Albuminuria within the Normal Range Can Predict All-Cause Mortality and Cardiovascular Mortality

Background: Despite interest in low-grade albuminuria and poor clinical outcomes, evidence from a large-scale population is lacking. Therefore, we identified the association of low-grade albuminuria within the normal range with all-cause and cardiovascular (CV) mortality.

Methods: After excluding individuals with urine albumin-creatinine ratio (ACR) ≥30 mg/g (n=6094), this cohort study analyzed 43,396 adults who participated in the National Health and Nutrition Examination Survey (1999-2016). Participants were divided into four quartiles of ACR. The primary outcome was all-cause mortality, and the secondary outcome was CV mortality. Multivariable Cox proportional hazards models were used.

Results: During a median 7.9 years of follow-up, 3516 (9%) participants died. Compared with the reference group (Q1, ACR <4.171 mg/g), low-grade albuminuria groups were associated with all-cause mortality (Q3, ACR ≥6.211 to <10.010 mg/g, hazard ratio [HR], 1.25 [95% CI, 1.11 to 1.41]; Q4, ACR ≥10.010 mg/g, HR, 1.57 [95% CI, 1.41 to 1.76]) in a multivariable hazards model. A similar pattern was also seen in the association of low-grade albuminuria with CV mortality. Subgroup analyses showed that low-grade albuminuria was also associated with all-cause mortality in the nondiabetic group, nonhypertensive group, and non-CKD group (eGFR ≥60 ml/min per 1.73 m²).

Conclusions: Our findings suggest that low-grade albuminuria is associated with all-cause and CV mortality. Low-grade albuminuria should be monitored, even for patients with low CV risk.