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

Abstract

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 <45mL/min/1.73m²) 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 59mL/min/1.73m². There was 44% higher risk for any cancer among those with eGFRs<45mL/min/1.73m² compared with those with eGFRs≥90mL/min/1.73m² (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/1.73m² 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.

Keywords: Estimated glomerular filtration rate (eGFR); cancer; cohort study; kidney function; proteinuria; renal damage; urine dipstick.