Abstract
The outcome of patients with acute myocardial infarction (AMI) has dramatically improved over recent decades, thanks to early detection and prompt interventions to restore coronary blood flow. In contrast, the prognosis of patients with hypoxic acute kidney injury (AKI) remained unchanged over the years. Delayed diagnosis of AKI is a major reason for this discrepancy, reflecting the lack of symptoms and diagnostic tools indicating at real time altered renal microcirculation, oxygenation, functional derangement and tissue injury. New tools addressing these deficiencies, such as biomarkers of tissue damage are yet far less distinctive than myocardial biomarkers and advanced functional renal imaging technologies are non-available in the clinical practice. Moreover, our understanding of pathogenic mechanisms likely suffers from conceptual errors, generated by the extensive use of the wrong animal model, namely warm ischemia and reperfusion. This model parallels mechanistically type I AMI, which properly represents the rare conditions leading to renal infarcts, whereas common scenarios leading to hypoxic AKI parallel physiologically type II AMI, with tissue hypoxic damage generated by altered oxygen supply/demand equilibrium. Better understanding the pathogenesis of hypoxic AKI and its management requires a more extensive use of models of type II-rather than type I hypoxic AKI.
Highlights
Despite the high incidence of acute kidney injury (AKI) and its association with an alarming increase in morbidity and mortality, the therapeutic approaches for AKI are still disappointing and rely mainly on supportive measures [1,2]. This deficiency stems from the poor understanding of the pathogenesis of AKI and due to the delayed detection of AKI, as this syndrome is often asymptomatic during its early stages. Concerning the latter, the diagnosis of AKI is challenging since it mainly relies on serum creatinine (Scr), which suffers from major limitations as reliable biomarker for measurement of kidney function [3]
The great development in molecular biology during recent decades has led to a major advance in the search for novel biomarkers for early detection of AKI [45], as evident by the discovery of several key biomarkers of myocardial injury with various specificity and sensitivity, including neutrophil gelatinase-associated lipocalin (NGAL), kidney injury molecule-1 (KIM-1), liver-type fatty acid-binding protein (L-FABP), netrin-1 and IL18 [45,46,47,48]
It is about time to try and correlate the extent of tubular injury at different segments with their corresponding cell-specific biomarkers in order to validate the sensitivity and specificity of these biomarkers in animal models of acute- and acute on chronic AKI. Such studies may improve our understanding of human AKI and may direct us in the generation of appropriate panels of biomarkers to appropriate for varied clinical conditions, for instance biomarkers for proximal tubular injury for suspected aminoglycoside nephrotoxicity, or a panel of distal tubular biomarkers following near drowning, or in AKI following the administration of SGLT2 antagonists
Summary
Despite the high incidence of acute kidney injury (AKI) and its association with an alarming increase in morbidity and mortality, the therapeutic approaches for AKI are still disappointing and rely mainly on supportive measures [1,2]. This deficiency stems from the poor understanding of the pathogenesis of AKI and due to the delayed detection of AKI, as this syndrome is often asymptomatic during its early stages. Increased workload in the presence of coronary stenosis (hypotension, anemia, tachycardia etc.)
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