Browsing by Author "Mannon, Roslyn B."

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    Cell-Free DNA and Active Rejection in Kidney Allografts
    (American Society of Nephrology, 2017-07) Bloom, Roy D.; Bromberg, Jonathan S.; Poggio, Emilio D.; Bunnapradist, Suphamai; Langone, Anthony J.; Sood, Puneet; Matas, Arthur J.; Mehta, Shikha; Mannon, Roslyn B.; Sharfuddin, Asif; Fischbach, Bernard; Narayanan, Mohanram; Jordan, Stanley C.; Cohen, David; Weir, Matthew R.; Hiller, David; Prasad, Preethi; Woodward, Robert N.; Grskovic, Marica; Sninsky, John J.; Yee, James P.; Brennan, Daniel C.; Circulating Donor-Derived Cell-Free DNA in Blood for Diagnosing Active Rejection in Kidney Transplant Recipients (DART) Study Investigators; Medicine, School of Medicine
    Histologic analysis of the allograft biopsy specimen is the standard method used to differentiate rejection from other injury in kidney transplants. Donor-derived cell-free DNA (dd-cfDNA) is a noninvasive test of allograft injury that may enable more frequent, quantitative, and safer assessment of allograft rejection and injury status. To investigate this possibility, we prospectively collected blood specimens at scheduled intervals and at the time of clinically indicated biopsies. In 102 kidney recipients, we measured plasma levels of dd-cfDNA and correlated the levels with allograft rejection status ascertained by histology in 107 biopsy specimens. The dd-cfDNA level discriminated between biopsy specimens showing any rejection (T cell-mediated rejection or antibody-mediated rejection [ABMR]) and controls (no rejection histologically), P<0.001 (receiver operating characteristic area under the curve [AUC], 0.74; 95% confidence interval [95% CI], 0.61 to 0.86). Positive and negative predictive values for active rejection at a cutoff of 1.0% dd-cfDNA were 61% and 84%, respectively. The AUC for discriminating ABMR from samples without ABMR was 0.87 (95% CI, 0.75 to 0.97). Positive and negative predictive values for ABMR at a cutoff of 1.0% dd-cfDNA were 44% and 96%, respectively. Median dd-cfDNA was 2.9% (ABMR), 1.2% (T cell-mediated types ≥IB), 0.2% (T cell-mediated type IA), and 0.3% in controls (P=0.05 for T cell-mediated rejection types ≥IB versus controls). Thus, dd-cfDNA may be used to assess allograft rejection and injury; dd-cfDNA levels <1% reflect the absence of active rejection (T cell-mediated type ≥IB or ABMR) and levels >1% indicate a probability of active rejection.
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    Operational challenges in the COVID‐19 era: Asymptomatic infections and vaccination timing
    (Wiley, 2021-11) Axelrod, David A.; Ince, Dilek; Harhay, Meera N.; Mannon, Roslyn B.; Alhamad, Tarek; Cooper, Matthew; Josephson, Michelle A.; Caliskan, Yasar; Sharfuddin, Asif; Kumar, Vineeta; Guenette, Alexis; Schnitzler, Mark A.; Ainapurapu, Sruthi; Lentine, Krista L.; Medicine, School of Medicine
    The coronavirus disease 2019 (COVID-19) pandemic has created unprecedented challenges for solid organ transplant programs. While transplant activity has largely recovered, appropriate management of deceased donor candidates who are asymptomatic but have positive nucleic acid test (NAT) for COVID-19 is unclear as this may reflect active infection or prolonged viral shedding. Furthermore, candidates who are unvaccinated or partially vaccinated continue to receive donor offers. In the absence of prospective data, transplant professionals at U.S. adult kidney transplant centers were surveyed to determine community practice (N: 92 centers, capturing 40.8% of centers and 56.6% of transplants performed). The majority (96.8%) of responding centers declined organs for asymptomatic NAT+ patients without documented prior infection. However, 31.6% of centers proceeded with kidney transplant in NAT+ patients who were at least 30 days from initial diagnosis with negative chest imaging. Less than 7% of programs reported inactivating patients who were unvaccinated or partially vaccinated. In conclusion, despite national recommendations to wait for negative testing, many centers are proceeding with transplant in patients with positive tests due to presumed viral shedding. Furthermore, very few centers are requiring COVID-19 vaccination prior to transplantation despite early evidence suggesting reduced immunogenicity in transplant patients on immunosuppression.