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Background: Tacrolimus (TAC) is a key immunosuppressant drug for kidney transplantation (KTx). However, the optimal serum trough level of TAC for good long-term outcomes remains unclear. This study aimed to investigate the relationship between the maintenance TAC trough level and the appearance of de novo donor-specific anti-human leukocyte antigen (HLA) antibodies (dnDSAs)., Methods: A total of 584 KTx recipients were enrolled in this study, of whom 164 developed dnDSAs during the follow-up period and 420 did not., Results: We found no significant relationship between TAC trough level during the follow-up period and dnDSA incidence. Patients who developed dnDSAs had a significantly greater number of HLA-A/B/DR mismatches (3.4 ± 1.3 versus 2.8 ± 1.5; P < 0.001), were more likely to have preformed DSAs (48.2% versus 27.1%; P < 0.001) and showed poor allograft outcome., Conclusions: There was no clear relationship between TAC trough level and dnDSA incidence for KTx recipients whose TAC trough levels were kept within the narrow range of 4-6 ng/mL during the immunosuppression maintenance period., (© The Author(s) 2020. Published by Oxford University Press on behalf of ERA-EDTA.)

Aim: Transplant glomerulopathy (TG) is a feature of chronic antibody-mediated injury in the glomerular capillaries in renal transplant recipients. TG is generally associated with proteinuria; however, renal function at the diagnosis of TG varies. This study aimed to determine which morphological abnormalities are associated with renal function and proteinuria at the diagnosis of TG., Methods: A total of 871 renal transplantations were performed at Tokyo Women's Medical University between 2005 and 2013. TG was diagnosed in 127 biopsies from 58 (6.7%) recipients. Renal function was evaluated by the estimated glomerular filtration rate (eGFR). Proteinuria was assessed by a dipstick test: positive for +1 and over., Results: At diagnosis, of 127 biopsies, 72, 37, and 18 had mild, moderate, and severe TG (Banff cg). The severity of TG was not associated with decreased eGFR at the time of biopsy (cg1: 36.1 ± 14.8, cg2-3: 38.8 ± 14.5 mL/min per 1.73 m(2) , P = 0.25), whereas the severity of interstitial fibrosis (IF) (Banff ci) was significantly associated with decreased eGFR (ci0-1: 42.75 ± 13.32, ci2-3: 27.69 ± 11.94 mL/min per 1.73 m(2) , P < 0.0001). The multivariate analysis revealed that IF was the only independent risk factors for decreased eGFR (OR = 4.38, P = 0.0006). Meanwhile, TG was identified as the only independent risk factor for the incidence of proteinuria (OR = 2.67, P = 0.014)., Conclusion: Interstitial fibrosis was a critical determinant of impaired renal function at the diagnosis of TG. The severity of TG was significantly associated with proteinuria, but did not contribute to renal dysfunction., (© 2016 Asian Pacific Society of Nephrology.)

Post-transplant lymphoproliferative disorder is a serious complication of solid organ transplantation; however, few large studies have been performed in Asian institutions. We review our single-center experience with post-transplant lymphoproliferative disorder patients in Japan. We retrospectively evaluated patients with post-transplant lymphoproliferative disorder following kidney transplantation between January 1985 and December 2013. The patients were divided into early-onset post-transplant lymphoproliferative disorder (<1 year) and late-onset post-transplant lymphoproliferative disorder (≥1 year) groups. Thirteen patients had the disorder, an incidence rate of 0.75% (13/1730). Early-onset post-transplant lymphoproliferative disorder (N = 3) had not occurred for the last two decades. In the late-onset group (N = 10), the median time of onset was 108.7 months. The Kaplan-Meier 10-year overall survival rates were 76.9% and 95.4% in patients with and without the disorder, respectively (P = 0.0001). Post-transplant lymphoproliferative disorder significantly affected transplant recipients' mortality. Late-onset occurred even > 10 years after transplantation; therefore, long-term monitoring of patients is needed., (© 2016 International Society for Apheresis, Japanese Society for Apheresis, and Japanese Society for Dialysis Therapy.)

ABO-incompatible living kidney transplantation (ABO-ILKT) has steadily become more widespread. However, the optimal immunosuppressive regimen for ABO-ILKT remains uncertain. We aimed to determine the longitudinal changes in the outcomes from ABO-ILKT compared with those from ABO-compatible living kidney transplantation (ABO-CLKT) over the last 25 years. Of 1195 patients who underwent living kidney transplantations (LKT) at our institute between 1989 and 2013, 1032-including 247 ABO-ILKT and 785 ABO-CLKT cases-were evaluated for graft survival, patient survival, infectious adverse events, and renal function. The patients were divided into four groups according to the transplantation era and ABO-compatibility. In the past decade, ABO-ILKT and ABO-CLKT recipients yielded almost equivalent outcomes with respect to the 9-year graft survival rates, which were 86.9% and 92.0%, respectively (hazard ratio [HR] 1.38, 95% confidence interval [CI] 0.59-3.22, p = 0.455). The graft survival rate for ABO-ILKT conducted between 2005 and 2013 was better than that for ABO-ILKT conducted between 1998 and 2004 (HR 0.30, 95% CI 0.13-0.72, p = 0.007). ABO-ILKT recipients showed substantial improvements in the graft survival rate over time. Graft survival was almost identical over the past decade, regardless of ABO-incompatibility. Currently, ABO-ILKT is an acceptable treatment for patients with end-stage renal disease., (© Copyright 2015 The American Society of Transplantation and the American Society of Transplant Surgeons.)

Focal segmental glomerulosclerosis commonly recurs following kidney transplantation. A 33-year-old man underwent living donor kidney transplantation. Proteinuria appeared two months after transplantation, and an episode biopsy on postoperative day 66 revealed recurrent focal segmental glomerulosclerosis lesions of the cellular variant by Columbia classification. We reviewed the native kidney biopsy and confirmed collapsing variant focal segmental glomerulosclerosis. Plasma exchange therapy was performed, and his proteinuria temporarily resolved. A second allograft biopsy performed on postoperative day 200 showed no evidence of focal segmental glomerurosclerosis. He experienced incomplete remission with a proteinuria of 0.5 g/day during the subsequent three years until his urinary protein level rose to 1.3 g/day. A third biopsy performed on postoperative day 1248 showed focal segmental glomerulosclerosis cellular variant lesions. Plasma exchange was resumed in combination with additional rituximab, but his proteinuria persisted. Intermittent plasma exchange was performed 42 times in total. However, his proteinuria continued, and his renal function gradually worsened. A fourth biopsy performed on postoperative day 2540 showed focal segmental glomerulosclerosis collapsing variant lesions with severe interstitial fibrosis and tubular atrophy. He ultimately required hemodialysis seven years after transplantation. Intensive therapy with long-term intermittent plasma exchange and rituximab suppressed proteinuria and preserved graft function for seven years, at which time graft failure occurred. We here present the clinical course and histological findings from consecutive allograft biopsies., (© 2015 Asian Pacific Society of Nephrology.)

Background: Outcomes of retroperitoneoscopic procurement of living kidneys with multiple renal arteries (MRA) in the recipients are largely unknown. Our aim is to access the effect of kidney allografts with MRA on donor and recipient outcomes after pure retroperitoneoscopic live donor nephrectomy (RPLDN)., Methods: From July 2001 to August 2010, 533 patients underwent live donor kidney transplants with allografts procured by RPLDN at our center. Of these 533 transplants, 406, 105, and 22 patients had one, two, and three renal arteries, respectively. We compared the retrospectively collected clinical data of each donor with MRA and the recipient using those with single renal artery as controls., Results: Significant differences were found among the one-renal artery and three-renal artery groups regarding operative time, estimated blood loss, warm and cold ischemic time, and incidence of slow graft function (SGF). However, there was no significant difference regarding patient and graft survival among the three groups. Major complications, such as open conversion, bleeding, and blood transfusion, were not found in patients with MRA. Five ureteral complications occurred. Of these, there was one patient with MRA. In univariate analysis, MRA patients had a risk factor of developing SGF (P=0.005) but not ureteral complications following RPLDN., Conclusion: Kidneys with MRA after RPLDN increase the risk of SGF in recipients. However, they provide similar outcomes as to long-term graft survival and complications compared with those of single renal artery. Renal artery multiplicity should not be a contraindication for live kidney donation and may not increase the risk of ureteral complications.

The aim of this study was to investigate the role of infiltrating macrophages in renal allograft fibrosis. Forty-six protocol renal allograft biopsies obtained 1 year after transplantation were stained with Sirius red to quantify fibrosis and double stained with CD68 and CD206 to identify the proportion of alternatively activated (M2) macrophages. Biopsies were analyzed for gene expression by microarray, which was correlated with macrophage infiltration and the severity of fibrosis. The number of infiltrating CD68+ cells strongly correlated with the percentage of interstitial fibrosis (r = 0.73, p < 0.0001). Macrophage infiltration at 1 year correlated with renal dysfunction at 1, 12 and 36 months posttransplant (estimated GFR low vs. high: 1 month 78 ± 26 vs. 54 ± 19 mL/min, p < 0.01; 12 months 87 ± 29 vs. 64 ± 19 mL/min, p < 0.05; 36 months 88 ± 33 vs. 60 ± 24 mL/min, p < 0.05). Ninety-two percent of infiltrating macrophages exhibited an M2 phenotype with CD68+ CD206+ dual staining. Gene microarrays demonstrated an alloimmune response with up-regulation of interferon-γ-response genes despite the lack of rejection or inflammatory infiltrate. Consistent with this was the presence of CXCL10 in proximal tubular cells at 3 months. This suggests that M2 macrophage proliferation, or infiltration, was associated with subclinical alloimmune inflammation, tubular injury and progression of fibrosis., (© Copyright 2014 The American Society of Transplantation and the American Society of Transplant Surgeons.)

Aim: Transplant glomerulopathy (TG) is included as one of the criteria of chronic active antibody-mediated rejection (c-AMR) in Banff 09 classification. In this report, we discuss the clinical and pathological analyses of cases of TG after renal transplantation., Patients: TG was diagnosed in 86 renal allograft biopsy specimens (BS) obtained from 50 renal transplant patients followed up at our institute between January 2006 and October 2012. We retrospectively reviewed the data of these 86 BS and 50 patients., Results: Among the 50 patients, 42 (84%) had a history of acute rejection (AR); of these, 30 (60%) had acute antibody-mediated rejection (a-AMR). Among the 86 BS of TG, the TG was mild in 35 cases (cg1 in Banff classification), moderate in 28 cases (cg2) and severe in 23 cases (cg3). Peritubular capillaritis was present in 74 BS (86%), transplant glomerulitis in 65 (76%), interstitial fibrosis and tubular atrophy (IF/TA) in 71 (83%), thickening of the peritubular capillary (PTC) basement membrane in 72 (84%), and interstitial inflammation in 40 (47%). C4d deposition in the PTC was present in 49 BS (57%); 39 of these 49 BS showed diffuse C4d deposits in the PTC (C4d3), while the remaining 10 BS showed focal deposits (C4d2). Diffuse C4d deposition in the glomerular capillaries (GC) was seen in 70 BS (81%), while focal C4d deposition in the GC was seen in 9 (11%). In the assay using plastic beads coated with HLA antigen performed in 67 serum samples obtained in the peri-biopsy period, circulating ant-HLA alloantibody was detected in 55 (82%); in 33 of the 55 (49%) samples, donor-specific antibodies (DSA) were detected. Among our study, the findings in 22 BS (26%) fully met the criteria for c-AMR in Banff '09 classification, including TG, C4d deposition in the PTC and presence of DSA, while those in 27 BS were suspicious of c-AMR. Deterioration of the renal allograft function after the biopsies was seen in 31 patients (62%), of which 11 lost their graft., Conclusions: We suggest that histopathological changes of transplant glomerulopathy might be accompanied by inflammation of the microvasculature, such as transplant glomerulitis and peritubular capillaritis, thickening of the peritubular capillary basement membrane, and circulating anti-HLA antibodies. C4d deposition in the PTC is not always present in biopsy specimens of TG. We speculated that C4d deposition in the GC, rather than that in the PTC might be a more characteristic manifestation of TG. Many of the patients with TG had a history of AR. Anti-HLA antibody Class II, particularly when the antibody was DSA Class II, appeared to be associated with the development of TG. The prognosis of grafts exhibiting TG was not too good even under the currently used immunosuppressive protocol., (© 2014 Asian Pacific Society of Nephrology.)

Purpose: A new protocol for ABO-incompatible (ABO-i) kidney transplantation including rituximab was introduced in January 2005 in our institute. This study reviewed the results and evaluated the use of low-dose rituximab in ABO-i kidney transplantation., Material and Methods: Seventy-four de novo ABO-i kidney transplantations were performed at Tokyo Women's Medical University between January 2005 and August 2010. The immunosuppressive protocol was consisting of tacrolimus, mycophenolate mofetil, and methylprednisolone. All the patients received induction therapy with basiliximab. The pre-conditioning protocol included double-filtration plasmapheresis and a single dose of rituximab. A dose of 500 mg/body rituximab was initially employed and yielded excellent results (Group I, n = 24). Afterward, the dose of rituximab was reduced to 200 mg/body in January 2007 (Group II, n = 50)., Results: Seventy-four de novo ABO-i recipients were treated with this protocol, and all patients underwent kidney transplantation successfully. Effective elimination of the peripheral blood CD19 cells was observed in both groups. However, the peripheral blood CD19 levels were still low in both groups at 24 months after treatment., Conclusion: The patients in Group II showed excellent results similar to Group I. These results suggest that the low dose of rituximab (200 mg/body) is the sufficient dose in ABO-i kidney transplantation., (© 2010 John Wiley & Sons A/S.)

We present a kidney transplantation patient who developed rhabdomyolysis. The patient was initially immunosuppressed with tacrolimus, mycophenolate mofetil, steroids, and chimeric CD25 monoclonal antibody. He complained of severe precordial and appendicular pain on 25th day after the operation. The patient developed rhabdomyolysis manifested as a rise in serum creatine phosphkinase (CPK) and elevation of urinary myoglobulin at approximately the same time as his symptoms. Although he was switched from tacrolimus to cyclosporine (CYA), his muscle pain and levels of serum CPK did not improve. However, dividing the daily total amount of the calcinuerin inhibitors into more frequent doses in order to reach lower serum levels resolved the rhabdomyolysis. Therefore, we conclude that his rhabdomyolysis might be a dose-related problem of calcineurin inhibitor.

Background: The etiology of de novo membranous nephropathy (MN) after kidney transplantation is still uncertain. Immunological response to various allograft antigens is speculated to be a candidate for the etiology., Methods: Seventeen patients with post-transplant de novo MN were studied clinically and pathologically in comparison with control post-transplant patients without MN. Double immunofluorescent staining was performed to identify the presence of donor-specific human leukocyte antigen (HLA) combined with IgG in the deposits on glomerular capillary walls., Results: De novo MN occurs in relatively late period after transplantation (102.1 ± 68.3 months), presenting various degree of proteinuria. Histological findings associated with antibody-mediated rejection (AMR), such as peritubular capillaritis and C4d deposition in peritubular capillary, were more frequently observed in the patients with de novo MN than the non-MN control patients. Donor-specific antibody (DSA) was detected in five patients at the time of biopsy. In one case of de novo MN with DSA, a donor-derived HLA was identified in the subepithelial deposits on the glomerular capillary walls combined with IgG deposition., Conclusions: DSA and AMR might play some roles for the pathogenesis in some patients with de novo MN after kidney transplantation., (© 2010 John Wiley & Sons A/S.)

Recipients of spousal donor transplantation (SDT) have poorer histocompatibility and higher human leukocyte antigen (HLA) sensitization due to pregnancy than those receiving related donor transplantation (RDT). Thus, SDT carries a higher risk of acute rejection (AR). In our department, patients at a high immunological risk, such as those with ABO incompatibility and HLA sensitization, were considered for desensitization by double filtration plasmapheresis and preoperative administration of rituximab. In this study we compared the AR incidence rates between SDT and RDT according to their immunological risk. We performed RDT in 279 and SDT in 100 patients, a total of 379 cases, between 2000 and 2008; 48.7% of RDT and 67.0% of SDT cases were considered to be at a high immunological risk and underwent preoperative desensitization (P=0.002). Even though the AR incident rate of SDT was higher than RDT in the low immunological risk group, in which the patients had undergone transplantation without desensitization (RDT 24.4%, SDT 37.0%, P=0.012), there was no significant difference between the two donor type groups in the high immunological risk group, in which transplantation with desensitization occurred (RDT 21.3%, SDT 31.3%, P>0.05). Preoperative administration of rituximab significantly reduced AR from 37.4% to 10.6% (P<0.001), especially T-cell mediated rejection (36.4% to 20.2%, P=0.01). SDT no longer carries a high risk when appropriate desensitization, including the use of rituximab, is performed. Overall, the five-year graft survival rates were similar between RDT and SDT., (© 2010 The Authors. Therapeutic Apheresis and Dialysis © 2010 International Society for Apheresis.)

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

Background: Blood group O individuals are known to have larger amounts of anti-ABO blood group (anti-A/B) IgG antibodies than A or B individuals. Therefore, in ABO-incompatible (ABOI) kidney transplantation (KTX), it is expected that blood group O recipients are more likely to suffer graft damage, because anti-A/B IgG antibodies are believed to be responsible for worse graft outcomes., Methods: This study assessed the graft outcomes between blood group O and non-O recipients in ABOI-KTX. A total of 164 consecutive recipients who underwent ABOI-KTX between 1990 and 2007 under three different immunosuppressive protocols were enrolled in this study. The study population was divided into two groups: (i) recipients with blood group O (n=87) and (ii) recipients with blood group A or B (non-O) (n=77)., Results: High anti-A/B IgG titers were predominant in the O group (P<0.001), whereas no significant difference was observed in the IgM titers. The overall graft survival rate did not differ between the two groups; however, the 6-month graft survival rate was significantly lower in the O group (86% vs. 97%, P=0.011). Among 14 recipients who suffered graft loss within 6 months after transplantation, 12 (86%) were O recipients. The cumulative incidence of acute antibody-mediated rejection was significantly higher in the O group (60 days, 31 vs. 14%, P=0.013)., Conclusion: Our results may indicate that being a blood group O recipient is at great risk for experiencing early allograft deterioration, probably caused by anti-A/B IgG antibodies in ABOI-KTX.

Anti-CD20 antibody (rituximab) is recently being used as a B cell-depleting agent in renal transplantation (RTx). However, the incidence of infectious complications associated with rituximab therapy remains uncertain. We evaluated the incidence of cytomegalovirus (CMV) infection associated with rituximab therapy in RTx. A total of 83 patients were enrolled. The immunosuppressive regimen consisted of tacrolimus or cyclosporin, mycophenolate mofetil, methylprednisolone and basiliximab. In 54 patients, only one dose of rituximab (200 or 500 mg/kg body weight) was given before RTx. A total of 25 of 43 (58.1%) recipients who were CMV seropositive prior to RTx and who received rituximab induction therapy developed CMV infection, compared to 18 of 24 (75%) CMV seropositive recipients who did not receive rituximab therapy (P = 0.1676). A total of 8 of 11 patients who were CMV seronegative prior to RTx and who received rituximab developed CMV infection. However, CMV seroconversion was seen in all 8 of these infected patients. Low-dose rituximab induction therapy in renal transplant recipients appears to have no influence on the incidence of CMV infection and CMV seroconversion. However, we have to consider anti-CMV prophylaxis therapy, because of high incidents of CMV infection, especially for CMV seronegative recipients who received rituximab.

The impact of acute antibody-mediated rejection (AAMR) on the long-term outcome on ABO-incompatible (ABOI) kidney transplantation is not well understood. We retrospectively analyzed the long-term impact of AAMR and risk factors for AAMR in 57 consecutive recipients performed between 1999 and 2004. Nineteen patients (33%) who developed AAMR within 3 months posttransplantation constituted of the AMR group. The graft survival rate was significantly lower in the AMR group (AMR vs. non-AMR, respectively; 5 years: 84% vs. 95%; 8 years: 45% vs. 95%; p = 0.009). The prevalence of transplant glomerulopathy at 1 year posttransplantation was significantly higher in the AMR group (AMR 64% vs. non-AMR 3%, p < 0.001). Multivariate analysis demonstrated that anti-blood group IgG antibody titers of 1:32 at the time of transplantation (OR, 9.52; p = 0.041) and donor-specific anti-HLA antibodies (DSHA) detected by Luminex single bead method (OR, 5.68; p = 0.015) were independent risk factors for AAMR regardless of baseline anti-blood group IgG antibody titers. Our results indicate that AAMR has a heavy impact on the long-term outcome and preoperative DSHA appears to have a more significant association with poor graft outcomes than anti-blood group antibodies, even in ABOI kidney transplantation.

Peritubular capillary basement membrane multilayering (PTCBMML) is a pathological landmark of chronic rejection-induced transplant capillaropathy (TC), but its cellular mechanisms are not fully understood. We observed de novo caveolae formation in endothelial cells in TC under electron microscopy. To examine the role of caveolae and their structural components in TC, biopsy samples from cases of chronic rejection were double-immunostained for Caveolin-1 (Cav-1) and Pathologische Anatomie Leiden-endothelium (PAL-E; a marker of peritubular capillary [PC]). Thirty-two cases of chronic rejection (group I) were compared with 18 cases of interstitial fibrosis and tubular atrophy with no evidence of any specific etiology (IF/TA; group II) and eight cases of peritubular capillaritis (group III). The Cav-1/PAL-E immunoreactivities in groups I-III (%Cav-1/PAL-E) were 41.8+/-23.1%, 8.1+/-7.3% (p < 0.01 vs. group I) and 12.7+/-7.4% (p < 0.01 vs. group I), respectively. Furthermore, multiple linear regression models demonstrated that %Cav-1/PAL-E was independently associated with the PTCBMML grade and reduced PC number. No correlation was observed between %Cav-1/PAL-E and PC C4d deposition in group I. We conclude that de novo caveolae formation in PC endothelia is involved in TC in chronic rejection.

A 58-year-old man underwent kidney transplantation on November 14, 2002 for end-stage kidney disease after Chinese herb nephropathy. Immunosuppressive therapy was maintained with tacrolimus, mycophenolate mofetil, and methylpredonisolone. He was diagnosed with right ureteral cancer and underwent right nephroureterectomy on December 13, 2003. Then, he underwent left nephroureterectomy for left ureteral cancer on March 5, 2004. Subsequently, he was diagnosed with multiple bladder cancers and carcinoma in situ. On August 31, he underwent radical cystectomy with an orthotopic ileal neobladder (Studer's method). The postoperative course was uneventful. After 3 years follow-up, this patient shows no evidence of recurrence and his serum creatinine level is stable (1.7 mg/dL). The continence is maintained during both day and night; he voids without intermittent self-catheterization. We suggest that an orthotopic ileal neobladder is a safe method of urinary diversion after cystectomy in kidney transplant recipients.

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

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