@article{0154795b-dce9-4c4d-9010-2ba9c0b3066f,
  abstract     = {{<p>Background: Severe COVID-19 frequently involves multi-organ dysfunction, including acute kidney injury (AKI), which affects up to 85% of critically ill patients. While both direct viral infection and systemic effects are implicated, the role of renal microthrombosis remains poorly defined in COVID-19 and AKI. Angiopoietin-2, a pro-inflammatory cytokine, and cleaved thrombomodulin is elevated in plasma in severe COVID-19 and has been linked to endothelial dysfunction and hypercoagulability. We hypothesize that renal microthrombi can contribute to decreased kidney function in critically ill COVID-19 patients. Methods: We performed histopathological and molecular analyses of postmortem kidney tissue from seven critically ill COVID-19 patients. Control tissue was obtained from nephrectomy specimens (n = 6) and postmortem tissue (n = 7). We assessed microthrombi, tubular necrosis, glomerulosclerosis, fibrosis, and expression of angiopoietin-2 and thrombomodulin. Immunofluorescence and SARS-CoV-2 nucleoprotein staining were used alongside clinical data. Results: AKI was observed in six of seven COVID-19 patients. Compared to controls, COVID-19 kidneys showed a significant reduction in tubular nuclear area (P &lt; 0.0003), presence of viral antigen in tubular epithelium, and marked glomerular and peritubular microthrombi (15.2 vs. 1.3 thrombi/mm²; P &lt; 0.0001). THBD expression was significantly reduced bith peritubular capillaries and glomeruli in COVID-19 kidneys. Glomerulosclerosis, glomerular area, and tubulointerstitial fibrosis were variable in both control and COVID-19 patients with no significant differences. Conclusions: This study identifies widespread renal microthrombi, tubular necrosis, and reduced THBD expression in COVID-19 patients with AKI, supporting a role for endothelial dysfunction and microvascular thrombosis in COVID-19-associated renal injury. The data implicates the disruption of endothelial anticoagulant signaling through thrombomodulin as a contributing mechanism.</p>}},
  author       = {{Bekhet, Matilda and Marks-Hultström, Amanda and Korkut, Gül Gizem and Schwarz, Angelina and Patrakka, Jaakko and Englund, Elisabet and Jeansson, Marie}},
  issn         = {{1471-2369}},
  keywords     = {{Acute kidney injury; Angiopoietin-2; COVID-19; Thrombomodulin; Thrombosis}},
  language     = {{eng}},
  number       = {{1}},
  publisher    = {{BioMed Central (BMC)}},
  series       = {{BMC Nephrology}},
  title        = {{Renal microthrombosis and thrombomodulin deficiency in COVID-19–associated acute kidney injury}},
  url          = {{http://dx.doi.org/10.1186/s12882-026-04788-2}},
  doi          = {{10.1186/s12882-026-04788-2}},
  volume       = {{27}},
  year         = {{2026}},
}