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

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 2007-2010), excluding those with a prior diagnosis of cancer. Estimated glomerular filtration rate (ml/min/1.73m2) 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 10.6-12.0) 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 1.03-1.04) and 1.06 (1.05-1.07) per 10 ml/min/1.73m2 decline, respectively). eGFRcr was not associated with either outcome (incidence: HR 1.00 (1.00-1.01); death: HR 0.99 (0.98-1.01) per 10 ml/min/1.73m2 decline). Relative to eGFRcys>90 or uACR<3 mg/mmol, eGFRcys60-89 (HR 1.04 (95% CI 1.02-1.07)), eGFRcys<60 (HR 1.19 (1.14-1.24)) and uACR≥3 mg/mmol (HR 1.09 (1.06-1.12)) were associated with higher risk of incident cancer. eGFRcys60-89 (HR 1.15 (1.10-1.21)); eGFRcys<60 (HR 1.48 (1.38-1.59)) and uACR≥3 mg/mmol (HR 1.17 (1.11-1.24)) 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. Funding Chief Scientist Office; ANID Becas Chile; Medical Research Council; British Medical Association; British Heart Foundation.