Measurement of renovascular circulating volume during hypothermic organ perfusion.

BACKGROUND: Kidney donation after cardiac death leads to vascular damage as a result of warm ischemia, affecting renovascular circulating volume. Novel ultrasound dilution techniques may be used to measure renovascular circulating volumes during hypothermic machine perfusion of donor kidneys. METHODS: Renovascular circulating volumes of machine-perfused porcine kidneys were repeatedly measured by ultrasound dilution at different perfusion pressures (30, 40, 50, and 60 mm Hg), durations of perfusion (1 and 24 hr), and warm ischemia times (15 and 45 min). Validity of ultrasound dilution was assessed by comparing volume changes after clamping of renal artery branches. RESULTS: Repeatability of ultrasound dilution measurements of renovascular circulating volumes was good (mean coefficient of variation, 7.6%). Renovascular circulating volumes significantly increased with higher perfusion pressures, remained constant over time, and significantly decreased with longer warm ischemia times. Changes in ultrasound dilution measurements after renal artery branch clamping did not correlate with changes in actual perfused volumes. CONCLUSIONS: Ultrasound dilution is a reproducible method to assess renovascular circulating volumes in machine-perfused kidneys, which is susceptible to changes in warm ischemia times. Future studies should evaluate the value of renovascular volume in pretransplantation kidney viability testing.

The value of machine perfusion biomarker concentration in DCD kidney transplantations.

BACKGROUND: Donation after cardiac death (DCD) increases the number of donor kidneys but is associated with more primary nonfunction (PNF) and delayed graft function (DGF). It has been suggested that biomarkers in the preservation solution of machine perfused kidneys may predict PNF, although evidence is lacking. METHODS: We analyzed the diagnostic accuracy of the perfusate biomarkers glutathione S-transferase, lactate dehydrogenase (LDH), heart-type fatty acid binding protein, redox-active iron, interleukin (IL)-18, and neutrophil gelatinase-associated lipocalin to predict PNF and DGF in 335 DCD kidneys preserved by hypothermic machine perfusion at our center between 1 January 1997 and 1 January 2008. The diagnostic accuracy of these biomarkers to predict PNF was evaluated with the area under the receiver operating characteristics curves. Additionally, the risk of DGF and graft failure was assessed. RESULTS: LDH and IL-18 concentrations were associated with PNF (odds ratio [95% confidence interval], 1.001 [1.000-1.002]; P=0.005 and 1.001 [1.000-1.002]; P=0.003, respectively) in a multivariate analysis; the diagnostic accuracy for PNF was "poor" for all biomarkers but increased to "fair" for redox-active iron and IL-18 in a multivariate analysis (area under the receiver operating characteristics curves, 0.701 and 0.700, respectively). LDH and IL-18 concentrations were associated with DGF; biomarker concentration was not associated with 1-year graft survival. CONCLUSIONS: The diagnostic accuracy of the perfusate biomarkers glutathione S-transferase, LDH, heart-type fatty acid binding protein, redox-active iron, IL-18, and neutrophil gelatinase-associated lipocalin to predict viability of DCD kidneys varies from "poor" to "fair". Therefore, DCD kidneys should not be discarded because of high biomarker perfusate concentration.

Transplantation of kidneys from paediatric DCD donors: a comparison with DBD donors.

BACKGROUND: Although acceptable outcomes have been reported in kidney transplantation from donation after cardiac death (DCD), little is known about kidney transplantation from paediatric DCD. The objective of this study was to compare the outcome of kidney transplantation using paediatric DCD with the outcome of paediatric donation after brain death (DBD). METHODS: Recipients from DCD and DBD donors <18 years of age transplanted in the Netherlands between January 1981 and July 2006 were included in this study. Ninety-one patients were transplanted with kidneys from paediatric DCD donors and 405 patients received grafts from paediatric DBD donors. RESULTS: Grafts from DCD donors were associated with higher percentage of primary non-function (9 versus 2%, P < 0.01) and delayed graft function (48 versus 8%, P < 0.001) compared with DBD donor grafts. Estimated glomerular filtration rate did not differ between groups (57 ± 17 versus 58 ± 21 mL/min at 1 year and 62 ± 14 versus 57 ± 22 mL/min at 5 years, respectively). After correction for confounding variables, the risk of graft failure was higher in the DCD group [hazard ratio 2.440 (95% confidence interval (CI) 1.280-4.650; P = 0.007]. Patient survival, however, was similar between groups [hazard ratio 1.559 (95% CI 0.848-2.867; P = 0.153)]. CONCLUSIONS: Paediatric DCD kidneys represent a valuable source of donor kidneys that has not been fully utilized. Although transplantation of paediatric DCD kidneys is associated with a higher risk of graft failure than transplantation of paediatric DBD kidneys, results are comparable with adult donors. We therefore conclude that paediatric DCD kidneys can be safely added to the donor pool.

Addition of a water-soluble propofol formulation to preservation solution in experimental kidney transplantation.

BACKGROUND: Novel interventions that protect against ischemia and reperfusion injury are needed to improve early graft function after kidney transplantation. Propofol, a widely used anesthetic, has proven an efficient membrane-targeted antioxidant and cytoprotective agent. METHODS: The cytoprotective effects of propofol and its reaction intermediate dipropofol on hypothermic proximal tubular epithelial cells were compared with other phenolic antioxidants. For delivery of propofol into kidney grafts, a water-soluble cyclodextrin complex of propofol was prepared. The therapeutic effects of this propofol formulation were studied in a porcine autotransplantation model using 45 min of warm ischemia and 22 hr of hypothermic preservation. RESULTS: Propofol and dipropofol effectively protected tubular cells from hypothermic injury in vitro. Delivery of propofol to porcine kidneys was achieved by adding the cyclodextrin complex of propofol to the preservation solution during machine perfusion. This preservation strategy significantly prevented lipid peroxidation and tended to attenuate the increase in renovascular resistance during the early reperfusion period after autologous kidney transplantation. The antioxidant effects of propofol were followed by a modest improvement in renal function in the first 10 days after transplantation. Treatment with propofol during organ preservation did not reduce neutrophil infiltration into the graft. CONCLUSION: We consider propofol to be a promising renoprotective agent that may attenuate hypothermic and ischemic acute kidney injury in renal transplantation. The novel application of cyclodextrin carrier systems enabled delivery of the water-insoluble propofol to the graft during hypothermic preservation.

MRI of renal oxygenation and function after normothermic ischemia-reperfusion injury.

The in vivo assessment of renal damage after ischemia-reperfusion injury, such as in sepsis, hypovolemic shock or after transplantation, is a major challenge. This injury often results in temporary or permanent nonfunction. In order to improve the clinical outcome of the kidneys, novel therapies are currently being developed that limit renal ischemia-reperfusion injury. However, to fully address their therapeutic potential, noninvasive imaging methods are required which allow the in vivo visualization of different renal compartments and the evaluation of kidney function. In this study, MRI was applied to study kidney oxygenation and function in a murine model of renal ischemia-reperfusion injury at 7 T. During ischemia, there was a strongly decreased oxygenation, as measured using blood oxygen level-dependent MRI, compared with the contralateral control, which persisted after reperfusion. Moreover, it was possible to visualize differences in oxygenation between the different functional regions of the injured kidney. Dynamic contrast-enhanced MRI revealed a significantly reduced renal function, comprising perfusion and filtration, at 24 h after reperfusion. In conclusion, MRI is suitable for the noninvasive evaluation of renal oxygenation and function. Blood oxygen level-dependent or dynamic contrast-enhanced MRI may allow the early detection of renal pathology in patients with ischemia-reperfusion injury, such as in sepsis, hypovolemic shock or after transplantation, and consequently may lead to an earlier intervention or change of therapy to minimize kidney damage.

Kidney donation from children after cardiac death.

OBJECTIVE: Pediatric kidney donation after cardiac death is an underutilized donor source because of ethical concerns and limited knowledge of the outcome after transplantation. The purpose of this study was to report the Dutch experience of kidney transplantation using pediatric donation after cardiac death. DESIGN: Observational cohort study of a series of consecutive kidney transplantations from pediatric donation after cardiac death from January 1995 to July 2006. SETTING: Kidneys were procured in seven Dutch procurement areas. PATIENTS: Recipients of kidneys from donors after cardiac death aged 2 to 17 yrs. MEASUREMENTS AND MAIN RESULTS: Prospectively collected data from the Dutch Organ Transplant Registry were analyzed. Donor, graft, and recipient characteristics of all pediatric donations after cardiac death kidney transplantations were documented. Recipients were followed-up for glomerular filtration rate, graft, and patient survival. Eighty-eight patients were transplanted with 90 pediatric donation-after-cardiac-death kidneys, which was 31% of the total number of transplanted pediatric donor kidneys. In 77% of recipients, organs were procured from controlled donors, after withdrawal of supportive treatment. Of all donors, 9% were younger than age 6 yrs. Two patients received their graft preemptively. In the others, the incidence of immediate function, delayed graft function, and primary nonfunction were 49%, 44%, and 7%, respectively. Warm ischemia time > or =25 mins was associated with primary nonfunction. Overall graft and patient survival 5 yrs after transplantation were 80% and 88%, respectively. Graft survival after immediate function and delayed graft function was not different. CONCLUSIONS: Kidneys from pediatric donation after cardiac death are suitable for transplantation and may substantially expand the donor pool with good transplant outcome.

Kidney transplantation and donation in children.

It has been shown that kidney transplantation results in superior life expectancy and quality of life compared with dialysis treatment for patients with end-stage renal disease. However, kidney transplantation in children differs in many aspects from adult kidney transplantation. This review focuses on specific issues of surgical care associated with kidney transplantation in children, including timing of transplantation, technical considerations, patient and graft survival, growth retardation and post-transplant malignancy. At the same time, there is a large discrepancy between the number of available donor kidneys and the number of patients on the waiting list for kidney transplantation. There is a general reluctance to use paediatric donor kidneys, because of relatively frequent complications such as graft thrombosis and early graft failure. We review the specific aspects of kidney transplantation from paediatric donors such as the incidence of graft thrombosis, hyperfiltration injury and 'en bloc' transplantation of two kidneys from one donor with an excellent long-term outcome, which is comparable with adult donor kidney transplantation. We also discuss the potential use of paediatric non-heart-beating donor kidneys, from donors whose heart stopped beating with the preservation techniques used.