How to improve the quality of kidneys from non-heart-beating donors: a randomised controlled trial of thrombolysis in non-heart-beating donors.

BACKGROUND: The growth in the prevalence of end-stage renal failure has been accompanied with a rise in the waiting list for renal transplantation, which has not been matched by an increase in the kidney donor pool. Non-heart-beating donors (NHBD) offer a potential source of kidneys that are not currently being significantly used. Cardiac arrest for a protracted period of time leads to in situ thrombosis, and, as a consequence, the discard rates for harvested kidneys is higher than brain-stem-dead donors. METHODS: A double-blinded, randomised, controlled trial of streptokinase preflush or placebo for NHBD was performed. An initial 30 donors were entered into the study. After routine nephrectomy, NHBD kidneys were machine perfused as part of viability screening before transplantation. Kidneys were then transplanted within 24 hours of cardiac arrest. The primary objectives were the improvements of viability parameters (perfusion, enzyme levels, and histopathology) of the kidneys. The secondary objective was to increase the number of kidneys passing the viability tests and thus transplanted. RESULTS: The two groups of NHBD donors and their kidneys were similar in their descriptive epidemiologic characteristics. The NHBD kidneys from the streptokinase-treated donors had a better appearance at procurement (P<0.001) and performed better during machine preservation (P<0.001). Enzyme biomarkers present in the kidney perfusate were all significantly reduced by the use of streptokinase. These included glutathione S-transferase (P<0.001), fatty acid binding protein (P<0.001), and alanine aminopeptidase (P<0.001). However, although there was a higher proportion of kidneys transplanted through the use of streptokinase (63.6% with streptokinase vs. 42.6% with placebo), this did not achieve significance. There was no difference with respect to postoperative bleeding and transfusion requirements in the recipient whether streptokinase preflush or placebo was used. CONCLUSION: This study using streptokinase preflush in the NHBD was found to improve the condition of the kidneys retrieved. The improvement in the quality of the donor kidneys was not associated with an increased morbidity in the recipient.

Do tissue damage biomarkers used to assess machine-perfused NHBD kidneys predict long-term renal function post-transplant?

BACKGROUND: Renal transplantation in many units is limited by the availability of donor organs. Kidneys obtained from non-heart-beating donors (NHBD) represent an important resource, with the potential to substantially increase the available donor organ pool. Such kidneys are associated with increased warm ischaemic tissue injury which may be assessed by hypothermic machine perfusion. Within our transplant centre, a key component of such damage assessment and viability screening involves the quantification of the tissue damage biomarkers glutathione S-transferase in kidney perfusates. METHODS: Since 1998, 126 NHBD kidneys were machine-perfused prior to implantation, resulting in 74 transplants. Kidney perfusate samples were assayed for glutathione S-transferase in "real time", and alanine aminopeptidase and fatty acid binding protein in "retrospect". RESULTS: The pre-transplant concentration of these tissue injury biomarkers determined pre-transplant did not correlate with subsequent longer-term renal function, as assessed by measurement of serum creatinine (tGST: Spearman correlation r=-0.02; Ala-AP: r=0.02; H-FABP: r=-0.05) and creatinine clearance (tGST: r=0.08; Ala-AP: r=-0.02; H-FABP: r=0.14) for those kidneys that had passed their viability tests. CONCLUSIONS: Thus whilst these biomarkers may represent reliable pre-transplant indicators of immediate kidney viability and short-term kidney function, they do not predict the efficacy of renal function in the longer term.

Long-term renal function in kidneys from non-heart-beating donors: A single-center experience.

BACKGROUND: Cadaveric kidneys from brain-stem-dead donors continue to be limited because the number of donors has reached a plateau. Wide recruitment of non-heart-beating donors (NHBD) could significantly increase the donor pool. NHBD renal transplants are underused because of the concern of poor quality graft function from such donors. In response to this perception, we reviewed 46 NHBD renal transplants performed in our center since 1998. METHODS: All NHBD kidneys were machine-perfused using the Newcastle continuous-hypothermic pulsatile preservation system before transplantation. A control heart-beating-donor (HBD) group was taken as the next consecutive HBD renal transplant to the NHBD transplant. The outcome and quality of function of the groups of renal transplants were analyzed for short-term and long-term performance. RESULTS: The renal transplant patients were matched for donor and recipient factors. Survival rates for allografts and patients were similar for 1 to 3 years. There was an increased incidence of delayed graft function in the NHBD renal transplants in the perioperative period. The creatinine clearance was 22.8+/-2.3 mL/minute for NHBD patients and 44.4+/-2.9 mL/minute for HBD patients at the time of discharge from hospital. This difference equalized after 3 months and the creatinine clearance for NHBD was 44.2+/-2.4 mL/minute and for HBD 49.2+/-3.4 mL/minute. CONCLUSIONS: Our results for NHBD renal transplants confirm that such grafts suffer primary warm ischemic injury, shown by the increased incidence of acute tubular necrosis and consequent delayed graft function. This produced poor renal function at the time of hospital discharge. After 3 months, the renal function of NHBD cases improved to the level seen in HBD patients.