Original Investigation
Factors Associated With Advanced Colorectal Neoplasia in Patients With CKD

https://doi.org/10.1053/j.ajkd.2021.07.011Get rights and content

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.

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.

Section snippets

Study Design and Population

This is a planned substudy of the Detecting Bowel Cancer in CKD (DETECT) study,7,18 an international, multicenter study to examine the performance of the fecal immunochemical test (FIT) as a screening test for advanced colorectal neoplasia. The DETECT study included patients aged 35 to 74 years with CKD stages 3-5 not receiving KRT, on dialysis, or with a functioning kidney transplant across 11 sites in Australia, New Zealand, Canada, and Spain (Gosford, Westmead, Royal North Shore, Blacktown,

Baseline Characteristics of Participants

A total of 1,706 participants (78.7% of eligible patients) were enrolled in the DETECT study, including 791 (46.4%) patients with CKD stages 3-5 not receiving KRT, 418 (24.5%) patients on dialysis, and 471 (29.1%) patients with a functioning kidney transplant (Fig 1). The baseline characteristics by kidney disease group are shown in Table 1. There were 674 (39.5%) female participants. The mean age of the participants was 58.7 ± 10.6 (SD) years. Daily antiplatelet agents were taken by 527

Discussion

In this large cohort analysis of patients across the CKD spectrum (stages 3-5 not receiving KRT, patients on dialysis, and patients with a functioning kidney transplant), we found that older age, male sex, azathioprine use, and ESA use are factors associated with advanced colorectal neoplasia. Male sex and older age are well known risk factors for colorectal cancer in the general population,24 but the use of azathioprine and ESA are factors that are specific to patients with kidney disease.

Article Information

Authors’ Full Names and Academic Degrees

Eric H. Au, MBBS, Germaine Wong MBBS, PhD, Kirsten Howard, PhD, Jeremy R. Chapman, MD, Antoni Castells, MD, PhD, Simon D. Roger, MD, Michael J. Bourke, MBBS, PhD, Petra Macaskill, PhD, Robin Turner, PhD, Wai H. Lim, MBBS, PhD, Charmaine E. Lok, MD, MSc, Fritz Diekmann, MD, PhD, Nicholas Cross, MBChB, PhD, Shaundeep Sen, MBBS, PhD, Richard D. Allen, MBBS, FRACS, PhD, Steven J. Chadban, MBBS, PhD, Carol A. Pollock, MBBS, PhD, Allison Tong, PhD, Armando Teixeira-Pinto, PhD, Jean Y. Yang, PhD, Anh

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    ∗

    EHA and GW contributed equally to this work.

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    © 2021 by the National Kidney Foundation, Inc.