A Low‐Cost,Small Volume Circuit for Autologous Blood Normothermic Perfusion of Rabbit Organs

We have designed a laboratory extracorporeal normothermic blood perfusion system for whole organs (e.g., kidney) that achieves pulsatile flow, low levels of hemolysis, and a blood priming volume of 60 mL or less. Using this uniquely designed extracorporeal circuit, we have achieved perfusion of two isolated ex vivo constructs. In the first experiment, we successfully perfused a rabbit epigastric flap based on the femoral vessels. In the second experiment, we were able to perfuse the isolated rabbit kidney for 48 h (range for all kidneys was 12–48 h) with excellent urine output, normal arterial blood gasses at 24 h, and normal ex vivo kidney histology at the conclusion of the experiments. These parameters have not been achieved before with any known or previously published laboratory extracorporeal circuits. The study has implications for prolonged organ perfusion prior to transplantation and for tissue engineering of vascularized tissues, such as by the perfusion of decellularized organs.     

Optimisation of Bile Production during Normothermic Preservation of Porcine Livers

Machine perfusion of livers may provide a mechanism for extended preservation of marginal donor organs before transplantation, as well as a method for viability assessment. It has proved possible in a series of experimental porcine liver perfusions to maintain liver viability for up to 72 h. However, a reduction in bile production with associated histological evidence of cholestasis was seen after 10 h of perfusion, damaging the biliary canaliculi during the preservation period and leaving these organs in an unacceptable condition for transplantation. It was proposed that reduction in bile production was the result of a relentless depletion of available bile salts, gut recirculation not being possible and de-novo synthesis being unable to keep up with loss. This was proved by measuring porcine native bile acids within serial perfusate and bile samples using gas chromatography mass spectrophotometry. It was shown that all three native pig bile acids were decreased to 30% of their original value by 20 h of unsupplemented perfusion. An infusion of taurocholate managed to maintain bile production at physiological levels throughout the 20-h period (8 mL/h +/- 0.75). It was successfully incorporated by the porcine livers into bile. We propose to use this circuit as a novel means of preserving donor livers for transplantation in which the organ is maintained at normal body temperature and perfused with blood. This will reduce ischaemia reperfusion injury and may enable prolonged preservation. The modification described ensures optimal bile production over the entire perfusion period, preventing inspissation and subsequent damage to the canaliculus.     

Perfusate lactate dehydrogenase level and intrarenal resistance could not be adequate markers of perfusion quality during isolated kidney perfusion

The main goal of this work was to study the influence of perfusion pressure and flow waveform during kidney perfusion, and the relationship between renal vascular resistance (RVR) and lactate dehydrogenase (LDH) concentration in the perfusate. Simultaneous constant pressure kidney perfusions were performed with either pulsatile or continuous flow at either 30 or 80 mm Hg of constant perfusion pressure. Mean flow, pressure, and RVR were displayed online during perfusion. Perfusate samples for LDH, creatine phosphatase kinase (CPK), and alkaline phosphatase (AP) determinations were taken. At the end of the perfusion, 2 ml of Evans blue was injected into the circuit to obtain images of perfusate distribution, and the kidneys were weighed. Also, hematoxylin/eosine studies were performed, showing more Bowman's space and tubular dilation in kidneys perfused with high pressure. We did not find differences in RVR between kidneys perfused at 30 and 80 mm Hg; nevertheless, perfusate distribution was better in the 80 mm Hg perfusions. We did not find any correlation between enzyme release and RVR in kidneys perfused with different mean pressures. These findings suggest that vascular resistance and LDH concentration cannot be independently considered as adequate markers of perfusate distribution.     

In Situ Normothermic Regional Perfusion for Controlled Donation After Circulatory Death—The United Kingdom Experience

Organs recovered from donors after circulatory death (DCD) suffer warm ischemia before cold storage which may prejudice graft survival and result in a greater risk of complications after transplant. A period of normothermic regional perfusion (NRP) in the donor may reverse these effects and improve organ function. Twenty‐one NRP retrievals from Maastricht category III DCD donors were performed at three UK centers. NRP was established postasystole via aortic and caval cannulation and maintained for 2 h. Blood gases and biochemistry were monitored to assess organ function. Sixty‐three organs were recovered. Forty‐nine patients were transplanted. The median time from asystole to NRP was 16 min (range 10–23 min). Thirty‐two patients received a kidney transplant. The median cold ischemia time was 12 h 30 min (range 5 h 25 min–18 h 22 min). The median creatinine at 3 and 12 months was 107 µmol/L (range 72–222) and 121 µmol/L (range 63–157), respectively. Thirteen (40%) recipients had delayed graft function and four lost the grafts. Eleven patients received a liver transplant. The first week median peak ALT was 389 IU/L (range 58–3043). One patient had primary nonfunction. Two combined pancreas–kidney transplants, one islet transplant and three double lung transplants were performed with primary function. NRP in DCD donation facilitates organ recovery and may improve short‐term outcomes.     

The isolated perfused porcine liver: assessment of viability during and after six hours of perfusion

Isolated liver perfusion was developed for the study of liver physiology and preservation. The recent development of new perfusion devices and appropriate liver preservation solutions prompted us to reconsider liver perfusion for the specific purpose of evaluating viability in terms of biochemical changes, paying special attention to modifications in the histological ultrastructure. Twenty-two isolated pig livers were perfused with autologous blood. Arterio-portal perfusions were carried out using an extracorporeal perfusion circuit with a hollow fibre membrane oxygenator. Four groups of pig livers were studied using three different liver flushing solutions [Ringer's lactate, ELOHES, and University of Wisconsin (UW)] and two different oxygenation modalities. Liver function tests and histological studies were done. Our results revealed that a high partial oxygen pressure (PO₂) level was deleterious to the ultrastructural elements of hepatocytes, in particular to the mitochondria. It was also associated with deficient metabolic performance, i. e., poor bile production and lack of aerobic metabolism. Normal blood gas values could be obtained with the use of air for liver oxygenation. Flushing of the liver with Ringer's lactate or a macromolecular solution such as ELOHES was associated with severe liver cell injuries, as reflected by a marked rise in liver enzymes and histological lesions. Satisfactory results were obtained when UW solution was used for liver harvesting. We conclude that an appropriate liver preservation solution, normal blood gas values, and normal physiological arterio-portal pressure and blood flow are essential for appropriate liver function with preservation of liver architecture and of hepatocyte ultrastructures. Total bilirubin in bile and Factor V are sensitive indicators of good liver function. Received: 24 January 1997 Received after revision: 18 April 1997 Accepted: 24 April 1997     

Fluorochemical perfusates for renal preservation.

We have evaluated the use of dispersed fluorochemicals in cryoprecipitated plasma as a perfusage for renal preservation. FC-43(47) has been shown to be a superior perfusate to FX-80 despite its lower oxygen binding capacity. Significant improvement in survival of transplanted kidneys following 24 hr hypothermic perfusion was experienced with the FC-43(47). When comparing the FC-43(47) dispersion with plasma, no significant differences were found in the perfusion characteristics of the kidney while on the perfusion apparatus aside from the creatinine clearances which were significantly higher with the fluorochemical perfusate. One hundred percent of the kidneys perfused with the FC-43(47) perfusate survived with normal creatinines at the end of 30 days compared to only 27% perfused with FX-80 and 62% perfused only with plasma. The maximum creatinine that developed with FC-43(47) was not significantly different from the value obtained with the plasma perfusates.While these experiments do not clearly establish fluorochemical perfusates as superior to plasma, they indicate that in longer term perfusions of 48 and 72 hr a significant difference may be observed.     

Iron chelators do not reduce cold-induced cell injury in the isolated perfused rat kidney model.

BACKGROUND: In vitro, cold-induced injury is an important contributor to renal tubular cell damage. It is mediated by iron-dependent formation of reactive oxygen species and can be prevented by iron chelation. We studied whether iron chelators can prevent cold-induced damage in the isolated perfused rat kidney (IPK) model both after cold perfusion (CP) and after cold storage (CS). We hypothesized that in the CP model iron-dependent cold-induced injury is more pronounced, since oxygen is constantly provided. METHODS: The IPK was either flushed with University of Wisconsin (UW) solution and stored for 4, 18 or 24 h at 4 degrees C or perfused during 4 h at 4 degrees C with UW for machine perfusion. The iron chelators 2,2'-dipyridyl or desferal, or the negative control 4,4'-dipyridyl were added during the cold perfusion. Kidney function was measured during 2 h reperfusion at 37.5 degrees C and compared to a control group (without cold preservation). RESULTS: Compared to control perfusion, kidney function was decreased in all experimental protocols. glomerular filtration rate and FR(H2O) were significantly decreased, while FE(gluc) and FE(Na) were higher after 4 h CS and CP. After 4 h CP, also renal vascular resistance was increased. Addition of 2,2'-dipyridyl did not improve kidney function after either CS or CP. Prolonged periods of CS worsened kidney function. The addition of 2,2'-dipyridyl or desferal did not improve kidney function after longer periods of CS. CONCLUSIONS: Addition of an iron chelator to the preservation solution UW did not improve kidney function after both CS and CP. Iron chelation is not able to prevent cold-induced damage in the isolated perfused rat kidney.     

Removal of blood group A/B antigen in organs by ex vivo and in vivo administration of endo-beta-galactosidase (ABase) for ABO-incompatible transplantation

BACKGROUND: ABO incompatibility in organ transplantation is still a high risk factor for antibody-mediated rejection, despite the progress in effective treatments. We have explored the possibility of using the enzyme to remove the blood type A/B antigen in organs. METHODS: Recombinant endo-beta-galactosidase (ABase), which releases A/B antigen, was produced in E. coli BL-21. Human A/B red blood cells (RBC) were digested with ABase, and subjected to flow cytometric analysis after incubation with human sera. Purified recombinant ABase was intravenously administered to a baboon. Biopsies were taken from kidney and liver before and 1, 4 and 24 h after in vivo administration. Excised baboon kidneys were perfused with cold UW solution+/-purified recombinant ABase and preserved at 4 degrees C. Biopsies were taken before and 1 and 4 h after ex vivo perfusion. The change in A/B antigen expression was analyzed by immunohistochemical study. RESULTS: ABase removed 82% of A antigen and 95% of B antigen in human A/B red blood cells, and suppressed anti-A/B antibody binding and complement activation effectively. ABase was also found to remain active at 4 degrees C. In vivo infusion of ABase into a blood type A baboon demonstrated a marked reduction of A antigen expression in the glomeruli of kidney (85% at 1 h, 9% at 4 h and 13% at 24 h) and the sinusoids of liver (47% at 1 h, 1% at 4 h and 3% at 24 h) without serious adverse effects. After ex vivo perfusion and cold storage of excised baboon kidney (blood type B) with ABase, the expression levels of B antigen in glomeruli were reduced to 49% at 1 h and 6% at 4 h. CONCLUSIONS: This alternative approach might be useful for minimizing antibody removal and anti-B cell immunosuppression as an adjuvant therapy in ABO-incompatible kidney, liver and possibly heart transplantation.     

Functional metabolic characteristics of intact pig livers during prolonged extracorporeal perfusion: potential for a unique biological liver-assist device

BACKGROUND: The clinical development of liver-support devices based on perfusion of either pig hepatocytes cartridges or whole pig livers has been hampered by the ability to use sufficient liver cell mass to provide adequate metabolic support, limited perfusion times, and the potential for patient exposure to pig zoonotic diseases. METHODS: We designed an original system in which an isolated intact pig liver was perfused extracorporeally under physiological conditions in a closed loop circuit with allogeneic pig blood and constant monitoring of major physiological and functional parameters. The perfusion circuit further included an interface membrane to provide for separation of patient and liver perfusion circulation. RESULTS: Prolonged (6-21 hr) liver perfusion did not produce significant liver damage as reflected by modest rises in the levels of the serum transaminases, stability of main biochemical parameters (including potassium), and the maintenance of normal cellular morphology. Optimal liver function was documented as measured by lactate consumption, control of glycemia, and the results of clotting studies and functional assays. The perfused liver cleared 82% and 79% of peak bilirubin and ammonia concentrations with clearing kinetics identical throughout perfusion. Indocyanine green clearance was identical to that observed in the living donor before explant surgery. CONCLUSIONS: In conclusion, the extracorporeal pig liver perfusion apparatus described here allows optimal pig liver function for prolonged periods of time. The microporous membrane to provide separation of donor organ and recipient and the high level of functional activity suggest that this form of liver metabolic support may have important clinical applications.     

A new liver perfusion and preservation system for transplantation research in large animals

A kidney perfusion machine, model MOX-100 (Waters Instruments, Ltd, Rochester, MN) was modified to allow continuous perfusion of the portal vein and pulsatile perfusion of the hepatic artery of the liver. Additional apparatus consists of a cooling system, a membrane oxygenator, a filter for foreign bodies, and bubble traps. This system not only allows hypothermic perfusion preservation of the liver graft, but furthermore enables investigation of ex vivo simulation of various circulatory circumstances in which physiological perfusion of the liver is studied. We have used this system to evaluate the viability of liver allografts preserved by cold storage. The liver was placed on the perfusion system and perfused with blood with a hematocrit of approximately 20%, and maintained at 37 degrees C for 3 h. The flows of the hepatic artery and portal vein were adjusted to 0.33 mL and 0.67 mL/g of liver tissue, respectively. Parameters of viability consisted of hourly bile output, oxygen consumption, liver enzymes, electrolytes, vascular resistance, and liver histology. This method of liver assessment in large animals will allow the objective evaluation of organ viability for transplantation and thereby improve the outcome of organ transplantation. Furthermore, this pump enables investigation into the pathophysiology of liver ischemia and preservation.     

Some functions of canine liver perfused ex vivo with bloodless fluorocarbon emulsion.

6 canine livers were perfused extracorporeally with bloodless fluorocarbon emulsion for 6 h. Perfusate was oxygenated in vitro with a mixture of oxygen and carbon dioxide. Biochemical studies were performed on the samples of perfusate taken from the arterial and venous lines of the perfusion circuit, and of the bile. Hepatic tissue was sampled prior to and following 6 h of perfusion for histological and biochemical studies. Changes, if any, found in the concentrations of various components of perfusate and bile, were considered due to the metabolic activity of the liver. Moderate changes of the liver architecture and a decrease of glycogen were found in hepatic tissues studied microscopically. Under the conditions of the present preliminary experiment, canine livers remained functional after 6 h of perfusion.     

Specific organ gene transfer in vivo by regional organ perfusion with herpes viral amplicon vectors: implications for local gene therapy

BACKGROUND: Many gene therapy strategies would benefit from efficient, regional organ delivery of therapeutic genes. METHODS: Regional perfusions of lung, liver, or bladder were performed to determine if rapid and efficient gene transfer can be accomplished in vivo, and to determine if in vivo gene transfer can be limited to the organ of interest. In addition, herpes simplex virus tumor necrosis factor (HSVtnf), carrying the human tumor necrosis factoralpha gene was used as a treatment for methylcholanthrene sarcoma in a syngeneic lung metastases model in Fisher rats. RESULTS: A 20-minute perfusion using HSV carrying beta-galactosidase (HSVlac) produced significant expression of this marker gene isolated to the target organs, without organ-specific tissue injury or inflammation. Regional perfusion of organs with HSV carrying the cytokine gene tumor necrosis factor alpha also resulted in high-level local organ production of this cytokine (2851 +/- 53 pg/g tissue in perfused lung versus 0 for the contralateral lung). For the current vector construct, expression of the gene of interest peaked between 2 and 4 days and was undetectable by 2 weeks after perfusion. In animals undergoing perfusion as treatment for pulmonary sarcoma, there was no difference between tumor counts in lungs perfused with HSVlac (17 +/- 6) or HSVtnf (22 +/- 8), but either treatment resulted in lower tumor counts than controls (111 +/- 24 nodules per lung, P <.02). CONCLUSIONS: Regional organ perfusion using herpes viral vectors is an effective and well-tolerated in vivo method of transiently delivering potentially toxic gene products to target organs in directing gene therapy. Regional lung perfusion with HSV amplicons reduces tumor burden in a rat model of pulmonary metastases, though HSVtnf cannot be demonstrated to augment the cytopathic effect of the HSV amplicon alone in the current model.     

Hypothermic perfusion preservation of liver: the role of phosphate in stimulating ATP synthesis studied by 31P NMR

Hypothermic perfusion of rat livers was investigated by ³¹phosphorus nuclear magnetic resonance (³¹P NMR) spectroscopy using a temperature-controlled module that allowed data acquisition at various time points during a 48-h period. The livers were perfused with an oxygenated lactobionate/raffinose-based solution containing adenosine and inorganic phosphate, and changes in tissue oedema were monitored by direct on-line measurements of liver weight changes. Liver tissue ATP concentrations, determined by fluorimetric assay, were low immediately after organ removal, probably reflecting metabolic stress during the removal period, and these increased slightly during the next 3 h. This was reflected by changes in the ³¹P NMR spectra. However, by 24 h ATP levels had increased significantly, and these were maintained for up to 48 h, suggesting a shift in the balance between energy production and consumption. When inorganic phosphate was replaced by another anion (citrate), ATP was maintained at a constant lower level during perfusion for 48 h. Tissue weight changes were similar in both groups, suggesting that volume control was not affected by the different ATP contents of the livers. By combining the temperature-controlled module with a separate perfusion circuit, NMR spectroscopy can provide a sensitive method for following energy metabolism in the same organ over long periods during hypothermic perfusion.     

Single vs. dual vessel porcine extracorporeal liver perfusion

BACKGROUND: The use of porcine extracorporeal liver perfusion (PECLP) to provide temporary hepatic support for patients in fulminant hepatic failure has been limited by the fact that individual perfusions can be sustained for only a few hours. Inadequate liver function and/or hemodynamic instability are the major contributing factors for early interruption of PECLP. Recent reports suggest that the choice of single (portal vein only) vs dual (portal vein and hepatic artery) vessel perfusion may influence the duration of perfusion. We hypothesize that PECLP with single vessel perfusion (SVP) is associated with worse liver function and greater hemodynamic instability than PECLP with dual vessel perfusion (DVP). MATERIALS AND METHODS: To eliminate the potentially confounding influences of liver failure and xenograft rejection, liver isografts procured from White-Landrace pig donors were perfused by either SVP or DVP via an extracorporeal circuit established with normal White-Landrace pig recipients. The function of perfused livers was evaluated by measuring production of bile and Factors V and VIII, clearance of ammonia and lactate, and extraction of O(2) at baseline and at 0, 1, 3, 6, 12, and 24 h after initiation of PECLP. The impact of PECLP on recipient hemodynamic status was assessed by monitoring BP, heart rate, urine output, O(2) saturation, etc. Among other parameters evaluated were serum albumin and total protein and hepatic release of IL-1beta and nitric oxide to assess their possible contributions to hemodynamic instability. RESULTS: DVP and SVP livers cleared ammonia and lactate similarly. Both approaches were associated with progressive hypoalbuminemia and hypoproteinemia. DVP livers produced more bile and Factor V and were associated with less recipient hypotension and IL-1beta and NO release than SVP livers. CONCLUSIONS: Livers with DVP function better than livers with SVP. The duration of PECLP can be limited by recipient hypotension, although this complication is less severe with DVP than with SVP.     

A Novel Oxygenated Machine Perfusion System for Preservation of the Liver

Machine perfusion (MP) is a potential method to increase the donor pool for organ transplantation. However, MP systems for liver grafts remain difficult to use because of organ‐specific demands. Our aim was to test a novel, portable MP system for hypothermic preservation of the liver. A portable, pressure‐regulated, oxygenated MP system designed for kidney preservation was adapted to perfuse liver grafts via the portal vein (PV). Three porcine livers underwent 20 h of hypothermic perfusion using Belzer MP solution. The MP system was assessed for perfusate flow, temperature, venous pressure, and pO₂/pCO₂ during the preservation period. Biochemical and histological parameters were analyzed to determine postpreservation organ damage. Perfusate flow through the PV increased over time from 157 ± 25 mL/min at start to 177 ± 25 mL/min after 20 h. PV pressure remained stable at 13 ± 1 mm Hg. Perfusate temperature increased from 9.7 ± 0.6°C at the start to 11.0 ± 0.0°C after 20 h. Aspartate aminotransferase and lactate dehydrogenase increased from 281 ± 158 and 308 ± 171 U/L after 1 h to 524 ± 163 and 537 ± 168 U/L after 20 h, respectively. Blood gas analysis showed a stable pO₂ of 338 ± 20 mm Hg before perfusion of the liver and 125 ± 14 mm Hg after 1 h perfusion. The pCO₂ increased from 15 ± 5 mm Hg after 1 h to 53 ± 4 mm Hg after 20 h. No histological changes were found after 20 h of MP. This study demonstrated the feasibility of a portable MP system for preservation of the liver and showed that continuous perfusion via the PV can be maintained with an oxygen‐driven pump system without notable preservation damage of the organ.     

Twenty‐four–hour normothermic perfusion of discarded human kidneys with urine recirculation

Transportable normothermic kidney perfusion for 24 hours or longer could enable viability assessment of marginal grafts, increased organ use, and improved transplant logistics. Eleven clinically declined kidneys were perfused normothermically, with 6 being from donors after brain death (median cold ischemia time 33 ± 36.9 hours) and 5 being from donors after circulatory death (36.2 ± 38.3 hours). Three kidneys were perfused using Ringer’s lactate to replace excreted urine volume, and 8 kidneys were perfused using urine recirculation to maintain perfusate volume without fluid replenishment. In all cases, normothermic perfusion either maintained or slightly improved the histopathologically assessed tubular condition, and there was effective urine production in kidneys from both donors after brain death and donors after circulatory death (2367 ± 1798 mL vs 744.4 ± 198.4 mL, respectively; P = .44). Biomarkers, neutrophil gelatinase–associated lipocalin, and kidney injury molecule‐1 were successfully detected and quantified in the perfusate. All kidneys with urine recirculation were readily perfused for 24 hours (n = 8) and exhibited physiological perfusate sodium levels (140.7 ± 1.2 mmol/L), while kidneys without urine recirculation (n = 3) achieved a reduced normothermic perfusion time of 7.7 ± 1.5 hours and significantly higher perfusate sodium levels (159.6 ± 4.63 mmol/:, P < .01). Normothermic machine perfusion of human kidneys for 24 hours appears to be feasible, and urine recirculation was found to facilitate the maintenance of perfusate volume and homeostasis.     

Impact of immunoadsorption on xenogeneic extracorporeal pig liver perfusion: assessment of organ function during autologous reperfusion

The shortage of liver grafts has resulted in an intensive search for alternative strategies of liver support in acute liver failure. Extracorporeal perfusion of pig livers (ECLP) is not a new concept, but recent improvements in cardiopulmonary bypass technology and new knowledge about xenogeneic immunologic mechanisms have made it a potential therapeutic modality. In previous suboptimal experimental and clinical models, no statements about the beneficial effect of long-lasting periods of ECLP were made. The aim of this study was to evaluate the capacity of pig liver for metabolic regeneration after xenogeneic ECLP under largely physiologic conditions. To delay hyperacute rejection (HAR), we utilized immunoadsorption (IA) of naturally preformed xenogeneic antibodies (XNAbs). This led to a stable xenogeneic ECLP for 45 min. However, IA was not able to prevent completely organ damage or loss of function resulting from insufficient autologous reperfusion. The inability to regenerate during autologous reperfusion provides a new measure of the function of a xenogeneic perfused pig liver. In addition, our results implicate that patients with fulminant liver failure will benefit from short perfusions with several fresh organs rather than from long perfusion with a single pig liver.     

Risk of Thyroid Cancer Among Solid Organ Transplant Recipients

Solid organ transplant recipients have an elevated incidence of thyroid cancer. We evaluated a wide range of potential risk factors in a cohort of 229 300 U.S. solid organ transplant recipients linked with 15 stage/regional cancer registries (1987–2012). Incidence rate ratios (IRRs) were adjusted for age, sex, race/ethnicity, transplanted organ, year of transplantation, and time since transplantation. Hazard ratios (HRs) for death and/or graft failure were adjusted for age, sex, race/ethnicity, transplanted organ, and year of transplantation. After transplantation, 356 thyroid cancers were diagnosed. Thyroid cancer incidence was 2.50‐fold higher in transplant recipients than the general population (95% confidence interval [CI] 2.25–2.77). Among recipients of different organs, kidney recipients had the highest incidence of thyroid cancer (IRR = 1.26, 95% CI 1.03–1.53). Elevated thyroid cancer incidence was associated with cholestatic liver disease/cirrhosis as an indication for liver transplantation (IRR = 1.69, 95% CI 1.09–2.63), hypertensive nephrosclerosis as an indication for kidney transplantation (IRR = 1.41, 95% CI 1.03–1.94), and longer prior dialysis among kidney recipients (5+ vs. <1 year, IRR = 1.92, 95% CI 1.32–2.80; p‐trend <0.01). Posttransplantation diagnosis of thyroid cancer was associated with modestly increased risk of death (HR = 1.33, 95% CI 1.02–1.73). Overall, our results suggest that end‐stage organ disease and longer duration of dialysis may contribute to higher thyroid cancer incidence in transplant recipients.     

Isolated Kidney Controlled Perfusion with True Physiological Pulsatile Waveform

A computer controlled perfusion system has been developed to study the behavior of perfused kidneys in several conditions. The system is designed to perform kidney perfusions at constant pressure and low temperature (about 4°C). We compared 2 types of perfusion pumps, a classical roller pump widely used in hemodialysis circuits and a vacuum powered tubular pump with active valves developed by our group and able to produce a flow pattern very similar to the pulse wave in the human circulatory system. In this preliminary study, we show the hydrodynamics obtained with both pumps in isolated hypothermic kidneys perfused with this system. The different flow patterns with both pumps seem to determine differences in the preservation conditions of the kidney.