Urinary albumin excretion and cancer risk

Abstract BACKGROUND AND AIMS Accumulating evidence has shown that chronic kidney disease (CKD) is associated with cancer development. However, the main focus in these studies was on patients with moderately or severely impaired kidney function, rather than on patients with milder CKD defined by higher albuminuria. We hypothesized that albuminuria may have an association with cancer risk that is independent of kidney function. This study examined therefore the association between urinary albumin excretion (UAE), considered the gold standard for albuminuria assessment, and the risk of cancer incidence, independent of estimated glomerular filtration rate (eGFR). METHOD We included 8490 subjects in the Prevention of Renal and Vascular End-Stage Disease (PREVEND) study, a prospective, population-based cohort of Dutch men and women. UAE was measured in two 24-h urine specimens at baseline (1997–8). Cancer incidence was ascertained by record linkage with the nationwide network and registry of histo and cytopathology in the Netherlands (PALGA). Non-melanoma skin cancer was excluded from analyses. eGFR was calculated by the 2012 CKD-EPI creatinine-cystatin C equation. Cox proportional hazards regression models were used to calculate hazard ratios [HRs, [95% confidence intervals (95% CIs)] crude and additionally adjusted for age, sex, BMI, smoking, alcohol, educational level, diabetes and baseline eGFR. To detect potential reverse causation, we excluded subjects with a follow-up time of <1 year and recalculated the fully adjusted models. RESULTS Overall, 50% of the included subjects were female, and the mean age was 49.8 ± 12.7 years old. Median baseline UAE was 9.4 (IQR: 6.3–17.8) mg/24 h, and the mean baseline eGFR was 94.6 ± 17.3 mL/min/1.73 m2. At baseline, subjects who had higher UAE were more likely to be male, older, have lower eGFR and to have hypertension or diabetes. During a median follow-up of 17.7 (IQR: 17.67–17.71) years, 1789 subjects developed a de novo cancer. In the age- and sex-adjusted model, every doubling of UAE was associated with a 7% (HR: 1.07, 95% CI 1.04–1.10) higher risk of overall cancer. This association remained essentially unchanged after additional multivariable adjustments, including eGFR (HR: 1.06, 95% CI 1.02–1.09). UAE was also independently associated with an increased risk of development of several site-specific cancers including urothelial cell carcinoma (HR: 1.13, 95% CI 1.02–1.25), as well as lung cancer (HR: 1.13, 95% CI 1.04–1.22), haematological cancer (HR: 1.12, 95% CI 1.00–1.25), and head and neck cancer (HR: 1.29, 95% CI 1.06–1.57). We did not observe significant associations of UAE with melanoma, breast, prostate and colorectal cancers. Additionally, the associations of UAE with overall cancer, UCC, lung cancer and head and neck cancer remained significant in the fully adjusted models after we excluded subjects with a follow-up time of <1 year. CONCLUSION Higher albuminuria, assessed in 24-h urine, is associated with an increased risk of overall cancer and several site-specific cancers, independent of baseline eGFR. Future studies are warranted to corroborate these findings and to examine mechanisms underlying these associations.