Browsing by Author "Goggins, William C."
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Item Antithymocyte Globulin Antibody Titer Congruent With Kidney Transplantation: Analysis of Incidence, Outcomes, Cost, and Alternative Targets(Wolters Kluwer, 2019-09-27) Lattimore, Sherene; Skill, Nicholas J.; Maluccio, Mary A.; Elliott, Holly; Dobben, Elizabeth; Shafuddin, Asif; Goggins, William C.; Surgery, School of MedicineRabbit antithymocyte globulin (rATG) use for immunosuppression induction is widespread but is contraindicated by the presence of anti-rATG antibodies. This study reports the incidence of positive anti-rATG antibody titers in patients before and after renal transplant and evaluates associated outcomes and costs. In addition, it will correlate CD40L and interleukin (IL)-21 with anti-rATG antibody titers. Methods: Clinical and billing records from the Indiana University Transplant Laboratory were reviewed for positive versus negative anti-rATG antibody titers, graft survival, and 7-day readmission costs between 2004 and 2018. Serum from patients with positive and negative rATG antibody titers were quantitated for CD40L and IL-21 by enzyme-linked immunosorbent assay. Results: On average, between 2004 and May 2018, 163 kidney transplants per year were performed. Anti-rATG antibody titers were ordered for 17 patients/year, of which 18.2% were positive at 1:100 titer either pre- or post-transplant. Time to graft loss correlated with a positive rATG titer at time of readmission. Moreover, second kidney transplant increased the anti-rATG positive rate. A weak correlation was observed between anti-rATG titer and recipient age. Seven-day readmission treatment costs were significantly lower in patients with positive anti-rATG titer. IL-21 and CD40L were significantly greater in patients with positive anti-rATG titers after transplant when compared with negative anti rATG patients. Conclusions: Positive anti-rATG antibody titer is associated with a significant negative impact on outcomes. Monitoring of anti-rATG antibody titer is recommended to optimize treatment options in patients, especially in the setting of second transplants. Elucidation of the mechanisms associated with positive anti-rATG antibody is required. IL-21 and CD40L are potential targets for future study.Item Bilateral Renal Auto-Transplantation for Retroperitoneal Sarcomas: Is It Underutilized?(MDPI, 2023-08-14) Robinson, Tyler P.; Milgrom, Daniel P.; Nagaraju, Santosh; Goggins, William C.; Samy, Kannan P.; Koniaris, Leonidas G.; Surgery, School of MedicineSarcomas are a rare tumor of mesenchymal origin. The liposarcoma is the most common sarcoma of the retroperitoneum. Liposarcomas are typically low grade, and present at an advanced stage and a large size. We report a case of a large retroperitoneal liposarcoma, approximately 50 kg, encasing both kidneys, which was managed via a two-stage resection and staged renal auto-transplantation into the intra-peritoneal pelvis. The patient maintained normal renal function throughout, and remains disease free two years post-resection. Renal auto-transplantation with pelvic placement may facilitate improved margin-free resection. Renal relocation may allow the use of curative-intent ablative therapies such as radiofrequency ablation and radiation in cases of retroperitoneal recurrence.Item DELAYED KIDNEY TRANSPLANTATION AFTER 83 HOURS OF COLD ISCHEMIA TIME IN COMBINED LIVER-KIDNEY TRANSPLANT(Wolters Kluwer, 2019-02) Ekser, Burcin; Chen, Angela M.; Kubal, Chandrashekhar A.; Fridell, Jonathan A.; Mihaylov, Plamen; Goggins, William C.; Powelson, John A.; Surgery, School of MedicineItem Efficacy and Safety of Bleselumab in Preventing the Recurrence of Primary Focal Segmental Glomerulosclerosis in Kidney Transplant Recipients: A Phase 2a, Randomized, Multicenter Study(Wolters Kluwer, 2024) Shoji, Jun; Goggins, William C.; Wellen, Jason R.; Cunningham, Patrick N.; Johnston, Olwyn; Chang, Shirley S.; Solez, Kim; Santos, Vicki; Larson, Tami J.; Takeuchi, Masahiro; Wang, Xuegong; Surgery, School of MedicineBackground: Focal segmental glomerulosclerosis (FSGS) is a common cause of end-stage kidney disease and frequently recurs after kidney transplantation. Recurrent FSGS (rFSGS) is associated with poor allograft and patient outcomes. Bleselumab, a fully human immunoglobulin G4 anti-CD40 antagonistic monoclonal antibody, disrupts CD40-related processes in FSGS, potentially preventing rFSGS. Methods: A phase 2a, randomized, multicenter, open-label study of adult recipients (aged ≥18 y) of a living or deceased donor kidney transplant with a history of biopsy-proven primary FSGS. The study assessed the efficacy of bleselumab combined with tacrolimus and corticosteroids as maintenance immunosuppression in the prevention of rFSGS >12 mo posttransplantation, versus standard of care (SOC) comprising tacrolimus, mycophenolate mofetil, and corticosteroids. All patients received basiliximab induction. The primary endpoint was rFSGS, defined as proteinuria (protein-creatinine ratio ≥3.0 g/g) with death, graft loss, or loss to follow-up imputed as rFSGS, through 3 mo posttransplant. Results: Sixty-three patients were followed for 12 mo posttransplantation. Relative decrease in rFSGS occurrence through 3 mo with bleselumab versus SOC was 40.7% (95% confidence interval, -89.8 to 26.8; P = 0.37; absolute decrease 12.7% [95% confidence interval, -34.5 to 9.0]). Central-blinded biopsy review found relative (absolute) decreases in rFSGS of 10.9% (3.9%), 17.0% (6.2%), and 20.5% (7.5%) at 3, 6, and 12 mo posttransplant, respectively; these differences were not statistically significant. Adverse events were similar for both treatments. No deaths occurred during the study. Conclusions: In at-risk kidney transplant recipients, bleselumab numerically reduced proteinuria occurrence versus SOC, but no notable difference in occurrence of biopsy-proven rFSGS was observed.Item Excellent outcomes in combined liver-kidney transplantation: Impact of KDPI and delayed kidney transplantation(Wiley, 2017) Ekser, Burcin; Mangus, Richard S.; Kubal, Chandrashekhar A.; Powelson, John A.; Fridell, Jonathan A.; Goggins, William C.; Surgery, School of MedicineThe positive impact of delayed kidney transplantation (KT) on patient survival for combined liver-KT (CLKT) has already been demonstrated by our group. The purpose of this study is to identify whether the quality of the kidneys (based on KDPI) or the delayed approach KT contributes to improved patient survival. 130 CLKT were performed between 2002-2015; 69 with simultaneous KT (Group S) and 61 with delayed KT (Group D) (performed as a second operation with a mean cold ischemia time [CIT] of 50±15h). All patients were categorized according to the KDPI score; 1-33%, 34-66%, and 67-99%. Recipient and donor characteristics were comparable within Groups S and D. Transplant outcomes were comparable within Groups S and D, including liver and kidney CIT, warm ischemia time, and delayed graft function. Lower KDPI kidneys (<34%) were associated with increased patient survival in both groups. Combination of delayed KT and KDPI 1-33% resulted in 100% patient survival at 3-years. These results support that delayed KT in CLKT improves patient survival. The combination of delayed KT and low KDPI offers excellent patient survival up to 3-years. Improved outcomes in the delayed KT group including high KDPI kidneys supports expansion of the donor pool with the use of more ECD and DCD kidneys.Item Genetic engineering of porcine endothelial cell lines for evaluation of human-to-pig xenoreactive immune responses(Springer Nature, 2021-06-23) Li, Ping; Walsh, Julia R.; Lopez, Kevin; Isidan, Abdulkadir; Zhang, Wenjun; Chen, Angela M.; Goggins, William C.; Higgins, Nancy G.; Liu, Jianyun; Brutkiewicz, Randy R.; Smith, Lester J.; Hara, Hidetaka; Cooper, David K.C.; Ekser, Burcin; Surgery, School of MedicineXenotransplantation (cross-species transplantation) using genetically-engineered pig organs offers a potential solution to address persistent organ shortage. Current evaluation of porcine genetic modifications is to monitor the nonhuman primate immune response and survival after pig organ xenotransplantation. This measure is an essential step before clinical xenotransplantation trials, but it is time-consuming, costly, and inefficient with many variables. We developed an efficient approach to quickly examine human-to-pig xeno-immune responses in vitro. A porcine endothelial cell was characterized and immortalized for genetic modification. Five genes including GGTA1, CMAH, β4galNT2, SLA-I α chain, and β2-microglobulin that are responsible for the production of major xenoantigens (αGal, Neu5Gc, Sda, and SLA-I) were sequentially disrupted in immortalized porcine endothelial cells using CRISPR/Cas9 technology. The elimination of αGal, Neu5Gc, Sda, and SLA-I dramatically reduced the antigenicity of the porcine cells, though the cells still retained their ability to provoke human natural killer cell activation. In summary, evaluation of human immune responses to genetically modified porcine cells in vitro provides an efficient method to identify ideal combinations of genetic modifications for improving pig-to-human compatibility, which should accelerate the application of xenotransplantation to humans.Item Impact of Recipient Age in Combined Liver-Kidney Transplantation: Caution Is Needed for Patients ≥70 Years(Wolters Kluwer, 2020-06) Ekser, Burcin; Goggins, William C.; Fridell, Jonathan A.; Mihaylov, Plamen; Mangus, Richard S.; Lutz, Andrew J.; Soma, Daiki; Ghabril, Marwan S.; Lacerda, Marco A.; Powelson, John A.; Kubal, Chandrashekhar A.; Surgery, School of MedicineBackground. Elderly recipients (≥70 y) account for 2.6% of all liver transplants (LTs) in the United States and have similar outcomes as younger recipients. Although the rate of elderly recipients in combined liver-kidney transplant (CLKT) is similar, limited data are available on how elderly recipients perform after CLKT. Methods. We have previously shown excellent outcomes in CLKT using delayed kidney transplant (Indiana) Approach (mean kidney cold ischemia time = 53 ± 14 h). Between 2007 and 2018, 98 CLKTs were performed using the Indiana Approach at Indiana University (IU) and the data were retrospectively analyzed. Recipients were subgrouped based on their age: 18–45 (n = 16), 46–59 (n = 34), 60–69 (n = 40), and ≥70 years (n = 8). Results. Overall, more elderly patients received LT at IU (5.2%) when compared nationally (2.6%). The rate of elderly recipients in CLKT at IU was 8.2% (versus 2% Scientific Registry of Transplant Recipient). Recipient and donor characteristics were comparable between all age groups except recipient age and duration of dialysis. Patient survival at 1 and 3 years was similar among younger age groups, whereas patient survival was significantly lower in elderly recipients at 1 (60%) and 3 years (40%) (P = 0.0077). Control analyses (replicating Scientific Registry of Transplant Recipient’s survival stratification: 18–45, 46–64, ≥65 y) showed similar patient survival in all age groups. Conclusions. Although LT can be safely performed in elderly recipients, extreme caution is needed in CLKT due to the magnitude of operation.Item Impact of Recipient Age in Combined Liver-Kidney Transplantation: Caution Is Needed for Patients ≥70 Years(Wolters Kluwer, 2020-06-01) Ekser, Burcin; Goggins, William C.; Fridell, Jonathan A.; Mihaylov, Plamen; Mangus, Richard S.; Lutz, Andrew J.; Soma, Daiki; Ghabril, Marwan S.; Lacerda, Marco A.; Powelson, John A.; Kubal, Chandrashekhar A.; Surgery, School of MedicineBackground. Elderly recipients (≥70 y) account for 2.6% of all liver transplants (LTs) in the United States and have similar outcomes as younger recipients. Although the rate of elderly recipients in combined liver-kidney transplant (CLKT) is similar, limited data are available on how elderly recipients perform after CLKT. Methods. We have previously shown excellent outcomes in CLKT using delayed kidney transplant (Indiana) Approach (mean kidney cold ischemia time = 53 ± 14 h). Between 2007 and 2018, 98 CLKTs were performed using the Indiana Approach at Indiana University (IU) and the data were retrospectively analyzed. Recipients were subgrouped based on their age: 18–45 (n = 16), 46–59 (n = 34), 60–69 (n = 40), and ≥70 years (n = 8). Results. Overall, more elderly patients received LT at IU (5.2%) when compared nationally (2.6%). The rate of elderly recipients in CLKT at IU was 8.2% (versus 2% Scientific Registry of Transplant Recipient). Recipient and donor characteristics were comparable between all age groups except recipient age and duration of dialysis. Patient survival at 1 and 3 years was similar among younger age groups, whereas patient survival was significantly lower in elderly recipients at 1 (60%) and 3 years (40%) (P = 0.0077). Control analyses (replicating Scientific Registry of Transplant Recipient’s survival stratification: 18–45, 46–64, ≥65 y) showed similar patient survival in all age groups. Conclusions. Although LT can be safely performed in elderly recipients, extreme caution is needed in CLKT due to the magnitude of operation.Item Is the kidney donor profile index (KDPI) universal or UNOS-specific?(Wiley, 2017) Ekser, Burcin; Powelson, John A.; Fridell, Jonathan A.; Goggins, William C.; Taber, Tim E.; Surgery, School of MedicineItem A National Survey of Practice Patterns for Accepting Living Kidney Donors With Prior COVID-19(Science Direct, 2021-08-01) Jan, Muhammad Y.; Jawed, Areeba T.; Barros, Nicolas; Adebiyi, Oluwafisayo; Diez, Alejandro; Fridell, Jonathan A.; Goggins, William C.; Yaqub, Muhammad S.; Anderson, Melissa D.; Mujtaba, Muhammad A.; Taber, Tim E.; Mishler, Dennis P.; Kumar, Vineeta; Lentine, Krista L.; Sharfuddin, Asif A.; Medicine, School of MedicineIntroduction A critical question facing transplant programs is whether, when, and how to safely accept living kidney donors (LKDs) who have recovered from COVID-19 infection. The purpose of the study is to understand current practices related to accepting these LKDs. Methods We surveyed US transplant programs from 3 September through 3 November 2020. Center level and participant level responses were analyzed. Results A total of 174 respondents from 115 unique centers responded, representing 59% of US LKD programs and 72.4% of 2019 and 72.5% of 2020 LKD volume (Organ Procurement and Transplantation Network-OPTN 2021). In all, 48.6% of responding centers had received inquiries from such LKDs, whereas 44.3% were currently evaluating. A total of 98 donors were in the evaluation phase, whereas 27.8% centers had approved 42 such donors to proceed with donation. A total of 50.8% of participants preferred to wait >3 months, and 91% would wait at least 1 month from onset of infection to LD surgery. The most common reason to exclude LDs was evidence of COVID-19−related AKI (59.8%) even if resolved, followed by COVID-19−related pneumonia (28.7%) and hospitalization (21.3%). The most common concern in accepting such donors was kidney health postdonation (59.2%), followed by risk of transmission to the recipient (55.7%), donor perioperative pulmonary risk (41.4%), and donor pulmonary risk in the future (29.9%). Conclusion Practice patterns for acceptance of COVID-19−recovered LKDs showed considerable variability. Ongoing research and consensus building are needed to guide optimal practices to ensure safety of accepting such donors. Long-term close follow-up of such donors is warranted.