Preoperative estimated glomerular filtration rate to predict cardiac events in major noncardiac surgery: a secondary analysis of two large international studies

Abstract

Chronic kidney disease; Risk prediction; Vascular events

Enfermedad renal crónica; Predicción de riesgo; Eventos vasculares

Malaltia renal crònica; Predicció de risc; Esdeveniments vasculars

Background Optimised use of kidney function information might improve cardiac risk prediction in noncardiac surgery. Methods In 35,815 patients from the VISION cohort study and 9219 patients from the POISE-2 trial who were ≥45 yr old and underwent nonurgent inpatient noncardiac surgery, we examined (by age and sex) the association between continuous nonlinear preoperative estimated glomerular filtration rate (eGFR) and the composite of myocardial injury after noncardiac surgery, nonfatal cardiac arrest, or death owing to a cardiac cause within 30 days after surgery. We estimated contributions of predictive information, C-statistic, and net benefit from eGFR and other common patient and surgical characteristics to large multivariable models. Results The primary composite occurred in 4725 (13.2%) patients in VISION and 1903 (20.6%) in POISE-2; in both studies cardiac events had a strong, graded association with lower preoperative eGFR that was attenuated by older age (Pinteraction<0.001 for VISION; Pinteraction=0.008 for POISE-2). For eGFR of 30 compared with 90 ml min−1 1.73 m−2, relative risk was 1.49 (95% confidence interval 1.26–1.78) at age 80 yr but 4.50 (2.84–7.13) at age 50 yr in female patients in VISION. This differed modestly (but not meaningfully) in men in VISION (Pinteraction=0.02) but not in POISE-2 (Pinteraction=0.79). eGFR contributed the most predictive information and mean net benefit of all predictors in both studies, most C-statistic in VISION, and third most C-statistic in POISE-2. Conclusions Continuous preoperative eGFR is among the best cardiac risk predictors in noncardiac surgery of the large set examined. Along with its interaction with age, preoperative eGFR would improve risk calculators. Clinical trial registration ClinicalTrials.gov NCT00512109 (VISION) and NCT01082874 (POISE-2).

The POISE-2 and VISION funding sources had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; or the decision to submit the manuscript for publication. The POISE-2 study was funded by the Canadian Institutes of Health Research, the National Health and Medical Research Council of Australia, and the Spanish Ministry of Health and Social Policy. Bayer Pharma provided the aspirin used in the POISE-2 study, and Boehringer Ingelheim provided the clonidine and some financial support for the POISE-2 study. Roche Diagnostics provided the troponin T assays as well as financial support for the VISION study. Funding for the VISION study came from more than 70 grants: Canada: Canadian Institutes of Health Research (seven grants); Heart and Stroke Foundation of Ontario (two grants); Academic Health Science Centres Alternative Funding Plan Innovation Fund Ontario; Population Health Research Institute; CLARITY Research Group; McMaster University Department of Surgery Surgical Associates; Hamilton Health Science New Investigator Fund; Hamilton Health Sciences; Ontario Ministry of Resource and Innovation; Stryker Canada; McMaster University, Department of Anesthesiology (two grants); St Joseph's Healthcare, Department of Medicine (two grants); Father Sean O'Sullivan Research Centre (two grants); McMaster University Department of Medicine (two grants); Roche Diagnostics Global Office (five grants); Hamilton Health Sciences Summer Studentships (six grants); McMaster University Department of Clinical Epidemiology and Biostatistics; McMaster University, Division of Cardiology; Canadian Network and Centre for Trials Internationally; Winnipeg Health Sciences Foundation; University of Manitoba Department of Surgery (two grants); Diagnostic Services of Manitoba Research; Manitoba Medical Services Foundation; Manitoba Health Research Council; University of Manitoba Faculty of Dentistry Operational Fund; University of Manitoba Department of Anesthesia; University Medical Group, Department of Surgery, University of Manitoba, Start-up Fund. Australia: National Health and Medical Research Council Program. Brazil: Projeto Hospitais de Excelência a Serviço do SUS (PROADI-SUS) grant from the Brazilian Ministry of Health in partnership with Hcor (Cardiac Hospital Sao Paulo–SP); National Council for Scientific and Technological Development (CNPq) grant from the Brazilian Ministry of Science and Technology. China: Public Policy Research Fund (grant CUHK-4002-PPR-3), Research Grant Council, Hong Kong SAR; General Research Fund (grant 461412), Research Grant Council, Hong Kong SAR; Australian and New Zealand College of Anaesthetists (grant 13/008). Colombia: School of Nursing, Universidad Industrial de Santander; Grupo de Cardiología Preventiva, Universidad Autónoma de Bucaramanga; Fundación Cardioinfantil–Instituto de Cardiología; Alianza Diagnóstica SA. France: Université Pierre et Marie Curie, Département d'anesthésie Réanimation, Pitié-Salpêtrière, Assistance Publique–Hôpitaux de Paris. India: St John's Medical College and Research Institute; Division of Clinical Research and Training. Malaysia: University of Malaya (grant RG302-14AFR); University of Malaya, Penyelidikan Jangka Pendek. Poland: Polish Ministry of Science and Higher Education (grant NN402083939). South Africa: University of KwaZulu-Natal. Spain: Instituto de Salud Carlos III; Fundació La Marató de TV3. USA: American Heart Association; Covidien; American Society of Nephrology Student Scholar Grant. UK: National Institute for Health Research. Pavel Roshanov is recipient of a career award from the Academic Medical Organization of Southwestern Ontario and his research is supported by the William F. Clark Chair in Nephrology from Western University. Flavia Borges is recipient of an Early Career Research Award from Hamilton Health Sciences. Tyrone Harrison is supported by a Kidney Research Scientist Core Education and National Training (KRESCENT) Program New Investigator Award (co-sponsored by the Kidney Foundation of Canada and Canadian Institutes of Health Research) and is supported as a new investigator by the Roy and Vi Baay Chair for Kidney Research and the Kidney Health and Wellness Institute at the University of Calgary. Vikram Fielding-Singh has received support from the American Heart Association (23CDA1053913) and the National Institute of Diabetes and Digestive and Kidney Diseases of the National Institutes of Health (K23DK138312).