Key Points Posoleucel was generally safe, well tolerated, and associated with a greater reduction of BK viremia compared with placebo. BK viremia reduction occurred coincident with an increase in the circulating frequency of BK virus–specific T cells in posoleucel recipients. The presence and persistence of posoleucel was confirmed by T-cell receptor variable β sequencing. Background Kidney transplant recipients with BK virus infection are at risk of developing BK virus–associated nephropathy, allograft rejection, and subsequent graft loss. There are no approved treatments for BK virus infection. Posoleucel is an off-the-shelf, allogeneic, multivirus-specific T-cell investigational therapy targeting BK virus, as well as five other opportunistic viruses: adenovirus, cytomegalovirus, Epstein–Barr virus, human herpesvirus 6, and John Cunningham virus. Methods In this phase 2, double-blind study, kidney transplant recipients with BK viremia were randomized 1:1:1 to receive posoleucel weekly for 3 weeks and then every 14 days (bi-weekly dosing) or every 28 days (monthly dosing) or placebo for 12 weeks. Participants were followed for 12 weeks after completing treatment. The primary objective was safety; the secondary objective was plasma BK viral load reduction. Results Sixty-one participants were randomized and dosed. Baseline characteristics were similar across groups. No deaths, graft-versus-host disease, or cytokine release syndrome occurred. The proportion of patients who had adverse events (AEs) judged by the investigators to be treatment-related was slightly lower in recipients of posoleucel: 20% (4 of 20 patients) and 18% (4 of 22) in those infused on a bi-weekly and monthly schedule, respectively, and 26% (5 of 19) in placebo recipients. None of the grade 3–4 AEs or serious AEs in any group were deemed treatment-related. No deaths, graft-versus-host disease, or cytokine release syndrome occurred. Three participants had allograft rejection, but none were deemed treatment-related by investigators. In posoleucel recipients, BK viremia reduction was associated with an increase in the circulating frequency of BK virus–specific T cells, and the presence and persistence of posoleucel was confirmed by T-cell receptor sequencing. Conclusions Posoleucel was generally safe, well tolerated, and associated with a larger reduction of BK viremia compared with placebo. Limitations of this study include the relatively short duration of follow-up and lack of power to detect significant differences in clinical outcomes. Clinical Trial registry name and registration number: Study of Posoleucel (Formerly Known as ALVR105; Viralym-M) in Kidney Transplant Patients With BK Viremia, NCT04605484.
Abstract The worldwide focus on work hour regulations and patient safety has led to the re‐examination of the merits of night‐time surgery, including kidney transplantation. The risks of operating during nontraditional work hours with potentially fatigued surgeons and staff must be weighed against the negative effects of prolonged cold ischemic time with resultant graft compromise. The aim of this study was to evaluate the impact of performing renal transplantation procedures during evening versus day time hours. The main outcome measures assessed between the day and night cohorts included comparisons of the postoperative complication rates and survival outcomes for both the renal allograft and the patient. A retrospective review of 633 deceased donor renal transplants performed at a single institution was analyzed. Three statistically significant results were noted, namely, a decrease in vascular complications in the nighttime cohort, an increase in urologic complications on subgroup analysis in the 3 AM to 6 AM cohort, and the 12 AM to 3 AM subgroup had the greatest odds of any complication. There was no statistical difference in either patient or graft survival over a twelve month period following transplantation. We conclude that although the complication rate varied among cohorts this was clinically insignificant and there was no overall clinically relevant impact on patient or graft survival.
Purpose of review Many sensitized patients have willing live donors but are unable to use them because of a human leukocyte antigen (HLA) incompatibility. The options for these patients include: remaining on the deceased-donor list, entering a kidney-paired donation scheme, or undergoing desensitization with high-dose IVIg or plasmapheresis and low-dose IVIg. Recent findings Mathematical simulations verified by actual data from several national kidney-paired donation (KPD) programs has shed light on which donor/recipient phenotypes are likely to benefit from each transplant modality. Pairs that are easy to match are likely to receive compatible kidneys in a KPD. Those who are hard to match may be better served by desensitization. The phenotype which is both hard to match and hard to desensitize due to board and strong HLA reactivity are most likely to be transplanted by a hybrid modality utilizing desensitization after identifying a more immunologically favorable donor in a KPD. Summary Recent outcomes from desensitization in which starting donor-specific antibody strength is low have been very good. For broadly sensitized patients with a high-strength cross-match, searching for a better donor in a KPD pool can facilitate a safer, less expensive, and more successful desensitization treatment course.
Introduction: Preliminary studies suggest that kidney transplant recipients (KTRs) show diminished humoral responses to SARS-CoV-2 vaccination. Although reports of allograft rejection around the time of SARS-CoV-2 vaccination have been rare, there is no recommended framework for monitoring for potential vaccine-related allograft injury. Here, we describe an approach for longitudinal assessment of immunogenicity and safety of SARS-COV-2 vaccination in KTRs. Methods: KTRs eligible for SARS-CoV-2 vaccination were identified through medical records, beginning March 12, 2021. Baseline and weekly blood samples were collected for routine assessment, SARS-CoV-2 spike protein antibody titers, dd-cfDNA (AlloSure, CareDx) and gene expression profiling (GEP) (AlloMap, CareDx) for 12 weeks. HLA DSA testing was performed at baseline, 2 weeks after completion of vaccine doses and at week 12. Antibody response was defined as a 10-fold increase in total binding IgG titers. Results: 49 KTRs were identified for analysis. Patient demographics are summarized in Table 1. 10 patients (20.4%) demonstrated a spike antibody response following completion of the vaccine series. Patients with a prior history of COVID-19 were more likely to mount a spike antibody response (n=8, 53.3%) compared to those with no reported history of COVID-19 (n=2, 5.8%). The odds ratio was 18.3 (95% CI 3.2, 105.0, p=0.0005). Median dd-cfDNA levels did not differ between pre- and post-vaccination (0.23% versus 0.21% respectively; Table 2). There was no significant difference between pre- and post-vaccination GEP scores (9.85 versus 10.4 respectively; Table 2). No patients developed clinically significant DSA, eGFR decline or allograft rejection following vaccination. Conclusions: Quantitative antibody responses were strongly associated with a diagnosis of prior SARS-CoV-2 infection. Stability of eGFR, dd-cfDNA, GEP profiles and lack of allosensitization reinforce the safety profile of SARS-CoV-2 vaccination in KTRs. Further studies are needed to better understand immunogenicity in SARS-CoV-2 naïve individuals, including whether cellular responses are protective in the absence of humoral responses.
