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.