• Adnan Aslan, Marius C van den Heuvel, Coen A Stegeman, Eliane R Popa, Annemarie M Leliveld, Grietje Molema, Jan G Zijlstra, Jill Moser, and Matijs van Meurs.
• Department of Critical Care, University of Groningen, University Medical Center Groningen, P.O. 30.001, Hanzeplein 1, 9700 RB, Groningen, Netherlands.
• Crit Care. 2018 Dec 27; 22 (1): 359.

PurposeThe histopathology of sepsis-associated acute kidney injury (AKI) in critically ill patients remains an understudied area. Previous studies have identified that acute tubular necrosis (ATN) is not the only driver of sepsis-AKI. The focus of this study was to identify additional candidate processes that may drive sepsis-AKI. To do this we immunohistochemically characterized the histopathological and cellular features in various compartments of human septic kidneys.MethodsWe studied the following histopathological features: leukocyte subsets, fibroblast activation, cellular proliferation, apoptosis, and fibrin deposition in the glomerulus and the tubulointerstitium in human post-mortem kidney biopsy tissue. Biopsy tissue samples from 27 patients with sepsis-AKI were collected 33 min (range 24-150) after death in the ICU. The unaffected part of the kidneys from 12 patients undergoing total nephrectomy as a result of renal carcinoma served as controls.ResultsImmunohistochemical analysis revealed the presence of more neutrophils and macrophages in the glomeruli and more neutrophils in the tubulointerstitium of renal tissue from patients with sepsis compared to control renal tissue. Type II macrophages were predominant, with some macrophages expressing both type I and type II markers. In contrast, there were almost no macrophages found in control kidneys. The number of activated (myo)fibroblasts was low in the glomeruli of sepsis-AKI kidneys, yet this was not observed in the tubulointerstitium. Cell proliferation and fibrin deposition were more pronounced in the glomeruli and tubulointerstitium of sepsis-AKI than in control kidneys.ConclusionsThe extensive heterogeneity of observations among and within patients emphasizes the need to thoroughly characterize patients with sepsis-AKI in a large sample of renal biopsy tissue from patients with sepsis.

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