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

https://doi.org/10.1053/j.ajkd.2017.03.018Get rights and content

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.

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.

Section snippets

Study Population

The Korean Heart Study included 430,920 individuals (266,782 men and 164,138 women) who had voluntarily undergone a health checkup in 18 centers located in the capital, Seoul, and 6 provinces in South Korea in 1996 to 2004.32 We excluded participants with a history of cancer diagnosis at baseline (n = 5,040) and missing information for serum creatinine (n = 57,556) and urine dipstick test results (n = 125,741), leaving the final study population of 242,583 participants (Fig S1, available as online

Baseline Characteristics

Mean age of study participants was 44.4 ± 9.6 years, and 33.1% were women. Current smoking was substantially more common in men (55.1%) than in women (4.5%). Average eGFR was 92.0 ± 13.8 mL/min/1.73 m2. Of the study participants, 1.0% had eGFRs < 60 mL/min/1.73 m2 or proteinuria by dipstick test (≥1+). Those with lower eGFRs (<60 mL/min/1.73 m2) or higher proteinuria (≥1+) were more likely to be older and have diabetes, hypertension, and hypercholesterolemia compared with those with higher eGFRs (≥60 

Discussion

In this large Korean cohort study, we observed that both low eGFR and high proteinuria were associated with cancer incidence, with some unique patterns for each CKD measure. Overall, the associations were much more robust and consistent for high proteinuria than for low eGFR. Even trace proteinuria contributed to increased overall cancer risk, and proteinuria was associated with a broad range of site-specific cancers. For eGFR, when we accounted for potential confounders, the lowest risk was

Acknowledgements

Support: This study was supported by a grant from the National R&D Program for Cancer Control, Ministry of Health & Welfare, Republic of Korea (1631020) and by a grant of the Korean Health, Technology R&D Project, Ministry of Health & Welfare, Republic of Korea (HI14C2686).

Financial Disclosure: The authors declare that they have no other relevant financial interests.

Contributions: Study concept and design: YM, KM, SHJ; data acquisition: SL, SHJ; data analysis/interpretation: YM, KM, SHB, YS,

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