Multi-parametric MRI of kidney disease progression for autosomal recessive polycystic kidney disease: mouse model and initial patient results.

TitleMulti-parametric MRI of kidney disease progression for autosomal recessive polycystic kidney disease: mouse model and initial patient results.
Publication TypeJournal Article
Year of Publication2021
AuthorsMacAskill CJ, Erokwu BO, Markley M, Parsons A, Farr S, Zhang Y, Tran U, Chen Y, Anderson CE, Serai S, Hartung EA, Wessely O, Ma D, Dell KM, Flask CA
JournalPediatr Res
Volume89
Issue1
Pagination157-162
Date Published2021 01
ISSN1530-0447
KeywordsAdolescent, Animals, Disease Models, Animal, Disease Progression, Humans, Kidney, Magnetic Resonance Imaging, Polycystic Kidney, Autosomal Recessive, Predictive Value of Tests
Abstract

BACKGROUND: Autosomal recessive polycystic kidney disease (ARPKD) is a rare but potentially lethal genetic disorder typically characterized by diffuse renal microcysts. Clinical trials for patients with ARPKD are not currently possible due to the absence of sensitive measures of ARPKD kidney disease progression and/or therapeutic efficacy.

METHODS: In this study, animal and human magnetic resonance imaging (MRI) scanners were used to obtain quantitative kidney T1 and T2 relaxation time maps for both excised kidneys from bpk and wild-type (WT) mice as well as for a pediatric patient with ARPKD and a healthy adult volunteer.

RESULTS: Mean kidney T1 and T2 relaxation times showed significant increases with age (p < 0.05) as well as significant increases in comparison to WT mice (p < 2 × 10). Significant or nearly significant linear correlations were observed for mean kidney T1 (p = 0.030) and T2 (p = 0.054) as a function of total kidney volume, respectively. Initial magnetic resonance fingerprinting assessments in a patient with ARPKD showed visible increases in both kidney T1 and T2 in comparison to the healthy volunteer.

CONCLUSIONS: These preclinical and initial clinical MRI studies suggest that renal T1 and T2 relaxometry may provide an additional outcome measure to assess cystic kidney disease progression in patients with ARPKD.

IMPACT: A major roadblock for implementing clinical trials in patients with ARPKD is the absence of sensitive measures of ARPKD kidney disease progression and/or therapeutic efficacy. A clinical need exists to develop a safe and sensitive measure for kidney disease progression, and eventually therapeutic efficacy, for patients with ARPKD. Mean kidney T1 and T2 MRI relaxation times showed significant increases with age (p < 0.05) as well as significant increases in comparison to WT mice (p < 2 ×10), indicating that T1 and T2 may provide sensitive assessments of cystic changes associated with progressive ARPKD kidney disease. This preclinical and initial clinical study suggests that MRI-based kidney T1 and T2 mapping could be used as a non-invasive assessment of ARPKD kidney disease progression. These non-invasive, quantitative MRI techniques could eventually be used as an outcome measure for clinical trials evaluating novel therapeutics aimed at limiting or preventing ARPKD kidney disease progression.

DOI10.1038/s41390-020-0883-9
Alternate JournalPediatr Res
PubMed ID32283547
PubMed Central IDPMC7554096
Grant ListP30 CA043703 / CA / NCI NIH HHS / United States
P30 DK097948 / DK / NIDDK NIH HHS / United States
R01 DK114425 / DK / NIDDK NIH HHS / United States