CLINICAL AND TRANSLATIONAL RESEARCH Inferior Kidney Allograft Outcomes in Patients With De Novo Donor-Specific Antibodies Are Due to Acute Rejection Episodes James E. Cooper, 1,4 Jane Gralla, 2 Linda Cagle, 3 Ryan Goldberg, 1 Laurence Chan, 1 and Alexander C. Wiseman 1 Background. Donor-specific antibodies (DSAs) after kidney transplantation have been associated with poor graft outcomes in multiple studies. However, these studies have generally used stored sera or a single cross sectional screening test to identify patients with DSA. We evaluated the effectiveness of a prospective DSA screening protocol in identifying kidney and kidney/pancreas recipients at risk for poor graft outcomes. Methods. From September 2007 through September 2009, 244 consecutively transplanted kidney and kidney/pancreas recipients without pretransplant DSA were screened for de novo DSA at 1, 6, 12, and 24 months and when clinically indicated. Results. DSA was detected in 27% of all patients by protocol or indication screening. Patients with DSA (DSA+) were significantly more likely to have experienced acute rejection (AR) compared with no DSA (DSA-) (29% vs. 9.5%, P0.001), and lower estimated 2-year graft survival (83% vs. 98%, P0.001). Only 3 of 19 DSA (+) patients with AR had DSA detected before the AR episode. When excluding patients with AR, 2-year graft survival was similar between DSA (+) and DSA (-) patients (100% vs. 99%) as was estimated glomerular filtration rate. Patients with DSA detected by protocol screening had similar outcomes compared with DSA (-), whereas those with DSA detected by indication experienced significantly worse outcomes. Conclusions. Patients with de novo DSA experience worse graft outcomes due to previous/concurrent episodes of AR. A prospective DSA screening protocol failed to identify patients at risk for AR or poor short-term graft outcomes. Keywords: Rejection, HLA antibody, Kidney transplantation. (Transplantation 2011;91: 1103–1109) C irculating donor-specific anti-human leukocyte antigen (HLA) antibodies (DSAs) after renal transplantation have been associated with acute rejection (AR) episodes (1–3). The presence of DSA at the time of diagnosis of any AR episode is predictive of worse graft outcomes (4), a phenom- enon that is particularly true for patients who do not experi- ence a significant reduction in DSA levels after the rejection episode (4, 5). A number of reports have demonstrated that DSA is also a marker for poor long-term graft outcomes (6 –11). Al- though these studies have included a large number of pa- tients, DSA detection was generally performed via retrospec- tive testing of stored sera in those with graft failure compared with “matched” controls (6, 7, 9, 11) or as a cross-sectional test of a number of patients at various points after transplant (8, 10). In these studies, details regarding the clinical situa- tions in which DSA was formed (e.g., the stable posttrans- plant patient vs. the patient with previous/ongoing AR epi- sodes) are not available. In contrast to these data, in a study by Bartel et al. (12), DSA (+) patients with stable graft function experienced similar outcomes compared with patients with- out DSA, raising the question of the predictive value of DSA in the absence of rejection. Beginning in September 2007, our center implemented a screening protocol in which patient sera is tested for DSA at 1, 6, 12, and 24 months posttransplant, in addition to when- ever clinically indicated (an increase in serum creatinine with clinical suspicion of rejection). By screening patients pro- The authors declare no conflict of interest. 1 Division of Renal Diseases and Hypertension, Transplant Center, Univer- sity of Colorado Denver, Aurora, CO. 2 Department of Pediatrics, University of Colorado Denver, Aurora, CO. 3 Linda Cagle, ClinImmune Labs, Bioscience Park Center, Aurora, CO. 4 Address correspondence to: James E. Cooper, M.D., Division of Renal Dis- eases and Hypertension, Transplant Center, University of Colorado Health Sciences Center, Mail Stop F749, AOP 7089, 1635 North Aurora Court, Aurora, CO 80045. E-mail: James.Cooper@ucdenver.edu J.E.C., L. Chan, and A.C.W. participated in research design, data analysis, and writing of the manuscript; J.G. participated in research design and data analysis of the manuscript; and L. Cagle and R.G. participated in research performance of the manuscript. Supplemental digital content is available for this article. Direct URL ci- tations appear in the printed text, and links to the digital files are provided in the HTML text of this article on the journal’s Web site (www.transplantjournal.com). Received 28 September 2010. Revision requested 19 October 2010. Accepted 1 February 2011. Copyright © 2011 by Lippincott Williams & Wilkins ISSN 0041-1337/11/9110-1103 DOI: 10.1097/TP.0b013e3182139da1 Transplantation • Volume 91, Number 10, May 27, 2011 www.transplantjournal.com | 1103