# Imaging Assessments of ARPKD Kidney Disease Progression

> **NIH NIH R01** · CLEVELAND CLINIC LERNER COM-CWRU · 2024 · $692,583

## Abstract

PROJECT SUMMARY / ABSTRACT
 Autosomal Recessive Polycystic Kidney Disease (ARPKD) is a potentially lethal inherited disorder that
affects approximately 1/20,000 children and is genetically and clinically distinct from the more common
Autosomal Dominant PKD (ADPKD). ARPKD is characterized by diffuse kidney microcysts resulting from
fusiform dilatations of the collecting tubules. As these kidneys cysts accumulate, the kidneys do not show
progressive enlargement, but instead accumulate more cysts and eventually become progressively more fibrotic,
resulting in end-stage kidney disease (ESKD). Approximately 40-50% of ARPKD children who survive the
neonatal period progress to ESKD by age 18, highlighting the significant disease burden. Importantly, there are
currently no disease-specific clinically-available therapies for patients with ARPKD. Despite several
potential therapies showing promise in ARPKD animal models, clinical trials are currently limited by the lack
of sensitive measures for ARPKD kidney disease progression across the spectrum of disease.
Conventional clinical endpoints for CKD progression (e.g., decline in glomerular filtration rate, GFR) lack the
sensitivity to detect ARPKD progression in the time frame of a typical clinical trial, as the rates of GFR decline
are relatively small and variable among patients, especially those with milder disease. Imaging assessments of
total kidney volume, successfully utilized in ADPKD patients, are also not applicable to ARPKD as kidney size
stabilizes over time despite cystic kidney disease progression. Our collaborative multi-center research team
has shown in previous (preclinical) and current (clinical) NIH R01 studies that novel MR Fingerprinting (MRF,
cystic burden) and non-contrast kidney Arterial Spin Labeling MRI (ASL, perfusion): (1) can accurately detect
and stage ARPKD kidney disease; and (2) can measure significant kidney disease progression in ARPKD
patients before conventional GFR measures. The Aims of the proposed studies are 1) to determine the capability
of our multimodal MRI biomarkers to accurately and repeatably detect and stage ARPKD kidney disease across
the full spectrum of disease from early-stage CKD characterized by diffuse kidney cysts (MRF) and reduced
kidney perfusion (ASL) to later-stage CKD characterized by progressive kidney fibrosis (MR elastography, MRE);
(2) determine the sensitivity of these MRI biomarkers to detect changes in ARPKD kidney disease progression
over time in comparison to gold-standard GFR assessments; and (3) determine the feasibility of a new free-
breathing MRF methodology that would allow infants and young children to be scanned without sedation. For
these studies, we will recruit ARPKD patients ≥6 years of age with early, mild, and moderate CKD from across
the US for 4 annual multimodal MRI scans and GFR measurements at our two collaborating sites (CC/CWRU
and CHOP). Age-matched healthy controls will also be recruited for an MRI scan. If success...

## Key facts

- **NIH application ID:** 10799149
- **Project number:** 2R01DK114425-04A1
- **Recipient organization:** CLEVELAND CLINIC LERNER COM-CWRU
- **Principal Investigator:** KATHERINE MACRAE DELL
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $692,583
- **Award type:** 2
- **Project period:** 2019-08-20 → 2029-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10799149

## Citation

> US National Institutes of Health, RePORTER application 10799149, Imaging Assessments of ARPKD Kidney Disease Progression (2R01DK114425-04A1). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10799149. Licensed CC0.

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