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COVID-19-associated acute renal failure in critically ill patients correlates with microthrombosis and renal loss of thrombomodulin (preprint)
medrxiv; 2024.
Preprint
en Inglés
| medRxiv | ID: ppzbmed-10.1101.2024.03.18.24304157
ABSTRACT
Critically ill COVID-19 patients have a high degree of acute kidney injury which develops in up to 85% of patients. We have previously shown that circulating levels of angiopoietin-2 increased in critically ill COVID-19 patients correlated to kidney injury, coagulopathy, and mortality. Furthermore, our experiments showed a causal effect on coagulopathy from angiopoietin-2 binding and inhibition of thrombomodulin mediated anticoagulation. In the current study we hypothesize that renal microthrombi may be a mechanism for reduced renal function in critically ill COVID-19 patients, and that local dysregulation of thrombomodulin and angiopoietin-2 may be involved. To investigate our hypothesis, we utilized postmortem kidney tissue from seven COVID-19 patients treated at the intensive care unit. We evaluated kidney function, thrombosis, tubular injury, fibrosis, glomerulosclerosis, glomerular size as well as renal expression of thrombomodulin and angiopoietin-2. Proximity ligation assay was utilized to evaluate the presence of angiopoietin-2 binding to thrombomodulin. Normal kidney tissue came from the healthy part of six nephrectomies due to cancer. Our experiments show renal thrombosis in 6/7 COVID-19 patients, on average 14.7 (6.9-22.5) thrombi per mm2. Most COVID-19 kidneys had extensive kidney injury, especially tubular necrosis, but also glomerular enlargement, glomerulosclerosis, and tubulointerstitial fibrosis which in some cases most likely resulted from underlying disease. Thrombomodulin expression was reduced in glomeruli and peritubular capillaries in kidneys from COVID-19 patients, whereas no change was found for angiopoietin-2. In summary, our study describes a high degree of acute renal failure, renal microthrombosis, and loss of thrombomodulin in postmortem tissue from critically ill COVID-19 patients.
Texto completo:
Disponible
Colección:
Preprints
Base de datos:
medRxiv
Asunto principal:
Psitacosis
/
Defectos Congénitos del Transporte Tubular Renal
/
Trombosis
/
Trastornos de la Coagulación Sanguínea
/
Fibrosis
/
Carcinoma de Células Renales
/
Enfermedad Crítica
/
Lesión Renal Aguda
/
COVID-19
/
Glomerulonefritis
Idioma:
Inglés
Año:
2024
Tipo del documento:
Preprint
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