Perioperative management of adult cadaveric and live donor renal transplantation in the UK: a survey of national practice

AbstractBackgroundThere is a limited evidence base and no national consensus regarding the perioperative management of patients undergoing renal transplantation. We developed an electronic survey to capture an overview of renal transplant perioperative practice across UK renal transplant centres and determine the need for future guidelines on patient management.MethodsA 29-question survey was developed to encompass the entire renal transplant perioperative pathway and input was sought from clinicians with expertise in renal transplant surgery, anaesthesia, nephrology and intensive care. The survey was sent to lead renal anaesthetists at each of the 23 transplant centres across the UK.ResultsA 96% response rate was achieved with 22 out of 23 centres returning complete responses. There was limited evidence of guideline-based approaches to preoperative workup. Questions regarding intraoperative fluid management, blood pressure targets, vasopressor administration and central venous pressure (CVP) monitoring identified a broad range of practice. Of note, the routine use of goal-directed fluid therapy based on cardiac output estimation was reported in six (27.3%) centres, while nine centres (40.9%) continue to target a specific CVP intraoperatively. In all, 12 (54.5%) centres perform transversus abdominis plane blocks with fentanyl-based patient-controlled analgesia as the most common mode of postoperative analgesia. A single centre reported a renal transplant-specific Enhanced Recovery after Surgery programme for cadaveric organ recipients.ConclusionsThis questionnaire highlighted a high degree of heterogeneity in current UK practice as regards the perioperative management of renal transplant recipients. Development of evidence-based national consensus guidelines to standardize the perioperative care of these patients is recommended in order to improve patient outcomes and focus areas of future research.</jats:sec

Goal-Directed Haemodynamic Therapy Improves Patient Outcomes in Kidney Transplantation

Introduction: Kidney transplant graft function depends on optimised haemodynamics. However, high fluid volumes risk hypervolaemic complications. The Edwards Lifesciences ClearSight™ device permits fluid titration through markers of preload and beat-to-beat blood pressure monitoring. We evaluated the implementation of a novel goal-directed haemodynamic therapy protocol to determine whether patient outcomes had improved. Design: A retrospective evaluation of standard care versus goal-directed haemodynamic therapy in adults undergoing kidney transplantation was performed in a single centre between April 2016 and October 2019. Twenty-eight standard-of-care patients received intraoperative fixed-rate infusion and 28 patients received goal-directed haemodynamic therapy. The primary outcome was volume of fluid administered intraoperatively. Secondary outcomes included blood product and vasoactive drug exposure, graft and recipient outcomes. Results: Intraoperative fluid administered was significantly reduced in the goal-directed haemodynamic therapy cohort (4325 vs 2751 ml, P &lt; .001). Exposure to vasopressor (67.9% vs 42.9%, P = .060) and blood products (17.9% vs 3.6%, P = .101) was unchanged. Immediate graft function (82.1% vs 75.0%, P = .515), dialysis requirement (14.3% vs 21.4%, P = .729) and creatinine changes post-operatively were unchanged. In the goal-directed haemodynamic therapy cohort, 1 patient had pulmonary oedema (3.6%) versus 21.4% in the standard cohort. Patients in the goal-directed haemodynamic therapy group were more likely to mobilise within 48 hours of surgery (number needed to treat = 3.5, P = .012). Conclusions: Protocolised goal-directed haemodynamic therapy in kidney transplantation was safe and may improve patient, graft, and surgical outcomes. Clinical trials assessing goal-directed approaches are needed. </jats:p

Superiority of thyroid peroxidase DNA over protein immunization in replicating human thyroid autoimmunity in HLA-DRB1*0301 (DR3) transgenic mice

Murine experimental autoimmune thyroiditis (EAT), characterized by thyroid destruction after immunization with thyroglobulin (Tg), has long been a useful model of organ-specific autoimmune disease. More recently, porcine thyroid peroxidase (pTPO) has also been shown to induce thyroiditis, but these results have not been confirmed. When (C57BL/6 × CBA)F(1) mice, recently shown to be susceptible to mouse TPO-induced EAT, were immunized with plasmid DNA to human TPO (hTPO) and cytokines IL-12 or GM-CSF, significant antibody (Ab) titres were generated, but minimal thyroiditis was detected in one mouse only from the TPO + GM-CSF immunized group. However, after TPO DNA immunization of HLA-DR3 transgenic class II-deficient NOD mice, thyroiditis was present in 23% of mice injected with TPO + IL-12 or GM-CSF. We also used another marker for assessing the closeness of the model to human thyroid autoimmunity by examining the epitope profile of the anti-TPO Abs to immunodominant determinants on TPO. Remarkably, the majority of the anti-TPO Abs was directed to immunodominant regions A and B, demonstrating the close replication of the model to human autoimmunity. TPO protein immunizations of HLA-DR3 transgenic mice with recombinant hTPO did not result in thyroiditis, nor did immunization of other mice expressing HLA class II transgenes HLA-DR4 or HLA-DQ8, with differential susceptibility to Tg-induced EAT. Moreover, our efforts to duplicate exactly the experimental procedures used with pTPO also failed to induce thyroiditis. The success of hTPO plasmid DNA immunization of DR3(+) mice, similar to our reports on Tg-induced thyroiditis and thyrotropin receptor DNA-induced Graves’ hyperthyroidism, underscores the importance of DR3 genes for all three major thyroid antigens, and provides another humanized model to study autoimmune thyroid disease