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Laparoscopic living donor nephrectomy（LDN）has become a standard procedure, and transperitoneal LDN is now performed at many centers. Since 2001, we have been developing a retroperitoneoscopic living donor nephrectomy（RPLDN）technique that allows LDN to be performed by a direct retroperitoneal approach that does not interfere with the abdominal organs. In this study, we examined the operating time, blood loss, total and warm ischemic times（TIT, WIT）, length of stay, number and length of renal arteries and vessels, graft function, and complications in 54 kidney donors（19 men, 35 women；mean age 57.1±11.8 years）who underwent living donor kidney transplantation with allografts obtained by RPLDN. Mean follow-up was 16.8 months. Donor nephrectomy was successful in all patients. Fifteen kidneys had ≥ 2 renal arteries. The complication rate was 5.6％. There were no serious complications. Ureteral complications occurred in four recipients, who were successfully treated by retrograde ureteral stent placement. Mean TIT was 87.7 min and mean WIT was 4.7 min. Mean serum creatinine levels in recipients were 3.5, l.5, and 1.4 mg/dL on postoperative days 1, 7, and 14, respectively. Slow graft function was noted in four cases（7.4％）, which normalized within 2 weeks of surgery. One-year donor survival was 100％ and 1-year graft survival was 98.1％. All RPLDNs were well tolerated and the impact on recipient graft function was excellent. RPLDN could be an option for LDN.

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Pyoderma gangrenosum (PG) is a skin disease characterized by an unknown neutrophilic infiltration in dermis and a nonbacterial destructive ulcer. Post-operative PG is an extremely rare type that occurs around surgical sites during the immediate post-operative period. It is usually diagnosed as surgical site infection at the time of presentation. The condition rapidly worsens despite antibiotic treatment and debridement. We report on a case of post-operative PG in a 64-year-old man after radical prostatectomy. Following the operation, redness and pus from surgical site rapidly progress although repeated antibiotic therapy and debridement were performed. Although the patient received appropriate debridement and broad-spectrum antibiotic treatment, the ulcerative lesion spread surrounding drain region and the condition of the skin region deteriorated. The diagnosis of PG was made by a skin biopsy that presented only neutrophilic invasion in the dermis without vasculitis, tumor, or malignancy. Finally, the patient died of lesion progression in whole body and multiple organ dysfunction. Considering PG along with ulcers, wounds, and post-operative complications is critical for prompt diagnosis and proper treatment.

The aim of this study was to evaluate the association between antibodies against cytomegalovirus (CMV) glycoprotein B (gB) and acute rejection after transplantation. Seventy-seven consecutive renal transplant recipients in a D + /R+ setting were studied. Biopsy-proven rejection occurred in 35% of the recipients. Among these recipients, 85% had antibodies against CMV gB. The rate of acute rejection was significantly higher in recipients with antibodies against gB than in those without them. Antibodies against gB can be a useful predictor of acute rejection in renal transplant recipients in a D + /R+ setting.

Background To evaluate the role of the oral glucose tolerance test (OGTT) before transplantation and to examine the risk factors for new-onset diabetes after transplantation (NODAT) during long-term follow-up of renal transplant recipients receiving FK-based therapy. Methods The study evaluated 378 patients pre-transplantation using the OGTT and assigned them to one of three groups: Group 1, normal pattern; Group 2, impaired fasting glucose (IFG)/impaired glucose tolerance (IGT) pattern (IFG/IGT); and Group 3, DM pattern. Results Although the incidence of NODAT was higher in Group 3 than in groups 1 and 2, no significant difference was found between the three groups with regard to graft survival during long-term follow-up. Multivariate analysis showed that only a family history of diabetes was a significant factor determining NODAT progression. Conclusions Impaired glucose tolerance appears to be a threshold influencing NODAT; however, it was not a significant factor in graft survival. Careful monitoring and management based on the result of the pre-transplantation OGTT appear to prevent the deterioration of impaired glucose tolerance in renal transplant recipients receiving FK-based therapy, even when a pre-operative OGTT shows impaired glycemic control.

In Japan, the complement-dependent cytotoxicity (CDC-crossmatch) test and the anti-donor antibody flow cytometric assay (FCXM) are used to evaluate presensitization among transplantation candidates. We introduced the flow cytometric panel reactive antibody method (FlowPRA) at our institution, and in this paper, we compared the results of FCXM and FlowPRA. Sera of a total of 238 patients receiving the first graft were analyzed by FlowPRA retrospectively. Specimens from 125 of these patients were also analyzed by FCXM, and the results obtained using the two methods were compared. In addition, postoperative pathological findings by graft biopsy were examined in patients with PRA class 1(+) or PRA class 2(+). (i) Class 1 antibodies were detected in 36 of the 238 patients (15%), class 2 antibodies in six patients (3%), and both class 1 and class 2 antibodies in five patients (2%). (ii) Totally 125 patients analyzed by both FCXM and FlowPRA, 28 patients (22%) who tested negative by FCXM were, however, found to be positive by FlowPRA, and 16 of these 28 patients (57%) had shown evidence of humoral rejection suspected of antibody-mediated in the early postoperative stage. A large proportion of patients who tested negative by FCXM but positive by FlowPRA experienced rejection. Thus, for detecting 'high responders' in patients receiving the first graft, use of FlowPRA to detect antibodies may be superior to that of FCXM.

Background Since a report on the first successful pregnancy of a woman on long-term haemodialysis in Japan in 1977, there has been a growing number of case reports on successful pregnancy in patients on dialysis. We undertook a nationwide survey on pregnancy in women on renal replacement therapy in 1996. Methods A preliminary questionaire was sent to 2504 dialysis units and 143 renal transplant units in Japan. For each reported pregnancy, a more detailed questionaire was sent to collect nephrological, obstetric and neonatal information. Results There were 172 pregnancies (0.44%) reported in 38889 women on dialysis, with 90 successful pregnancies (0.23%), and 194 pregnancies reported in 852 female renal transplant recipients. Detailed pregnancy information was collected from 74 women on dialysis and 194 renal transplant recipients. Of the 74 pregnancies in the women on dialysis, 36 (48.6%) resulted in surviving infants, nine (12.2%) in neonatal death, nine (12.2%) spontaneous abortions and 14 (18.9% elective abortions were reported. The outcome of six pregnancies (8.1%) was unknown. Of 194 pregnancies in renal transplant recipients, 159 (82.0%) resulted in surviving infants, two (1.4%) in neonatal death and 28 (14.4%) in spontaneous or elective abortion. In five cases the pregnancy outcome was not reported. No congenital anomalies were reported, except two infants with mental retardation and one with epilepsy. Conclusion The current survey revealed that the rate of successful pregnancy in women on dialysis has improved. More than half of the pregnancies resulted in infant survival. But, premature birth is a major problem for the children of women on dialysis and there is a higher rate of neonatal death. There are significant differences in gestational age, birth weight, frequency and severity of prematurity and rates of neonatal death between pregnancies of women undergoing dialysis and those who are renal transplant recipients.

Although there have been some reports describing the serostatus of cytomegalovirus, strain-specific antibody responses and their distribution remain unknown. In this study, ELISA using fusion proteins encompassing epitope of glycoprotein H from both AD169 and Towne strains was used to test 352 blood donors. Of these 352 donors, 207 were analyzed for strain-specific glycoprotein H antibodies. Of the 44 donors whose serum contained antibodies against both AD169 and Towne, 27 (60%) were aged 50 years or over (p = 0.0003). This may indicate serological evidence of reinfection with cytomegalovirus in the elder population. The nucleotide sequence analysis of cytomegalovirus glycoprotein H from the peripheral blood of the cytomegalovirus-positive renal transplant recipients showed that our strain-specific ELISA can reveal cytomegalovirus reinfection after transplantation.

Numerous studies have shown that protocol biopsies have predictive power. We retrospectively examined the histologic findings and C4d staining in 89 protocol biopsies from 48 ABO-incompatible (ABO-I) transplant recipients, and compared the results with those of 250 controls from 133 ABO-compatible (ABO-C) transplant recipients given equivalent maintenance immunosuppression. Others have shown that subclinical rejection (borderline and grade I) in ABO-C grafts decreased gradually after transplantation. In our study, however, subclinical rejection in the ABO-I grafts was detected in 10%, 14% and 28% at 1, 3 and 6-12 months, respectively. At 6-12 months, mild tubular atrophy was more common in the ABO-C grafts whereas the incidence of transplant glomerulopathy did not differ between the two groups (ABO-C: 7%; ABO-I: 15%; p = 0.57). In the ABO-I transplants, risk factors for transplant glomerulopathy in univariate analysis were positive panel reactivity (relative risk, 45.0; p < 0.01) and a prior history of antibody-mediated rejection (relative risk, 17.9; p = 0.01). Furthermore, C4d deposition in the peritubular capillaries was detected in 94%, with diffuse staining in 66%. This deposition, however, was not linked to antibody-mediated rejection. We conclude that, in the ABO-I kidney transplantation setting, detection of C4d alone in protocol biopsies might not have any diagnostic or therapeutic relevance.

Background. Cytomegalovirus (CMV) is the most important pathogen affecting the outcome of renal transplantation. The combination of CMV-seronegative transplant recipients with CMV-seropositive transplant donors places recipients at the highest risk of CMV disease. In cases of congenital CMV infection, existing immunity only partially protected mothers from reinfection with a different genotypic strain. The effect of differences in infected CMV strains between CMV-seropositive transplant donors and CMV seropositive transplant recipients on the outcome of transplantation remains unclear. Methods. In this prospective multicenter study, the presence of antibodies against strain-specific glycoprotein H epitopes in 84 CMV-seropositive transplant donor/CMV-seropositive transplant recipient renal transplantation cases were determined, and their relationships to acute transplant rejection, CMV infection, degree of antigenemia, and CMV disease were evaluated. Results. Among the 84 donor/recipient pairs, 45 and 32 had matched and mismatched strain-specific glycoprotein H antibodies, respectively. Acute transplant rejection in the mismatched group was more frequent than it was in the matched group (63% vs. 22%; P = .005). CMV disease was also more frequently observed in the mismatched group (28% vs. 9%; P = .026). The mismatched group had a higher level of antigenemia (P = .019). Conclusions. Our results illustrate more adverse events in the cases with a CMV-seropositive transplant donor and a CMV-seropositive transplant recipient in which the glycoprotein H antibodies are mismatched, suggesting that reinfection with a different CMV strain results in more complications.

Several protocols allow the successful ABO incompatible living-related kidney transplantation (ABO-ILKT), yet no single method has emerged as the best. We have made several substantial changes to our ABO-ILKT protocol over the past decade and a half and have attempted to determine whether the changes in immunosuppressive agents have resulted in a better outcome. We used methylprednisolone (MP), cyclosporine (CsA), azathioprine (AZ), antilymphocyte globulin (ALG) and deoxyspergualine (DSG) in the 105 cases of ABO-ILKT (group 1) between 1989 and 1999, and MP, tacrolimus (FK506), mycophenolate mofetil (MMF) in the 117 cases of ABO-ILKT (group 2) between 2000 and 2004. We compared the patient and graft survival rates as well as the incidence rate of acute rejection in these two eras, when different regimens were used. There were significant differences in the 1- and 5-year graft survival rates between groups 1 and 2 (1-year: 78% in group 1 vs. 94% in group 2; 5-year: 73% in group 1 vs. 90% in group 2, p = 0.008). Also, a higher incidence rate of acute rejection was significantly observed in group 1 (50/105, 48%) than in group 2 (18/117, 15%) (p < 0.001). We conclude that the FK/MMF combination regimen provides excellent graft survival results in ABO-ILKT.

We tried to establish the technique of retroperitoneoscopic live donor nephrectomy (RPLDN). Between July 2001 and March 2004, 135 renal transplant donors underwent RPLDN. Low (average: 7 mmHg) CO2 gas pressure was employed during the procedure. All procedures were performed through a three-port retroperitoneal approach without opening the peritoneal cavity. The hand-assisted technique was not used. One hundred and twenty-seven cases were of left and eight cases were of right nephrectomy. Donor nephrectomy was carried out successfully in all patients. In one donor, the procedure was changed to open donor nephrectomy because of severe adhesion around the renal vein due to previous surgery. No serious complications, such as massive bleeding or bowel injury were encountered. Return of bowel function took 0.7 days on average. Post-operative hospital stay was 4.9 days on average, and return to work was 12 days on average. Ureteral complications occurred in 2 patients and were treated with temporally retrograde ureteral stenting. Average serum creatinine levels were 1.5 mg/dL, 1.3 mg/dL and 1.3 mg/dL at 3, 7 and 14 days after transplantation, respectively. No patients required hemodialysis after transplantation due to acute tubular necrosis. RPLDN could be an option for laparoscopic live donor nephrectomy.

BK polyomavirus (BKV) is ubiquitous in the human population, infecting children without obvious symptoms, and persisting in the kidney in a latent state. In immunosuppressed patients, BKV is reactivated and excreted in urine. BKV isolates have been classified into four subtypes (I–IV) using either serological or genotyping methods. To elucidate the subtypes of BKV prevalent in Japan, the 287 bp typing region in the viral genome was PCR-amplified from urine samples of 45 renal transplant (RT) and 31 bone-marrow transplant (BMT) recipients. The amplified fragments were subjected to a phylogenetic or RFLP analysis to determine the subtypes of BKV isolates in urine samples. Subtypes I, II, III and IV were detected, respectively, in 70–80, 0, 2–3 and 10–20 % of the BKV-positive patients in both patient groups. This pattern of distribution was virtually identical to patterns previously demonstrated in England, Tanzania and the United States, suggesting that BKV subtypes are distributed similarly in various human populations. Furthermore, transcriptional control regions (TCRs) were PCR-amplified from the urine samples of 25 RT and 20 BMT recipients, and their nucleotide sequences were determined. The basic TCR structure (the so-called archetype configuration) was observed in most isolates belonging to subtypes I, III and IV (subtype II isolates were not available), albeit with several nucleotide substitutions and a few single-nucleotide deletions (or insertions). Only three TCRs carried extensive sequence rearrangements. Thus, it was concluded that the archetypal configuration of the BKV TCR has been conserved during the evolution of BKV.

Since June 1983, 27 kidneys have been shipped to the Kidney Center at the Tokyo Women's Medical College (TWMC) from the United States. These organs were divided into two groups, based on the years of their donation; 13 kidneys were assigned to group 1 and 14 to group 2. The differences between the two groups were as follows: donor age 19.8 +/- 10.0 years vs 51.9 +/- 14.5 years in group 2 (P0.0001); total ischemic time 42 h 12 min in group 1 vs. 65 h 42 min in group 2 (P = 0.0002); and Euro-Collins preservation solution in group 1 vs University of Wisconsin (UW) solution in group 2. One hundred percent of the kidneys in group 1 and 85.7% of those in group 2 recovered their function. The lowest serum creatinine levels averaged 96 +/- 38.4 mumol/l and 185.8 +/- 101.0 mumol/l, respectively (P = 0.01). The viability of 9 out of 14 grafts in group 2 were tested using 31P magnetic resonance spectroscopy (31P-MRS). The results showed that all of the grafts having a monophosphate/inorganic phosphate (MP/Pi) ratio higher than 0.3 recovered their function and those lower than 0.2 did not. The problems associated with international organ sharing are discussed, along with the difficulties encountered at TWMC.

Hemolysis may occur after organ transplantation. In most cases, hemolysis is drug-related, such as to cyclosporin, etc. However, it is important to consider graft-versus-host antibody formation as one of the causes of hemolysis. We evaluated the effect of local graft irradiation as a method of preventing hemolysis arising from ABO antibody formation after ABO-mismatched renal transplantations. The participants in this study were 44 patients who had undergone ABO-mismatched renal transplantation. Of these patients, 23 were subjected to postoperative local irradiation, and 21 were not. We examined the characteristics of anti-blood-type antibodies, and we also compared the frequency of the development of antibody formation and hemolysis development between the groups. The development rates of anti-ABO-antibody formation and hemolysis were significantly higher in the patients without local irradiation (15/21, 71%; 6/21, 29%) than in those with local irradiation (1/23, 4%; 0/23, 0%). The elevated antibodies mainly belonged to the IgG class, not the IgM class. The hemolysis- and antibody formation observed in the patients originally without postoperative local irradiation was dramatically improved by graft irradiation. Local graft irradiation after ABO-mismatched renal transplantations may be needed to prevent the formation of anti-ABO antibodies and to impede the development of hemolysis.