Expansion of the kidney donor pool by using cardiac death donors with prolonged time to cardiorespiratory arrest.

Donation after Cardiac Death (DCD) is an increasingly important source of kidney transplants, but because of concerns of ischemic injury during the agonal phase, many centers abandon donation if cardiorespiratory arrest has not occurred within 1 h of controlled withdrawal of life-supporting treatment (WLST). We report the impact on donor numbers and transplant function using instead a minimum 'cut-off' time of 4 h. The agonal phase of 173 potential DCD donors was characterized according to the presence or absence of: acidemia; lactic acidosis; prolonged (>30 min) hypotension, hypoxia or oliguria, and the impact of these characteristics on 3- and 12-month transplant outcome evaluated by multivariable regression analysis. Of the 117 referrals who became donors, 27 (23.1%) arrested more than 1 h after WLST. Longer agonal-phase times were associated with greater donor instability, but surprisingly neither agonal-phase instability nor its duration influenced transplant outcome. In contrast, 3- and 12-month eGFR in the 190 transplanted kidneys was influenced independently by donor age, and 3-month eGFR by cold ischemic time. DCD kidney numbers are increased by 30%, without compromising transplant outcome, by lengthening the minimum waiting time after WLST from 1 to 4 h.

Electrical and optical spectroscopy for quantitative screening of hepatic steatosis in donor livers.

Macro-steatosis in deceased donor livers is increasingly prevalent and is associated with poor or non-function of the liver upon reperfusion. Current assessment of the extent of steatosis depends upon the macroscopic assessment of the liver by the surgeon and histological examination, if available. In this paper we demonstrate electrical and optical spectroscopy techniques which quantitatively characterize fatty infiltration in liver tissue. Optical spectroscopy showed a correlation coefficient of 0.85 in humans when referenced to clinical hematoxylin and eosin (H&E) sections in 20 human samples. With further development, an optical probe may provide a comprehensive measure of steatosis across the liver at the time of procurement.

Cold machine perfusion versus static cold storage of kidneys donated after cardiac death: a UK multicenter randomized controlled trial.

One third of deceased donor kidneys for transplantation in the UK are donated following cardiac death (DCD). Such kidneys have a high rate of delayed graft function (DGF) following transplantation. We conducted a multicenter, randomized controlled trial to determine whether kidney preservation using cold, pulsatile machine perfusion (MP) was superior to simple cold storage (CS) for DCD kidneys. One kidney from each DCD donor was randomly allocated to CS, the other to MP. A sequential trial design was used with the primary endpoint being DGF, defined as the necessity for dialysis within the first 7 days following transplant. The trial was stopped when data were available for 45 pairs of kidneys. There was no difference in the incidence of DGF between kidneys assigned to MP or CS (58% vs. 56%, respectively), in the context of an asystolic period of 15 min and median cold ischemic times of 13.9 h for MP and 14.3 h for CS kidneys. Renal function at 3 and 12 months was similar between groups, as was graft and patient survival. For kidneys from controlled DCD donors (with mean cold ischemic times around 14 h), MP offers no advantage over CS, which is cheaper and more straightforward.

Donor kidney disease and transplant outcome for kidneys donated after cardiac death.

BACKGROUND: Although outcomes of kidney transplants following donation after cardiac death (DCD) and donation after brainstem death (DBD) are similar, generally only optimal younger DCD donors are considered. This study examined the impact of pre-existing donor kidney disease on the outcome of DCD transplants. METHODS: This retrospective study compared the outcome of all DCD kidney transplants performed during 1996-2006 with contemporaneous kidney transplants from DBD donors. Implantation biopsies were scored for glomerular, tubular, parenchymal and vascular disease (global histology score). There were 104 DCD and 104 DBD kidney transplants. RESULTS: Delayed graft function (DGF) occurred more frequently in DCD than DBD kidneys (64.4 versus 28.8 per cent; P < 0.001). Long-term graft outcome was similar. The only donor factor that influenced outcome was baseline kidney disease, which was similar in both groups, even though DCD donors were younger, with a higher predonation estimated glomerular filtration rate. The global histology score predicted DGF (odds ratio 1.85 per unit; P = 0.006) and graft failure (relative risk 1.55 per unit; P = 0.001), although there was no difference for DCD and DBD kidneys. CONCLUSION: Transplant outcomes for DCD and DBD kidneys are comparable. Baseline donor kidney disease influences DGF and graft survival but the impact is no greater for DCD kidneys.

Selective use of ultrasonographic vascular mapping in the assessment of patients before haemodialysis access surgery.

BACKGROUND: Use of routine preoperative ultrasonography to determine the optimum site for haemodialysis access surgery increases the number of distal arteriovenous fistulas formed and improves overall patency rates. Nevertheless its use in all patients is time consuming and costly. This study examined whether clinical parameters could be used to determine the requirement for preoperative ultrasonography. METHODS: Between March 2002 and October 2003, 145 consecutive patients were reviewed in the vascular access clinic. Patients were first assessed clinically, a site for vascular access surgery was proposed, and the need for radiological mapping studies recorded. A second, blinded, clinician determined the site for vascular access surgery using ultrasonography. The correlation between clinical and ultrasonographic findings was then examined. RESULTS: Ultrasonography was considered unnecessary using clinical criteria in 106 patients. Subsequent ultrasonographic mapping altered the management of only one patient. In contrast, the management of 18 of the 39 patients in whom ultrasonography was thought necessary was influenced by radiological imaging. A 1-year primary patency rate of 77.0 per cent was achieved following vascular access surgery on the study population. CONCLUSION: Clinical parameters could be used to determine the need for preoperative vascular ultrasonographic mapping; imaging was not required in the majority of patients.

HER2 and COX2 expression in human prostate cancer.

COX2 and HER2 expression are associated with a poor prognosis in prostate cancer and HER2 has been linked to COX2 expression in colorectal cancer. The association between COX2 and HER2 expression was investigated in 117 patients with prostate cancer (89) or Benign prostatic hyperplasia (BPH) (28). Tissue was analysed for HER2 amplification by fluorescent in situ hybridisation, and HER2 and COX2 protein expression by immunohistochemistry (IHC). All tumours analysed expressed COX2 at a significantly higher level than BPH tissue (P=0.041). Only low levels of HER2 gene amplification (8%, 7/89) and HER2 protein expression (12%, 11/89) were observed. HER2 protein expression was rarely observed and did not correlate with HER2 amplification or COX2 expression. Although HER2 does not drive COX2 expression in prostate cancer, this study identified high levels of COX2 expressed in locally advanced prostate cancer, suggesting COX2 could be a potential therapeutic target. COX2 inhibitors are currently being used in clinical trials for the treatment of other tumour types.

Deposition in the lung and uptake to blood of motor exhaust labelled with 203Pb.

Inhalation of airborne lead from automobile exhaust is a significant source of intake. In these experiments a radioactive isotope of lead was used to label tetraethyl lead consumed in petrol engines. The resulting aerosols were inhaled by human volunteers to determine the percentage deposition in the lung, the pattern of removal from the lung and the resulting levels in the blood and excreta. Deposition in lung was shown to depend on particle size, varying from 40% for fresh, highly diluted aerosols to 14% for mature, aggregated aerosols, at a breathing rate of 15 breaths per minute. For aggregated aerosols the influence of rate of breathing, tidal volume and reserve volume was investigated. Uptake from the lung was rapid (T 1/2=6.6 h) and virtually complete with little, if any, ciliary clearance. Fifty per cent of the labelled lead remained in the blood, the concentration peaking after 2 days and subsequently declining exponentially (T 1/2 = 16 d). Total excretion was of the order of 1% of the intake per day up to 15 days.