# Mechanisms of Brain Hemorrhage in Chronic Kidney Disease

> **NIH NIH R21** · UNIVERSITY OF CALIFORNIA-IRVINE · 2022 · $235,500

## Abstract

PROJECT SUMMARY
Intracerebral hemorrhage (ICH) affects over two million people per year worldwide and is associated with a 54%
one-year mortality. One important risk factor for ICH is chronic kidney disease (CKD), an entity that affects over
20 million people in the United States and is associated with higher ICH incidence and worse outcomes. ICH
patients with advanced CKD have a 2.3-fold larger hematoma volume and a >4-fold increase in 1-year mortality.
Given a prevalence as high as 14% in the U.S. population, CKD is a prime yet understudied disease in the
pathogenesis of ICH.
In this mechanistic clinical investigation, we hypothesize that CKD-induced vascular injury leading to ICH can be
characterized by two intermediate imaging biomarkers: (1) intracranial arterial calcification (IAC), and (2) cerebral
microbleeds (CMB). Specifically, we hypothesize that arteriolar injury in CKD results in higher IAC and CMB
burden, which are predictive of ICH volume and hematoma expansion. To better characterize these
relationships, this study leverages a 10-year institutional database of 1,500 spontaneous ICH patients spanning
July 2011 and June 2020 as well as 150 prospective ICH patients aggregated over the first study year. For each
patient, deep learning imaging analysis is used to quantify ICH volume as well as IAC burden on computed
tomography scans. For patients with corresponding brain magnetic resonance imaging within 2-weeks of hospital
admission, deep learning analysis will also be used to quantify CMB burden. Key target outcomes include
prediction of ICH volume and hematoma expansion as a function of IAC and CMB burden stratified by CKD
stage. In Specific Aim 1, the relationship between CKD status and IAC burden is characterized, which is used
in combination with clinical risk factors to predict ICH volume and hematoma expansion. In Specific Aim 2, the
relationship between CKD status and CMB burden is characterized, which is used in combination with IAC
burden and clinical risk factors to predict ICH volume and hematoma expansion. All statistical models derived
from the 10-year historic cohort of 1,500 patients are validated against the prospective cohort of 150 patients.
Through an improved understanding of the shared pathophysiology between these disease states, quantitative
models derived from the proposed analysis can be used for early identification of patients at high-risk for ICH
and associated complications, who in turn are optimal candidates for aggressive management of underlying
CKD.

## Key facts

- **NIH application ID:** 10528021
- **Project number:** 1R21NS125325-01A1
- **Recipient organization:** UNIVERSITY OF CALIFORNIA-IRVINE
- **Principal Investigator:** Peter Chang
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $235,500
- **Award type:** 1
- **Project period:** 2022-08-15 → 2024-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10528021

## Citation

> US National Institutes of Health, RePORTER application 10528021, Mechanisms of Brain Hemorrhage in Chronic Kidney Disease (1R21NS125325-01A1). Retrieved via AI Analytics 2026-05-28 from https://api.ai-analytics.org/grant/nih/10528021. Licensed CC0.

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