Abstract
Alport Syndrome (AS) is a genetic disorder characterized by impaired kidney function. The development of a noninvasive tool for early diagnosis and monitoring of renal function during disease progression is of clinical importance. Hyperpolarized 13C MRI is an emerging technique that enables non-invasive, real-time measurement of in vivo metabolism. This study aimed to investigate the feasibility of using this technique for assessing changes in renal metabolism in the mouse model of AS. Mice with AS demonstrated a significant reduction in the level of lactate from 4- to 7-week-old, while the levels of lactate were unchanged in the control mice over time. This reduction in lactate production in the AS group accompanied a significant increase of PEPCK expression levels, indicating that the disease progression in AS triggered the gluconeogenic pathway and might have resulted in a decreased lactate pool size and a subsequent reduction in pyruvate-to-lactate conversion. Additional metabolic imaging parameters, including the level of lactate and pyruvate, were found to be different between the AS and control groups. These preliminary results suggest that hyperpolarized 13C MRI might provide a potential noninvasive tool for the characterization of disease progression in AS.
Highlights
Alport syndrome (AS) is an inherited disease manifested by impaired kidney function, ocular abnormalities, and hearing loss [1]
Our finding identified the changes in renal metabolism, which were associated with the disease progression of Alport syndrome
The albumin-to-creatinine ratio (ACR) of KO mice significantly increased from 198.3 milligrams of albumin per gram of creatinine at 4-week-old to 11,423.3 mg/gCr at 7-week-old (p = 0.029), while the ACRs of WT mice were similar over the same period (8.4 mg/gCr at 4-week-old and 13.3 mg/gCr at 7-week-old, p = 0.11)
Summary
Alport syndrome (AS) is an inherited disease manifested by impaired kidney function, ocular abnormalities, and hearing loss [1]. Mutations of type IV collagen chains, which are major components of the capillary basement membranes, cause Alport syndrome. There is currently no therapy to prevent end-stage renal disease in these patients, early treatment with renin angiotensin aldosterone system inhibitors was shown to delay endstage renal disease in patients with Alport syndrome, especially in children with family history [5]. And accurate diagnosis is crucial for providing an appropriate treatment option. Genetic testing proved to be efficient and accurate in detecting genetic abnormality [6], it requires an invasive procedure and a high implementation cost. The development of a noninvasive technique for early characterization of the disease is of clinical importance
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