Predictors of renal damage in systemic lupus erythematous patients: data from a multiethnic, multinational Latin American lupus cohort (GLADEL)

AimA decrease in proteinuria has been considered protective from renal damage in lupus nephritis (LN), but a cut-off point has yet to be established. The aim of this study was to identify the predictors of renal damage in patients with LN and to determine the best cut-off point for a decrease in proteinuria.MethodsWe included patients with LN defined clinically or histologically. Possible predictors of renal damage at the time of LN diagnosis were examined: proteinuria, low complement, anti-double-stranded DNA antibodies, red cell casts, creatinine level, hypertension, renal activity (assessed by the Systemic Lupus Erythematosus Disease Activity Index (SLEDAI)), prednisone dose, immunosuppressive drugs and antimalarial use. Sociodemographic variables were included at baseline. Proteinuria was assessed at baseline and at 12 months, to determine if early response (proteinuria <0.8 g/day within 12 months since LN diagnosis) is protective of renal damage occurrence. Renal damage was defined as an increase of one or more points in the renal domain of The Systemic Lupus International Collaborating Clinics (SLICC)/American College of Rheumatology (ACR) Damage Index (SDI). Cox regression models using a backward selection method were performed.ResultsFive hundred and two patients with systemic lupus erythematosus patients were included; 120 patients (23.9%) accrued renal damage during their follow-up. Early response to treatment (HR=0.58), antimalarial use (HR=0.54) and a high SES (HR=0.25) were protective of renal damage occurrence, whereas male gender (HR=1.83), hypertension (HR=1.86) and the renal component of the SLEDAI (HR=2.02) were risk factors for its occurrence.ConclusionsEarly response, antimalarial use and high SES were protective of renal damage, while male gender, hypertension and higher renal activity were risk factors for its occurrence in patients with LN.

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The number of flares patients experience impacts on damage accrual in systemic lupus erythematosus: data from a multiethnic Latin American cohort

Annals of the Rheumatic Diseases ◽

10.1136/annrheumdis-2013-204620 ◽

2014 ◽

Vol 74 (6) ◽

pp. 1019-1023 ◽

Cited By ~ 42

Author(s):

Manuel F Ugarte-Gil ◽

Eduardo Acevedo-Vásquez ◽

Graciela S Alarcón ◽

Cesar A Pastor-Asurza ◽

José L Alfaro-Lozano ◽

...

Keyword(s):

Risk Factors ◽

Systemic Lupus Erythematosus ◽

Latin American ◽

Lupus Erythematosus ◽

Crossover Design ◽

Systemic Lupus ◽

Case Crossover ◽

Damage Accrual ◽

The Mean ◽

Patients Experience

PurposeTo determine the association between the number of flares systemic lupus erythematosus (SLE) patients experience and damage accrual, independently of other known risk factors.MethodsSLE patients (34 centres, nine Latin American countries) with a recent diagnosis (≤2 years) and ≥3 evaluations were studied. Disease activity was ascertained with the Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) and damage with the SLICC/ACR Damage Index (SDI). Flare was defined as an increase ≥4 points in the SLEDAI between two study visits. An ambidirectional case- crossover design was used to determine the association between the number of flares and damage accrual.Results901 patients were eligible for the study; 500 of them (55.5%) experienced at least one flare, being the mean number of flares 0.9 (SD: 1.0). 574 intervals from 251 patients were included in the case-crossover design since they have case and control intervals, whereas, the remaining patients did not. Their mean age at diagnosis was 27.9 years (SD: 11.1), 213 (84.9%) were women. The mean baseline SDI and SLEDAI were 1.3 (1.3) and 13.6 (8.1), respectively. Other features were comparable to those of the entire sample. After adjusting for possible confounding variables, the number of flares, regardless of their severity, was associated with damage accrual (SDI) OR 2.05, 95% CI 1.43 to 2.94, p<0.001 (OR 2.62, 95% CI 1.31 to 5.24, p=0.006 for severe and OR 1.91, 95% CI 1.28 to 2.83, p=0.001for mild-moderate).ConclusionsThe number of flares patients experience, regardless of their severity, increases the risk of damage accrual, independently of other known risk factors.

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Association between organ damage and mortality in systemic lupus erythematosus: a systematic review and meta-analysis

BMJ Open ◽

10.1136/bmjopen-2019-031850 ◽

2020 ◽

Vol 10 (5) ◽

pp. e031850 ◽

Cited By ~ 1

Author(s):

Irene B Murimi-Worstell ◽

Dora H Lin ◽

Henk Nab ◽

Hong J Kan ◽

Oluwadamilola Onasanya ◽

...

Keyword(s):

Systematic Review ◽

Systemic Lupus Erythematosus ◽

Latin American ◽

Lupus Erythematosus ◽

Meta Analysis ◽

Damage Index ◽

Organ Damage ◽

Cochrane Library ◽

Systemic Lupus ◽

Cross Sectional

ObjectiveAt least half of patients with systemic lupus erythematosus (SLE) develop organ damage as a consequence of autoimmune disease or long-term therapeutic steroid use. This study synthesised evidence on the association between organ damage and mortality in patients with SLE.DesignSystematic review and meta-analysis.MethodsElectronic searches were performed in PubMed, Embase, Cochrane Library and Latin American and Caribbean Health Sciences Literature for observational (cohort, case-control and cross-sectional) studies published between January 2000 and February 2017. Included studies reported HRs or ORs on the association between organ damage (measured by the Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index (SDI) score) and mortality. Study quality was assessed using the modified Newcastle-Ottawa assessment. Pooled HRs were obtained using the DerSimonian and Laird random-effects model. Heterogeneity was assessed using the Cochrane Q (Q) and I2 statistics.ResultsThe search yielded 10 420 articles, from which 21 longitudinal studies were selected. Most studies (85%) were of high quality. For 10 studies evaluating organ damage (SDI) as a continuous variable and reporting HR as a measure of association, a 1-unit increase in SDI was associated with increased mortality; pooled HR was 1.34 (95% CI: 1.24 to 1.44, p<0.001; Q p=0.027, I2=52.1%). Exclusion of one potential outlying study reduced heterogeneity with minimal impact on pooled HR (1.33 (95% CI: 1.25 to 1.42), p<0.001, Q p=0.087, I2=42.0%). The 11 remaining studies, although they could not be aggregated because of their varying patient populations and analyses, consistently demonstrated that greater SDI was associated with increased mortality.ConclusionsOrgan damage in SLE is consistently associated with increased mortality across studies from various countries. Modifying the disease course with effective therapies and steroid-sparing regimens may reduce organ damage, improve outcomes and decrease mortality for patients with SLE.

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Serum uric acid is associated with damage in patients with systemic lupus erythematosus

Lupus Science & Medicine ◽

10.1136/lupus-2019-000366 ◽

2020 ◽

Vol 7 (1) ◽

pp. e000366 ◽

Cited By ~ 1

Author(s):

Claudia Elera-Fitzcarrald ◽

Cristina Reátegui-Sokolova ◽

Rocio Violeta Gamboa-Cardenas ◽

Mariela Medina ◽

Francisco Zevallos ◽

...

Keyword(s):

Systemic Lupus Erythematosus ◽

Uric Acid ◽

Serum Uric Acid ◽

Lupus Erythematosus ◽

Cox Regression ◽

Activity Index ◽

Damage Index ◽

Systemic Lupus ◽

The Impact

IntroductionSerum 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.ObjectiveTo determine whether serum uric acid levels are associated with new damage in patients with SLE.MethodsThis 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.ResultsWe 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).ConclusionHigher serum uric acid levels are associated with global damage in patients with SLE.

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Differences in clinical manifestations and increased severity of systemic lupus erythematosus between two groups of Hispanics: European Caucasians versus Latin American mestizos (data from the RELESSER registry)

Lupus ◽

10.1177/0961203319889667 ◽

2019 ◽

Vol 29 (1) ◽

pp. 27-36 ◽

Cited By ~ 1

Author(s):

B Hernández Cruz ◽

F Alonso ◽

J Calvo Alén ◽

J M Pego-Reigosa ◽

F J López-Longo ◽

...

Keyword(s):

Systemic Lupus Erythematosus ◽

Latin American ◽

Lupus Erythematosus ◽

Hospital Admissions ◽

Damage Index ◽

Clinical Manifestations ◽

Good Clinical Practice ◽

Activity Levels ◽

Systemic Lupus ◽

Co Morbidity

Background Systemic lupus erythematosus (SLE) is regarded as a prototype autoimmune disease because it can serve as a means for studying differences between ethnic minorities and sex. Traditionally, all Hispanics have been bracketed within the same ethnic group, but there are differences between Hispanics from Spain and those from Latin America, not to mention other Spanish-speaking populations. Objectives This study aimed to determine the demographic and clinical characteristics, severity, activity, damage, mortality and co-morbidity of SLE in Hispanics belonging to the two ethnic groups resident in Spain, and to identify any differences. Methods This was an observational, multi-centre, retrospective study. The demographic and clinical variables of patients with SLE from 45 rheumatology units were collected. The study was conducted in accordance with Good Clinical Practice guidelines. Hispanic patients from the registry were divided into two groups: Spaniards or European Caucasians (EC) and Latin American mestizos (LAM). Comparative univariate and multivariate statistical analyses were carried out. Results A total of 3490 SLE patients were included, 90% of whom were female; 3305 (92%) EC and 185 (5%) LAM. LAM patients experienced their first lupus symptoms four years earlier than EC patients and were diagnosed and included in the registry younger, and their SLE was of a shorter duration. The time in months from the first SLE symptoms to diagnosis was longer in EC patients, as were the follow-up periods. LAM patients exhibited higher prevalence rates of myositis, haemolytic anaemia and nephritis, but there were no differences in histological type or serositis. Anti-Sm, anti-Ro and anti-RNP antibodies were more frequently found in LAM patients. LAM patients also had higher levels of disease activity, severity and hospital admissions. However, there were no differences in damage index, mortality or co-morbidity index. In the multivariate analysis, after adjusting for confounders, in several models the odds ratio (95% confidence interval) for a Katz severity index >3 in LAM patients was 1.45 (1.038–2.026; p = 0.02). This difference did not extend to activity levels (i.e. SLEDAI >3; 0.98 (0.30–1.66)). Conclusion SLE in Hispanic EC patients showed clinical differences compared to Hispanic LAM patients. The latter more frequently suffered nephritis and higher severity indices. This study shows that where lupus is concerned, not all Hispanics are equal.

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Atrial Fibrillation/flutter Hospitalizations among US Medicaid Recipients with and without Systemic Lupus Erythematosus

The Journal of Rheumatology ◽

10.3899/jrheum.190502 ◽

2019 ◽

Vol 47 (9) ◽

pp. 1359-1365 ◽

Cited By ~ 1

Author(s):

Sarah K. Chen ◽

Medha Barbhaiya ◽

Daniel H. Solomon ◽

Hongshu Guan ◽

Kazuki Yoshida ◽

...

Keyword(s):

Risk Factors ◽

Atrial Fibrillation ◽

Systemic Lupus Erythematosus ◽

Lupus Erythematosus ◽

Cox Regression ◽

The United States ◽

Incidence Rates ◽

Systemic Lupus ◽

Cox Models ◽

Age And Sex

Objective.Systemic lupus erythematosus (SLE) is a multisystem chronic inflammatory autoimmune disease with high prevalence of several risk factors for atrial fibrillation/flutter (AF). However, the incidence and risk of AF in SLE have not been well quantified.Methods.We used the United States Medicaid Analytic eXtract from 2007 to 2010 to identify beneficiaries aged 18–65 years, with prevalent SLE, each matched by age and sex to 4 non-SLE general Medicaid recipients. We estimated the incidence rates (IR) per 1000 person-years (PY) for AF hospitalizations and used multivariable Cox regression to estimate the HR for AF hospitalization.Results.We identified 46,876 US Medicaid recipients with SLE, and 187,504 age- and sex-matched non-SLE controls (93% female; mean age 41.5 ± 12.2 yrs). Known AF risk factors such as hypertension (HTN), cardiovascular disease (CVD), and kidney disease were more prevalent in patients with SLE. During a mean followup of 1.9 ± 1.1 years for SLE, and 1.8 ± 1.1 years for controls, the IR per 1000 PY for AF was 1.4 (95% CI 1.1–1.6) among patients with SLE and 0.7 (95% CI 0.6–0.8) among non-SLE controls. In age- and sex-matched and race-adjusted Cox models, the HR for AF was 1.79 (95% CI 1.43–2.24); after adjustment for baseline HTN and CVD, the adjusted HR was reduced to 1.17 (95% CI 0.92–1.48).Conclusion.SLE was associated with a doubled rate of hospitalization for AF compared to age- and sex-matched general Medicaid patients. In a race-adjusted model, the risk was 80% higher. However, the AF risk factors HTN and CVD were more prevalent among patients with SLE and accounted for the excess risk.

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Remission and Low Disease Activity Status (LDAS) protect lupus patients from damage occurrence: data from a multiethnic, multinational Latin American Lupus Cohort (GLADEL)

Annals of the Rheumatic Diseases ◽

10.1136/annrheumdis-2017-211814 ◽

2017 ◽

Vol 76 (12) ◽

pp. 2071-2074 ◽

Cited By ~ 41

Author(s):

Manuel Francisco Ugarte-Gil ◽

Daniel Wojdyla ◽

Guillermo J Pons-Estel ◽

Luis J Catoggio ◽

Cristina Drenkard ◽

...

Keyword(s):

Disease Activity ◽

Latin American ◽

Lupus Erythematosus ◽

Lower Risk ◽

Cox Regression ◽

Activity Index ◽

Damage Index ◽

Systemic Lupus ◽

Low Disease Activity ◽

The Impact

ObjectiveTo evaluate disease activity statuses’ (DAS’) impact on systemic lupus erythematosus (SLE) outcomes.Materials and methodsFour DAS were defined: remission off-therapy: SLE Disease Activity Index (SLEDAI)=0, no prednisone or immunosuppressive drugs (IS); remission on-therapy: SLEDAI=0, prednisone ≤5 mg/day and/or IS (maintenance); low (L) DAS: SLEDAI ≤4, prednisone ≤7.5 mg/day and/or IS (maintenance); non-optimally controlled: SLEDAI >4 and/or prednisone >7.5 mg/day and/or IS (induction). Antimalarials were allowed in all. Predefined outcomes were mortality, new damage (increase of at least one Systemic Lupus International Collaborating Clinics/American College of Rheumatology (SLICC/ACR) damage index (SDI) point) and severe new damage (increase of at least 3 SDI points). Univariable and multivariable Cox regression models were performed to define the impact of DAS, as time-dependent variable, on these outcomes.Results1350 patients were included, 79 died during follow-up, 606 presented new and 177 severe new damage. In multivariable analyses, remission (on/off-therapy) was associated with a lower risk of new (HR 0.60; 95% CI 0.43 to 0.85), and of severe new damage (HR 0.32; 95% CI 0.15 to 0.68); low disease activity status (LDAS) was associated with a lower risk of new damage (HR 0.66; 95% CI 0.48 to 0.93) compared with non-optimally controlled. No significant effect on mortality was observed.ConclusionsRemission was associated with a lower risk of new and severe new damage; LDAS with a lower risk of new damage after adjusting for other damage confounders.

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IgM Anti-ß2Glycoprotein I Is Protective Against Lupus Nephritis and Renal Damage in Systemic Lupus Erythematosus

The Journal of Rheumatology ◽

10.3899/jrheum.100650 ◽

2010 ◽

Vol 38 (3) ◽

pp. 450-453 ◽

Cited By ~ 32

Author(s):

TARANEH MEHRANI ◽

MICHELLE PETRI

Keyword(s):

Systemic Lupus Erythematosus ◽

Lupus Nephritis ◽

Protective Effect ◽

Lupus Erythematosus ◽

Renal Damage ◽

Damage Index ◽

Clinical Manifestations ◽

Systemic Lupus ◽

American College Of Rheumatology ◽

Glycoprotein I

Objective.Antibodies to ß2glycoprotein I (IgG and IgM isotypes) have recently been added to the laboratory criteria of the revised antiphospholipid syndrome classification criteria. We investigated whether IgM anti-ß2-glycoprotein I (anti-ß2-GPI) is associated with clinical manifestations of systemic lupus erythematosus (SLE).Methods.Anti-ß2-GPI was measured in 796 patients with SLE (93% women, 53% white, 38% African American, mean age 45 yrs). IgM anti-ß2-GPI (> 20 phospholipid units) was found in 16%. Associations were determined with clinical manifestations of SLE and with components of the Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index.Results.As expected, IgM anti-ß2-GPI was highly associated with both the lupus anticoagulant and with anticardiolipin. It was associated with transient ischemic attack (OR 2.64, p = 0.04), but not significantly with venous or arterial thrombosis. IgM anti-ß2-GPI was protective against lupus nephritis (OR 0.54, p = 0.049), renal damage (p = 0.019), and hypertension (OR 0.58, p = 0.008). This protective effect remained after adjustment for ethnicity.Conclusion.In SLE, IgM anti-ß2-GPI is not associated with thrombosis but is protective against lupus nephritis and renal damage. “Natural” autoantibodies of the IgM isotype may have a protective effect.

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Epidemiologic Profile of Erectile Dysfunction in Patients with Systemic Lupus Erythematosus: The Latin American Landscape

The Journal of Rheumatology ◽

10.3899/jrheum.180292 ◽

2019 ◽

Vol 46 (4) ◽

pp. 397-404 ◽

Cited By ~ 4

Author(s):

Javier Merayo-Chalico ◽

Ana Barrera-Vargas ◽

Sandra Morales-Padilla ◽

Roberto Reyna-De la Garza ◽

Ricardo Vázquez-Rodríguez ◽

...

Keyword(s):

Risk Factors ◽

Systemic Lupus Erythematosus ◽

Erectile Dysfunction ◽

Latin American ◽

Lupus Erythematosus ◽

Tertiary Care ◽

Systemic Lupus ◽

American College Of Rheumatology ◽

Epidemiologic Profile ◽

Tertiary Care Centers

Objective.The aim of this study was to describe the prevalence of erectile dysfunction (ED), as well as associated demographic and clinical features, in men with systemic lupus erythematosus (SLE), by means of a systematic, standardized evaluation.Methods.We performed a transversal study in 8 tertiary care centers in Latin America. We included male patients ≥ 16 years who fulfilled ≥ 4 American College of Rheumatology criteria for SLE and had regular sexual activity, and evaluated them with the International Index of Erectile Function-5 questionnaire. Relevant demographic, clinical, and serological characteristics were recorded. We included 2 control groups: the first was made up of healthy men and the second of men with autoimmune diseases other than SLE (non-SLE group).Results.We included 590 subjects (174 SLE, 55 non-SLE, and 361 healthy controls). The prevalence of ED in the SLE group was 69%. Mean age in that group was 36.3 ± 1.03 years. Among SLE patients with and without ED, these factors were significantly different: the presence of persistent lymphopenia (p = 0.006), prednisone dose (9.3 ± 1.2 vs 5.3 ± 1.3 mg, p = 0.026), and the Systemic Lupus International Collaborating Clinics damage score (1.25 ± 0.14 vs 0.8 ± 0.16 points, p = 0.042). Independent risk factors for ED in patients with SLE were persistent lymphopenia (OR 2.79, 95% CI 1.37–5.70, p = 0.001) and corticosteroid use in the previous year (OR 2.15, 95% CI 1.37–3.37, p = 0.001).Conclusion.Regardless of comorbidities, treatment (excluding steroids), and type of disease activity, patients with SLE have a high prevalence of ED, especially considering that most patients are young. Recent corticosteroid use and persistent lymphopenia, which could be related to endothelial dysfunction, are risk factors for this complication in men with SLE.

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Risk factors for thrombotic events in Korean patients with systemic lupus erythematosus

Scientific Reports ◽

10.1038/s41598-021-03074-5 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Dong-Jin Park ◽

Chang-Seok Yoon ◽

Sung-Eun Choi ◽

Haimuzi Xu ◽

Ji-Hyoun Kang ◽

...

Keyword(s):

Risk Factors ◽

Systemic Lupus Erythematosus ◽

Lupus Erythematosus ◽

Protective Factor ◽

Proportional Hazards ◽

Damage Index ◽

Cox Proportional Hazards ◽

Systemic Lupus ◽

Vein Thrombosis ◽

Deep Vein

AbstractThrombotic events (TE), including deep vein thrombosis, stroke, and myocardial infarction, occur in 30–40% of patients with systemic lupus erythematosus (SLE) resulting in substantial morbidity and mortality. We explored the risk factors for TE in SLE patients. We analyzed data obtained during a prospective cohort based on the KORean lupus NETwork (KORNET) registry, and enrolled 259 SLE patients with clinical data available at the onset of SLE. TE was defined as the presence of arterial or venous thrombosis. Multivariate Cox-proportional hazards analysis was performed to investigate risk factors for TE. During a mean follow-up of 103.3 months (SD 53.4), 27 patients (10.4%) had a TE. In multivariate analysis, hypertension (hazard ratio [HR] 7.805, 95% confidence interval [CI]: 1.929–31.581; P = 0.004), anti-phospholipid syndrome (APS) (HR 12.600, 95% CI: 4.305–36.292; P < 0.001), mean daily prednisolone > 5 mg/day (HR 3.666, 95% CI: 1.318–10.197; P = 0.013), and SLICC/ACR Damage Index (SDI) score (HR 1.992, 95% CI: 1.465–2.709; P < 0.001) were significantly associated with the development of TE in SLE patients. Instead, use of an ACEi or ARB (HR 0.159, 95% CI: 0.043–0.594; P = 0.006) was a protective factor against TE development in these patients. In conclusion, hypertension, higher mean daily dose of prednisolone, diagnosis of APS, and higher SDI were risk factors for TE in patients with SLE. On the other hand, the use of an ACEi or ARB was associated with a reduced risk of TE.

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