Longitudinal changes in MRI markers in a reversible unilateral ureteral obstruction mouse model: Preliminary experience

Haque, Muhammad E; Franklin, Tammy; Bokhary, Ujala; Mathew, Liby; Hack, Bradley K.; Chang, Anthony; Puri, Tipu S.; Prasad, Pottumarthi V.

doi:10.1002/jmri.24235

Cited by 13 publications

(18 citation statements)

References 29 publications

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“…In this chronic injury condition, we speculate that the observed increase in AUC ratio reflects a shift in the relative metabolism from oxidative phosphorylation towards glycolysis, perhaps in response to increased cellular demand to meet the additional functional workload of resorption. This situation is probably exacerbated by the observed decrease in perfusion that could drive metabolism in the cortex further towards anaerobic glycolysis in response to inflammation and hypoxia . Inflammation and fibrotic injury, typical of chronic kidney injury, are supported by our histological results at day 14.…”

Section: Discussionsupporting

confidence: 67%

Evaluation of renal metabolic response to partial ureteral obstruction with hyperpolarized ¹³C MRI

et al. 2017

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Hyperpolarized C magnetic resonance imaging (MRI) may be used to non-invasively image the transport and chemical conversion of C-labeled compounds in vivo. In this study, we utilize hyperpolarized C MRI to evaluate metabolic markers in the kidneys longitudinally in a mouse model of partial unilateral ureteral obstruction (pUUO). Partial obstruction was surgically induced in the left ureter of nine adult mice, leaving the right ureter as a control. H and hyperpolarized [1- C]pyruvate MRI of the kidneys was performed 2 days prior to surgery (baseline) and at 3, 7 and 14 days post-surgery. Images were evaluated for changes in renal pelvis volume, pyruvate, lactate and the lactate to pyruvate ratio. After 14 days, mice were sacrificed and immunohistological staining of both kidneys for collagen fibrosis (picrosirius red) and macrophage infiltration (F4/80) was performed. Statistical analysis was performed using a linear mixed effects model. Significant kidney × time interaction effects were observed for both lactate and pyruvate, indicating that these markers changed differently between time points for the obstructed and unobstructed kidneys. Both kidneys showed an increase in the lactate to pyruvate ratio after obstruction, suggesting a shift towards glycolytic metabolism. These changes were accompanied by marked hydronephrosis, fibrosis and macrophage infiltration in the obstructed kidney, but not in the unobstructed kidney. Our results show that pUUO is associated with increased pyruvate to lactate metabolism in both kidneys, with injury and inflammation specific to the obstructed kidney. The work also demonstrates the feasibility of the use of hyperpolarized C MRI to study metabolism in renal disease.

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Section: Discussionsupporting

confidence: 67%

Evaluation of renal metabolic response to partial ureteral obstruction with hyperpolarized ¹³C MRI

et al. 2017

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“…Irreversible UUO allows the study of inflammation and tissue injury including the role of various leukocytes and mediators [1][2][3]10 whilst study of the R-UUO model enables researchers to explore the resolution of renal injury and associated tissue remodeling. 6,7,[11][12][13][14][15] Other investigators have used different methods to induce and reverse ureteric obstruction. In the first description of the R-UUO model, the left ureter of male C57BL/6 mice was obstructed with an atraumatic microvascular clamp via a flank incision.…”

Section: Discussionmentioning

confidence: 99%

“…This experimental approach was adopted by another research group who explored the use of MRI imaging to assess renal oxygenation. 15 It should also be noted that complete, reversible as well as variable ureteric obstruction has also been described in neonatal rats and mice 18,19 as a model of congenital ureteropelvic junction obstruction: an important congenital abnormality that leads to renal atrophy and loss of function.…”

Section: Discussionmentioning

confidence: 99%

A Murine Model of Irreversible and Reversible Unilateral Ureteric Obstruction

Hesketh

Vernon

Ding

et al. 2014

JoVE

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Obstruction of the kidney may affect native or transplanted kidneys and results in kidney injury and scarring. Presented here is a model of obstructive nephropathy induced by unilateral ureteric obstruction (UUO), which can either be irreversible (UUO) or reversible (R-UUO). In the irreversible UUO model, the ureter may be obstructed for variable periods of time in order to induce increasingly severe renal inflammation and interstitial fibrotic scarring. In the reversible R-UUO model the ureter is obstructed to induce hydronephrosis, tubular dilation and inflammation. After a suitable period of time the ureteric obstruction is then surgically reversed by anastomosis of the severed previously obstructed ureter to the bladder in order to allow complete decompression of the kidney and restoration of urinary flow to the bladder. The irreversible UUO model has been used to investigate various aspects of renal inflammation and scarring including the pathogenesis of disease and the testing of potential anti-inflammatory or anti-fibrotic therapies. The more challenging model of R-UUO has been used by some investigators and does offer significant research potential as it allows the study of inflammatory and immune processes and tissue remodeling in an injured and scarred kidney following the removal of the injurious stimulus. As a result, the R-UUO model offers investigators the opportunity to explore the resolution of kidney inflammation together with key aspects of tissue repair. These experimental models are of relevance to human disease as patients often present with obstruction of the renal tract that requires decompression and are commonly left with significant residual kidney impairment that has no current treatment options and may lead to eventual end stage kidney failure. Video LinkThe video component of this article can be found at

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“…Neugarten and Golestaneh In contrast, unilateral ureteral obstruction increased cortical oxygenation in a susceptible strain of mice. 77 In human subjects with partial unilateral ureteral obstruction due to renal stones and treated with nonsteroidal anti-inflammatory drugs, medullary and, to a lesser extent, cortical oxygenation were enhanced. 78 The contralateral nonobstructed kidney showed reduced medullary oxygenation.…”

Section: Obstructive Uropathymentioning

confidence: 99%

Blood oxygenation level-dependent MRI for assessment of renal oxygenation

Neugarten¹,

Golestaneh²

2014

IJNRD

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Blood oxygen level-dependent magnetic resonance imaging (BOLD MRI) has recently emerged as an important noninvasive technique to assess intrarenal oxygenation under physiologic and pathophysiologic conditions. Although this tool represents a major addition to our armamentarium of methodologies to investigate the role of hypoxia in the pathogenesis of acute kidney injury and progressive chronic kidney disease, numerous technical limitations confound interpretation of data derived from this approach. BOLD MRI has been utilized to assess intrarenal oxygenation in numerous experimental models of kidney disease and in human subjects with diabetic and nondiabetic chronic kidney disease, acute kidney injury, renal allograft rejection, contrast-associated nephropathy, and obstructive uropathy. However, confidence in conclusions based on data derived from BOLD MRI measurements will require continuing advances and technical refinements in the use of this technique.

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Longitudinal changes in MRI markers in a reversible unilateral ureteral obstruction mouse model: Preliminary experience

Abstract: These methods may prove valuable in better understanding the natural progression of kidney diseases and in evaluating novel interventions to limit progression.

Cited by 13 publications

References 29 publications

Evaluation of renal metabolic response to partial ureteral obstruction with hyperpolarized ¹³C MRI

Evaluation of renal metabolic response to partial ureteral obstruction with hyperpolarized ¹³C MRI

A Murine Model of Irreversible and Reversible Unilateral Ureteric Obstruction

Blood oxygenation level-dependent MRI for assessment of renal oxygenation

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Longitudinal changes in MRI markers in a reversible unilateral ureteral obstruction mouse model: Preliminary experience

Abstract: These methods may prove valuable in better understanding the natural progression of kidney diseases and in evaluating novel interventions to limit progression.

Cited by 13 publications

References 29 publications

Evaluation of renal metabolic response to partial ureteral obstruction with hyperpolarized 13C MRI

Evaluation of renal metabolic response to partial ureteral obstruction with hyperpolarized 13C MRI

A Murine Model of Irreversible and Reversible Unilateral Ureteric Obstruction

Blood oxygenation level-dependent MRI for assessment of renal oxygenation

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Evaluation of renal metabolic response to partial ureteral obstruction with hyperpolarized ¹³C MRI

Evaluation of renal metabolic response to partial ureteral obstruction with hyperpolarized ¹³C MRI