Recent cross‐sectional studies suggest an important role for transitional B lymphocytes (CD19 + CD24hiCD38hi) in promoting transplant tolerance, and protecting from late antibody‐mediated rejection (ABMR). However, prospective studies are lacking. This study enrolled 73 de novo transplant recipients, and collected serial clinical, immunological and biochemical information over 48 ± 6 months. Cell phenotyping was conducted immediately prior to transplantation, and then on five occasions during the first year posttransplantation. When modeled as a time‐dependent covariate, transitional B cell frequencies (but not total B cells or “regulatory” T cells) were associated with protection from acute rejection (any Banff grade; HR: 0.60; 95% CI: 0.37–0.95; p = 0.03). No association between transitional B cell proportions and either de novo donor‐specific or nondonor‐specific antibody (dnDSA; dnNDSA) formation was evident, although preserved transitional B cell proportions were associated with reduced rejection rates in those patients developing dnDSA. Three episodes of ABMR occurred, all in the context of nonadherence, and all associated with in vitro anti‐HLA T cell responses in an ELISPOT assay (p = 0.008 versus antibody‐positive patients not experiencing ABMR). This prospective study supports the potential relevance of transitional (“regulatory”) B cells as a biomarker and therapeutic intervention in transplantation, and highlights relationships between humoral immunity, cellular immunity and nonadherence.

Calcineurin-inhibitor-sparing strategies in kidney transplantation may spare patients the adverse effects of these drugs, but the efficacy of these strategies is unknown. Here, we conduct a meta-analysis to assess outcomes associated with reducing calcineurin inhibitor exposure from the time of transplantation. We search Medline, Embase, and Cochrane Register of Controlled Trials for randomized controlled trials published between 1966 and 2010 that compared de novo calcineurin-inhibitor-sparing regimens to calcineurin-inhibitor-based regimens. In this analysis, we include 56 studies comprising data from 11337 renal transplant recipients. Use of the contemporary agents belatacept or tofacitinib, in combination with mycophenolate, decreased the odds of overall graft failure (OR 0.61; 95% CI 0.39 -0.96; P ϭ 0.03). Similarly, minimization of calcineurin inhibitors in combination with various induction and adjunctive agents reduces the odds of graft failure (OR 0.73; 95% CI 0.58 -0.92; P ϭ 0.009). Conversely, the use of inhibitors of mammalian target of rapamycin (mTOR), in combination with mycophenolate, increases the odds of graft failure (OR 1.43; 95% CI 1.08 -1.90; P ϭ 0.01). Calcineurin-inhibitor-sparing strategies are associated with less delayed graft function (OR 0.89; 95% CI 0.80 -0.98; P ϭ 0.02), improved graft function, and less new-onset diabetes. The more contemporary protocols did not seem to increase rates of acute rejection. In conclusion, this meta-analysis suggests that reducing exposure to calcineurin inhibitors immediately after kidney transplantation may improve clinical outcomes.

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SummaryDiagnosing new onset diabetes after transplantation (NODAT) by glycated haemoglobin (HbA1c) has not been validated against the gold-standard oral glucose tolerance test (OGTT). We analysed the predictive and optimum value of HbA1c to diagnose NODAT amongst nondiabetic renal transplant recipients. Assessment of glucose metabolism (OGTT and HbA1c) was prospectively undertaken at 3 and 12 months post-transplantation in 71 nondiabetic renal transplant recipients. Receiver operator characteristic (ROC) curve analyses were performed to determine accuracy, sensitivity, specificity and area under curve (c-statistic). Incidence of NODAT at 3 and 12 months post-transplantation was 14.3% and 9.5% respectively. At 3 months, optimum HbA1c cut-off value for predicting NODAT based on fasting glucose was 7.35 [AUC 1.00 (sensitivity 100.0%, specificity 100.0%, P = 0.004)] and for postprandial glucose-defined NODAT was 6.20 [AUC 0.98 (sensitivity 100.0%, specificity 88.9%, P < 0.001)]. At 12 months, optimum HbA1c cut-off value for both fasting-and postprandial glucose-defined NODAT was 6.45 [AUC 0.92 (sensitivity 100.0%, specificity 87.5%, P = 0.048) and AUC 0.84 (sensitivity 75.0%, specificity 89.5%, P = 0.026) respectively]. Concordance between diagnosis of NODAT (OGTT+, HbA1c+) and nondiagnosis of NODAT (OGTTÀ, HbA1cÀ) was 88.9% and 98.7% respectively. To conclude, HbA1c ( ! 6.5%) can be utilized to diagnose NODAT beyond 3 months post-transplantation but the OGTT remains the gold-standard tool.