# Cleveland Precision Medicine Chronic Kidney Disease Cohort

> **NIH NIH UH3** · CLEVELAND CLINIC LERNER COM-CWRU · 2021 · $300,000

## Abstract

Project Abstract
Although hypertension is associated with ~25% of end-stage renal disease (H-ESRD) in the United States, the
pathogenic mechanisms that drive the initiation and progression of hypertension-associated chronic kidney
disease (HTN-CKD) are unclear. The incidence of H-ESRD is 4- to 5-fold greater in African American
populations than in whites. To address this health disparity, the Cleveland KPMP Recruiting Network will
recruit a cohort of CKD patients with HTN-CKD. Prospective participants with CKD stage 3a will be identified
by automated, scheduled queries of the electronic health records (EHR) of two large health care delivery
systems in Cleveland, OH, the Cleveland Clinic and MetroHealth. Eligible candidates will be enriched for
subjects likely to progress by using the Kidney Failure Risk Equation to identify individuals with > 15%
probability of developing ESRD in 5 years. This Network plans enrollment of 10 participants each year during
the two year UG3 exploratory phase and 40 to 50 subjects each year for the subsequent, three year UH3
implementation phase. Once kidney research biopsy safety is established in UG3, HTN-CKD subject inclusion
criteria in UH3 will be modified to include proteinuric CKD Stage 2 patients. Subjects with other CKD
phenotypes can be recruited to support consortium goals. After informed consent, enrolled subjects will
undergo a baseline MRI to image kidney structure and a research kidney biopsy and then be followed every 6
months at standard of care visits for the duration of the KPMP. Baseline and longitudinal biosamples will be
collected and linked through REDCap to clinical data in the EHRs. The Network plans to obtain additional
healthy and disease kidney samples from living donor kidney implant biopsies and an additional tissue core
obtained at an indication biopsy from HTN-CKD patients, respectively. Clinical data, biopsy blocks and
biosamples will be submitted to Central Hub repositories. The Network includes a Community Partnership
Committee composed of CKD patients and families, physicians and an ethicist to guide implementation of this
KPMP Network. In anticipation of Opportunity Pool funding, the PIs have recruited co-investigators, who will
utilize the rich KPMP molecular, radiologic and histopathologic phenotypes and longitudinal clinical data for
discovery. Since excess risk in African Americans for HTN-CKD is largely explained by genetic variations in
APOL1, our initial research goal in UH3 is to identify the molecular mechanisms underlying this association.
We will integrate molecular and clinical phenotypes with visual and subvisual morphologic descriptors to
discover the cells and associated molecular pathways mediating APOL1-associated HTN-CKD. In pilot, proof-
of-principle studies, we used computational methods and identified a set of sub-visual morphologic features
that discriminated 10 African American kidney transplant implant biopsies with high risk APOL1 genotypes
from 6 implant b...

## Key facts

- **NIH application ID:** 10223909
- **Project number:** 5UH3DK114908-05
- **Recipient organization:** CLEVELAND CLINIC LERNER COM-CWRU
- **Principal Investigator:** JOHN F. O'TOOLE
- **Activity code:** UH3 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $300,000
- **Award type:** 5
- **Project period:** 2017-09-15 → 2022-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10223909

## Citation

> US National Institutes of Health, RePORTER application 10223909, Cleveland Precision Medicine Chronic Kidney Disease Cohort (5UH3DK114908-05). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10223909. Licensed CC0.

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