Browsing by Author "Poggio, Emilio D."

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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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    Molecular Signatures of Diabetic Kidney Disease Hiding in a Patient with Hypertension-Related Kidney Disease: A Clinical Pathologic Molecular Correlation
    (Wolters Kluwer, 2022) Patel, Jiten; Torrealba, Jose R.; Poggio, Emilio D.; Bebiak, Jack; Alpers, Charles E.; Grewenow, Stephanie M.; Toto, Robert D.; Eadon, Michael T.; Kidney Precision Medicine Project; Medicine, School of Medicine
    The Kidney Precision Medicine Project (KPMP) seeks to establish a molecular atlas of the kidney in health and disease and improve our understanding of the molecular drivers of CKD and AKI. Herein, we describe the case of a 66-year-old woman with CKD who underwent a protocol KPMP kidney biopsy. Her clinical history included well-controlled diabetes mellitus, hypertension, and proteinuria. The patient’s histopathology was consistent with modest hypertension-related kidney injury, without overt diabetic kidney disease. Transcriptomic signatures of the glomerulus, interstitium, and tubular subsegments were obtained from laser microdissected tissue. The molecular signatures that were uncovered revealed evidence of early diabetic kidney disease adaptation and ongoing active tubular injury with enriched pathways related to mesangial cell hypertrophy, glycosaminoglycan biosynthesis, and apoptosis. Molecular evidence of diabetic kidney disease was found across the nephron. Novel molecular assays can supplement and enrich the histopathologic diagnosis obtained from a kidney biopsy.