Principles of pediatric lupus nephritis in a prospective contemporary multi-center cohort

Vazzana, K.; Daga, Ankana; Goilav, Béatrice; Ogbu, Ekemini A.; Okamura, Daryl M.; Park, Catherine; Sadun, Rebecca E.; Smitherman, Emily A.; Stotter, Brian R.; Dasgupta, Abhijit; Knight, Andrea; Hersh, Aimee O.; Wenderfer, Scott E.; Lewandowski, Laura B.

doi:10.1177/09612033211028658

Cited by 29 publications

(27 citation statements)

References 44 publications

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“…Use of B cell–depleting therapies also became increasingly common—up to 25% of lupus nephritis patients in the CARRA registry's contemporary pediatric lupus cohort have received rituximab (9). There have also been several initiatives to develop standards for pediatric lupus care, including international consensus recommendations for quality indicators in 2013 (10), and European guidelines for management of pediatric lupus in 2016 (11,21).…”

Section: Discussionmentioning

confidence: 99%

“…Over the last 2 decades, there have been several advances in the care of children with lupus, including an expansion of therapeutic options and increasing emphasis on quality metrics that may be associated with improved renal outcomes (7). Mycophenolate mofetil (MMF) has become a mainstay of therapy for pediatric lupus nephritis (8), and the use of B cell-depleting therapies has also become increasingly common (9). Simultaneously, several consensus guidelines for management of pediatric lupus have been released (10,11).…”

Section: Introductionmentioning

confidence: 99%

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Racial Disparities in Renal Outcomes Over Time Among Hospitalized Children With Systemic Lupus Erythematosus

Chang

Sears

Torres

et al. 2022

Arthritis & Rheumatology

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Objective Racial and ethnic minority groups have excess morbidity related to renal disease in pediatric‐onset systemic lupus erythematosus (SLE). This study was undertaken to evaluate temporal trends in renal outcomes and racial disparities among hospitalized children with SLE over a period of 14 years. Methods We identified patients 21 years old or younger with discharge diagnoses of SLE in the Pediatric Health Information System inpatient database (2006–2019). Adverse renal outcomes included end‐stage renal disease (ESRD), dialysis, or transplant, analyzed as a composite and separately. We estimated the odds of adverse renal outcomes at any hospitalization or the first occurrence of an adverse renal outcome, adjusted for calendar period, patient characteristics, and clustering by hospital. We tested whether racial disparities differed by calendar period. Results There were 20,893 admissions for 7,434 SLE patients, of which 32%, 16%, 12%, and 8% were Black, Hispanic White, Hispanic Other, and Asian, respectively. Proportions of admissions with adverse renal outcomes decreased over time (P < 0.01). Black children remained at the highest risk of adverse renal outcomes at any admission (odds ratio [OR] 2.5 [95% confidence interval (95% CI) 1.8–3.5] versus non‐Hispanic White patients). Black and Asian children remained at a higher risk of incident adverse renal outcomes, driven by ESRD among Black children (OR 1.6 [95% CI 1.2–2.1]) and dialysis among Asians (OR 1.7 [95% CI 1.1–2.7]). Relative disparities did not change significantly over time. Conclusion Significant reductions in ESRD and dialysis occurred over time for children with SLE across all racial and ethnic groups. The lack of corresponding reductions in racial disparities highlights the need for targeted interventions to achieve greater treatment benefit among higher risk groups.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Racial Disparities in Renal Outcomes Over Time Among Hospitalized Children With Systemic Lupus Erythematosus

Chang

Sears

Torres

et al. 2022

Arthritis & Rheumatology

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“…Our subgroup analysis indicated that young patients with SLE were less likely to develop end-stage renal disease (ESRD). Another epidemiological investigation found that most children with LN had unchanged or normal kidney function, and that ESRD was rare ( Vazzana et al, 2021 ). In addition, the probability of death from active SLE was much lower in children than adult men ( Brunner et al, 2008 ).…”

Section: Discussionmentioning

confidence: 99%

Imbalance of helper T cell type 1, helper T cell type 2 and associated cytokines in patients with systemic lupus erythematosus: A meta-analysis

Xiang

Zhang²,

Zhang³

et al. 2022

Front. Pharmacol.

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Objective: Th1 and Th2 cells and their associated cytokines function in the pathogenesis of systemic lupus erythematosus (SLE), but their exact roles are uncertain. We performed a meta-analysis to examine the relationship of these cells and cytokines with SLE.Methods: Multiple databases were searched to identify publications that reported the percentages of Th1 and Th2 cells and their associated cytokines in SLE patients and healthy controls (HCs). Meta-analysis was performed using Stata MP version 16.Results: SLE patients had a lower percentage of Th1 cells, a higher percentage of Th2 cells, and higher levels of Th1- and Th2-associated cytokines than HCs. SLE treatments normalized some but not all of these indicators. For studies in which the proportion of females was less than 94%, the percentage of Th2 cells and the level of IL-10 were higher in patients than HCs. SLE patients who had abnormal kidney function and were younger than 30 years old had a higher proportion of Th1 cells than HCs. SLE patients more than 30 years old had a higher level of IL-6 than HCs.Conclusion: Medications appeared to restore the balance of Th1 cells and other disease indicators in patients with SLE. Gender and age affected the levels of Th1 and Th2 cells, and the abnormally elevated levels of Th2 cells appear to be more pronounced in older patients and males.Systematic Review Registration: [https://www.crd.york.ac.uk/prospero/], identifier [CRD42022296540].

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“…Data are limited on the comparative effectiveness of most diagnostic and management approaches in childhood SLE. Up to 20% of all SLE cases are diagnosed before age 18 years (1)(2)(3)(4)(5)(6), and 35%-70% develop kidney involvement (2,3,7,8). Lupus nephritis develops earlier and behaves more aggressively in childhood SLE compared with adult-onset SLE (9).…”

Section: Introductionmentioning

confidence: 99%

Using a Multi-Institutional Pediatric Learning Health System to Identify Systemic Lupus Erythematosus and Lupus Nephritis

Wenderfer¹,

Chang²,

Davies³

et al. 2022

CJASN

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Background: Performing adequately powered clinical trials in pediatric diseases such as systemic lupus erythematosus (SLE) is challenging. Improved recruitment strategies are needed for identifying patients. Design, Setting, Participants, and Measurements: Electronic health record (EHR) algorithms were developed and tested to identify children with SLE both with and without lupus nephritis. We used single center EHR data to develop computable phenotypes comprised of diagnosis, medication, procedure, and utilization codes. These were evaluated iteratively against a manually assembled SLE patient database. The highest performing phenotypes were then evaluated across institutions in PEDSnet, a national healthcare systems network of >6.7 million children. Reviewers blinded to case status used standardized forms to review random samples of cases (n=350) and non-cases (n=350). Results: Final algorithms consisted of both utilization and diagnostic criteria. For both, utilization criteria included ≥2 in-person visits with nephrology or rheumatology and ≥60 days follow-up. SLE diagnostic criteria included absence of neonatal lupus, ≥1 hydroxychloroquine exposure, and either ≥3 qualifying diagnosis codes separated by ≥30 days, or ≥1 diagnosis code and ≥1 kidney biopsy procedure code. Sensitivity was 100% (95%CI, 99-100); specificity, 92% (95% CI, 88-94); positive predictive value, 91% (95%CI, 87-94); negative predictive value, 100% (95%CI, 99-100). Lupus nephritis diagnostic criteria included either ≥3 qualifying lupus nephritis diagnosis codes (or SLE codes on same day as glomerular/kidney codes) separated by ≥30 days, or ≥1 SLE diagnosis code and ≥1 kidney biopsy procedure code. Sensitivity was 90% (95%CI, 85-94); specificity, 93% (95% CI, 89-97); positive predictive value, 94% (95%CI, 89-97); negative predictive value, 90% (95%CI, 84-94). Algorithms identified 1,508 children with SLE at PEDSnet institutions (537 with LN), 809 of whom were seen in the past 12 months. Conclusions: EHR-based algorithms for SLE and Lupus nephritis demonstrated excellent classification accuracy across PEDSnet institutions.

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Principles of pediatric lupus nephritis in a prospective contemporary multi-center cohort

Cited by 29 publications

References 44 publications

Racial Disparities in Renal Outcomes Over Time Among Hospitalized Children With Systemic Lupus Erythematosus

Racial Disparities in Renal Outcomes Over Time Among Hospitalized Children With Systemic Lupus Erythematosus

Imbalance of helper T cell type 1, helper T cell type 2 and associated cytokines in patients with systemic lupus erythematosus: A meta-analysis

Using a Multi-Institutional Pediatric Learning Health System to Identify Systemic Lupus Erythematosus and Lupus Nephritis

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