# Imaging Assessments of ARPKD Kidney Disease Progression

> **NIH NIH R01** · CLEVELAND CLINIC LERNER COM-CWRU · 2020 · $122,700

## Abstract

PROJECT SUMMARY
 Autosomal Recessive Polycystic Kidney Disease (ARPKD) is a potentially lethal inherited disorder that
affects approximately 1/20,000 children and is clinically and genetically distinct from the more common
Autosomal Dominant PKD (ADPKD). ARPKD is characterized by diffuse renal microcysts resulting from fusiform
dilatations of the collecting tubules. Morbidity and mortality is significant: only 70% of ARPKD children survive
the neonatal period and 40% progress to end-stage renal disease (ESRD) by age 15 years. There are currently
no disease-specific clinically-available therapies for ARPKD and treatment is directed at management of chronic
kidney disease (CKD) complications. Several novel therapies have, however, shown promise in both ARPKD
animal models and adult ADPKD patients. Unfortunately, the major roadblock for implementing clinical trials in
ARPKD patients is the absence of sensitive measures of ARPKD kidney disease progression. Conventional
measures of kidney disease progression, such as declines in estimated glomerular filtration rate (eGFR) are
variable in ARPKD, and GFR may remain unchanged despite ongoing kidney damage. Imaging assessments of
kidney volume, which have been successfully utilized in ADPKD clinical trials, have limited applicability to
ARPKD, as kidney size stabilizes over time despite worsening cystic disease. Therefore, alternative markers are
needed to stage and monitor ARPKD kidney disease progression.
 As part of funded preclinical and clinical studies, our multidisciplinary imaging team has identified T2-MRI as
a sensitive measure of ARPKD progression. In studies in the PCK rat and bpk mouse models, we utilized high
resolution T2-MRI to establish renal cystic burden as an accurate and sensitive marker for ARPKD progression
and therapeutic response. In preliminary studies in ARPKD patients, we show that ARPKD patients have
increased mean kidney T2-MRI values in comparison to healthy control subjects and demonstrate phenotypic
variations in mean kidney T2 values that are consistent with differences in kidney disease severity. Our imaging
team has also pioneered novel Magnetic Resonance Fingerprinting (MRF) technologies that are resistant to
motion artifacts and allow for rapid, simultaneous acquisition of multiple imaging parameters. The overall
objective of this proposal is to establish mean kidney T2 values as a sensitive, quantitative MRI biomarker to
stage and longitudinally monitor ARPKD kidney disease. We will utilize these techniques to obtain both cross-
sectional and longitudinal assessments of kidney disease in pediatric and young adult ARPKD patients recruited
from across the U.S. The proposed studies, conducted at two US sites, will be the first to systematically apply
these quantitative MRI techniques to assess renal cystic burden in ARPKD patients, with the long term goal of
developing MRI biomarkers for ARPKD kidney disease that can be used to identify patients at high risk for
disease...

## Key facts

- **NIH application ID:** 10236909
- **Project number:** 3R01DK114425-02S1
- **Recipient organization:** CLEVELAND CLINIC LERNER COM-CWRU
- **Principal Investigator:** KATHERINE MACRAE DELL
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $122,700
- **Award type:** 3
- **Project period:** 2019-08-20 → 2022-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10236909

## Citation

> US National Institutes of Health, RePORTER application 10236909, Imaging Assessments of ARPKD Kidney Disease Progression (3R01DK114425-02S1). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10236909. Licensed CC0.

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