition, hyperuricaemia has been shown to be related to factors that would increase the risk of stroke, such as high blood pressure, hyperlipidaemia and history of arterial thrombosis, and has been independently associated with the occurrence of cerebrovascular events and polyneuropathy.<xref rid="R7" ref-type="bibr">7</xref></p><p>Uric acid can generate urate radicals when it is exposed to oxidising agents<xref rid="R27" ref-type="bibr">27</xref> and itself has been shown in an in vitro study to stimulate the synthesis of monocyte chemoattractant protein-1, interleukin-1b, intereukin-6 and tumour necrosis factor-a, all of which are proinflammatory molecules.<xref rid="R28" ref-type="bibr">28</xref> In contrast, it also represents one of the most important low-molecular-mass antioxidants in the human biological fluids.<xref rid="R29" ref-type="bibr">29–31</xref> It is a powerful scavenger of peroxyl radicals, hydroxyl radicals and singlet oxygen,<xref rid="R29" ref-type="bibr">29</xref> and may contribute to increased lifespan in humans by providing protection against oxidative stress-provoked ageing and cancer. Also, uric acid is an oxidisable substrate for hem protein/H<sub>2</sub>O<sub>2</sub> systems and is able to protect against oxidative damage by acting as an electron donor.<xref rid="R32" ref-type="bibr">32</xref> Despite this, we did not demonstrate how low the uric acid level needs to be to avoid damage in patients with SLE.</p><p>Keeping uric acid levels low is recommended to avoid damage in SLE, as it has been observed in studies that increasing uric acid is related to anaemia in SLE,<xref rid="R33" ref-type="bibr">33</xref> and also associated with the occurrence of stroke, peripheral neuropathy, hypertension, hyperlipidaemia and history of arterial thrombosis.<xref rid="R7" ref-type="bibr">7</xref> Even normal values of uric acid have been associated with renal damage in patients with SLE.<xref rid="R9" ref-type="bibr">9 24</xref></p><p>This study has some limitations. As it is not an inception cohort, it is not possible to define if the interaction between serum uric acid levels and damage is bidirectional, that is, damage increases the level of serum uric acid and this in turn determines new damage. Other limitations include the fact that randomisation was not possible in terms of the type of treatment that patients received. In addition, some medications have not been recorded in the database, such as losartan. Finally, the cumulative dose of steroids could not be obtained since this is not an inception cohort. On the other hand, being a cohort of mostly Mestizo patients, the results cannot be extrapolated to patients from other ethnic groups. An important strength of this study, however, is that for the first time it is reported that higher serum uric acid levels are associated with global damage. It will be necessary to conduct longitudinal studies with a larger number of patients to confirm these findings.</p><p>In conclusion, we describe for the first time the association between uric acid levels and global damage in patients with SLE, independently of age at diagnosis, sex, disease duration, socioeconomic status, disease activity, comorbidities, prednisone use, antimalarials and immunosuppressive drugs at baseline.</p></sec></body><back><fn-group><fn fn-type="other"><p><bold>Twitter:</bold> @VictorioPQ, @mugartegil</p></fn><fn fn-type="other"><p><bold>Presented at:</bold> The manuscript is based on a work previously presented at a conference and published as a conference abstract in 2018 (SAT0426 Serum uric acid levels predict damage accrual in systemic lupus erythematosus patients, <italic>Annals of the Rheumatic Diseases</italic> 2018; doi: 10.1136/annrheumdis-2018-eular.6128).</p></fn><fn fn-type="other"><p><bold>Contributors:</bold> All authors were involved in drafting or revising this article critically for important intellectual content, and all approved the final version to be published. CE-F has full access to all of the data from the study and takes responsibility for their integrity and the accuracy of the analyses performed.</p></fn><fn fn-type="other"><p><bold>Funding:</bold> This work was partially supported by an institutional grant from EsSalud (1483-GCGP-ESSALUD-2013, 1733-GCGP-ESSALUD-2014 and 04-IETSI-ESALUD-2016 2015, Kaelin Prize) and one from the Panamerican League of Associations for Rheumatology (PANLAR) (2015 PANLAR Prize).</p></fn><fn fn-type="COI-statement"><p><bold>Competing interests:</bold> None declared.</p></fn><fn fn-type="other"><p><bold>Patient consent for publication:</bold> Not required.</p></fn><fn fn-type="other"><p><bold>Ethics approval:</bold> The study had been approved by the Institutional Review Board of Hospital Nacional Guillermo Almenara Irigoyen, EsSalud (3474-OCID-G-RAA-ESSALUD-11, 271-CEI-CID-G-RAA-ESSALUD-13, 302-CEI-ICD-G-RAA-14, 3027-OCID-G-RAA-ESSALUD-15). Patients who signed the informed consent were recruited into the cohort.</p></fn><fn fn-type="other"><p><bold>Provenance and peer review:</bold> Not commissioned; externally peer reviewed.</p></fn><fn fn-type="other"><p><bold>Data availability statement:</bold> All data relevant to the study are included in the article or uploaded as supplementary information. 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