Estimated Glomerular Filtration Rate and the Risk of Cancer

Abstract

Background and objectives: Community-based reports regarding eGFR and the risk of cancer are conflicting. We here explore plausible links between kidney function and cancer incidence in a large Scandinavian population-based cohort.

Design, setting, participants, & measurements: In the Stockholm Creatinine Measurements project, we quantified the associations of baseline eGFR with the incidence of cancer among 719,033 Swedes ages ≥40 years old with no prior history of cancer. Study outcomes were any type and site-specific cancer incidence rates on the basis of International Classification of Diseases-10 codes over a median follow-up of 5 years. To explore the possibility of detection bias and reverse causation, we divided the follow-up time into different time periods (≤12 and >12 months) and estimated risks for each of these intervals.

Results: In total, 64,319 cases of cancer (affecting 9% of participants) were detected throughout 3,338,226 person-years. The relationship between eGFR and cancer incidence was U shaped. Compared with eGFR of 90-104 ml/min, lower eGFR strata associated with higher cancer risk (adjusted hazard ratio, 1.08; 95% confidence interval, 1.05 to 1.11 for eGFR=30-59 ml/min and adjusted hazard ratio, 1.24; 95% confidence interval, 1.15 to 1.35 for eGFR<30 ml/min). Lower eGFR strata were significantly associated with higher risk of skin, urogenital, prostate, and hematologic cancers. Any cancer risk as well as skin (nonmelanoma) and urogenital cancer risks were significantly elevated throughout follow-up time, but they were higher in the first 12 months postregistration. Associations with hematologic and prostate cancers abrogated after the first 12 months of observation, suggesting the presence of detection bias and/or reverse causation.

Conclusions: There is a modestly higher cancer risk in individuals with mild to severe CKD driven primarily by skin and urogenital cancers, and this is only partially explained by bias.

Keywords: Bias; Cancer; Confidence Intervals; Follow-Up Studies; Hematologic Neoplasms; Incidence; International Classification of Diseases; Proportional Hazards Models; Prostatic Neoplasms; Renal Insufficiency, Chronic; Risk; Urogenital Neoplasms; chronic kidney disease; detection bias; estimated glomerular filtration rate; glomerular filtration rate; reverse causation.

Graphical abstract

Figure 1.

U-shape association between eGFR (continuous) and overall cancer risk. Shown are linear splines adjusted for age, sex, and comorbidity (hypertension, cardiovascular disease, diabetes, chronic obstructive pulmonary disease, rheumatoid disease, dementia, peptic ulcer disease, liver disease, hemiplegia/paraplegia, and chronic infections). Data are reported as hazard ratios and 95% confidence intervals (shaded in gray). The reference is set at eGFR of 90 ml/min per 1.73 m². Histograms represent the eGFR distribution.