CKD and the Risk of Incident Cancer

Abstract

Previous studies report a higher risk of cancer in patients with ESRD, but the impact of less severe CKD on risk of cancer is uncertain. Our objective was to evaluate the association between level of kidney function and subsequent cancer risk. We performed a retrospective cohort study of 1,190,538 adults who were receiving care within a health care delivery system, had a measurement of kidney function obtained between 2000 and 2008, and had no prior cancer. We examined the association between level of eGFR and the risk of incident cancer; the primary outcome was renal cancer, and secondary outcomes were any cancer and specific cancers (urothelial, prostate, breast, lung, and colorectal). During 6,000,420 person-years of follow-up, we identified 76,809 incident cancers in 72,875 subjects. After adjustment for time-updated confounders, lower eGFR (in milliliters per minute per 1.73 m 2 ) was associated with an increased risk of renal cancer (adjusted hazard ratio [HR], 1.39; 95% confidence interval [95% CI], 1.22 to 1.58 for eGFR=45-59; HR, 1.81; 95% CI, 1.51 to 2.17 for eGFR=30-44; HR, 2.28; 95% CI, 1.78 to 2.92 for eGFR,30). We also observed an increased risk of urothelial cancer at eGFR,30 but no significant associations between eGFR and prostate, breast, lung, colorectal, or any cancer overall. In conclusion, reduced eGFR is associated with an independently higher risk of renal and urothelial cancer but not other cancer types.

CKD and Risk of Renal Cell Carcinoma

“…Lowrance et al 7 sought to account for bias resulting from reverse causation by restricting their analysis to individuals without a history of dialysis or renal transplantation before study entry, by excluding incident cancers diagnosed during the first 2 years of follow-up, and by excluding serum creatinine measurements obtained ,3 months before an incident cancer diagnosis. Although these exclusion criteria should provide some reassurance that the observed association reflects an etiologic role of CKD in renal carcinogenesis, future studies characterizing kidney function earlier in time before RCC diagnosis would further strengthen the argument against reverse causation bias.…”

The Nephrologist’s Tumor: Basic Biology and Management of Renal Cell Carcinoma

“…51 For example, the increased risk for RCC was 100-fold for patients with ESRD, 51 and it was increased for patients with CKD (stage 3/4) as well. 52 The incidence of renal cancers rose incrementally with higher CKD stages, and the strongest association was with ccRCC. 52 Remarkably, the incidence of renal cancers also varied according to periods of renal function (transplant) versus nonfunction (graft failure requiring dialysis) among 202,195 renal transplant candidates.…”

“…52 The incidence of renal cancers rose incrementally with higher CKD stages, and the strongest association was with ccRCC. 52 Remarkably, the incidence of renal cancers also varied according to periods of renal function (transplant) versus nonfunction (graft failure requiring dialysis) among 202,195 renal transplant candidates. 53 Incident rates of renal cancer rose when renal function was lost and fell after transplantation, and this pattern recurred during subsequent transplantations.…”

“…53 The mechanism for these findings is largely unknown, but proposed explanations include uremiarelated chronic inflammation, oxidative stress, compromised immune function, dialysis, medications, and/or common comorbid diseases further increasing cancer risk. 52,54,55 For example, type 2 diabetes mellitus (a risk factor for both RCC and CKD) increases cancer risk for many organs, including the kidney, where hyperinsulinemia (as a growth factor), insulin resistance, and obesity-related inflammatory cytokines are plausible mechanisms. 55 The biologic basis for increased cancer risk among those with CKD or ESRD is not clear, but understanding these factors may not only help determine treatment of renal causes but will likely lower the risk of or even prevent renal cancers.…”

Obesity, Diabetes Mellitus, Hypertension and other Risk Factors for Renal Cell Carcinoma in Japan: A Mini-Review

“…Recently, Lowrance et al [32] found a positive association between demonstrated that chronic kidney disease increased the risk of kidney cancer in the American population while Lai et al [29] found a positive association between chronic kidney disease and the risk of kidney cancer in the Taiwanese population.…”