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Background: Because of the organ shortage, donation after cardiac death (DCD) kidney transplantation (KTx) is an alternative way of achieving KTx using brain-dead donors (BDs). Although the prognosis of DCD-KTx is improving, the graft suffers from delayed graft function (DGF), the management of which is essential. With progress in understanding the characteristics of cell-free DNA (CF-DNA), we consider plasma total CF-DNA (tCF-DNA) to be a useful biomarker for predicting DGF in DCD-KTx., Study Design and Method: Consecutive patients from living donors (LDs; n = 9), BDs (n = 8), or DCD donors (n = 13) were enrolled. Plasma samples were collected after KTx and on postoperative days 3 and 5. CF-DNA was isolated, and tCF-DNA was quantified using the TapeStation 2200 software program., Results: The tCF-DNA levels after BD-KTx and DCD-KTx were higher than those after LD-KTx (LD, 78 ± 27 (ng/mL); BD, 99 ± 20; DCD, 150 ± 23); the difference between DCD-KTx and LD-KTx was statistically significant (P < .05). The tCF-DNA levels declined at postoperative day 5 (LD, 45 ± 10; BD, 51 ± 11; DCD, 66 ± 13). tCF-DNA levels were significantly increased in patients with DGF after KTx (DGF, 139 ± 22; immediate function, 91 ± 18; P < .05). The tCF-DNA level was correlated with the duration of DGF (r = 0.5825, P < .05)., Conclusion: Although the mechanism underlying DNA release from transplanted grafts into the recipient circulation remains unclear, cell death by apoptosis or necrosis and the active secretion of the immune system may play important roles in DGF. These data suggest that monitoring tCF-DNA may help predict graft recovery after DCD-KTx., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Objectives: To evaluate the prognostic value of the warm ischemic time and the validity of the Kidney Donor Profile Index/Kidney Donor Risk Index for predicting the survival of donors after cardiac death grafts., Methods: We retrospectively assessed 315 kidneys retrieved from donors after cardiac death at Fujita Health University Hospital, Toyoake, Aichi, Japan. The Kidney Donor Profile Index/Kidney Donor Risk Index was calculated and the grafts were enrolled., Results: The median follow-up period was 11.9 years. The Kidney Donor Profile Index had a markedly asymmetric distribution (median 94%), and the Kidney Donor Risk Index had high index rates (0.79-2.94, median 1.70). The overall 5-, 10- and 15-year graft survival rates were 67.5%, 52.1% and 38.9%, respectively. The Kidney Donor Profile Index correlated with graft survival. The 5-, 10- and 15-year graft survival rates for the Kidney Donor Profile Index <1.2 were 87.7%, 73.5% and 59.2%; those for the Kidney Donor Risk Index >2.0 were 55.0%, 34.7% and 22.1%, respectively. A Cox multivariate analysis identified the Kidney Donor Risk Index (hazard ratio 2.06, 95% confidence interval 1.48-2.86, P < 0.0001) and warm ischemic time (hazard ratio 1.21, 95% confidence interval 1.09-1.34, P = 0.0010) as independent risk factors for graft loss. The addition of warm ischemic time >30 min had a significant effect, as measured by the C-index (0.708-0.731, P = 0.032), improving the net reclassification improvement score (0.256, P = 0.0039) and integrated discrimination improvement score (0.042, P = 0.0022)., Conclusions: The Kidney Donor Profile Index/Kidney Donor Risk Index is a good prognostic tool for determining the outcomes of donors after cardiac death grafts. However, the warm ischemic time should also be included in the allocation system for donors after cardiac death grafts., (© 2018 The Japanese Urological Association.)

Background: Kidney transplant recipients are at increased risk of developing cancer in comparison with the general population. To effectively manage post-transplantation malignancies, it is essential to proactively monitor patients. A long-term intensive screening program was associated with a reduced incidence of cancer after transplantation. This study evaluated the usefulness of the gene expression profiling of peripheral blood samples obtained from kidney transplant patients and adopted a screening test for detecting cancer of the digestive system (gastric, colon, pancreas, and biliary tract)., Study Design and Method: Nineteen patients were included in this study and a total of 53 gene expression screening tests were performed. The gene expression profiles of blood-delivered total RNA and whole genome human gene expression profiles were obtained. We investigated the expression levels of 2665 genes associated with digestive cancers and counted the number of genes in which expression was altered. A hierarchical clustering analysis was also performed. The final prediction of the cancer possibility was determined according to an algorithm., Results: The number of genes in which expression was altered was significantly increased in the kidney transplant recipients in comparison with the general population (1091 ± 63 vs 823 ± 94; P = .0024). The number of genes with altered expression decreased after the induction of mechanistic target of rapamycin (mTOR) inhibitor (1484 ± 227 vs 883 ± 154; P = .0439). No cases of possible digestive cancer were detected in this study period., Conclusion: The gene expression profiling of peripheral blood samples may be a useful and noninvasive diagnostic tool that allows for the early detection of cancer of the digestive system., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Objectives: Kidneys procured from the deceased hold great potential for expanding the donor pool. The aims of the present study were to investigate the post-transplant outcomes of renal allografts recovered from donors after cardiac death, to identify risk factors affecting the renal prognosis and to compare the long-term survival from donors after cardiac death according to the number of risk factors shown by expanded criteria donors., Methods: A total of 443 grafts recovered using an in situ regional cooling technique from 1983 to 2011 were assessed. To assess the combined predictive value of the significant expanded criteria donor risk criteria, the patients were divided into three groups: those with no expanded criteria donor risk factors (no risk), one expanded criteria donor risk factor (single-risk) and two or more expanded criteria donor risk factors (multiple-risk)., Results: Among the donor factors, age ≥50 years, hypertension, maximum serum creatinine level ≥1.5 mg/dL and a warm ischemia time ≥30 min were identified as independent predictors of long-term graft failure on multivariate analysis. Regarding the expanded criteria donors criteria for marginal donors, cerebrovascular disease, hypertension and maximum serum creatinine level ≥1.5 mg/dL were identified as significant predictors on univariate analysis. The single- and multiple-risk groups showed 2.01- and 2.40-fold higher risks of graft loss, respectively., Conclusions: Renal grafts recovered from donors after cardiac death donors have a good renal function with an excellent long-term graft survival. However, an increased number of expanded criteria donors risk factors increase the risk of graft loss., (© 2016 The Japanese Urological Association.)

A 53-year-old woman who had undergone deceased donor kidney transplantation twice, at 35 and 43 years of age, presented with renal impairment. She was infected with hepatitis C virus (HCV). The histology of the graft kidney revealed post-transplant membranous nephropathy (MN) with podocytic infolding and antibody-mediated rejection (AMR). IgG subclass staining showed fine granular deposits of IgG1 and IgG3, but not IgG4, in the glomerular capillary walls. Panel reactive antibody scores for human leukocyte antigen class I and class II were 92.67% and 66.68%, respectively. Thus, this case of post-transplanted MN was considered to be associated with AMR and HCV infection.

Background: The waiting time for deceased-donor kidney-only transplantations in Japan is long. Herein, we assessed the effect of length of dialysis on the outcomes of these patients., Methods: We divided patients into 2 groups based on length of dialysis (Group A, <15 years, and Group B, ≥15 years), and compared the background and outcomes after kidney transplantation., Results: Group A included 210 patients and Group B included 35 patients. In Group B, 20% of transplants were from living donors. Patient age (P = .017) and the hepatitis C infection rate (P = .018) were significantly higher in Group B, whereas hypertension (P = .011), diabetes (P = .041), and ABO-incompatibility rates (P = .015) were significantly higher in Group A. The 5- and 10-year survival rates were 97.0% and 95.4%, respectively, in Group A and 97.1% and 97.1%, respectively, in Group B. The 5- and 10-year graft survival rates were 95.4% and 84.8%, respectively, in Group A and 97.1% and 73.1%, respectively, in Group B. There were no significant differences between the groups in patient survival (P = .74) and graft survival (P = .72). The 5- and 10-year cardiovascular event-free survival rates were 95.9% and 92.4%, respectively, in Group A and 88.6% and 76.8%, respectively, in Group B. Cardiovascular event-free survival was significantly higher in Group A (P = .038). Cox stepwise multivariate analysis indicated that length of dialysis was a significant predictor of cardiovascular events (hazard risk, 1.007; range, 1.001-1.012; P = .012)., Conclusion: The prognosis after kidney transplantation is promising even after a long length of dialysis, although evaluation of the cardiovascular risk is needed in these cases., (Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.)

Introduction: Three-dimensional (3-D) printing systems allow for the creation of surgical models mimicking real tissue. We developed a kidney graft and pelvic cavity replica as a patient-specific 3-D model using a 3-D printing system with simultaneous jetting of different materials and subsequently evaluated the usefulness of surgical simulation and navigation of living kidney transplantation., Methods: After generating a stereolithographic file of the organ surface based on multidetector computed tomographic data, we created a 3-D organ model using an inkjet 3-D printer and manufactured a pelvic cavity replica using patient-specific data., Results: The patients' individual 3-D printed models were used to plan and guide the surgical procedures for laparoscopic donor nephrectomy and recipient transplantation surgery. The 3-D organ replicas obtained using transparent materials allowed for the creation of models that showed the visceral organs, blood vessels, and other details, thereby overcoming the limitations of conventional image-guided navigation. Our pelvic replicas can be made according to each patient's specific anatomical data, thus representing personalized surgical procedures. This level of detail of the anatomy enables the surgeons and trainees to virtually treat various pelvic conditions before they perform the surgical procedure. The use of these replicas may also reduce the length of the operation and provide better anatomical reference tools for tailor-made simulation and navigation of kidney transplantation surgery, consequently helping to improve training for the operating room staff, students, and trainees., Conclusions: We believe that our sophisticated personalized donor graft and pelvic replications obtained using a 3-D printing system are advantageous for kidney transplantation surgery., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Background: Nutritional status affects clinical outcomes in patients with chronic renal failure. Glucose intolerance, dyslipidemia, obesity, hypertension, and a calcium-phosphorus-vitamin D imbalance are the major nutritional and metabolic problems that occur in posttransplant patients. In this study, we assessed the daily intake in long-term renal transplant recipients to determine whether they have sufficient nutrients based on the Japanese nutrition recommendations (recommended dietary allowances [RDA] in Japan 2010)., Subjects and Methods: Thirty-one renal allograft recipients followed for >10 years (median, 16.3) were recruited. The median serum creatinine level was 1.2 g/dL (95% CI, 0.6-3.4). We estimated the intake of nutrients, including protein and salt, using a simple food frequency questionnaire., Results: The median body mass index was 20.1 kg/m(2). The median total energy intake was 1566 kcal/d (95% CI, 892-2556). The daily intake of protein and salt was 65.1 and 9.1 g/d, respectively. The calcium, iron, vitamin D, and vitamin K intakes were 423 mg, 7.0 mg/d, 9.7 μg/d, and 197 μg/d, respectively. Patients with dyslipidemia displayed greater amounts of lipid and calcium than those with normal lipid levels., Discussion: Our findings suggest that long-term renal transplant recipients in Japan seem to restrict caloric intake, while maintaining appropriate intake of protein, lipids, carbohydrates, and vitamins A, D, and K. However, daily calcium and iron intake were insufficient; salt intake was greater than the recommended dietary allowances in all subjects. In patients with dyslipidemia, calcium intake was lower than those in patients without dyslipidemia, although their intake of lipids was also lower than those without dyslipidemia., Conclusion: Nutritional guidance beginning during the early posttransplant phase helps to foster a healthy body mass index and nutritional balances for long-term renal transplant recipients. However, greater salt restriction was needed, and additional nutritional guidance aiming to prevent osteoporosis seems to be considered., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Kidneys procured by donation after cardiac death (DCD) may increase the donor pool but are associated with high incidence of delayed graft function (DGF). Urinary liver-type fatty acid-binding protein (L-FABP) level is an early biomarker of renal injury after kidney transplantation (KTx); however, its utility is limited in DGF cases owing to urine sample unavailability. We examined whether serum L-FABP level predicts functional recovery of transplanted DCD kidneys. Consecutive patients undergoing KTx from living related donors (LD), brain-dead donors (BD), or DCD were retrospectively enrolled. Serum L-FABP levels were measured from samples collected before and after KTx. Serum L-FABP decreased rapidly in patients with immediate function, slowly in DGF patients, and somewhat increased in DGF patients requiring hemodialysis (HD) for >1 wk. Receiver-operating characteristic curve analysis demonstrated that DGF was predicted with 84% sensitivity (SE) and 86% specificity (SP) at cutoff of 9.0 ng/mL on post-operative day (POD) 1 and 68% SE and 90% SP at 6.0 on POD 2. DGF >7 d was predicted with 83% SE and 78% SP at 11.0 on POD 1 and 67% SE and 78% SP at 6.5 on POD 2. Serum L-FABP levels may predict graft recovery and need for HD after DCD KTx., (© 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Purpose: Kidneys procured from donors after cardiac death hold great potential to expand the donor pool. However, they have not yet been fully used, in part due to the high incidence of delayed graft function. Although urine neutrophil gelatinase-associated lipocalin is a well-known early biomarker for renal injury after kidney transplantation, its usefulness is limited in cases with delayed graft function because of the unavailability of a urine sample. We evaluated serum neutrophil gelatinase-associated lipocalin as a potential biomarker to predict the functional recovery of kidneys transplanted from donors after cardiac death., Materials and Methods: Consecutive patients transplanted with a kidney from a living related (39), brain dead (1) or post-cardiac death (27) donor were retrospectively enrolled in the study. Serum samples were collected serially before and after kidney transplantation. Serum neutrophil gelatinase-associated lipocalin was measured using the ARCHITECT® assay., Results: Average serum neutrophil gelatinase-associated lipocalin was markedly high during the pre transplantation period. It decreased rapidly after transplantation. The slope of the decrease correlated well with the recovery period. By analyzing ROC curves we determined cutoffs to predict immediate, slow or delayed graft function requiring hemodialysis for longer than 1 week with high sensitivity and specificity., Conclusions: These data suggest that serial monitoring of serum neutrophil gelatinase-associated lipocalin may allow us to predict graft recovery and the need for hemodialysis after kidney transplantation from a donor after cardiac death., (Copyright © 2012 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.)

Donors after cardiac death (DCD) have recently become an important source of renal transplants to alleviate the shortage of renal grafts in kidney transplantation (KTx), although DCD kidneys often have complications associated with a delayed graft function (DGF). A microarray-based approach using renal biopsy samples obtained at 1 h after KTx from DCD identified the tissue inhibitor of metalloproteinases 1 (TIMP-1) gene as a potential predictive marker for DGF. The current study measured serum TIMP-1 in patients undergoing KTx and analyzed the time course after KTx. The average serum TIMP-1 level before KTx was 240 ± 10 ng/ml (n = 34). In patients undergoing KTx from a living donor (n = 23), the serum TIMP-1 levels showed no increase after KTx (POD1: 226 ± 12, POD2: 211 ± 12, and POD3: 195 ± 10 ng/ml), but in one case, the only patient who required post-KTx HD due to DGF, the level on POD1 was the highest among subjects (361 ng/ml). In contrast, patients undergoing KTx from DCDs (n = 11), the serum TIMP-1 levels increased rapidly after a KTx (POD1: 418 ± 32, POD2: 385 ± 42, and POD3: 278 ± 25 ng/ml). However, two patients who avoided post-KTx HD due to the immediate function of the graft did not show increased levels (<370 ng/ml) on either POD1 or POD2. The peak serum TIMP-1 values appeared to correlate to the post-KTx dialysis period. Furthermore, the increment of serum TIMP-1 on the early POD was found to be predictive of immediate or delayed function of the grafts. These data suggest that monitoring of serum TIMP-1 levels allow the prediction of graft recovery and the need for HD after a KTx from a DCD.

Because of the worldwide shortage of renal grafts, kidney transplantation (KTx) from donors after cardiac death (DCD) is an alternative way to obtain KTx from brain-dead donors. Although the prognosis of DCD KTx is gradually improving, the graft often undergoes delayed graft function (DGF), rendering the control of DGF essential for post-KTx patient care. In an attempt to characterize etiology of DGF, genome-wide gene expression profiling was performed using renal biopsy samples performed at 1 h after KTx from DCD and the data were compared with those of KTx from living donors (LD). A total of 526 genes were differentially expressed between them. Genes involved in acute inflammation were activated, while metabolic pathways were consistently downregulated in DCD. These findings imply the inferior performance of the DCD grafts relative to LD grafts. Several genes were identified where the expression levels were correlated well with parameters indicating short- and long-term prognosis of the DCD patients. In addition, several genes encoding secretory proteins were identified that might reflect the performance of the graft and be potential noninvasive biomarkers. These data provide a good source for candidates of biomarkers that are potentially useful for the control of DGF.

Because of a worldwide shortage of renal grafts, kidneys procured from donors after cardiac death (DCD) have recently become an important source of renal transplants. However, DCD kidneys often have complications with delayed graft function (DGF) and recipients require hemodialysis (HD) in the early period after kidney transplantation (KTx). This study evaluated serum NGAL as a potential specific parameter to predict early functional recovery of transplanted DCD kidneys. The average serum neutrophil gelatinase-associated lipocalin (NGAL) level in normal samples was 53 +/- 30 ng/ml, while that in patients with chronic renal failure requiring HD was markedly raised at 963 +/- 33 ng/ml. In patients undergoing a living-related KTx from a living donor (n=11), serum NGAL level decreased rapidly after KTx, and only in two cases, with serum NGAL levels over 400 ng/ml on postoperative day 1 (POD1), was HD required due to DGF. In contrast, all patients undergoing a KTx from a DCD (n=5) required HD due to DGF. Even in these cases, serum NGAL levels decreased rapidly several days after a KTx prior to the recovery of urine output and preceding the decrease in serum creatinine level. The pattern of decline in serum NGAL was biphasic, the decrease after the second peak indicating a functional recovery within the next several days. These data suggest that monitoring of serum NGAL levels may allow us to predict graft recovery and the need for HD after a KTx from a DCD.

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.

Background: It has been well documented that two factors, brain death (BD) and ischemia/reperfusion (I/R) injury, have distinct but overlapping adverse influences on the clinical outcome of renal transplantation., Method: We previously established a rat model of renal isografting from brain dead donors. In the present study, we performed genomic expression profiling with a high-density oligonucleotide microarray to identify genes that were upregulated or downregulated by BD and/or I/R injury., Results: Among a total of 20,550 genes, most of those upregulated by BD were genes for adhesion molecules and cytokines or for chemokines such as Gro1 and IP-10. When overexpression of these genes was assessed by real-time reverse transcriptase-polymerase chain reaction, it was only observed one hr after the engraftment of kidneys from BD donors and returned to baseline thereafter, indicating the presence of an acute systemic inflammatory response to BD. Analysis of biologic networks demonstrated the activation of specific pathways that were clearly different for BD and I/R injury. The p53 and NFkappaB pathway was involved in the acute response to BD, whereas the Myc, Jun, and c-fos pathway was involved in I/R injury. Investigation of secretory protein genes identified LCN2 and SPP1 as candidate genes for biologic markers., Conclusion: Because our experimental system is a good model of renal transplantation from brain dead or living human donors, our data may be useful for elucidating the pathologic processes involved and for identification of novel markers for graft dysfunction of renal transplantation.

Background: There has been a considerable literature describing the use of pulsatile perfusion (PP) to evaluate the efficacy of organs from deceased donors. Since 1979, we recovered 469 kidneys from deceased donors after cardiac death (DCDs), using an in situ regional cooling technique and preservation by simple cold storage. In this study, the posttransplantation outcomes as well as long-term survivals of renal grafts from DCDs were compared with PP data in the recent literature., Materials and Methods: We compared our recent data with 176 kidneys recovered between 1993-2002 using an in situ regional cooling technique. Patient and graft survivals were compared with those from the Scientific Registry of Transplant Recipients (SRTR) database., Results: Following transplantation, 4.5% of the grafts never recovered; 10.3% of the grafts showed immediate renal function; 85.2% of the grafts had delayed graft function (DGF) with an average acute tubular necrosis (ATN) period of 13.1 days compared with 54.3% DGF from DCD using PP. Graft survival rates at 1, 3, 5, and 10 years were 90.8%, 86.5%, 77.8%, and 69.0%, respectively, compared with 89% at 1 year and 80% at 3 years reported for DCD by the SRTR in which almost 30% of the grafts underwent PP., Conclusions: Although PP seemed to have some advantage to decrease the DGF ratio, an in situ regional cooling technique with simple cold storage may provide excellent graft function and long-term graft survival as well as having benefits in cost and transportation.

Purpose: The objective of this study was to investigate the outcome of transplantation using kidney grafts donated after cardiac death (DCD) with a total ischemic time (TIT) longer than 24 hours., Patients and Methods: We followed 373 kidneys recovered from DCD donors and transplanted at 41 centers. All kidneys were procured from uncontrolled DCD donors. Grafts were classified into two groups according to TIT. We recorded renal function and duration of the survival period for each graft., Results: Fifty-three grafts had a TIT longer than 24 hours (group 1). The other 320 grafts had a TIT less than 24 hours (group 2). The number of never functioning grafts were three in group 1 (5.7%) and 17 in group 2 (5.3%). Delayed graft function (DGF) occurred in 44 group 1 (83.0%) and 254 group 2 kidneys (79.4%) for intervals of 13.5 +/- 12.6 versus 10.9 +/- 12.6 days, respectively. Graft survival rates at 3, 5, and 10 years posttransplant were 84.9%, 73.0%, 64.1% for group 1, and 76.3%, 69.9%, 57.1% for group 2. In a Cox proportional hazards model, TIT longer than 24 hours was not a significant independent risk factor., Conclusion: Our results showed that even kidneys with TITs of over 24 hours yielded comparable results despite a higher incidence of DGF.

Post transplant infection is one of the serious complications of the organ recipients. We detected the donor infections and allograft contaminations in a limited period of time by polymerase chain reaction (PCR) and rapid shaking culture (RSC). The pre-procurement blood from 86 possible renal donors as well as the preservation solution (PS) and renal pelvic urine (PU) from 158 grafts were examined in order to detect highly virulent organisms such as methicillin resistant Staphylococcus aureus (MRSA), Pseudomonas aeruginosa, and fungi. The average age of donors was 48.8 years old. The average period between the admission and brain death was 4.9 days, and the average period between the brain death and cardiac arrest was 3.6 days. The inflammatory indices such as body temperature, white blood cell count and C-reactive protein increased to 37.9 +/- 1.1 degree C, 12,600 +/- 6300/microl, and 20.2 +/- 11.6 mg/dl, respectively. Following PCR and RSC, procurement operations of the three possible donors were cancelled because of systemic bacterial infections by MRSA or Bacteroides fragilis. Six out of 158 grafts were discarded due to the diagnoses of MRSA or Candida albicans in PS and/or PU. All the other 148 grafts were transplanted. Following transplant, no single infectious complication transmitted by the graft was noted. We conclude that PCR combined with RSC is very accurate and useful for detecting donor infections and allograft contaminations, which may cause severe complications in the recipients.

Background: Brain death (BD) and following ischemia/reperfusion(I/R) injury has cardinal implications in kidney transplantation (Tx). We hypothesize that inflammation, apoptosis, and drug nephrotoxicity are central mechanisms leading to initial organ damage in transplantation from BD donors. In this study, the gene kinetics of a chemokine (IP-10), an apotosis-related gene, and of calcineurin (Cn) subtype were compared using kidney isografts from BD versus living donors., Methods: Donors were intubated and mechanically ventilated for 6 hours. Grafts were harvested 6 hours after BD, and at 1, 6, and 24 hours and 5 days after engraftment. Messenger RNA (mRNA) expression was assessed using real-time reverse transcriptase-polymerase chain reaction., Results: Gene expression of IP-10 was up-regulated only among BD donor kidneys, particularly following I/R injury. These changes recovered to baseline levels thereafter. Bcl-2 was suppressed within 6 hours of BD and 1 hour after engraftment. In contrast, Bax in kidneys from BD donors was significantly up-regulated at 6 hours after engraftment. These changes were minimal in the controls. Cn Aalpha and Abeta were decreased in kidneys from BD donors before and within 1 hour after engraftment. However, these differences became insignificant thereafter., Conclusions: Marked up-regulation of IP-10 may predict the initial graft injury and the onset of delayed graft function. Apoptotic gene changes may lead kidney grafts to a preapoptotic condition and up-regulate renal toxicity caused by Cn inhibitors. This initial antigen-independent donor circumstance may be one risk factor for chronic rejection.

Although the precise mechanisms are unclear, not only alloantigen-dependent but also antigen-independent factors are generally thought to influence the development of chronic allograft nephropathy (CAN). Among the non-immunological determinants, there are various factors related with donor, recipient and graft procurement. As donor factors, age and cause of death were demonstrated to be significantly independent in long-term graft survival of cadaveric kidney transplantation. Grafts from aged donors and from donors with athelosclerosis showed poor prognosis on graft survival. Regarding recipient factors, cardiovascular complications, as hypertension and hyperlipidemia, were responsible for graft as well as patient survival. In addition, CMV infection and drug nephrotoxicity were also shown to affect graft survival. For procurement factors, warm ischemia was determined to possess the strongest impact on long-term graft survival in our series of kidney transplant using grafts from non-heart beating donors (NHBDs). Delayed graft function, which correlated well with length of warm ischemia, also influenced long-term graft survival. These results proved that the supply of viable donor nephrons and the physiologic demands of the recipient are important determinants of long-term graft survival. So far there seems to be neither definitive nor specific treatment for CAN. It is basically essential to avoid graft damage before transplant and keep recipients from risk factors after transplant as much as possible. To improve long-term graft survival in cadaveric kidney transplantation, recipient selection is greatly important in terms of not only immunological compatibility but also body to nephron mass imbalance and ischemic time, which might cause fatal damage to grafts before engraftment.

We report the case of a 52-year-old man who underwent a renal transplantation and subsequently developed extrapulmonary tuberculosis. The immunosuppressive agent was intravenously administered continuously together with antituberculosis drugs. The tuberculosis improved and renal function has been well preserved for more than 3 years post transplantation.

Diagnosis of acute rejection (AR) is difficult during acute tubular necrosis (ATN), and a delay of rejection treatment could result in negative impacts on the renal transplant outcome. At our center, 68 cadaveric kidneys were transplanted during the past 7 years. The 1-, 3- and 5-year graft survival rates were 95.4%, 93.8% and 81.4%, respectively. After the transplants, 16 patients had immediate graft function (G-I), 51 patients experienced ATN for 12.0 +/- 9.3 days, and one patient had a non-functioning graft due to diffuse arteriolar thrombosis caused by DIC in the donor. During ATN, 41 patients had no rejection episodes (G-II) and 10 patients had ARs (G-III). Nine patients were treated with bolus steroid and one with steroid and OKT-3. Although scintigraphic and sonographic examinations were routinely employed, only the histopathological findings of needle biopsies were helpful for the diagnosis of AR during ATN. When the transplant outcome was compared, the serum creatinene level was highest in G-III and lowest in G-I (1.48 vs 1.06 mg/dl, p < 0.05). The posttransplant ATN period was also longer in G-III compared to G-II (23.9 vs 9.1 days, p < 0.005). The 5-year graft survival rate was 85.2% in G-I, 88.0% in G-II and 59.3% in G-III. We conclude that routine serial renal biopsies should be scheduled when ATN develops after the cadaveric renal transplant, since only the histopathological diagnosis is reliable during ATN.

The fates of 359 kidneys harvested from 181 non-heart beating donors (NHBD) at a single center, using a regional in situ cooling technique were retrospectively investigated. 1. Thirty-five kidneys (9.7%) were discarded mainly due to poor arterial perfusion and bacterial contamination. 2. The incidence of primary nonfunction in patients treated with Aza was significantly higher than that in patients receiving CsA or FK (20.5% [8 grafts] vs 6.0% [17 grafts], respectively, p < 0.01). 3. The incidences of immediate and delayed graft function were 16.1% and 77.9%, respectively, among 285 recipients treated with CsA/FK. The average of duration of posttransplant dialysis required in recipients with DGF was 13.7 days and the average lowest serum creatinine level in patients who recovered graft function was 1.58 mg/dl. 4. Patient survival rates in the CsA/FK group were 97.2%, 95.0%, 93.2% and 89.3% at one, 3, 5 and 10 years, respectively, and the graft survival rates at one, 3, 5 and 10 years were 83.3%, 72.0%, 64.7% and 48.6%, respectively. 5. Increasing donor age showed a significant correlation with increased serum creatinine levels as well as with prolonged posttransplant dialysis (p < 0.001 and p < 0.01, respectively). 6. Renal grafts from donors with cerebrovascular disease (CVD) had significantly higher lowest serum creatine levels than grafts from non-CVD donors (p < 0.0001). 7. Renal grafts harvested from NHBD using our in situ cooling technique had excellent renal function when the donor was young or the cause of death was non-CVD. However, when the donor was older (> or = 56 years) and the cause of death was CVD, the grafts were acceptable but the early posttransplant function was often impaired. 8. The current NHBD graft survival rate, the UNOS cadaveric renal graft survival rate and the Japanese living-related donor renal graft survival rate were almost identical at 10 years posttransplant. 9. NHBDs should provide an excellent opportunity to increase organ availability.

When the concept of brain death is not widely accepted, the viability of renal allografts of non-heart-beating cadaveric donors is one of the serious concerns for transplant surgeons. At our center, 200 kidneys were harvested from cardiac arrest donors using the regional in situ cooling technique, and they were transplanted into recipients treated with cyclosporine (CS). The ages of donors ranged from 7 months to 67 years. At the bedside a specially designed double balloon catheter, 14F, was inserted into the aorta through the femoral artery just before or immediately after the cardiac arrest. A venous drainage tube was also placed in the vena cava. Following the cardiac arrest, both balloons of the aortic catheter were inflated, and regional in situ cooling with cold Lactate Ringer's solution started using the infusion pump at 20 mL/kg/min. In the OR, both kidneys were removed en bloc and preserved in Collins'type solution. They were then transplanted into 200 patients treated with CS and steroid. After the transplant operations, 33 patients (16.5%) had immediate renal function, but 14 grafts (7.0%) were not successful and the patients have never had renal function. When several factors such as donor age, warm ischemic time (WIT; 12.3 ± 14.1 minutes), in situ cooling time (IST; 78.1 ± 18.0 minutes) and total ischemic time (TIT; 619 ± 340 minutes) were associated with the post-transplant renal function, only the donor age had significant correlation both with the posttransplant dialysis period and lowest serum creatine level, as follows: 10.5 days ( ≤ 40 years) vs. 14.6 days ( > 40 years); P < 0.05, and 1.16 mg/dL ( ≤ 30 years) vs. 1.83 mg/dL ( > 50 years) P < 0.001, respectively. Our findings indicate; 1) Due to the in situ cooling technique, the renal grafts of non-heart-beating cadavers can be expected to have relatively good function in the CS-treated recipients; 2) donor age is instrumental in predicting post-transplant renal function as well as the duration of ATN; 3) WIT, 1ST and TIT have no association with the post-transplant renal function if the duration of renal ischemia is within the acceptable range.

Abstract: Aims: Since April 1979, 471 kidneys were retrieved from donors after cardiac death (DCD) using an in situ regional cooling technique, with excellent renal function and good long-term graft survival. However, the precise cascade of events following transplantation of DCD kidneys and the influence of ischemia-reperfusion injury remain unclear. In this study, we performed gene expression profiling using 1-hour biopsy samples from DCD kidneys versus those from living sources. Methods: All kidney grafts were procured at our center using an in situ regional cooling technique from DCD. Living donor kidneys (LD) were harvested by open nephrectomy. All graft biopsies were performed 1 hour after reperfusion (DCD n = 8, LD n = 9). We analyzed the expression profile of 20,173 genes. Results: One hundred seventy eight genes were up-regulated (>2-fold difference and DCD/LD > 1.5) and 120 down-regulated (<1/2-fold and LD/DCD > 1.5) in DCD kidneys. Expression of osteopontin (22.5 ± 2.6–fold DCD vs 7.7 ± 1.7 LD; P < .001), chemokines (CCL4 4.4 ± 0.7 vs 2.5 ± 0.3; P < .01), (CCL2 6.0 ± 1.3 vs 2.8 ± 0.5), CXCL1 (9.5 ± 0.4 vs 2.0 ± 0.2), and CXCL2 (16.7 ± 5.3 vs 4.8 ± 1.3; P < .05), adhesion molecule (ICAM-1 4.7 ± 0.7 vs 2.5 ± 0.4; P < .05), and heat shock proteins (HSPA1L 6.7 ± 0.7 vs 1.6 ± 0.3, HSPA1A 17.7 ± 2.6 vs 2.4 ± 0.5, HSPA1B 13.3 ± 0.2 vs 3.0 ± 0.7, HSPA5 6.7 ± 0.8 vs 3.2 ± 0.3, HSPB1 2.9 ± 0.2 vs 1.0 ± 0.1, and HSPH1 19.4 ± 3.0 vs 5.9 ± 1.1; P < .001) were up-regulated in the kidneys from DCD. Conclusion: This report analyzed global gene expression using 1-hour biopsy samples from DCD kidneys. These results may provide new insight into the identification of novel target genes for the development of therapeutic approaches and for determining graft viability of kidneys from DCD. [Copyright &y& Elsevier]