IntroductionThe impact of deceased donor characteristics on kidney transplant outcomes is controversial. Correspondingly, the predictive performance of deceased donor scores remains moderate, and many transplant centers lack validated criteria for graft acceptance decisions. To better dissect donor-related risk from recipient and periprocedural variables, we analyzed outcomes of kidney donor pairs transplanted in different individuals.MethodsThis study explored (a)symmetry of early outcomes of 328 cadaveric kidney transplant recipients from 164 donor pairs transplanted at three Eurotransplant centers. The primary discriminatory factor was (a)symmetry of partner graft function, defined as early graft loss or impaired graft function [estimated glomerular filtration rate (eGFR) <30 mL/min] 3 months after transplantation. We reasoned that a relevant impact of donor factors would result in a high concordance rate of limited graft function or failure.ResultsThe observed number of symmetric graft failure after transplantation was less than statistically expected (3 months: 1 versus 2, p = 0.89; and 12 months: 3 versus 5, p = 0.26). However, we found a trend toward an impaired 5-year graft survival of grafts with good function 3 months after transplantation but a failed or impaired partner graft compared to symmetrically well-functioning grafts (p = 0.09). Subsequently, we explored the impact of individual donor and recipient variables on early transplant outcomes. Generalized estimating equations after feature selection with LassoGEE bootstrap selected donor age, donor body mass index, and donor eGFR as the relevant risk factors.DiscussionOur findings indicate that donor factors impact early outcomes in kidney transplantation but may have a limited role in long-term graft survival, once a graft has been accepted for transplantation. Utilizing donor-based clinical scores has the potential to aid clinicians in acceptance decisions, giving them an estimate of individual posttransplant outcomes. However, the ultimate decision for acceptance should rest with clinicians, who must consider the complex interplay of donor factors, as well as recipient and periprocedural characteristics.
Abstract Background and Aims Delayed graft function (DGF) frequently occurs following kidney transplantation, and prolonged duration of DGF adversely affects 1-year graft function and long-term graft survival. Recently, Proenkephalin A 119-159 (penKid) was shown to reflect kidney function and predict acute kidney injury (AKI) in critically ill patients. Given the similarities between DGF in transplanted and AKI in native kidneys, we hypothesized that penKid may aid in identifying and risk-stratifying DGF post-transplantation. Method In a prospective study of 159 consecutive kidney transplant recipients at Heidelberg University Hospital from November 2021 to July 2023, penKid was quantified using an immunoluminometric assay until patient discharge. DGF was primarily defined as the necessity for dialysis within 7 days post-transplant. Additionally, penKid was examined in the context of DGF severity, discriminating the different durations of post-transplant dialysis treatment. Similarly, penKid was assessed to differentiate uptake of graft function, defined as slow or immediate by a serum creatinine reduction ratio of pre-transplant and 7 days post-transplant levels of <0.7 and ≥0.7, respectively. Results DGF, defined as the need for dialysis within the first week post-transplant, occurred in 53/159 (33.3%) patients. penKid enabled the differentiation of patients with and without DGF from the first day post-transplant onward (P < 0.001, Fig. 1), and consistently outperformed SCr in discriminating DGF from no DGF at all time points studied (P < 0.001). Additionally, penKid allowed identification of DGF severity from the first day post-transplant (P < 0.001) and early differentiation between slow and delayed graft function (AUC 0.79 [95% CI 0.68-0.90]). In a multivariate model, delta penKid from pre-transplant to the first day post-transplant emerged as the strongest predictor for DGF (C index = 0.88). On the first day post-transplant, penKid, with a cut-off at 300 pmol/L, discriminated DGF from no DGF with a sensitivity of 95.1% (95% CI 83.9–98.7) and a specificity of 56.5% (95% CI 46.3–66.2). Conclusion penKid is a promising biomarker shown to accurately differentiate DGF from no DGF as early as the first day post-transplant and to predict DGF severity, allowing for earlier intervention in these at-risk patients. Due to its high discriminatory power to identify and predict DGF post-transplantation, penKid shows great potential to accompany future studies examining the occurrence of DGF in transplant programs, where DCD is introduced into practice, machine perfusion techniques are assessed, or in trials that assess potential therapeutic interventions in patients with DGF.
Extracorporeal liver-support therapies remain controversial in critically ill patients, as most studies have failed to show an improvement in outcomes. However, heterogeneous timing and inclusion criteria, an insufficient number of treatments, and the lack of a situation-dependent selection of available liver-support modalities may have contributed to negative study results. We retrospectively investigated the procedural characteristics and safety of the three liver-support therapies CytoSorb, Molecular Adsorbent Recirculating System (MARS) and therapeutic plasma exchange (TPE). Whereas TPE had its strengths in a shorter treatment duration, in clearing larger molecules, affecting platelet numbers less, and improving systemic coagulation and hemodynamics, CytoSorb and MARS were associated with a superior reduction in particularly small protein-bound and water-soluble substances. The clearance magnitude was concentration-dependent for all three therapies, but additionally related to the molecular weight for CytoSorb and MARS therapy. Severe complications did not appear. In conclusion, a better characterization of disease-driving as well as beneficial molecules in critically ill patients with acute liver dysfunction is crucial to improve the use of liver-support therapy in critically ill patients. TPE may be beneficial in patients at high risk for bleeding complications and impaired liver synthesis and hemodynamics, while CytoSorb and MARS may be considered for patients in whom the elimination of smaller toxic compounds is a primary objective.