Department of Radiology, Case Western Reserve University, Cleveland, OH, USA.
Department of Radiology, University Hospitals Cleveland Medical Center, Cleveland, OH, USA.
Pediatr Res. 2021 Jan;89(1):157-162. doi: 10.1038/s41390-020-0883-9. Epub 2020 Apr 13.
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.
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.
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.
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.
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.
常染色体隐性多囊肾病 (ARPKD) 是一种罕见但潜在致命的遗传疾病，其典型特征是弥漫性肾脏微囊肿。由于缺乏 ARPKD 肾病进展和/或治疗效果的敏感衡量标准，目前无法对 ARPKD 患者进行临床试验。
本研究使用动物和人体磁共振成像 (MRI) 扫描仪，分别获取 bpk 小鼠和野生型 (WT) 小鼠的离体肾脏以及一名 ARPKD 儿科患者和一名健康成年志愿者的肾脏 T1 和 T2 弛豫时间定量图谱。
肾脏 T1 和 T2 弛豫时间的平均值随年龄显著增加 (p<0.05)，与 WT 小鼠相比也显著增加 (p<2×10)。肾脏 T1 (p=0.030) 和 T2 (p=0.054) 的平均值与肾脏总容量之间存在显著或近乎显著的线性相关性。在一名 ARPKD 患者的初步磁共振指纹图谱评估中，与健康志愿者相比，其肾脏 T1 和 T2 均可见增加。
这些临床前和初步临床 MRI 研究表明，肾脏 T1 和 T2 弛豫率可能为评估 ARPKD 患者囊性肾病进展提供额外的结果衡量标准。
在 ARPKD 患者中开展临床试验的主要障碍是缺乏 ARPKD 肾病进展和/或治疗效果的敏感衡量标准。因此，需要开发一种安全、敏感的 ARPKD 患者肾脏疾病进展，最终是治疗效果的衡量标准。肾脏 T1 和 T2 MRI 弛豫时间的平均值随年龄显著增加 (p<0.05)，与 WT 小鼠相比也显著增加 (p<2×10)，表明 T1 和 T2 可能敏感评估与进行性 ARPKD 肾病相关的囊性变化。这项临床前和初步临床研究表明，基于 MRI 的肾脏 T1 和 T2 测绘可作为 ARPKD 肾脏疾病进展的非侵入性评估方法。这些非侵入性、定量 MRI 技术最终可作为评估旨在限制或预防 ARPKD 肾脏疾病进展的新型治疗方法的临床试验的结果衡量标准。
