Pathologic Perspectives on Acute Tubular Injury Assessment in the Kidney Biopsy

The molecular mechanisms in acute tubular injury (ATI) are complex and enigmatic. Moreover, we currently lack validated tissue injury markers that can be integrated into the kidney biopsy analysis to guide nephrologists in their patient's management of AKI. Although recognizing the ATI lesion by light microscopy is fairly straightforward, the staging of tubular lesions in the context of clinical time course and etiologic mechanism currently is not adapted to the renal pathology practice. To the clinician, the exact time point when an ischemic or toxic injury has occurred often is not known and cannot be discerned from the review of the biopsy sample. Moreover, the assessment of the different types of organized necrosis as the underlying cell death mechanism, which can be targeted using specific inhibitors, has not yet reached clinical practice. The renal pathology laboratory is uniquely qualified to assess the time course and etiology of ATI using established analytic techniques, such as immunohistochemistry and electron microscopy. Recent advances in the understanding of pathophysiological mechanisms of ATI and the important role that certain types of tubular cell organelles play in different stages of the ATI lesions may allow differentiation of early versus late ATI. Furthermore, the determination of respective cell injury pathways may help to differentiate ischemic versus toxic etiology in a reliable fashion. In the future, such a kidney biopsy-based classification system of ATI could guide the nephrologist's management of patients in regard to treatment modality and drug choice.