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  1. Article: Neural Network-Based Calculator for Rat Glomerular Filtration Rate.

    Pellicer-Valero, Óscar J / Massaro, Giampiero A / Casanova, Alfredo G / Paniagua-Sancho, María / Fuentes-Calvo, Isabel / Harvat, Mykola / Martín-Guerrero, José D / Martínez-Salgado, Carlos / López-Hernández, Francisco J

    Biomedicines

    2022  Volume 10, Issue 3

    Abstract: Glomerular filtration is a pivotal process of renal physiology, and its alterations are a central pathological event in acute kidney injury and chronic kidney disease. Creatinine clearance (ClCr), a standard method for glomerular filtration rate (GFR) ... ...

    Abstract Glomerular filtration is a pivotal process of renal physiology, and its alterations are a central pathological event in acute kidney injury and chronic kidney disease. Creatinine clearance (ClCr), a standard method for glomerular filtration rate (GFR) measurement, requires a long and tedious procedure of timed (usually 24 h) urine collection. We have developed a neural network (NN)-based calculator of rat ClCr from plasma creatinine (pCr) and body weight. For this purpose, matched pCr, weight, and ClCr trios from our historical records on male Wistar rats were used. When evaluated on the training (1165 trios), validation (389), and test sets (660), the model committed an average prediction error of 0.196, 0.178, and 0.203 mL/min and had a correlation coefficient of 0.863, 0.902, and 0.856, respectively. More importantly, for all datasets, the NN seemed especially effective at comparing ClCr among groups within individual experiments, providing results that were often more congruent than those measured experimentally. ACLARA, a friendly interface for this calculator, has been made publicly available to ease and expedite experimental procedures and to enhance animal welfare in alignment with the 3Rs principles by avoiding unnecessary stressing metabolic caging for individual urine collection.
    Language English
    Publishing date 2022-03-05
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2720867-9
    ISSN 2227-9059
    ISSN 2227-9059
    DOI 10.3390/biomedicines10030610
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: Biomarkers of persistent renal vulnerability after acute kidney injury recovery.

    Fuentes-Calvo, Isabel / Cuesta, Cristina / Sancho-Martínez, Sandra M / Hidalgo-Thomas, Omar A / Paniagua-Sancho, María / López-Hernández, Francisco J / Martínez-Salgado, Carlos

    Scientific reports

    2021  Volume 11, Issue 1, Page(s) 21183

    Abstract: Acute kidney injury (AKI) is a risk factor for new AKI episodes, chronic kidney disease, cardiovascular events and death, as renal repair may be deficient and maladaptive, and activate proinflammatory and profibrotic signals. AKI and AKI recovery ... ...

    Abstract Acute kidney injury (AKI) is a risk factor for new AKI episodes, chronic kidney disease, cardiovascular events and death, as renal repair may be deficient and maladaptive, and activate proinflammatory and profibrotic signals. AKI and AKI recovery definitions are based on changes in plasma creatinine, a parameter mostly associated to glomerular filtration, but largely uncoupled from renal tissue damage. The evolution of structural and functional repair has been incompletely described. We thus aimed at identifying subclinical sequelae persisting after recovery from cisplatin-induced AKI in rats. Compared to controls, after plasma creatinine recovery, post-AKI kidneys showed histological alterations and attendant susceptibility to new AKI episodes. Tubular function (assessed by the furosemide stress test, FST) also remained affected. Lingering parenchymal and functional subclinical alterations were paralleled by tapering, but abnormally high levels of urinary albumin, transferrin, insulin-like growth factor-binding protein 7 (IGFBP7), tissue inhibitor of metalloproteinases-2 (TIMP-2) and, especially, the [TIMP-2]*[IGFBP7] product. As subclinical surrogates of incomplete renal recovery, the FST and the urinary [TIMP-2]*[IGFBP7] product provide two potential diagnostic tools to monitor the sequelae and kidney vulnerability after the apparent recovery from AKI.
    MeSH term(s) Acute Kidney Injury/etiology ; Acute Kidney Injury/pathology ; Acute Kidney Injury/urine ; Animals ; Antineoplastic Agents/toxicity ; Biomarkers/urine ; Cisplatin/toxicity ; Insulin-Like Growth Factor Binding Proteins/urine ; Kidney/drug effects ; Kidney/pathology ; Kidney/physiopathology ; Male ; Rats ; Rats, Wistar ; Tissue Inhibitor of Metalloproteinase-2/urine
    Chemical Substances Antineoplastic Agents ; Biomarkers ; Insulin-Like Growth Factor Binding Proteins ; insulin-like growth factor binding protein-related protein 1 ; Tissue Inhibitor of Metalloproteinase-2 (127497-59-0) ; Cisplatin (Q20Q21Q62J)
    Language English
    Publishing date 2021-10-27
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2615211-3
    ISSN 2045-2322 ; 2045-2322
    ISSN (online) 2045-2322
    ISSN 2045-2322
    DOI 10.1038/s41598-021-00710-y
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article ; Online: Urinary Plasminogen Activator Inhibitor-1: A Biomarker of Acute Tubular Injury.

    Paniagua-Sancho, María / Quiros, Yaremi / Casanova, Alfredo G / Blanco-Gozalo, Víctor / Agüeros-Blanco, Consuelo / Benito-Hernández, Adalberto / Ramos-Barron, María A / Gómez-Alamillo, Carlos / Arias, Manuel / Sancho-Martínez, Sandra M / López-Hernández, Francisco J

    American journal of nephrology

    2021  Volume 52, Issue 9, Page(s) 714–724

    Abstract: Introduction: Acute kidney injury (AKI) is a threatening, multiaetiological syndrome encompassing a variety of forms and damage patterns. AKI lacks sufficiently specific diagnostic tools to evaluate the distinct combination of pathophysiological events ... ...

    Abstract Introduction: Acute kidney injury (AKI) is a threatening, multiaetiological syndrome encompassing a variety of forms and damage patterns. AKI lacks sufficiently specific diagnostic tools to evaluate the distinct combination of pathophysiological events underlying each case, which limits personalized and optimized handling. Therefore, a pathophysiological diagnosis based on new urinary biomarkers is sought for practical (readiness and noninvasiveness) and conceptual reasons, as the urine is a direct product of the kidneys. However, biomarkers found in the urine may also have extrarenal origin, thus conveying pathophysiological information from other organs or tissues. Urinary plasminogen activator inhibitor-1 (PAI-1) has been associated to AKI, although its origin and traffic to the urine are not known.
    Methods: Herein, we studied the blood or renal origin of urinary PAI-1 (uPAI-1) in experimental AKI in Wistar rats, by means of the in situ renal perfusion method. For this purpose, urine was collected while the kidneys of rats with AKI showing increased uPAI-1 excretion, and controls, were in situ perfused with a saline solution.
    Results: Our results show that during perfusion, PAI-1 remained in the urine of AKI rats, suggesting that renal cells shed this protein directly to the urine. PAI-1 is also significantly increased in the urine of AKI patients. Its low correlation with other urinary markers such as NGAL or NAG suggests that PAI-1 provides complementary and distinct phenotypical information.
    Conclusion: In conclusion, uPAI-1 is a biomarker produced by damaged kidneys following AKI, whose precise pathophysiological meaning in AKI needs to be further investigated.
    MeSH term(s) Acute Kidney Injury/urine ; Adult ; Aged ; Animals ; Biomarkers/urine ; Female ; Humans ; Kidney Tubules ; Male ; Middle Aged ; Plasminogen Activator Inhibitor 1/urine ; Rats ; Rats, Wistar
    Chemical Substances Biomarkers ; Plasminogen Activator Inhibitor 1 ; SERPINE1 protein, human
    Language English
    Publishing date 2021-09-08
    Publishing country Switzerland
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 604540-6
    ISSN 1421-9670 ; 0250-8095
    ISSN (online) 1421-9670
    ISSN 0250-8095
    DOI 10.1159/000518455
    Database MEDical Literature Analysis and Retrieval System OnLINE

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