Kidney Function, Proteinuria, and Cancer Incidence: The Korean Heart Study

Background Reported associations of estimated glomerular filtration rate (eGFR) with cancer risk are inconsistent, and data for the proteinuria-cancer relationship are sparse. We sought to quantify the associations of cancer incidence with eGFR and with proteinuria in a large population-based cohort. Study Design A prospective cohort study. Setting & Participants 242,583 adults (30-74 years old) without a diagnosis of cancer at baseline in the Korean Heart Study, based on health checkups in 1996 to 2004 with follow-up until 2012. Predictors Creatinine-based eGFR (≥90, 60-89, 45-59, and <45 mL/min/1.73 m2) and dipstick proteinuria (undetectable/trace, 1+, 2+, and ≥3+). Outcomes Overall and site-specific cancer incidence based on ICD-10 codes. Results 15,165 cases of cancer were detected. The relationship between eGFR and incidence of any cancer was J shaped, with the lowest risk at 45 to 59 mL/min/1.73 m2. There was 44% higher risk for any cancer among those with eGFRs < 45 mL/min/1.73 m2 compared with those with eGFRs ≥ 90 mL/min/1.73 m2 (HR, 1.44; 95% CI, 1.11-1.87). High proteinuria was also associated with cancer risk, showing a dose-response relationship (HRs of 1.24 [95% CI, 1.13-1.35], 1.38 [95% CI, 1.17-1.63], and 1.66 [95% CI, 1.30-2.12] for 1+, 2+, and ≥3+ vs undetectable/trace). Examining site-specific cancer, eGFR < 45 (vs ≥45) mL/min/1.73 m2 was significantly associated with kidney and ureteral cancer, multiple myeloma, and leukemia, whereas proteinuria ≥ 1+ (vs undetectable/trace) was related to a broader set of cancers (ie, stomach, rectal, liver, lung, ovarian, kidney, bladder, and multiple myeloma). After excluding study participants with follow-up less than 3 years, the associations remained consistent for kidney cancer and myeloma with eGFR and for rectal, liver, lung, and ovarian cancer with proteinuria. Limitations Relatively small number of participants with severely reduced eGFR or 70 years or older. Conclusions Kidney measures, particularly proteinuria, were associated with increased incidence of cancer. Future studies are needed to better understand the pathophysiologic mechanisms underlying these associations. Reported associations of estimated glomerular filtration rate (eGFR) with cancer risk are inconsistent, and data for the proteinuria-cancer relationship are sparse. We sought to quantify the associations of cancer incidence with eGFR and with proteinuria in a large population-based cohort. A prospective cohort study. 242,583 adults (30-74 years old) without a diagnosis of cancer at baseline in the Korean Heart Study, based on health checkups in 1996 to 2004 with follow-up until 2012. Creatinine-based eGFR (≥90, 60-89, 45-59, and <45 mL/min/1.73 m2) and dipstick proteinuria (undetectable/trace, 1+, 2+, and ≥3+). Overall and site-specific cancer incidence based on ICD-10 codes. 15,165 cases of cancer were detected. The relationship between eGFR and incidence of any cancer was J shaped, with the lowest risk at 45 to 59 mL/min/1.73 m2. There was 44% higher risk for any cancer among those with eGFRs < 45 mL/min/1.73 m2 compared with those with eGFRs ≥ 90 mL/min/1.73 m2 (HR, 1.44; 95% CI, 1.11-1.87). High proteinuria was also associated with cancer risk, showing a dose-response relationship (HRs of 1.24 [95% CI, 1.13-1.35], 1.38 [95% CI, 1.17-1.63], and 1.66 [95% CI, 1.30-2.12] for 1+, 2+, and ≥3+ vs undetectable/trace). Examining site-specific cancer, eGFR < 45 (vs ≥45) mL/min/1.73 m2 was significantly associated with kidney and ureteral cancer, multiple myeloma, and leukemia, whereas proteinuria ≥ 1+ (vs undetectable/trace) was related to a broader set of cancers (ie, stomach, rectal, liver, lung, ovarian, kidney, bladder, and multiple myeloma). After excluding study participants with follow-up less than 3 years, the associations remained consistent for kidney cancer and myeloma with eGFR and for rectal, liver, lung, and ovarian cancer with proteinuria. Relatively small number of participants with severely reduced eGFR or 70 years or older. Kidney measures, particularly proteinuria, were associated with increased incidence of cancer. Future studies are needed to better understand the pathophysiologic mechanisms underlying these associations.