Higher Donor Age and Severe Microvascular Inflammation Are Risk Factors for Chronic Rejection After Treatment of Active Antibody-Mediated Rejection.

Recent developments in intensive desensitization protocols have enabled kidney transplantation in human leukocyte antigen (HLA)-sensitized recipients. However, cases of active antibody-mediated rejection (AABMR), when they occur, are difficult to manage, graft failure being the worst-case scenario. We aimed to assess the impact of our desensitization and AABMR treatment regimen and identify risk factors for disease progression. Among 849 patients who underwent living-donor kidney transplantation between 2014 and 2021 at our institution, 59 were diagnosed with AABMR within 1 year after transplantation. All patients received combination therapy consisting of steroid pulse therapy, intravenous immunoglobulin, rituximab, and plasmapheresis. Multivariable analysis revealed unrelated donors and preformed donor-specific antibodies as independent risk factors for AABMR. Five-year death-censored graft survival rate was not significantly different between patients with and without AABMR although 27 of 59 patients with AABMR developed chronic AABMR (CABMR) during the study period. Multivariate Cox proportional hazard regression analysis revealed that a donor age greater than 59 years and microvascular inflammation (MVI) score (g + ptc) ≥4 at AABMR diagnosis were independent risk factors for CABMR. Our combination therapy ameliorated AABMR; however, further treatment options should be considered to prevent CABMR, especially in patients with old donors and severe MVI.

Letermovir safety and efficacy for cytomegalovirus prophylaxis in adult Japanese kidney transplant recipients: a multicenter, open-label, noncomparative Phase 3 study.

BACKGROUND: Letermovir is approved for cytomegalovirus (CMV) prophylaxis in adult allogeneic hematopoietic cell transplantation recipients worldwide and is also approved in the United States for CMV prophylaxis in adult high-risk (D+/R-) kidney transplant recipients (KTRs). The safety and efficacy of letermovir for CMV prophylaxis in adult Japanese KTRs are reported here. METHODS: In this Phase 3, single-arm, open-label study, adult Japanese KTRs with CMV serostatuses D+/R-, D+/R+, and D-/R+ received letermovir 480 mg daily orally within 7 days post-transplant through Week 28. Participants were followed through Week 52. The primary objective was to evaluate letermovir safety and tolerability. Efficacy was a secondary objective, measured by CMV disease, CMV disease or infection requiring intervention, and quantifiable CMV DNAemia. All CMV disease cases were confirmed by an independent adjudication committee. RESULTS: Among 22 participants (12 were D+/R-) who received letermovir prophylaxis, 20 (90.9%) experienced ≥ 1 AE through Week 28. Most AEs were mild to moderate in severity; no deaths were reported. During the prophylaxis period through Week 28, one transient case of quantifiable CMV DNAemia was detected, but no CMV disease or infection requiring intervention was reported. Through Week 52, four D+/R- participants met the endpoint of CMV disease or infection requiring intervention, of whom two had committee-confirmed CMV syndrome; all recovered with CMV therapy. A total of 5 participants had quantifiable CMV DNAemia through Week 52. CONCLUSION: Letermovir was generally well tolerated, and the data support its use for the prevention of CMV disease/infection in adult Japanese KTRs. TRIAL REGISTRATION: ClinicalTrials.gov NCT04129398.

Renal outcome of living kidney donors aged more than 70 years.

BACKGROUND: The number of marginal living kidney donors has increased. Medically complex donors who have hypertension, older age, or low estimated glomerular filtration rate (eGFR) have been more likely to be used. METHODS: We conducted a retrospective cohort study of living kidney donors at a single center. We analyzed 309 living donors and divided them into three groups: group with older donors (aged ≥70 years) (n = 41), middle-aged (aged 46-69 years) (n = 239), and young donors (aged <46 years) (N = 29). Donor factors associated with chronic kidney disease (CKD) stage 3b or worse within 5 years post-donation were investigated. RESULTS: Of the 309 live donors, 86 (27.8%) developed CKD stage3b or worse within 5 years post-donation. The incidence of CKD stage3b or worse within 5 years post-donation was significantly higher in older donor (p < 0.01). Cox regression models revealed that older donor ages and lower eGFR were significantly related to the development of CKD stage3b or worse, independent of comorbidities such as obesity and hypertension [hazard ratio (95% CI); 4.59 (1.02-20.6), p = 047, 0.95 (0.94-0.96), p ≤ 0.01, respectively]. However, recovery of eGFR 4-5 years after donation was noted in the middle-aged and older donor groups, whereas the level of eGFR remained unchanged in the young group. CONCLUSIONS: Older donors tend to develop CKD stage3b within 5 years post-donation but with the potential of recovery. Healthy older people (aged ≥70 years) could be candidates for living donors under careful monitoring of kidney function after donation.

The medical cost and outcome of desensitization protocol in kidney transplantation recipients with high immunological risks.

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.

Comparison of BNT162b2 and mRNA1273 vaccines in solid organ transplant recipients: Post-Hoc analysis of a Japanese national prospective study.

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.

Pregnancy Complications and Impact on Kidney Allograft After Kidney Transplantation in IgA Nephropathy.

Pregnancy in kidney transplantation (KT) recipients has been challenging because of the high risk of maternal, fetal, and renal complications. Although patients with immunoglobulin A nephropathy (IgAN)-chronic kidney disease (CKD) are at a high risk for hypertension in pregnancy (HIP), the maternal risk in KT recipients with IgAN as the etiology remains unclear. We retrospectively reviewed the medical records of pregnant KT recipients who delivered at our hospital. The incidence of maternal and fetal complications and the impact on kidney allografts between the group with IgAN as the primary kidney disease and the group with other primary diseases were compared. The analysis included 73 pregnancies in 64 KT recipients. The IgAN group had a higher incidence of HIP than the non-IgAN group (69% vs. 40%, p = 0.02). IgAN as primary kidney disease and interval from transplantation to conception were associated with HIP (OR 3.33 [1.11-9.92], p = 0.03, OR 0.83 [0.72-0.96], p < 0.01, respectively). The 20-year graft survival or prevention of CKD stage 5 in group with IgAN was lower than that in the group with other primary disease (p < 0.01). KT recipients should be informed of the risk of HIP and possibility of long-term worsening of postpartum renal function.

Long-term prolonged-release tacrolimus outcomes in living donor kidney transplantation: The Japan Academic Consortium of Kidney Transplantation study-II.

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.

Significance of revised criteria for chronic active T cell-mediated rejection in the 2017 Banff classification: Surveillance by 1-year protocol biopsies for kidney transplantation.

Diagnostic criteria for chronic active T cell-mediated rejection (CA-TCMR) were revised in the Banff 2017 consensus, but it is unknown whether the new criteria predict graft prognosis of kidney transplantation. We enrolled 406 kidney allograft recipients who underwent a 1-year protocol biopsy (PB) and investigated the diagnostic significance of Banff 2017. Interobserver reproducibility of the 3 diagnosticians showed a substantial agreement rate of 0.68 in Fleiss's kappa coefficient. Thirty-three patients (8%) were classified as CA-TCMR according to Banff 2017, and 6 were previously diagnosed as normal, 12 as acute TCMR, 10 with borderline changes, and 5 as CA-TCMR according to Banff 2015 criteria. Determinant factors of CA-TCMR were cyclosporine use (vs tacrolimus), previous acute rejection, and BK polyomavirus-associated nephropathy. In survival analysis, the new diagnosis of CA-TCMR predicted a composite graft endpoint defined as doubling serum creatinine or death-censored graft loss (log-rank test, P < .001). In multivariate analysis, CA-TCMR was associated with the second highest risk of the composite endpoint (hazard ratio: 5.42; 95% confidence interval, 2.02-14.61; P < .001 vs normal) behind antibody-mediated rejection. In conclusion, diagnosis of CA-TCMR in Banff 2017 may facilitate detecting an unfavorable prognosis of kidney allograft recipients who undergo a 1-year PB.

Influence of a low-dose tacrolimus protocol on the appearance of de novo donor-specific antibodies during 7 years of follow-up after renal transplantation.

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.

Development and validation of a risk score for the prediction of cardiovascular disease in living donor kidney transplant recipients.

BACKGROUND: Cardiovascular disease (CVD) is a major cause of death in kidney transplant (KT) recipients. To improve their long-term survival, it is clinically important to estimate the risk of CVD after living donor KT via adequate pre-transplant CVD screening. METHODS: A derivation cohort containing 331 KT recipients underwent living donor KT at Kyushu University Hospital from January 2006 to December 2012. A prediction model was retrospectively developed and risk scores were investigated via a Cox proportional hazards regression model. The discrimination and calibration capacities of the prediction model were estimated via the c-statistic and the Hosmer-Lemeshow goodness of fit test. External validation was estimated via the same statistical methods by applying the model to a validation cohort of 300 KT recipients who underwent living donor KT at Tokyo Women's Medical University Hospital. RESULTS: In the derivation cohort, 28 patients (8.5%) had CVD events during the observation period. Recipient age, CVD history, diabetic nephropathy, dialysis vintage, serum albumin and proteinuria at 12 months after KT were significant predictors of CVD. A prediction model consisting of integer risk scores demonstrated good discrimination (c-statistic 0.88) and goodness of fit (Hosmer-Lemeshow test P = 0.18). In a validation cohort, the model demonstrated moderate discrimination (c-statistic 0.77) and goodness of fit (Hosmer-Lemeshow test P = 0.15), suggesting external validity. CONCLUSIONS: The above-described simple model for predicting CVD after living donor KT was accurate and useful in clinical situations.

Effect of renin-angiotensin system blockade on graft survival and cardiovascular disease in kidney transplant recipients: retrospective multicenter study in Japan.

BACKGROUND: Renin-angiotensin system blockers (RASBs) reduce end-stage kidney disease and cardiovascular event (CVE) development in chronic kidney disease. However, whether RASBs improve long-term prognosis in kidney transplant (KT) recipients remain unknown. METHOD: We investigated 900 kidney transplant patients in a multicenter retrospective cohort study in Japan and compared death-censored graft survival and CVE (total, cardiac events, stroke) based on RASB use within 12 months after KT. The associations were examined using a Cox hazard model and propensity score-matching analysis. RESULTS: The cohort comprised 375 patients treated with RASBs (RASB group) and 525 patients without RASBs (control group). The median observational period was 82 months, with 68 patients reaching graft loss: 79 total CVE, 36 cardiac events, 26 stroke. In a matching cohort comprising 582 patients, death-censored graft survival, total CVE, and cardiac events were not different between the two groups. Only stroke incidence rate was significantly lower in the RASB group compared with the control group (1.4 vs. 6.4 per 1000 patients/year, log-ranked P = 0.005). In a multivariable analysis, stroke events were also significantly lower in the RASB group compared with the control group (Hazard ratio and 95% confidence interval, 0.20 [0.04-0.62]). CONCLUSION: Thus, RASBs potentially reduce stroke events in KT recipients.

Impact of donor-related arteriosclerosis in pretransplant biopsy on long-term outcome of living-kidney transplantation: A propensity score-matched cohort study.

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.

Outcomes, complications, and economic impact of ABO-incompatible living kidney transplantation: A single-center Japanese cohort study.

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.

Fate of full-house immunofluorescence staining in renal allograft: A case report.

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.

The interaction between post-transplant anemia and allograft function in kidney transplantation: The Japan Academic Consortium of Kidney Transplantation-II study.

BACKGROUND: The interaction between post-transplant anemia (PTA) and allograft function in kidney transplantation has not been evaluated directly. PTA, defined by WHO/AST criteria, was investigated in 1307 adult kidney transplant recipients between 2000 and 2015 (median follow-up, 7 years). METHODS: We investigated the impact of hemoglobin (Hb) on graft failure (non-censored for death) and their interactions, time-dependent Cox model, and subgroup analysis were used. RESULTS: PTA prevalence was 43.6% at 7 years and varied according to allograft function, recipient sex, and follow-up period. Decreased Hb considering the time-varying effect was associated with an increased risk of graft failure (hazard ratio = 1.83, 95% CI 1.66-2.02, P < 0.001). In subgroup analysis, allograft function (post-transplant time-averaged estimated glomerular filtration rate and cut point: 45 mL/min/1.73 m2) had significant interaction (P = 0.032). The 7-year graft failure rate in recipients with PTA and high eGFR was 7.7% (HR 1.52, 95% CI 1.25-1.84), whereas in those with PTA and low eGFR was 19.9% (HR 2.00, 95% CI 1.74-2.31). CONCLUSIONS: The unfavorable impact of PTA was significantly enhanced by low allograft function. PTA is likely to be associated with graft failure due to interaction with allograft function. Therefore, we should consider both Hb level and allograft function while determining the treatment strategy.

Serum Magnesium Levels and Mortality in Japanese Maintenance Hemodialysis Patients.

BACKGROUND/AIMS: Although hypomagnesemia was found to be a risk for cardiovascular diseases in the general population, the relationship between serum magnesium (Mg) levels and prognosis of patients on maintenance hemodialysis (MHD) has not been extensively studied. This study sought to determine the relationship of serum Mg levels with aortic arch calcification (AoAC) and mortality in Japanese MHD patients. METHODS: We measured serum Mg levels in a cohort of 392 patients on MHD, classified the patients into 3 groups according to these levels, and followed their course for 4 years. AoAC was assessed using chest-X-rays. RESULTS: During follow-up, there were 117 deaths. Kaplan-Meier analyses showed that the high serum Mg group tended to have better survival rates than the low and middle serum Mg groups but this did not reach statistical significance. We also found that patients in the high serum Mg group had better nutritional status associated with higher serum albumin, triglyceride, and phosphate levels and had a significantly lower serum C-reactive protein level. In total, 83 patients (59.3%) in the high serum Mg group had been prescribed Mg oxide (MgO). CONCLUSIONS: Hypermagnesemia tended to be associated with better survival and a higher prescription rate of MgO. Interventional studies are needed to clarify whether Mg supplementation is beneficial for improving patient prognosis.

Association between response to rituximab and antibody-mediated rejection in ABO-incompatible living kidney transplantation.

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.

Higher immunoglobulin A nephropathy recurrence in related-donor kidney transplants: The Japan Academic Consortium of Kidney Transplantation study.

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.

Once-daily vs twice-daily tacrolimus for de novo living kidney transplantation patients including ABO/HLA compatible and incompatible: A randomized trial.

Tacrolimus (TAC) is available as a twice-daily capsule (TAC-BID), once-daily capsule (TAC-QD), and once-daily tablet. Recipients with ABO-incompatible/anti-human leukocyte antigen (HLA)-incompatible transplantation were excluded in previous trials and have thus not been evaluated. We conducted a 5-year trial to determine whether TAC-QD is noninferior to TAC-BID for transplant outcomes. Adults who underwent de novo living kidney transplantation were randomly assigned (62 TAC-QD; 63 TAC-BID). We did not exclude ABO-/HLA- incompatible transplantation. TAC was initiated 7 days preoperatively (0.10 mg/kg/d). Mycophenolate mofetil, methylprednisolone, and basiliximab were administered. The primary endpoint was graft failure (non-censored for death). We performed a noninferiority test. The noninferiority margin was 10% in risk difference. Five-year graft failure rates were 6.5% and 9.5% for TAC-QD and TAC-BID, respectively (noninferiority, P = 0.009). The estimated glomerular filtration rates were similar between the groups (noninferiority, P < 0.001). TAC-QD did not have point estimates of risk difference above the inferiority margin in any assessed endpoints. However, a tendency of interaction was observed between biopsy-proven acute rejection and the follow-up period. In a living kidney transplant population with 40% of patients with ABO/HLA incompatibility, the effect of TAC-QD was not appreciably worse on various clinical transplant outcomes than that of TAC-BID over 5 years.

Outcome of the risk-stratified desensitization protocol in donor-specific antibody-positive living kidney transplant recipients: a retrospective study.

Acceptable outcomes of donor-specific antibody (DSA)-positive living kidney transplantation (LKT) have recently been reported. However, LKT in crossmatch (XM)-positive patients remains at high-risk and requires an optimal desensitization protocol. We report our intermediate-term outcomes of XM-positive LKT vs. XM-negative LKT in patients who underwent LKT between January 2012 and June 2015 in our institution. The rate of acute antibody-mediated rejection (ABMR) within 90 days postoperation, graft function, and patient, and graft survival rates at 4 years were investigated. Patients were divided into three groups: XM-DSA- (n = 229), XM-DSA+ (n = 36), and XM + DSA+ (n = 15). The XM + DSA+ group patients underwent desensitization with high-dose intravenous immunoglobulin, plasmapheresis, and rituximab. The rates of ABMR within 90 days in the XM-DSA-, XM-DSA+, and XM + DSA+ groups were 1.3%, 9.4%, and 60.0%, respectively (P < 0.001). There were no significant differences in the graft function throughout the observational period, the 4-year patient or graft survival rates among three groups. This study showed that intermediate-term outcomes of XM-positive LKT were comparable to XM-negative LKT. However, our current desensitization protocol cannot avert ABMR within 90 days, and XM positivity is still a significant risk factor for ABMR. Further refinement of the current desensitization regimen is required.