Dynamic contrast-enhanced MRI promotes early detection of toxin-induced acute kidney injury

Abstract

Acute kidney injury (AKI) is a common cause of morbidity and mortality in hospitalized patients. Nevertheless, there is limited ability to diagnose AKI in its earliest stages through the collection of structural and functional information. Magnetic resonance imaging (MRI) is increasingly being used to provide structural and functional data that characterize the injured kidney. Dynamic contrast-enhanced (DCE) MRI is an imaging modality with robust spatial and temporal resolution; however, its ability to detect changes in kidney function following AKI has not been determined. We hypothesized that DCE MRI would detect a prolongation in contrast transit time following toxin-induced AKI earlier than commonly used serum and tissue biomarkers. To test our hypothesis, we injected mice with either vehicle or cisplatin (30 mg/kg) and performed DCE MRI at multiple time points. We found that commonly used kidney injury biomarkers, including creatinine, blood urea nitrogen, and neutrophil gelatinase-associated lipocalin, did not rise until day 2 following cisplatin. Tissue levels of the proinflammatory cytokines and chemokines, tumor necrosis factor-α, interleukin (IL)-1β, IL-1α, IL-6, C-C motif chemokine ligand 2, and C-X-C motif chemokine ligand 2 similarly did not upregulate until day 2 following cisplatin. However, the time to peak intensity of contrast in the renal collecting system was already prolonged at day 1 following cisplatin compared with vehicle-treated mice. This intensity change mirrored changes in kidney injury as measured by histological analysis and in transporter expression in the proximal tubule. Taken together, DCE MRI is a promising preclinical imaging modality that is useful for assessing functional capacity of the kidney in the earliest stages following AKI.

Chronic effects of repeated low-dose cisplatin treatment in mouse kidneys and renal tubular cells

“…Cisplatin is a potent chemotherapeutic drug, but its efficacy is often limited by its nephrotoxicity (24,26,28). It is well recognized that cisplatin may induce acute kidney injury (AKI) during chemotherapy.…”

Multivariate analysis of CT imaging, laboratory, and demographical features for prediction of acute kidney injury in COVID-19 patients: a Bi-centric analysis

“…Ultrasound Doppler-based renal flow and velocity measurements have previously shown promise in terms of prediction of AKI in critically ill, non-COVID-19 patients [ 5 , 6 ]. Recently, dynamic contrast-enhanced MRI was identified as an early predictor of AKI in a mouse model after administration of toxins [ 7 ].…”

Clinical and experimental approaches for imaging of acute kidney injury

“…Several currently available imaging techniques can evaluate renal blood flow in AKI [57]. Dynamic contrast-enhanced MRI, which uses iron oxide nanoparticles or gadoliniumbased contrast agents with low molecular weight, can determine the spatial distribution of renal perfusion and vascular reactivity [55,[58][59][60]. Of note, single-kidney GFR/ split function can be estimated using this method [61].…”

“…In particular, imaging methods such as CEST imaging or SPIO nanoparticles can help to evaluate sCre-negative but damage biomarker-positive patients with subclinical or incipient AKI [ 152 ]. Privratsky et al [ 59 ] reported renal tissue damage detection using dynamic contrast-enhanced MRI after cisplatin treatment from an early stage when sCre and NGAL levels were not elevated. In the context of clinical settings, cutoff values for novel damage biomarkers and imaging information need to be evaluated against patient outcomes (e.g., need for renal replacement therapy) independent of functional biomarkers (e.g., sCre) [ 13 , 153 ].…”