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Recent advances in the pathogenetic mechanisms of sepsis-associated acute kidney injury

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Abstract

Sepsis is a serious medical condition that can lead to multi-organ failure and shock, and it is associated with increased mortality. Acute kidney injury (AKI) is a frequent complication of sepsis in critically ill patients, and often requires renal replacement therapy. The pathophysiology of AKI in sepsis has not yet been fully defined. In the past, classic theories were mainly focused on systemic hemodynamic derangements, underscoring the key role of whole kidney hypoperfusion due to reduced renal blood flow. However, a growing body of experimental and clinical evidence now shows that, at least in the early phase of sepsis-associated AKI, renal blood flow is normal, or even increased. This could suggest a dissociation between renal blood flow and kidney function. In addition, the scant data available from kidney biopsies in human studies do not support diffuse acute tubular necrosis as the predominant lesion. Instead, increasing importance is now attributed to kidney damage resulting from a complex interaction between immunologic mechanisms, inflammatory cascade activation, and deranged coagulation pathways, leading to microvascular dysfunction, endothelial damage, leukocyte/platelet activation with the formation of micro-thrombi, epithelial tubular cell injury and dysfunction. Moreover, the same processes, through maladaptive responses leading to fibrosis acting from the very beginning, may set the stage for progression to chronic kidney disease in survivors from sepsis-associated AKI episodes. The aim of this narrative review is to summarize and discuss the latest evidence on the pathophysiological mechanisms involved in septic AKI, based on the most recent data from the literature.

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Authors and Affiliations

  1. Acute and Chronic Renal Failure Unit, Department of Medicine and Surgery, University of Parma, Parma, Italy

    Filippo Fani, Giuseppe Regolisti, Marco Delsante & Enrico Fiaccadori

  2. Nephrology and Kidney Transplantation Unit, Department of Translational Medicine, University of Eastern Piedmont “A. Avogadro”, “Maggiore della Carità” University Hospital, Novara, Italy

    Vincenzo Cantaluppi

  3. Nephrology, Dialysis and Transplantation Unit, University of Bari, Bari, Italy

    Giuseppe Castellano & Loreto Gesualdo

  4. Anesthesiology and Intensive Care, University of Florence, Florence, Italy

    Gianluca Villa

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  1. Filippo Fani
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  2. Giuseppe Regolisti
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  4. Vincenzo Cantaluppi
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Correspondence to Enrico Fiaccadori.

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On behalf of all authors, the corresponding author states that there is no conflict of interest.

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This article does not contain any studies with animals or human participants performed by any of the authors.

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This paper was partially funded by the Progetto Giovani Ricercatori Bando 2011–2012, funding number Prot. 2010J4458Z.

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Fani, F., Regolisti, G., Delsante, M. et al. Recent advances in the pathogenetic mechanisms of sepsis-associated acute kidney injury. J Nephrol 31, 351–359 (2018). https://doi.org/10.1007/s40620-017-0452-4

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