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OBJECTIVES Rituximab treatment strategies vary in ABOincompatible pediatric kidney transplant recipients. Here, we present the efficacy of 2 doses of rituximab and subsequent outcomes in ABO-incompatible pediatric kidney transplant patients. MATERIALS AND METHODS Our study of ABO-incompatible pediatric kidney transplant recipients included 21 who were pretreated with desensitization that included 2 doses of 100 mg rituximab (rituximab group) at 10 and 1 day pretransplant and 14 who received splenectomy without rituximab (splenectomy group). Both groups received immunosuppression. Basiliximab was administered during transplant and 4 days posttransplant. Double-filtration plasmapheresis and/or plasma exchange procedures were performed pretransplant in those with higher antidonor antibody titers. CD19-positive and CD20-positive B cells were measured sequentially in the rituximab group. Maximum titers of antidonor antibody pre- and posttransplant, patient and graft survival, biopsy-proven rejection, and complications/infections were compared between groups. RESULTS In the rituximab group, CD19- and CD20-positive B cells were depleted on transplant, persistently depleted at 3 months, and under 5% until 1 year posttransplant. Maximum titers of antidonor antibodies decreased significantly posttranplant in the rituximab (P < .001) but not in the splenectomy group (P = .174), with maximum titers posttransplant significantly lower than shown in the splenectomy group (P < .001). No rituximab patients had clinical rejection, but 5 splenectomy group patients had clinical T-cell-mediated rejection, with 2 also having antibody-mediated rejection. Six in the rituximab group had cytomegalovirus viremia but no cytomegalovirus disease; however, 5 splenectomy group recipients had cytomegalovirus disease and viremia. In the rituximab group, 3 had late-onset neutropenia. One child died of hypertrophic cardio myopathy with a functioning graft; all others survived with no failed grafts. All splenectomy group children survived, although 2 had deteriorated graft function. CONCLUSIONS Two doses of rituximab were effective in long-term B-cell depletion to suppress antidonor antibodies. The possibility of late-onset neutropenia must be considered.

Extensive data have been accumulated for adults who have undergone ABO-incompatible (ABOi)-living kidney transplantation (LKT). In contrast, available published data on pediatric recipients who underwent ABOi-LKT from the early to middle 2000s is very limited. Thus, pediatric ABOi-LKT has remained relatively rare, and there is a lack of large, multicenter data.We analyzed data from the Japanese Kidney Transplant Registry to clarify the patient and graft outcomes of pediatric recipients who underwent ABOi-LKT from 2002 to 2015. A total of 102 ABOi and 788 ABO-compatible (ABOc) recipients were identified in this study. All recipients had received basiliximab and a triple immunosuppressive protocol comprising calcineurin inhibitors, mycophenolate mofetil, and steroids. The ABOi recipients also received preconditioning therapies including B-cell depletion by a splenectomy or rituximab treatment and therapeutic apheresis.Death rates for ABOi and ABOc recipients were 0.17 versus 0.17 deaths per 100 patient-years. Graft loss rates for ABOi and ABOc recipients were 1.58 versus 1.45 events per 100 patient-years. No particular causes of death or graft loss predominantly affected ABOi or ABOc recipients.The results of this registry analysis suggest that pediatric ABOi-LKT can be performed efficiently. Although further studies are clearly required to perform pediatric ABOi-LKT more safely and less invasively, ABOi-LKT is now an acceptable treatment for pediatric patients with end-stage renal disease.

Background We investigated whether serum uric acid (SUA) levels before kidney transplantation predict new-onset diabetes after kidney transplantation (NODAT) and compared SUA levels with known risk factors for NODAT by prospective cohort study. Methods A total of 151 adult kidney recipients without diabetes (84 men, 67 women) who underwent living-donor kidney transplantation between 2001 and 2011 were followed in this study. The Cox proportional hazards model was used to analyse the risk of NODAT. Results During the follow-up period (median 3.3 years, range 0–10 years), 32 (21.2%) adult kidney recipients without diabetes developed NODAT, and an incidence rate was 5.6 per 100 person-years and a 10-year cumulative incidence of 26.9%. When subjects were stratified by SUA levels into tertiles, the patients in the highest tertile (> 8.6 mg/dl for men, > 7.7 mg/dl for women) had a significantly higher risk of NODAT than the patients in the lower 2 tertiles (log-rank test, P = 0.03). In the univariate analysis, increased level of SUA was associated with NODAT (hazard ratio 1.27 [95% CI 1.04–1.55], P = 0.01). In the multivariate analysis, increased level of SUA was significantly associated with NODAT after correction by any factors, e.g. (age, sex, family history of diabetes, BMI, HbA1c, serum creatinine, tacrolimus, HCV) factors directly affecting the SUA value (1.26 [1.02–1.56], P = 0.03), risk factors for T2DM onset (1.34 [1.10–1.64], P = 0.03), and factors previously reported risk factors for NODAT (1.36 [1.11–1.66], P = 0.003). Conclusion SUA independently predicts NODAT in living-donor kidney transplantation patients.

A shortage of donors poses a serious problem for organ transplantation around the world. In response, the concept of the expanded criteria donor (ECD) has been defined to include donors with traditionally less favorable characteristics. That definition has now been accepted and is being applied in kidney transplantation in the United States and Europe. However, the ECD has not yet been defined for deceased donor kidney transplantation in Japan.We analyzed data on graft survival and relevant risk factors in patients who received deceased donor kidney transplants through the East Japan Branch of the Japan Organ Transplant network (n = 1051). Recipients were divided into two groups: the standard-function group (estimated glomerular filtration rate [eGFR] ≥20 mL/min/1.73 mThe 10-year survival rate was significantly lower in the poor-function group than in the standard-function group (85.5% vs 22.5%; P .0001). The two groups differed significantly in recipient and donor risk for graft failure. Recipient risk factors were length of time on dialysis before renal transplantation and incidence of acute rejection after transplantation. Donor risk factors were donor category (heart death), age, history of hypertension, presence of cerebrovascular disease, mean urine output, and donor creatinine level immediately before donor nephrectomy, total ischemic time, and warm ischemic time.Data from deceased donor transplantation should be analyzed in depth to determine which factors influence renal function after transplantation. In addition, ECD standards should be reconsidered for use in a Japanese context.

Objectives We investigated outcomes in living-donor kidney transplant recipients with preformed donor-specific antibodies (detected with flow cytometry and specified with the LABScreen single antigen test) under desensitization pretransplant and immunosuppression posttransplant. Materials and methods Of 15 recipients included, 8 had ABO-incompatible kidney transplant. Six patients had sensitization caused by pregnancy, 8 by blood transfusion, 5 by previous transplants, and 1 by unknown cause. Desensitization was initiated using calcineurin inhibitors, methylprednisolone, and mycophenolate mofetil 30 days pretransplant, with rituximab administered 1 and 10 days pretransplant. Patients underwent plasmapheresis 1, 3, and 5 days pretransplant. Antithymocyte globulin was admi nistered for 5 days posttransplant as induction therapy. At 3 and 12 months posttransplant, all recipients underwent protocol renal allograft biopsies, with donor-specific antibodies simultaneously measured with the single antigen test. Results T-cell complement-dependent cytotoxicity crossmatch was negative in all 15 recipients, but T-cell and B-cell flow cytometry was positive in 8 and 14 recipients, respectively. Anti-HLA class I antibodies became negative, except in 1 recipient 3 months posttransplant. Class II antibodies remained positive in 8 recipients 3 months posttransplant. No clinical or subclinical T-cell-mediated rejection occurred, but 1 recipient experienced clinical acute antibody-mediated rejection. At 3 and 12 months posttransplant, 8 and 5 recipients had subclinical acute antibody-mediated rejection. Cytomegalovirus test showed positivity in 14 recipients, but none developed cytomegalovirus disease. BK viremia was detected in 2 recipients, with 1 developing BK virus nephropathy, which was reversed by reducing immunosuppression. Conclusions Transplant patients with preformed donor-specific antibodies showed good outcomes in terms of desensitization and immunosuppression. However, most anti-HLA class II donor-specific antibodies remained, and microvascular inflammation score could indicate long-term risk of renal allograft dysfunction.

Deceased organ donations are rare in Japan, with most kidney transplants performed from a limited number of living donors. Researchers have thus developed highly successful ABO-incompatible transplantation procedures, emphasizing preoperative desensitization and postoperative immunosuppression. A recent open-label, single-arm, multicenter clinical study prospectively examined the efficacy and safety of rituximab/mycophenolate mofetil desensitization in ABO-incompatible kidney transplantation without splenectomy. Mycophenolate mofetil and low dose steroid were started 28 days pretransplant, followed by two doses of rituximab 375 mg/m2 at day −14 and day −1, and postoperative immunosuppression with tacrolimus or ciclosporin and basiliximab. The primary endpoint was the non-occurrence rate of acute antibody-mediated rejection. Patient survival and graft survival were monitored for 1 year posttransplant. Eighteen patients received rituximab and underwent ABO-incompatible kidney transplantation. CD19-positive peripheral B cell count decreased rapidly after the first rituximab infusion and recovered gradually after week 36. The desensitization protocol was tolerable, and most rituximab-related infusion reactions were mild. No anti-A/B antibody-mediated rejection occurred with this series. One patient developed anti-HLA antibody-mediated rejection (Banff 07 type II) on day 2, which was successfully managed. Patient and graft survival were both 100 % after 1 year. Our desensitization protocol was confirmed to be clinically effective and with acceptable toxicities for ABO-I-KTx (University Hospital Medical Information Network Registration Number: UMIN000006635).

In Japan, there are very few cases of organ donation, including kidneys. The number of deceased donor kidney transplants (DDKTs) is much less than that of other developed Asian and Western countries, although donation after brain death is increasing slowly. Living donor kidney transplants (LDKTs) are more popular than DDKTs in Japan. However, the number of LDKTs per million population was still less than that in Korea, the UK, and the USA. Living donor ABO-incompatible kidney transplants have been performed in Japan since 1989, and long-term outcomes proved similar to those for ABO-compatible kidney transplants. Preemptive kidney transplants comprised 30% of LDKTs. In spite of the small number of kidney transplants, patient, and graft survival rates in Japan are superior to those of any other country. The infusion of regulatory T cells may induce immunotolerance in kidney transplants although acute rejection frequently occurred when immunosuppression was withdrawn and anti-donor-specific antibodies (DSAs) production could not always be suppressed. Combined kidney and bone marrow transplantation may induce immunotolerance, although a few recipients produced DSA. Kidney regeneration has become a reality. Nephron progenitor cells have been generated from human-induced pluripotent stem cells, readily reconstituting three-dimensional nephrons, including vascularized glomeruli with podocytes. The niche method has been used to generate kidney, urinary tract, and bladder tissue. Many Japanese scientists are researching kidney regeneration, and a kidney regenerated from a recipient’s cells could be transplanted without immunosuppression in the near future.

Background Pre-emptive kidney transplantation (PEKT) is beneficial for patients, improves graft survival and minimizes the complications associated with chronic kidney disease. Reports on pediatric PEKT, however, are limited, and little is known about the parathyroid hormone (PTH) abnormalities and calcium-phosphorus disorders (CPD) in this condition. This study was the first to report on mineral disorders in pediatric PEKT patients during a 1 year period. Methods We conducted a comparative examination of the abnormalities in calcium, phosphorus, calcium-phosphorus products and PTH before and 1 year after living donor kidney transplantation in PEKT and non-PEKT patients. Results Thirty-one patients were included. The patients were divided into two groups: PEKT (n = 11; 5 months in CKD stage 4-5) and non-PEKT (n = 20; 31.5 months in dialysis). Mean age at transplantation was 9.4 ± 5.0 years. Hypercalcemia and hyperphosphatemia were observed before and after transplantation in the PEKT and non-PEKT groups, and >15% of patients in each group had bone disorder and ectopic calcification associated with mineral disorder. Mineral disorder was present for approximately 3 months after transplantation in both treatment groups. Conclusions No significant differences in PTH or CPD were noted between PEKT and non-PEKT groups; moreover, normalization of abnormal values did not differ between the PEKT and non-PEKT groups. Compared with non-PEKT, PEKT did not improve the course of mineral metabolism disorders. Mineral and bone disorder treatment was likely insufficiently provided to pediatric PEKT patients. To obtain the maximum advantage of PEKT, calcium and phosphorus levels should be strictly controlled before kidney transplantation.

Post-transplant recurrent nephritis is the third common complication that leads to graft loss, which affects the long-term graft survival of kidney transplant patients. Immunoglobulin A nephropathy (IgAN) is the most common for recurrent nephritis, with a recurrence rate of 13–53%. In this study, 12 patients diagnosed with recurrent IgAN were divided into two groups, one which underwent tonsillectomy and another which did not, to analyze the effect of treating IgAN recurrent with or without tonsillectomy. Urinary findings, estimated GFR (eGFR), and histopathological alteration (Banff and Oxford classifications) were examined for >5 years after kidney transplantation. We found that tonsillectomy protected graft function and prevented pathological alterations. The levels of urinary proteins increased in the no tonsillectomy group, whereas no difference was observed in the severity of hematuria between two groups. eGFR declined and mesangial hypercellularity score increased in the no tonsillectomy group. Tonsillectomy not only results in a favorable clinical outcome but also protects against the histological damage caused by recurrent IgAN after kidney transplantation.

The Japanese ABO-Incompatible Transplantation Committee officially collected and analyzed data on pediatric ABO-incompatible living-donor kidney transplantation in July 2012. The age of a child was defined as

Background Recurrence of focal segmental glomerulosclerosis (FSGS) in pediatric kidney allografts is associated with poor graft survival. Several therapeutic regimens have been proposed, with conflicting results. Methods Ten pediatric patients with recurrent FSGS after kidney transplantation were treated with a protocol of methylprednisolone (MP) infusions in combination with cyclosporine (CsA)-based immunosuppression. The patients received a drug regimen with infusions of 20 mg/kg MP on three consecutive days at week 1, week 3, and week 5, and then monthly until six months after transplantation. If a complete or partial remission (PR) was obtained, MP pulse continued every three months until 24 months after transplantation. The CsA dose was adjusted according to AUC0–4. Results Seven of 10 patients (70%) achieved complete remission (CR) with stable renal function within 18 months of beginning of treatment. One of two patients with PR entered CR 3.5 yr after transplantation. One patient lost her graft due to recurrence four months after transplantation. After observation for 26–119 months, seven patients maintained remission with normal glomerular filtration rate. Few major side effects were observed in association with the high-dose MP infusion therapy. Conclusions MP infusion therapy in combination with CsA-based immunosuppression could be safe and effective in treating recurrent FSGS after kidney transplantation.

A girl aged 11 years and 3 months with occlusion of the inferior vena cava had experienced two renal transplant graft failures since birth. The third renal transplant from a live donor was carried out. Preoperative evaluation showed that the arteries from the right common to the right external iliac artery were absent, and the ilio-caval vein was occluded below the level of the renal vein. The donor's renal artery was anastomosed to the aorta. The donor's ovarian and large saphenous veins were used to extend the transplant renal vein to the recipient's patent inferior vena cava. The present report concludes that the extension of a short donor renal vein using other donor veins is a viable therapeutic option for pediatric patients with vascular occlusions.

国内小児腎移植におけるミコフェノール酸モフェチル (MMF) の有効性・安全性，薬物動態を評価するために，多施設共同オープンラベル臨床試験を行った。 小児腎移植患者25例に，多剤免疫抑制薬併用下にMMF (600∼1,200mg/m2/日 分2経口投与) を1年間投与し，経過観察した。評価項目は，腎移植後6か月の拒絶反応発現割合，腎移植後1年の生着割合および生存割合，有害事象発現頻度とした。AUC0-12，Cmax，Tmaxなどの薬物動態態パラメータを算出した。 腎移植後6か月の拒絶反応発現割合は24%，腎移植後1年の生着割合は100%であった。有害事象発現頻度は68%であった。MMF投与後3か月時平均AUC0-12は，48.7±27.6μg hr/mLであった。推定AUC0-12の経時的推移は，米国小児腎移植患者と同様であった。 本試験には試験デザインと登録症例数が少ないという制限があるものの，国内小児腎移植患者における，MMFの拒絶反応抑制効果と安全性が示唆された。また国内小児腎移植患者は，国内成人患者，米国小児患者と同様の薬物動態を示すことが認められた。

We discuss a renal transplant patient with focal segmental glomerulosclerosis (FSGS) treated with plasma exchange and rituximab. A 45-yr-old woman underwent cadaveric renal transplantation in May 2008. She had started hemodialysis support in 1991. Immediately after transplantation, massive proteinuria (1-5 g/d) appeared. Graft biopsy at one h showed minor glomerular abnormalities with partial foot process effacement on electric microscopy. Protocol biopsy at three months after transplantation for persistent proteinuria showed obvious FSGS under light microscopy. Plasma exchange and rituximab administration were subsequently initiated in August 2008, and proteinuria disappeared within a month after starting these treatments. Protocol graft biopsy one yr after transplantation (2009) showed increased global sclerosis and a decrease in segmental sclerosis. In addition, foot process effacement had recovered by one yr after transplantation. Plasma exchange and subsequent rituximab administration led to clinical remission of post-transplant FSGS with improvement in podocyte structure. Rituximab should be considered soon after several sessions of plasmapheresis in transplant patients with recurrent FSGS.

We discuss a renal transplant patient with recurrent IgA nephropathy (IgAN) before and after tonsillectomy. A 36-year-old man started on hemodialysis support in 1996 due to biopsy-proven IgAN, living related renal transplantation was then performed in 1997. Six years after transplantation, the patient presented with microhematuria and proteinuria. Graft biopsy for these urinary abnormalities showed recurrent IgAN. Tonsillectomy was subsequently performed in December 2003, proteinuria remitted 6 months after the tonsillectomy and microhematuria disappeared three years later. Protocol graft biopsy was subsequently performed twice, at 2 yr after the tonsillectomy (2005) and 4 yr after (2008). Comparing the findings of the pre-tonsillectomy biopsy and the two post-tonsillectomy biopsies, an increase in mesangial cells and matrix in 2005, and an expansion of the mesangial matrix and proliferation of mesangial interposition in 2008. In addition, global sclerosis of glomeruli increased over time, the area of tubulointerstitial damage has extended as well. While the tonsillectomy led to clinical remission of recurrent IgAN, the chronicity progressed on these protocol biopsies. This is the first report of the efficacy and the limitations of tonsillectomy in a case of recurrent IgAN in a transplant patient.

Purpose: The aim of this study is to investigate the mechanism of long-term acceptance of ABO-incompatible renal allograft. Methods: Thirty-four ABO-incompatible kidney transplant recipients with blood group O were entered in this study. Eighteen and 16 recipients received a blood group B (B-to-O) and A1 (A1-to-O) allograft, respectively. Sixteen (O-to-O) recipients were control subjects. The titers of blood group antibodies were measured before pre-conditioning and following transplantation. Blood group antigens were stained in 32 graft biopsy specimen. Results: In 18 (B-to-O) and 16 (A1-to-O) recipients, only anti-B and anti-A1 antibodies, respectively, were significantly suppressed compared with those in 16 (O-to-O) more than 1 year post-transplantation. In eight (B-to-O) and seven (A1-to-O) recipients, only anti-B and anti-A1 antibodies, respectively, were significantly suppressed 1 year post-transplantation, compared with those pre-conditioning. Blood group antigens were stained with same intensity and pattern in any biopsy specimen under all conditions. There was no significant deposition of IgG and IgM in any biopsy specimen. These suggested that production of anti-donor blood group antibodies appeared to be specifically suppressed in long-term stable ABO-incompatible kidney transplant recipients. Conclusion: Accommodation of ABO-incompatible kidney transplantation could be explained by donor-specific blood group antibody suppression.

We reviewed the transplantation data and results of histopathological studies with additional angiotensin II (AII) immunostaining of renal graft biopsies of nine cases (10 grafts) with recurrent proteinuria and three controls without recurrent proteinuria that received renal transplantation for primary focal segmental glomerulosclerosis (FSGS) between 1986 and 2002. Recurrent FSGS was confirmed in six grafts from nine cases by light microscopy. In cases with recurrent proteinuria, loss of graft function was noted in all six renal grafts received between 1986 and early 1992 but in none of four grafts received between late 1992 and 2002. Two of four patients of the late group but none of those of the early group received angiotensin converting enzyme (ACEI) or angiotensin II receptor blocker (ARB) with plasma exchange (PE). In control cases without proteinuria, AII immunostaining was detected in tubules but not in glomeruli in 1-hour biopsies as well as later on. In cases with recurrent proteinuria, AII immunostaining was detected in both tubules and glomeruli, although glomerular AII staining was not observed in 1-hour biopsies. Our results suggest that effective treatment of post-transplantation recurrent FSGS requires ACEI or ARB with PE in the absence of another etiology.

To determine the significance of early subclinical rejection of renal allografts, we reviewed 127 biopsy specimens obtained soon after transplantation. Histological finding was categorized according to a modification of the Banff scheme as: acute rejection (AR), borderline changes (BL); non-specific inflammatory changes, (NI) and no rejection (NR). Subclinical rejection was defined as AR, BL or NI. Patients with BL or NI were divided into two groups; one was treated with high-dose methylprednisolone (MP), the other remained untreated. Freedom from chronic allograft dysfunction (defined as non-doubling of serum creatinine 5 yr after transplantation) was significantly more frequent in the NR group (89%) than in the BL (70%) and AR (64%) groups. At 1 yr after transplantation, mean serum creatinine had increased significantly only in the untreated group (p

Background: Various invasive and non-invasive methods have been investigated for their prognostic value in predicting the outcome of renal allografts. In the present study, vimentin expression in tubular epithelial cells (TEC) was determined by the immunohistochemical examination of biopsy specimens and the prognostic value of this method was assessed. Methods: Ninety-two renal transplant recipients were recruited for the present study. Protocol biopsy of the renal graft was performed 1, 3 and 5 years after transplantation in each case. All biopsy specimens were treated with conventional stains and immunostained with an antivimentin antibody. The correlation between vimentin expression and glomerular filtration rate (GFR) and the association between vimentin expression and histopathological findings were determined. Results: Vimentin was localized in TEC adjacent to interstitial lesions with lymphocyte infiltration and also in TEC with tubulitis or in atrophic tubules. Vimentin positivity significantly correlated with GFR and both vimentin positivity and GFR were significantly associated with the extent of chronic allograft nephropathy, but not with acute rejection. Additionally, vimentin expression and GFR 3 and 5 years after transplantation were higher in cases where graft loss occurred between 5 and 7 years after transplantation compared with graft survival cases. Conclusions: These results suggest that immunohistochemistry using antivimentin antibodies on protocol biopsy specimens is useful for the detection of injured TEC and as a predictor of allograft outcome.

We discuss a patient with Alport syndrome who received a renal transplant from a donor with thin basement membrane disease. A 30-year-old woman, diagnosed with Alport syndrome on the basis of sensorineural hearing loss, characteristic renal biopsy findings and a family history of microhaematuria, entered chronic haemodialysis therapy. She then received a renal transplant donated from her father, who had sensorineural hearing loss and persistent microhaematuria. On the day of renal transplantation, a 1-h graft biopsy after reperfusion showed thin basement membrane disease. We re-tested the patient's native kidney biopsy specimen by immunohistochemical staining using alpha-chain-specific collagen type IV monoclonal antibodies. There was no expression of collagen type IV alpha3-, alpha4- and alpha5-chain on glomerular basement membrane, but positive staining of alpha5-chain on Bowman's capsular basement membrane was noted. A diagnosis of autosomal-recessive Alport syndrome was made. We concluded that this family might display different phenotypic expressions of the same genotype: one suffered end-stage renal disease and the other thin basement membrane disease.

6p duplication syndrome is a rare chromosomal disorder that frequently manifests renal complications, including proteinuria, hypoplastic kidney, and hydronephrosis. We report a girl with the syndrome, manifesting left hydronephrosis, proteinuria/hematuria, and focal segmental glomerular sclerosis (FSGS) resulting in chronic end-stage renal failure, successfully treated with renal transplantation. Microarray comparative genomic hybridization showed the derivative chromosome 6 to have a 6.4-Mb duplication at 6p25.3-p25.1 with 32 protein-coding genes and a 220-Kb deletion at 6p25.3 with two genes of no possible relation to the renal pathology. Review of the literature shows that variation of renal complications in the syndrome is compatible with congenital anomalies of the kidney and urinary tract (CAKUT). FSGS, observed in another patient with 6p duplication syndrome, could be a non-coincidental complication. FOXC1, located within the 6.4-Mb duplicated region at 6p25.3-p25.2, could be a candidate gene for CAKUT, but its single gene duplication effect would not be sufficient. FSGS would be a primary defect associated with duplicated gene(s) albeit no candidate could be proposed, or might occur in association with CAKUT.

Microchimerism in 23 female renal transplant recipients from male donors was studied using nested polymerase chain reaction (nPCR) and fluorescence in situ hybridization (FISH) to detect Y-chromosome. nPCR was a sensitive and specific assay enabling a detection rate of 1/10(6) male/female cells, compared with a sensitivity of 1/10(2) by standard PCR (sPCR). None of the 23 patients with a male allograft demonstrated Y-chromosome using sPCR. In contrast, 1 3 (56.5%) patients demonstrated Y-chromosome with nPCR. Of 9 patients proven to have microchimerism by nPCR, only 3 also demonstrated Y-chromosome using FISH. The existence of B cells and CD8 cells in donor chimeric cells were proved by separation with Dynabeads class I and class II. Dynamic changes of microchimerism occurred in 4 of 5 patients. Four patients were proven to have microchimerism within a year of transplantation and the microchimerism later disappeared in 3, although the sequential change was variable in individual patients. There was no correlation between microchimerism and patients'clinical factors such as donor-specific blood transfusion, HLA matching, immunosuppression, past history of acute rejection and chronic rejection. The degree of microchimerism in renal transplant recipients was relatively low, and its existence did not seem to be compatible with long-term graft acceptance. However, further studies are required to elucidate the immunological mechanism of microchimerism, and it might be an important clue to immunological tolerance.

Background. As of December 1997, more than 170 000 patients in Japan were receiving hemodialysis, 30% to 50% of whom were waiting for a kidney transplant. However, in contrast to the situation in the United States and Europe, kidney transplantation is uncommon, because of the small number of cadaveric kidneys that are donated. As a result, living-related kidney transplantation is performed in as many patients as possible, even in ABO-incompatible cases. Methods. We statistically analyzed the data for 167 ABO-incompatible living donor kidney transplantations that were carried out between January 1989 and December 1997. Results. The overall patient survival rates at 1, 3, 5, and 7 years after transplantation were 90.2%, 90.2%, 88.0%, and 84.8%, respectively, with respective overall graft survival rates of 79.6%, 76.1%, 66.3%, and 56.5%. Conclusions. ABO-incompatible living kidney transplantation is an effective radical treatment for endstage renal disease (ESRD).

Monitoring of cyclosporine A in 40 whole blood samples from renal transplantation patients by high performance liquid chromatography with aryl oxalate-sulforhodamine 101 chemiluminescence detection is described. These data were compared with fluorescence polarized immunoassay (Cyclosporine-SP DynapackTM using monoclonal antibody for whole blood), with good results (r = 0.88, y = 0.80 + 5.07). These values are the same as reported by high performance liquid chromatography with photometric detection. By using a solid phase extraction cartridge, cyclosporine A was analyzed within 30 min. The analysis time could be shortened to one tenth that previously reported. The proposed method has the same sensitivity as fluorescence polarized immunoassay.

We examined psychiatric problems before and after kidney transplantation in a sample of 36 patients with end-stage renal failure. The prevalence rate of psychiatric disorders was 11.1% (4 of 36 cases) before the transplantation and 36.1% (13 of 36 cases) within 2 months after the transplantation. Except for a patient with schizophrenic disorder, no patients were found to have a psychiatric disorder from 2 to 6 months after the transplantation. In this study, we also examined anxieties and/or conflicts related to the transplantation using the synthetic house-tree-person (HTP) drawing test, a measure of mood states by means of a non-verbal expression method. The upper part of the tree trunk was not drawn in 25% of this sample (5 of 20 cases). In the HTP drawing tests immediately after the transplantation, however, trees missing the upper part of trunk were not drawn. Based on these findings, we discussed psychiatric problems in kidney transplantation.

The authors examined the case of an adolescent patient with dissociative identity disorder secondary to psychological shock of a transplant rejection response. Psychiatric symptoms consisted of three components: visual hallucinations and delusions as a psychological defense against the anxiety of a transplant rejection; appearance of three personalities including proper self, the dead child (donor), and a prophet with strong predicting power; and a twilight state. These psychiatric symptoms may have been related to two psychological factors: immature personality characteristics formed during hemodialysis, and post-traumatic stress caused by a chronic rejection reaction from the patient's first transplant.

ABO incompatible kidney transplantation (ABOi-KT) was previously considered to be an absolute contraindication for patients with end-stage kidney disease (ESKD) due to hyperacute rejection related to blood type barrier. Since the first successful series of ABOi-KT was reported, ABOi-KT is performed increasingly all over the world. ABOi-KT has led to an expanded donor pool and reduced the number of patients with ESKD awaiting deceased kidney transplantation (KT). Intensified immunosuppression and immunological understanding has helped to shape current desensitization protocols. Consequently, in recent years, ABOi-KT outcome is comparable to ABO compatible KT (ABOc-KT). However, many questions still remain unanswered. In ABOi-KT, there is an additional residual immunological risk that may lead to allograft damage, despite using current diverse but usually intensified immunosuppressive protocols at the expense of increasing risk of infection and possibly malignancy. Notably, in ABOi-KT, desensitization and antibody reduction therapies have increased the cost of KT. Reassuringly, there has been an evolution in ABOi-KT leading to a simplification of protocols over the last decade. This review provides an overview of the history, outcome, protocol, advantages and disadvantages in ABOi-KT, and focuses on whether ABOi-KT should be recommended as a therapeutic option of KT in the future.

Introduction Multiorgan procurement is not an easy procedure and requires special technique and training. Since sufficient donors are not available for on-site training in Japan, establishment of the educational program for multiorgan procurement is mandatory. Materials and methods Development of e-learning and simulation using pigs are our main goals. E-learning contains three dimensional computer graphic (3DCG) animations of the multiorgan procurement, explanation of both donor criteria and procurement procedure, and self-assessment examination. To clarify the donor criteria, the risk factors to 3-month survival of the recipients were analyzed in 138 adult cases of liver transplantation. The 3DCG animation for liver procurement was developed, which was used in the lecture prior to the simulation on August 10, 2013. The results of the examination after this lecture (exam 2013) were compared with the results after the lecture without using animation in 2012 (exam 2012). The simulation was performed by 97 trainees divided into 9 teams, and the surveys were conducted. Results The risk factors for early outcome of the recipients were cold ischemia time (≥10 hours), Model for End-stage Liver Disease score (≥20), and donor age (≥55 years). Results of examination showed that overall percentage of the correct answers was significantly higher in exam 2013 than in exam 2012 (48.3% vs 32.7%; P = .0001). The survey after the simulation of multiorgan procurement revealed that most trainees thought that the simulation was useful and should be continued. Conclusion The novel educational program could allow young surgeons to make precise assessments and perform the exact procedure in the multiorgan procurement.

Two hundred and sixty-eight renal transplant operations were done in 244 children over the past 20 years. The donors were parents in 229 cases, living relatives in another 1 3 eases, and cadavers in the remaining 26 cases. There were 242 first grafts, 22 second grafts, and 4 third grafts. The initial 130 grafts were carried out with conventional immunosuppressive regimens and the subsequent 1 38 were done using immunosuppression including cyclosporin-A. In January 1995, 186 recipients (76.2%) were alive with functioning grafts, 33 (1 3.5%) were alive on dialyses, and 25 (10.2%) were dead. The management results in terms of patient and graft survival, as well as the causes of graft failure and patient death are described.

Background Children with a compromised inferior vena cava (IVC) were previously considered unsuitable for kidney transplantation because of the technical difficulties and the increased risk of graft thrombosis secondary to inadequate renal venous outflow. Methods We conducted a retrospective study of 11 transplants in 9 patients with end-stage renal disease and thrombosed IVCs who received adult kidney allografts between 2000 and 2015. The mean age at transplantation was 7.5 ± 3.5 years. A pretransplant diagnosis of the IVC thrombosis was made in 7 patients by magnetic resonance imaging and computerized tomography, whereas there were 2 instances of intraoperative discovery of the IVC thrombosis. Results In the early cases, a kidney was placed intraperitoneally at the right iliac fossa with a venous anastomosis to the patent segment of the suprarenal IVC. After 2008, however, 6 adult-sized kidneys were subsequently placed in the left orthotopic position. Venous drainage was attained to the infrahepatic IVC (n = 3), left native renal vein (n = 2), and ascending lumbar vein (n = 1). Moreover, a venous bypass was created between the graft and the splenic vein in 2 children who showed high return pressure after the vessel was declamped. The mean glomerular filtration rate of the functioning 8 grafts 1 year posttransplant was 73.4 ± 20.4 mL/min per 1.73 m2. Of note, 6 of the grafts have been functioning well, with a mean follow-up of 66 months. Both 1- and 5-year graft survival were 81.8%. Conclusions Transplantation into the left orthotopic position and the revascularization methods are an effective set of surgical techniques that could potentially be adopted as safe and reliable transplant approaches in children with IVC thrombosis.

Wilms’ tumor (WT), also called nephroblastoma, is an embryonic neoplasm of the developing kidney. A previously healthy Japanese female infant had WT in a single kidney without associated congenital malformations. Preoperative chemotherapy was started for the preservation of renal tissue and function. Tumor lysis syndrome, disseminated intravascular coagulopathy, and acute renal failure were accompanying. The infant needed surgical intervention and permanent replacement therapy. At the start of emergency hemodialysis, the infant had posterior reversible leukoencephalopathy syndrome because of severe hypertension. During ongoing peritoneal dialysis, the infant suffered from anemia, dietary and fluid restriction, and restriction of time and mobility. Despite alfacalcidol and calcium supplementation, the infant had secondary hyperparathyroidism and remarkably short stature. After waiting for the completion of chemotherapy, renal transplantation from the mother was completed. Successful kidney transplantation promptly corrected preexisting metabolic abnormalities causing secondary hyperparathyroidism. Subsequently, the infant often complained of headache. Computed tomographic scanning revealed calcification in the cerebellum. Refractory secondary hyperparathyroidism was inferred as the cause. A well-functioning graft provided the infant with a greater sense of well-being and enabled her to enjoy a lifestyle free of dialysis, although the infant must continue taking transplant medications and has retained unresolved issues of short stature and ectopic intracranial calcification.

THE CLINICAL course and pathology of acute vascular rejection (AVR) in ABO-incompatible kidney transplantation (ABOIncKTx) seems to be different from acute rejection (AR) in ABO-compatible KTx. The anti-A or B blood type antibody (Ab) may react on the blood type A or B antigen (Ag) of the renal allografts as an Ab-mediated immunologic reaction. However, the mechanism of AVR in ABOIncKTx is still unknown and there were many ABOIncKTx patients without AVR under the existence of antidonor blood type antibody. Therefore we investigated the localization of the blood type Ag in renal allografts and the sequential change of blood type Ab following pretreatment and Tx and characteristic pathologic findings of AVR in ABOIncKTx.

Background: The prognosis of Japanese patients with congenital nephrotic syndrome (CNS) and Denys-Drash syndrome (DDS) is not clear. Methods: Five patients with CNS and four patients with DDS, which causes secondary CNS, were studied retrospectively. Results: Seven patients were sporadic and two DDS patients were identical twins. Five CNS patients presented with edema within 3 months of birth. In four DDS patients, edema was not noted and end-stage renal disease developed between 7 months and 6 years of age. Of these five CNS patients, one patient had cerebral thrombosis and cytomegalovirus pneumonia at the onset and another patient died during dialysis. Frequent intravenous albumin administration required, growth and development during infancy were varied. Of the nine patients with CNS and DDS, seven received renal transplantation and were alive with functioning grafts at the last follow up. Catch-up growth was observed in five patients after transplantation. Five school-aged patients attended school and received adequate grades and two adults worked full-time. Of the DDS patients, dysuria due to hypospadias persisted in one patient and treatment for hypogonadism was needed in one patient. Conclusions: CNS and DDS were diagnosed early after onset and adequate treatment was started. Growth and development after renal transplantation were relatively good. Thrombotic episodes or severe infection in CNS patients was difficult to manage and complications resulting from DDS affected the quality of life.

The aim of this study was to investigate whether glomerular sclerosis (GS) at the time of engraftment affects subsequent morphology and clinical course of renal allografts. Eighty-one renal transplant recipients were recruited for this study. Protocol biopsies of the renal allografts were performed at engraftment, as well as at 1, 3, 5, and 7 years after transplantation. All cases were divided into 2 groups based on the presence of GS at engraftment, namely, non-GS and GS groups. Morphological changes in the renal allografts were graded from 0 to 3+ based on the severity of chronic allograft nephropathy (CAN) of the Banff classification based on 5 factors: percentage of GS, extent of interstitial fibrosis, tubular atrophy, arterial intimal thickening, and arteriolar hyalinosis. Furthermore, the level of serum creatinine (s-Cr) at each year was examined by recipient age and gender, donor age and gender, type of donor (living/cadaver), delayed graft function, acute rejection within 1 year after transplantation, mean blood pressure, and use of calcineurin inhibitors as well as the presence of GS at engraftment. The extent of GS at engraftment significantly correlated with donor age (P = .0038) but with a weak correlation coefficient. Although the severity of CAN developed gradually in both non-GS and GS groups, differences in morphological changes at engraftment between the 2 groups persisted throughout 7 years. Donor age and recipient gender influenced s-Cr significantly. In conclusion, the presence of GS at engraftment aggravates subsequent morphological changes and affects short-term but not long-term allograft prognosis.

This retrospective study was designed to compare the efficacy of cyclosporin A (CyA) and tacrolimus (FK506) on chronic rejection (CR) associated with nuclear factor-kappa B (NF-κB) activation and macrophage invasion. Non-episodic day 50 protocol renal biopsy was performed in 63 consecutive patients with renal transplants from living donors, treated with either CyA or FK506. Southwestern histochemistry for NF-κB, immunostaining for CD68, and Banff classification were performed, and these findings were compared with outcome over 34 ± 13 months. Compared with specimens from FK506-treated patients (n = 20), specimens from CyA-treated patients (n = 43) showed a significant increase in tubulointerstitial CD68-positive cells (1.5 ± 0.9 vs. 0.9 ± 0.8, p

This report describes a successful renal Tx in a patient with chronic renal failure, caused by dysplastic kidneys, who received a cadaveric kidney with post-infectious glomerulonephritis. Sequential renal biopsies were performed at 12 h before Tx, and at 1 h and on days 8 and 58 post-Tx. Post-operative hematuria disappeared on day 9 and proteinuria on day 13. Normal graft function was observed within 1 month, with histologic resolution. Our study suggests that while the donor kidney facilitates deposition of certain immune reactants, this is a host (environmental) problem and when transplanted into a new host (new environment), the problem is no longer sustained.

Protocol biopsies were performed to detect and treat sub-clinical rejection in eight living related pediatric renal transplant recipients who had been withdrawn from steroids. Low-grade tubulitis (t1) and mononuclear cell interstitial inflammation (i1), typical of borderline rejection and low-grade interstitial fibrosis (ci1), and tubular atrophy (ct1), characteristic of chronic rejection, appeared frequently in protocol biopsies more than 3 yr after steroid withdrawal. In contrast, early-type glomerulitis (g), allograft glomerulopathy (cg), arteriolar hyaline thickening (ah), intimal arteritis (v), and fibrous intimal thickening (cv) were not observed in protocol biopsies after steroid withdrawal. Low-dose pulse therapy (methylprednisolone (MP) 250 or 500 mg/d for 3 d) was administered to five patients for borderline and/or acute grade 1a rejection, as determined by protocol biopsies in the absence of clinical rejection. No oral steroids were administered. Renal function in all patients remained satisfactory, without proteinuria, in follow-up periods ranging from 22 to 68 months after steroid withdrawal. Of the eight patients, three grew to almost normal height (>mean – 2SD) and four exhibited catch-up growth. Thus, steroid withdrawal can be safe and improves growth in pediatric renal transplant recipients if undertaken with careful clinical follow-up, including protocol biopsies.