Abstract
Acute kidney injury (AKI) is a rapid onset of kidney failure or damage occurring over a brief period, typically within hours or a few days, leading to impaired glomerular filtration rate, elevated proteinuria, and disturbed electrolyte levels. Studies already pointed out AKI as one important risk factor for the development of chronic kidney disease (CKD). An estimated 30-70% of AKI cases progress to CKD or end-stage renal disease (ESRD), while only 12% recovered normal renal function. Recently, it was shown that AKI patients present a 9-fold higher risk of CKD progression. This progression occurs predominantly when metabolic disorders, such as diabetes, obesity, dysbiosis in gut microbiota, hypertension, and notably cardiovascular diseases (CVD) are present. In this sense, it is well known that renal disease impairs cardiac function, with half of all patients with CKD eventually dying from CVD, also named cardiorenal syndrome (CRS). Many mechanisms are being studied to understand the impact of renal injury on the heart; however, studies have yet to provide a comprehensive understanding of the mechanism underlying AKI-CKD progression in cardiac dysfunction. Thus, we hypothesize that AKI-CKD transition contributes to cardiovascular disease with subsequent pathophysiological changes on cardiovascular function and immune cell dysfunction. In this proposal, we aim to: i)Study the temporal course of cardiac structural, electrical, and molecular remodeling during the AKI-CKD transition, in a well-stablished AKI-CKD mouse model; ii) Characterize the local (cardiac) and systemic immune profile at different time points of AKI-CKD transition; iii) Employ multi-omics and bioinformatics to refine the understanding of mechanisms and identify potential therapeutic targets; iv) Propose biomarkers for the AKI-CKD transition, and transition-induced CVD. The experimental mouse model chosen is the induction of kidney injury by administration of adenine (0,3%) in the diet, for 90 days. To achieve this, we will comprehensively assess cardiac structural, electrical, and molecular changes throughout the AKI-CKD progression in vivo and clinically. A clinical prospective cohort study will be performed to identify potential biomarkers and biochemical molecules that help improve clinical procedures in patients during the AKI-CKD transition. (AU)
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