Acute tubular injury - Pathophysiology and clinical implications
Acute tubular necrosis (ATN) is the most common cause of acute kidney injury (AKI) in hospitalized patients and is associated with a high morbidity and mortality. Incidence of ATN varies widely, depending on the criteria used to define an AKI, with up to 20% in patients hospitalized and 75% in patients admitted to the intensive care unit. Since the introduction of hemodialysis over four decades ago, the mortality rates from ATN in patients hospitalized and in the ICU have stayed the same, up to 30% and 80%, respectively [1]. One of the main reasons for the lack of significant progress in the area of ATN is its complex and multifaceted pathophysiology, involving changes in glomerular hemodynamics, tubular cell metabolism, changes in microvasculature of the kidney, activation of inflammatory pathways, innate/adaptive immune system response, and fibrogenesis. Additionally, the criteria used to define AKI - rise in serum creatinine and a fall in urine output - are late consequences to kidney injury that has already occurred to the most sensitive part of the proximal tubule. Thus, leading to delayed implementation of therapeutic strategies. In the last decade, tremendous progress has been made in basic and translational research in ATN, providing new insights into pathogenesis of ATN. Novel strategies that hold promises as potential therapeutics have emerged from these findings and are under various stages of investigation. In this chapter, we focus on the etiologies of ATN, innate protective mechanisms of the kidney against ATN, the underlying pathophysiological mechanisms, and morphological features of ATN. We discuss the clinical and laboratory markers of ATN, urine microscopy findings, and novel biomarkers of AKI. We then proceed to discuss evidence-based fluid management strategies for management of ATN, trials on the timing of kidney replacement therapy, and novel therapeutics under current investigations.
