Comparison of HTK and hypertonic citrate to intraarterial cooling in human non-heart-beating kidney donors.

Intraarterial cooling (IAC) of non-heart-beating donors (NHBD) for renal donation requires a cheap, low-viscosity solution. HTK contains a high hydrogen ion buffer level that theoretically should reduce the observable acidosis associated with ongoing anaerobic metabolism. A retrospective comparison of all retrieved NHBD kidneys as well as of viability on the Organ Recovery Systems Lifeporter machine perfusion circuit was performed with respect to the preservation solution HTK or Marshall's HOC. Forty-two NHBD kidneys (19 HTK and 23 HOC) were machine perfused between February 2004 and May 2005. Most of the HTK kidneys were obtained from uncontrolled donors (12 vs 5; Fisher exact test, P = .01). As a consequence, the glutathione-s-transferase viability assay (411 vs 292 IU/L, P = .12) and the lactate concentrations (2.33 vs 1.94 mmol/L, P = .13) were higher among the HTK cohort. There was evidence of greater buffering capacity in HTK, since the lactate:hydrogen ion ratios were consistently lower during the first 2 perfusion hours (1 hour P = .03, 2 hour P = .02). A linear regression analysis confirmed that this was related to the IAC solution (ANCOVA, P < .001). All controlled donor kidneys passed viability testing and were transplanted. In contrast, 83% (10/12) of the uncontrolled donor kidneys preserved with HTK passed the viability test and were transplanted, compared with only 20% (1/5) of the HOC-treated comparators (Fisher exact test, P = .03). It may be concluded that the postulated advantages of improved pH buffering with HTK appear to have clinical relevance.

Evaluation of daclizumab to reduce delayed graft function in non-heart-beating renal transplantation: a prospective, randomized trial.

Daclizumab (DZB), an interleukin-2 receptor blocker, has been shown to reduce the rate of acute rejection, while non-heart-beating kidney recipients have high rates of delayed graft function that may be prolonged by high levels of calcineurin inhibitors. This study assessed whether DZB could safely replace calcineurin inhibitors in the immediate postoperative period and promote recovery from ischemic acute tubular necrosis. Patients were randomized into one of two groups: DZB induction and daily mycophenolate mofetil (MMF; 2 g) with steroids (20 mg prednisone) or standard triple therapy with tacrolimus, MMF, and prednisone. Patients in the DZB arm were converted to the control arm when either the serum creatinine dropped to <350 micromol/L or there was biopsy evidence of acute rejection. Over 2 years, Leicester and Newcastle non-heart-beating donor (NHBD) centers recruited 51 patients. There was one patient death in the DZB arm, during the study period, after a nonfunctioning graft was removed. A total of two (8%) grafts in the DZB arm and three (11.5%) grafts in the control arm failed to function. The overall rate of immediate function improved from around 5% (pre-2001) to 28%. There were no significant differences in the incidence of acute rejection or graft function (GFR) at 3 months. Machine-perfused kidneys in DZB-treated recipients had the highest rates of immediate function (53%, P = .015). We found that a calcineurin-sparing regime is safe and may be beneficial for recipients of machine-perfused grafts damaged by warm ischemia.

Randomized clinical trial of daclizumab induction and delayed introduction of tacrolimus for recipients of non-heart-beating kidney transplants.

BACKGROUND: Kidneys from non-heart-beating donors (NHBDs) have high rates of delayed graft function (DGF). Use of calcineurin inhibitors is associated with a reduction in renal blood flow, which may delay graft recovery from ischaemic acute tubular necrosis. METHODS: To assess whether daclizumab (DZB) could safely replace tacrolimus in the immediate postoperative period, patients were randomized to receive DZB induction and daily mycophenolate mofetil with steroids (DZB group) or standard tacrolimus-based triple therapy (control group). Tacrolimus was given to patients in the DZB group when the serum creatinine level dropped below 350 micromol/l. RESULTS: Fifty-one patients were recruited at two centres over a 2-year interval between 2000 and 2003. The overall rate of immediate function was 28 per cent (13 of 46 grafts), with the highest rate in recipients of machine-perfused kidneys treated with DZB (eight of 15 patients). CONCLUSION: Induction with DZB and delayed introduction of tacrolimus reduced the incidence of DGF in recipients of machine-perfused NHBD kidneys.