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

Abstract

Abstract 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 13C-acetate during isolated perfusion. After injection of the tracer, 13CO2 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.