# Leveraging Proteomics to Understand the Link Between Chronic Kidney Disease and Cognitive Impairment

> **NIH NIH K01** · UNIVERSITY OF CALIFORNIA, SAN DIEGO · 2022 · $124,798

## Abstract

PROJECT SUMMARY
This is the initial submission of a K01 application by Lindsay Miller Ph.D., under the mentorship of Joachim Ix
M.D., at the University of California, San Diego (UCSD). This proposal will establish Dr. Miller as an
independent investigator and will leverage large-scale proteomics to understand the association and predictive
ability of the proteome with cognitive impairment (CI), a clinical symptom of Alzheimer’s Disease and Related
Dementias (ADRD) in older adults with chronic kidney disease (CKD).
Candidate: Dr. Miller’s training objectives and career goals through this proposal include: 1) to become an
expert in CKD and CI in older adults 2) to develop skills in advanced methods for the application to proteomic
data, and 3) to develop skills in grant writing, lab management and career development. Dr. Miller will
accomplish these objectives through mentorship, coursework, and workshops. She has assembled a
multidisciplinary mentorship team comprised of her primary mentor, Dr. Ix, an established leader in nephrology,
and the following co-mentors: Dr. Marquine, an expert in neuropsychology; Dr. Scherzer, the Director of
Biostatistics at the Kidney Health Research Collaboration at the University of California, San Francisco.
Research: CI is a clinical symptom of ADRD, with mild CI being often a precursor to the development of
ADRD. CI is common among patients with CKD; however, CI has received much less investigation than
complications such as CVD and end-stage kidney disease. Studies have primarily used estimated glomerular
filtration rate (eGFR) and urine albumin to creatinine ratio (ACR) to evaluate the relationship between CKD and
CI. However, in recent work the applicant demonstrated that a panel of markers reflecting kidney tubule health
was associated with CI independent of eGFR and ACR in older adults, indicating that these markers of kidney
health do not fully explain its link with CI. Still, the relationship is likely more complex that what can be
identified using a few targeted biomarkers. Thus, Dr. Miller proposes to utilize large-scale proteomic data to
understand the multifactorial relationship between CKD and cognition with the long-term objective that these
insights might lead to novel approaches and therapies to prevent or ameliorate the development of CI in the
CKD population. Next, while large-scale proteomics is optimally suited to understand biological pathways
between CKD and CI, it will not be feasible to utilize in clinical practice to identify individuals at highest risk for
CI. As such, variable selection methods are needed to identify and validate subsets of proteins that will allow
clinical prediction of cognitive impairment. In aim 1, she will identify protein clusters and biological pathways
that associate with CI. This aim will be conducted in 3419 adults with CKD in the Chronic Renal Insufficiency
Cohort Study (CRIC). In aim 2 she will test different penalized variable selection methods to identify a...

## Key facts

- **NIH application ID:** 10507677
- **Project number:** 1K01AG078486-01
- **Recipient organization:** UNIVERSITY OF CALIFORNIA, SAN DIEGO
- **Principal Investigator:** Lindsay M. Miller
- **Activity code:** K01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $124,798
- **Award type:** 1
- **Project period:** 2022-09-01 → 2027-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10507677

## Citation

> US National Institutes of Health, RePORTER application 10507677, Leveraging Proteomics to Understand the Link Between Chronic Kidney Disease and Cognitive Impairment (1K01AG078486-01). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10507677. Licensed CC0.

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