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1. Donor-derived Cell-free DNA Identifies Antibody-mediated Rejection in Donor Specific Antibody Positive Kidney Transplant Recipients

Author

Stanley C. Jordan, MD, FASN, FAST, Suphamai Bunnapradist, MD, Jonathan S. Bromberg, MD, PhD, Anthony J. Langone, MD, David Hiller, PhD, James P. Yee, MD, PhD, John J. Sninsky, PhD, Robert N. Woodward, PhD, and Arthur J. Matas, MD

Subjects
Surgery, RD1-811
Abstract

Background. Elevated levels of donor-derived cell-free DNA (dd-cfDNA) in the plasma of renal allograft recipients indicates organ injury and an increased probability of active rejection. Donor-specific antibodies (DSA) to HLA antigens are associated with risk of antibody-mediated rejection (ABMR). This study assessed the combined use of dd-cfDNA and DSA testing to diagnose active ABMR. Methods. Donor-derived cell-free DNA was assayed in 90 blood samples with paired DSA and clinically indicated biopsies from 87 kidney transplant patients. Sixteen cases met criteria for active ABMR. Performance characteristics of dd-cfDNA for diagnosis of active ABMR were determined for samples with prior or current positive DSA (DSA+, n = 33). Results. The median level of dd-cfDNA (2.9%) in DSA+ patients with active ABMR was significantly higher than the median level (0.34%) in DSA+ patients without ABMR (P < 0.001). The median level of dd-cfDNA in DSA− patients was 0.29%. The positive predictive value of dd-cfDNA (at 1%) to detect active ABMR in DSA+ patients was 81%, whereas the negative predictive value was 83%. The positive predictive value for DSA+ alone was 48%. Conclusions. The combined use of dd-cfDNA and DSA testing may improve the noninvasive diagnosis of active ABMR in kidney transplant patients. Patients with dd-cfDNA+/ DSA+ results have a high probability of active ABMR.

Published
2018
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2. Mammalian target of rapamycin inhibitors in organ transplantation: an unkept promise

Author

Anthony J, Langone and J Harold, Helderman

Subjects
Proteinuria, Podocytes, Risk Factors, TOR Serine-Threonine Kinases, Humans, Anemia, Hyperlipidemias, Organ Transplantation, Enzyme Inhibitors, Thrombocytopenia, Immunosuppressive Agents
Abstract

The initial enthusiasm for the advent of a potentially nonnephrotoxic immunosuppressant has been muted by data unmasking nephrotoxicity of mammalian target of rapamycin inhibitors, including renal podocyte injury resulting in proteinuria. Adverse reactions, including anemia, thrombocytopenia, hyperlipidemia, and especially diabetogenesis, have limited its use to niche indications such as prevention or amelioration of malignancy in organ transplant. The class seems to be best used to address malignancy in organ allograft recipients and as a first-line therapy in lymphangioleiomyomatosis.

Published
2012

3. List of Contributors

Author

Mauro Abbate, Horacio J. Adrogué, Seth L. Alper, Robert J. Alpern, Radhakrishna Baliga, Daniel Batlle, José F. Bernardo, Theresa J. Berndt, Mark O. Bevensee, Jürg Biber, René J.M. Bindels, Henrik Birn, Walter F. Boron, D. Craig Brater, Edward M. Brown, Gerhard Burckhardt, Simone M.R. Camargo, Michael J. Caplan, Andrés Cárdenas, Sheldon Chen, Erik Ilsø Christensen, Moonja Chung-Park, Fredric L. Coe, Kirk P. Conrad, Christopher J. Cooper, Norman P. Curthoys, Prasad Devarajan, Matthew Diamond, Cristina Dumitru, Lance D. Dworkin, Kai-Uwe Eckardt, Zoltán Huba Endre, Andrew Evan, Ronald J. Falk, Ian C. Forster, Peter A. Friedman, Clarice Kazue Fujihara, John P. Geibel, Kathleen M. Giacomini, Pere Ginès, Simin Goral, Mitchell Halperin, L. Lee Hamm, Syed K. Haque, Steven C. Hebert, J. Harold Helderman, William L. Henrich, Nati Hernando, Joost G.J. Hoenderop, Jonathon W. Homeister, Charles S. Hummel, J. Charles Jennette, Kamel S. Kamel, S. Ananth Karumanchi, Clifford E. Kashtan, Charbel Khoury, Robert Kleta, Hermann Koepsell, Martin Konrad, Reto Krapf, Rajiv Kumar, Armin Kurtz, Ira Kurtz, Anthony J. Langone, Shih-Hua Lin, Marshall D. Lindheimer, Christopher Y. Lu, Daniela Macconi, Michael Madaio, Nicolaos E. Madias, Victoria Makrides, Anup Manoharon, Pär Matsson, William E. Mitch, Orson W. Moe, Bruce A. Molitoris, Heini Murer, Eugene Nattie, Rikke Nielsen, Biff F. Palmer, Patricia A. Preisig, Gary A. Quamme, L. Darryl Quarles, Mohan Rajapurkar, Giuseppe Remuzzi, Daniela Riccardi, Heidi Schaefer, Jeffrey R. Schelling, Karl P. Schlingmann, Robert W. Schrier, John R. Sedor, Yoav Segal, Donald W. Seldin, Sudhir V. Shah, Asif Sharfuddin, Stefan Somlo, Andrew K. Stewart, Peter J. Tebben, Vicente E. Torres, François Verrey, Robert James Walker, Roland H. Wenger, Elaine Worcester, Biruh T. Workeneh, Ernest M. Wright, John Wysolmerski, Sung-Sen Yang, Roberto Zatz, Fuad N. Ziyadeh, and Carla Zoja

Published
2012

4. Contributors

Author

MAURO ABBATE, DALE R. ABRAHAMSON, MARCIN ADAMCZAK, HORACIO J. ADROGUÉ, SETH L. ALPER, ROBERT J. ALPERN, THOMAS E. ANDREOLI, ANITA C. APERIA, MATTHEW A. BAILEY, DANIEL BATLLE, MICHEL BAUM, THERESA J. BERNDT, MARK O. BEVENSEE, JÜRG BIBER, DANIEL G. BICHET, RENÉ J.M. BINDELS, ROLAND C. BLANTZ, WALTER F. BORON, D. CRAIG BRATER, JOSEPHINE P. BRIGGS, ALEX BROWN, NIGEL J. BRUNSKILL, GERHARD BURCKHARDT, GEOFFREY BURNSTOCK, LLOYD CANTLEY, CHUNHUA CAO, GIOVAMBATTISTA CAPASSO, MICHAEL J. CAPLAN, HUGH J. CARROLL, LAURENCE CHAN, MOONJA CHUNG-PARK, FREDRIC L. COE, THOMAS M. COFFMAN, WAYNE D. COMPER, KIRK P. CONRAD, STEVEN D. CROWLEY, NORMAN P. CURTHOYS, PEDRO R. CUTILLAS, THEODORE M. DANOFF, EDWARD S. DEBNAM, HENRIK DIMKE, ALAIN DOUCET, RAGHVENDRA K. DUBEY, ADRIANA DUSSO, KAI-UWE ECKARDT, DAVID H. ELLISON, HITOSHI ENDOU, ZOLTÁN HUBA ENDRE, FRANKLIN H. EPSTEIN, ANDREW EVAN, RONALD J. FALK, KAMBIZ FARBAKHSH, NICHOLAS R. FERRERI, PEYING FONG, MANASSES CLAUDINO FONTELES, IAN FORSTER, LEONARD RALPH FORTE, HAROLD A. FRANCH, LYNDA A. FRASSETTO, PETER A. FRIEDMAN, JØRGEN FRØKLÆR, JOHN P. GEIBEL, MICHAEL GEKLE, GERHARD GIEBISCH, PERE GINÈS, STEVE A.N. GOLDSTEIN, SIMIN GORAL, SIAN V. GRIFFIN, WILLIAM B. GUGGINO, THERESA A. GUISE, SUSAN B. GURLEY, STEPHEN D. HALL, MITCHELL L. HALPERIN, L. LEE HAMM, STEVEN C. HEBERT, MATTHIAS A. HEDIGER, J. HAROLD HELDERMAN, WILLIAM L. HENRICH, AILLEEN HERAS-HERZIG, NATI HERNANDO, JOOST G.J. HOENDEROP, ULLA HOLTBÄCK, JEAN-DANIEL HORISBERGER, EDITH HUMMLER, TRACY E. HUNLEY, EDWIN K. JACKSON, J. CHARLES JENNETTE, EDWARD J. JOHNS, JOHN P. JOHNSON, BRIGITTE KAISSLING, KAMEL S. KAMEL, S. ANANTH KARUMANCHI, CLIFFORD E. KASHTAN, BERTRAM L. KASISKE, ADRIAN I. KATZ, BRIAN F. KING, SAULO KLAHR, THOMAS R. KLEYMAN, HERMANN KOEPSELL, VALENTINA KON, MARTIN KONRAD, ULLA C. KOPP, RETO KRAPF, WILHELM KRIZ, RAJIV KUMAR, CHRISTINE E. KURSCHAT, ARMIN KURTZ, TAE-HWAN KWON, CHRISTOPHER P. LANDOWSKI, ANTHONY J. LANGONE, FLORIAN LANG, HAROLD E. LAYTON, THU H. LE, DANIEL I. LEVY, SHIH-HUA LIN, MARSHALL D. LINDHEIMER, CHRISTOPHER Y. LU, MICHAEL P. MADAIO, NICOLAOS E. MADIAS, GERHARD MALNIC, KARL S. MATLIN, WILLIAM C. McCLELLAN, JOHN C. MCGIFF, C. CHARLES MICHEL, JEFFREY H. MINER, WILLIAM E. MITCH, HIROKI MIYAZAKI, ORSON W. MOE, BRUCE A. MOLITORIS, R. CURTIS MORRIS, SALIM K. MUJAIS, HEINI MURER, SHIGEAKI MUTO, EUGENE NATTIE, ERIC G. NEILSON, SØREN NIELSEN, SANJAY K. NIGAM, JOSEPH M. NOGUEIRA, MAN S. OH, MARK D. OKUSA, TANYA M. OSICKA, THOMAS L. PALLONE, BIFF F. PALMER, LAWRENCE G. PALMER, MARK D. PARKER, JOAN H. PARKS, PATRICIA A. PREISIG, GARY A. QUAMME, L. DARRYL QUARLES, RAYMOND QUIGLEY, W. BRIAN REEVES, GIUSEPPE REMUZZI, LUIS REUSS, DANIELA RICCARDI, BRIAN RINGHOFER, EBERHARD RITZ, CHRISTOPHER J. RIVARD, GARY L. ROBERTSON, ROBERT M. ROSA, BERNARD C. ROSSIER, LEILEATA M. RUSSO, HENRY SACKIN, HIROYUKI SAKURAI, JEFF M. SANDS, LISA M. SATLIN, HEIDI SCHAEFER, JEFFREY R. SCHELLING, LAURENT SCHILD, KARL P. SCHLINGMANN, JÜRGEN B. SCHNERMANN, ROBERT W. SCHRIER, ANTHONY SEBASTIAN, JOHN R. SEDOR, YOAV SEGAL, TAKASHI SEKINE, DONALD W. SELDIN, MARTIN SENITKO, MALATHI SHAH, SUDHIR V. SHAH, STUART J. SHANKLAND, ASIF A. SHARFUDDIN, KUMAR SHARMA, SHAOHU SHENG, DAVID G. SHIRLEY, STEFAN SILBERNAGL, STEPHEN M. SILVER, MEL SILVERMAN, EDUARDO SLATOPOLSKY, STEFAN SOMLO, RICHARD H. STERNS, ANDREW K. STEWART, YOSHIRO SUZUKI, PETER J. TEBBEN, SCOTT C. THOMSON, VICENTE E. TORRES, ROBERT J. UNWIN, FRANÇOIS VERREY, DAVID L. VESELY, CARSTEN A. WAGNER, MERYL WALDMAN, ROBERT JAMES WALKER, WEI WANG, WEN-HUI WANG, YINGHONG WANG, ALAN M. WEINSTEIN, PAUL A. WELLING, GUNTER WOLF, ELAINE WORCESTER, FUAD N. ZIYADEH, and CARLA ZOJA

Published
2008

5. The management of the failed renal allograft: an enigma with potential consequences

Author

Anthony J, Langone and Peale, Chuang

Subjects
Graft Rejection, Immunosuppression Therapy, Inflammation, Drug Resistance, Kidney Transplantation, Nephrectomy, Recombinant Proteins, Diuresis, Renal Dialysis, Antibody Formation, Retreatment, Humans, Kidney Failure, Chronic, Erythropoietin
Abstract

The number of patients returning to dialysis after their renal allograft fails is increasing in absolute numbers year after year. The management of the failed allograft that is not immediately symptomatic remains controversial. Surgical mortality and morbidity, a rising number of circulating antibodies, reduced erythropoietin, and diuresis are among the arguments to support simply observing the failed allograft. Chronic inflammation, potential for malignancy, infection, and the need for low-dose immunosuppression are concerns that might goad one into performing a preemptive nephrectomy. Based on the current literature and our own clinical experience, we believe allograft nephrectomies should not be routinely performed. They should be reserved for those patients who develop particular symptoms attributable to the allograft or those who require space for retransplantation. Future studies that address this issue in addition to testing various immunosuppression attrition rates may be able to discern a protocol that minimizes drug exposure while leading to reduced nephrectomy rates after returning to dialysis.

Published
2005

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