2. Pathophysiology of AKI

The etiology and pathophysiology of AKI are complex and multifactorial. AKI can be classified into three different types: pre-renal, intrinsic and post-renal. Pre-renal AKI is associated to a decreased renal blood flow by hypovolemia, impaired cardiac function, systemic vasodilation or increased vascular resistance, thus leading to a reduced glomerular filtration rate (GFR). Intrinsic AKI is related to direct injury or nephrotoxicity of parenchymal renal cells (glomeruli, tubules, interstitium and endothelial cells). Post-renal AKI is mainly related to a reduction in GFR as consequence of increased intra-tubular pressure by obstruction of urinary tract [7].

The underlying pathophysiological mechanisms in AKI include hemodynamic changes, direct tubular toxicity (mainly in proximal tubular cells), obstruction and dysfunction of microvascular vessels, congestion of tubular lumen, and renal inflammation [8]. These pathogenic mechanisms may co-exist in AKI-patients, thus complicating diagnosis and treatment.

AKI depends on the duration and severity of the insult [9]. When acute renal damage occurs, there is a first phase of tubular death, followed by a phase of cell regeneration and recovery of the renal function. Massive tubular cell death results from different causes, such as toxic insults, sepsis, oxidative stress, or ischemia, among others [10]. If the cause of kidney damage is prolonged over time, it can trigger more severe tubular cell death. During this process, tubular cells release chemokines, cytokines and other inflammatory stimuli that promote leucocyte infiltration in the kidney [11,12]. Inflammation is important for the regeneration and replacement of necrotic cells during AKI [13,14]. However, exacerbated or unresolved inflammation triggers the activation of fibrosis, a phenomenon that may be involved in progression to CKD after AKI [8].

3. Biomarkers in AKI

In the current clinical practice, AKI diagnosis is mostly based in determination of serum creatinine concentration [15]. However, the levels of this nitrogen-containing compound only increase when kidney injury is well stablished, restricting the possibility to detect early phases of AKI [16]. In addition, many factors influence serum creatinine concentration e.g., age, gender, diet, muscle mass, and hydration status), limiting its utility as an AKI biomarker. For these reasons, there is a great interest in the search of new AKI biomarkers for early detection, differential diagnosis and prognosis [17,18]. In this context, the most promising AKI biomarkers are listed in Table 1. These novel biomarkers are related with pathological processes involved in AKI development, such as inflammation, oxidative stress and renal cells death [19,20]. Furthermore, current studies support the potential value of circulating and urinary miRNAs as novel AKI biomarkers e.g., miR-21, miR-30a-e and miR-494, among others [18,21,22].