TUBULAR INJURY IN SEPSIS-ASSOCIATED ACUTE KIDNEY INJURY: HISTOPATHOLOGICAL FINDINGS AND PROPOSED MECHANISMS

Abstract. Background. Sepsis is the most common cause of acute kidney injury (AKI) in critically ill patients, and for decades the underlying lesion was assumed to be ischemic acute tubular necrosis (ATN). Aim. To summarize what human and experimental tissue studies show about tubular injury in septic AKI and to relate the findings to current pathogenetic models. Findings. A systematic review of six human studies (184 patients) found tubular necrosis in about one fifth of specimens. In 67 patients who died of sepsis, tubular injury was focal and most tubular cells appeared normal. Immediate post-mortem biopsies show patchy tubular changes (vacuolization, edema, epithelial flattening) together with leukocyte accumulation in peritubular capillaries and fibrin deposition. In experimental models, necrosis was found mainly where cardiac output or renal blood flow was reduced. These observations fit a model in which inflammation and peritubular microvascular dysfunction act on tubular cells that respond with an adaptive, mitochondria-driven reduction of function. Conclusion. The histological picture is mild relative to the loss of filtration, so renal function in sepsis cannot be inferred from the degree of tubular necrosis. Human tissue data remain scarce and heterogeneous. Keywords: sepsis; acute kidney injury; renal tubule; histopathology; acute tubular necrosis; microcirculation; mitochondria.