Risk of Cancer and Cancer-Related Mortality in Patients with CKD

The estimated worldwide prevalence of chronic kidney disease (CKD) is 11% to 13%. Compared with the general population, patients with CKD may face an increased risk of cancer, possibly related to heightened inflammation and immune dysfunction. According to Abhijat Kitchlu, MD, MSc, FRCPC, and colleagues, there are few clinical data available on increased cancer risk among patients with CKD.

The researchers utilized data from a population-based cohort of individuals with serum creatinine measurements, along with linked registries of dialysis and kidney transplant registries, to examine the overall and site-specific cancer incidence and cancer-specific mortality across the spectrum of CKD. Results were reported in the American Journal of Kidney Diseases [2022;80(4):436-448].

The study included all patients ≥18 years of age with data on serum creatinine level in the provincewide Ontario Laboratory Information System or registration in the Canadian Organ Replacement Register as maintenance dialysis or kidney transplant recipients between April 1, 2007, and October 31, 2016. Patients with prior cancer diagnoses (10 years prior to the index date) and non-Ontario residents were excluded. Ontario residents receive single-payer publicly funded health care under the Ontario Health Insurance Plan.

Patients were categorized as of the first date they had two assessments of estimated glomerular filtration rate (eGFR) or were registered as receiving maintenance dialysis or having received a kidney transplant. Patients were further categorized based on eGFR: ≥60, 45 to 59, 30 to 44, 15 to 29, and <15 mL/min/1.73 m2. The latter four categories meet Kidney Disease: Improving Global Outcomes criteria for CKD G3a, G3b, G4, and G5, respectively.

The outcomes of interest were overall and site-specific cancer incidence and mortality. Fine and Gray subdistribution hazard models were used in the data analyses.

A total of 5,882,388 individuals had data on eGFR; of those, 7.4% (n=439,554) had CKD G3a to G5; there  were 29,809 patients on maintenance dialysis and 4951 who had received a kidney transplant, for a total follow-up of 29,938,374 person-years.

Median age of the cohort was 60 years and 57% were women. Those with CKD G3 to G5 and those on maintenance dialysis were older than those with eGFR ≥60 mL/min/1.73 m2 and those who had received a kidney transplant. The comorbidity burden was greater among those with CKD G4 to G5 and those receiving kidney replacement therapy (maintenance dialysis or transplant), with a higher Charlson index and more frequent emergency department visits and hospitalizations.

During a median follow-up of 5.33 years, there were 325,895 cancer diagnoses. The overall 1-year cumulative incidences of all cancer diagnoses in patients with eGFR ≥60 mL/min/1.73 m2; those with CKD G3a, G3b, G4, or G5; patients receiving dialysis; 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%), 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.

The malignancies with the highest cumulative incidences in patients with eGFR ≥60 mL/min/1.73 m2 were prostate (2.6%), breast (2.5%), lung (1.2%), and colorectal (1.0%) cancers and non-Hodgkin lymphoma (o.4%). In individuals with CKD G4 and G5, dialysis patients, and transplant recipients, kidney cancers were among the top five most frequent cancers. In transplant recipients, kidney cancers were the third most common after breast cancer and lung cancer. Kidney cancers were the fourth most common among patients on dialysis.

Compared with patients with eGFR ≥60 mL/min/1.73 m2, adjusted hazard ratios (aHRs) for all cancer diagnoses among patients with CKD G3a, G3b, G4 or G5, patients on maintenance dialysis, and transplant recipients were 1.08 (95% CI, 1.07-1.10), 0.99 (95% CI, 0.97-.01), 0.85 (95% CI, 0.81-0.88), 0.81 (95% CI, 0.73-0.90), 1.01 (95% CI, 0.96-1.07), and 1.25 (95% CI, 1.12-1.39), respectively.

Cancers with increased risk among patients with kidney disease included bladder cancer (in CKD G3a-G4), kidney cancer, and multiple myeloma. The risks of kidney cancers and diagnoses of multiple myeloma increased with worsening eGFR. There was a lower hazard of breast and prostate cancer among patients with kidney disease

A total of 72,143 deaths were attributed to cancer. There was an increased risk of cancer-specific mortality among patients with CKD G3a, G3b, and G4, and transplant recipients (aHRs, 1.27 [95% CI, 1.23-1.32], 1.29 [95% CI, 1.24-1.35], 1.25 [95% CI, 1.18-1.33], and 1.48 [95% CI, 1.18-1.87], respectively). There were no increased risks for cancer-specific mortality among patients with CKD G5 and those receiving dialysis.

Across all of the study categories, bladder and kidney cancer risk became progressively greater. With the exception of those with CKD G5, mortality related to multiple myeloma also increased in all groups. Compared with participants with eGFR ≥60 mL/min/1.73 m2, the incidences of breast, colorectal, and prostate cancer diageneses were lower in most categories of kidney disease. Cancer-specific mortality was greater in CKD G3a and G3b and similar in other categories.

Compared with those with eGFR ≥60 mL/min/1.73 m2, the proportion of stage 4 cancers at the time of diagnosis was higher among those in all categories of kidney disease. In all kidney function categories, the median cancer stage at diagnosis was 2. There was no association between time from dialysis initiation or time since transplant and increased risk of cancer among those on dialysis and transplant recipients.

In patients with CKD G3a to G5, cardiovascular-related mortality exceeded cancer-related mortality. In those with eGFR ≥60 mL/min/1.73 m2 and in kidney transplant recipients, cancer and cardiovascular mortality were comparable.

Citing limitations to the study, the researchers noted the possibility of residual confounding related to measured covariates or due to missing cancer factors such as family history or smoking, the possibility that death certificates may have misclassified cause of death, and the inability to generalize the findings to other jurisdictions.

In conclusion, the authors said, “In a population-wide cohort of patients across the spectrum of kidney disease, we found that incident cancer affected as many as 15% of patients with CKD. However, cancer risk did not consistently vary with CKD severity. Specific cancers including kidney and bladder cancers and multiple myeloma were more frequent in patients with kidney disease. Overall cancer mortality rates were significantly higher in those with moderate to severe CKD and in kidney transplant recipients relative to patients with eGFR ≥60 mL/min/1.73 m2. Efforts to improve cancer treatment strategies in this population are needed, particularly for urologic cancers and multiple myeloma.”

Takeaway Points

  1. Researchers reported results of a population-based cohort study designed to examine cancer incidence and mortality across the spectrum of chronic kidney disease (CKD).
  2. Cancer risk was increased in mild to moderate CKD and among recipients of kidney transplant, but not in patients with advanced kidney disease.
  3. Cancer-related mortality was significantly higher among patients with kidney disease, particularly urologic cancers and multiple myeloma.