R. Shiroki

Should We Discard the Graft? Analysis of the Renal Grafts with a Total Ischemia Time of More Than 24 Hours Donated After Cardiac Death

The objective is to investigate the outcome of transplantation using kidney grafts from donors after cardiac death (DCDs) with a total ischemia time (TIT) longer than 24 h. All 373 kidneys were procured from DCDs. They were procured using the in‐situ regional cooling technique. Grafts were classified into two groups according to TIT. Fifty‐three grafts had a TIT longer than 24 h (group 1), and the other 320 grafts (group 2) were less than 24 h. The numbers of never functioning grafts (PGF) were 3 in group 1 (5.7%) and 17 in group 2 (5.3%), a nonsignificant difference. Graft survival rates at 3, 5 and 10 years posttransplant were 84.9%, 73.0% and 64.1% in group 1, and 76.3%, 69.9% and 57.1% in group 2, which demonstrate no significant difference. The significant risk factors for graft failure were donor age, serum creatinine level on hospitalization and WIT. However, TIT longer than 24 h was not employed. Multivariate logistic regression indicated that only WIT was associated with an increase in the risk of PGF. Our results demonstrate that kidneys from DCDs, even if their TIT is more than 24 h, should be considered a worthwhile source of renal grafts.

Neurotrophin levels in cerebrospinal fluid of adult patients with meningitis and encephalitis.

Background: The data on cerebrospinal fluid (CSF) levels of neurotrophins (NTs) in patients with meningoencephalitis are scarce, especially in adult patients. Methods: We measured CSF levels of NTs such as nerve growth factor (NGF), brain-derived neurotrophic factor, and neurotrophin-3 (NT-3) in adult patients with various meningitis (n = 10) and encephalitis (n = 10) in both acute phase and recovery phase and adult control subjects (n = 21) by the enzyme-linked immunosorbent assay for NTs. Results: Data show that NGF and NT-3 CSF levels were markedly elevated in the patient group in the acute phase compared with non-neurological controls (p < 0.001 and p < 0.05, respectively) and later returned to the levels of controls. Most intriguingly, we only recognized a significant correlation between NGF and NT-3 CSF levels in the patients in the acute phase. Conclusion: Such strong correlation of NGF and NT-3 CSF levels strongly suggests that in adult patients, some common regulatory mechanism(s) might be present among various kinds of NTs to cope with central nervous system infection.

Long-Term Graft Survival Was Affected By Several Donor’s Factors in Renal Transplants Engrafting DCD Kidneys. - Based On Data From a Single Center Having Recovered Over 500 DCD Renal Grafts.: Abstract# 652

652 Long-Term Graft Survival Was Affected By Several Donor’s Factors in Renal Transplants Engrafting DCD Kidneys. – Based On Data From a Single Center Having Recovered Over 500 DCD Renal Grafts. K. Hoshinaga,1 M. Kusaka,1 H. Takahashi,2 Y. Kubota,1 N. Fukami,1 H. Sasaki,1 T. Kenmochi,3 R. Shiroki.1 1Department of Urology, Fujita Health University School of Medicine, Toyoake, Aichi, Japan; 2Division of Medical Statistics, Fujita Health University School of Medicine, Toyoake, Aichi, Japan; 3Department of Organ Transplant Surgery, Fujita Health University School of Medicine, Toyoake, Aichi, Japan. The kidneys procured from deceased donors in donation after cardiac death (DCD) hold great potential to expand the donor pool. In this study, the posttransplant outcome of renal allografts recovered from DCD donors is investigated and the risk factors affecting the renal prognoses were analyzed. From 1979, 537 kidneys were retrieved from 271 DCD donors at our center, using in situ regional cooling technique.443 grafts transplanted since 1983 through 2011 were enrolled. The age of the donors and recipients ranged from 0.7 to 75 (mean; 47.6) and from 7 to 72 (mean; 41.7). The warm ischemic time ranged from 1 to 71 minutes (mean; 11.7). The serum creatinine level before cardiac arrest ranged from 0.4 to 5.4 mg/dl (mean; 1.49). Following renal transplants, primary non function (PNF) was noted in 27 (6.5%), immediate function (IF) was 58 (13.1%), and DGF was 358 (80.9%). The 1, 3, 5, and 10 year graft survival rates were 86.1%, 75.6%, 68.5%, and 52.8%, respectively. Upon Cox multivariate analysis, age ≥ 50 years, hypertension, highest sCr ≥ 1.5 mg/dl and WIT ≥ 30 min were identifi ed as independent predictors for long-term graft failure. Univariate Multivariate HR (95%CI) P value HR (95%CI) P value Male 1.10 (0.85-1.42) 0.46 Age ≥ 50 years 1.78 (1.36-2.33) <0.0001 2.00 (1.45-2.74) <0.0001 Hypertension 1.71 (1.32-2.21) <0.0001 1.62 (1.18-2.22) 0.0028 Cerebrovascular death 1.36 (1.03-1.79) 0.031 1.02 (0.72-1.44 0.91 sCr ≥ 1.5 mg/dl (Highest) 1.55 (1.14-2.13) 0.0059 1.40 (1.00-1.96) 0.047 sCr ≥ 1.0 mg/dl (admission) 1.33 (1.02-1.73) 0.034 1.26 (0.94-1.68) 0.12 WIT ≥ 30 min 1.68 (1.16-2.44) 0.0060 1.69 (1.07-2.67) 0.023 TIT ≥ 24 hr 0.87 (0.57-1.32) 0.51 In contrast, for short-term graft failure (PNF), only WIT ≥ 30min was the independent predictor. Renal grafts recovered from DCDs had good renal function as well as excellent long term graft survival, when in situ regional cooling technique was applied. DCD donors should be the excellent resources of deceased donor kidneys, and they can increase the number of renal transplantation in the era of sever organ shortage. Abstract# 653 Combined Predictive Value of ECD Criteria for Long-Term Graft Survival of Kidneys From Donors After Cardiac Death. M. Kusaka,1 Y. Kubota,1 H. Takahashi,2 N. Fukami,1 H. Sasaki,1 T. Kenmochi,3 R. Shiroki,1 K. Hoshinaga.1 1Department of Urology, Fujita Health University School of Medicine, Toyoake, Aichi, Japan; 2Division of Medical Statistics, Fujita Health University School of Medicine, Toyoake, Aichi, Japan; 3Department of Organ Transplant Surgery, Fujita Health University School of Medicine, Toyoake, Aichi, Japan. Introduction: Kidneys procured from deceased donors after cardiac death (DCD) hold great potential to expand the donor pool. This study investigated the posttransplant outcomes of renal allografts recovered from DCD and identifi ed risk factors affecting the renal prognosis. In addition, the long-term survival of renal grafts from DCD was compared according to the number of ECD risk factors. Methods: Since 1979, 537 kidneys were retrieved from 271 DCD donors using the in situ regional cooling technique. A total of 443 grafts transplanted between 1983 and 2011 were assessed. Results: Among donor’s factors, an age ≥ 50 years, hypertension, highest sCr ≥ 1.5 mg/dl and WIT ≥ 30 minutes were identifi ed as independent predictors of long-term graft failure in a Cox multivariate analysis. Regarding the ECD criteria for marginal donors, cerebrovascular disease, hypertension and highest sCr ≥ 1.5 mg/dl were identifi ed as signifi cant predictors in a Cox univariate analysis after adjustment for WIT ≥ 30 minutes and sCr ≥ 1.0 mg/dl on admission. To assess the combined predictive value of signifi cant ECD risk criteria, the patients were divided into three groups: no ECD risk factors (no risk group), one ECD risk factor (single-risk) and two or more ECD risk factors (multiple-risk). Following adjustment for WIT and sCr, the single-and multiple-risk groups had 2.04and 2.51-fold higher risks of graft failure than the no risk group. 653 Combined Predictive Value of ECD Criteria for Long-Term Graft Survival of Kidneys From Donors After Cardiac Death. M. Kusaka,1 Y. Kubota,1 H. Takahashi,2 N. Fukami,1 H. Sasaki,1 T. Kenmochi,3 R. Shiroki,1 K. Hoshinaga.1 1Department of Urology, Fujita Health University School of Medicine, Toyoake, Aichi, Japan; 2Division of Medical Statistics, Fujita Health University School of Medicine, Toyoake, Aichi, Japan; 3Department of Organ Transplant Surgery, Fujita Health University School of Medicine, Toyoake, Aichi, Japan. Introduction: Kidneys procured from deceased donors after cardiac death (DCD) hold great potential to expand the donor pool. This study investigated the posttransplant outcomes of renal allografts recovered from DCD and identifi ed risk factors affecting the renal prognosis. In addition, the long-term survival of renal grafts from DCD was compared according to the number of ECD risk factors. Methods: Since 1979, 537 kidneys were retrieved from 271 DCD donors using the in situ regional cooling technique. A total of 443 grafts transplanted between 1983 and 2011 were assessed. Results: Among donor’s factors, an age ≥ 50 years, hypertension, highest sCr ≥ 1.5 mg/dl and WIT ≥ 30 minutes were identifi ed as independent predictors of long-term graft failure in a Cox multivariate analysis. Regarding the ECD criteria for marginal donors, cerebrovascular disease, hypertension and highest sCr ≥ 1.5 mg/dl were identifi ed as signifi cant predictors in a Cox univariate analysis after adjustment for WIT ≥ 30 minutes and sCr ≥ 1.0 mg/dl on admission. To assess the combined predictive value of signifi cant ECD risk criteria, the patients were divided into three groups: no ECD risk factors (no risk group), one ECD risk factor (single-risk) and two or more ECD risk factors (multiple-risk). Following adjustment for WIT and sCr, the single-and multiple-risk groups had 2.04and 2.51-fold higher risks of graft failure than the no risk group. Conclusions: Renal grafts recovered from DCD have a good renal function with excellent long-term graft survival. However, an increased number of ECD risk factors affects the incidence of graft failure. Abstract# 654 Determinants of Discard of Kidneys From Expanded Criteria Donors Undergoing Donation After Circulatory Death. S. Singh,1,4 S. Kim.1,2,3,4 1Division of Nephrology, Department of Medicine, University of Toronto, Toronto, ON, Canada; 2Division of Nephrology and the Kidney Transplant Program, University Health Network, Toronto, ON, Canada; 3Division of Nephrology and the Renal Transplant Program, St. Michael’s Hospital, Toronto, ON, Canada; 4Institute of Health Policy, Managment and Evaluation, University of Toronto, Toronto, ON, Canada. 654 Determinants of Discard of Kidneys From Expanded Criteria Donors Undergoing Donation After Circulatory Death. S. Singh,1,4 S. Kim.1,2,3,4 1Division of Nephrology, Department of Medicine, University of Toronto, Toronto, ON, Canada; 2Division of Nephrology and the Kidney Transplant Program, University Health Network, Toronto, ON, Canada; 3Division of Nephrology and the Renal Transplant Program, St. Michael’s Hospital, Toronto, ON, Canada; 4Institute of Health Policy, Managment and Evaluation, University of Toronto, Toronto, ON, Canada.

THE INCREMENT OF SERUM TISSUE INHIBITOR OF METALLOPROTEINASES 1 (TIMP-1) PREDICTS ORGAN RECOVERY FROM DELAYED GRAFT FUNCTION AFTER KIDNEY TRANSPLANTATION FROM DONORS AFTER CARDIAC DEATH: 556

M. Kusaka1, Y. Kuroyanagi2, M. Ichino3, H. Sasaki3, T. Maruyama3, K. Hayakawa3, R. Shiroki3, A. Sugitani2, H. Kurahashi4, K. Hoshinaga3 1Dept. Of Urology, Fijita-Health University, Toyoake /JAPAN, 2Department Of Organ Transplantation And Regenerative Medicine, Fijita-Heath University, Toyoake Aichi/JAPAN, 3Dept. Of Urology, FijitaHealth University, Toyoake/JAPAN, 4Division Of Molecular Genetics, Fujita-Health University, Toyoake Aichi/JAPAN

RAPID DETECTION OF NON-HEART BEATING DONORS’ INFECTIONS AND THEIR RENAL GRAFT CONTAMINATIONS BY POLYMERASE CHAIN REACTION

Aims: Since the pre-procurement hospitalization period of non-heart beating donors (NHBD) is apt to be longer than that of brain dead donors, the opportunity of bacterial or fungal infection of NHBD is significantly increased through the tracheal tubes, intravenous lines and urethral catheters. The purpose of this study is to detect serious bacterial / fungal infections of NHBD before the procurements or to detect bacterial / fungal contaminations of allografts before the transplants. The targeted organisms in this study are hardly treatable organisms such as methicillin resistant Staphyllococcus aureus (MRSA), Pseudomonas aeruginosa (P. aeruginosa) and Candida albicans. Methods: The pre-procurement blood samples from 86 possible renal donors were examined by PCR, and 158 kidneys from 83 donors in whom infection was denied by PCR and 23 renal grafts transferred from other centers were also tested. The preservation solution (PS) and renal pelvic urine (PU) obtained from a total of 181 grafts were examined by PCR. In PCR, appropriate primers were used to detect following genes; fem A specific for Staphylococcus aureus (S.aureus), mec A specific for methicillin resistant Staphylococcus species, P.aeruginosa gyr A specific for P.aerginosa and 18S rRNA specific for most of the clinically critical fungi. It takes 4 to 6 hours for making a definite diagnosis by PCR. In order to confirm the PCR diagnosis, rapid shaking culture (RSC) was also done in parallel with PCR and the result was judged at intervals of 6 hours. The pre-procurement clinical conditions of possible donors were as follows; ages ranging from 1 to 73 years (mean: 47.5), periods between admission and brain death ranging from 1 to 44 days (mean: 4.7) and periods between brain death and cardiac arrest ranging from 1 to 14 days (mean: 3.3). The values of inflammatory indices such body temperature, WBC and CRP elevated up to 37.9 /-1.1°C, 12,600 /-6,300 / l, and 20.3 11.6 mg/dl. Results: Two possible donors were diagnosed to have systemic MRSA infection by PCR and RSC, and one possible donor was diagnosed to have systemic bacteroides infection by RSC, and the procurements were cancelled immediately before the operations. Eight kidneys were discarded because of the diagnoses of PS / PU contamination with S.aureus (1), MRSA (2) and Candida albicans(5) by PCR and RSC. In 20 grafts, the PCR diagnoses of PS / PU were positive but the results of RSC at 6 or 12 hours were negative, and all the grafts were finally transplanted. The other 148 kidneys were transplanted without delay since all the specimens were negative by PCR. Following the 168 renal transplants, no infectious complication transmitted by the engrafted kidneys was noted. Conclusions: CONCLUSION; PCR combined with RSC is very useful for detecting donor infection or organ contamination with hardly treatable bacteria or fungi in a pretransplant limited time period. Moreover, the opportunity of organ donations from the marginal donors will be increased if the organ contamination is denied by applying PCR, even when the donor infection might be highly suspected by the elevated inflammatory indices values. P91 STEROID ADMINISTRATION BEFORE PARTIAL HEPATECTOMY WITH TEMPORARY INFLOW OCCLUSION DOES NOT INFLUENCE CYCLIN D1 AND KI-67 RELATED LIVER REGENERATION IN REDUCED-SIZE LIVERS. M. Glanemann, S. Münchow, A. Schirmeier, H. Al-Abadi, F. Lippek, J.M. Langrehr, M. Dietel, P. Neuhaus, A.K. Nussler Department of General-, Visceraland Transplantation Surgery and Institute of Pathology, Charité, Campus Virchow Klinikum, Universitätsmedizin Berlin, Germany, Fresenius-Biotech, BadHomburg, Germany