Episode Biopsy Research Articles

Nationwide Survey of Post-Transplant Glomerular Diseases, Based on the Japan Renal Biopsy Registry (J-RBR).

BackgroundNationwide data on allograft kidney biopsies have been limited in number, in contrast to the large amount of accumulated data on native kidney biopsies. In this context, we have surveyed transplant biopsy data based on the nationwide database, the Japan Renal Biopsy Registry (J-RBR).Material/MethodsA total of 2430 transplant biopsy cases were registered in the web-based J-RBR from January 2007 to January 2018. We categorized the entries regarding both the purpose of the biopsy and pathological diagnosis, and confirmed transplant glomerular diseases based on the clinical and pathological diagnosis.ResultsOf the 2430 total transplant biopsy cases, 637 cases, including 9 cases of baseline biopsy, 216 cases of protocol biopsy, and 232 cases of episode biopsy, had a pathological diagnosis, including glomerular diseases, rejection, calcineurin inhibitor nephropathy, and interstitial fibrosis and tubular atrophy. Of these, 127 cases presented with glomerular disease, including 8 cases of baseline biopsy, 23 of protocol biopsy, 59 of episode biopsy, and 37 of unknown purpose). A total of 127 biopsies with glomerular disease revealed a high prevalence of immunoglobulin A nephropathy (n=38, 29.9%), followed by mesangial proliferative glomerulonephritis (n=29, 22.8%) and focal segmental glomerulosclerosis (n=8, 6.3%) when focused on protocol and episode biopsies.ConclusionsThe nationwide transplant biopsy database demonstrated the pathological characteristics of 637 cases, including 127 cases of post-transplant glomerular disease. The protocol and episode biopsies included high prevalence rates of IgAN, followed by FSGS.

Successful Treatment of Antibody-Mediated Rejection by De Novo Donor Specific Antibody After Primary Renal Transplantation in a Recipient From a Cadaveric Donor: A Case Report

A 19-year-old Japanese male recipient, who received a living related kidney transplantation from his father at 5 years old, was hospitalized for second renal transplantation from a cadaveric donor. The recipient had had an antibody-mediated rejection (AMR) to the first transplanted kidney. HLA typing of A, B, and DRB showed 2 of 6 mismatches. Lymphocyte cytotoxicity test (LCT) and flow cytometry crossmatches (FCXM) were negative on T cells. Tacrolimus, mycophenolate mofetil, methylprednisolone, and basiliximab induction were used as the standard immunosuppressive therapy. After second renal transplantation, his serum creatinine level favorably decreased until postoperative day (POD) 7, but his serum creatinine level raised from POD 8. We performed steroid pulse and intravenous immunoglobulin (IVIG). The episode biopsy showed AMR although FCXM and LCT were still negative on T cell. To determine the cause of AMR, we examined LABScreen single antigen test (One Lambda, Canoga Park, Calif., United States), and there was a donor-specific antibody (DSA) that is DQB8 in pre- and post-second renal transplantation. The DSA was suspected de novo DSA for the first transplanted kidney. AMR was successfully treated with plasma exchange, IVIG, and rituximab.

Effect of Rabbit Antithymocyte Globulin on Acute and Chronic Active Antibody-Mediated Rejection After Kidney Transplantation

BackgroundRabbit antithymocyte globulin (rATG) induction is associated with reduction in the occurrence of de novo donor-specific antibody (DSA) and antibody-mediated rejection (AMR). Therefore, rATG administration is considered as a treatment for AMR. However, only a few studies have investigated the treatment of AMR with rATG after kidney transplantation. MethodsBetween April 2013 and March 2018, 162 consecutive de novo kidney transplantations were performed with induction immunosuppressive therapy comprising tacrolimus, mycophenolate mofetil, methylprednisolone, and basiliximab. AMR was diagnosed on the basis of the presence of DSA and episode biopsy findings. For DSA-positive recipients, plasmapheresis was performed to remove DSA before rATG administration (1.5 mg/kg for 5 days). Patients treated with rATG against active AMR were retrospectively analyzed for graft function. ResultsA total of 13 kidney transplant recipients developed active AMR within 302 days after transplantation. After rATG administration, the mean serum creatinine and urine protein levels significantly declined from 3.03 mg/dL to 1.68 mg/dL (P = .002) within 46 days and from 3.01 g/gCr to 0.54 g/gCr (P = .006) within 106 days, respectively. The peripheral blood lymphocyte count rapidly decreased after rATG administration and remained low for 12 months. With regard to adverse events, fever (84.6%), cytomegaloviremia (84.6%), thrombocytopenia (61.5%), anemia (30.8%), and neutropenia (15.4%) occurred within 3 months after rATG administration. ConclusionsrATG improved graft function by suppressing peripheral blood lymphocytes in kidney transplant recipients with active AMR. The rATG administration as a treatment for active AMR may contribute to positive graft outcomes after kidney transplantation.

Conversion to Everolimus in Kidney Transplant Recipients With Calcineurin Inhibitor-Induced Nephropathy: 3 Case Reports

BackgroundCalcineurin inhibitors (CNIs), which remain the most important immunosuppressants in kidney transplant recipients, are a major cause of renal dysfunction due to CNI-induced nephropathy. However, a safe and effective CNI-sparing protocol is yet to be established. Herein, we report a case series of kidney transplant recipients experiencing CNI nephropathy, whose renal function is improved after conversion from CNIs to everolimus. CasesThe 3 kidney transplant recipients included in this study were diagnosed with CNI arteriolopathy by episode biopsy between 9 months and 11 years after transplantation. All patients received triple immunosuppressive therapy consisting of CNI (tacrolimus or cyclosporine), mycophenolate mofetil, and methylprednisolone. All allografts were transplanted from elderly living donors to ABO-compatible and donor-specific antibody-negative recipients. All allograft biopsy specimens exhibited CNI arteriolopathy with alternative quantitative criteria for hyaline arteriolar thickening (aah score: 2 or 3), according to the Banff classification; however, histopathologic assessment did not show any evidence of allograft rejection. Conversely, total dose and blood concentrations of CNIs were within appropriate ranges. After conversion from CNIs to everolimus (1.5 mg/day, twice daily; trough level, 3–5 ng/mL), serum creatinine levels returned to baseline levels measured before the diagnosis of CNI arteriolopathy. In all patients, renal allograft function remained stable, with no evidence of donor-specific antibodies, 1 year after conversion from CNIs to everolimus. ConclusionConversion from CNIs to everolimus can safely and effectively improve renal function in kidney transplant recipients experiencing CNI-induced nephropathy.

Thrombotic microangiopathy associated with anticardiolipin antibody in a kidney transplant recipient with polycythemia

Thrombotic microangiopathy (TMA) develops from various etiologies, and it is often difficult to distinguish the etiology of TMA in kidney transplantation. Antiphospholipid syndrome (APS) is one of the differential diagnoses for TMA that may cause acute loss of graft function or fatal thrombotic complications. This report details a 66-year-old male patient with polycythemia after ABO-incompatible kidney transplantation. Antibody screening tests were negative before transplant. Despite administration of an adequate desensitization therapy including plasmapheresis and rituximab, he developed acute graft dysfunction on postoperative day 112 and graft biopsy revealed prominent microvascular inflammation in the glomerular capillaries without immunoglobulin deposits. Flow cytometric panel-reactive antibody screening failed to detect donor-specific antibodies at both pre-transplant and episode biopsies. Anticardiolipin antibody was repeatedly positive, but neither thrombosis nor previous thrombotic episodes were detected. After excluding several differential diagnoses, the graft dysfunction with unexplained TMA was treated with steroid pulse, plasmapheresis and rituximab re-induction. Anticardiolipin antibody disappeared after this intensive treatment and graft function recovered gradually and stabilized for 52months. This report suggests that asymptomatic anticardiolipin antibody may be associated with acute graft dysfunction. Even if thrombotic episodes are not observed, an exist of anticardiolipin antibody may be one of the risk factors of renal TMA after kidney transplantation.

Protocol graft biopsy in kidney transplantation

Accurate interpretation of renal allograft biopsy is necessary to guide therapy, especially when an episode biopsy is taken to rescue the graft. Contrarily, a protocol biopsy is carried out routinely to identify baseline conditions (biopsy at 0 or 1 h), subclinical rejection, histological change under current immunosuppression regimen, drug nephrotoxicity, viral infection, and recurrence of glomerulonephritis. Semiquantitative scoring for active lesions including tubulitis, glomerulitis, capillaritis, arteritis, arteriopathy, and others such as polyomavirus infection are key factors in transplant pathology. Recently, the Banff classification has proposed several novel concepts focused on antibody-mediated rejection (ABMR). This review presents the interpretation of transplant pathology from rejection to infection, recurrence of glomerulonephritis, and drug nephrotoxicity, with a description of ABMR according to the 2013 and 2017 Banff classification.

Recurrence of native kidney disease after kidney transplantation.

The extent of recurrence of original kidney disease after kidney transplantation has been underestimated for several reasons. First, the duration of observation varies among studies. Second, the criteria used to schedule protocol and episode biopsies differ among institutions. And third, diagnostic modalities used for early detection of recurrent original kidney disease also vary. Thus, rates of graft loss attributable to a recurrence of original kidney disease vary among institutions and are often underestimated. However, the recurrence of original disease is often thought to be less important than chronic rejection followed by loss of a functioning allograft. It is important to note that recent data have shown that in patients with certain limited primary kidney diseases (e.g., membranous proliferative glomerulonephritis [MPGN], IgA nephritis [IgAN], focal segmental glomerulonephritis [FSGS], and membranous nephropathy [MN]), the predominant (60%) cause of graft loss is the recurrence of original kidney disease. In addition, the rate of 5-year graft survival in patients with recurrent original kidney disease averages 45%. Thus, research must address the recurrence of original kidney disease. Here we focus on this recurrence and discuss diagnoses, preventive strategies, treatments, and future research directions.

Successful treatment of recurrent immunoglobulin a nephropathy using steroid pulse therapy plus tonsillectomy 10\xa0years after kidney transplantation: a case presentation

BackgroundBoth prevention and treatment of recurrent immunoglobulin A nephropathy (IgAN) in kidney transplant recipients are important since recurrent IgAN seems to affect long-term graft survival. We present here a case of recurrent IgAN that was successfully treated using steroid pulse therapy plus tonsillectomy 10 years after kidney transplantation.Case presentationA 46-year-old male was admitted for an episode biopsy with a serum creatinine level of 1.8 mg/dl and proteinuria (0.7 g/day). Histological features showed recurrent IgAN (only focal segmental mesangial proliferation) and severe arteriolar hyalinosis partly associated with calcineurin inhibitor toxicity, with limited interstitial fibrosis and tubular atrophy (5%) (IF/TA) 8 years after transplantation. Sodium restriction and conversion from cyclosporine to tacrolimus successfully reduced his proteinuria to the level of 0.15 g/day. However, 2 years later, his proteinuria increased again (1.0 g/day) and a second episode biopsy showed global mesangial proliferation with glomerular endocapillary and extracapillary proliferation accompanied by progressive IF/TA (20%). The steroid pulse therapy plus tonsillectomy successfully decreased his proteinuria and he achieved clinical remission 3 years after this treatment.ConclusionThis case, presented with a review of relevant literature, demonstrates the difficulty and importance of the treatment of recurrent IgAN and calcineurin inhibitor arteriolopathy, especially in long-term kidney allograft management.

A case report of recurrent C3 glomerulonephritis 18 months after renal transplantation

The recurrence of glomerulonephritis (GN) is critical to the prognosis of long-term renal transplant graft survival. C3 GN is a rare GN with a poor prognosis, and there are only a few reports of recurrent cases after renal transplantation. We recently experienced a case highly suspected of C3 GN recurrence. The patient was a 67-year-old male who had suffered from end-stage renal disease (ESRD) and started dialysis at the age of 60. His primary renal disease was unknown. At the age of 63, renal transplantation was successfully performed. His serum creatinine (Cr) level was maintained at 1.2 to 1.5 mg/dl, with no urinary protein or occult blood until 18 months after the transplant when urinary occult blood and protein became constant, along with an elevated Cr level at 1.5 to 1.6 mg/dl. The tentative diagnosis following a protocol biopsy at 36 months was dense-deposit disease. However, the pathological findings of an episode biopsy performed 1 year later, when his Cr level elevated to 2.0 mg/dl after varicella zoster virus reactivation, revealed no acute rejection but were compatible with C3 GN. These findings are consistent with a previous report on recurrent C3 GN that revealed relatively rapid loss of graft function, contrasting well with slow progression occurring in the native kidney. This case is possibly the first report in Japan of recurrent C3 GN after renal transplantation.

Plasma Cell–Rich Rejection After Kidney Transplantation and the Role of Donor-Specific Antibodies: A Case Report and Review of the Literature

ObjectiveWe report a case of the clinical course and pathologic findings for a kidney transplant recipient with plasma cell–rich rejection (PCRR) accompanied by antibody-mediated rejection (ABMR). MethodsA 29-year-old man with end-stage renal disease caused by lupus nephritis received an ABO-compatible living kidney transplant. ResultsEighteen months after transplantation, the patient presented with proteinuria and increased serum creatinine. An episode biopsy revealed severe tubulointerstitial infiltration with plasma cells accompanied by peritubular capillaritis and positive findings on immunofluorescent C4d staining. Donor-specific antibodies were positive for DR52, and the patient was subsequently diagnosed with PCRR accompanied by ABMR. Treatment was initiated with high-dose steroids, intravenous immunoglobulin, gusperimus hydrochloride, muronmonab antibody CD3, and rituximab. However, ABMR persisted and allograft failure developed 20 months after onset. ConclusionsWe argue that PCRR accompanied by ABMR is a subtype of PCRR that can progress to allograft failure owing to persistent ABMR.

Association Between Post-transplantation Immunoglobulin A Deposition and Reduced Allograft Function

BackgroundPost-transplantation de novo and recurrent immunoglobulin A (IgA) deposition (IgAD) in the allograft is commonly observed. However, the association between post-transplantation IgAD and reduced allograft function has not been determined. We therefore investigated the association between reduced allograft function and post-transplantation IgAD using serial allograft biopsies. MethodsIgAD was retrospectively analyzed in 45 adults who underwent kidney transplantation for chronic glomerulonephritis, including IgA nephropathy, at Kagawa University Hospital. Allograft biopsy samples were obtained from per protocol biopsies obtained 1 and 3 years after transplantation, as well as from episode biopsies. Factors contributing to post-transplantation IgAD were assessed by calculating adjusted odds ratios (AORs) using logistic regression analysis. ResultsOf the 45 recipients, 18 had post-transplantation allograft IgAD. The estimated glomerular filtration rates (eGFR) 1, 2, and 3 years after transplantation were lower in the recipients with than without IgAD. Urinalysis was normal in 61% of recipients with IgAD. Reduced allograft function (eGFR <40 mL/min/1.73 m2) 1 year after transplantation was significantly associated with post-transplantation IgAD (AOR = 34.4 [95% CI = 2.35–502], P = .01). Conversely, blood concentrations of mycophenolic acid and latent IgAD from donor kidneys were not significantly associated with post-transplantation IgAD. ConclusionReduced allograft function may be associated with post-transplantation IgAD in the allograft.

Tonsillectomy and IgA Nephropathy Recurrence After Kidney Transplantation.

[Background and purpose] The pathophysiology of IgA nephropathy (IgAN) remains poorly understood, although it frequently recurs after kidney transplantation, and its recurrence has been reported to depend on some factors. We studied a retrospective single-center analysis of renal transplant recipients with IgAN as the cause of end-stage renal failure to examine factors that may affect IgAN recurrence after kidney transplantation and the preventative and therapeutic effects of tonsillectomy on IgAN recurrence. [Material and method] From January 1987 to December 2012, 126 kidney transplantations were performed at Ryuku University Hospital, among which 14 cases (10 men; and 4 women) were identified with IgAN as their primary disease. Their mean age at transplantation was 38.1 ± 8.4 years.Donor types were as follows: 2 cadaveric, and 12 living (10 related; 2 unrelated). Tonsillectomy was performed for 8 cases; 2 were for therapeutic purposes for IgAN recurrence, and 6 were to prevent IgAN recurrence. IgAN recurrence diagnosis was based on light microscopic findings showing mesangioproliferative changes and mesangial IgA deposition on the basis of immunofluorescence analysis. [Result] Among the 14 patients, 2 cases were identified as IgAN recurrence based on episode biopsies. Both the recurrent cases had living related kidney donors. One patient with recurrent transplant IgAN progressed to graft failure 2.0 years after tonsillectomy, whereas the other subsequently retained renal function for 7.0 years. No pathological IgAN recurrence was found in 6 preventative tonsillectomy cases and in 2 cadaveric transplants that did not undergo tonsillectomy. Among 6 preventative tonsillectomy patients, 5 had improved urinary findings (protein urine and/or microscopic hematuria) after tonsillectomy. The 10 years living kidney donor graft survival rate of the IgAN group was lower than that of the non IgAN group (50 % vs. 88 %; P< 0.05). [Conclusion] Our data suggest that IgAN recurs more frequently after living related kidney transplantation than with cadaveric and living unrelated donor transplantation. Furthermore, no pathological IgAN recurrence was found after preventative tonsillectomy, and it was found that tonsillectomy could improve urinary findings. Thus, tonsillectomy has preventive and/or therapeutic effects for IgAN recurrence after kidney transplantation.

Usefulness of Follow-up Biopsies at One Year After ABO-Incompatible Kidney Transplantation

BackgroundDue to the shortage of deceased donor kidneys, we have expanded the indications for living-donor kidney transplantation (LKT) including ABO-incompatible (ABO-i) donors in Japan. In this study, the utility of protocol biopsies was discussed in ABO-i LKT. MethodsProtocol biopsies have been performed on kidney graft 1 hour, 3 weeks, and 1 year after LKT in our institution. The relationship between biopsies and clinical courses was considered retrospectively in 38 cases of ABO-i LKT. The immunosuppressive regimen consisted of anti-CD20 antibody, mycophenolate mofetil, prednisolone, calcineurin inhibitor (cyclosporine or tacrolimus), and anti-CD25 antibody. Anti-ABO blood type antibody removal by plasmapheresis was performed before LKT up to 32 times. The post-transplantation regimen consisted of mycophenolate mofetil or mizoribine as an antimetabolite. ResultsEpisode biopsies have been performed in 6 cases within 3 weeks post-transplantation. Each pathological diagnosis was as follows: antibody-mediated rejection (AMR; 5 cases) and calcineurin inhibitor (CNI) nephrotoxicity (1 case). Subclinical chronic active AMR was found at 1 year post-transplantation follow-up biopsies in 4 of the 6 cases. Episode biopsies have been done in the other 6 cases from 1 month to 1 year post-transplantation. Each pathological diagnosis was as follows: acute T-cell–mediated rejection (TMR; 1 case), vesicoureteral reflux (VUR; 3 cases), CNI nephrotoxicity (2 cases), and VUR + CNI nephrotoxicity (1 case). AMR was also not found at 1 year post-transplantation follow-up biopsies in them. In all cases episode biopsies were performed based on pathological diagnosis and had no graft dysfunction after that. ConclusionsPathological study revealed that acute AMR was found early (ie, within 3 weeks) following transplantation. Although appropriate treatment made AMR go into remission once, chronic active AMR was often found at 1-year follow-up biopsies.

Acute Antibody-mediated Rejection Possibly Due to Anti–human Leukocyte Antigen DQB1 Antibodies after Renal Transplantation – Case Report

A 61-year-old Japanese woman, who had undergone hemodialysis because of chronic glomerulonephritis, received a living renal transplant from her ABO blood type–compatible spouse. HLA typing of A, B and DRB showed 3/6 mismatches. Complement-dependent cytotoxicity crossmatches, HLA antibody screening with the use of flow panel reactive antibody (PRA), and flow cytometry crossmatches (FCXM) were all negative. Tacrolimus, mycophenolate mofetil, methylprednisolone (MP), and basiliximab induction were used as the standard immunosuppressive therapy. After renal transplantation, her serum creatinine level favorably decreased, but urine output was not sufficiently obtained, contrary to our expectations. Doppler sonography revealed disappearance of diastolic arterial flow on postoperative day 2. The episode biopsy showed acute antibody-mediated rejection (AMR) based on the current Banff classification, although FCXM and flow PRA were still negative. To determine the cause of acute AMR, we expanded the HLA typing at high resolution levels to Cw, DQB1, and DPB1. Retrospective analysis of perioperative sera demonstrated the presence of low levels of donor-specific HLA IgG and moderate levels of IgM antibody against DQB1 before transplantation. There was an elevation of IgM antibody at the time of rejection, whereas IgG antibody showed no remarkable change. AMR was successfully treated with plasma exchange, low-dose intravenous immunoglobulin, high-dose intravenous MP pulse, and rituximab.

The Impact of Donor Specific Antibodies on the Long-Term Liver Allograft after Pediatric Living Donor Liver Transplantation

Introduction: The protocol biopsies of liver allograft revealed that some pediatric liver transplant recipients on the way of weaning of immunosuppressants (IS) showed fibrosis in their liver allograft though their blood examination indicated normal liver function tests. The method of evaluation for immunological state against donor-derived alloantigens after liver transplantation has not been established yet. The absence of donor-specific antibodies (DSA) against human leukocyte antigens (HLA) has been expected as a promising biomarker for safe withdrawal of IS. In this study, we analyzed DSA in sera and the pathological findings of liver biopsies more than 12 months after pediatric living donor liver transplantation (LDLT) to elucidate the relevance of DSA against HLA to the late post-transplant liver allograft. Methods: 75 pediatric LDLT recipients were undertaken liver biopsies more than 12 months after operation in 2011; including 73 protocol biopsies and 2 episode biopsies. DSA in sera from those recipients were determined and quantified by single antigen beads method, where mean fluorescence intensity (MFI) over 1,000 was considered as positive. In pathological findings, each evaluation was blindly conducted by pathologists, and fibrosis was graded following Metavir fibrosis socring system. Results: Thirty-two recipients showed DSA in sera; the numbers of recipients with DSA against HLA class I, HLA class II, and both HLA calss I and class II (DSA-positive) were 2, 28, and 2, respectively, while 43 recipients did not show DSA (DSA-negative). MFI of DSA against HLA class I was not high; median 3520, (range 1170-6310). On the other hand, MFI of DSA against HLA Class II showed high; HLA-DRB1 9356, (2216-23140) and HLA-DQB1 20844, (2862-24834). The pathological findings of DSA-negative recipients were no remarkable finding in 14 (32.6%), idiopathic chronic hepatitis in 2 (4.7%), fibrosis in 20 (46.5%), and rejection including acute cellular rejection, late acute rejection, and central perivenulitis in 7 (16.3%). On the other hand, those of DSA-positive recipients were no remarkable finding in 1 (3.1%), fibrosis in 17 (53.1%) and rejection in 13 (40.6%). Most of normal finding of liver biopsy were showed in DSA-negative recipients. (p=0.002) The frequency of rejection was significantly higher in DSA-positive recipients than DSA-negative. (p=0.009) The fibrosis graded more than F2 was observed in 7 of DSA-negative (16.3%) and 12 of DSA-positive recipients (37.5%). (p=0.037) Conclusion: The existence of DSA in sera from pediatric LDLT recipients more than 12 months after operation has been related to severe fibrosis and allo-immune responses, such as acute cellular rejection and central perivenulitis. The measurement of DSA suggests that immunosuppressive therapy should be maintained or strengthened for DSA-positive recipients.

The Impact of Donor Specific Antibodies on the Long-Term Liver Allograft after Pediatric Living Donor Liver Transplantation

Introduction: The protocol biopsies of liver allograft revealed that some pediatric liver transplant recipients on the way of weaning of immunosuppressants (IS) showed fibrosis in their liver allograft though their blood examination indicated normal liver function tests. The method of evaluation for immunological state against donor-derived alloantigens after liver transplantation has not been established yet. The absence of donor-specific antibodies (DSA) against human leukocyte antigens (HLA) has been expected as a promising biomarker for safe withdrawal of IS. In this study, we analyzed DSA in sera and the pathological findings of liver biopsies more than 12 months after pediatric living donor liver transplantation (LDLT) to elucidate the relevance of DSA against HLA to the late post-transplant liver allograft. Methods: 75 pediatric LDLT recipients were undertaken liver biopsies more than 12 months after operation in 2011; including 73 protocol biopsies and 2 episode biopsies. DSA in sera from those recipients were determined and quantified by single antigen beads method, where mean fluorescence intensity (MFI) over 1,000 was considered as positive. In pathological findings, each evaluation was blindly conducted by pathologists, and fibrosis was graded following Metavir fibrosis socring system. Results: Thirty-two recipients showed DSA in sera; the numbers of recipients with DSA against HLA class I, HLA class II, and both HLA calss I and class II (DSA-positive) were 2, 28, and 2, respectively, while 43 recipients did not show DSA (DSA-negative). MFI of DSA against HLA class I was not high; median 3520, (range 1170-6310). On the other hand, MFI of DSA against HLA Class II showed high; HLA-DRB1 9356, (2216-23140) and HLA-DQB1 20844, (2862-24834). The pathological findings of DSA-negative recipients were no remarkable finding in 14 (32.6%), idiopathic chronic hepatitis in 2 (4.7%), fibrosis in 20 (46.5%), and rejection including acute cellular rejection, late acute rejection, and central perivenulitis in 7 (16.3%). On the other hand, those of DSA-positive recipients were no remarkable finding in 1 (3.1%), fibrosis in 17 (53.1%) and rejection in 13 (40.6%). Most of normal finding of liver biopsy were showed in DSA-negative recipients. (p=0.002) The frequency of rejection was significantly higher in DSA-positive recipients than DSA-negative. (p=0.009) The fibrosis graded more than F2 was observed in 7 of DSA-negative (16.3%) and 12 of DSA-positive recipients (37.5%). (p=0.037) Conclusion: The existence of DSA in sera from pediatric LDLT recipients more than 12 months after operation has been related to severe fibrosis and allo-immune responses, such as acute cellular rejection and central perivenulitis. The measurement of DSA suggests that immunosuppressive therapy should be maintained or strengthened for DSA-positive recipients.

Plasma cell‐rich acute rejection after renal transplantation in a patient with pyoderma gangrenosum: a case report

A 40-yr-old female received a living-related renal transplantation on January 29, 2008. She had type I diabetes mellitus and pyoderma gangrenosum (PG). Induction immunosuppressive therapy consisted of tacrolimus, mycophenolate mofetil, basiliximab, and prednisolone. Intravenous methylprednisolone pulse therapy was administered to prevent ulceration at the surgical site. The postoperative outcome was almost uneventful, and renal graft function was well preserved for 11 months. Her graft function deteriorated on December 24, 2008 and thus an episode biopsy was performed. The histopathological findings were consistent with plasma cell-rich acute rejection (PCAR). During hospitalization, it was noted that the patient was non-compliant. We then performed steroid pulse therapy, and her graft function and histological findings improved. This is the first report of PCAR in a patient with PG who received a renal allograft. It was thought that PCAR was triggered because of her non-compliance. Thus, we should recognize the importance of enhancing compliance in transplant recipients.

Mechanism of Acute Antibody-Mediated Rejection in ABO-Incompatible Kidney Transplantation: Which Anti-A/Anti-B Antibodies are Responsible, Natural or de Novo?

Mechanism of Acute Antibody-Mediated Rejection in ABO-Incompatible Kidney Transplantation: Which Anti-A/Anti-B Antibodies are Responsible, Natural or de Novo?

A case of acute rejection with adenovirus infection after ABO‐incompatible kidney transplantation

We report clinical and histopathologic findings of a case of acute rejection with adenovirus infection after kidney transplantation. A 63-yr-old woman with end-stage renal disease caused by lupus nephritis received an ABO-incompatible living kidney transplantation from her husband. On the 7th post-operative day (POD), she had fever, hematuria, and bladder irritation. Although she was treated with an antibiotic, the symptoms were not improved. We diagnosed adenovirus infection as positive with the urine shell vial method and blood PCR analysis. Cyclophosphamide was interrupted and immunoglobulin therapy was performed. However, urine output decreased and serum creatinine levels increased. An episode biopsy was performed on POD 20. We diagnosed acute antibody-mediated rejection. She was treated with plasma exchange for acute rejection and antiviral drug (rivabirin) for active adenovirus infection. However, the renal graft dysfunction was deemed irreversible and the renal graft was removed on POD 34. The graftectomy specimen showed acute rejection and acute tubular necrosis with adenovirus infection.

A case of accelerated acute rejection after ABO‐compatible living unrelated kidney transplantation

A 59-yr-old Japanese woman with chronic renal failure caused by IgA nephropathy and antineutrophil cytoplasmic antibody (ANCA)-related glomerulonephritis underwent kidney transplantation from a living unrelated spousal donor. The blood type was compatible, while the human leukocyte antigen (HLA) typing showed a 5/6 locus mismatch. She had become pregnant twice by her donor and had never received blood transfusions. Complement-dependent cytotoxicity cross-match, flow cytometry cross-match (FCXM), and flow panel reactive antibody (PRA) were negative. She initially underwent one week of immunosuppression with mycophenolate mofetil (MMF) and double filtration plasmapheresis (DFPP) immediately before transplantation to reduce the risk of antibody-mediated rejection. Induction therapy consisted of MMF, tacrolimus (TAC), methylprednisolone (MP), and basiliximab. The allograft function was excellent immediately after the operation. However, the urine output and platelet count declined rapidly on post-operative day (POD) 3, while the serum creatinine (sCr) and lactate dehydrogenase levels rose gradually. Subsequently, we could not detect the diastolic arterial flow on Doppler sonography. We diagnosed accelerated acute rejection and treated her with plasma exchange (PEX), intravenous MP pulse therapy, and rituximab. The first episode biopsy on POD 7 revealed acute vascular rejection and acute antibody-mediated rejection (Banff score AMR II). Her urinary excretion increased beginning on POD 13, while the sCr level decreased gradually and reached 0.9 mg/dL on POD 22. In our retrospective analysis, the LAB screen detected donor-specific antibody (DSA). This case suggested that, for successful kidney transplantation in highly sensitized recipients, such as husband-to-wife spousal kidney transplantation with a history of pregnancy, we should keep the risk of AMR in mind, even if the sensitive antibody detection tests are negative.