Eric H Au1, Germaine Wong2, Kirsten Howard3, Jeremy R Chapman4, Antoni Castells5, Simon D Roger6, Michael J Bourke7, Petra Macaskill3, Robin Turner8, Wai H Lim9, Charmaine E Lok10, Fritz Diekmann11, Nicholas Cross12, Shaundeep Sen13, Richard D Allen14, Steven J Chadban14, Carol A Pollock15, Allison Tong16, Armando Teixeira-Pinto16, Jean Y Yang17, Anh Kieu16, Laura James16, Jonathan C Craig18. 1. Sydney School of Public Health, Faculty of Medicine and Health, University of Sydney, Sydney, Australia; Centre for Kidney Research, The Children's Hospital at Westmead, Westmead, Australia; Centre for Transplant and Renal Research, Westmead Hospital, Westmead, Australia. Electronic address: e.au@sydney.edu.au. 2. Sydney School of Public Health, Faculty of Medicine and Health, University of Sydney, Sydney, Australia; Centre for Kidney Research, The Children's Hospital at Westmead, Westmead, Australia; Centre for Transplant and Renal Research, Westmead Hospital, Westmead, Australia. 3. Sydney School of Public Health, Faculty of Medicine and Health, University of Sydney, Sydney, Australia. 4. Centre for Transplant and Renal Research, Westmead Hospital, Westmead, Australia. 5. Gastroenterology Department, Hospital Clínic, University of Barcelona, Barcelona, Spain. 6. Department of Renal Medicine, Gosford Hospital, Gosford, Australia. 7. Department of Gastroenterology, Westmead Hospital, Westmead, Australia. 8. Sydney School of Public Health, Faculty of Medicine and Health, University of Sydney, Sydney, Australia; Biostatistics Unit, Dunedin School of Medicine, Otago University, Christchurch, New Zealand. 9. Department of Renal Medicine, Sir Charles Gairdner Hospital, Perth, Australia. 10. Department of Medicine, University Health Network-Toronto General Hospital, Toronto, Ontario, Canada. 11. Department of Nephrology and Kidney Transplantation, Hospital Clínic, University of Barcelona, Barcelona, Spain. 12. Department of Nephrology and Kidney Transplantation, Christchurch Hospital, Otago University, Christchurch, New Zealand. 13. Department of Renal Medicine, Concord Repatriation General Hospital, Concord, Australia. 14. Department of Renal Medicine, Royal Prince Alfred Hospital, and Charles Perkins Centre, University of Sydney, Sydney, Australia. 15. Department of Medicine, Northern Clinical School, Kolling Institute of Medical Research, Sydney, Australia. 16. Sydney School of Public Health, Faculty of Medicine and Health, University of Sydney, Sydney, Australia; Centre for Kidney Research, The Children's Hospital at Westmead, Westmead, Australia. 17. School of Mathematics and Statistics, University of Sydney, Sydney, Australia. 18. College of Medicine and Public Health, Flinders University, Adelaide, Australia.
Abstract
RATIONALE & OBJECTIVE: The risk of developing colorectal cancer in patients with chronic kidney disease (CKD) is twice that of the general population, but the factors associated with colorectal cancer are poorly understood. The aim of this study was to identify factors associated with advanced colorectal neoplasia in patients with CKD. STUDY DESIGN: Prospective cohort study. SETTING & PARTICIPANTS: Patients with CKD stages 3-5, including those treated with maintenance dialysis or transplantation across 11 sites in Australia, New Zealand, Canada, and Spain, were screened for colorectal neoplasia using a fecal immunochemical test (FIT) as part of the Detecting Bowel Cancer in CKD (DETECT) Study. EXPOSURE: Baseline characteristics for patients at the time of study enrollment were ascertained, including duration of CKD, comorbidities, and medications. OUTCOME: Advanced colorectal neoplasia was identified through a 2-step verification process with colonoscopy following positive FIT and 2-year clinical follow-up for all patients. ANALYTICAL APPROACH: Potential factors associated with advanced colorectal neoplasia were explored using multivariable logistic regression. Sensitivity analyses were performed using grouped LASSO (least absolute shrinkage and selection operator) logistic regression. RESULTS: Among 1,706 patients who received FIT-based screening-791 with CKD stages 3-5 not receiving kidney replacement therapy (KRT), 418 receiving dialysis, and 497 patients with a functioning kidney transplant-117 patients (6.9%) were detected to have advanced colorectal neoplasia (54 with CKD stages 3-5 without KRT, 34 receiving dialysis, and 29 transplant recipients), including 9 colorectal cancers. The factors found to be associated with advanced colorectal neoplasia included older age (OR per year older, 1.05 [95% CI, 1.03-1.07], P<0.001), male sex (OR, 2.27 [95% CI, 1.45-3.54], P<0.001), azathioprine use (OR, 2.99 [95% CI, 1.40-6.37], P=0.005), and erythropoiesis-stimulating agent use (OR, 1.92 [95% CI, 1.22-3.03], P=0.005). Grouped LASSO logistic regression revealed similar associations between these factors and advanced colorectal neoplasia. LIMITATIONS: Unmeasured confounding factors. CONCLUSIONS: Older age, male sex, erythropoiesis-stimulating agents, and azathioprine were found to be significantly associated with advanced colorectal neoplasia in patients with CKD.
RATIONALE & OBJECTIVE: The risk of developing colorectal cancer in patients with chronic kidney disease (CKD) is twice that of the general population, but the factors associated with colorectal cancer are poorly understood. The aim of this study was to identify factors associated with advanced colorectal neoplasia in patients with CKD. STUDY DESIGN: Prospective cohort study. SETTING & PARTICIPANTS: Patients with CKD stages 3-5, including those treated with maintenance dialysis or transplantation across 11 sites in Australia, New Zealand, Canada, and Spain, were screened for colorectal neoplasia using a fecal immunochemical test (FIT) as part of the Detecting Bowel Cancer in CKD (DETECT) Study. EXPOSURE: Baseline characteristics for patients at the time of study enrollment were ascertained, including duration of CKD, comorbidities, and medications. OUTCOME: Advanced colorectal neoplasia was identified through a 2-step verification process with colonoscopy following positive FIT and 2-year clinical follow-up for all patients. ANALYTICAL APPROACH: Potential factors associated with advanced colorectal neoplasia were explored using multivariable logistic regression. Sensitivity analyses were performed using grouped LASSO (least absolute shrinkage and selection operator) logistic regression. RESULTS: Among 1,706 patients who received FIT-based screening-791 with CKD stages 3-5 not receiving kidney replacement therapy (KRT), 418 receiving dialysis, and 497 patients with a functioning kidney transplant-117 patients (6.9%) were detected to have advanced colorectal neoplasia (54 with CKD stages 3-5 without KRT, 34 receiving dialysis, and 29 transplant recipients), including 9 colorectal cancers. The factors found to be associated with advanced colorectal neoplasia included older age (OR per year older, 1.05 [95% CI, 1.03-1.07], P<0.001), male sex (OR, 2.27 [95% CI, 1.45-3.54], P<0.001), azathioprine use (OR, 2.99 [95% CI, 1.40-6.37], P=0.005), and erythropoiesis-stimulating agent use (OR, 1.92 [95% CI, 1.22-3.03], P=0.005). Grouped LASSO logistic regression revealed similar associations between these factors and advanced colorectal neoplasia. LIMITATIONS: Unmeasured confounding factors. CONCLUSIONS: Older age, male sex, erythropoiesis-stimulating agents, and azathioprine were found to be significantly associated with advanced colorectal neoplasia in patients with CKD.