BACKGROUND: Previous studies have reported that granzyme B (GZMB) and perforin (PRF) could serve as noninvasive biomarkers in the diagnosis of acute rejection (AR) after kidney transplant. Yet, their noninvasive diagnostic value in clinical practice is still unknown. METHODS: To assess the noninvasive diagnostic performance of GZMB and PRF for AR, we performed a systematic search. After reviewing published studies in which both GZMB and PRF were detected, data on the diagnostic accuracy of separate and combined evaluation of GZMB and PRF were pooled. RESULTS: Across 16 studies (680 subjects), summary sensitivity, specificity, positive likelihood ratios, and negative likelihood ratios with 95% confidence intervals were calculated. For overall GZMB analysis, the indices were 0.76 (0.71-0.81), 0.86 (0.82-0.89), 4.58 (3.36-6.25), and 0.32 (0.22-0.47), respectively. For overall PRF analysis, the indices were 0.83 (0.78-0.88), 0.86 (0.82-0.89), 4.82 (3.66-6.35), and 0.26 (0.18-0.37), respectively. Subgroup analyses showed similar results compared to overall study analyses. In analyses of combined evaluation of GZMB and PRF, the above indices were 0.65 (0.53-0.76), 0.96 (0.91-0.98), 12.66 (5.83-27.50), and 0.40 (0.23-0.69), respectively, when both markers were positive. The probability of developing AR in kidney transplant recipients increased from 15% to 73% when both GZMB and PRF tests were positive and was reduced to 2% if that were negative. CONCLUSIONS: Currently, neither GZMB nor PRF, if evaluated alone, could be a convincing noninvasive diagnostic marker for AR in clinical practice. Combined use of PRF and GZMB post-kidney transplant may be a better choice in AR evaluation to direct allograft biopsy execution and earlier therapeutic intervention.
BACKGROUND: Previous studies have reported that granzyme B (GZMB) and perforin (PRF) could serve as noninvasive biomarkers in the diagnosis of acute rejection (AR) after kidney transplant. Yet, their noninvasive diagnostic value in clinical practice is still unknown. METHODS: To assess the noninvasive diagnostic performance of GZMB and PRF for AR, we performed a systematic search. After reviewing published studies in which both GZMB and PRF were detected, data on the diagnostic accuracy of separate and combined evaluation of GZMB and PRF were pooled. RESULTS: Across 16 studies (680 subjects), summary sensitivity, specificity, positive likelihood ratios, and negative likelihood ratios with 95% confidence intervals were calculated. For overall GZMB analysis, the indices were 0.76 (0.71-0.81), 0.86 (0.82-0.89), 4.58 (3.36-6.25), and 0.32 (0.22-0.47), respectively. For overall PRF analysis, the indices were 0.83 (0.78-0.88), 0.86 (0.82-0.89), 4.82 (3.66-6.35), and 0.26 (0.18-0.37), respectively. Subgroup analyses showed similar results compared to overall study analyses. In analyses of combined evaluation of GZMB and PRF, the above indices were 0.65 (0.53-0.76), 0.96 (0.91-0.98), 12.66 (5.83-27.50), and 0.40 (0.23-0.69), respectively, when both markers were positive. The probability of developing AR in kidney transplant recipients increased from 15% to 73% when both GZMB and PRF tests were positive and was reduced to 2% if that were negative. CONCLUSIONS: Currently, neither GZMB nor PRF, if evaluated alone, could be a convincing noninvasive diagnostic marker for AR in clinical practice. Combined use of PRF and GZMB post-kidney transplant may be a better choice in AR evaluation to direct allograft biopsy execution and earlier therapeutic intervention.
Authors: Stephen T Bartlett; James F Markmann; Paul Johnson; Olle Korsgren; Bernhard J Hering; David Scharp; Thomas W H Kay; Jonathan Bromberg; Jon S Odorico; Gordon C Weir; Nancy Bridges; Raja Kandaswamy; Peter Stock; Peter Friend; Mitsukazu Gotoh; David K C Cooper; Chung-Gyu Park; Phillip OʼConnell; Cherie Stabler; Shinichi Matsumoto; Barbara Ludwig; Pratik Choudhary; Boris Kovatchev; Michael R Rickels; Megan Sykes; Kathryn Wood; Kristy Kraemer; Albert Hwa; Edward Stanley; Camillo Ricordi; Mark Zimmerman; Julia Greenstein; Eduard Montanya; Timo Otonkoski Journal: Transplantation Date: 2016-02 Impact factor: 4.939
Authors: Hee Yeon Jung; Yong Jin Kim; Ji Young Choi; Jang Hee Cho; Sun Hee Park; Yong Lim Kim; Hyung Kee Kim; Seung Huh; Dong Il Won; Chan Duck Kim Journal: J Korean Med Sci Date: 2017-06 Impact factor: 2.153
Authors: Allison Tong; Klemens Budde; John Gill; Michelle A Josephson; Lorna Marson; Timothy L Pruett; Peter P Reese; David Rosenbloom; Lionel Rostaing; Anthony N Warrens; Germaine Wong; Jonathan C Craig; Sally Crowe; Tess Harris; Brenda Hemmelgarn; Braden Manns; Peter Tugwell; Wim Van Biesen; David C Wheeler; Wolfgang C Winkelmayer; Nicole Evangelidis; Benedicte Sautenet; Martin Howell; Jeremy R Chapman Journal: Transplant Direct Date: 2016-05-19
Authors: Constantin J Thieme; Benjamin J D Weist; Annemarie Mueskes; Toralf Roch; Ulrik Stervbo; Kamil Rosiewicz; Patrizia Wehler; Maik Stein; Peter Nickel; Andreas Kurtz; Nils Lachmann; Mira Choi; Michael Schmueck-Henneresse; Timm H Westhoff; Petra Reinke; Nina Babel Journal: Sci Rep Date: 2019-12-13 Impact factor: 4.379