Antibody-Mediated Rejection Management Following Lung Transplantation.

BACKGROUND: Although antibody-mediated rejection (AMR) is described in other solid organ transplant populations, the literature describing the management following lung transplantation is limited. OBJECTIVE: The purpose of this study is to evaluate the management strategies of AMR in lung transplant recipients. METHODS: This single-center, retrospective study described the management of AMR in adult lung transplant recipients who received treatment with rabbit antithymocyte globulin, bortezomib, rituximab, intravenous immune globulin (IVIG), and/or plasmapheresis between September 2015 and June 2019. RESULTS: A total of 270 medication orders for 55 patient admissions were included in the primary outcome analysis. The most commonly used regimen consisted of IVIG, plasmapheresis, and rituximab (49.1%; n = 27), followed by IVIG and plasmapheresis alone (27.3%, n = 15). A total of 51 patients (93%) received plasmapheresis as part of their AMR treatment, with a median of 4 [3, 5] sessions per encounter; 86% of patients with positive donor-specific antibodies (DSAs) had a reduction in DSAs following AMR treatment. Overall, 23.5% of patients had noted allograft failure or need for retransplantation. A total of 10 patients died during the AMR treatment hospital admission, and an additional 11 patients died within 1 year of the initial encounter. CONCLUSION AND RELEVANCE: This represents the largest report describing management strategies of AMR in lung transplant recipients. Although practice varied, the most commonly used regimen consisted of plasmapheresis, IVIG, and rituximab.

Respiratory failure and sepsis are the major causes of ICU admissions and mortality in survivors of lung transplants.

STUDY OBJECTIVE: To identify outcome predictors and prognostic factors in long-term survivors (> 30 days post-transplant) of single-lung and double-lung transplants on readmission to the medical ICU (MICU). DESIGN: Retrospective study. SETTING: MICU of the Cleveland Clinic Foundation, a lung transplantation center. PATIENTS: As of August 2000, 210 lung transplantations have been performed at our institution. The records of 33 lung transplant recipients who required readmission to the MICU after the initial 30-day post-transplant period over a 4-year period from August 16, 1996 to August 15, 2000 were reviewed. RESULTS: Thirty-three patients had a total of 46 MICU readmissions. Twenty-seven MICU admissions (59%) were due to respiratory deterioration with mechanical ventilation (10 deaths), and 16 MICU admissions (35%) were due to the systemic inflammatory response syndrome (SIRS; 8 deaths). The MICU mortality rate was 37% per admission in our group of patients. A preadmission diagnosis of bronchiolitis obliterans syndrome was observed in 7 of 14 nonsurvivors (50%) and in 5 of 25 patients (20%) surviving to hospital discharge. CONCLUSIONS: Respiratory failure and SIRS are the predominant causes of MICU readmissions and are frequent causes of death. APACHE (acute physiology and chronic health evaluation) III scores, nonpulmonary organ system dysfunction, initial serum albumin level, and duration of mechanical ventilation are important prognostic factors.

Effects of adding steroids, in vitro irradiation, or both to cyclosporine immunosuppression in the murine laryngeal transplantation model.

Adding oral prednisone or in vitro organ irradiation to an immunosuppressive regimen for laryngeal transplantation may allow cyclosporine dosage to be decreased without compromising organ rejection rates. Using an established rat laryngeal transplant model, we sought to determine whether combined immunosuppressive regimens decreased rejection rates. Twenty-two treatment groups of 10 animals each were studied. Cyclosporine was administered at 2 different historically low dosages (1.5 and 2 mg/kg per day) alone, in combination with prednisone, and with in vitro irradiation of the harvested larynx. At 15 days after transplantation, cyclosporine combined with prednisone did not significantly alter the mean severity of rejection. At 30 days after transplantation, rats treated with a combination of cyclosporine 2 mg/kg and prednisone 1 mg/kg showed the least amount of rejection. Rejection rates were significantly higher with 2 mg/kg cyclosporine alone (p < .00024). Irradiation did not significantly decrease the severity of rejection. These results demonstrate that at 1 month after transplantation, a combined steroid and cyclosporine regimen reduces the severity of rejection after laryngeal transplantation in an animal model. Our findings suggest that laryngeal transplant patients may be treated with low cyclosporine doses without experiencing organ rejection if steroids are added to the immunosuppressive regimen.

Cyclosporine dose, serum trough levels, and allograft preservation in a rat model of laryngeal transplantation.

Using a rat model of laryngeal transplantation, we sought to define the relationships between acute laryngeal rejection grade (RG) and cyclosporin A (CSA) concentration and CSA dosage. Five recipient Lewis rat groups (N = 10 per group) were administered intramuscular CSA doses of 1.0 (group 1), 2.5 (group 2), 5.0 (group 3), 7.5 (group 4), and 10 mg/kg per day (group 5) for 14 days. Immediately before sacrifice, 5 mL of whole blood was obtained to assay CSA trough levels by high-performance liquid chromatography. The specimens were graded microscopically by blinded reviewers by day of RG, 0 to 14 days after transplantation, as described in earlier reports. Despite high intragroup variability in CSA levels, significantly different mean CSA concentrations were achieved among all CSA dosage groups: 1, 2, 3, 4, and 5 (.0001 < p < .02). The mean laryngeal RGs did not test significantly different from each other with groups 3, 4, and 5 (RG, 2.3 +/- 1.3 versus 1.9 +/- 1.1 versus 1.7 +/- 0.3, respectively, .2 < p < .6). The RG for group 1 was significantly greater than those for groups 2 through 5 (p < .001), and the group 2 RG was greater (p < .02) than those for groups 3, 4, and 5. Polynomial fitting was used to determine the continuous relationship between each individual specimen's CSA concentration and the RG. Significant pathological allograft rejection correlated with CSA concentrations below 250 ng/mL.

Dialysis after lung transplantation: prevalence, risk factors and outcome.

BACKGROUND: Renal failure requiring dialysis after lung transplantation represents a major source of morbidity for patients and compromises their quality of life. We sought to ascertain the prevalence of dialysis after lung transplantation and to identify risk factors for its occurrence. We also assessed outcomes after institution of dialysis. METHODS: From our program's inception in February 1990 until January 2005, 425 patients underwent lung transplantation. Data on dialysis occurrence, timing, management and outcome were extracted from the Unified Transplant Database, patient follow-up and medical record review. RESULTS: Thirty-seven patients developed a need for dialysis, a prevalence of 0.6%, 4%, 9%, 13%, 16% and 19%, at 30 days and 1, 3, 5, 7 and 9 years after transplant, respectively. Lower creatinine clearance (p = 0.03) and greater recipient height (p = 0.0002) increased the risk for dialysis, whereas donor blood type O (p = 0.001) and head trauma as donor cause of death (p = 0.01) lowered it. Higher doses of calcineurin inhibitors correlated with the period of highest risk for dialysis. Median survival of patients requiring dialysis was 5 months, considerably lower than expected. Four patients underwent renal transplantation, 3 of whom were still alive 3, 6 and 9 months later. CONCLUSIONS: Dialysis after lung transplantation is common and cumulative over time. Risk factors for its development may be modifiable because they appear to be linked to nephrotoxicity secondary to immunosuppression. The low threshold for creatinine clearance appears to be 50 ml/min/1.73 m(2). Survival after institution of dialysis is poor, highlighting the need for prevention. Renal transplantation may be a reasonable therapeutic option.