Urinary TCP1-eta: A Cortical Damage Marker for the Pathophysiological Diagnosis and Prognosis of Acute Kidney Injury
| Autor: | Isabel Fuentes-Calvo, C. Gómez-Alamillo, Laura Prieto-García, Fernando Sánchez-Juanes, Sandra M. Sancho-Martínez, José Manuel González-Buitrago, M.A. Ramos-Barron, Francisco J. López-Hernández, Ana I. Morales, Víctor Blanco-Gozalo, José M. López-Novoa, Miguel Fontecha-Barriuso, Carlos Martínez-Salgado, Manuel Arias |
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| Rok vydání: | 2019 |
| Předmět: |
Male
0301 basic medicine medicine.medical_specialty Urinary system 030232 urology & nephrology Urology Apoptosis Urine Urinalysis urologic and male genital diseases Toxicology Cell Line 03 medical and health sciences 0302 clinical medicine Predictive Value of Tests medicine Animals Rats Wistar Acute tubular necrosis Kidney urogenital system business.industry Acute kidney injury Acute Kidney Injury Prognosis medicine.disease Pathophysiology Disease Models Animal Renal Elimination Early Diagnosis Kidney Tubules 030104 developmental biology medicine.anatomical_structure Case-Control Studies Etiology Biomarker (medicine) business Biomarkers Chaperonin Containing TCP-1 |
| Zdroj: | Toxicological Sciences. 174:3-15 |
| ISSN: | 1096-0929 1096-6080 |
| DOI: | 10.1093/toxsci/kfz242 |
| Popis: | Acute kidney injury (AKI) is a serious syndrome with increasing incidence and health consequences, and high mortality rate among critically ill patients. Acute kidney injury lacks a unified definition, has ambiguous semantic boundaries, and relies on defective diagnosis. This, in part, is due to the absence of biomarkers substratifying AKI patients into pathophysiological categories based on which prognosis can be assigned and clinical treatment differentiated. For instance, AKI involving acute tubular necrosis (ATN) is expected to have a worse prognosis than prerenal, purely hemodynamic AKI. However, no biomarker has been unambiguously associated with tubular cell death or is able to provide etiological distinction. We used a cell-based system to identify TCP1-eta in the culture medium as a noninvasive marker of damaged renal tubular cells. In rat models of AKI, TCP1-eta was increased in the urine co-relating with renal cortical tubule damage. When kidneys from ATN rats were perfused in situ with Krebs-dextran solution, a portion of the urinary TCP1-eta protein content excreted into urine disappeared, and another portion remained within the urine. These results indicated that TCP1-eta was secreted by tubule cells and was not fully reabsorbed by the damaged tubules, both effects contributing to the increased urinary excretion. Urinary TCP1-eta is found in many etiologically heterogeneous AKI patients, and is statistically higher in patients partially recovered from severe AKI. In conclusion, urinary TCP1-eta poses a potential, substratifying biomarker of renal cortical damage associated with bad prognosis. |
| Databáze: | OpenAIRE |
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