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Background: Kidney transplantation is a well‐established alternative in renal replacement therapy. Compared with hemodialysis, low‐immunological‐risk kidney transplantation can reduce the medical treatment costs associated with end‐stage renal disease. However, there are few reports on whether high‐immunological‐risk kidney transplantation reduces the financial burden on governments. We investigated the medical costs of high‐immunological‐risk kidney transplantation in comparison with the cost of hemodialysis in Japan. Methods: We compared the medical costs of high‐immunological‐risk kidney transplantation with those of hemodialysis. 15 patients who underwent crossmatch‐positive and/or donor‐specific antibody‐positive kidney transplantations between 2020 and 2021 were enrolled in this study. The patients received intravenous immunoglobulin, plasmapheresis, and rituximab as desensitizing therapy. Results: Acute antibody‐mediated rejection was detected in nine (60%) recipients, while there were no indications of graft function deterioration during the follow‐up. For each patient, the transplant hospitalization cost was 38 428 ± 8789 USD. However, the cumulative costs were 59 758 ± 10 006 USD and 79 781 ± 16 366 USD, at 12 and 24 months, respectively. Compared with hemodialysis (34 286 USD per year), high‐immunological‐risk kidney transplantation tends to be expensive in the first year, but the cost is likely to be lower than that of hemodialysis after 3 years. Conclusions: Although kidney transplantation is initially expensive compared with hemodialysis, the medical cost becomes advantageous after 3 years even in kidney transplant recipients with high immunological risk. [ABSTRACT FROM AUTHOR]

Objectives: To examine the surgical and functional outcomes of patients who have undergone repeat open partial nephrectomy (reOPN) or robot‐assisted laparoscopic partial nephrectomy (reRAPN). Methods: Until May 2022, 3310 patients with renal tumors underwent nephron‐sparing surgery (NSS) at affiliated institutions. Of these, 22 and 17 patients who underwent reOPN and reRAPN, respectively, were included in this study. Results: No significant differences were found between the groups in terms of sex, age, comorbidities, recurrent tumor size at repeat NSS, interval from recurrence to initial NSS, and nephrometry score. ReRAPN had a shorter operative time (median: 138.0 vs. 214.0 min; p = 0.0023) and less estimated blood loss (median: 50.0 vs. 255.0 mL; p = 0.0261) than reOPN. The incidence of complications with Clavien–Dindo grade ≥ 2 was higher in the reOPN group than in the reRAPN group (31.8 vs. 5.9%; p = 0.0467). The mean decrease in the estimated glomerular filtration rate at 3 months postoperatively was not significantly different between the groups. The trifecta achievement rates in the reRAPN (64.7%) and reOPN (27.3%) groups were significantly different (p = 0.0194). On multivariate analysis, age and surgical method were significant predictors of trifecta achievement after partial nephrectomy. Conclusions: There were no differences in postoperative renal functional outcomes between reOPN and reRAPN. ReRAPN is superior to reOPN in terms of surgical burden. Therefore, ReRAPN is an important minimally invasive surgery for recurrent renal cell carcinoma. [ABSTRACT FROM AUTHOR]

Aim: We compared survival and perioperative outcomes of robot‐assisted laparoscopic partial nephrectomy (RAPN) and laparoscopic radical nephrectomy (LRN) for older patients (age 70 years or older) with stage 1 renal cell carcinoma (RCC). Methods: This retrospective, single‐center study included 260 patients who underwent RAPN and 44 patients who underwent LRN. The overall survival (OS) and perioperative outcomes were compared between these two groups using an inverse probability of treatment weighting (IPTW) analysis. Results: Compared with the LRN group, a trend of more complications was observed in the RAPN group, including a higher body mass index (24 vs. 22 kg/m2; P = 0.0002) and higher rates of hypertension (77% vs. 55%; P = 0.0029) and chronic kidney disease (62% vs. 36%; P = 0.0027). After adjustment by the IPTW analysis, the RAPN group had a shorter operative time (143 vs. 282 min; P = 0.033), shorter postoperative length of hospital stay (PLOS) (4.1 vs. 7.9 days; P = 0.004), and less change in the estimated glomerular filtration rate during surgery (−8.4% vs. −32%; P < 0.0001) than the LRN group; however, the perioperative complication rates were similar. Patients who underwent RAPN had better 5‐year OS than those who underwent LRN (95% vs. 90%; log‐rank, P = 0.017). Conclusion: RAPN resulted in better OS and surgical outcomes, with shorter operative time, shorter PLOS, and better renal function preservation, than LRN for older patients with stage 1 RCC. Therefore, RAPN may be the primary option for patients indicated for surgical intervention. Geriatr Gerontol Int 2024; 24: 269–274. [ABSTRACT FROM AUTHOR]

The coronavirus disease‐19 (COVID‐19) vaccine efficacy and immunogenicity in the immunocompetent population are well established. However, in solid organ transplant (SOT) recipients, because of their use of immunosuppressive medication, the immunogenicity of these severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) vaccines remains suboptimal. Both BNT162b2 and mRNA1273 have been used for some time, but their immunogenicity has not been directly compared in this immunocompromised patient group. We performed a post‐hoc analysis of a previous prospective cohort study. The inclusion criteria were adult SOT recipients with active grafts at least 1 month after SOT. After giving consent, participants chose to receive either BNT162b2 or mRNA1273 vaccine. Anti‐spike‐protein‐S antibody against SARS‐CoV‐2 was measured. Propensity scores were calculated via logistic regression to transform the probability of having received either BNT162b2 or mRNA1273 vaccine, and a model was developed. We enrolled 623 SOT recipients. In the propensity score‐matched analysis, 100 recipients were selected for BNT162b2 and 100 for mRNA1273. SARS‐CoV‐2 anti‐spike protein antibody positivity with BNT162b2 versus mRNA1273 at 3 weeks after the first dose, 1 month after the second dose, 3 months after the second dose, and 6 months after the second dose were 10% versus 19% (P =.07), 51% versus 58% (P =.30), 74% versus 88% (P =.01), and 78% versus 87% (P =.13), respectively. We conducted a propensity score‐matched comparison of BNT162b2 and mRNA1273 vaccines as the primary series of COVID‐19 vaccines in SOT recipients. We found significantly better immunogenicity with the mRNA1273 vaccine than with BNT162b2. [ABSTRACT FROM AUTHOR]

Objectives: To evaluate the 10‐year efficacy and safety of a prolonged‐release tacrolimus‐based combination immunosuppressive regimen on longer‐term outcomes in living donor kidney transplantation. Methods: Data from Japanese living donor kidney transplant recipients (n = 410) maintained on continuous prolonged‐release tacrolimus‐based immunosuppression from 2009–2013 were analyzed with a median follow‐up of 9.9 years. Results: A prolonged‐release, tacrolimus‐based combination regimen provided death‐censored graft failure and all‐cause death rates at 10 years of 7.0% and 6.8%, respectively. In multivariable analyses, acute and chronic rejection and 'throughout' (new‐onset plus preexisting) diabetes mellitus were risk factors for death‐censored graft failure. Recipient age ≥ 65 years, throughout diabetes mellitus and malignancy were common risk factors for all‐cause death. Throughout diabetes mellitus was the most common risk factor for both death‐censored graft failure and all‐cause death. Additional analyses showed 10‐year cumulative rates of death‐censored graft failure were 14.0% and 5.4% for recipients with or without preexisting diabetes mellitus, respectively (log‐rank test: p = 0.009). All‐cause death rates were 12.7% and 5.4% in the preexisting and non‐diabetes mellitus groups, respectively (log‐rank test: p = 0.023). Conclusions: In this real‐world, retrospective, living donor kidney transplantation study, a prolonged‐release tacrolimus‐based immunosuppressive combination regimen provided 10‐year death‐censored graft failure rates of 14.0% and 5.4% in diabetes mellitus and non‐diabetes mellitus patients, respectively; Similarly, 10‐year all‐cause death rates were 12.7% and 5.4% in diabetes mellitus and non‐diabetes mellitus patients, respectively. To our knowledge, the data in this study are the first to provide 10‐year transplant outcomes in living donor kidney transplant recipients under prolonged‐release tacrolimus‐based regimen. [ABSTRACT FROM AUTHOR]

Solid‐phase single antigen bead (SAB) assay for detection of anti‐human leukocyte antigen (HLA) antibodies and high‐resolution HLA typing have enabled tremendous progress in virtual crossmatch (VXM) technology in recent years. However, misinterpretation of the SAB assay may result in detrimental consequences after kidney transplantation. Meanwhile, epitope analysis could be an effective method to estimate immunizing eplets, which may provide ancillary information for better understanding of the SAB assay. To perform epitope analysis appropriately, it is necessary to understand the basic principles related to histocompatibility testing and the characteristics of the SAB assay. Therefore, knowledge of the properties and limitations of the SAB assay is critical. In this review, we aim to describe the fundamental concepts regarding immunobiological assessment, including HLA, anti‐HLA antibodies, and SAB assay, and explain epitope analysis using examples. [ABSTRACT FROM AUTHOR]

Objectives: To compare surgical and functional outcomes between robot‐assisted laparoscopic partial nephrectomy and open partial nephrectomy in patients with renal cell carcinoma with stage 4 chronic kidney disease. Methods: This was a retrospective analysis of 60 patients with stage 4 chronic kidney disease (estimated glomerular filtration rate 15–30 ml/min/1.73 m2) who underwent partial nephrectomy for T1 renal cell carcinoma between April 2004 and April 2020. We compared perioperative outcomes according to the surgical approach. Multivariable analysis was performed to identify predictive factors for end‐stage renal disease. Results: Robot‐assisted laparoscopic partial nephrectomy and open partial nephrectomy were performed in 31 and 29 patients, respectively. The median age was 68 years and 17% of all patients were women. Patient and tumor characteristics did not differ between groups. The operative time (155.2 vs. 221.0 min, p < 0.0001) and the postoperative length of hospital stay (5.2 vs. 10.6 days, p = 0.0083) were significantly shorter, and the estimated blood loss was lower (53.4 vs. 363.2 ml, p = 0.0003) in the robot‐assisted laparoscopic partial nephrectomy group than in the open partial nephrectomy group. Preoperative estimated glomerular filtration rate was the only significant predictor of end‐stage renal disease after partial nephrectomy on multivariable analysis. Conclusions: Both procedures preserved renal function in this patient cohort, delaying the requirement for postoperative dialysis. Furthermore, robot‐assisted laparoscopic partial nephrectomy was associated with shorter operative time and postoperative length of hospital stay, as well as lesser estimated blood loss than open partial nephrectomy. [ABSTRACT FROM AUTHOR]

Monoclonal tubular basement membrane immune deposits (TBMID) are associated with progression of interstitial injury in renal allograft. However, the significance of monoclonal and polyclonal TBMID in the native kidney remains unclear. We retrospectively analyzed 1894 native kidney biopsies and 1724 zero‐hour biopsies performed between 2008 and 2018 in our institution. The rate of immunoglobulin G (IgG) TBMID was found to be 8.4% among native kidney biopsies and 0.4% among zero‐hour biopsies. Polyclonal TBMID is common in IgG4‐related tubulointerstitial nephritis (37.5%), diabetic nephropathy (31.3%) and lupus nephritis (25.5%). Monoclonal IgG TBMID was identified in seven cases, including three zero‐hour biopsies. The combination of IgG1κ was observed in two cases, IgG1λ in three, and IgG2κ in two. Electron microscopy revealed powdery electron‐dense deposits in all cases. Monoclonal gammopathy of undetermined significance was diagnosed in one case. Although one patient with focal segmental glomerulosclerosis developed renal failure, all others exhibited stable renal function. Monoclonal IgG TBMID in the native kidney is not associated with renal prognosis. However, this may be an interesting immunopathological finding that would help clarify the pathogenesis of TBM immune deposits. Further study for both monoclonal and polyclonal TBMID is required in the future. [ABSTRACT FROM AUTHOR]

Objective: To evaluate the quality of recovery in patients who underwent robot‐assisted partial nephrectomy and to compare the outcomes of the transperitoneal or retroperitoneal approach. Methods: This study included 121 patients who underwent robot‐assisted partial nephrectomy under general anesthesia from April 2019 to September 2019 at Tokyo Women's Medical University, Tokyo, Japan. Quality of recovery was defined according to the QoR‐40 Japanese version. The participants responded to the QoR‐40 Japanese version on three designated days. The patients were assigned to two groups according to the surgical approach: transperitoneal or retroperitoneal. A multivariate logistic regression analysis was carried out to identify independent factors associated with better quality of recovery. Results: Out of the 121 patients, 56 (46%) and 65 (54%) patients were included in the transperitoneal and retroperitoneal group, respectively. Although the QoR‐40 Japanese version scores were not different between the two groups at admission, a better quality of recovery was observed in the retroperitoneal group than in the transperitoneal group at discharge based on the total score: physical comfort, emotional state, physical independence and pain. A multivariate analysis showed that the retroperitoneal approach and male sex were associated with a better QoR‐40 Japanese version score at discharge. Conclusions: A retroperitoneal approach offers better quality of recovery than a transperitoneal approach, and therefore it might represent the optimal approach in selected patients undergoing robot‐assisted partial nephrectomy. [ABSTRACT FROM AUTHOR]

Objectives: To compare the efficacy of nivolumab with that of molecular‐targeted therapy as a second‐line therapy for metastatic renal cell carcinoma using real‐world data. Methods: We retrospectively evaluated patients who received nivolumab or molecular‐targeted therapy after the failure of first‐line molecular‐targeted therapy between January 2008 and December 2019 at two Japanese institutions. Progression‐free survival and overall survival after the initiation of second‐line therapy were calculated using the Kaplan‐Meier method and compared using the log‐rank test. Objective response rate was assessed based on the Response Evaluation Criteria in Solid Tumors version 1.1. Results: Among 159 patients, 43 (27%) and 116 (73%) patients received nivolumab and molecular‐targeted therapy as second‐line therapy, respectively. During follow up (median 11.1 months), 129 (81%) and 98 (62%) patients had disease progression and died, respectively. Progression‐free survival was comparable between the two treatments (median 5.06 vs 5.95 months, P = 0.881), whereas overall survival was significantly longer with nivolumab than with molecular‐targeted therapy (not reached vs 13.0 months, P = 0.0008). Multivariate analysis further showed that nivolumab therapy was an independent favorable factor for overall survival (hazard ratio 0.33, P = 0.0007). In 151 patients with eligible radiographic data, the objective response rate was significantly higher in nivolumab than in molecular‐targeted therapy (n = 14/41 [34%] vsn = 20/110 [18%], P = 0.0485). Conclusions: Real‐world data analysis suggests superior efficacy of nivolumab over molecular‐targeted therapy as second‐line therapy for metastatic renal cell carcinoma. [ABSTRACT FROM AUTHOR]

Objectives: To compare the long‐term outcome and complications of living‐kidney grafts with arteriosclerosis to those without abnormal findings diagnosed using pretransplant graft biopsy, and to assess the impact of the arteriosclerosis in living‐donor kidneys. Methods: The influence of arteriosclerosis in pretransplant biopsy on long‐term outcomes and complications was evaluated in both unmatched (n = 1351, without arteriosclerosis n = 788 vs with arteriosclerosis n = 563) and propensity score‐matched cohorts (n = 984, without arteriosclerosis n = 492 vs with arteriosclerosis n = 492) of adults who underwent living‐kidney transplant. Results: In both the unmatched and matched cohort, there was no significant difference in patient and death‐censored graft survival at 10 years between the without arteriosclerosis and with arteriosclerosis groups. The with arteriosclerosis group had a higher incidence rate of overall rejection than did the without arteriosclerosis group in both the unmatched (P = 0.026) and matched (P = 0.060) cohorts. The with arteriosclerosis group had significantly higher chronic antibody‐mediated rejection than did the without arteriosclerosis group (P = 0.006) in the unmatched cohort. The with arteriosclerosis group had a significantly lower estimated glomerular filtration rate in recipients, but there was no significant difference after matching. The incidence rates of calcineurin inhibitor nephrotoxicity and post‐transplant anemia were significantly higher in the with arteriosclerosis group than in the without arteriosclerosis group in both the unmatched and matched cohorts. Long‐term postoperative kidney function of living donors was lower in the with arteriosclerosis group. Conclusions: Kidney graft with arteriosclerosis might affect the incidence of rejection, complications and postoperative kidney function of donors. Long‐term careful observation is required for both the recipients who received grafts with arteriosclerosis and the donors who had kidneys with arteriosclerosis. [ABSTRACT FROM AUTHOR]

Management of children with autosomal recessive polycystic kidney disease (ARPKD) who develop end‐stage renal disease (ESRD) remains challenging because of concomitant liver disease. Patients with recurrent cholangitis are candidates for liver‐kidney transplantation, while the treatment for patients with splenomegaly and pancytopenia due to portal hypertension is controversial. Herein, we report 7 children who were treated using an individualized treatment strategy stratified by liver disease. Two patients with recurrent cholangitis underwent sequential liver‐kidney transplantation, while 4 patients with splenomegaly and pancytopenia but without recurrent cholangitis underwent splenectomy followed by isolated kidney transplantation. The remaining patient, who did not have cholangitis and pancytopenia, underwent isolated kidney transplantation. Blood cell counts were normalized after splenectomy was performed at the median age of 8.7 (range, 7.4‐11.7) years. Kidney transplantation was performed at the median age of 8.8 (range, 1.9‐14.7) years in all patients. Overwhelming post‐splenectomy infections and cholangitis did not occur during the median follow‐up period of 6.3 (range, 1.0‐13.2) years. The estimated glomerular filtration rate at the last follow‐up was 53 (range, 35‐107) mL/min/1.73 m2. No graft loss occurred. Our individualized treatment strategy stratified by recurrent cholangitis and pancytopenia can be a feasible strategy for children with ARPKD who develop ESRD and warrants further evaluation. [ABSTRACT FROM AUTHOR]

Introduction: Previous studies have demonstrated an association between low serum creatinine levels and adverse outcomes in patients undergoing maintenance hemodialysis. However, little is known regarding whether long‐term changes in serum creatinine predict outcomes independently and incrementally over a single point evaluation. Methods: Serum creatinine data at index (June 2013) and for the 18 months prior to the index blood sampling (between January 2012 and June 2013) were evaluated in 346 hemodialysis patients. Patients were followed from the index blood sampling for primary (all‐cause mortality) and secondary (cardiovascular death) endpoints. Findings: During a median follow‐up of 5.7 years, there were 82 all‐cause and 25 cardiovascular deaths. Compared to patients who survived, those who died displayed a greater time‐dependent reduction in creatinine levels during the 18 months prior to the index assessment, coupled with a greater decrease in predialysis body weight (interaction p = 0.007). Patients who displayed creatinine decline over the prior 18 months (∆ creatinine<0 mg/dL) had higher all‐cause mortality than those who maintained creatinine levels (∆ creatinine≥0 mg/dL). After adjustment for clinical factors and baseline creatinine index, antecedent creatinine decrease was independently associated with an increased risk of all‐cause mortality, with an incremental prognostic value over baseline creatinine index alone. A reduction in creatinine levels was also associated with cardiovascular death independent of the baseline creatinine index. Discussion: A long‐term antecedent decrease in serum creatinine levels is independently associated with clinical outcomes in hemodialysis patients, with an incremental prognostic value over baseline creatinine index alone. Our data suggest that serial creatinine measurements are a useful prognosticator in practice. [ABSTRACT FROM AUTHOR]

Objectives: To examine the association of response to rituximab and the incidence of antibody‐mediated rejection in preconditioning of rituximab and plasma exchange without post‐transplant plasmapheresis in patients undergoing ABO‐incompatible living kidney transplantation. Methods: A total of 115 patients who underwent ABO‐incompatible living kidney transplantation at Tokyo Women's Medical University Hospital, Tokyo, Japan, were divided into two groups based on the response to rituximab: good response (n = 75) or poor response (n = 40). The rituximab good response and poor response patients were defined as patients whose CD19+ cells were non‐detected (0%) and detected on the day of transplantation (2–5 days, median 3 days, after rituximab administration), respectively. Results: Rituximab response and anti‐A/B blood antibody titer after plasmapheresis were significant risk factors for antibody‐mediated rejection (P = 0.036, 0.045, respectively). The occurrence of antibody‐mediated rejection was higher in the poor response group than in the good response group (22.5% vs 8.0%; P = 0.028). The 14‐day, 3‐month and 1‐year cumulative incidence of antibody‐mediated rejection was 2.7%, 5.3% and 8.0% in the good response group, and 17.5%, 20.0% and 22.5% in the poor response group after ABO‐incompatible living kidney transplantation. The patient survival was not significantly different between the two groups. However, graft survival 1 month after transplantation was lower in the poor response group. There is no significant difference in graft function and in the incidence of complications, including infection, after transplantation between the two groups. Conclusions: Antibody‐mediated rejection after ABO‐incompatible living kidney transplantation was significantly associated with the response to rituximab in our preconditioning protocol. [ABSTRACT FROM AUTHOR]

Here, we report the case of a patient with renal allograft with full‐house immunofluorescence staining in the zero‐hour biopsy. Full‐house immunofluorescence staining is a well‐known characteristic of lupus nephritis. Previous studies have reported patients with full‐house immunofluorescence staining, but without other symptoms or serological findings; this condition is referred to as full‐house nephropathy. We identified only one case out of 2203 zero‐hour biopsies over 13 years. Zero‐hour biopsy presented no glomerular changes but showed full‐house immunofluorescence staining. Electron microscopy revealed a nonorganized electron‐dense deposit mainly in the mesangial lesion. Systemic lupus erythematosus (SLE)‐associated antibodies were negative, and complement deficiency was not observed in the donor patients. Deposition of immunoglobulin and complement levels markedly decreased within 1–3 years post transplantation. Neither donor nor recipient developed clinical or biological features of SLE; they showed good renal prognosis. [ABSTRACT FROM AUTHOR]

Objective: To investigate the 10‐year biopsy‐proven recurrence rates and risk factors for immunoglobulin A nephropathy recurrence in kidney transplant recipients. Methods: We included 299 kidney transplant recipients from 1995 to 2015, who had biopsy‐proven underlying immunoglobulin A nephropathy and underwent zero‐hour biopsy. The primary end‐point was recurrence of immunoglobulin A nephropathy. We compared clinical, treatment and graft failure among those with and without recurrent immunoglobulin A nephropathy. A time‐to‐recurrence analysis was carried out using the competing risk analysis and time‐dependent Cox model. Results: Of 299 recipients, 80 had recurrent immunoglobulin A nephropathy (66.3% with clinical biopsy and 33.7% with protocol biopsy, post‐transplant biopsy rate: 90.6%). The 10‐year recurrence rate was 34.3% (95% confidence interval 27.6–41.1). Related‐donor transplantation (hazard ratio 2.28, P = 0.009) and post‐transplant increased proteinuria (hazard ratio 1.59, P < 0.001) were identified as potential risk factors for immunoglobulin A nephropathy recurrence. The 10‐year rates were 41.5% in related donor recipients and 16.3% in unrelated donor recipients. There was no conclusive evidence that the calcineurin inhibitor, antimetabolites, basiliximab and rituximab reduce immunoglobulin A nephropathy recurrence. Immunoglobulin A nephropathy recurrence was associated with an increased risk of death‐censored graft failure (hazard ratio 5.29, 95% confidence interval 1.39–20.17, P = 0.015). However, related donor itself was not associated with an increased risk of graft failure. Conclusions: The present results have clinical implications in that the signs of recurrent immunoglobulin A nephropathy should be evaluated carefully in recipients receiving related‐donor transplants. There is a need for further studies related to genetic and/or familial interactions in kidney transplant recipients with immunoglobulin A nephropathy and related donors. [ABSTRACT FROM AUTHOR]

Objective: To evaluate the change in the operated parenchymal volume during robot‐assisted partial nephrectomy limited to the enucleation technique, and to analyze the predictors of decrease in operated parenchymal volume, including the tumor contact surface area. Methods: The study included 135 patients who underwent robot‐assisted partial nephrectomy for T1 renal tumors using the enucleation technique. Measurements of the parenchymal volume, tumor volume and contact surface area were obtained in the venous phase on enhanced computed tomography. All measurements, including volumetric and renal function analysis, were carried out <2 months before and 6 months after surgery. Results: The mean age of included participants was 56 years, and the mean tumor size was 33 mm. The mean tumor volume was 26 cc, and the mean contact surface area was 22 cm2. In the complete cohort, the mean preoperative and postoperative normal parenchymal volumes of the operated kidney were 158 and 141 cc, respectively. The mean change in parenchymal volume of the operated kidney was −10%. In contrast, the mean change in global estimated glomerular filtration was just −4.0%. Univariate analysis showed that the RENAL nephrometry score, contact surface area, tumor volume and warm ischemia time were associated with the change in the operated kidney parenchymal volume. However, in the multivariate analysis, a large contact surface area was the only independent predictor of decreased operated parenchymal volume <10 cm3. Conclusion: Contact surface area is a strong predictor of the decrease in the parenchymal volume in the operated kidney during robot‐assisted partial nephrectomy carried out using the enucleation technique for T1 renal tumors. [ABSTRACT FROM AUTHOR]

ABO‐incompatible kidney transplantation (ABO‐ILKT) has been reported to have a higher rate of early complications and higher medical costs than ABO‐compatible kidney transplantation (ABO‐CLKT). We aimed to compare the clinical outcomes, complications, and medical costs between ABO‐ILKTs and ABO‐CLKTs at 2 years post‐transplantation. We included 65 ABO‐ILKTs and 94 ABO‐CLKTs in this retrospective analysis. The patient survival, graft survival, rejection incidence, and graft function were similar between ABO‐CLKT and ABO‐ILKT. The hospitalization costs for ABO‐CLKT and ABO‐ILKT were 26 544 ± 4168 USD and 34 906 ± 18 732 USD, respectively (P = 0.0001). Total 2‐year medical costs were 77 117 ± 15 609 USD and 85 325 ± 33 997 USD for ABO‐CLKT and ABO‐ILKT, respectively, indicating that the medical costs of ABO‐ILKT recipients were non‐significantly higher than those of ABO‐CLKT recipients at 2 years post‐transplantation (P = 0.0866). ABO‐ILKT and ABO‐CLKT recipients showed similar infectious adverse events and complications. In conclusion, medical cost at 2 years post‐transplantation, including transplant hospitalization cost, and the frequency of early complications were not significantly higher in the ABO‐ILKT group than in the ABO‐CLKT group. ABO‐ILKT is an acceptable treatment for patients with ESRD and is comparable to ABO‐CLKT not only in terms of outcomes but also in terms of medical cost. [ABSTRACT FROM AUTHOR]

Objective: To investigate peritumoral pseudocapsule status in patients with renal cell carcinoma who underwent robot‐assisted laparoscopic partial nephrectomy, and to examine predictive factors associated with the absence of peritumoral pseudocapsule. Methods: A total of 367 patients with clinical T1 renal cell carcinoma who underwent robot‐assisted laparoscopic partial nephrectomy were divided into two groups according to peritumoral pseudocapsule status. The groups were compared in terms of patient and tumor characteristics. Multivariate logistic regression analysis was carried out to identify predictive factors for the absence of peritumoral pseudocapsule. Results: Of the 367 tumors, 323 (88%) were surrounded by a peritumoral pseudocapsule. The mean tumor size was 30 mm, and 70% of the patients were male. Tumors with a peritumoral pseudocapsule had a larger diameter than those without (31 vs 26 mm; P = 0.0008). A peritumoral pseudocapsule was observed in 92% of the clear cell, in 89% of the papillary and in 86% of the clear cell papillary renal cell carcinoma cases compared with just 50% in the chromophobe renal cell carcinoma cases (P < 0.0001). Sex, age, Fuhrman grade and tumor complexity did not differ among patients. A multivariate analysis showed that smaller tumor size (≥34 vs <34 mm, odds ratio 3.31; P = 0.0023) and chromophobe renal cell carcinoma (vs other subtypes, odds ratio 12.5; P < 0.0001) predicted an absence of peritumoral pseudocapsule. Conclusions: Small tumor size and chromophobe renal cell carcinoma were significant predictors of a lack of peritumoral pseudocapsule, suggesting that a positive surgical margin must be avoided for these tumors when an enucleation technique is used for robot‐assisted laparoscopic partial nephrectomy. [ABSTRACT FROM AUTHOR]

Objective: To investigate kidney function change during adrenalectomy in patients with primary aldosteronism and assess predictors of kidney function decline. Methods: The present study included 90 patients who underwent adrenalectomy for primary aldosteronism between 2004 and 2017. Kidney function was evaluated 1 month after surgery. Predictors associated with a ≥10% decline in the estimated glomerular filtration rate were investigated. Kidney parenchymal volume was compared before and after surgery in 10 patients using volumetric studies. Results: The mean estimated glomerular filtration rate decline in the total cohort at 1 month after surgery was 13.3% (before: 72.9 mL/min/1.73 m2, after: 64.9 mL/min/1.73 m2, P < 0.0001). The mean serum plasma aldosterone concentration (before: 373 pg/mL vs after: 78 pg/mL, P < 0.0001) and potassium level (before: 3.7 mEq/L vs after: 3.9 mEq/L, P = 0.0001) were also significantly different after surgery. Age (odds ratio 6.37, P = 0.0006), preoperative plasma aldosterone concentration (odds ratio 3.12, P = 0.0209) and preoperative serum potassium level (odds ratio 2.87, P = 0.0010) were independent predictors of a ≥10% decline in estimated glomerular filtration rate. Volumetric studies in 10 patients showed that mean postoperative parenchymal volume was significantly decreased compared with the preoperative volume (263 cc vs 312 cc, P = 0.0003), with decreases in estimated glomerular filtration rate from 63 to 56 mL/min/1.73 m2 (P = 0.0146). Conclusions: Kidney function deterioration after adrenalectomy can be detected in patients with primary aldosteronism. Age, preoperative plasma aldosterone concentration and preoperative potassium level are significant predictors of a decrease in the estimated glomerular filtration rate. Normal parenchymal volume decreases in line with renal functional deterioration. [ABSTRACT FROM AUTHOR]

ABSTRACT: Proliferative glomerulonephritis with monoclonal immunoglobulin (Ig)G deposits (PGNMID) is a rare disease with a treatment that is not well established. Several cases of recurrent PGNMID after kidney transplantation have been documented, but almost all cases reported symptoms such as elevated serum creatinine and/or urinary protein levels; subsequently, episode biopsies were performed and a diagnosis was made. This is the case of a 27‐year‐old man who underwent living‐donor kidney transplantation. The aetiology of renal failure was membranoproliferative glomerulonephritis type III, which had been diagnosed at the age of 9 years. Protocol biopsy performed on postoperative day 62 revealed isolated granular C3 deposits in the glomerular capillaries and mesangium. We reviewed the native kidney biopsy and confirmed IgG3 deposition alone, with strong glomerular staining for lambda light chains and negative staining for kappa light chains. Accordingly, we re‐diagnosed the aetiology of his renal failure as PGNMID and suspected recurrent PGNMID in the early stage; therefore, we administered plasma exchange therapy. Thereafter, protocol biopsies were performed twice, which revealed persistent isolated C3 deposition; therefore, we made a diagnosis of recurrent PGNMID or C3 glomerulonephritis. Currently, the patient has normal renal function, with negative urine findings for >1 year. Here, we present the histological findings of consecutive allograft biopsies performed in this patient. [ABSTRACT FROM AUTHOR]

ABSTRACT: Aim: De novo membranous nephropathy (dnMN) contributes to graft failure, but the pathophysiology of the disease remains poorly understood. We defined cases exhibiting granular Immunoglobulin G (IgG) immunofluorescence staining but lacking dense deposits on electron microscopy as being of ‘dnMN stage 0’; we studied the associated clinicopathological features. Methods: We studied 4653 allograft biopsy specimens (from 1747 cases treated in the Department of Urology, Tokyo Women’s Medical University) and found 42 cases of allograft membranous nephropathy, of which 28 (1.6%) were diagnosed as dnMN. Of these, five cases (0.06%) fulfilled the criteria for dnMN stage 0. Results: All five cases were diagnosed based on biopsies indicating increased serum levels of creatinine. Proteinuria status varied from negative to 2+. The median period from transplantation to allograft biopsy was 4068 days. Four of the five cases exhibited suspicious antibody‐mediated rejection together with dnMN. The glomerular capillaries of all cases were C4d‐positive, as were the peritubular capillaries of three of the four ABO‐compatible transplants. In terms of IgG subclass, IgG1 and IgG3 predominated in all cases, and phospholipase A2 receptor status (evaluated via immunoreactivity) was negative in all cases. We examined two cases by immunoelectron microscopy using anti‐IgG and anti‐C4d antibodies. We found subendothelial and intramembranous deposits expressing both IgG and C4d, corresponding to positivity in immunofluorescence analysis. Conclusion: We confirmed the existence of dnMN stage 0 by focusing on granular IgG immunofluorescence positivity. [ABSTRACT FROM AUTHOR]

Objectives: To compare surgical outcomes, including renal function and the preserved renal parenchymal volume, between robot‐assisted laparoscopic partial nephrectomy and laparoscopic partial nephrectomy using propensity score‐matched analyses. Methods: In total, 253 patients, with a normal contralateral kidney, who underwent laparoscopic partial nephrectomy (n = 131) or robot‐assisted laparoscopic partial nephrectomy (n = 122) with renal arterial clamping between 2010 and 2015, were included. Patients’ background and tumor factors were adjusted by propensity score matching. Surgical outcomes, including postoperative renal function, complications, warm ischemia time and preserved renal parenchymal volume, evaluated by volumetric analysis, were compared between the surgical procedures. Results: After matching, 64 patients were assigned to each group. The mean age was 56–57 years, and the mean tumor size was 22 mm. Approximately 50% of patients had low complexity tumors (RENAL nephrometry score 4–7). The incidence rate of acute kidney failure was significantly lower in the robot‐assisted laparoscopic partial nephrectomy (11%) than laparoscopic partial nephrectomy (23%) group (P = 0.049), and warm ischemia time shorter in the robot‐assisted laparoscopic partial nephrectomy (17 min) than laparoscopic partial nephrectomy (25 min) group (P < 0.0001). The preservation rate of renal function, measured by the estimated glomerular filtration rate, at 6 months post‐surgery was 96% for robot‐assisted laparoscopic partial nephrectomy and 90% for laparoscopic partial nephrectomy (P < 0.0001). The preserved renal parenchymal volume was higher for robot‐assisted laparoscopic partial nephrectomy (89%) than laparoscopic partial nephrectomy (77%; P < 0.0001). The rate of perioperative complications, surgical margin status and length of hospital stay were equivalent for both techniques. Conclusions: Robot‐assisted laparoscopic partial nephrectomy allows to achieve better preservation of renal function and parenchymal volume than laparoscopic partial nephrectomy. [ABSTRACT FROM AUTHOR]

Objective To compare transplant outcomes among elderly (aged ≥60 years) and non-elderly recipients, and to evaluate the acceptability of elderly living donor kidney transplantation in practice after consideration of living donor type. Methods We included 830 adult patients with living donor kidney transplantation between 2000 and 2011 in this retrospective cohort study. We compared death-censored graft survival, patient survival, biopsy-proven rejection, complications, and renal function in elderly ( n = 119) and non-elderly recipients ( n = 278). Results There was no significant difference in 10-year death-censored graft survival ( P = 0.980). Corresponding patient survival rates in the elderly and non-elderly groups were 84.1% and 98.1%, respectively (hazard ratio 6.15, 95% confidence interval 2.12-17.82, P < 0.001). Elderly patients had more complications and chronic T-cell-mediated rejection. Factors associated with death in elderly recipients with functioning grafts were residual advanced recipient age ( hazard ratio 1.39), decreased hemoglobin ( hazard ratio 4.10), hepatitis B virus ( hazard ratio 7.89), hepatitis C virus ( hazard ratio 13.12) and elevated alanine aminotransferase ( hazard ratio 1.13). Conclusions Elderly living donor kidney transplantation seems to provide adequate acceptable outcomes. However, physicians should be cautious when evaluating elderly patients with hepatitis, and further studies are required to improve long-term outcomes. [ABSTRACT FROM AUTHOR]

We compared the clinical features, pathological features, and prognoses of patients with renal cell carcinoma (RCC) arising in the native kidney after kidney transplantation (RCC-transplant) or on hemodialysis (RCC-HD), and analyzed predictive factors for survival at a Japanese single institution. This cohort included 42 patients in the RCC-transplant group and 467 patients in the RCC-HD group. RCC-transplant patients were younger (53 years vs. 56 years, P = 0.0358) and had less frequent symptoms (12% vs. 27%, P = 0.0344) than RCC-HD patients. Although tumor size, tumor stage, and histological subtype were not significantly different, the RCC-transplant group had less frequent multifocal occurrences and ACDK. Overall 5-year survival (RCC-transplant, 80%; RCC-hemodialysis, 76%; P = 0.3217) and 5-year cancer-specific survival (CSS; RCC-transplant, 84%; RCC-hemodialysis, 89%; P = 0.8916) were not significantly different between the two groups. Tumor stage and grade were significant predictors for CSS. Although kidney transplantation and hemodialysis were not associated with CSS, tumor stage was an independent predictor of CSS. [ABSTRACT FROM AUTHOR]

Objectives To clarify the incidence rate of post-transplant diabetes mellitus and associated risk factors in Japanese kidney transplant recipients, and to explore which treatment components are most effective in reducing post-transplant diabetes mellitus. Methods We analyzed 849 Japanese non-diabetic adult recipients who had undergone living kidney transplantation and had received tacrolimus-based immunosuppression from 1996 to 2013 with a median follow-up of 5 years. Results In all, 127 patients developed post-transplant diabetes mellitus during the follow-up period. The incidence rate of post-transplant diabetes mellitus was 15.1% (95% confidence interval 12.7-17.5) at 5 years. Recipient age (hazard ratio 1.05, 95% confidence interval 1.05-1.06, P < 0.001 for every 5-year increase), obesity (hazard ratio 1.70, 95% confidence interval 1.06-2.73, P = 0.028), tacrolimus trough level at 2 weeks post-transplantation (hazard ratio 1.06, 95% confidence interval 1.03-1.09, P < 0.001 for a 1-ng/mL increase) and mycophenolate mofetil use (hazard ratio 0.46, 95% confidence interval 0.28-0.77, P = 0.003) were significant predictors of post-transplant diabetes mellitus. Estimated 5-year predicted incidence rate after adjusting for age and obesity was 9.4% for recipients with a low tacrolimus trough level, and receiving mycophenolate mofetil and 38.4% for recipients with a high tacrolimus trough level and not receiving mycophenolate mofetil. Conclusions Post-transplant diabetes mellitus is a common complication in Japan, similar to that in other Western countries. The present results show that an appropriate immunosuppressive regimen with a combination of tacrolimus and mycophenolate mofetil can reduce the likelihood of developing post-transplant diabetes mellitus. Clinical trials are required to confirm these findings. [ABSTRACT FROM AUTHOR]

Passenger lymphocyte syndrome (PLS) often occurs after ABO-mismatched solid organ and/or bone marrow transplantation between a donor and recipient. Viable donor B-lymphocytes transferred during organ transplantation produce antibodies against recipient red cell antigens, leading to hemolysis. The incidence of PLS has been reported to be around 9% after renal transplantation. A previous report showed that rituximab (Rit) was useful for treatment of PLS in allogeneic stem cell transplantation, bowel transplant and severe cases of hemolysis. However, the effectiveness of Rit in preventing PLS after renal transplantation has not yet been evaluated. The participants in this study were 85 patients who had undergone ABO-mismatched renal transplantation from January 2005 to April 2013. Rit was administered to these patients before transplantation. None of the patients that received Rit treatment developed PLS. Thus administration of Rit before transplantation effectively controlled the production of antibodies by B-lymphocytes, which probably prevented the development of PLS. [ABSTRACT FROM AUTHOR]

The low sensitivity of C4d immunoreactivity in peritubular capillaries ( PTCs) hinders its use in the diagnosis of chronic active antibody-mediated rejection ( CAAMR). C4d-negative CAAMR was defined in the 2013 Banff classification, which included the expression of endothelial-associated transcripts ( ENDATs). We previously showed that the ENDAT caveolin-1 ( CAV-1) is a distinct feature of CAAMR. In this study, we investigated the prognostic value of CAV-1 immunoreactivity in PTCs in kidney transplant patients. Ninety-eight kidney transplant recipients were included in this study. The prognostic value of CAV-1 immunoreactivity in PTCs was evaluated by double immunostaining for CAV-1 and pathologische Anatomie Leiden endothelium ( PAL-E, a PTC marker) in the PTCs of kidney allograft biopsy samples. The patients were divided into two groups: CAV-1/ PAL-E<50% and CAV-1/ PAL-E≥50%. Kaplan-Meier curves showed that CAV-1/ PAL-E≥50% patients had a significantly worse prognosis than that of CAV-1/ PAL-E<50% patients (log-rank; P<.001). C4d staining of PTCs was not associated with the development of graft failure (log-rank; P=.345), whereas in a multivariate Cox regression analysis, CAV-1 immunoreactivity in PTCs was independently associated with graft failure (hazard ratio: 11.1; P=.0324). CAV-1 immunoreactivity in PTCs may serve as a prognostic marker for kidney allograft survival. [ABSTRACT FROM AUTHOR]

Objective To evaluate the impact of pretransplant body mass index on graft failure and mortality in Japanese patients undergoing living kidney transplant. Methods A cohort of 888 living kidney transplant recipients who received standard immunosuppressive therapy between 2000 and 2013 were identified from the Japan Academic Consortium of Kidney Transplantation database. Pretransplant body mass index was divided into three categories according to the following tertiles: <19.4, 19.5-22.2 and ≥22.3 kg/m2. A multivariable time-to-event analysis was carried out. Results Estimated hazard ratios of the body mass index effects regarding graft failure were 1.62 (95% confidence interval 0.83-3.18) for the first tertile and 2.20 (95% confidence interval 1.24-3.90) for the third tertile. Patient mortality was 1.21 (95% confidence interval 0.32-4.54) for the first tertile and 1.52 (95% confidence interval 0.56-4.13) for the third tertile. In a subgroup analysis, the effects of body mass index according to sex were substantially heterogeneous ( P = 0.029 for interaction). Pretransplant body mass index had a non-linear J-shaped association with graft failure that resulted from qualitative interaction between body mass index and the recipient's sex. Conclusions Sex differences and interaction effects must be considered when evaluating the effects of pretransplant body mass index on post-transplant outcomes in Japanese patients undergoing living kidney transplant. [ABSTRACT FROM AUTHOR]

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 m2, 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 m2, 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. [ABSTRACT FROM AUTHOR]

Aim We carried out a clinicopathological analysis of cases presenting with interstitial fibrosis and tubular atrophy (IF/TA) after renal transplantation in an attempt to clarify the mechanisms underlying the development and prognostic significance of IF/TA. Methods IF/TA was diagnosed in 35 renal allograft biopsy specimens (BS) obtained from 35 renal transplant recipients under follow up at the Department of Transplant Surgery, Kidney Center, Toda Chuo General Hospital, between January 2014 and March 2015. Results IF/TA was diagnosed at a median of 39.9 months after the transplantation. Among the 35 patients with IF/TA, 19 (54%) had a history of acute rejection. Among the 35 BS showing evidence of IF/TA, the IF/TA was grade I in 25, grade II in 9, and grade III in 1. Arteriosclerosis of the middle-sized arteries was observed in 30 BS (86%). We then classified the 35 BS showing evidence of IF/TA according to their overall histopathological features, as follows; IF/TA alone (6 BS; 17%), IF/TA + medullary ray injury (12 BS; 34%), and IF/TA + rejection (12 BS; 34%). Loss of the renal allograft occurred during the observation period in one of the patients (3%). Of the remaining patients with functioning grafts, deterioration of the renal allograft function after the biopsies occurred in 15 patients (43%). Conclusions The results of our study suggests that rejection contributes to IF/TA in 30-40% of cases, medullary ray injury in 30-40% of cases, and nonspecific injury in 20% of cases. IF/TA contributes significantly to deterioration of renal allograft function. [ABSTRACT FROM AUTHOR]

Transplantation-associated thrombotic microangiopathy (TA-TMA) is relatively rare and requires immediate intervention to avoid irreversible organ damage or death; however, consensus regarding the treatment approach is lacking. Atypical haemolytic uraemic syndrome (aHUS) is a rare disease caused by dysregulation of the alternative complement pathway resulting in TMA. aHUS is histologically similar to TA-TMA; approximately 60% of TA-TMA patients have complement dysregulation. Eculizumab, a humanized anti-C5 monoclonal antibody, inhibits terminal membrane-attack complex formation and TMA progression. Eculizumab has been successfully used to treat aHUS post-transplant. We present two cases of kidney TA-TMA due to unknown causes, suspected antibody-mediated rejection, or calcineurin inhibitor (CNI)-related toxicity that developed on day 1 or 2 post-kidney transplantation. Low platelet count and haemoglobin level with red cell fragments were detected. Despite steroid pulse, plasma exchange (PE), and intravenous immunoglobulin therapy, TA-TMA did not improve; therefore, eculizumab was administered despite no genetic testing. Laboratory data, including renal function, improved immediately. TA-TMA treatment primarily involves PE initiation or CNI discontinuation; eculizumab can be used to safely treat TA-TMA and then be ceased in the short term. Therefore, eculizumab administration might be beneficial for kidney TA-TMA as early as the diagnosis of refractory to PE. [ABSTRACT FROM AUTHOR]

Immunoglobulin (Ig) A nephropathy (IgAN) is a known autoimmune disease due to abnormal glycosylation of IgA1, and occasionally, IgG co-deposition occurs. The prognosis of IgG co-deposition with IgAN is adverse, as shown in the previous studies. However, in the clinical setting, monoclonality of IgG co-deposition with IgAN has not been observed. We describe a case of proliferative glomerulonephritis with monoclonal IgG deposits (PGNMID) combined with IgAN in a renal allograft. A-21-year-old man developed end-stage renal failure with unknown aetiology and underwent living-donor kidney transplantation from his mother 2 years after being diagnosed. One year after kidney transplantation, proteinuria 2+ and haematuria 2+ were detected; allograft biopsy revealed mesangial IgA and C3 deposits, indicating a diagnosis of IgAN. After tonsillectomy and steroid pulse therapy, proteinuria and haematuria resolved. However, 4 years after transplantation, pedal oedema, proteinuria (6.89 g/day) and allograft dysfunction (serum creatinine (sCr) 203.3 µmol/L) appeared. A second allograft biopsy showed mesangial expansion and focal segmental proliferative endocapillary lesions with IgA1λ and monoclonal IgG1κ depositions. Electron microscopic analysis revealed a massive amount of deposits, located in the mesangial and subendothelial lesions. A diagnosis of PGNMID complicated with IgAN was made, and rituximab and plasmapheresis were added to steroid pulse therapy. With this treatment, proteinuria was alleviated to 0.5 g/day, and the allograft dysfunction recovered to sCr 132.6 µmol/L. This case suggests a necessity for investigation of PGNMID and IgA nephropathy in renal allografts to detect monoclonal Ig deposition disease. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Aim Calcineurin inhibitors reduce the acute rejection rate and greatly improve renal allograft survival. However, they are associated with some adverse events, including nephrotoxicity, a risk factor for allograft failure. Chronic calcineurin inhibitor-induced nephrotoxicity causes irreversible damage to renal components, such as arteriolar hyaline thickening. The aim of this study is to investigate the risk factors for tacrolimus-induced chronic nephrotoxicity using zero-time biopsy specimens. Methods Between January 2001 and December 2010, 483 patients who underwent living-related kidney transplantation and had also been placed on a tacrolimus-based regimen were enrolled in this study. There were 1859 specimens evaluated comprising 483 zero-time biopsy specimens and 1376 protocol and for-cause biopsy specimens. De novo arteriolar hyaline thickening due to tacrolimus-induced chronic nephrotoxicity was scored according to the Banff classification aah score. In this study, tacrolimus-induced nephrotoxicity was defined as a positive aah score. Results Of the 483 patients, 108 patients (22.4%) had biopsy-proven tacrolimus-induced chronic nephrotoxicity. Multivariate analysis showed that interlobular arteriosclerosis proven by zero-time biopsy ( OR: 2.23, 95% CI: 1.38-3.58, P < 0.01) and acute rejection episodes ( OR: 1.58, 95% CI: 1.00-2.47, P = 0.04) were independent risk factors for tacrolimus-induced chronic nephrotoxicity. However, tacrolimus-induced chronic nephrotoxicity did not affect long-term graft survival. Conclusion This is the first report showing that arteriosclerosis in zero-time biopsy specimens is a risk factor for histological tacrolimus-induced chronic nephrotoxicity. [ABSTRACT FROM AUTHOR]

Aim We discuss the clinicopathological analysis of cases of chronic vascular rejection ( CVR) cases after renal transplantation and clarify the mechanisms underlying the development and prognostic significance of CVR. Patients CVR was diagnosed in 46 renal allograft biopsy specimens ( BS) obtained from 34 renal transplant patients being followed up at the Department of Urology, Tokyo Women's Medical University, between January 2009 and December 2013. Results CVR was diagnosed at a median of 47.4 months post-transplant. Among the 36 patients, 23 had a history of acute rejection. Among the 46 BS showing evidence of CVR, the CVR was mild (cv1 in Banff's classification) in 23, moderate (cv2) in 17, and severe (cv3) in 6. Of the 40 samples obtained at the time of the biopsy and assayed with plastic beads coated with HLA antigen, 31 (78%) showed circulating ant- HLA alloantibody, and 15 (38%) showed donor-specific antibodies. We then classified the 46 BS showing evidence of CVR by their overall histopathological features, as follows; cv alone was seen in 16 (35%) BS, cv + antibody-mediated rejection ( AMR) in 26 (56%), and cv + T-cell-mediated rejection in 9 (19%). Loss of the renal allograft occurred during the observation period in nine of the patients (26%). Of the remaining patients with functioning grafts, deterioration of the renal allograft function after the biopsies occurred in 11 patients (32%). Conclusion The results of our study suggest that AMR may underlie CVR in many cases, while T cell-mediated rejection may play an important role in some cases. [ABSTRACT FROM AUTHOR]

Previous studies have reported negative impacts of long-term dialysis on kidney transplantation ( KTx) outcomes. However, advances in surgical techniques, immunosuppressive therapies, and post-transplant monitoring have led to an impressive increase in patient and allograft survival. Thus, the number of KTx among patients on long-term dialysis is increasing. We evaluated the influence of dialysis duration on the outcome of living donor KTx. Between January 2000 and October 2011, we performed 1098 first KTx from living donors in adults (>18 years). We divided the patients into six groups, A group: pre-emptive kidney transplantation, B group: <24 months duration of dialysis, C group: 25-60 months duration, D group: 61-120 months duration, E group: 121-240 months duration, and F group: ≥241 months duration. The 5-year patient survival rates were 95.7, 98.8, 99.0, 99.0, 97.3, and 100% in groups A- F, respectively. The 5-year graft survival rates were 91.3, 95.6, 94.2, 96.3, 90.7, and 100% in groups A- F, respectively. No significant differences were observed in patient or graft survival among the six groups. Longer dialysis duration was correlated with lower rates of preoperative hypertension and diabetes mellitus. Survivors of long-term dialysis tended to be in good compliance with self-management. If recipients of living KTx have few complications, good prognoses are expectable even if dialysis periods are very long. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

We investigated the risk factors for recurrence of IgA nephropathy after kidney transplantation. Of the 184 recipients of allografts for end-stage renal disease caused by primary IgA nephropathy at our institution and affiliated hospitals between 1990 and 2005, 70 developed recurrent IgA nephropathy (group 1), while the remaining 114 did not develop recurrent IgA nephropathy (group 2). The diagnosis of recurrent IgA nephropathy was based on case and/or protocol renal biopsies. We examined the risk factors for recurrence of IgA nephropathy by comparing the two groups. In addition, we also investigated the risk factors for graft loss in the patients with recurrent IgA nephropathy. The recipient's age at transplantation was significantly younger in group 1 than in group 2 (33.4 ± 10.4 vs. 36.7 ± 10.7, P = 0.037). No significant influence of the immunosuppressive regimens used was observed on the likelihood of recurrence of IgA nephropathy. In the analysis of the risk factors for graft loss, the mean age of the donor was significantly higher in the patient group with graft loss (59.1 ± 9.5 vs. 53.9 ± 9.0, P = 0.033), and the serum creatinine level at one year after surgery was also significantly higher in the patient group with graft loss (1.62 ± 0.52 vs. 1.34 ± 0.34, P = 0.022). Recipients with recurrent IgA nephropathy after transplantation, especially younger patients, need to be followed up carefully. [ABSTRACT FROM AUTHOR]

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

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

Shirakawa H, Ishida H, Shimizu T, Omoto K, Iida S, Toki D, Tanabe K. The low dose of rituximab in ABO-incompatible kidney transplantation without a splenectomy: a single-center experience. Clin Transplant 2011: 25: 878-884. © 2010 John Wiley & Sons A/S. Abstract: 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. [ABSTRACT FROM AUTHOR]

Shimizu T, Ishida H, Tanabe T, Shirakawa H, Tanabe K, Honda K, Koike J. A case of transplant glomerulopathy early after kidney transplantation. Clin Transplant 2011: 25 (Suppl. 23): 34-38. © 2011 John Wiley & Sons A/S. Transplant glomerulopathy (TG) has commonly been described as a late manifestation of allograft injury, occurring years after renal transplantation. We describe herein a patient who developed TG early (49 days) after kidney transplantation (KTx). A 44-yr-old woman received a second living-related KTx from her younger brother in October 2009. Pre-transplant donor-specific anti-human leukocyte antigen antibodies (DSA) were positive for both class I and class II. During the renal transplant operation, she suffered from hyperacute antibody-mediated rejection (AMR) and intravenous immune globulin therapy was immediately performed. Once hyperacute AMR was resolved, accelerated acute AMR occurred on the first post-transplant day (PTD). The renal allograft biopsy performed on PTD 19 diagnosed acute AMR type II. The renal allograft biopsy performed on PTD 49 showed focal lesions of double contours of glomerular basement membranes in some glomeruli. Interstitial fibrosis showed a strong, diffuse staining of C4d in peritubular capillaries (PTCs). The DSA examined on PTD 39 were still positive for both class I and class II. From these histopathological findings of TG, C4d deposition in PTC and presence of circulating DSA, we diagnosed this case to have c-AMR. TG might be recognized in early after KTx. [ABSTRACT FROM AUTHOR]

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

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. [ABSTRACT FROM AUTHOR]