ORIGINAL CLINICAL SCIENCE Incorporation of renal function in mortality risk assessment for pulmonary arterial hypertension Jason G.E. Zelt, MSc, a,b Alomgir Hossain, PhD, c Louise Y. Sun, MD, SM, c,d Sanjay Mehta, MD, e George Chandy, MD, MSc, b,f Ross A. Davies, MD, b Vladimir Contreras-Dominguez, MD, f Rosemary Dunne, RN, b Caroyln Doyle-Cox, RN, b George Wells, PhD, c Duncan J. Stewart, MD, a,b,g and Lisa M. Mielniczuk, MD, MSc a,b From the a Department of Cellular and Molecular Medicine, Faculty of Medicine, University of Ottawa, Ottawa, Ontario, Canada; b Division of Cardiology, University of Ottawa Heart Institute and University of Ottawa, Ottawa, Ontario, Can- ada; c School of Epidemiology and Public Health, University of Ottawa, Ottawa, Ontario, Canada; d Division of Cardiac Anesthesiology, Department of Anesthesiology and Pain Medicine, University of Ottawa Heart Institute, Ottawa, Ontario, Canada; e Division of Respirology, Department of Medicine, London Health Sciences Centre, Schulich School of Medicine and Dentistry, Western University, London, Ontario, Canada; f Division of Respirology and Internal Medicine, University of Ottawa, Ottawa, Ontario, Canada; and the g Sinclair Centre for Regenerative Medicine, Ottawa Hospital Research Insti- tute, Ottawa, Ontario, Canada. BACKGROUND: Risk assessment is important for prognostication and individualized treatment decisions for patients with pulmonary arterial hypertension (PAH). The purpose was (1) to com- pare contemporary risk assessment tools and (2) to determine the prognostic significance of risk parameters of kidney function and whether they can further improve risk prediction for patients with PAH. METHODS: We identified a cohort of treatment-naive patients (n = 211) who received an incident diag- nosis of PAH at the University of Ottawa Heart Institute. Using demographics, disease characteristics, and hemodynamic data at diagnosis, we categorized patients as low, intermediate, or high risk accord- ing to current European guidelines (European Society of Cardiology [ESC]) and registry to evaluate early and long-term pulmonary arterial hypertension disease management (REVEAL) risk scores. The primary end-point was transplant-free survival (TFS). RESULTS: Patients were predominantly women (64.6%) with World Health Organization function Class III symptoms (66.5%). The median TFS was 7.09 years. There was little agreement between ESC- and REVEAL-based risk estimates (weighted kappa = 0.21-0.34). Although both the ESC (log- rank, p = 0.0002) and REVEAL algorithms stratified TFS risk (p < 0.0001), the REVEAL score provided superior discrimination (C-statistic = 0.70 vs 0.59, p = 0.004). Renal function at diagnosis (p < 0.0001) and D renal function at 6 months (p < 0.0001) were identified as novel risk parameters and served to reclassify some patients in the intermediate-risk category to a lower or higher risk stra- tum (p < 0.0001). CONCLUSION: REVEAL-based strategies provide superior TFS risk discrimination to ESC/European Respiratory Society-based approaches. However, the classification of intermediate-risk patients varied significantly across tools. We demonstrate the importance of renal function, which further KEYWORDS: pulmonary arterial hypertension; risk assessment; renal disease; transplant free survival; REVEAL Reprint requests: Lisa M. Mielniczuk, MD, MSc, Department of Cellular and Molecular Medicine, University of Ottawa, 40 Ruskin Street, Ottawa, Ontario K1Y 4W7, Canada. Telephone: +613-761-4877. Fax: +613-761-4059. E-mail address: lmielniczuk@ottawaheart.ca 1053-2498/$ - see front matter Ó 2020 International Society for Heart and Lung Transplantation. All rights reserved. https://doi.org/10.1016/j.healun.2020.03.026 ARTICLE IN PRESS http://www.jhltonline.org