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Donors with resolved hepatitis B virus (HBV) infection may be a solution for the organ shortage for kidney transplantation (KT). The purpose of this study was to clarify the current state of HBV markers after KT from donors with resolved HBV infection to HBV naïve recipients and the rate of HBV reactivation in recipients with resolved HBV infection. Furthermore, we investigated HBV covalently closed circular DNA (cccDNA) in transplanted organs from donors with resolved HBV infection and the capability of HBV replication in kidney cell lines. We retrospectively analysed the HBV status of 340 consecutive donors and recipients who underwent KT in a single centre. We prospectively measured cccDNA by real-time polymerase chain reaction in kidney biopsy specimens of 32 donors with resolved HBV infection. HBV reactivation was found in three recipients with resolved HBV infection (4.8%, 3/63) after KT. We analysed 45 cases of transplantation from donors with resolved HBV infection to HBV-naive recipients. One case (2.2%, 1/45) became seropositive for hepatitis B core antibody (anti-HBc) and in another case (2.2%, 1/45), HBV-DNA was detected qualitatively in an HBV naive recipient with a donor with resolved HBV infection. In the latter case, cccDNA was measured in the donor kidney during KT. HBV replication was observed in kidney cell lines with HBV plasmid transfection. In conclusion, the risk of reactivation in anti-HBc-positive donors is relatively low. However, post-transplant HBV monitoring should be conducted in all at-risk cases.

Background Introduction of rituximab in the desensitization protocols for ABO-incompatible (ABOI) kidney transplantation (KTX) has afforded excellent results. However, the acceptability of minimal dosage of rituximab in these protocols remains to be defined. Methods Sixty-three patients who underwent ABOI KTX were included in this study. The desensitization protocol consisted of plasmapheresis, tacrolimus, mycophenolate mofetil, methylprednisolone, intravenous immunoglobulin, basiliximab, and low-dose rituximab (100 mg/body). We evaluated the efficacy, safety, and long-term outcome of this protocol (group R, n = 39) and compared them with those of patients who underwent splenectomy (group S, n = 24). Results Graft and patient survival at 10 years after KTX were comparable between the groups (94.4% [group R] vs 95.4% [group S] and 94.6% [group R] vs 95.8% [group S], respectively). The incidence of acute antibody-mediated rejection (AAMR) was similar in the 2 groups (10.2% vs 12.5%). There were no significant differences in the incidence of chronic active antibody-mediated rejection. Of the patients, 7 developed AAMR and 3 of these patients (1 in group R and 2 in group S) lost their grafts. There were no significant differences in the incidence of chronic active antibody-mediated rejection. The incidence of postoperative cytomegalovirus infection in group R was significantly lower than that in group S. Furthermore, the incidence of postoperative late-onset neutropenia was low in group R. Conclusions A low-dose rituximab regimen for ABOI KTX is acceptable for preventing AAMR with a low incidence of delayed adverse events.

Introduction Femoral nerve palsy is a rare but serious complication of kidney transplantation. We report a case of femoral nerve palsy following kidney transplantation and conduct a review of the literature on this complication. Case presentation A 35-year-old woman with end-stage kidney disease, underwent kidney transplantation in the right iliac fossa. The day after the transplantation, she could not straighten her right leg. Physical examination revealed a paresis of her right quadriceps muscle. The patient's sensation of her right thigh was also impaired. We diagnosed her with femoral nerve palsy caused by inappropriate compression from a self-retaining retractor. Rehabilitation was started immediately. The patient's motor weakness gradually improved, and the patient became able to walk independently 4 weeks later. However, the patient's neuropathic pain sustained 6 months after her kidney transplantation. Conclusion The improper use of self-retaining retractors can lead to femoral nerve palsy in patients undergoing kidney transplantation.

Introduction: Laparoscopic surgery has been a standard procedure of living donor nephrectomy (LDN). Transperitoneal hand-assisted laparoscopic LDN (HALDN) has been commonly reported by man...

Considerable shortages in the supply of available organs continue to plague the field of solid organ transplantation. Despite changes in allocation, as well as the utilization of extended criteria and living donors, the number of patients waiting for organs continues to grow at an alarming pace. Xenotransplantation, cross-species solid organ transplantation, offers one potential solution to this dilemma. Previous extensive research dedicated to this field has allowed for resolution of xenograft failure due to acute rejection, leaving new areas of unresolved challenges as barriers to success in large animal models. Specific to kidney xenotransplantation, recent data seems to indicate that graft compromise can occur due to discrepancies in growth between breeds of donors and significant proteinuria leading to nephrotic syndrome in the recipient. Given these potential limitations, herein, we review potential pathways behind proteinuria, as well as potential causative factors related to growth discrepancies. Control of both of these has the potential to allow xenotransplantation to become clinically applicable in an effort to resolve this organ shortage crisis.

In our studies of life-supporting α-1,3-galactocyltransferase knockout (GalT-KO) pig-to-baboon kidneys, we found that some recipients developed increased serum creatinine with growth of the grafts, without histological or immunological evidence of rejection. We hypothesized that the rapid growth of orthotopic pig grafts in smaller baboon recipients may have led to deterioration of organ function. To test this hypothesis for both kidneys and lungs, we assessed whether the growth of outbred (Yorkshire) organ transplants in miniature swine was regulated by intrinsic (graft) or extrinsic (host environment) factors. Yorkshire kidneys exhibited persistent growth in miniature swine, reaching 3.7 times their initial volume over 3 mo versus 1.2 times for miniature swine kidneys over the same time period. Similar rapid early growth of lung allografts was observed and, in this case, led to organ dysfunction. For xenograft kidneys, a review of our results suggests that there is a threshold for kidney graft volume of 25 cm3 /kg of recipient body weight at which cortical ischemia is induced in transplanted GalT-KO kidneys in baboons. These results suggest that intrinsic factors are responsible, at least in part, for growth of donor organs and that this property should be taken into consideration for growth-curve-mismatched transplants, especially for life-supporting organs transplanted into a limited recipient space.

Interspecies transplantation, xenotransplantation, is becoming a realistic strategy to solve the organ shortage crisis. Here, we focus on seminal publications that have driven research in xenotransplantation, as well as recently published literature and future endeavors. Advances in gene editing technology have allowed for the efficient production of multitransgenic porcine donors leading improved xenograft survival in baboons, up to 2 years following heterotopic heart xenotransplantation and from weeks to several months following life-supporting kidney xenotransplanation. As technology evolves, additional challenges have arisen, including the development of proteinuria, early graft loss associated with porcine CMV, disparities in organ growth between donors and recipients, as well as high-dose continuous immunosuppression requirements. To address these issues, our laboratory developed a tolerance-inducing protocol which has allowed for >6-month survival of a life-supporting kidney with further approaches currently underway to address the challenges mentioned above. Our recent findings, reviewed in this article, led us to develop methods to overcome obstacles, which, in conjunction with the work of others, are promising for future clinical applications of xenotransplantation.

Chronic active antibody-mediated rejection (CAAMR) is a particular problem in kidney transplantation (KTx), and ~25% of grafts are lost by CAAMR. Further, the pathogenesis remains unclear, and there is no effective cure or marker. We previously found that a hyper NFκB-activating mechanism in non-immune cells, called the IL-6 amplifier, is induced by the co-activation of NFκB and STAT3, and that this activation can develop various chronic inflammatory diseases. Here, we show that synaptotagmin-17 (SYT17) is increased in an exosomal fraction of the urine from CAAMR patients, and that this increase is associated with activation of the IL-6 amplifier. Immunohistochemistry showed that SYT17 protein expression was increased in renal tubule cells of the CAAMR group. While SYT17 protein was not detectable in whole-urine samples by western blotting, urinary exosomal SYT17 levels were significantly elevated in the CAAMR group compared to three other histology groups (normal, interstitial fibrosis and tubular atrophy, and calcineurin inhibitors toxicity) after KTx. On the other hand, current clinical laboratory data could not differentiate the CAAMR group from these groups. These data suggest that urinary exosomal SYT17 is a potential diagnostic marker for CAAMR.

We have previously reported that co-transplantation of the kidney with vascularized donor thymus from α-1,3-galactosyltransferase gene knockout pigs with an anti-CD154 with rituximab-based regimen led to improved xenograft survival in baboons with donor-specific unresponsiveness. However, nephrotic syndrome emerged as a complication in which the glomeruli showed mild mesangial expansion with similarities to minimal change disease (MCD) in humans. Since MCD is associated with CD80 expression in glomeruli and elevated urinary excretion, we evaluated a potential role for CD80 in xenograft nephropathy. Study 1 confirmed high urinary CD80 excretion in nephrotic animals with renal xenografts showing CD80 expression in glomeruli. In Study 2, baboons receiving xenografts received CTLA4-Ig once a week from the second postoperative week or no CTLA4-Ig. The non-CTLA4-Ig group developed severe proteinuria with modest mesangial expansion with high urinary excretion of CD80 and documented CD80 expression in glomerular podocytes. All of the recipients in non-CTLA4-Ig groups had to be euthanized before POD 60. In contrast, CTLA4-Ig group showed a marked reduction in proteinuria and survived significantly longer, up to 193 days. These results demonstrate that anti-CD80 targeted therapy represents a promising strategy for reduction of proteinuria following renal xeno-transplantation with improved survival.

Shortages in the availability of transplantable organs have forced the transplant community to seek alternative methods to increase the supply of available organs. In our recent study following α-1,3-galactocyltransferase knockout (GalT-KO) pig-to-baboon kidney xenotransplantation, we found that certain recipients developed increased serum creatinine, possibly due to the rapid growth of orthotopic pig grafts in smaller baboon recipients. To test our hypothesis, we assessed whether the growth of outbred (Yorkshire) organ transplants (kidney and lung) in miniature swine was regulated by intrinsic (graft) factors. Yorkshire kidneys reached 3.7x their initial volume over 3 months vs. 1.2x for miniature swine kidneys over a similar time period. A similar pattern was seen in porcine lung allografts as well. Following xenotransplantation, a review of our results suggests that there is a threshold for kidney graft volume of 25 cm3/kg of recipient body weight at which cortical ischemia is induced in transplanted GalT-KO kidneys in baboons. These results suggest that intrinsic factors are in part responsible for the growth of donor organs and this should be taken into consideration for growth-curve-mismatched transplants.

Protocol biopsies for the detection and treatment of subclinical rejection in the early period after kidney transplantation are useful for preventing allograft dysfunction. However, little has been reported on the relationship between subclinical rejection and long-term protocol biopsies. In this review, we examine the potential benefits associated with long-term allograft biopsies focusing on the issue of immunological and non-immunological factors. Early detection and treatment of subclinical rejection improves outcome. However, the benefit of long-term allograft biopsies is largely unproved, and the strategy is yet to be widely implemented. The procurement of long-term protocol biopsies for the sole purpose of detecting subclinical rejection may be unwarranted. On the other hand, the early detection of IgA nephropathy using long-term protocol biopsy may improve graft survival. In addition, assessment of long-term protocol biopsies is useful not only for detection of calcineurin inhibitor nephrotoxicity, but also for follow-up after withdrawal of calcineurin inhibitor regimens. Also, identifying normal histology on a protocol biopsy may inform us about the safety of reducing overall immunosuppression. Thus, the potential benefit of long-term protocol biopsy may be of clinical significance for the detection of graft dysfunction as a result of non-immune factors, such as recurrence of glomerulonephritis and calcineurin inhibitor nephrotoxicity, rather than subclinical rejection.

Aim Recurrence of immunoglobulin A (IgA) nephropathy (IgAN) after renal transplantation is important as a cause of graft failure under improving rejection control. However, no specific therapy for recurrent IgAN is currently available. In this study, we evaluated the histological efficacy of tonsillectomy for allograft IgAN. Methods Fifteen kidney recipients (male 9, female 6, mean age 40.9 ± 9.3 years), who received a diagnosis of IgA nephropathy by allograft biopsy, were enrolled in this study. Tonsillectomy was performed 44.1 ± 27.1 months after the kidney transplantation. All patients underwent a repeat graft biopsy at 23.8 ± 15.8 months after tonsillectomy. Results Six patients had microhematuria before tonsillectomy. At 12 months after treatment, the microhematuria disappeared in five of these patients and one patient had mild hematuria. Three patients had severe proteinuria (more than 1.0 g/gCr) before tonsillectomy and improved after treatment. On histological analysis, four patients had acute lesions including cellular or fibrocellular crescents. The acute lesions disappeared after these treatments in all patients. Eleven patients had chronic lesions including global sclerosis, segmental sclerosis and fibrous crescents. The chronic lesion was ameliorated in six patients, unchanged in three and deteriorated in two patients. Conclusions Tonsillectomy improves not only clinical findings but also ameliorates histological damage caused by recurrent IgAN after kidney transplantation. Tonsillectomy is a novel and effective treatment for recurrent IgAN.

Alloantibodies contribute significantly to renal transplant rejection by activation of complement and various cytokines with a variety of effector cells, and are a major cause of allograft loss. Although there is clinical evidence of antibody- and complement-mediated injury in renal transplantation, the mechanism of antibody-mediated rejection remains largely unknown. In order to understand the sequential production of antibodies and complement components, we presensitized recipient rats by skin transplantation. Anti-donor-specific IgG levels reached a maximum 2 weeks following presensitization after which the rats underwent renal transplantation from the same donor strain. We then evaluated sequential pathological findings based on the Banff classification and several factors related to graft rejection. In this presensitized model, peritubular capillaries were already dilated and stained for C4d. Neutrophil and mononuclear cell infiltration in these capillaries was detected beginning 2 h after transplantation. Donor-specific antibody IgG levels decreased rapidly and anti-IgG antibody stained glomerular and peritubular capillaries in the grafts beginning 2 h after transplantation. Additionally, several cytokines and complement components showed marked changes in the presensitized group. Thus, in the donor-specific presensitized recipient, alloantibodies and complement were activated immediately after transplant. C4d deposition in peritubular capillaries appears to be a key factor for the diagnosis of antibody-associated rejection.

Background A prolonged-release formulation of tacrolimus (Tacrolimus QD) was developed to allow once-daily dosing and to have similar safety and efficacy profiles to twice-daily tacrolimus (Tacrolimus BID). This study compared the pharmacokinetics (PK) and renal pathology by protocol biopsy in de novo living kidney transplant recipients treated with either low-dose Tacrolimus QD or Tacrolimus BID. Methods Between November 2009 and January 2011, 102 consecutive adult patients were randomized to receive either low-dose Tacrolimus QD or Tacrolimus BID. All patients underwent PK study and protocol biopsy on postoperative day 14. Additional protocol biopsies were performed between 6 and 12 months after renal transplantation. Results During the 1-year follow up, the incidence of biopsy-proven acute rejection and toxic tubulopathy was low and similar in both groups. Twenty-four hours area under the curve (AUC0-24) was not different in both groups (285 ± 78.7 and 281 ± 62.4 ng hr/mL in Tacrolimus QD and Tacrolimus BID, respectively). C0 was well correlated with AUC0-24 in both groups and AUC0-24 between 260 and 280 in the Tacrolimus QD group was achieved by 6 to 8 ng/mL of C0. Acute nephrotoxicity was less than 10% in both groups without any clinical manifestation. Conclusion Clinical efficacy, safety, and PK profile of Tacrolimus QD is same as those of Tacrolimus BID.

Transplant glomerulopathy (TG) is involved in the criteria of chronic active antibody-mediated rejection (c-AMR) in Banff ‘09 classification. Patients TG was diagnosed in 58 renal allograft biopsy specimens (BS) from 37 renal transplant patients. Results Among 58 BS of TG, 27 BS were mild (cg1), 16 were moderate (cg2), and 15 were severe (cg3). Peritubular capillaritis was present in 49 (84%), transplant glomerulitis was seen in 47 BS (81%), interstitial fibrosis and tubular atrophy in 47 (81%) and the thickening of the peritubular capillary (PTC) basement membrane (PTCBM) in 44 (76%), and interstitial inflammation was present in 26 BS (45%). C4d deposition in PTC was presented in 32 BS (55%). The circulating anti-HLA alloantibody was detected in 38 times (76%), of which 27/38 (54%) were donor-specific antibodies. Deterioration of renal allografts’ function after biopsies was seen in 12 patients (32%) with six of them lost their graft. Conclusions We suggest that histopathological changes of TG accompanying by transplant glomerulitis, peritubular capillaritis, the thickening of the PTCBM, and circulating anti-HLA antibodies might indicate c-AMR, even if C4d deposition in PTC is negative. The prognosis of the graft exhibiting TG was relatively good under the present immunosuppression protocol in short time.

Histopathological changes of acute vascular rejection (AVR) are characterized by intimal arteritis and transmural arteritis. According to the Banff 1997 classification, the quantitative criteria for intimal arteritis (v score) are classified: v0, v1, v2, and v3. According to Banff '09 classification, AVR may fall into one of four categories: acute T cell-mediated rejection (ATMR) Type IIA, ATMR Type IIB, ATMR Type III, and acute antibody-mediated rejection (AAMR) Type III. Both cellular and humoral immunity play roles in vascular rejection, and in some cases, AVR may be provoked by anti-donor antibodies. Anti-rejection therapies were effective in most of the v1 cases but were less effective in the v2 cases and were ineffective in the v3 cases. Some reports have indicated that the prognosis of grafts exhibiting AVR is poor, but in our series, the outcome of AVR was relatively good using recent immunosuppressive protocols. A definition for "isolated v-lesion" was originally characterized by arteritis with minimal interstitial inflammation and tubulitis. The 11th Banff conference was concluded that "isolated v1-lesions" comprised two types, T cell-mediated rejection and injury, and did not have any independent prognostic significance. However, we speculate that "isolated v-lesion" might be regarded as AAMR and ATMR.

Introduction Histopathologic change of acute vascular rejection (AVR) is characterized by intimal arteritis and transmural arteritis. In this report, we discuss the clinicopathologic analysis of AVR cases after renal transplantation. Patients AVR was diagnosed in 28 renal transplant recipients followed up in our institute between January 2003 and November 2010. Results Among 28 cases of AVR, 18 were mild (v1 in Banff 07 classification), 8 were moderate (v2), and 2 were severe (v3). Interstitial inflammation was present in 25 biopsy specimens. Moderate to severe tubulitis (t2–t3) was present in 10 biopsy specimens and transplant glomerulitis in 17; peritubular capillaritis was in 25 of the 28 biopsy specimens. C4d deposition in peritubular capillaries was observed in 11/28 cases. By using assays with plastic beads coated with human leukocyte antigen (HLA) in the 28 cases, we detected circulating anti-HLA alloantibody in 18 patients, among which 11/28 were donor-specific. Acute antibody-mediated rejection was diagnosed in 6 cases. Among AVR cases, 19/28 displayed steroid-resistant rejection (SRR) requiring greater anti-rejection therapy (ART), including muromonab CD3 injection, gusperimus injections, plasmapheresis, intravenous immune globulin, and/or rituximab injections. Twenty of 28 patients recovered renal allograft function after ART, and 26/28 grafts are functioning. Among the 2 cases of graft loss, only 1 patient lost his graft due to AVR. Conclusions In some cases, AVR might be provoked by anti-donor antibodies. The prognosis of the graft exhibiting AVR was relatively good using available immunosuppression.

Transplant glomerulopathy (TG) has commonly been described as a late manifestation of allograft injury, occurring years after renal transplantation. We describe herein a patient who developed TG early (49 days) after kidney transplantation (KTx). Case report: A 44-yr-old woman received a second living-related KTx from her younger brother in October 2009. Pre-transplant donor-specific anti-human leukocyte antigen antibodies (DSA) were positive for both class I and class II. During the renal transplant operation, she suffered from hyperacute antibody-mediated rejection (AMR) and intravenous immune globulin therapy was immediately performed. Once hyperacute AMR was resolved, accelerated acute AMR occurred on the first post-transplant day (PTD). The renal allograft biopsy performed on PTD 19 diagnosed acute AMR type II. The renal allograft biopsy performed on PTD 49 showed focal lesions of double contours of glomerular basement membranes in some glomeruli. Interstitial fibrosis showed a strong, diffuse staining of C4d in peritubular capillaries (PTCs). The DSA examined on PTD 39 were still positive for both class I and class II. From these histopathological findings of TG, C4d deposition in PTC and presence of circulating DSA, we diagnosed this case to have c-AMR. Conclusions: TG might be recognized in early after KTx.

Regulatory T cells (Treg) play an important role in modulating the immune response and has attracted increasing attention in diverse fields such as cancer treatment, transplantation and autoimmune diseases. CC chemokine receptor 4 (CCR4) is expressed on the majority of Tregs, especially on effector Tregs. Recently we have developed a diphtheria-toxin based anti-human CCR4 immunotoxin for depleting CCR4(+) cells in vivo. In this study, we demonstrated that the anti-human CCR4 immunotoxin bound and depleted monkey CCR4(+) cells in vitro. We also demonstrated that the immunotoxin bound to the CCR4(+)Foxp3(+) monkey Tregs in vitro. In vivo studies performed in two naive cynomolgus monkeys revealed 78-89% CCR4(+)Foxp3(+) Treg depletion in peripheral blood lasting approximately 10 days. In lymph nodes, 89-96% CCR4(+)Foxp3(+) Tregs were depleted. No effect was observed in other cell populations including CD8(+) T cells, other CD4(+) T cells, B cells and NK cells. To our knowledge, this is the first agent that effectively depleted non-human primate (NHP) Tregs. This immunotoxin has potential to deplete effector Tregs for combined cancer treatment.

Calcineurin inhibitors (CNIs) have considerably improved renal allograft survival. However, their chronic use has various adverse effects, including hypertension, hyperlipidemia, and nephrotoxicity. We conducted a retrospective study of kidney transplant recipients using a CNI withdrawal protocol. Eleven of 13 patients who had stable graft function on triple-drug therapy including a cyclosporine (CsA) were enrolled in this study. The dose of CsA was reduced by 20% every two wks until complete withdrawal. The mean period between the baseline and last biopsies was 97 (range: 21-123) months. No patient had an acute rejection episode during follow-up. Progression of interstitial fibrosis and tubular atrophy was seen in five and six cases, respectively. Arteriolar hyalinosis improved in three cases, but worsened in four. No patient lost his graft during the study. The mean serum creatinine level was 1.30 ± 0.26 mg/dL at baseline and stable for 10 yr after elimination (1.26 ± 0.11 mg/dL). At the end of the study, four of the eleven patients had reduced their antihypertensive drugs, and one patient had stopped hyperlipidemia treatment. CNI withdrawal can be implemented safely in stable renal transplant recipients and might lead to improved patient outcomes. Additional specific evidence of CNI nephrotoxicity should be elucidated.

The first case of kidney transplantation at our institution was carried out in 1971, and this first renal transplant recipient is still living with a functioning kidney. From 1971 through the end of 2011, more than 3000 cases of kidney transplantation have been carried out at our institution. Since 1983, cyclosporine-based immunosuppression has been employed at our center. During this period, most of the patients were treated with cyclosporine- or tacrolimus-based immunosuppression. The latest outcomes of kidney transplantation seem to have significantly improved compared to earlier periods. Since 2000, 10 year-graft survival is more than 90% in living donor kidney transplantation and 82% in deceased donor kidney transplantation. To resolve the serious problem of donor organ shortage, expansion of the donor pool by various options such as transplantation using extended criteria donation, donation after cardiac death, ABO-incompatible (ABO-ILKT) donors, or crossmatch-positive donors, has been carried out at our institution over the last decade. We performed the first case of ABO-ILKT in 1989, and have performed more than 400 cases at our institution as of 2011. We will describe our experience of kidney transplantation, including ABO-ILKT, sensitized recipients, pathological analysis, pediatric renal transplantation, laparoscopic donor nephrectomy, and recurrent glomerulonephritis. The data shows good outcomes, however, we still have many issues to resolve to improve long-term renal transplant outcome and to reduce complications.

BACKGROUND Endothelial chimerism in transplanted organs can be defined as the presence of recipient-derived endothelial cells in the donor organ. The mechanism of endothelial chimerism is not well understood and remains controversial. The purpose of this study was twofold. First, we investigated the presence of chimerism in renal allografts of ABO-incompatible kidney transplantation recipients. Second, we analyzed the association between chimerism and the clinical course and histopathological changes. METHODS We investigated the presence of chimerism in renal allografts of ABO-incompatible kidney transplantation recipients by immunohistochemical detection of blood type A and B antigens and assessed the association between chimerism, the clinical course, and histopathological changes. Among a total of 56 patients (29 blood group A incompatible and 27 blood group B incompatible), 49 cases (28 blood group A incompatible and 21 blood group B incompatible) were enrolled in this study. Blood group antigens were stained using immunohistochemistry. RESULTS Twelve of the 49 patients (12/49, 24.5%) exhibited endothelium chimerism in a biopsy sample. Among the 12 patients with endothelium chimerism, 7 patients (7/12, 59%) had acute and chronic active antibody-mediated rejection and 2 patients (2/12, 17%) had severe calcineurin inhibitor toxicity. The graft survival rate in the chimerism group was significantly lower than that in the no-chimerism group ([chimerism vs. no-chimerism] 3 years, 83.3% vs. 97.1%; 5 years, 74.1% vs. 97.1%; 8 years, 46.3% vs. 97.1%; P

We present a case of severe BK polyomavirus nephropathy (BKVN) complicated with persistent acute T-cell-mediated rejection (ATMR) that progressed to allograft failure. A 54-yr-old man received a living donor kidney transplant from his wife. Approximately four months after transplantation, the patient's serum creatinine (SCr) increased from a baseline value of 1.5-2.4 mg/dL. A histological analysis showed BKVN, and the SV40 antigen was detected in the tubular nuclei. The doses of immunosuppressants were reduced, and immunoglobulin was administered intravenously. The SCr increased further, to 5.3 mg/dL, and a second renal biopsy revealed the presence of severe ATMR. Antirejection treatment was performed, and low-dose cidofovir was started. The SCr decreased, to 3 mg/dL, and BK virus antigen in the serum and urine samples became negative at the time of hospital discharge. However, the histological findings subsequently showed gradually progressive interstitial fibrosis and tubular atrophy, and the SCr increased gradually. Two years after the transplantation, the patient resumed hemodialysis. BK polyomavirus nephropathy is usually treated with a reduction in immunosuppressant therapy, although in some patients, the reduction in immunosuppressants induces a subsequent exacerbation of acute rejection and results in progressive graft failure, which suggests difficulty in treating BKVN after kidney transplantation.

Transplant glomerulopathy (TG) has commonly been described as a late manifestation of allograft injury, occurring years after renal transplantation. We describe herein a patient who developed TG early (49 days) after kidney transplantation (KTx). A 44-yr-old woman received a second living-related KTx from her younger brother in October 2009. Pre-transplant donor-specific anti-human leukocyte antigen antibodies (DSA) were positive for both class I and class II. During the renal transplant operation, she suffered from hyperacute antibody-mediated rejection (AMR) and intravenous immune globulin therapy was immediately performed. Once hyperacute AMR was resolved, accelerated acute AMR occurred on the first post-transplant day (PTD). The renal allograft biopsy performed on PTD 19 diagnosed acute AMR type II. The renal allograft biopsy performed on PTD 49 showed focal lesions of double contours of glomerular basement membranes in some glomeruli. Interstitial fibrosis showed a strong, diffuse staining of C4d in peritubular capillaries (PTCs). The DSA examined on PTD 39 were still positive for both class I and class II. From these histopathological findings of TG, C4d deposition in PTC and presence of circulating DSA, we diagnosed this case to have c-AMR. TG might be recognized in early after KTx.

Background Few studies have investigated the changes in the antigenicities of the transplanted organs after transplantation. Methods We examined, by immunohistochemical assay, the changes in expression of the blood-type antigens on the transplanted kidneys over the long-term after ABO-incompatible kidney transplantation with A- or B-antigen incompatibility (blood type A to B and B to A). The subjects were six patients, including one case with graft loss, who had received ABO-incompatible kidney allografts more than ten years previously. As normal controls, four cases of ABO-compatible transplantation during the same period, including two recipient/donor pairs each with blood group A1 and blood group B were enrolled. Results Expression of the blood-type A or B antigens decreased gradually to 91.8% during the first three months after transplantation, 85.8% during the first five years, 64.1% during the first ten years, and 57.6% over ten years after transplantation on average in ABO-incompatible transplant recipients. In one patient with graft loss due to severe antibody-mediated rejection, the donor's type B blood-type antigens on the transplanted graft had changed but partially to the recipient's blood-type A antigen by 2582 days after the transplantation, suggestive of the occurrence of blood-type chimerism on the endothelium. In ABO-compatible transplant recipients, such changes in expression were not observed. The average percentage of blood-type antigen-positive vessels at more than ten years after the renal transplantation was 99.8%. Conclusions Decrease in the expression of the donor's blood-type antigen on the endothelium of the graft has been considered as one of the mechanisms underlying the accommodation occurring over the long-term after ABO-incompatible kidney transplantation. On the other hand, establishment of antigenic chimerism on the graft endothelium could be one of the hallmarks of the immunological reaction associated with antibody-mediated rejection.

Japan A 56-yr-old Japanese male with a history of diabetic nephropathy underwent a HLA 5/6 mismatch and ABO-compatible living-related kidney transplantation (donor: his 49-yr-old wife). A pre-transplant standard NIH complement-dependent cytotoxicity cross-match (Xm) test, a flow-cytometric T-cell Xm, and a FlowPRA test were totally negative. Inductionimmunosuppressive protocol consisted of tacrolimus, mycophenolate mofetil, methylprednisolone, and basiliximab (BAS). The patient's post-operative course was almost uneventful, and the graft was functioning well (sCr 1.1 mg/dL). He developed general fatigue, and his sCr was elevated to 2.2 mg/dL 792 d after transplant. A graft biopsy showed acute T-cell mediated rejection Banff grade IB (i3, t3, g0, v0, ptc0, C4d staining negative). The conventional anti-rejection therapy could not improve his graft function; therefore, we added BAS to eliminate activated graft-infiltrating T-cells. He responded to the rescue therapy, and the improvement in graft function was confirmed by a subsequent graft biopsy. He enjoyed his health without any opportunistic infections.