TY - JOUR
T1 - Albuminuria and Estimated GFR as Risk Factors for Dementia in Midlife and Older Age
T2 - Findings From the ARIC Study
AU - Scheppach, Johannes B.
AU - Coresh, Josef
AU - Wu, Aozhou
AU - Gottesman, Rebecca F.
AU - Mosley, Thomas H.
AU - Knopman, David S.
AU - Grams, Morgan E.
AU - Sharrett, A. Richey
AU - Koton, Silvia
N1 - Funding Information:
Johannes B. Scheppach, MD, Josef Coresh, PhD, Aozhou Wu, PhD, Rebecca F. Gottesman, PhD, Thomas H. Mosley, PhD, David S. Knopman, MD, Morgan E. Grams, PhD, A. Richey Sharrett, DrPH, and Silvia Koton, PhD, MOccH, RN. Concept and design: JBS, JC, AW, ARS, SK; acquisition, analysis, or interpretation of data: all authors; statistical analysis: JBS; supervision: JC, ARS, SK. Each author contributed important intellectual content during manuscript drafting or revision and agrees to be personally accountable for the individual's own contributions and to ensure that questions pertaining to the accuracy or integrity of any portion of the work, even one in which the author was not directly involved, are appropriately investigated and resolved, including with documentation in the literature if appropriate. The ARIC Study is carried out as a collaborative study supported by National Heart, Lung, and Blood Institute (NHLBI) contracts (HHSN268201700001I, HHSN268201700002I, HHSN268201700003I, HHSN268201700005I, and HHSN268201700004I). Neurocognitive data were collected with support by grants 2U01HL096812, 2U01HL096814, 2U01HL096899, 2U01HL096902, 2U01HL096917 from the National Institutes of Health (NIH; NHLBI, with support from the National Institute of Neurological Disorders and Stroke, National Institute on Aging, and National Institute on Deafness and Other Communication Disorders) and with previous brain MRI examinations funded by R01-HL70825 from the NHLBI. The funding sources had no role in the design and conduct of the study; collection, management, analysis, reporting, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication. Dr Grams received travel support from DCI in May 2019. Dr Knopman serves on a Data Safety Monitoring Board for the DIAN study; is an investigator in clinical trials sponsored by Biogen, Eli Lilly & Co, and the University of Southern California; and receives research support from the NIH. The remaining authors declare that they have no relevant financial interests. We thank the staff and participants of the ARIC Study for important contributions. Received November 2, 2019. Evaluated by 2 external peer reviewers, with direct editorial input from a Statistics/Methods Editor and an Associate Editor, who served as Acting Editor-in-Chief. Accepted in revised form March 8, 2020. The involvement of an Acting Editor-in-Chief was to comply with AJKD's procedures for potential conflicts of interest for editors, described in the Information for Authors & Journal Policies.
Funding Information:
Dr Grams received travel support from DCI in May 2019. Dr Knopman serves on a Data Safety Monitoring Board for the DIAN study; is an investigator in clinical trials sponsored by Biogen, Eli Lilly & Co, and the University of Southern California; and receives research support from the NIH. The remaining authors declare that they have no relevant financial interests.
Funding Information:
The ARIC Study is carried out as a collaborative study supported by National Heart, Lung, and Blood Institute (NHLBI) contracts ( HHSN268201700001I , HHSN268201700002I , HHSN268201700003I , HHSN268201700005I , and HHSN268201700004I ). Neurocognitive data were collected with support by grants 2U01HL096812 , 2U01HL096814 , 2U01HL096899 , 2U01HL096902 , 2U01HL096917 from the National Institutes of Health ( NIH ; NHLBI , with support from the National Institute of Neurological Disorders and Stroke , National Institute on Aging , and National Institute on Deafness and Other Communication Disorders ) and with previous brain MRI examinations funded by R01-HL70825 from the NHLBI . The funding sources had no role in the design and conduct of the study; collection, management, analysis, reporting, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication.
Publisher Copyright:
© 2020 National Kidney Foundation, Inc.
PY - 2020/12
Y1 - 2020/12
N2 - Rationale & Objective: Evidence is limited on how estimated glomerular filtration rate (eGFR) and urinary albumin-creatinine ratio (UACR) relate to dementia at different ages. We evaluated eGFR and UACR in midlife and older age as risk factors for dementia. Additionally, we assessed whether the association between eGFR and dementia is altered when cystatin C and β2-microglobulin (B2M) levels are used for GFR estimation. Study Design: Prospective cohort study. Setting & Participants: Two baselines from the Atherosclerosis Risk in Communities (ARIC) Study were used: visit 4 (1996-1998), including 9,967 participants 54 to 74 years old, and visit 5 (2011-2013), including 4,626 participants 70 to 90 years old. Participants were followed up until 2017. Predictors: Log(UACR); eGFR based on creatinine, cystatin C, creatinine and cystatin C, or B2M levels (denoted as eGFRcr, eGFRcys, eGFRcr-cys, and eGFRB2M). Outcome: Incident dementia. Analytical Approach: Multivariable Cox proportional hazards regression models fit separately for each of the 5 predictors and based on a change in the predictor equivalent to the interquartile range for that predictor at visit 4 (IQRV4). eGFR models were adjusted for log(UACR) and log(UACR) models were adjusted for eGFRcys. Results: We observed 1,821 dementia cases after visit 4 and 438 cases after visit 5. Dementia risk increased with higher albuminuria levels (HRs per IQRV4 [equivalent to 4.2-fold greater log albuminuria] of 1.15 [95% CI, 1.09-1.21] after visit 4 and 1.27 [95% CI, 1.13-1.42] after visit 5). An association with lower eGFR was seen for only eGFRcys (HRs per IQRV4 [equivalent to 24.3 mL/min/1.73 m2 lesser eGFRcys] of 1.12 [95% CI, 1.04-1.21] after visit 4 and 1.30 [95% CI, 1.12-1.52] after visit 5) and eGFRB2M (HRs per IQRV4 [equivalent to 18.3 mL/min/1.73 m2 lesser eGFRB2M] of 1.15 [95% CI, 1.07-1.23] after visit 4 and 1.34 [95% CI, 1.17-1.55] after visit 5). Differences between these associations in midlife and older age were not statistically significant. Limitations: Changes in potentially time-varying covariates were not measured. Dementia was not subclassified by cause. Conclusions: Albuminuria was consistently associated with dementia incidence. Lower eGFR based on cystatin C or B2M, but not creatinine, levels was also associated with dementia. Risk associations were similar when kidney measures were assessed at midlife and older age.
AB - Rationale & Objective: Evidence is limited on how estimated glomerular filtration rate (eGFR) and urinary albumin-creatinine ratio (UACR) relate to dementia at different ages. We evaluated eGFR and UACR in midlife and older age as risk factors for dementia. Additionally, we assessed whether the association between eGFR and dementia is altered when cystatin C and β2-microglobulin (B2M) levels are used for GFR estimation. Study Design: Prospective cohort study. Setting & Participants: Two baselines from the Atherosclerosis Risk in Communities (ARIC) Study were used: visit 4 (1996-1998), including 9,967 participants 54 to 74 years old, and visit 5 (2011-2013), including 4,626 participants 70 to 90 years old. Participants were followed up until 2017. Predictors: Log(UACR); eGFR based on creatinine, cystatin C, creatinine and cystatin C, or B2M levels (denoted as eGFRcr, eGFRcys, eGFRcr-cys, and eGFRB2M). Outcome: Incident dementia. Analytical Approach: Multivariable Cox proportional hazards regression models fit separately for each of the 5 predictors and based on a change in the predictor equivalent to the interquartile range for that predictor at visit 4 (IQRV4). eGFR models were adjusted for log(UACR) and log(UACR) models were adjusted for eGFRcys. Results: We observed 1,821 dementia cases after visit 4 and 438 cases after visit 5. Dementia risk increased with higher albuminuria levels (HRs per IQRV4 [equivalent to 4.2-fold greater log albuminuria] of 1.15 [95% CI, 1.09-1.21] after visit 4 and 1.27 [95% CI, 1.13-1.42] after visit 5). An association with lower eGFR was seen for only eGFRcys (HRs per IQRV4 [equivalent to 24.3 mL/min/1.73 m2 lesser eGFRcys] of 1.12 [95% CI, 1.04-1.21] after visit 4 and 1.30 [95% CI, 1.12-1.52] after visit 5) and eGFRB2M (HRs per IQRV4 [equivalent to 18.3 mL/min/1.73 m2 lesser eGFRB2M] of 1.15 [95% CI, 1.07-1.23] after visit 4 and 1.34 [95% CI, 1.17-1.55] after visit 5). Differences between these associations in midlife and older age were not statistically significant. Limitations: Changes in potentially time-varying covariates were not measured. Dementia was not subclassified by cause. Conclusions: Albuminuria was consistently associated with dementia incidence. Lower eGFR based on cystatin C or B2M, but not creatinine, levels was also associated with dementia. Risk associations were similar when kidney measures were assessed at midlife and older age.
KW - Albuminuria
KW - Atherosclerosis Risk in Communities (ARIC) Study
KW - albuminuria
KW - beta-2-microglobulin (B2M)
KW - chronic kidney disease (CKD)
KW - cognitive decline
KW - creatinine
KW - cystatin C
KW - dementia
KW - elderly
KW - estimated glomerular filtration rate (eGFR)
KW - geriatric
KW - midlife
KW - older age
KW - renal function
KW - urine albumin-creatinine ratio (UACR)
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U2 - 10.1053/j.ajkd.2020.03.015
DO - 10.1053/j.ajkd.2020.03.015
M3 - Article
C2 - 32428540
AN - SCOPUS:85087680315
SN - 0272-6386
VL - 76
SP - 775
EP - 783
JO - American Journal of Kidney Diseases
JF - American Journal of Kidney Diseases
IS - 6
ER -