CKD, Recent Transplant May Increase Cancer Risk, Study Finds

A study published in American Journal of Kidney Diseases found that the risk of cancer was higher in patients with mild to moderate chronic kidney disease (CKD) and in kidney transplant recipients vs patients with normal kidney function. Patients with kidney disease also had a higher risk of cancer-related mortality.

Patients were included in this analysis if they were 18 years and older with serum creatinine data in the Ontario Laboratory Information System (OLIS) or registration within the Canadian Organ Replacement Register (CORR) between April 1, 2007, and October 31, 2016.

Patients were categorized by their kidney function status by using serum creatinine values within OLIS or registration as a maintenance dialysis or kidney transplant recipient within CORR. Mortality data came from death certificates.

Patients were followed from index date to their first cancer diagnosis, censoring events (transition to dialysis or kidney transplant or end of follow-up), or death, whichever came first.

There were 439,554 participants who had stage 3a-5 CKD; 29,809 maintenance dialysis recipients; and 4951 kidney transplant recipients. Median (IQR) follow-up was 5.33 (3.2-7.1) years, the median age of the participants was 60 (46-74) years, and 57% were female.

Patients with stage G3-5 CKD and end-stage kidney disease (ESKD) on dialysis were older than both patients who had an estimated glomerular filtration rate (eGFR) of at least 60 mL/min/1.73 m² and kidney transplantation recipients. Patients with stage G4/5 CKD and ESKD had a greater burden of comorbidities.

There was a total of 325,895 cancer diagnoses in the follow-up period. The cumulative incidences of cancer diagnoses in patients with eGFR greater than or equal to 60 mL/min/1.73 m²; CKD stages 3a, 3b, 5, and 5; dialysis recipients; and transplant recipients were 9.0% (95% CI, 8.6%-9.3%); 15.3% (95% CI, 14.4%-16.3%), 13.7% (95% CI, 13.5%-14.0%), 11.5% (95% CI, 11.1%-11.9%), and 10.8% (95% CI, 9.5%-12.3%); 11.5% (95% CI, 11.0%-12.1%); and 13.2% (95% CI, 11.6%-14.8%), respectively.

Malignancies with the highest incidence in patients with eGFR of at least 60 mL/min/1.73 m² were prostate (2.6%), breast (2.5%), lung (1.2%), colorectal (1.0%), and non-Hodgkin lymphoma (0.4%). Kidney cancers were the top 5 most frequent cancers in patients with CKD G4-5, dialysis recipients, and transplant recipients.

The adjusted HRs of all cancer diagnoses in patients with CKD stages G3a, 3b, 4, and 5 were 1.08 (95% CI, 1.07-1.10), 0.99 (95% CI, 0.97-1.01), 0.85 (95% CI, 0.81-0.88), and 0.81 (95% CI, 0.73-0.90) respectively; on dialysis, the aHR was 1.01 (95% CI, 0.96-1.07), while for transplant recipients it was 1.25 (95% CI, 1.12-1.39).

Risks for bladder cancer (in CKD 3a to 4), kidney cancer, and multiple myeloma were elevated among patients with kidney disease, and the risk of kidney cancer increased with worsening kidney function. The risks for breast and prostate cancer were lower.

There were 72,143 deaths that were attributed to cancer. Patients with CKD stages G3a (aHR, 1.27; 95% CI, 1.23-1.32), 3b (aHR, 1.29; 95% CI, 1.24-1.35), and 4 (aHR, 1.25; 95% CI, 1.18-1.33) and transplant recipients (aHR, 1.48; 95% CI, 1.18-1.87) had an increased risk of cancer-specific mortality. Bladder and kidney cancer mortality risk increased in CKD through stages G3a to 5, dialysis, and transplant recipients.

Patients with kidney disease also had a higher number of stage 4 cancer cases at the time of diagnosis. Death attributed to cardiovascular causes exceeded cancer-related mortality in all categories of CKD.

There were some limitations to this study. Residual confounding, such as family history and smoking status, may have biased the effect of the study; patients with advanced CKD may have limited power to detect associations for some cancer outcomes, which may influence the estimates for overall risk; and death certificates may misclassify cause of death.

The researchers concluded that incident cancer affected up to 15% of patients with CKD, with kidney, bladder, and multiple myeloma being the most frequent cancers in patients with kidney disease. Cancer mortality was higher in patients with mild to severe CKD and kidney transplant recipients compared with patients with normal kidney function.

Reference

Kitchlu A, Reid J, Jeyakumar N, et al. Cancer risk and mortality in patients with kidney disease: a population-based cohort study. Am J Kidney Dis. Published online April 8, 2022. doi:10.1053/j.ajkd.2022.02.020