Noninvasive Assessment of Fibrosis Following Ischemia/Reperfusion Injury in Rodents Utilizing Na Magnetic Resonance Imaging

Nielsen, Per Mose; Mariager, Christian Østergaard; Rasmussen, Daniel Guldager Kring; Mølmer, Marie; Genovese, Federica; Karsdal, Morten A.; Laustsen, Christoffer; Nørregaard, Rikke

doi:10.3390/pharmaceutics12080775

Cited by 5 publications

(8 citation statements)

References 39 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Our findings of a decreased sodium cortico‐medullary gradient and correlations between 23 Na‐MRI and skGFR and fibrosis in IRI, but not in UUO, are somewhat in accordance with a previous study conducted by Nielsen et al 27 Their data suggested a decreased gradient after 7 days of IRI, but, unlike us, they also observed a decrease of the gradient in UUO rats. However, these changes were normalized on day 14 and day 21 after reperfusion, corresponding to no significant changes in fibrosis.…”

Section: Discussionsupporting

confidence: 93%

“…Furthermore, the study found a positive correlation between fibrosis and total 23 Na-MRI signal, probably because of necrosis, resulting in increased extracellular matrix for sodium distribution, although no correlation was found between fibrosis and the corticomedullary sodium gradient. 27 We found a negative correlation between fibrosis and the 23 Na medulla/cortex ratio in IRI, but not in UUO. Combined, the observed differences in UUO are probably a result of the cortical thinning and associated uncertainties observed in this model.…”

Section: Discussionmentioning

confidence: 52%

“…Thus 23 Na‐MRI may have the potential to assess renal function by imaging the corticomedullary sodium gradient and thereby contribute to renal diagnostic procedures 26 . This explains the increased focus on the relationship between fibrosis and the corticomedullary sodium gradient in current research, and 23 Na‐MRI in combination with extracellular matrix markers of fibrosis has been suggested as a potential method for monitoring kidney fibrosis 27 . But it is unclear how it will add to current multiparametric MRI protocols for renal pathology assessment.…”

Section: Introductionmentioning

confidence: 99%

“…26 This explains the increased focus on the relationship between fibrosis and the corticomedullary sodium gradient in current research, and 23 Na-MRI in combination with extracellular matrix markers of fibrosis has been suggested as a potential method for monitoring kidney fibrosis. 27 But it is unclear how it will add to current multiparametric MRI protocols for renal pathology assessment. The kidney's complex function and pathophysiology means that it is unlikely that one single biomarker is specific for pathological phenomena such as fibrosis.…”

mentioning

confidence: 99%

See 3 more Smart Citations

Fibrosis imaging with multiparametric proton and sodium MRI in pig injury models

et al. 2022

Self Cite

View full text Add to dashboard Cite

Chronic kidney disease (CKD) is common and has huge implications for health and mortality. It is aggravated by intrarenal fibrosis, but the assessment of fibrosis is limited to kidney biopsies, which carry a risk of complications and sampling errors. This calls for a noninvasive modality for diagnosing and staging intrarenal fibrosis. The current, exploratory study evaluates a multiparametric MRI protocol including sodium imaging (23Na‐MRI) to determine the opportunities within this modality to assess kidney injury as a surrogate endpoint of fibrosis. The study includes 43 pigs exposed to ischemia–reperfusion injury (IRI) or unilateral ureteral obstruction (UUO), or serving as healthy controls. Fibrosis was determined using gene expression analysis of collagen. The medulla/cortex ratio of 23Na‐MRI decreased in the injured kidney in the IRI pigs, but not in the UUO pigs (p = 0.0180, p = 0.0754). To assess the combination of MRI parameters in estimating fibrosis, we created a linear regression model consisting of the cortical apparent diffusion coefficient, ΔR2*, ΔT1, the 23Na medulla/cortex ratio, and plasma creatinine (R2 = 0.8009, p = 0.0117). The 23Na medulla/cortex ratio only slightly improved the fibrosis prediction model, leaving 23Na‐MRI in an ambiguous place for evaluation of intrarenal fibrosis. Use of multiparametric MRI in combination with plasma creatinine shows potential for the estimation of fibrosis in human kidney disease, but more translational and clinical work is warranted before MRI can contribute to earlier diagnosis and evaluation of treatment for acute kidney injury and CKD.

show abstract

Section: Discussionsupporting

confidence: 93%

Section: Discussionmentioning

confidence: 52%

Section: Introductionmentioning

confidence: 99%

mentioning

confidence: 99%

See 2 more Smart Citations

Fibrosis imaging with multiparametric proton and sodium MRI in pig injury models

et al. 2022

Self Cite

View full text Add to dashboard Cite

show abstract

“…In addition, it may steer interstitial fibrosis or renal tubular atrophy. The pathogenesis of RHR injury consists of apoptosis, endothelial dysfunction, immune system activation, and transcriptional alternation. , The hypoxic microenvironment forces cells to switch to anaerobic respiration, resulting in lactate formation due to a drop in adenosine triphosphate production. Moreover, intracellular ionic imbalance results in the generation of reactive oxygen species (ROS).…”

Section: Introductionmentioning

confidence: 99%

Renal Hypoxic Reperfusion Injury-on-Chip Model for Studying Combinational Vitamin Therapy

Salih

Asif

Samantasinghar

et al. 2022

ACS Biomater. Sci. Eng.

View full text Add to dashboard Cite

Renal ischemic-reperfusion injury decreases the chances of long-term kidney graft survival and may lead to the loss of a transplanted kidney. During organ excision, the cycle of warm ischemia from the donor and cold ischemia is due to storage in a cold medium after revascularization following organ transplantation. The reperfusion of the kidney graft activates several pathways that generate reactive oxygen species, forming a hypoxic-reperfusion injury. Animal models are generally used to model and investigate renal hypoxic-reperfusion injury. However, these models face ethical concerns and present a lack of robustness and intraspecies genetic variations, among other limitations. We introduce a microfluidics-based renal hypoxic-reperfusion (RHR) injury-on-chip model to overcome current limitations. Primary human renal proximal tubular epithelial cells and primary human endothelial cells were cultured on the apical and basal sides of a porous membrane. Hypoxic and normoxic cell culture media were used to create the RHR injury-on-chip model. The disease model was validated by estimating various specific hypoxic biomarkers of RHR. Furthermore, retinol, ascorbic acid, and combinational doses were tested to devise a therapeutic solution for RHR. We found that combinational vitamin therapy can decrease the chances of RHR injury. The proposed RHR injury-on-chip model can serve as an alternative to animal testing for injury investigation and the identification of new therapies.

show abstract

Assessment of Acute Kidney Injury using MRI

Selby,

Francis

2024

Magnetic Resonance Imaging

View full text Add to dashboard Cite

There has been growing interest in using quantitative magnetic resonance imaging (MRI) to describe and understand the pathophysiology of acute kidney injury (AKI). The ability to assess kidney blood flow, perfusion, oxygenation, and changes in tissue microstructure at repeated timepoints is hugely appealing, as this offers new possibilities to describe nature and severity of AKI, track the time‐course to recovery or progression to chronic kidney disease (CKD), and may ultimately provide a method to noninvasively assess response to new therapies. This could have significant clinical implications considering that AKI is common (affecting more than 13 million people globally every year), harmful (associated with short and long‐term morbidity and mortality), and currently lacks specific treatments. However, this is also a challenging area to study. After the kidney has been affected by an initial insult that leads to AKI, complex coexisting processes ensue, which may recover or can progress to CKD. There are various preclinical models of AKI (from which most of our current understanding derives), and these differ from each other but more importantly from clinical AKI. These aspects are fundamental to interpreting the results of the different AKI studies in which renal MRI has been used, which encompass different settings of AKI and a variety of MRI measures acquired at different timepoints. This review aims to provide a comprehensive description and interpretation of current studies (both preclinical and clinical) in which MRI has been used to assess AKI, and discuss future directions in the field.Level of Evidence1Technical EfficacyStage 3

show abstract

Noninvasive Assessment of Fibrosis Following Ischemia/Reperfusion Injury in Rodents Utilizing Na Magnetic Resonance Imaging

Cited by 5 publications

References 39 publications

Fibrosis imaging with multiparametric proton and sodium MRI in pig injury models

Fibrosis imaging with multiparametric proton and sodium MRI in pig injury models

Renal Hypoxic Reperfusion Injury-on-Chip Model for Studying Combinational Vitamin Therapy

Assessment of Acute Kidney Injury using MRI

Contact Info

Product

Resources

About