Ischemic Renal Injury: Can Renal Anatomy and Associated Vascular Congestion Explain Why the Medulla and Not the Cortex Is Where the Trouble Starts?

Ray, Sarah; Mason, June; O’Connor, Paul

doi:10.1016/j.semnephrol.2019.10.002

Cited by 35 publications

(45 citation statements)

References 60 publications

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“…Although Ransick et al ., 16 also described the spatial diversity of collecting duct cells reflecting their development process, they have not discussed the functional differences involved in the ischaemic state or ammonium transport observed here. However, these spatially distinct characterizations are reasonable by considering the renal anatomy 37 and consistent with the previous knowledge, 38 thus the differentially expressed genes identified here aided the characterization of spatial positioning and may still harbour additional information. In comparison with humans, Lake et al ., 39 have also described the spatially distinct profiles of collecting duct by snRNA-seq with experimental zonation.…”

Section: Discussionsupporting

confidence: 87%

“…These results indicate the possibility that the medullary region resided in a more ischaemic condition, which has been considered based on the renal anatomy. 37 In addition, the GO term ‘transepithelial ammonium transport’ was listed with the highest P -value for the medullary sub-population. CDICa has a role to reabsorb ammonium excreted from TAL mainly through Na+-K+-ATPase whose efficiency is known to be affected by the ambient ammonium concentration.…”

Section: Resultsmentioning

confidence: 99%

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Spatial and single-cell transcriptome analysis reveals changes in gene expression in response to drug perturbation in rat kidney

et al. 2022

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The kidney is a complex organ that consists of various types of cells. It is occasionally difficult to resolve molecular alterations and possible perturbations that the kidney experiences due to drug-induced damage. In this study, we performed spatial and single-cell transcriptome analysis of rat kidneys and constructed a precise rat renal cell atlas with spatial information. Using the constructed catalog, we were able to characterize cells of several minor populations, such as macula densa or juxtaglomerular cells. Further inspection of the spatial gene expression data allowed us to identify the upregulation of genes involved in the renin regulating pathway in losartan-treated populations. Losartan is an angiotensin II receptor antagonist drug, and the observed upregulation of the renin pathway-related genes could be due to feedback from the hypotensive action of the drug. Furthermore, we found spatial heterogeneity in the response to losartan among the glomeruli. These results collectively indicate that integrated single-cell and spatial gene expression analysis is a powerful approach to reveal the detailed associations between the different cell types spanning the complicated renal compartments.

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Section: Discussionsupporting

confidence: 87%

Section: Resultsmentioning

confidence: 99%

Spatial and single-cell transcriptome analysis reveals changes in gene expression in response to drug perturbation in rat kidney

et al. 2022

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“…In this study, the CEUS-driven TIC parameters of the medulla were not reduced compared to those of cortex. This was unexpected, as the renal medulla receives lower blood flow than the cortex [29]. We speculate that a medullary blood congestion and consequent slowing of the blood flow occurred in our patients with AKI.…”

Section: Plos Onementioning

confidence: 67%

A pilot trial to evaluate the clinical usefulness of contrast-enhanced ultrasound in predicting renal outcomes in patients with acute kidney injury

Yoon

Kim

et al. 2020

PLoS ONE

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Objectives Contrast-enhanced ultrasound (CEUS) enables the assessment of real-time renal microcirculation. This study investigated CEUS-driven parameters as hemodynamic predictors for renal outcomes in patients with acute kidney injury (AKI). Methods Forty-eight patients who were diagnosed with AKI were prospectively enrolled and underwent CEUS at the occurrence of AKI. Parameters measured were the wash-in slope (WIS), time to peak intensity, peak intensity (PI), area under the time-intensity curve (AUC), mean transit time (MTT), time for full width at half maximum, and rise time (RT). The predictive performance of the CEUS-driven parameters for Kidney Disease Improving Global Outcomes (KDIGO) AKI stage, initiation of renal replacement therapy (RRT), AKI recovery, and chronic kidney disease (CKD) progression was assessed. Receiver operating characteristic (ROC) analysis was performed to evaluate the diagnostic performance of CEUS. Results Cortical RT (Odds ratio [OR] = 1.21) predicted the KDIGO stage 3 AKI. Cortical MTT (OR = 1.07) and RT (OR = 1.20) predicted the initiation of RRT. Cortical WIS (OR = 76.23) and medullary PI (OR = 1.25) predicted AKI recovery. Medullary PI (OR = 0.78) and AUC (OR = 1.00) predicted CKD progression. The areas under the ROC curves showed reasonable performance for predicting the initiation of RRT and AKI recovery. The sensitivity and specificity of the quantitative CEUS parameters were 60-83% and 62-77%, respectively, with an area under the curve of 0.69-0.75.

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“…The kidneys are among the highest perfused organs in the body and are extremely susceptible to changes in blood perfusion 1 . Renal ischemia-reperfusion injury (IRI) remains the leading cause of acute renal failure 2 , 3 and is associated with high morbidity and high mortality in hospitalized patients 4 .…”

Section: Introductionmentioning

confidence: 99%

An Effective Mouse Model of Unilateral Renal Ischemia-Reperfusion Injury

Godoy

Watson

Raspante

et al. 2021

JoVE

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Ischemia-reperfusion injury (IRI) is the leading cause of acute renal failure and is a significant contributor to delayed graft function. Animal models are the only available resources that mimic the complexities of the IRI-associated damage encountered in vivo. This paper describes an effective mouse model of unilateral renal IRI that delivers highly reproducible data. Ischemia is induced by occluding the right renal pedicle for 30 min followed by reperfusion. In addition to the surgical procedure, a sequential overview of the expected physiological and histopathological changes following renal IRI will be provided by comparing data from seven different reperfusion times (4 h, 8 h, 16 h, 1 day, 2 days, 4 days, and 7 days). Critical data for planning experiments ahead, such as mean surgical time, average anesthetic consumption, and body weight changes over time, will be shared. This work will help researchers implement a reliable renal IRI model and select the appropriate reperfusion time that aligns with their intended investigative goals.

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Ischemic Renal Injury: Can Renal Anatomy and Associated Vascular Congestion Explain Why the Medulla and Not the Cortex Is Where the Trouble Starts?

Cited by 35 publications

References 60 publications

Spatial and single-cell transcriptome analysis reveals changes in gene expression in response to drug perturbation in rat kidney

Spatial and single-cell transcriptome analysis reveals changes in gene expression in response to drug perturbation in rat kidney

A pilot trial to evaluate the clinical usefulness of contrast-enhanced ultrasound in predicting renal outcomes in patients with acute kidney injury

An Effective Mouse Model of Unilateral Renal Ischemia-Reperfusion Injury

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