Biomarkers of persistent renal vulnerability after acute kidney injury recovery

• Published in: Scientific reports 2021-10, Vol.11 (1), p.21183-21183, Article 21183
• Main Authors: Fuentes-Calvo, Isabel, Cuesta, Cristina, Sancho-Martínez, Sandra M., Hidalgo-Thomas, Omar A., Paniagua-Sancho, María, López-Hernández, Francisco J., Martínez-Salgado, Carlos
• Format: Article
• Language: English
• Subjects: 631/443; 631/443/272; 692/4022; 692/53; Acute Kidney Injury - etiology; Acute Kidney Injury - pathology; Acute Kidney Injury - urine; Animals; Antineoplastic Agents - toxicity; Biomarkers - urine; Cisplatin; Cisplatin - toxicity; Complications; Creatinine; Furosemide; Humanities and Social Sciences; Inflammation; Insulin; Insulin-Like Growth Factor Binding Proteins - urine; Kidney - drug effects; Kidney - pathology; Kidney - physiopathology; Kidney diseases; Kidneys; Male; multidisciplinary; Rats; Rats, Wistar; Recovery (Medical); Risk factors; Science; Science (multidisciplinary); Structure-function relationships; Tissue inhibitor of metalloproteinase 2; Tissue Inhibitor of Metalloproteinase-2 - urine; Transferrins
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/s41598-021-00710-y

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.