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American Journal of Kidney Diseases

Association of Kidney Function Measures With Signs of Neurodegeneration and Small Vessel Disease on Brain Magnetic Resonance Imaging: The Atherosclerosis Risk in Communities (ARIC) Study

Published:September 27, 2022DOI:https://doi.org/10.1053/j.ajkd.2022.07.013

      Rationale & Objective

      Chronic kidney disease (CKD) is a risk factor for cognitive decline, but evidence is limited on its etiology and morphological manifestation in the brain. We evaluated the association of estimated glomerular filtration rate (eGFR) and urinary albumin-creatinine ratio (UACR) with structural brain abnormalities visible on magnetic resonance imaging (MRI). We also assessed whether this association was altered when different filtration markers were used to estimate GFR.

      Study Design

      Cross-sectional study nested in a cohort study.

      Setting & Participants

      1,527 participants in the Atherosclerosis Risk in Communities (ARIC) Study.

      Predictors

      Log(UACR) and eGFR based on cystatin C, creatinine, cystatin C and creatinine in combination, or β2-microglobulin (B2M).

      Outcomes

      Brain volume reduction, infarcts, microhemorrhages, white matter lesions.

      Analytical Approach

      Multivariable linear and logistic regression models fit separately for each predictor based on a 1-IQR difference in the predictor value.

      Results

      Each 1-IQR lower eGFR was associated with reduced cortex volume (regression coefficient: −0.07 [95% CI, −0.12 to −0.02]), greater white matter hyperintensity volume (logarithmically transformed; regression coefficient: 0.07 [95% CI, 0.01-0.15]), and lower white matter fractional anisotropy (regression coefficient: −0.08 [95% CI, −0.17 to −0.01]). The results were similar when eGFR was estimated with different equations based on cystatin C, creatinine, a combination of cystatin C and creatinine, or B2M. Higher log(UACR) was similarly associated with these outcomes as well as brain infarcts and microhemorrhages (odds ratios per 1-IQR-fold greater UACR of 1.31 [95% CI, 1.13-1.52] and 1.30 [95% CI, 1.12-1.51], respectively). The degree to which brain volume was lower in regions usually susceptible to Alzheimer disease and LATE (limbic-predominant age-related TDP-43 [Tar DNA binding protein 43] encephalopathy) was similar to that seen in the rest of the cortex.

      Limitations

      No inference about longitudinal effects due to cross-sectional design.

      Conclusions

      We found eGFR and UACR are associated with structural brain damage across different domains of etiology, and eGFR- and UACR-related brain atrophy is not selective for regions typically affected by Alzheimer disease and LATE. Hence, Alzheimer disease or LATE may not be leading contributors to neurodegeneration associated with CKD.

      Graphical abstract

      Index Words

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      Linked Article

      • Kidney Disease and Brain Health: Current Knowledge and Next Steps
        American Journal of Kidney Diseases
        • Preview
          The growing public health burden of nondialysis chronic kidney disease (CKD) as the population ages is mirrored by concomitant cerebrovascular and neurodegenerative aging changes on brain magnetic resonance imaging (MRI) and associated cognitive impairment in CKD. Cerebrovascular changes in CKD are demonstrated by microvascular white matter changes; decreased white matter integrity, reflecting microvascular disease in the kidney; and micro- and macroinfarcts. Neurodegenerative changes are represented by decreased cortical gray matter volume, or atrophy of the cerebral lobes (especially temporal and frontal in Alzheimer disease [AD] and related dementias), and enlarged ventricular volume.    
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