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Nicholas R Brook

Publications and source records attributed to Nicholas R Brook.

4 recordsLinked to original sources

Cardiac allograft vasculopathy: current concepts and treatment.

Cardiac allograft vasculopathy (CAV) remains the leading limiting factor of patient and graft survival after the first post-operative year. The pathogenesis involves both immunological and non-immunological factors. Here, we present recent advances and discuss potential preventative and treatment regimens. A review of the current literature of heart transplantation, detailing molecular mechanisms, pharmacological risk factors and novel immunosuppression regimens was performed. Recent findings demonstrate the pivotal role of the endothelium, resulting in release of pro-fibrotic cytokines, recruitment of circulating leucocytes, proliferation of vascular smooth muscle cells, and deposition of extracellular matrix proteins (ECMs). The role of HMG-CoA reductase inhibitors and anti-hypertensives remains controversial, but there is increasing evidence advocating their prophylactic use. We can conclude that novel immunosuppressive agents such as rapamycin, mycophenolate mofetil and FTY-720 are experimental immunosuppressive agents that are undergoing evaluation in clinical trials. The prophylactic use of statins and anti-hypertensive drugs needs to be defined but needs to suggest potential strategies to prolong cardiac allograft survival.

Heart Transplantation↗

Non-heart beating donor kidneys with delayed graft function have superior graft survival compared with conventional heart-beating donor kidneys that develop delayed graft function.

Delayed graft function may have an association with reduced graft survival, and nonheart-beating donor (NHBD) kidneys have higher rates of delayed graft function (DGF) than heart-beating donor (HBD) kidneys. This study compared outcome of renal transplants from HBDs who developed DGF, with NHBDs who developed DGF. All recipients of HBD and NHBD kidneys who developed DGF were identified during a 10-year period. All patients with graft primary nonfunction were excluded from analysis. Four hundred and fifty-six functioning transplants were performed. Delayed graft function occurred in 69 (17%) HBD and 55 (93%) NHBD kidneys. The grafts developing DGF were well matched for donor and recipient age. The rate of acute rejection was similar; [n = 16/69 (23%) HBD vs. n = 13/55 (24%) NHBD]. Cold ischaemia was 21 h in the HBD group and 17 h in NHBD group (p > 0.05). Serum creatinine was similar for both groups at 1.3 and 6 years (p > 0.05 for all time points). Graft survival in the NHBD recipients with DGF was significantly better at 3 years (84%) compared with recipients of a HBD renal transplant that developed DGF (73%) (p < 0.05), and at 6 years (62% survival for HBDs and 84% survival for NHBDs). This study shows that graft survival was better for NHBD kidneys up to 6 years after transplantation.

Adult↗

Nonheart-beating kidney donation: current practice and future developments.

BACKGROUND: Nonheart-beating kidney donation (NHBD) is gaining acceptance as a method of donor pool expansion. However, a number of practitioners have concerns over rates of delayed graft function, acute rejection, and long-term graft survival. The ethical issues associated with NHBD are complex and may be a further disincentive. Tailored strategies for preservation, viability prediction, and immunosuppression for kidneys from this source have the potential to maximize the number of available organs. This review article presents the current practice of NHBD kidney transplantation, examines the results and draws comparisons with cadaveric kidneys, and explores some areas of potential development. METHODS: A review of the current literature on NHBD kidney donation was performed. RESULTS: The renewed interest in NHBD kidneys is driven by a continuing shortfall in available organs. Those centers involved in NHBD report an increase in kidney transplants of the order of 16% to 40% and there is no evidence that the financial costs are higher with NHBDs. The majority of experience comes from Maastricht category 2 NHBDs, where an estimation of warm time is possible. This is generally limited to 40 minutes. There are variations in the technique for kidney preservation prior to retrieval, but most centers use an aortic balloon catheter. Much work has looked at the ideal technique for kidney preservation prior to implantation. Evidence suggests that machine perfusion produces the best initial function rates, decreased use of adjuvant immunotherapy and fewer haemodialysis sessions than static cold storage. CONCLUSION: Despite being associated with poorer initial graft function, the long-term allograft survival of NHBD kidneys does not differ from the results of transplantation from cadaveric kidneys. Further, serum creatinine levels are generally equivalent. Constant reassessment of the ethical issues is required for donation to be increased while respecting public concerns. Use of viability assessment and tailoring of immune suppression for NHBD kidneys may allow a further increase in donation from this source.

Heart Arrest↗

Intra-renal resistance reflects warm ischaemic damage, and is further increased by static cold storage: a model of non-heart-beating donor kidneys.

BACKGROUND: Non-heart beating donor kidneys increase transplant activity, but their use is associated with a higher rate of both primary non-function and delayed graft function than cadaveric kidneys, due to a period of cold ischaemic damage superimposed on a period of warm ischaemia. We aimed to measure intra-renal resistance in machine perfused porcine kidneys subjected to different periods of warm ischaemic injury, with additional, varying, cold ischaemic times, in an attempt to mimic the injury suffered by NHBD kidneys and test the predictive power of viability testing. MATERIAL/METHODS: Landrace pigs were killed by lethal injection, and the kidneys were subjected to varying WITs of 10-90 minutes prior to explantation. Kidneys were subsequently stored for varying cold times of 2 to 48 hours. IRR (pressure/flow) was calculated during 6 hours cold pulsatile machine perfusion. RESULTS: For all WITs, IRR was higher at the start than at the end of machine perfusion (P<0.001). There was a strong correlation between IRR on MP, and WIT, but no correlation after 6 hours MP. Intra-renal resistance increased as kidneys were exposed to longer CITs; this effect was most marked for the longer WITs (P<0.004), However, the slope gradient was similar for the different WITs. CONCLUSIONS: Early IRR accurately reflects kidney in-situ WIT, and machine perfusion reduces IRR whilst cold ischaemia imposed on periods of warm ischaemia increases IRR and attenuates the beneficial effect of MP. Machine perfusion may partially ameliorate the effects of WIT in terms of IRR, and may prove useful in pre-transplant viability assessment of NHBD kidneys.

Animals↗