The relationship between low levels of albuminuria and mortality among adults without major cardiovascular risk factors

Aims The aim of this study is to determine whether elevated levels of albuminuria within the low range [urinary albumin-to-creatinine ratio (UACR) <30 mg/g] are linked to cardiovascular death in adults lacking major cardiovascular risk factors. Methods and results The association between UACR and cardiovascular mortality was investigated among 12 835 participants in the 1999-2014 National Health and Nutrition Examination Survey using Cox proportional hazard models and confounder-adjusted survival curves. We excluded participants with baseline cardiovascular disease, hypertension, diabetes, pre-diabetes, an estimated glomerular filtration rate <60 mL/min/1.73 m2, currently pregnant, and those who received dialysis last year. Over a median follow-up of 12.3 years, 110 and 621 participants experienced cardiovascular and all-cause mortality. In multivariable-adjusted models, each doubling of UACR was associated with a 36% higher risk of cardiovascular death [hazard ratio (HR) 1.36, 95% confidence interval (CI) 1.02-1.82] and a 24% higher risk of all-cause mortality (HR 1.24, 95% CI 1.10-1.39). The 15-year adjusted cumulative incidences of cardiovascular mortality were 0.91, 0.99, and 2.1% for UACR levels of <4.18, 4.18 to <6.91, and >= 6.91 mg/g, respectively. The 15-year adjusted cumulative incidences of all-cause mortality were 5.1, 6.1, and 7.4% for UACR levels of <4.18, 4.18 to <6.91, and >= 6.91 mg/g, respectively. Conclusion Adults with elevated levels of albuminuria within the low range (UACR <30 mg/g) and no major cardiovascular risk factors had elevated risks of cardiovascular and all-cause mortality. The risk increased linearly with higher albuminuria levels. This emphasizes a risk gradient across all albuminuria levels, even within the supposedly normal range, adding to the existing evidence.