Association between 24-h proteinuria and phenotypic age acceleration in adults with preserved kidney function: a cross-sectional study.

PURPOSE: Phenotypic age acceleration (PhenoAgeAccel) captures biological aging beyond chronological age and has been associated with adverse health outcomes. Proteinuria is a common manifestation of kidney injury, yet its relationship with biological aging acceleration in individuals with preserved kidney function remains unclear.

METHODS

We conducted a cross-sectional study among adult nephrology outpatients with an estimated glomerular filtration rate (eGFR) > 60 mL/min/1.73 m2. Participants who completed a valid 24-h urinary protein excretion measurement were included. Phenotypic age was calculated using established clinical and laboratory parameters, and PhenoAgeAccel was defined as the difference between phenotypic age and chronological age. Associations between natural log-transformed 24-h urinary protein excretion and PhenoAgeAccel were evaluated using multivariable linear regression and spline-based analyses.

RESULTS

Among 253 adults with preserved eGFR (median age 44 years; median eGFR 93 mL/min/1.73 m2), Ln-transformed 24-h proteinuria (LnUPE) was positively correlated with PhenoAgeAccel (r = 0.488, 95% CI 0.388-0.576; P < 0.001). In multivariable analysis, LnUPE remained independently associated with PhenoAgeAccel (β = 3.55, 95% CI 2.74-4.37; P < 0.001). The association remained significant after excluding serum albumin from the PhenoAge algorithm (β = 1.78, 95% CI 1.01-2.54; P < 0.001) and persisted after further exclusion of both serum albumin and creatinine (β = 1.28, 95% CI 0.59-1.96; P < 0.001). No evidence of nonlinearity was observed (P for nonlinearity = 0.437). Mediation analysis suggested that total cholesterol, triglycerides, and low-density lipoprotein cholesterol statistically accounted for 30.0%, 12.6%, and 21.8% of the observed association, respectively (all P < 0.001), while the direct association remained significant.

CONCLUSIONS

Elevated proteinuria is associated with accelerated biological aging in adults with preserved kidney function, highlighting a potential link between early kidney injury and accelerated biological aging.