Role of abnormal energy metabolism in the progression of chronic kidney disease and drug intervention

Liu, Xuyan; Du, Huasheng; Sun, Yan; Shao, Leping

doi:10.1080/0886022x.2022.2072743

Cited by 24 publications

(16 citation statements)

References 168 publications

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“…ATP and ADP signals were acquired via live fluorescence microscopy, and the ATP/ADP ratios were computationally visualized based on the signal intensities of ATP and ADP (Figure 6B). The ATP/ADP ratios appeared to be higher in nephron-like structures than the surrounding stromal cells, consistent with high ATP production in epithelial cells (Liu et al, 2022) (Figure 6A).…”

Section: Generation Of Atp Reporter Organoids With a Biosensor Percev...supporting

confidence: 65%

ATP/ADP biosensor organoids for drug nephrotoxicity assessment

Susa

Kobayashi

Galichon

et al. 2023

Front. Cell Dev. Biol.

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Drug nephrotoxicity is a common healthcare problem in hospitalized patients and a major limitation during drug development. Multi-segmented kidney organoids derived from human pluripotent stem cells may complement traditional cell culture and animal experiments for nephrotoxicity assessment. Here we evaluate the capability of kidney organoids to investigate drug toxicity in vitro. Kidney organoids express renal drug transporters, OAT1, OAT3, and OCT2, while a human proximal tubular cell line shows the absence of OAT1 and OAT3. Tenofovir and aristolochic acid (AA) induce proximal tubular injury in organoids which is ameliorated by an OAT inhibitor, probenecid, without damage to podocytes. Similarly, cisplatin causes proximal tubular damage that can be relieved by an OCT inhibitor, cimetidine, collectively suggesting the presence of functional OATs and OCTs in organoid proximal tubules. Puromycin aminonucleoside (PAN) induced segment-specific injury in glomerular podocytes in kidney organoids in the absence of tubular injury. Reporter organoids were generated with an ATP/ADP biosensor, which may be applicable to high-throughput screening in the future. In conclusion, the kidney organoid is a useful tool for toxicity assessment in the multicellular context and may contribute to nephrotoxicity assessment during drug development.

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Section: Generation Of Atp Reporter Organoids With a Biosensor Percev...supporting

confidence: 65%

ATP/ADP biosensor organoids for drug nephrotoxicity assessment

Susa

Kobayashi

Galichon

et al. 2023

Front. Cell Dev. Biol.

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“…Similarly, when compared to the control, the urine of stage 1 CKD patients with HUA still contained significantly lower β-hydroxybutyric acid levels ( p = 0.000, see Supplementary Table S2 ). Previous studies have shown that CKD patients have disordered energy metabolism ( Liu et al, 2022 ), with low levels of β-hydroxybutyric acid ( Galindo et al, 2021 ). Under physiological conditions, renal proximal tubules are mainly powered by fatty acid oxidation ( Forbes and Thorburn, 2018 ).…”

Section: Discussionmentioning

confidence: 99%

“…For such patients, it has been speculated that there could be a specific energy supply and signal transduction processes that cause CKD. Thus, it was hypothesized that for HUA patients, there is a need to maintain a constant internal environment by relying on uric acid oxidation during the early stages of the disease ( Liu et al, 2022 ). However, with disease progression, it becomes increasingly difficult for HUA patients to maintain the internal environment in a stable state.…”

Section: Introductionmentioning

confidence: 99%

Rapid identification of early renal damage in asymptomatic hyperuricemia patients based on urine Raman spectroscopy and bioinformatics analysis

Kong

Liang

et al. 2023

Front. Chem.

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Objective: The issue of when to start treatment in patients with hyperuricemia (HUA) without gout and chronic kidney disease (CKD) is both important and controversial. In this study, Raman spectroscopy (RS) was used to analyze urine samples, and key genes expressed differentially CKD were identified using bioinformatics. The biological functions and regulatory pathways of these key genes were preliminarily analyzed, and the relationship between them as well as the heterogeneity of the urine components of HUA was evaluated. This study provides new ideas for the rapid evaluation of renal function in patients with HUA and CKD, while providing an important reference for the new treatment strategy of HUA disease.Methods: A physically examined population in 2021 was recruited as the research subjects. There were 10 cases with normal blood uric acid level and 31 cases with asymptomatic HUA diagnosis. The general clinical data were collected and the urine samples were analyzed by Raman spectroscopy. An identification model was also established by using the multidimensional multivariate method of orthogonal partial least squares discriminant analysis (OPLS-DA) model for statistical analysis of the data, key genes associated with CKD were identified using the Gene Expression Omnibus (GEO) database, and key biological pathways associated with renal function damage in CKD patients with HUA were analyzed.Results: The Raman spectra showed significant differences in the levels of uric acid (640 cm−1), urea, creatinine (1,608, 1,706 cm−1), proteins/amino acids (642, 828, 1,556, 1,585, 1,587, 1,596, 1,603, 1,615 cm−1), and ketone body (1,643 cm−1) (p < 0.05). The top 10 differentially expressed genes (DEGs) associated with CKD (ALB, MYC, IL10, FOS, TOP2A, PLG, REN, FGA, CCNA2, and BUB1) were identified. Compared with the differential peak positions analyzed by the OPLS-DA model, it was found that the peak positions of glutathione, tryptophan and tyrosine may be important markers for the diagnosis and progression of CKD.Conclusion: The progression of CKD was related to the expression of the ALB, MYC, IL10, PLG, REN, and FGA genes. Patients with HUA may have abnormalities in glutathione, tryptophan, tyrosine, and energy metabolism. The application of Raman spectroscopy to analyze urine samples and interpret the heterogeneity of the internal environment of asymptomatic HUA patients can be combined with the OPLS-DA model to mine the massive clinical and biochemical examination information on HUA patients. The results can also provide a reference for identifying the right time for intervention for uric acid as well as assist the early detection of changes in the internal environment of the body. Finally, this approach provides a useful technical supplement for exploring a low-cost, rapid evaluation and improving the timeliness of screening. Precise intervention of abnormal signal levels of internal environment and energy metabolism may be a potential way to delay renal injury in patients with HUA.

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“…The main function of mitochondria, the most susceptible organelles to oxidative damage, is to generate large amounts of ATP via OXPHOS, thus ensuring the operation of normal physiological kidney function. 75 , 76 Mitochondrial dysfunction caused by hyperglycemia plays a role in promoting the development of DN. Altered energy metabolism or altered mitochondrial dysfunction in DN can lead to renal dysfunction and eventually CKD.…”

Section: Research Progress In Nanoplatforms In the Treatment Of Dnmentioning

confidence: 99%

“…Altered energy metabolism or altered mitochondrial dysfunction in DN can lead to renal dysfunction and eventually CKD. 75 A dynamic balance between oxidative eustress and distress (ie, cellular redox homeostasis) is the basis for proper mitochondrial function. Biocompatible transition metal oxide NPs are highly sought after for their wide range of remarkable properties and applications, particularly their electron-donating and accepting activity, which is considered the best type of NP to maintain the balance of the redox potential of cellular mitochondria.…”

Section: Research Progress In Nanoplatforms In the Treatment Of Dnmentioning

confidence: 99%

Current Strategies and Potential Prospects for Nanoparticle-Mediated Treatment of Diabetic Nephropathy

Liu¹,

Wu²,

Gao³

et al. 2022

DMSO

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Diabetic nephropathy (DN), a severe microvascular complication of diabetes mellitus (DM), is the most common form of chronic kidney disease (CKD) and a leading cause of renal failure in end-stage renal disease. No currently available treatment can achieve complete cure. Traditional treatments have many limitations, such as painful subcutaneous insulin injections, nephrotoxicity and hepatotoxicity with oral medication, and poor patient compliance with continual medication intake. Given the known drawbacks, recent research has suggested that nanoparticle-based drug delivery platforms as therapeutics may provide a promising strategy for treating debilitating diseases such as DN in the future. This administration method provides multiple advantages, such as delivering the loaded drug to the precise target of action and enabling early prevention of CKD progression. This article discusses the development of the main currently used nanoplatforms, such as liposomes, polymeric NPs, and inorganic NPs, as well as the prospects and drawbacks of nanoplatform application in the treatment of CKD.

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Role of abnormal energy metabolism in the progression of chronic kidney disease and drug intervention

Cited by 24 publications

References 168 publications

ATP/ADP biosensor organoids for drug nephrotoxicity assessment

ATP/ADP biosensor organoids for drug nephrotoxicity assessment

Rapid identification of early renal damage in asymptomatic hyperuricemia patients based on urine Raman spectroscopy and bioinformatics analysis

Current Strategies and Potential Prospects for Nanoparticle-Mediated Treatment of Diabetic Nephropathy

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