Browsing by Subject "Transplant outcomes"

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    Discrepant Outcomes between National Kidney Transplant Data Registries in the United States
    (Wolters Kluwer, 2023) Yu, Miko; King, Kristen L.; Husain, S. Ali; Huml, Anne M.; Patzer, Rachel E.; Schold, Jesse D.; Mohan, Sumit; Surgery, School of Medicine
    Significance statement: Effects of reduced access to external data by transplant registries to improve accuracy and completeness of the collected data are compounded by different data management processes at three US organizations that maintain kidney transplant-related datasets. This analysis suggests that the datasets have large differences in reported outcomes that vary across different subsets of patients. These differences, along with recent disclosure of previously missing outcomes data, raise important questions about completeness of the outcome measures. Differences in recorded deaths seem to be increasing in recent years, reflecting the adverse effects of restricted access to external data sources. Although these registries are invaluable sources for the transplant community, discrepancies and incomplete reporting risk undermining their value for future analyses, particularly when used for developing national transplant policy or regulatory measures. Background: Central to a transplant registry's quality are accuracy and completeness of the clinical information being captured, especially for important outcomes, such as graft failure or death. Effects of more limited access to external sources of death data for transplant registries are compounded by different data management processes at the United Network for Organ Sharing (UNOS), the Scientific Registry of Transplant Recipients (SRTR), and the United States Renal Data System (USRDS). Methods: This cross-sectional registry study examined differences in reported deaths among kidney transplant candidates and recipients of kidneys from deceased and living donors in 2000 through 2019 in three transplant datasets on the basis of data current as of 2020. We assessed annual death rates and survival estimates to visualize trends in reported deaths between sources. Results: The UNOS dataset included 77,605 deaths among 315,346 recipients and 61,249 deaths among 275,000 nonpreemptively waitlisted candidates who were never transplanted. The SRTR dataset included 87,149 deaths among 315,152 recipients and 60,042 deaths among 259,584 waitlisted candidates. The USRDS dataset included 89,515 deaths among 311,955 candidates and 63,577 deaths among 238,167 waitlisted candidates. Annual death rates among the prevalent transplant population show accumulating differences across datasets-2.31%, 4.00%, and 4.03% by 2019 from UNOS, SRTR, and USRDS, respectively. Long-term survival outcomes were similar among nonpreemptively waitlisted candidates but showed more than 10% discordance between USRDS and UNOS among transplanted patients. Conclusions: Large differences in reported patient outcomes across datasets seem to be increasing, raising questions about their completeness. Understanding the differences between these datasets is essential for accurate, reliable interpretation of analyses that use these data for policy development, regulatory oversight, and research. Podcast: This article contains a podcast at https://dts.podtrac.com/redirect.mp3/www.asn-online.org/media/podcast/JASN/2023_10_24_JASN0000000000000194.mp3.
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    Posoleucel in Kidney Transplant Recipients with BK Viremia: Multicenter, Randomized, Double-Blind, Placebo-Controlled Phase 2 Trial
    (Wolters Kluwer, 2024) Chandraker, Anil; Regmi, Anil; Gohh, Reginald; Sharma, Akhil; Woodle, E. Steve; Ansari, Mohammed J.; Nair, Vinay; Chen, Ling-Xin; Alhamad, Tarek; Norman, Silas; Cibrik, Diane; Singh, Manpreet; Alper, Arnold; Jain, Divya; Zaky, Ziad; Knechtle, Stuart; Sharfuddin, Asif; Gupta, Gaurav; Lonze, Bonnie E.; Young, Jo-Anne H.; Adey, Deborah; Faravardeh, Arman; Dadhania, Darshana M.; Rossi, Ana P.; Florescu, Diana; Cardarelli, Francesca; Ma, Julie; Gilmore, Sarah; Vasileiou, Spyridoula; Jindra, Peter T.; Wojciechowski, David; Medicine, School of Medicine
    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.