Association between kidney function and the risk of cancer: Results from the China Health and Retirement longitudinal study (CHARLS)

Abstract

Objective: Increased cancer risk after dialysis or transplantation has been recognized, but studies of cancer in pre-dialysis chronic kidney disease (CKD) are extremely limited. Therefore, we aim to investigate the risk of cancer in individuals with reduced kidney function. Methods: This study was based on China Health and Retirement Longitudinal Study (CHARLS), a nationally representative population aged ≥ 45 years old. We included 11 508 (5364 male) individuals with measurement of serum creatinine and without history of cancer at baseline. Incident cancer cases were documented in the biennial questionnaire. Results: The mean age was 58.7 ± 9.8 years. Participants with estimated glomerular filtration rate (eGFR) ≥ 90 ml/min/1.73m 2 , 60 to 89 ml/min/1.73m 2 , and eGFR < 60 ml/min/1.73m 2 accounted for 62.9%, 33.7% and 3.4%, respectively. During 42 895 person-years' follow-up, 217 new cases of cancer were recorded. In participants with eGFR < 90 ml/min/1.73m 2 , cubic spline showed linear relationship between the risk of cancer and eGFR, while remained stable and no association in participants with eGFR > 90 ml/min/1.73m 2. Compared to participants with eGFR ≥ 90 ml/min/1.73m 2 , those with eGFR < 60 ml/min/1.73m 2 was associated with the increased risk of cancer in the fully adjusted model (hazard ratio 2.08; 95% confidence interval 1.22-3.53); and the risk for kidney and lung cancers was higher among those with eGFR < 60 ml/min/1.73m 2. Conclusion: Reduced kidney function is associated with a higher risk of cancer and should be integrated into risk-stratification of cancer screening and management.

Kidney function and cancer risk: An analysis using creatinine and cystatin C in a cohort study

“…To our knowledge, this is the first study to compare eGFRcr, eGFRcys and eGFRcr-cys for cancer risk. In contrast to studies that assessed the association between eGFRcr[ 3 , 5 , [7] , [8] , [9] , [10] , [11] , 27 ] or eGFRcr-cys [4] with cancer incidence and death, we have shown that eGFRcys 60–89 ml/min/1.73m 2 is associated with small but significant increases in cancer incidence, and a more pronounced association with cancer death.…”

“…A more consistent association is observed between CKD and cancers of the urinary tract [ 1 , 3 , [7] , [8] , [9] , 29 ], which share common risk factors, such as the metabolic syndrome, smoking, prior nephrectomy, genetic conditions (such as tuberous sclerosis), occupational exposures and use of medications. Acute kidney injury (AKI) is known to contribute to CKD development [30] and is more likely to occur in those with CKD.…”

“…Lung cancer has previously been associated with reduced eGFR [3] and more consistently with albuminuria [ [3] , [4] , [5] , 14 ]. This effect is slightly attenuated when taking account of history of smoking [ 4 , 14 ], suggesting that albuminuria may be a marker of susceptibility to cancer or tissue damage associated with smoking.…”

“…As kidney function, defined by estimated glomerular filtration rate (eGFR), falls below 60 ml/min/1.73m 2 , there is a well described increased risk of cardiovascular disease [2] but this is less clear for cancer risk. Several studies have demonstrated a potential association between markers of CKD (below eGFR 60 ml/min/1.73m 2 , alone or in combination with albuminuria) with higher risk of incidence and death from overall [3] , [4] , [5] , [6] and site-specific urinary [ 3 , [7] , [8] , [9] ], lung [3] and haematological [10] cancers. However, the data are inconsistent [ 1 , 4 , 7 , 11 ], possibly as most studies have assessed associations with eGFR calculated from serum creatinine [ 1 , 3 , 5 , [7] , [8] , [9] , [10] , [11] , [12] ], which has been shown to have a U-shaped relationship with cancer risk [12] .…”

“…Several studies have demonstrated a potential association between markers of CKD (below eGFR 60 ml/min/1.73m 2 , alone or in combination with albuminuria) with higher risk of incidence and death from overall [3] , [4] , [5] , [6] and site-specific urinary [ 3 , [7] , [8] , [9] ], lung [3] and haematological [10] cancers. However, the data are inconsistent [ 1 , 4 , 7 , 11 ], possibly as most studies have assessed associations with eGFR calculated from serum creatinine [ 1 , 3 , 5 , [7] , [8] , [9] , [10] , [11] , [12] ], which has been shown to have a U-shaped relationship with cancer risk [12] . Independent of the effect of eGFR and diabetes, albuminuria has been associated with higher risk of cancer overall [ 4 , 5 , 13 ], and particularly site-specific lung [ 4 , 5 , 13 , 14 ] and urinary tract [ 4 , 14 ] cancers.…”