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

Abstract

Background: We examined whether an increased risk of cancer incidence and death is associated with kidney function and albuminuria and whether the risk is more readily identified when kidney function is estimated using cystatin C. Methods: Participants were from UK Biobank (recruitment spanning 2007À2010), excluding those with a prior diagnosis of cancer. Estimated glomerular filtration rate (ml/min/1.73m 2 ) was calculated using creatinine (eGFRcr), cystatin C (eGFRcys) and creatinine-cystatin C (eGFRcr-cys). Cox proportional hazards models tested associations between eGFR, urinary albumin:creatinine ratio (uACR) and cancer incidence and death. Findings: In 431,263 participants over median follow-up of 11.3 (IQR 10.6À12.0) years, there were 41,745 incident cancers and 11,764 cancer deaths. eGFRcys was most strongly associated with cancer incidence and death (HR 1.04 (95% CI 1.03À1.04) and 1.06 (1.05À1.07) per 10 ml/min/1.73m 2 decline, respectively). eGFRcr was not associated with either outcome (incidence: HR 1.00 (1.00À1.01); death: HR 0.99 (0.98À1.01) per 10 ml/min/1.73m 2 decline). Relative to eGFRcys>90 or uACR<3 mg/mmol, eGFRcys60À89 (HR 1.04 (95% CI 1.02À1.07)), eGFRcys<60 (HR 1.19 (1.14À1.24)) and uACR3 mg/mmol (HR 1.09 (1.06À1.12)) were associated with higher risk of incident cancer. eGFRcys60À89 (HR 1.15 (1.10À1.21)); eGFRcys<60 (HR 1.48 (1.38À1.59)) and uACR3 mg/mmol (HR 1.17 (1.11À1.24)) were associated with cancer death. Interpretation: Excess risk of cancer incidence and cancer death is more readily captured in early chronic kidney disease by eGFRcys than by current measures. The association between kidney function, uACR and cancer death in particular is concerning and warrants further scrutiny.

Association of plasma cystatin C with all-cause and cause-specific mortality among middle-aged and elderly individuals: a prospective community-based cohort study

“…Furthermore, a higher cystatin C concentration was also associated with incident prediabetes 30 , hypertension 31 , coronary heart disease 32 , 33 , myocardial infarction 8 , and stroke 8 , 34 , all of which could contribute to increased mortality. With regard to cancer mortality, there is very limited evidence examining the association of cystatin C with cancer mortality 18 . Our study indicated that a higher cystatin C concentration is associated with an increased risk of cancer mortality.…”

“…CKD has also been shown to contribute to cancer morbidity and mortality 14 – 16 . Nonetheless, evidence regarding the relationship between cystatin C concentration and cancer mortality is very limited 17 , 18 . In addition, whether the associations of cystatin C concentrations with mortality vary by potential modifying factors, such as gender and age group, remain controversial 13 , 19 , 20 , which may have important implications for the application of cystatin C.…”

Risk of malignancy in patients with chronic kidney disease

“…Similarly, another Korean study found that the overall incidence of cancer in patients with CKD was >1000/100,000 person-years [ 19 ]. A third study from the United Kingdom also found that a lower GFR was associated with an increased risk of incident cancer [ 20 ]. In contrast, other studies have not found an increased risk of cancer with lower eGFR [ 7 , 21 ].…”

“…Similar findings were seen in an Australian study which showed increased cancer mortality in patients with an estimated glomerular filtration rate < 60 mL/min/1.73 m 2 [ 28 ]. A large study from the UK also suggested that an eGFR <90 ml/min/1.73m 2 was associated with increased cancer mortality [ 20 ]. This is not particularly surprising, since treatment modification may commonly be needed in patients with decreased eGFR to decrease toxicity of chemotherapy agents.…”

Effect of M2-like macrophages of the injured-kidney cortex on kidney cancer progression

“…Moreover, several studies have shown that CKD increases cancer mortality [ 4 , 5 ]. Specifically, CKD is associated with an increased risk of cancer death among kidney cancer patients [ 6 ]. The association between CKD and cancer mortality remained evident after adjusting for chemotherapy and patients’ factors, including performance status [ 7 ].…”