title: Kidney function and microstructural integrity of brain white matter.
abstract: OBJECTIVE
  To investigate the association of kidney function with white matter microstructural integrity.
  
  
  METHODS
  We included 2,726 participants with a mean age of 56.6 years (45% men) from the population-based Rotterdam Study. Albumin-to-creatinine ratio, and estimated glomerular filtration rate (eGFR), using serum cystatin C (eGFRcys) and creatinine (eGFRcr), were measured to evaluate kidney function. Diffusion-MRI was used to assess microstructural integrity of the normal-appearing white matter. Multiple linear regression models, adjusted for macrostructural MRI markers and cardiovascular risk factors, were used to model the association of kidney function with white matter microstructure.
  
  
  RESULTS
  Participants had average eGFRcr of 86.1 mL/min/1.73 m(2), average eGFRcys of 86.2 mL/min/1.73 m(2), and median albumin-to-creatinine ratio of 3.4 mg/g. Lower eGFRcys was associated with worse global white matter microstructural integrity, reflected as lower fractional anisotropy (standardized difference per SD: -0.053, 95% confidence interval [CI]: -0.092, -0.014) and higher mean diffusivity (0.036, 95% CI: 0.001, 0.070). Similarly, higher albumin-to-creatinine ratio was associated with lower fractional anisotropy (-0.044, 95% CI: -0.078, -0.011). There was no linear association between eGFRcr and white matter integrity. Subgroup analyses showed attenuation of the associations after excluding subjects with hypertension. The associations with global diffusion tensor imaging measures did not seem to be driven by particular tracts, but rather spread across multiple tracts in various brain regions.
  
  
  CONCLUSIONS
  Reduced kidney function is associated with worse white matter microstructural integrity. Our findings highlight the importance for clinicians to consider concomitant macro- and microstructural changes of the brain in patients with impaired kidney function.
authors.affiliation: From the Departments of Epidemiology (S.S., L.G.M.C., M.d.G., A.H., O.H.F., M.W.V., A.D., M.A.I.), Radiology (L.G.M.C., M.d.G., A.v.d.L., M.W.V., M.A.I.), Medical informatics (M.d.G.), Internal Medicine (E.J.H.), and Neurology (M.A.I.), Erasmus University Medical Center, Rotterdam, the Netherlands.
authors.forename: Sanaz
authors.initials: S
authors.lastname: Sedaghat
authors.affiliation: From the Departments of Epidemiology (S.S., L.G.M.C., M.d.G., A.H., O.H.F., M.W.V., A.D., M.A.I.), Radiology (L.G.M.C., M.d.G., A.v.d.L., M.W.V., M.A.I.), Medical informatics (M.d.G.), Internal Medicine (E.J.H.), and Neurology (M.A.I.), Erasmus University Medical Center, Rotterdam, the Netherlands.
authors.forename: Lotte G M
authors.initials: LG
authors.lastname: Cremers
authors.affiliation: From the Departments of Epidemiology (S.S., L.G.M.C., M.d.G., A.H., O.H.F., M.W.V., A.D., M.A.I.), Radiology (L.G.M.C., M.d.G., A.v.d.L., M.W.V., M.A.I.), Medical informatics (M.d.G.), Internal Medicine (E.J.H.), and Neurology (M.A.I.), Erasmus University Medical Center, Rotterdam, the Netherlands.
authors.forename: Marius
authors.initials: M
authors.lastname: de Groot
authors.affiliation: From the Departments of Epidemiology (S.S., L.G.M.C., M.d.G., A.H., O.H.F., M.W.V., A.D., M.A.I.), Radiology (L.G.M.C., M.d.G., A.v.d.L., M.W.V., M.A.I.), Medical informatics (M.d.G.), Internal Medicine (E.J.H.), and Neurology (M.A.I.), Erasmus University Medical Center, Rotterdam, the Netherlands.
authors.forename: Ewout J
authors.initials: EJ
authors.lastname: Hoorn
authors.affiliation: From the Departments of Epidemiology (S.S., L.G.M.C., M.d.G., A.H., O.H.F., M.W.V., A.D., M.A.I.), Radiology (L.G.M.C., M.d.G., A.v.d.L., M.W.V., M.A.I.), Medical informatics (M.d.G.), Internal Medicine (E.J.H.), and Neurology (M.A.I.), Erasmus University Medical Center, Rotterdam, the Netherlands.
authors.forename: Albert
authors.initials: A
authors.lastname: Hofman
authors.affiliation: From the Departments of Epidemiology (S.S., L.G.M.C., M.d.G., A.H., O.H.F., M.W.V., A.D., M.A.I.), Radiology (L.G.M.C., M.d.G., A.v.d.L., M.W.V., M.A.I.), Medical informatics (M.d.G.), Internal Medicine (E.J.H.), and Neurology (M.A.I.), Erasmus University Medical Center, Rotterdam, the Netherlands.
authors.forename: Aad
authors.initials: A
authors.lastname: van der Lugt
authors.affiliation: From the Departments of Epidemiology (S.S., L.G.M.C., M.d.G., A.H., O.H.F., M.W.V., A.D., M.A.I.), Radiology (L.G.M.C., M.d.G., A.v.d.L., M.W.V., M.A.I.), Medical informatics (M.d.G.), Internal Medicine (E.J.H.), and Neurology (M.A.I.), Erasmus University Medical Center, Rotterdam, the Netherlands.
authors.forename: Oscar H
authors.initials: OH
authors.lastname: Franco
authors.affiliation: From the Departments of Epidemiology (S.S., L.G.M.C., M.d.G., A.H., O.H.F., M.W.V., A.D., M.A.I.), Radiology (L.G.M.C., M.d.G., A.v.d.L., M.W.V., M.A.I.), Medical informatics (M.d.G.), Internal Medicine (E.J.H.), and Neurology (M.A.I.), Erasmus University Medical Center, Rotterdam, the Netherlands. m.vernooij@erasmusmc.nl.
authors.forename: Meike W
authors.initials: MW
authors.lastname: Vernooij
authors.affiliation: From the Departments of Epidemiology (S.S., L.G.M.C., M.d.G., A.H., O.H.F., M.W.V., A.D., M.A.I.), Radiology (L.G.M.C., M.d.G., A.v.d.L., M.W.V., M.A.I.), Medical informatics (M.d.G.), Internal Medicine (E.J.H.), and Neurology (M.A.I.), Erasmus University Medical Center, Rotterdam, the Netherlands.
authors.forename: Abbas
authors.initials: A
authors.lastname: Dehghan
authors.affiliation: From the Departments of Epidemiology (S.S., L.G.M.C., M.d.G., A.H., O.H.F., M.W.V., A.D., M.A.I.), Radiology (L.G.M.C., M.d.G., A.v.d.L., M.W.V., M.A.I.), Medical informatics (M.d.G.), Internal Medicine (E.J.H.), and Neurology (M.A.I.), Erasmus University Medical Center, Rotterdam, the Netherlands.
authors.forename: M Arfan
authors.initials: MA
authors.lastname: Ikram
mesh_terms: D001921:Brain / Q000473:pathology*; D038524:Diffusion Magnetic Resonance Imaging; D005260:Female; D006801:Humans; D007674:Kidney Diseases / Q000150:complications*; D007677:Kidney Function Tests; D008297:Male; D008875:Middle Aged; D066127:White Matter / Q000473:pathology*