RESUMEN
The burden of chronic kidney disease and associated risk of kidney failure are increasing in Africa. The management of people with chronic kidney disease is fraught with numerous challenges because of limitations in health systems and infrastructures for care delivery. From the third iteration of the International Society of Nephrology Global Kidney Health Atlas, we describe the status of kidney care in the ISN Africa region using the World Health Organization building blocks for health systems. We identified limited government health spending, which in turn led to increased out-of-pocket costs for people with kidney disease at the point of service delivery. The health care workforce across Africa was suboptimal and further challenged by the exodus of trained health care workers out of the continent. Medical products, technologies, and services for the management of people with nondialysis chronic kidney disease and for kidney replacement therapy were scarce due to limitations in health infrastructure, which was inequitably distributed. There were few kidney registries and advocacy groups championing kidney disease management in Africa compared with the rest of the world. Strategies for ensuring improved kidney care in Africa include focusing on chronic kidney disease prevention and early detection, improving the effectiveness of the available health care workforce (e.g., multidisciplinary teams, task substitution, and telemedicine), augmenting kidney care financing, providing quality, up-to-date health information data, and improving the accessibility, affordability, and delivery of quality treatment (kidney replacement therapy or conservative kidney management) for all people living with kidney failure.
RESUMEN
Organ transplantation is a life-saving procedure affecting over 100,000 people on the transplant waitlist. Ischemia reperfusion injury (IRI) is a major challenge in the field as it can cause post-transplantation complications and limit the use of organs from extended criteria donors. Machine perfusion technology has the potential to mitigate IRI; however, it currently fails to achieve its full potential due to a lack of highly sensitive and specific assays to assess organ quality during perfusion. We developed a real-time and non-invasive method of assessing organs during perfusion based on mitochondrial function and injury using resonance Raman spectroscopy. It uses a 441 nm laser and a high-resolution spectrometer to quantify the oxidation state of mitochondrial cytochromes during perfusion. This index of mitochondrial oxidation, or 3RMR, was used to understand differences in mitochondrial recovery of cold ischemic rodent livers during machine perfusion at normothermic temperatures with an acellular versus cellular perfusate. Measurement of the mitochondrial oxidation revealed that there was no difference in 3RMR of fresh livers as a function of normothermic perfusion when comparing acellular versus cellular-based perfusates. However, following 24 h of static cold storage, 3RMR returned to baseline faster with a cellular-based perfusate, yet 3RMR progressively increased during perfusion, indicating injury may develop over time. Thus, this study emphasizes the need for further refinement of a reoxygenation strategy during normothermic machine perfusion that considers cold ischemia durations, gradual recovery/rewarming, and risk of hemolysis.
Asunto(s)
Trasplante de Hígado , Humanos , Trasplante de Hígado/métodos , Preservación de Órganos/métodos , Espectrometría Raman , Hígado/metabolismo , Perfusión/métodos , MitocondriasRESUMEN
Organ transplantation is a life-saving procedure affecting over 100,000 people on the transplant waitlist. Ischemia reperfusion injury is a major challenge in the field as it can cause post-transplantation complications and limits the use of organs from extended criteria donors. Machine perfusion technology is used to repair organs before transplant, however, currently fails to achieve its full potential due to a lack of highly sensitive and specific assays to predict organ quality during perfusion. We developed a real-time and non-invasive method of assessing organ function and injury based on mitochondrial oxygenation using resonance Raman spectroscopy. It uses a 441 nm laser and a high-resolution spectrometer to predict the oxidation state of mitochondrial cytochromes during perfusion, which vary due to differences in storage compositions and perfusate compositions. This index of mitochondrial oxidation, or 3RMR, was found to predict organ health based on clinically utilized markers of perfusion quality, tissue metabolism, and organ injury. It also revealed differences in oxygenation with perfusates that may or may not be supplemented with packed red blood cells as oxygen carriers. This study emphasizes the need for further refinement of a reoxygenation strategy during machine perfusion that is based on a gradual recovery from storage. Thus, we present a novel platform that provides a real-time and quantitative assessment of mitochondrial health during machine perfusion of livers, which is easy to translate to the clinic.