Renal Transplantation After Ex Vivo Normothermic Perfusion: The First Clinical Study

Transcription

1 American Journal of Transplantation 2013; 13: Wiley Periodicals Inc. C Copyright 2013 The American Society of Transplantation and the American Society of Transplant Surgeons doi: /ajt Renal Transplantation After Ex Vivo Normothermic Perfusion: The First Clinical Study M. L. Nicholson and S. A. Hosgood Department of Infection, Immunity and Inflammation, Transplant Group, Leicester General Hospital, University of Leicester, Leicester, UK Corresponding author: Michael L. Nicholson, mln2@le.ac.uk Ex vivo normothermic perfusion (EVNP) is a novel method of preservation that restores circulation and allows an organ to regain function prior to transplantation. The aim of this study was to assess the effects of EVNP in kidneys from marginal donors. Eighteen kidneys from extended criteria donors (ECD) underwent a period of EVNP immediately before transplantation. Kidneys were perfused with a plasma free redcell based solution at a mean temperature of 34.6 C. The outcome of these kidneys was compared to a control group of 47 ECD kidneys that underwent static cold storage (CS). The mean donor age was 61 ± 1 years in the EVNP and 62 ± 6 years in the CS group (p = 0.520). EVNP kidneys were perfused for an average of 63 ± 16 min and all were transplanted successfully. The delayed graft function rate (DGF), defined as the requirement for dialysis within the first 7 days was 1/18 patients (5.6%) in the EVNP group versus 17/47 (36.2%) in the CS group (p = 0.014). There was no difference in graft or patient survival at 12 months (p = 0.510, 1.000). This first series of EVNP in renal transplantation demonstrates that this technique is both feasible and safe. Our preliminary data suggests that EVNP offers promise as a new technique of kidney preservation. Key words: Kidney, preservation, transplantation Abbreviations: ATP, Adenosine triphosphate; CS, Cold storage; CIT, Cold ischemic time; DBD, Donation after brain death; DCD, Donation after circulatory death; DGF, Delayed graft function; ECD, Extended criteria donors; EVNP, Ex vivo normothermic perfusion; HMP, Hypothermic machine perfusion; HOC, Hyperosmolar citrate; IRR, Intra renal resistance; RBF, Renal blood flow; PNF, Primary non function; WIT, Warm ischemia time. Received 19 October 2012, revised 14 December 2012 and accepted for publication 03 January 2013 Introduction Ever since the inception of clinical renal transplantation, organs have been preserved under hypothermic conditions. This technique is simple, inexpensive and reliable but is 1246 limited by the fact that it depends on refrigeration. This affords protection by reducing the metabolic rate of the preserved organ, but it also has deleterious effects, leading to a metabolic profile that programs an inevitable degree of tissue injury at the time of reperfusion with oxygenated blood (1 3). Kidney transplantation continues to be limited by a shortage of organ donors. In response to this, there has been an increase in the use of kidneys from marginal donors and a significant proportion of transplant kidneys are now taken from so-called marginal donors including donation after circulatory death (DCDs) and extended criteria donors (ECDs). The definition of ECDs includes any donor aged 60 years or a donor aged 50 years plus two of three of the following features: a history of hypertension, a raised terminal serum creatinine (>1.5 mg/dl) or death from a cerebrovascular accident (4). Marginal kidneys have often been subjected to increased ischemia and this is reflected in high rates of delayed graft function (DGF), which can increase the risk of acute rejection and reduce long-term allograft survival (5 10). Normothermic perfusion techniques offer an alternative form of organ preservation and resuscitation that has the potential to limit some of the effects of hypothermic preservation techniques (11). Here, we report the results of the first clinical series of kidney transplants performed after a period of ex vivo normothermic perfusion (EVNP) using a red cell-based plasma-free solution. The study was designed to test the feasibility, safety and efficacy of EVNP versus traditional cold storage (CS) in renal transplantation. Methods Patients All data were collected prospectively and the transplants performed at this single center. Between December 2010 and August kidneys that fell into the ECD category underwent EVNP. These 18 patients were compared to a control group of 47 recipients of ECD kidneys that underwent static cold storage from March 2008 to August 2012 in the same center. The groups were matched for donor and recipient age, cold ischemic time (CIT) and included recipients of a first transplant only. Ethical approval The University Hospitals of Leicester NHS Trust Clinical Ethics Committee and New Interventional Procedures Advisory Group approved the implementation of EVNP into clinical practice for kidneys from marginal donors (ECD). Approval was also granted from the Kidney Advisory Group, NHS

2 Normothermic Kidney Perfusion Blood & Transplant. Written informed consent was gained from the recipients before the transplant procedure. Kidney retrieval All kidneys were retrieval by UK national retrieval teams. Following in situ flushing of the abdominal organs with University of Wisconsin (UW) solution, kidneys were removed and then placed individually in UW solution and packed in ice. EVNP The ex vivo kidney perfusion circuit was designed using paediatric cardiopulmonary bypass technology (Medtronic, Watford, UK) and consisted of a centrifugal blood pump (Bio-pump 560), a heat exchanger (Chalice Medical, Nottinghamshire, UK), a 5-L venous reservoir (Medtronic), 1/4 inch PVC tubing and an Affinity membrane oxygenator (Medtronic). The hardware included a speed controller, a TX50P flow transducer and a temperature probe (Cole-Parmer, London, UK). Two Alaris infusion pumps (Carefusion, Basingstoke, UK) were also incorporated into the system. The circuit was primed with perfusate solution (Ringer s solution ml, Baxter Healthcare, Thetford, Norfolk, UK) and one unit of ABO compatible cross-matched packed red cells from the blood bank (mean ± SD; 294 ± 14 ml). Manntiol 10% 25 ml (Baxter Healthcare), dexamethasone 8 mg (Organon Laboratories, Cambridge, UK) and heparin 1000 iu/ml 2 ml (CP Pharmaceuticals, Wrexham, UK) were added to the perfusate. Sodium bicarbonate 8.4% (Fresenius Kabi, Cheshire, UK) was added to normalize the ph. A nutrient solution (Nutriflex, B. Braun, Sheffield, UK, South Yorkshire, UK) with sodium bicarbonate 25 ml 8.4%, insulin 100 iu (Novo Nordisk, Denmark) and multivitamins (Cernevit, Baxter Healthcare) was infused into the circuit at a rate of 20 ml/h. Prostacyclin 0.5 mg (Flolan, Glaxo-Wellcome, Middlesex, UK) was infused into the arterial arm of the circuit at a rate of 4 ml/h and glucose 5% (Baxter Healthcare) at 7 ml/h. Ringer s solution was used to replace urine output ml for ml. ECD donors were defined as age 60 years or 50 years with two of the following conditions: death caused by a cerebrovascular accident, raised terminal serum creatinine 1.5 mg/dl or a history of hypertension. The warm ischemic time (WIT) was defined as the period after cardiac arrest and before in situ organ perfusion. The first CIT was defined as the time from in situ organ perfusion until the start of EVNP. The second CIT was defined as the time from EVNP until the kidney was taken out of ice at the start of the anastomosis. The total ischemic time was defined as the time from in situ organ perfusion until reperfusion and included any WIT. Transplantation Kidneys were transplanted into the right iliac fossa with anastomosis of the artery and vein to the external iliac vessels and the ureter to the bladder as an extravesical onlay over a double J stent. Immunosuppression All patients were immunosuppressed with the standard unit regimen of basiliximab (20 mg on days 0 and 4), tacrolimus (0.1 mg/kg/day to maintain trough levels of 6 10 ng/ml), mycophenolate mofetil (500 mg twice daily) and prednisolone (20 mg daily). Outcome measures Primary nonfunction (PNF) was defined as failure of a graft to function ever, irrespective of cause. DGF was defined as the need for dialysis within the first week following transplantation. Graft failure was defined as the need for graft nephrectomy or return to renal replacement therapy. Renal allograft rejection was biopsy-proven and defined by Banff criteria. Statistical analysis Continuous data are presented as mean ± SD, median and range where appropriate. Data was compared using the student s t-test for parametric or Mann Whitney U test for nonparametric variables. Categorical variables were analyzed by Fisher s exact test. p < was considered statistically significant. Correlations were made using the Pearson rank test. GraphPad Prism 5 was used for statistical analysis (GraphPad Software, La Jolla, CA, USA). All kidneys undergoing EVNP were placed in a custom designed sterile perfusion chamber and the renal artery and vein were cannulated and primed with cold 0.9% sodium chloride. Care was taken to exclude any air from the circuit at the start of perfusion. Kidneys were perfused at a set mean arterial pressure (52 70 mmhg). The plasma-free red cell-based perfusate was circulated from the venous reservoir through the centrifugal pump into the membrane oxygenator, where it was oxygenated and also warmed to C. It then flowed through the arterial limb of the circuit to the renal artery. Venous return from the renal vein was fed back into the reservoir (Figure 1A C). Renal blood flow (RBF) was monitored continuously during EVNP. Intrarenal resistance (IRR) was calculated (mean arterial pressure/rbf) every 5 min for the first 15 min then every 15 min until the end of perfusion. The total urine output was recorded. Blood gas analysis was used to measure the acid base balance pre and post EVNP. After EVNP, kidneys were flushed with approximately 500 ml of cold (4 C) hyperosmolar citrate (HOC, Baxter Healthcare, UK) to remove the perfusate and then placed back in ice until transplanted. Prior to transplantation the arterial Carrel patch was excised along with a short segment of vein in order to remove the cannula ligature sites. American Journal of Transplantation 2013; 13: Results Donor and recipient demographics and transplant characteristics are summarized in Table 1. There were significantly more predialysis patients and more receiving hemodialysis (HD) in the EVNP group compared to the CS (p = 0.001, 0.047). The cold ischemic and total ischemic time were not significantly different between the groups (p = 0.240, 0.614). The second CIT after EVNP was relatively short (26 ± 20 min). However, in one case the intended recipient suffered an anaphylactic reaction shortly after the induction of anesthesia and while the kidney was undergoing EVNP. The patient was resuscitated but did not proceed with the transplant procedure. The kidney underwent EVNP for 60 min and was then flushed with HOC at 4 C and placed back on ice. Another recipient was identified and the kidney was successfully transplanted after an additional 5 h and 21 min of cold ischemia. The anastomosis time was marginally longer in the control group and this reached statistical significance (p = 0.010). 1247

3 Nicholson and Hosgood Figure 1: (A) Schematic diagram of the clinical ex vivo normothermic perfusion (EVNP) system. The arrows show the direction of blood flow. The system hardware was based on paediatric cardiopulmonary bypass technology (Bioconsole 560). Under sterile conditions the renal artery, vein and ureter were cannulated and the kidney placed in a custom made stainless steel perfusion chamber on the perfusion trolley. The perfusate was pumped from the venous reservoir via the centrifugal pump into the membrane oxygenator and heat exchanger before entering the arterial arm of the circuit. The oxygenated and warmed blood entered the kidney via the renal artery andwasthenallowedtodrainfrom the vein back into the reservoir where it was recirculated. The arterial pressure was fixed allowing the kidney to autoregulate its own blood flow. The urine was collected into a sterile container. Nutrients, fluids and glucose were continually infused into the circuit. (B) Photograph of the ex vivo normothermic perfusion (EVNP) system and (C) kidney in the perfusion chamber during EVNP. Three out of 18 kidneys in the EVNP group and 14 of 47 in the CS group had multiple vessels (p = 0.357). Kidney function during EVNP The perfusion parameters of the 18 kidneys undergoing EVNP are detailed in Tables 2 and 3. All EVNP kidneys were perfused without any complications and all produced urine, although the amount varied significantly ranging from 50 to 450 ml. There was some fluctuation in the IRR during EVNP over the first 15 min in all kidneys but overall there was a general decline throughout perfusion. Three kidneys had particularly high levels of IRR throughout EVNP (mean IRR > 0.78 mmhg/ml/100 g). Two of these kidneys appeared evenly perfused but only produced 50 ml of urine. The third was from a 79-year-old donor and the kidney had a blotchy appearance throughout EVNP but did produce 75 ml of urine. IRR correlated significantly with donor age (p = 0.027; Figure 2A) and was associated with a lower production of urine during EVNP (p = 0.035; Figure 2B). Outcome There were no incidences of PNF in the EVNP group (0%) and 1 in the CS group (2%) (p = 1.000). The rate of DGF was 1/18 patients (5.6%) in the EVNP group versus 17/47 (36.2%) in the control group (p = 0.014). There were no differences in graft or patient survival at 12 months (p = 0.510, 1.000; Figure 3A, B). The incidence of acute 1248 American Journal of Transplantation 2013; 13:

4 Normothermic Kidney Perfusion Table 1: Donor and recipient demographics and transplant characteristics EVNP CS p Value (18) (47) Donor Age (years) 61 ± 1 62± M:F 4:14 17: Cause of death ICH Hypoxia Other Recipient Age (years) 58 ± ± M:F 12:6 27: Dialysis HD CAPD Predialysis Total HLA-A,B,-DR mismatches Transplant characteristics First CIT (h) 10.6 ± ± EVNP (min) 63 ± 16 Second CIT (h) 26 ± 20 Anastomosis (min) 26 ± 6 31± Total ischemia (h) 12.9 ± ± Values are mean ± SD and range. CAPD = continuous ambulatory peritoneal dialysis; CIT = cold ischemic time; EVNP = ex vivo normothermic perfusion; HD = hemodialysis; HLA = human leukocyte antigen; ICH = intracranial hemorrhage. Unpaired t-test for parametric data. Table 2: Ex vivo normothermic perfusion parameters of the 18 ECD kidneys Mean Range Ex vivo normothermic perfusion parameters MAP (mmhg) 62 ± RBF (ml/min/100 g) 67 ± IRR (mmhg/ml/min/100 g) 0.35 ± Total urine output (ml) 189 ± Temperature ( C) 34.6 ± IRR = Intrarenal resistance; MAP = mean arterial pressure; RBF = renal blood flow. rejection was similar in both groups (EVNP 5/18 [27.7%] vs. CS 11/47 [23.4%]; p = 0.753). The median length of follow up was 640 (range ) days in the CS kidneys and 356 (range ) days in the EVNP kidneys. The recipients of the three kidneys with a higher mean IRR during EVNP were all dialysis dependent patients and all had immediate graft function after transplantation, although in one patient there was a slow decline in serum creatinine levels during the first week. The kidney of the only patient with DGF had good perfusion parameters and produced 250 ml of urine during EVNP. The recipient was a 72-year-old hemodialysis dependent gentleman who suffered a period of hypotension immediately after transplan- American Journal of Transplantation 2013; 13: A B Mean IRR (mmhg/ml/min/100g) Mean IRR (mmhg/ml/min/100g) Donor age (years) Total urine output (ml) Figure 2: Correlations between (A) mean intrarenal resistance (IRR) (mmhg/ml/min) and donor age (years); p = 0.027, R 2 = and (B) mean intrarenal resistance (mmhg/ml/min) and the total urine output (ml); p = 0.035, R 2 = during ex vivo normothermic perfusion (EVNP). Pearson rank test. Table 3: Perfusion parameters pre and at the end of ex vivo normothermic perfusion Pre End p Value ph 7.43 ± ± HCT % 23 ± 5 22± PO 2 kpa 64.0 ± ± PCO 2 kpa 5.55 ± ± HCT = Hematocrit; (PO 2 ) = partial pressure of oxygen; (PCO 2 ) = partial pressure of carbon dioxide. Student s t-test for parametric data values are mean ± SD and range. tation. He had two episodes of dialysis for azotemia and fluid overload 8 days posttransplant. He was treated for 2A rejection 3 months posttransplant. He suffered reccurring urinary tract infections and at 7 months was diagnosed with an in situ bladder carcinoma. His immunosuppressive therapy was withdrawn and he is now dialysis dependent. The recipient of the kidney that had an additional 5 h 21 min of CS was a predialysis patient. She had good initial graft function with her serum creatinine levels falling from 1249

5 Nicholson and Hosgood Percent survival A Percent survival B Graft Survival Days Post-Transplant Patient Survival Days Post-Transplant CS EVNP CS EVNP Figure 3: (A) Kaplan Meier estimates of survival in recipients of static cold stored (CS and ex vivo normothermic perfusion kidneys. (B) Kaplan Meier estimates of patient survival in recipients of static cold stored (CS) and ex vivo normothermic perfusion kidneys. 315 lmol/l pretransplant to 105 lmol/l on postoperative day 7. Discussion This study describes the first human series of renal transplants performed after a short period of ex vivo normothermic perfusion with an oxygenated red cell-based plasmafree perfusate. This early experience demonstrates the feasibility and safety of the technique. In addition, the rate of DGF in marginal donor kidneys undergoing EVNP was significantly lower than the consecutive historical control group of kidneys preserved by traditional CS. This is an important finding because DGF is associated with higher rates of acute rejection and poorer long-term allograft survival (6,8). There is a good deal of published literature showing that kidney transplants from marginal donors and ECDs have poorer early graft function compared to kidneys from standard criteria DBD donors, with reported DGF rates ranging from 11% (10) to 63% (4). In our initial experience DGF, defined as the requirement for dialysis in the first 7 postoperative days, only occurred in 1/18 kidneys (5.6%) undergoing EVNP. The protocol used in this study was straightforward and was translated into clinical practice without difficulty, although the technique does require a trained perfusionist. The circuit was designed using cardiopulmonary bypass technology and the perfusate was based on cross-matched packed red cells from the local blood bank. The logistics of the technique were relatively undemanding as the ex vivo perfusions were carried out in the operating theatre during the anesthetic time and the period in which the transplant bed was being prepared for engraftment; this was both convenient and safe. The fail-safe procedure for problems during EVNP would be to prematurely remove the kidney from the circuit and to revert to cold preservation. This was not necessary in any of the cases described. All 18 kidneys were perfused without complications and with no apparent deleterious effects to the transplant kidneys or the recipients. There were no clinical episodes of graft infection. The underlying principle of EVNP is to expose the transplant kidney to a period of ideal perfusion before final reperfusion in the recipient. The red cell-based perfusate was designed to reduce the likelihood of inflammation and oxidative injury (12 14). The optimal arterial pressure was informed by preclinical testing, being set at the lower end of the physiological range for renal autoregulation in order to reduce endothelial injury (14). This should allow some resuscitation of the graft by replenishment of ATP levels (15). The absence of white cells during EVNP eliminates the interaction between neutrophils and endothelial cells and allows oxygen to be reintroduced with fewer consequences (12,16). Although 60 min of EVNP immediately before transplantation appears to be beneficial, the optimal duration or timing of EVNP has not been determined. In experimental models we have previously used 120 min of EVNP (15) and the acellular technique reported by the Brasile group relied on 180 min of perfusion to recover function (17). Longer resuscitation times may be needed to recover function in more ischemically damaged kidneys but further evidence is required to examine this. In the liver, prolonged normothermic perfusion (20 h) showed no benefit after warm and cold ischemic injury; however, this was possibly due to the liver s low tolerance to cold ischemic injury (18). The encouraging result in the kidney that had a further 5 h of CS after EVNP suggests that the timing of EVNP may be varied and again further evidence is required to determine the benefits of this. Experimentally, oxygenated hypothermic perfusion techniques have also been used to reduce preservation injury in ischemically damaged livers (19) and kidneys (20). Providing oxygen for a short period under these circumstances appears to support a low level of metabolism that can condition an organ and reduce the injury incurred during reperfusion. EVNP aims to restore 1250 American Journal of Transplantation 2013; 13:

6 Normothermic Kidney Perfusion a higher level metabolism and function to enhance recovery and this may be more advantageous than hypothermic conditions, although this has not been determined. This study is limited by the small number of patients and the historical nature of the control group. The groups were matched for the inclusion of ECDs only, recipient age, CIT and the recipients of a first transplant only. Nonetheless, the successful application of EVNP has important implications for the future of marginal donor kidney transplantation. Pretransplant viability testing will become more important as greater numbers of marginal organs are being offered for transplantation. So far attempts at pretransplant viability testing have concentrated on assessments of injury (21). In contrast, by establishing renal function ex vivo, EVNP may offer a method to measure the potential for recovery. This has been adopted in marginal lung transplantation (22) and is an important area for development in kidney transplantation as approximately 11 20% of retrieved kidneys in the United Kingdom and the United States are discarded, many due to concerns over viability (23,24). The number of kidneys undergoing EVNP in this study was insufficient to predict outcome. However, it was encouraging that simple measurements of IRR and urine output were reflective of donor age. With increasing cases these parameters, in addition to measures of glomerular and tubular function, may also be useful in the prediction of outcome. Stem cell and gene therapy are growing areas of research and could be applied during EVNP to target the longstanding problems of rejection and fibrosis. This would allow direct manipulation of the kidney and overcome the problems associated with targeting specific organs and the unwanted side effects when these therapies are administered directly to the patient. In conclusion, short duration EVNP in renal transplantation is a novel technique that is both feasible and safe. The next step should be to establish the technique in other transplant centers in order to test its efficacy in the setting of a multicenter randomised clinical trial. Acknowledgments This study was supported by Kidney Research UK (Registered charity No ). Disclosure The authors of this manuscript have no conflicts of interest to disclose as described by the American Journal of Transplantation. References 1. McAnulty JF. Hypothermic organ preservation by static storage methods: Current status and a view to the future. Cryobiology 2010; 60(Suppl): S13 S19. American Journal of Transplantation 2013; 13: Fuller BJ, Lee CY. Hypothermic perfusion preservation: The future of organ preservation revisited? Cryobiology 2007; 54: Salahudeen AK. Cold ischemic injury of transplanted kidneys: New insights from experimental studies. Am J Physiol Renal Physiol 2004; 287: F181 F Pascual J, Zamora J, Pirsch JD. A systematic review of kidney transplantation from expanded criteria donors. Am J Kidney Dis 2008; 52: Saidi RF, Elias N, Kawai T, et al. Outcome of kidney transplantation using expanded criteria donors and donation after cardiac death kidneys: Realities and costs. Am J Transplant 2007; 7: van der Vliet JA, Warle MC, Cheung CL, Teerenstra S, Hoitsma AJ. Influence of prolonged cold ischemia in renal transplantation. Clin Transplant 2011; 25: E612 E Snoeijs MG, Winkens B, Heemskerk MB, et al. Kidney transplantation from donors after cardiac death: A 25-year experience. Transplantation 2010; 90: Yarlagadda SG, Coca SG, Formica RN, Jr, Poggio ED, Parikh CR. Association between delayed graft function and allograft and patient survival: A systematic review and meta-analysis. Nephrol Dial Transplant 2009; 24: Rao PS, Ojo A. The alphabet soup of kidney transplantation: SCD, DCD, ECD fundamentals for the practicing nephrologist. Clin J Am Soc Nephrol 2009; 4: Quiroga I, McShane P, Koo DD, et al. Major effects of delayed graft function and cold ischaemia time on renal allograft survival. Nephrol Dial Transplant 2006; 21: Hosgood SA, Nicholson ML. First in man renal transplantation after ex vivo normothermic perfusion. Transplantation 2011; 92: Harper S, Hosgood S, Kay M, Nicholson M. Leucocyte depletion improves renal function during reperfusion using an experimental isolated haemoperfused organ preservation system. Br J Surg 2006; 93: Hosgood SA, Barlow AD, Yates PJ, Snoeijs MG, van Heurn EL, Nicholson ML. A pilot study assessing the feasibility of a short period of normothermic preservation in an experimental model of non heart beating donor kidneys. J Surg Res 2011; 171: Hosgood S, Harper S, Kay M, Bagul A, Waller H, Nicholson ML. Effects of arterial pressure in an experimental isolated haemoperfused porcine kidney preservation system. Br J Surg 2006; 93: Bagul A, Hosgood SA, Kaushik M, Kay MD, Waller HL, Nicholson ML. Experimental renal preservation by normothermic resuscitation perfusion with autologous blood. Br J Surg 2008; 95: Bonventre JV. Complement and renal ischemia-reperfusion injury. Am J Kidney Dis 2001; 38: Brasile L, Stubenitsky BM, Booster MH, Arenada D, Haisch C, Kootstra G. Hypothermia A limiting factor in using warm ischaemically damaged kidneys. Am J Transplant 2001; 1: Reddy SP, Bhattacharjya S, Maniakin N, et al. Preservation of porcine non-heart-beating donor livers by sequential cold storage and warm perfusion. Transplantation 2004; 77: de Rougemont O, Breitenstein S, Leskosek B, et al. One hour hypothermic oxygenated perfusion (HOPE) protects nonviable liver allografts donated after cardiac death. Ann Surg 2009; 250: Minor T, Efferz P, Lüer B. Hypothermic reconditioning by gaseous oxygen persufflation after cold storage of porcine kidneys. Cryobiology 2012; 65: Warnecke G, Moradiellos J, Tudorache I, et al. Normothermic perfusion of donor lungs for preservation and assessment with the 1251

7 Nicholson and Hosgood Organ Care System Lung before bilateral transplantation: A pilot study of 12 patients. Lancet 2012; 380: Jochmans I, Lerut E, van Pelt J, Monbaliu D, Pirenne J. Circulating AST, H-FABP, and NGAL are early and accurate biomarkers of graft injury and dysfunction in a preclinical model of kidney transplantation. Ann Surg 2011; 254: UK Transplant transplant_activity_report/current_activity_reports/ukt/slide_set_ odt_website.ppt. Accessed October 5, Klein AS, Messersmith EE, Ratner LE, Kochik R, Baliga PK, Ojo AO. Organ donation and utilization in the United States, Am J Transplant 2010; 10: American Journal of Transplantation 2013; 13: