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Chronic kidney disease (CKD) has been associated with brain structural changes in late life. We evaluated whether kidney measures—urinary albumin to creatinine ratio (UACR) and estimated glomerular filtration rate (eGFR)—are associated with brain aging and adverse neuroimaging markers in midlife.
We analyzed data from the brain MRI sub-study in the CARDIA Year 30 participants (n=650, mean age = 55 ± 3.5 years). UACR (mean = 32 ± 272.67 mg/g) was analyzed continuously (log-transformed) and categorically (<30 mg/g: normal, ≥30 mg/g; albuminuria). eGFR (mean = 91 ± 19.0 ml/min per 1.73 m2) was estimated using serum creatinine, age, sex, and race. Brain aging gap was defined as the residual of predicted brain aging (BA) (using machine learning-based Spatial Pattern of Atrophy for Recognition of BA (SPARE-BA)) after adjusting for chronological age. Cross-sectional associations with brain aging gap and MRI markers-including gray matter volume (GMV), hippocampal volume and white matter hyperintensity (WMH) volume- were evaluated using multivariable linear models, adjusting for demographics, BMI, smoking, (Model1) and additionally for diabetes, hypertension, depression, and APOE ε4 (Model 2).
Higher UACR was associated with greater brain aging and lower GMV after adjusting for all covariates, both continuously (β=1.08, p<0.001; β=–4.78, p=0.03) and as albuminuria (β=3.38, p=0.001; β=–16.55, p=0.04) (Table 1). While UACR was linked to greater WMH in Model 1 only (β=0.12, p=0.04), eGFR was inversely associated with WMH (β = –0.008, p = 0.01) in both models. UACR or eGFR were not associated with hippocampal volume.
Table 1. Association of kidney measures with brain aging and adverse neuroimaging markers at Y30 exam in CARDIA
*Model 1 adjusted for age, sex, race, field center, education, BMI and smoking
**Model 2 = Model 1 + diabetes, hypertension, depression, and the APOE ε4.
Kidney measures
Analysis models
Beta;
p-value
Brain aging gap (years)
White matter hyperintensity (WMH) volume (cm3)
Gray matter volume (GMV) (cm3)
Hippocampal volume (cm3)
Log transformed UACR (continuous)
ln (UACR) (mg/g) (n=650)
Model 1*
1.253; <0.001
0.119; 0.040
-5.308; 0.010
-0.019; 0.206
ln (UACR) (mg/g) (n=596)
Model 2**
1.079; <0.001
0.102; 0.092
-4.783; 0.026
-0.016; 0.327
eGFR
eGFR (ml/min per 1.73 m2) (n=648)
0.020; 0.147
-0.008; 0.006
0.008; 0.943
0.0009; 0.244
eGFR (ml/min per 1.73 m2) (n=593)
0.023; 0.113
-0.008; 0.013
-0.010; 0.927
0.0014; 0.091
Albuminuria (binary with ‘normal’ as reference)
Albuminuria (≥30 mg/g, n=42) vs. normal (<30 mg/g, reference n=608)
3.234; 0.002
0.198; 0.377
-15.99; 0.045
-0.049; 0.403
Albuminuria (≥30 mg/g, n=41) vs. normal (<30 mg/g, reference n=555)
3.383; 0.001
0.267; 0.245
-16.55; 0.043
-0.041; 0.499
Measures of kidney damage, particularly albuminuria, are linked to accelerated brain aging and adverse MRI volumes in midlife, highlighting the preservation of kidney health as a potential target for brain health earlier in the life course.
