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Toor, Kirandeep

University of British Columbia

Pediatric-onset anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) is a rare, systemic disease involving inflammation and damage to small and medium sized blood vessels, primarily affecting the lungs and kidneys. The rarity of AAV in childhood precludes pediatric-specific clinical trials, thus treatment strategies have been adopted from trials in adult-onset AAV. Although these ‘adult’ treatment approaches have substantially decreased mortality in children with AAV, significant concerns persist around the toxicity risks specific to children and the appropriateness of applying adult-based recommendations to pediatric-onset disease. Our previous research demonstrated that, compared to adult-onset AAV, pediatric-onset AAV is more likely to be severe and have major organ dysfunction, such as significantly reduced renal function and severe lung disease. The intent of this thesis is to investigate the course of renal and pulmonary disease in children with AAV in the first 12-months, and to evaluate any predictors of these outcomes. This thesis research used both retrospectively and prospectively collected clinical data from the largest multi-center, international registry of children with vasculitis hosted at the University of British Columbia and the BC Children’s Hospital Research Institute. This thesis reports that despite the majority of patients receiving aggressive treatment, two-thirds of patients have reduced kidney function at 12 - and 24–month follow-up and more than one-third of patients have evidence of permanent kidney damage at 12-months. Kidney function at diagnosis (eGFR) is a strong predictor of kidney function at 12-months. Additionally, >50% of children with AAV present with pulmonary disease; however, the majority achieve inactive disease by 12-months, and few are left with pulmonary damage. This research characterized pulmonary and renal disease course, described early outcomes, and demonstrated the utility of using eGFR as a biomarker in childhood-onset AAV. Our research identified a cutpoint eGFR value (‘threshold’) at diagnosis, below which children have a higher likelihood of having significant renal dysfunction by 12-months. Identification of a clinical ‘threshold’ is appealing as a simple and easy-to-use clinical tool and warrants further study. Improved understanding of disease course, outcomes and predictors of outcomes will contribute to better prognostication and management of childhood-onset AAV.

Text

2025-01-09

Attribution-NonCommercial-NoDerivatives 4.0 International

http://hdl.handle.net/2429/90074

Women+ and Children’s Health Sciences

University of British Columbia

UBCV

http://creativecommons.org/licenses/by-nc-nd/4.0/