Lysis of cold-storage-induced microvascular obstructions for ex vivo revitalization of marginal human kidneys.
Am J Transplant
; 21(1): 161-173, 2021 01.
Article
en En
| MEDLINE
| ID: mdl-32627324
ABSTRACT
Thousands of kidneys from higher-risk donors are discarded annually because of the increased likelihood of complications posttransplant. Given the severe organ shortage, there is a critical need to improve utilization of these organs. To this end, normothermic machine perfusion (NMP) has emerged as a platform for ex vivo assessment and potential repair of marginal organs. In a recent study of 8 transplant-declined human kidneys on NMP, we discovered microvascular obstructions that impaired microvascular blood flow. However, the nature and physiologic impact of these lesions were unknown. Here, in a study of 39 human kidneys, we have identified that prolonged cold storage of human kidneys induces accumulation of fibrinogen within tubular epithelium. Restoration of normoxic conditions-either ex vivo during NMP or in vivo following transplant-triggered intravascular release of fibrinogen correlating with red blood cell aggregation and microvascular plugging. Combined delivery of plasminogen and tissue plasminogen activator during NMP lysed the plugs leading to a significant reduction in markers of renal injury, improvement in indicators of renal function, and improved delivery of vascular-targeted nanoparticles. Our study suggests a new mechanism of cold storage injury in marginal organs and provides a simple treatment with immediate translational potential.
Palabras clave
Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
Preservación de Órganos
/
Trasplante de Riñón
Límite:
Humans
Idioma:
En
Año:
2021
Tipo del documento:
Article