Tatsu Tanabe

Decrease of blood type antigenicity over the long-term after ABO-incompatible kidney transplantation.

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 donors type B blood-type antigens on the transplanted graft had changed but partially to the recipients blood-type A antigen by 2582days 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 donors 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.

Comparison of pharmacokinetics and pathology for low-dose tacrolimus once-daily and twice-daily in living kidney transplantation: prospective trial in once-daily versus twice-daily tacrolimus.

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.

Acute vascular rejection after renal transplantation and isolated v-lesion

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.

Endothelial chimerism after ABO-incompatible kidney transplantation.

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<0.0001). Conclusions. Endothelial chimerism seems to be a hallmark of vigorous immune or nonimmune responses, such as antibody-mediated rejection or calcineurin inhibitor toxicity, and not of the induction of tolerance.

Tonsillectomy ameliorates histological damage of recurrent immunoglobulin A nephropathy after kidney transplantation.

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.

BK polyomavirus nephropathy complicated with acute T-cell-mediated rejection in a kidney transplant recipient: a case report

Tanabe T, Shimizu T, Sai K, Miyauchi Y, Shirakawa H, Ishida H, Honda K, Koike J, Yamaguchi Y, Tanabe K. BK polyomavirus nephropathy complicated with acute T‐cell‐mediated rejection in a kidney transplant recipient: a case report.
Clin Transplant 2011: 25 (Suppl. 23): 39–43.
© 2011 John Wiley & Sons A/S.

Clinical and pathological analysis of transplant glomerulopathy cases

Transplant glomerulopathy (TG) is involved in the criteria of chronic active antibody‐mediated rejection (c‐AMR) in Banff ‘09 classification.

Sequential analysis of donor-specific antibodies and pathological findings in acute antibody-mediated rejection in a rat renal transplantation model

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.

The value of long‐term protocol biopsies after kidney transplantation

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.

Clinicopathologic Analysis of Acute Vascular Rejection Cases After Renal Transplantation

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.