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

Abstract

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.

Development and evaluation of a scalable alternative to chart review for phenotype case adjudication using standardized structured data from electronic health records

“…KEEPER is efficient if the structured data contain the necessary elements for valid inference and therefore its performance may depend on comprehensiveness of data capture and specifics of patient population in a given data source. Data is likely to be sufficient to infer prevalent conditions and conditions requiring drug therapy or operative procedures [49][50][51]. On contrary, it is commonly acknowledged that asymptomatic conditions and some co-morbidities are underrepresented in structured data [52].…”

Use of renin angiotensin aldosterone system inhibitors in children with lupus and time to glucocorticoid discontinuation

“…17 As data regarding provider specialty were unavailable for 13% of encounters, the definition for nephritis was expanded to also include those with >2 kidney disease diagnosis codes and a kidney biopsy procedure code, based on our previous work suggesting that including kidney biopsy as a criterion improves sensitivity without a significant negative impact on specificity. 18…”

“…First, we limited the IPTW competing risk regression model to those with at least 1 hydroxychloroquine prescription to improve the specificity of the cohort definition and reduce potential misclassification of SLE cases, as all children with SLE should be treated with hydroxychloroquine. 18 Second, we trimmed weights at the 1 st and 99 th percentiles to evaluate for bias from large or small weights. 26,28 Third, we ran a standard IPTW Cox regression model using first ESKD diagnosis as a censoring event rather than a competing risk.…”

“…Here, we sought to characterize RAAS inhibitor use in pediatric SLE and determine whether early RAAS inhibitor initiation among children with incident lupus nephritis is associated with decreased duration of chronic glucocorticoid exposure. A retrospective cohort study was performed of children (ages [5][6][7][8][9][10][11][12][13][14][15][16][17][18] with SLE and/or lupus nephritis in the Truven MarketScanä Medicaid and Commercial databases (2013-2018) and estimated RAAS inhibitor use. Among incident nephritis cases, we used competing risk hazard models with inverse probability of treatment weighting to estimate the association between RAAS inhibitor initiation less than 180 days after diagnosis and time to glucocorticoid discontinuation with kidney failure as a competing event.…”

Urine ALCAM, PF4 and VCAM-1 Surpass Conventional Metrics in Identifying Nephritis Disease Activity in Childhood-Onset Systemic Lupus Erythematosus

“…Compared to aSLE, cSLE exhibits higher frequencies of kidney, neuropsychiatric, and hematologic involvement (1,4). Lupus nephritis (LN) continues to be a prominent source of morbidity and mortality in SLE, reported in 30-40% of cSLE patients (3)(4)(5)(8)(9)(10)(11). LN is more frequent in Hispanics, and African descendants, showing higher levels of disease activity and risk of developing kidney failure compared to non-Hispanic whites (6).…”