A Prospective Randomised Paired Trial of Sirolimus versus Tacrolimus as Primary Immunosuppression following Non-Heart Beating Donor Kidney Transplantation.

INTRODUCTION: With calcineurin inhibitors potentiating damage from ischaemia-reperfusion injury in kidneys from donors after cardiac death we wanted to investigate the role of substituting sirolimus for tacrolimus in the delayed introduction of calcineurin inhibitor regime used in our centre. METHOD: A prospective randomised paired open-label study was performed taking pairs of kidneys from each donor and randomising one to a tacrolimus-based regime and the other to a similar regime based on sirolimus. Graft function at one year was the primary endpoint. RESULTS: Total 31 pairs of kidneys were randomised to each group, with 19 pairs of recipients available for analysis after post-randomisation study exclusions. Despite a higher incidence of biopsy proven acute rejection in the sirolimus group, renal allograft function was similar in both groups at three-monthly intervals up to one year post-transplant. All episodes of acute rejection in the sirolimus group occurred in the first three months. Graft and patient survival at one year was 100% in the tacrolimus group, with one death with functioning graft in the sirolimus group (95% survival). Unfortunately, 10 of the 19 patients in the sirolimus arm required switch of medication to tacrolimus due to acute rejection or intolerable drug side effects. CONCLUSIONS: Graft survival and function were very similar in the two groups despite the higher rate of acute rejection in the sirolimus arm, raising the possibility that the damage done by acute rejection was adequately offset by the nephron-sparing effect of sirolimus compared to tacrolimus. Sirolimus may have a role as a longer-term maintenance immunosuppressant after initial treatment with a different agent such as tacrolimus or belatacept.

The modified Barry technique to prevent vesicoureteric reflux in paediatric renal transplant recipients: initial recipient outcomes.

OBJECTIVE: We present the initial clinical results of the 'modified Barry technique' for the prevention of VUR in paediatric renal transplant grafts. Ours is the only centre in the UK using this technique, as confirmed in a questionnaire developed in our department. PATIENTS AND METHODS: We retrospectively analysed data of 15 paediatric renal transplant patients (operated June 2006-November 2009) who had their vesicoureteric anastomosis performed using the modified Barry technique with a 2-cm submucosal anti-reflux tunnel. The original Barry technique involved the creation of a 4-cm tunnel; this was modified by us to reduce the risk of ureteric stenosis. RESULTS: At a median follow up of 23.7 months (6.3-39.4), the incidence of VUR was 7% (1/15). There was no evidence of postoperative urological complications, such as urinary leak, primary ureteric obstruction including anastomotic stricture/stenosis, transplant graft renal calculi and chronic rejection. At current follow up, graft and patient survival are 100%. CONCLUSION: With the introduction of the modified Barry technique, the incidence of VUR in our series fell 10-fold to 7%, compared with our earlier study (P<0.0001), without any urological complications. Although the initial results are encouraging, larger patient numbers and longer follow up are required to validate this technique further.

The influence of perfusion solution on renal graft viability assessment.

BACKGROUND: Kidneys from donors after cardiac or circulatory death are exposed to extended periods of both warm ischemia and intra-arterial cooling before organ recovery. Marshall's hypertonic citrate (HOC) and Bretschneider's histidine-tryptophan-ketoglutarate (HTK) preservation solutions are cheap, low viscosity preservation solutions used clinically for organ flushing. The aim of the present study was to evaluate the effects of these two solutions both on parameters used in clinical practice to assess organ viability prior to transplantation and histological evidence of ischemic injury after reperfusion. METHODS: Rodent kidneys were exposed to post-mortem warm ischemia, extended intra-arterial cooling (IAC) (up to 2 h) with preservation solution and reperfusion with either Krebs-Hensleit or whole blood in a transplant model. Control kidneys were either reperfused directly after retrieval or stored in 0.9% saline. Biochemical, immunological and histological parameters were assessed using glutathione-S-transferase (GST) enzymatic assays, polymerase chain reaction and mitochondrial electron microscopy respectively. Vascular function was assessed by supplementing the Krebs-Hensleit perfusion solution with phenylephrine to stimulate smooth muscle contraction followed by acetylcholine to trigger endothelial dependent relaxation. RESULTS: When compared with kidneys reperfused directly post mortem, 2 h of IAC significantly reduced smooth muscle contractile function, endothelial function and upregulated vascular cellular adhesion molecule type 1 (VCAM-1) independent of the preservation solution. However, GST release, vascular resistance, weight gain and histological mitochondrial injury were dependent on the preservation solution used. CONCLUSIONS: We conclude that initial machine perfusion viability tests, including ischemic vascular resistance and GST, are dependent on the perfusion solution used during in situ cooling. HTK-perfused kidneys will be heavier, have higher GST readings and yet reduced mitochondrial ischemic injury when compared with HOC-perfused kidneys. Clinicians should be aware of this when deciding which kidneys to transplant or discard.