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Metabolic reprogramming associated with progression of renal ischemia reperfusion injury assessed with hyperpolarized [1-¹³C]pyruvate.

ABSTRACT: Acute kidney injury is a major clinical challenge affecting as many as 1 percent of all hospitalized patients. Currently it is not possible to accurately stratify and predict the outcome of the individual patient. Increasing evidence supports metabolic reprogramming as a potential target for new biomarkers. Hyperpolarized [1-¹³C]pyruvate imaging is a promising new tool for evaluating the metabolic status directly in the kidneys. We here investigate the prognostic potential of hyperpolarized [1-¹³C]pyruvate in the setting of acute kidney injury in a rodent model of ischemia reperfusion. A significant correlation was found between the intra-renal metabolic profile 24?hours after reperfusion and 7 days after injury induction, as well as a correlation with the conventional plasma creatinine biomarker of renal function and markers of renal injury. This leads to a possible outcome prediction of renal function and injury development from a metabolic profile measured in vivo. The results support human translation of this new technology to renal patients as all experiements have been performed using clinical MRI equipment.

SUBMITTER: Nielsen PM

PROVIDER: S-EPMC7265284 | biostudies-literature | 2020 Jun

REPOSITORIES: biostudies-literature

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Metabolic reprogramming associated with progression of renal ischemia reperfusion injury assessed with hyperpolarized [1-<sup>13</sup>C]pyruvate.

Nielsen Per Mose PM Qi Haiyun H Bertelsen Lotte Bonde LB Laustsen Christoffer C

Scientific reports 20200602 1

Acute kidney injury is a major clinical challenge affecting as many as 1 percent of all hospitalized patients. Currently it is not possible to accurately stratify and predict the outcome of the individual patient. Increasing evidence supports metabolic reprogramming as a potential target for new biomarkers. Hyperpolarized [1-<sup>13</sup>C]pyruvate imaging is a promising new tool for evaluating the metabolic status directly in the kidneys. We here investigate the prognostic potential of hyperpol ...[more]

PMID: 32488151

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Project description:BackgroundOptimal treatment selection for localized renal tumors is challenging because of their variable biologic behavior and limitations in the preoperative assessment of tumor aggressiveness. The authors investigated the emerging hyperpolarized (HP) 13 C magnetic resonance imaging (MRI) technique to noninvasively assess tumor lactate production, which is strongly associated with tumor aggressiveness.MethodsEleven patients with renal tumors underwent HP 13 C pyruvate MRI before surgical resection. Tumor 13 C pyruvate and 13 C lactate images were acquired dynamically. Five patients underwent 2 scans on the same day to assess the intrapatient reproducibility of HP 13 C pyruvate MRI. Tumor metabolic data were compared with histopathology findings.ResultsEight patients had tumors with a sufficient metabolite signal-to-noise ratio for analysis; an insufficient tumor signal-to-noise ratio was noted in 2 patients, likely caused by poor tumor perfusion and, in 1 patient, because of technical errors. Of the 8 patients, 3 had high-grade clear cell renal cell carcinoma (ccRCC), 3 had low-grade ccRCC, and 2 had chromophobe RCC. There was a trend toward a higher lactate-to-pyruvate ratio in high-grade ccRCCs compared with low-grade ccRCCs. Both chromophobe RCCs had relatively high lactate-to-pyruvate ratios. Good reproducibility was noted across the 5 patients who underwent 2 HP 13 C pyruvate MRI scans on the same day.ConclusionsThe current results demonstrate the feasibility of HP 13 C pyruvate MRI for investigating the metabolic phenotype of localized renal tumors. The initial data indicate good reproducibility of metabolite measurements. In addition, the metabolic data indicate a trend toward differentiating low-grade and high-grade ccRCCs, the most common subtype of renal cancer.Lay summaryRenal tumors are frequently discovered incidentally because of the increased use of medical imaging, but it is challenging to identify which aggressive tumors should be treated. A new metabolic imaging technique was applied to noninvasively predict renal tumor aggressiveness. The imaging results were compared with tumor samples taken during surgery and showed a trend toward differentiating between low-grade and high-grade clear cell renal cell carcinomas, which are the most common type of renal cancers.

Project description:The detection and treatment monitoring of inflammatory states remain challenging in part due to the multifactorial mechanisms of immune activation and spectrum of clinical manifestations. Currently, diagnostic strategies tend to be subjective and limited quantitative tools exist to monitor optimal treatment strategies. Pro-inflammatory M1 polarized macrophages exhibit a distinct metabolic glycolytic phenotype compared to the continuum of M2 polarization states. In the present study, the distinct metabolic phenotypes of resting and activated macrophages were successfully characterized and quantified using hyperpolarized carbon-13 (13C) labeled pyruvate and its metabolic products, i.e. lactate, as a biomarker of resting, disease and treated states. Methods: Mouse macrophage J774A.1 cells were used as a model system in an NMR compatible bioreactor to facilitate dynamic hyperpolarized 13C measurements. The glycolytic metabolism of the cells in the quiescent or resting state were compared with macrophages stimulated by lipopolysaccharide, a classical M1 activator using hyperpolarized 13C labeled pyruvate. Additionally, the activated macrophages were also treated with a non-steroidal anti-inflammatory drug to assess the changes in hyperpolarized lactate signal. The hyperpolarized lactate signals were then correlated using biochemical and molecular assays. Results: We first validated our model system of inflammatory cells by the hallmarks of M1 polarization using steady state metabolic profiling with high resolution NMR in conjunction with nitric oxide Greiss assay, enzyme activity, and mRNA expression. Subsequently, we clearly showed that the cutting edge technology of hyperpolarized 13C NMR can be used to detect elevated lactate levels in M1 polarized macrophages in comparison to control and non-steroidal anti-inflammatory drug treated M2 states. Conclusion: Hyperpolarized 13C lactate has the potential to serve as a biomarker to non-invasively detect and quantify pro-inflammatory state of immune regulatory cells and its response to therapy.

Dataset Information

Metabolic reprogramming associated with progression of renal ischemia reperfusion injury assessed with hyperpolarized [1-¹³C]pyruvate.

Publications

Metabolic reprogramming associated with progression of renal ischemia reperfusion injury assessed with hyperpolarized [1-<sup>13</sup>C]pyruvate.

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Dataset Information

Metabolic reprogramming associated with progression of renal ischemia reperfusion injury assessed with hyperpolarized [1-13C]pyruvate.

Publications

Metabolic reprogramming associated with progression of renal ischemia reperfusion injury assessed with hyperpolarized [1-<sup>13</sup>C]pyruvate.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets

Metabolic reprogramming associated with progression of renal ischemia reperfusion injury assessed with hyperpolarized [1-¹³C]pyruvate.