Association of kidney function biomarkers with brain MRI findings

The BRINK study

Prashanthi D Vemuri, David S Knopman, Clifford R Jr. Jack, Emily S. Lundt, Stephen D. Weigand, Samantha M. Zuk, Kaely B. Thostenson, Robert I. Reid, Kejal M Kantarci, Yelena Slinin, Kamakshi Lakshminarayan, Cynthia S. Davey, Anne Murray

Research output: Contribution to journalArticle

7 Citations (Scopus)

Abstract

Background: Chronic kidney disease (CKD) studies have reported variable prevalence of brain pathologies, in part due to low inclusion of participants with moderate to severe CKD. Objective: To measure the association between kidney function biomarkers and brain MRI findings in CKD. Methods: In the BRINK (BRain IN Kidney Disease) study, MRI was used to measure gray matter volumes, cerebrovascular pathologies (white matter hyperintensity (WMH), infarctions, microhemorrhages), and microstructural changes using diffusion tensor imaging (DTI). We performed regression analyses with estimated glomerular filtration rate (eGFR) and urine albumin to creatinine ratio (UACR) as primary predictors, and joint models that included both predictors, adjusted for vascular risk factors. Results: We obtained 240 baseline MRI scans (150 CKD with eGFR <45 in ml/min/1.73 m2; 16 mild CKD: EGFR 45-59; 74 controls: EGFR≥60). Lower eGFR was associated with greater WMH burden, increased odds of cortical infarctions, and worsening diffusion changes throughout the brain. In eGFR models adjusted for UACR, only cortical infarction associations persisted. However, after adjusting for eGFR, higher UACR provided additional information related to temporal lobe atrophy, increased WMH, and whole brain microstructural changes as measured by increased DTI mean diffusivity. Conclusions: Biomarkers of kidney disease (eGFR and UACR) were associated with MRI brain changes, even after accounting for vascular risk factors. UACR adds unique additional information to eGFR regarding brain structural and diffusion biomarkers. There was a greater impact of kidney function biomarkers on cerebrovascular pathologies and microstructural brain changes, suggesting that cerebrovascular etiology may be the primary driver of cognitive impairment in CKD.

Original languageEnglish (US)
Pages (from-to)1069-1082
Number of pages14
JournalJournal of Alzheimer's Disease
Volume55
Issue number3
DOIs
StatePublished - 2017

Fingerprint

Kidney Diseases
Glomerular Filtration Rate
Biomarkers
Chronic Renal Insufficiency
Kidney
Brain
Albumins
Creatinine
Urine
Infarction
Diffusion Tensor Imaging
Pathology
Temporal Lobe
Atrophy
Joints
Regression Analysis
Magnetic Resonance Imaging
White Matter

Keywords

  • Cerebrovascular disease
  • chronic kidney disease
  • infarctions
  • magnetic resonance imaging

ASJC Scopus subject areas

  • Clinical Psychology
  • Geriatrics and Gerontology
  • Psychiatry and Mental health

Cite this

Association of kidney function biomarkers with brain MRI findings : The BRINK study. / Vemuri, Prashanthi D; Knopman, David S; Jack, Clifford R Jr.; Lundt, Emily S.; Weigand, Stephen D.; Zuk, Samantha M.; Thostenson, Kaely B.; Reid, Robert I.; Kantarci, Kejal M; Slinin, Yelena; Lakshminarayan, Kamakshi; Davey, Cynthia S.; Murray, Anne.

In: Journal of Alzheimer's Disease, Vol. 55, No. 3, 2017, p. 1069-1082.

Research output: Contribution to journalArticle

Vemuri, PD, Knopman, DS, Jack, CRJ, Lundt, ES, Weigand, SD, Zuk, SM, Thostenson, KB, Reid, RI, Kantarci, KM, Slinin, Y, Lakshminarayan, K, Davey, CS & Murray, A 2017, 'Association of kidney function biomarkers with brain MRI findings: The BRINK study', Journal of Alzheimer's Disease, vol. 55, no. 3, pp. 1069-1082. https://doi.org/10.3233/JAD-160834
Vemuri, Prashanthi D ; Knopman, David S ; Jack, Clifford R Jr. ; Lundt, Emily S. ; Weigand, Stephen D. ; Zuk, Samantha M. ; Thostenson, Kaely B. ; Reid, Robert I. ; Kantarci, Kejal M ; Slinin, Yelena ; Lakshminarayan, Kamakshi ; Davey, Cynthia S. ; Murray, Anne. / Association of kidney function biomarkers with brain MRI findings : The BRINK study. In: Journal of Alzheimer's Disease. 2017 ; Vol. 55, No. 3. pp. 1069-1082.
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abstract = "Background: Chronic kidney disease (CKD) studies have reported variable prevalence of brain pathologies, in part due to low inclusion of participants with moderate to severe CKD. Objective: To measure the association between kidney function biomarkers and brain MRI findings in CKD. Methods: In the BRINK (BRain IN Kidney Disease) study, MRI was used to measure gray matter volumes, cerebrovascular pathologies (white matter hyperintensity (WMH), infarctions, microhemorrhages), and microstructural changes using diffusion tensor imaging (DTI). We performed regression analyses with estimated glomerular filtration rate (eGFR) and urine albumin to creatinine ratio (UACR) as primary predictors, and joint models that included both predictors, adjusted for vascular risk factors. Results: We obtained 240 baseline MRI scans (150 CKD with eGFR <45 in ml/min/1.73 m2; 16 mild CKD: EGFR 45-59; 74 controls: EGFR≥60). Lower eGFR was associated with greater WMH burden, increased odds of cortical infarctions, and worsening diffusion changes throughout the brain. In eGFR models adjusted for UACR, only cortical infarction associations persisted. However, after adjusting for eGFR, higher UACR provided additional information related to temporal lobe atrophy, increased WMH, and whole brain microstructural changes as measured by increased DTI mean diffusivity. Conclusions: Biomarkers of kidney disease (eGFR and UACR) were associated with MRI brain changes, even after accounting for vascular risk factors. UACR adds unique additional information to eGFR regarding brain structural and diffusion biomarkers. There was a greater impact of kidney function biomarkers on cerebrovascular pathologies and microstructural brain changes, suggesting that cerebrovascular etiology may be the primary driver of cognitive impairment in CKD.",
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AU - Vemuri, Prashanthi D

AU - Knopman, David S

AU - Jack, Clifford R Jr.

AU - Lundt, Emily S.

AU - Weigand, Stephen D.

AU - Zuk, Samantha M.

AU - Thostenson, Kaely B.

AU - Reid, Robert I.

AU - Kantarci, Kejal M

AU - Slinin, Yelena

AU - Lakshminarayan, Kamakshi

AU - Davey, Cynthia S.

AU - Murray, Anne

PY - 2017

Y1 - 2017

N2 - Background: Chronic kidney disease (CKD) studies have reported variable prevalence of brain pathologies, in part due to low inclusion of participants with moderate to severe CKD. Objective: To measure the association between kidney function biomarkers and brain MRI findings in CKD. Methods: In the BRINK (BRain IN Kidney Disease) study, MRI was used to measure gray matter volumes, cerebrovascular pathologies (white matter hyperintensity (WMH), infarctions, microhemorrhages), and microstructural changes using diffusion tensor imaging (DTI). We performed regression analyses with estimated glomerular filtration rate (eGFR) and urine albumin to creatinine ratio (UACR) as primary predictors, and joint models that included both predictors, adjusted for vascular risk factors. Results: We obtained 240 baseline MRI scans (150 CKD with eGFR <45 in ml/min/1.73 m2; 16 mild CKD: EGFR 45-59; 74 controls: EGFR≥60). Lower eGFR was associated with greater WMH burden, increased odds of cortical infarctions, and worsening diffusion changes throughout the brain. In eGFR models adjusted for UACR, only cortical infarction associations persisted. However, after adjusting for eGFR, higher UACR provided additional information related to temporal lobe atrophy, increased WMH, and whole brain microstructural changes as measured by increased DTI mean diffusivity. Conclusions: Biomarkers of kidney disease (eGFR and UACR) were associated with MRI brain changes, even after accounting for vascular risk factors. UACR adds unique additional information to eGFR regarding brain structural and diffusion biomarkers. There was a greater impact of kidney function biomarkers on cerebrovascular pathologies and microstructural brain changes, suggesting that cerebrovascular etiology may be the primary driver of cognitive impairment in CKD.

AB - Background: Chronic kidney disease (CKD) studies have reported variable prevalence of brain pathologies, in part due to low inclusion of participants with moderate to severe CKD. Objective: To measure the association between kidney function biomarkers and brain MRI findings in CKD. Methods: In the BRINK (BRain IN Kidney Disease) study, MRI was used to measure gray matter volumes, cerebrovascular pathologies (white matter hyperintensity (WMH), infarctions, microhemorrhages), and microstructural changes using diffusion tensor imaging (DTI). We performed regression analyses with estimated glomerular filtration rate (eGFR) and urine albumin to creatinine ratio (UACR) as primary predictors, and joint models that included both predictors, adjusted for vascular risk factors. Results: We obtained 240 baseline MRI scans (150 CKD with eGFR <45 in ml/min/1.73 m2; 16 mild CKD: EGFR 45-59; 74 controls: EGFR≥60). Lower eGFR was associated with greater WMH burden, increased odds of cortical infarctions, and worsening diffusion changes throughout the brain. In eGFR models adjusted for UACR, only cortical infarction associations persisted. However, after adjusting for eGFR, higher UACR provided additional information related to temporal lobe atrophy, increased WMH, and whole brain microstructural changes as measured by increased DTI mean diffusivity. Conclusions: Biomarkers of kidney disease (eGFR and UACR) were associated with MRI brain changes, even after accounting for vascular risk factors. UACR adds unique additional information to eGFR regarding brain structural and diffusion biomarkers. There was a greater impact of kidney function biomarkers on cerebrovascular pathologies and microstructural brain changes, suggesting that cerebrovascular etiology may be the primary driver of cognitive impairment in CKD.

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