Noninvasive measurement of 13Carbon turnover for evaluation of porcine renal grafts during ex vivo machine perfusion

• Published in: Communications medicine Vol. 3; no. 1; p. 192
• Main Authors: Minor, Thomas, Malkus, Laura, Zlatev, Hristo, Lüer, Bastian, von Horn, Charlotte
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 21.12.2023; Springer Nature B.V; Nature Portfolio
• Subjects: 692/308/53; 692/4022/272; Blood & organ donations; Cold storage; Ischemia; Kidney transplants; Laboratory animals; Medicine; Medicine & Public Health; Metabolism; Metabolites; Morphology; Skin & tissue grafts; Spectrum analysis; Surgical apparatus & instruments; Germany
• ISSN: 2730-664X; 2730-664X
• DOI: 10.1038/s43856-023-00422-6

Background Kidney transplantation suffers from a shortage of donor organs. Despite this, a lot of grafts are discarded due to inadequate quality. As many kidneys are afflicted by transient filtration failure early after preservation, classical renal function tests are not applicable to differentiate between prospective recovery or continuing deficit of renal function. Methods Using normothermic machine perfusion as a platform for pre-implantation evaluation of the graft, we present a novel evaluative approach based on the metabolic turnover of 13 C-acetate during isolated perfusion. After injection of the tracer, 13 CO 2 as a metabolic end-product can be quantified by high-precision laser-based spectroscopy in the gas outflow of the oxygenator. Three groups of porcine kidneys with graduated ischemic injury were investigated. Results This quantitative approach is able to discriminate acceptable quality kidneys, most likely to recover within days from poor kidney grafts that are unlikely to regain notable glomerular function with high discriminatory power (area under the ROC curve 0.91; P  < 0.001 By contrast, conventional renal function tests are rather ineffective under these circumstances. Conclusions This assessment method offers the potential to quantitatively assess donor kidney quality using a measurable output, salvaging donors that would otherwise have been discarded. Plain language summary Kidney transplant surgery continues to face donor shortages. One consideration to tackle the shortage is to improve the way in which donor organ quality is assessed, so that fewer organs may be discarded. Here, we develop and test a non-invasive quantitative method that can measure the biochemical reaction that correlates to the viability of isolated kidneys using pig kidneys as a model system. We find the method could discriminate donor kidneys of good, intermediate, or poor quality with a discriminatory power superior to all other conventional parameters. Although the application needs to be tested in human kidney donors, it offers the potential to improve evaluation criteria for kidney grafts for transplantation. Minor et al. present and evaluate a quantitative approach to measuring metabolic turnover of 13 C-acetate during isolated perfusion to ascertain the quality of porcine donor kidneys. This approach effectively discriminates varying degrees of organ graft quality, where conventional renal function tests are ineffective.