Twenty-six million adults in the US are affected by chronic kidney disease (CKD) including more than 400,000 individuals with end-stage renal disease (ESRD), and more than half are elderly (e65 years). Cognitive impairment is also common among elderly individuals and associated with higher morbidity and mortality. Yet the nature and long term course of cognitive decline among those with CKD, especially as they transition to ESRD is virtually unknown. The NIDDK- sponsored Chronic Renal Insufficiency Cohort (CRIC) study, which follows a large cohort of adults with CKD through the transition to ESRD, presents a unique opportunity to address this critical gap in knowledge. Our ongoing work in CRIC is characterizing cognitive function in CKD prior to the development of ESRD. In this application, a competitive renewal of R01-DK069406, we plan to investigate cognitive trajectories of individuals transitioning from advanced CKD to ESRD. First, we will leverage our prior work in CRIC in order to investigate the long term (6-8 year) course of cognitive decline among 3000 adults with CKD and to determine how this course affects management of CKD and geriatric outcomes including timing of dialysis, catheter use and risk of mortality and frailty. In addition, we propose to conduct semi-annual telephone cognitive assessments among approximately 420 participants with advanced CKD in order to characterize cognitive trajectory during the CKD-ESRD transition. We will also measure several biomarkers associated with advanced CKD that may also be linked with cognitive decline such as markers of oxidative stress, cystatin-c, anemia and advanced glycated end products. We hypothesize that trajectory of cognitive decline accelerates at the onset of ESRD, that dialysis initiation influences cognitive decline in vulnerable individuals, and that selected biomarkers associated with advanced CKD identify individuals at high risk for decline. Results stemming from this proposal will be critical for assessing the risks and benefits of dialysis in older adults, for determining natural course of cognitive function among those with CKD, and for devising effective prevention and management strategies for cognitive decline in this population. We have assembled an outstanding group of investigators from a variety of disciplines with a track record of productive collaboration and dedication who will address these important and innovative aims.

Public Health Relevance

Many millions of US adults are affected by chronic kidney disease (CKD) and many of them will progress to end-stage renal disease (ESRD), a condition associated with significant morbidity and mortality. Yet, the nature and long term course of cognitive decline among those with CKD, especially as they transition to ESRD is virtually unknown. We will investigate cognitive function, its outcomes and biomarkers, among a large group of adults with CKD and ESRD in order to eventually improve the care of those with CKD and ideally, prevent cognitive decline among this vulnerable group. NOTE: The criteria scores and the critiques given below were provided by the reviewers assigned to this application. These do not necessarily reflect the positions of the reviewers at the close of the group discussion or the final majority opinion of the group, although the reviewers were asked to amend their criteria scores and critiques if their positions changed during the discussion. Please note that the criteria scores are not averaged in arriving at the final overall impact scores. If the reviewers have not changed their criteria scores after the discussion, those shown in the critiques may reflect the opinion of the reviewers before the meeting. The Resume and other initial sections of the summary statement are the authoritative representations of the final outcome of the group discussion. If there is any discrepancy between the reviewers'commentaries and the priority/impact score on the face page of this summary statement, the priority/impact score should be considered the most accurate representation of the final outcome of the group discussion.

National Institute of Health (NIH)
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Research Project (R01)
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Study Section
Special Emphasis Panel (ZDK1-GRB-7 (M3))
Program Officer
Kusek, John W
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Northern California Institute Research & Education
San Francisco
United States
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Harhay, Meera N; Xie, Dawei; Zhang, Xiaoming et al. (2018) Cognitive Impairment in Non-Dialysis-Dependent CKD and the Transition to Dialysis: Findings From the Chronic Renal Insufficiency Cohort (CRIC) Study. Am J Kidney Dis 72:499-508
Kurella Tamura, Manjula; Tam, Karman; Vittinghoff, Eric et al. (2017) Inflammatory Markers and Risk for Cognitive Decline in Chronic Kidney Disease: The CRIC Study. Kidney Int Rep 2:192-200
Kurella Tamura, Manjula; Vittinghoff, Eric; Hsu, Chi-Yuan et al. (2017) Loss of executive function after dialysis initiation in adults with chronic kidney disease. Kidney Int 91:948-953
Kurella Tamura, Manjula; Vittinghoff, Eric; Yang, Jingrong et al. (2016) Anemia and risk for cognitive decline in chronic kidney disease. BMC Nephrol 17:13
Kurella Tamura, Manjula; Yaffe, Kristine; Hsu, Chi-Yuan et al. (2016) Cognitive Impairment and Progression of CKD. Am J Kidney Dis 68:77-83
James, Bryan D; Leurgans, Sue E; Hebert, Liesi E et al. (2014) Contribution of Alzheimer disease to mortality in the United States. Neurology 82:1045-50
Lee, Sei J; Ritchie, Christine S; Yaffe, Kristine et al. (2014) A clinical index to predict progression from mild cognitive impairment to dementia due to Alzheimer's disease. PLoS One 9:e113535
Yaffe, Kristine; Kurella-Tamura, Manjula; Ackerson, Lynn et al. (2014) Higher levels of cystatin C are associated with worse cognitive function in older adults with chronic kidney disease: the chronic renal insufficiency cohort cognitive study. J Am Geriatr Soc 62:1623-9
Gardner, Raquel C; Yaffe, Kristine (2014) Traumatic brain injury may increase risk of young onset dementia. Ann Neurol 75:339-41
Yaffe, Kristine; Ackerson, Lynn; Hoang, Tina D et al. (2013) Retinopathy and cognitive impairment in adults with CKD. Am J Kidney Dis 61:219-27

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