Gene Expression Profiling of Peripheral Blood From Kidney Transplant Recipients for the Early Detection of Digestive System Cancer.

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.

Kidney Transplantation, Cardiovascular Risk, and Long-Term Dialysis in Japan.

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.

Initial experience with a tailor-made simulation and navigation program using a 3-D printer model of kidney transplantation surgery.

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.

Nutritional status in Japanese renal transplant recipients with long-term graft survival.

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.

A novel screening test for detecting graft thrombosis after pancreatic transplantation using contrast-enhanced ultrasonography with sonazoid.

Pancreatic graft thrombosis is the primary cause of nonimmunologic graft loss, with an incidence ranging from 5% to 15%. Therefore, developing a screening test to detect graft thrombosis after pancreatic transplantation is important. We created a screening test to assess graft thrombosis after pancreatic transplantation using contrast-enhanced ultrasonography (CEUS) with Sonazoid in addition to Doppler ultrasonography. A total of seven patients were examined using CEUS after undergoing pancreatic transplantation. All patients were observed to have a clear blood flow from the horizontal region to the peripheral region of the splenic vein in the pancreatic graft, and only one of the seven patients exhibited a blood flow in the horizontal portion of the splenic vein on Doppler ultrasonography performed immediately after pancreatic transplantation. Results from CEUS with Sonazoid showed the blood flow in the splenic vein and parenchyma of the pancreatic graft in detail, despite the slow and lateral blood flow in the splenic vein of the pancreatic graft immediately after transplantation.

Pharmacokinetics of everolimus when combined with cyclosporine in Japanese de novo renal transplant recipients.

BACKGROUND: Currently, there are no published data on pharmacokinetics (PK) of everolimus in combination with cyclosporine in Japanese renal transplant patients. We evaluated the PK of everolimus in Japanese de novo renal transplant patients who received everolimus in combination with cyclosporine. METHODS: In this phase 3, multicenter, randomized, open-label study, patients were randomized (1:1) to 1 of the 2 groups: everolimus 1.5 mg (targeted C0 of 3-8 ng/mL) plus reduced-dose cyclosporine or mycophenolate mofetil 2 g/d plus standard-dose cyclosporine. PK assessments for everolimus were performed on day 28 (month 1) in the PK subpopulation. RESULTS: A total of 11 patients (7 men), mean age 47.5 ± 11.21 years, were enrolled for PK analysis of everolimus. Starting at 1.5 mg (0.75 mg twice a day), the mean dose over a period of 28 days was 0.705 ± 0.1011 mg. Everolimus mean trough concentration was 4.307 ± 1.2459 ng/mL and mean peak concentration was 13.539 ± 3.5330 ng/mL, which peaked at 1 to 2 hours postdose. The average concentration was 7.558 ± 1.4723 ng/mL, area under the concentration-time curve was 90.70 ± 17.667 ng·h/mL, and peak-trough fluctuation was 122.6%. The PK parameters of everolimus were comparable to those in the earlier phase 3 studies (A2306 and A2307). The mean everolimus trough levels were within the target ranges at all time points ranging from 3.4 to 5.5 ng/mL (everolimus 0.75 mg twice a day, safety population). The majority of patients (>85% from day 7 onward) were maintained within the targeted everolimus trough blood levels (safety population). These data were similar to a non-Japanese study (A2309). CONCLUSIONS: The pharmacokinetic characteristics of everolimus in Japanese de novo renal transplant patients did not differ from those previously observed in non-Japanese patients, hence the same dosage of everolimus may be acceptable in Japanese patients.

Organ donation from brain-dead and circulatory-dead donors: single-institution experiences.

Although the number of organ donations is extremely small in Japan, organ donation from brain dead (DBD) donors is increasing since the revised Law for Organ Transplantation was enacted on July 17, 2010. In our institution, organ donations had so far been performed from 247 donors (DCD 242, DBD 5), which is the largest number in Japan. In this study, we analyzed the status of organ donation before and after the enforcement of the revised law. After the enforcement of the revised law, the option of organ donation was shown to the more families of potential donors by the doctors or donor coordinators. However, the final number of donors was almost the same. The frequency of DBD donors of all donors increased (33.3%) as compared to 9.1% before the enforcement of the revised law. Reasons for rejection of donation from donor families were mainly based on the lack of understanding of brain death. To increase organ donation, we should promote social recognition of brain death, having the Organ Donation Card, and discussion of organ donation in each family.

Utility of glucagon stimulation test in type 1 diabetes after pancreas transplantation.

BACKGROUND: Despite recent progress of immunosuppressive therapy with newly developed agents, long-term pancreatic graft survival after pancreas transplantation still remains low. Therefore, precise assessment of ß-cell function after pancreas transplantation is necessary. METHODS: Pancreatic ß-cell secretory activity was measured by means of the peripheral plasma fasting serum C-peptide (CPR) response to 1 mg of glucagon intravenously in 23 patients after pancreas transplantation. The utility of ΔCPR after injection was compared with other indices that reflect insulin secretion. RESULTS: When we performed the test, 6 patients still needed insulin injection after the transplantation. Mean CPR before and after glucagon intravenously were 1.9 ± 0.98 ng/mL and 4.6 ± 2.29 ng/mL, respectively. Fasting serum CPR, secretory unit of islet in transplantation (SUIT) index, and ΔCPR after glucagon injection were significantly different between insulin users and nonusers. During follow-up (501 ± 228 days), 3 patients could stop using insulin, and their increase of CPR (1.8 ± 0.5 ng/mL) was significantly higher than that in continuous insulin users (0.3 ± 0.3 ng/mL). CONCLUSION: Fasting CPR, SUIT index, and ΔCPR after glucagon injection could reflect ß-cell function for post-pancreas transplant patients, and glucagon stimulation test could give us additional information to predict insulin-free treatment.

Single-institution outcomes in the first year of pancreas transplantation from brain-dead donors.

BACKGROUND: Under a revision to the law in 2010, the number of pancreas transplantations from brain-dead donors has been increasing in Japan. We started a new Pancreatic Transplant Program at Fujita Health University Hospital in September 2012. METHODS: A total of 11 cases of pancreas transplantation from brain-dead donors performed at Fujita Health University Hospital were analyzed in terms of the background characteristics of the donors and recipients and the outcomes. RESULTS: The mean age of the recipients was 45.2 years, and all recipients had a long-term history of diabetes (mean: 32.5 years). In the simultaneous pancreas and kidney transplantation (SPK) cases, the patients also had a long history of hemodialysis (mean: 8.0 years). Although the average donor age was 42.5 years, 90% of the donors were marginal donors, defined according to the following factors: (1) >45 years old, (2) death from cardiovascular disease, (3) episodes of cardiac arrest, (4) use of high doses of catecholamines. The pancreatic graft survival rate was 100%, although 1 patient required a small amount of insulin to maintain euglycemia. In addition, the kidney graft survival rate was also 100% in the SPK cases. CONCLUSIONS: The new Pancreatic Transplant Program at Fujita Health University has provided excellent outcomes for type 1 diabetic patients.

A Japanese multicenter study of high-dose mizoribine combined with cyclosporine, basiliximab, and corticosteroid in renal transplantation (the fourth report).

We examined the efficacy and safety of 4-drug combination therapy using high-dose mizoribine (MZR) (8 mg/kg/d), cyclosporine (CsA), basiliximab (BXM), and steroid (STR) in 39 renal transplant recipients. Acute rejection episodes (ARE), which occurred in 9 (23.1%) patients, correlated with lower blood levels of MZR (trough levels ≥ 2 µg/mL). In addition, lower MZR concentrations tended to be associated with a higher incidence of rejection episodes in children aged ≤ 10 years than in those aged ≥ 11 years. The area under the received operating characteristics (ROC) curve of MZR trough level to pred ARE was 0.825 (95% confidence interval, 0.690-0.962; P = .002). Based on the ROC analysis, are MZR cut-off of 1.6 µg/mL showed a sensitivity of 81.8% and a specificity of 75.0%. Adverse events were observed in 23 patients, including infections in 11 (7 patients positive for cytomegalovirus [CMV] antigen and 4 treated with anti-CMV drugs). The MZR trough levels seemed to be higher among patients with adverse events than in those free of them, but it was no significant. All patients experienced successful engraftment except 1 who died of unknown cause with a functioning graft. In conclusion, our study showed that low MZR trough levels correlated with the incidence of ARE. No serious adverse effects were encountered with this therapy.

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.

Up-regulation of osteopontin, chemokines, adhesion molecule, and heat shock proteins in 1-hour biopsy from cardiac death donor kidneys.

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.

Should we discard the renal allografts from cardiac death donors that have total ischemic time longer than 24 hours?

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.

Is pulsatile perfusion necessary for renal transplantation engrafting kidneys from cardiac death donors?

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.

Regimen of tacrolimus-based immunosuppression with basiliximab, mycophenolate mofetil, and low-dose steroid reduces acute rejection in kidney transplants.

BACKGROUND: Acute rejection is a major problem in kidney transplantation. To reduce its likelihood, we investigated the efficacy and safety of an immunosuppressive regimen including tacrolimus, basiliximab, mycophenolate mofetil, and low-dose steroids. METHODS: Fifty-seven patients, including 14 pediatric patients, were enrolled in this study. The mean age at the time of transplantation was 33.5 years, and the mean observation period was 8.2 months. The mean trough concentrations of FK at 1, 6, and 12 months posttransplant were 10.2, 6.6, and 6.0 ng/mL, respectively. RESULTS: All recipients survived without graft loss. The cumulative incidence of acute rejection in adults was 2.3% and 8.4% at 6 and 12 months posttransplant, respectively. Of the adverse events, 11 recipients (19.3%) were positive for CMV antigenemia or had CMV infections. Four recipients (7.0%) exhibited mild hyperglycemia. CONCLUSIONS: Our immunosuppressive regimen demonstrated favorable results, reducing the incidence of acute rejection without causing severe adverse events, especially in adults.

IP-10, apoptotic genes, and calcineurin subtype messenger RNA kinetics occurring in rat renal isografts from brain-dead donors.

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.

Gene expression profile in rat renal isografts from brain dead donors.

BACKGROUND: Brain death (BD) and the subsequent ischemia/reperfusion (I/R) injury have cardinal implications for the pathogenesis of kidney transplantation (Tx). However, the precise mechanistic pathway of BD and the subsequent I/R injury are unknown. In this study, we performed genome-wide analysis for differential gene expression in kidney isografts from BD donors. Their gene expressions were compared with those from living sources. METHODS: Kidneys from BD rats were engrafted and their gene expressions were compared with those from living controls. Donors were intubated, and mechanically ventilated for 6 hours. Grafts were harvested 6 hours after BD, and 1 hour after engraftment. The expression profile of approximately 20,500 genes was analyzed. RESULTS: Gene expression of chemokines (Scya2 and Gro1), cytokines (IL-1 and -6) and adhesion molecules (E- and P-selectin and ICAM-1) were upregulated in the BD kidneys and 1 hour after engraftment. An antiapoptotic gene (Birc2), IkappaB-zeta, and protective gene (HO-1) were also upregulated. Other upregulated genes included oncogenes (lipocalin2, Bcl3, and CCAAT/enhancer binding protein delta), Calgranulin B, DEXRAS1, insulin-like growth factor binding protein-1, inhibin beta-B-subunit gene, IgG Fc receptor, and FK 506 binding protein 5. We also observed downregulation of the genes Amphiphsin, Jagged 1, Pace 4, Slc15a2, Kcnn2, and gap junction membrane channel protein alpha5 only in kidneys from BD donors. CONCLUSIONS: This is the first demonstration of global gene expression analysis using the rat brain-death isograft model. These results provide new insights for the detection of novel target genes for treatment and prognosis of grafts from brain-dead and extended marginal donors.

ABO-incompatible living-donor kidney transplantation in children.

BACKGROUND: Due to a severe shortage of suitable cadaveric allografts for children awaiting kidney transplants, we have performed a series of ABO-incompatible living kidney transplantations (LKT) at our institution. METHODS: Between July 1989 and March 2000, 16 pediatric patients (3 female, 13 male) underwent ABO-incompatible LKT. The mean age at transplantation was 10.9+/-4.3 years (range 5.1-15.0 years). The donor to recipient ABO blood antigen incompatibility was as follows: A1-->O, 5 patients; B-->O, 6 patients; A1B-->B, 2 patients; and A1B -->B, A1-->B, or B-->A1, 1 patient each. The median pretransplantation anti-A1 titers of eight A-incompatible recipients were 1:128 (IgM, range 1:16 to 1:512) and 1:32 (IgG, range 1:2 to 1:128). Median anti-B titers of seven B-incompatible recipients were 1:32 (IgM, range 1:4 to 1:128) and 1:8 (IgG, range 1:2 to 1:64). All patients received three or four sessions of plasmapheresis (PP) and/or immunoadsorption (IA) to remove the anti-A and/or anti-B antibodies before transplantation. Immunosuppression initially consisted of cyclosporine, methylprednisolone, cyclophosphamide, and antilymphocyte globulin. Splenectomy was performed on all recipients at the time of transplantation. RESULTS: The patients were followed for 6 to 122 months with a mean follow-up of 63 months. All 16 recipients who underwent ABO-incompatible LKT achieved a pretransplant isoagglutinin titer less than 1:8 with 3-4 sessions of PP/IA treatment. Of 16 patients, 10 patients had rebound increase in their IgM and/or IgG anti-A/B titers to greater than 1:64 or predepletion levels within 10 days posttransplantation. In addition, nine patients developed renal dysfunction in association with the rebound increase in their anti-A/B. One patient lost his graft because of uncontrolled delayed hyperacute rejection, whereas eight other recipients recovered completely with pulse steroids and PP/IA therapy. After the third week posttransplant, there was no correlation between the occurrence of AR and their isoagglutinin titers. Moreover, no antibody-mediated rejection was observed, even in recipients with continued high titer anti-A and/or anti-B antibodies. Patient survival is 100% to date. The actuarial 1-year and 5-year graft survival rates are 87% and 85%, respectively. No fatal infectious complications occurred despite the combination of splenectomy and immunosuppressive drugs. CONCLUSIONS: We have demonstrated that with adequate pre- and posttransplant management, successful kidney transplantation across the ABO barrier is possible in the pediatric population. "Accommodation" of the allografts occurred within 2 weeks of transplantation. Subsequently, the long-term graft outcome of ABO-incompatible LKT was comparable to that of ABO-compatible LKT.

Epidemiological study of vancomycin-resistant enterococcus isolated from a single medical university hospital in Japan.

Since 1998 more than 50 reports have described the isolation of high-level vancomycin-resistant enterococci (VRE) in Japan. Here, we report on our clinical isolates of VRE and an epidemiological study carried out using chemical and genetic techniques. VRE isolates were screened for high resistance to vancomycin (VCM) with a cutoff value of 6 microg/ml and VCM-resistant gene was confirmed by polymerase chain reaction (PCR). The epidemiological studies used pulsed-field gel electrophoresis (PFGE) and plasmid analysis. Six strains of VRE were isolated from six different patients on two wards during a 3-months period. All of the isolates possessed vanA on their plasmid, and the isolates were divided into two similar groups. Furthermore, three different patterns were defined by PFGE. Although all of the asymptomatic carriers were hospitalized for more than 3 months, we were able to prevent an outbreak of VRE in our hospital by using our guidelines for infection control, which are stricter than those for methicillin-resistant Staphylococcus aurens. From the results of this epidemiological study, we propose that there was a possibility of contamination in this hospital, and that three of the six isolates may have acquired vanA independently. In this study, we demonstrated that infection control, according to appropriate prevention guidelines, as well as regular surveillance for VRE, are essential for designing interventions to prevent the further spread of VRE.

Mycobacterium tuberculosis infection of bilateral cervical lymph nodes after renal transplantation.

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.