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.
Highlights
Summarizing, the histological analysis shows that there are remarkable structural alterations in the renal tissue after an episode of cisplatin-induced acute kidney injury (AKI), which persist when the renal function parameters return to baseline values
Our study shows that after the apparent clinical recovery from an AKI episode, the kidney’s structure remains affected, at least for two weeks in the rat
These lingering structural alterations coincide with an increased subclinical predisposition to new renal damage, and with an altered furosemide stress test (FST) response and an increased urinary excretion of tubular injury biomarkers, including transferrin, IGFBP7 and tissue metalloproteinase 2 (TIMP-2)
Summary
alterations[3,11,12,13]. The limitations of pCr to assess renal recovery are reinforced by epidemiological data showing an association between AKI and progression to CKD even when pCr has returned to basal levels[14,15]. During the last two decades, new biomarkers have been identified that detect kidney damage independently of pCr, even in subclinical circumstances. Of special interest is the stage 0A of AKD in which pCr has returned to basal levels and there is no evidence of injury or functional loss, but patients still retain a risk of further kidney damage[2]. The objective of this study was to characterize the evolution of renal repair and potential functional and structural sequelae after pCr had returned to baseline levels following an episode of AKI in rats. We aimed at evaluating whether and for how long animals retain enhanced sensibility to AKI (i.e. higher risk of AKI) after pCr recovery and, if so, whether such a condition may be detected by known biomarkers of subclinical renal damage
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