BK polyomavirus (BKPyV) causes premature kidney transplant (KT) failure in 1–15% of patients. Because antivirals are lacking, most programs screen for BKPyV‐viremia and, if positive, reduce immunosuppression. To evaluate the relationship of viremia and BKPyV‐specific immunity, we examined prospectively cryopreserved plasma and peripheral blood mononuclear cells at the time of transplantation (T0) and at 6 mo (T6) and 12 mo (T12) after transplant from 28 viremic KT patients and 68 nonviremic controls matched for the transplantation period. BKPyV IgG seroprevalence was comparable between cases (89.3%) and controls (91.2%; p = 0.8635), but cases had lower antibody levels (p = 0.022) at T0. Antibody levels increased at T6 and T12 but were not correlated with viremia clearance. BKPyV‐specific T cell responses to pools of overlapping 15mers (15mer peptide pool [15mP]) or immunodominant CD8 9mers (9mer peptide pool [9mP]) from the early viral gene region were not different between cases and controls at T0; however, clearance of viremia was associated with stronger 9mP responses at T6 (p = 0.042) and T12 (p = 0.048), whereas 15mP responses were not informative (T6 p = 0.359; T12 p = 0.856). BKPyV‐specific T cells could be expanded in vitro from all patients after transplant, permitting identification of 78 immunodominant 9mer epitopes including 50 new ones across different HLA class I. Thus, 9mP‐responses may be a novel marker of reconstituting CD8 T cell function that warrants further study as a complement of plasma BKPyV loads for guiding immunosuppression reduction.

Panel‐reactive antibodies are widely regarded as an important immunological risk factor for rejection and graft loss. The broadness of sensitization against HLA is most appropriately measured by the “calculated population‐reactive antibodies” (cPRA) value. In this study, we investigated whether cPRA represent an immunological risk in times of sensitive and accurate determination of pretransplantation donor‐specific HLA antibodies (DSA). Five hundred twenty‐seven consecutive transplantations were divided into four groups: cPRA 0% (n = 250), cPRA 1–50% (n = 129), cPRA 51–100% (n = 43), and DSA (n = 105). Patients without DSA were considered as normal risk and received standard immunosuppression without T cell–depleting induction. Patients with DSA received an enhanced induction therapy and maintenance immunosuppression. Surveillance biopsies were performed at 3 and 6 months. Median follow‐up was 5.7 years. Among the three cPRA groups, there were no differences regarding the 1‐year incidence of ABMR (p = 0.16) and TCMR (p = 0.75). The 5‐year allograft survival rates were similar and around 87% (p = 0.28). The estimated glomerular filtration rate at last follow‐up was 50–53 mL/min (p = 0.45). On multivariable Cox proportional hazard analysis, the strongest independent predictor for ABMR and (death‐censored) graft survival was pretransplantation DSA. cPRA were not predictive for ABMR, TCMR, or (death‐censored) graft survival. We conclude that with current DSA assignment, the broadness of sensitization measured by cPRA does not imply an immunological risk.

Significance Statement: This study is the first randomized controlled trial to investigate the clinical utility of a noninvasive monitoring biomarker in renal transplantation. Although urine CXCL10 monitoring could not demonstrate a beneficial effect on 1-year outcomes, the study is a rich source for future design of trials aiming to explore the clinical utility of noninvasive biomarkers. In addition, the study supports the use of urine CXCL10 to assess the inflammatory status of the renal allograft. Background: Urine CXCL10 is a promising noninvasive biomarker for detection of renal allograft rejection. The aim of this study was to investigate the clinical utility of renal allograft monitoring by urine CXCL10 in a randomized trial. Methods: We stratified 241 patients, 120 into an intervention and 121 into a control arm. In both arms, urine CXCL10 levels were monitored at three specific time points (1, 3, and 6 months post-transplant). In the intervention arm, elevated values triggered performance of an allograft biopsy with therapeutic adaptations according to the result. In the control arm, urine CXCL10 was measured, but the results concealed. The primary outcome was a combined end point at 1-year post-transplant (death-censored graft loss, clinical rejection between month 1 and 1-year, acute rejection in 1-year surveillance biopsy, chronic active T-cell–mediated rejection in 1-year surveillance biopsy, development of de novo donor-specific HLA antibodies, or eGFR <25 ml/min). Results: The incidence of the primary outcome was not different between the intervention and the control arm (51% versus 49%; relative risk (RR), 1.04 [95% confidence interval, 0.81 to 1.34]; P = 0.80). When including 175 of 241 (73%) patients in a per-protocol analysis, the incidence of the primary outcome was also not different (55% versus 49%; RR, 1.11 [95% confidence interval, 0.84 to 1.47]; P = 0.54). The incidence of the individual end points was not different as well. Conclusions: This study could not demonstrate a beneficial effect of urine CXCL10 monitoring on 1-year outcomes (ClinicalTrials.gov_NCT03140514).

Solid-phase assays for human leukocyte antigens (HLA) antibody detection have clearly revolutionized the field of HLA diagnostics and transplantation. The key advantages are a high sensitivity and specificity for the detection of HLA antibodies compared with cell-based assays, as well as the potential for standardization. Solid-phase assays enabled the broad introduction of tools such as "virtual crossmatching" and "calculated panel reactive antibodies," which are essential components in many organ allocation systems, kidney-paired donation programs, and center-specific immunological risk stratification procedures. The most advanced solid-phase assays are the so-called single antigen beads (SAB). They are available now for more than 15 years, and the transplant community embraced their significant advantages. However, SAB analysis and interpretation is complex and many pitfalls have to be considered. In this review, we will discuss problems, limitations, and challenges using SAB. Furthermore, we express our wishes for the improvements of SAB as well as their future use for immunological assessment and research purposes.

Eplets are defined as distinct amino acid configurations on the surface of HLA molecules. The aim of this study was to estimate the immunogenicity of HLA‐DQ eplets in a cohort of 221 pregnancies with HLA‐DQ mismatches. We defined the immunogenicity of an eplet by the frequency of antibody responses against it. Around 90% of all listed DQB1 or DQA1 eplets were at least five times mismatched and thus included for the calculation of their immunogenicity. The DQB1 eplets with the five highest immunogenicity scores were 55PP, 52PR, 52PQ, 85VG and 45EV; 25% of all DQB1 eplets were not reacting. The DQA1 eplets with the five highest immunogenicity scores were 25YS, 47QL, 55RR, 187T and 18S; 17% of all DQA1 eplets were not reacting. The immunogenicity score had a slightly higher area under the curve to predict development of child‐specific antibodies than various molecular mismatch scores (eg, eplet mismatch load, amino acid mismatch load). Overlapping eplets were identified as a barrier to unambiguously assign the immunogenicity score based on HLA antibody reaction patterns. In this conceptual study, we explored the immunogenicity of HLA‐DQ eplets and created a map of potentially immunogenic regions on HLA‐DQ molecules, which requires validation in clinical transplant cohorts.

In this study, we investigated the clinical impact of different urinary tract infection (UTI) phenotypes occurring within the first year after renal transplantation. The population included 2368 transplantations having 2363 UTI events. Patients were categorized into four groups based on their compiled UTI events observed within the first year after transplantation: (i) no colonization or UTI (n = 1404; 59%), (ii) colonization only (n = 353; 15%), (iii) occasional UTI with 1–2 episodes (n = 456; 19%), and (iv) recurrent UTI with ≥3 episodes (n = 155; 7%). One‐year mortality and graft loss rate were not different among the four groups, but patients with recurrent UTI had a 7‐10 ml/min lower eGFR at year one (44 ml/min vs. 54, 53, and 51 ml/min; p < .001). UTI phenotypes had no impact on long‐term patient survival (p = .33). However, patients with recurrent UTI demonstrated a 10% lower long‐term death‐censored allograft survival (p < .001). Furthermore, recurrent UTI was a strong and independent risk factor for reduced death‐censored allograft survival in a multivariable analysis (HR 4.41, 95% CI 2.53–7.68, p < .001). We conclude that colonization and occasional UTI have no impact on pertinent outcomes, but recurrent UTI are associated with lower one‐year eGFR and lower long‐term death‐censored allograft survival. Better strategies to prevent and treat recurrent UTI are needed.