THE NEPHROLOGIST'S ROLE IN THERAPEUTIC PLASMA EXCHANGE FOR SUCCESSFUL ABO-INCOMPATIBLE LUNG TRANSPLANTATION: A CASE REPORT

The successful application of ABO-incompatible (ABO-i) kidney transplantation has led to a growing interest in its application to lung transplantation (LTx), as it may alleviate potential organ shortages. Worldwide, LTx rates have decreased during the COVID-19 pandemic, which has had a significant impact on waiting list mortality. According to the National Institute of Health's 2022 annual report, LTx accounted for only 3.6% of all transplants in Colombia [1]. 

LTx is generally avoided in ABO-i (A, B, or AB to O) grafts because of the risk of hyperacute or acute antibody-mediated rejection (AMR) as a contributor to limited allograft survival. There is a legitimate interest in the role of ABO-i LTx as a justified life-saving therapy for recipients with type O blood in urgent status. The lack of immunosuppression and desensitization protocols described in the literature on ABOi LTx has led to reliance on useful experience in kidney transplant centers and few observational studies [2–5]. 

Therapeutic plasma exchange (TPE) is commonly used for allograft rejection after transplantation. In our hospital, TPE is prescribed by nephrologists based on evidence-based guidelines. However, there is a lack of evidence for managing ABO-i LTx. We report three cases of brain-dead donor ABO-i LTx where TPE was used without rituximab or IVIG as a prophylactic strategy to prevent AMR.

Case presentation 

Case 1:  A 29-year-old man with no medical history was admitted to the ICU for COVID19-related acute respiratory distress syndrome. After 16 days, he required invasive mechanical ventilation and underwent early tracheostomy. Severe pulmonary fibrosis led to initiation of venovenous extracorporeal membrane oxygenation (VV-ECMO). Seven months later, he underwent sequential bilateral ABO-i LTx (donor type B, recipient type O) as status 0 (Fig. 1a). Extubation occurred on day 7 with adequate lung graft function. Immunosuppressive induction included methylprednisolone, antithymocyte globulin and mycophenolate. Conventional membrane TPE (Baxter PRISMAFLEX TPE 2000 Hemofilter Set; 100% fresh frozen plasma, 1 plasma volume) was started on day 2 post-op. Fifteen TPE sessions were performed based on anti-B isoagglutinin titers, with clearance and stability achieved on day 23 post-LTx (Fig. 2). Maintenance immunosuppression with tacrolimus and prednisone was started with monitoring of levels after the TPE sessions. He was discharged on day 33 and started pulmonary rehabilitation. At 12 months follow-up, significant improvement in lung function and quality of life was observed. 

Case 2: A 16-year-old female with advanced cystic fibrosis, carrying a heterozygous CFTR gene mutation (c.3484 C > T p.Arg1162*), had frequent pulmonary exacerbations. She had 7 intensive care admissions in the past year. Prior to transplantation, she developed mixed respiratory failure, unresponsive to invasive mechanical ventilation. Urgent VV-ECMO cannulation and tracheostomy were required, with prolonged weaning. One month later, she underwent sequential bilateral ABO-i LTx (donor type A, recipient type O) as status 0 (Fig. 1b). Lung graft function allowed extubation on day 17. Immunosuppressive induction therapy included methylprednisolone, anti-thymocyte globulin and mycophenolate. Conventional membrane TPE (Baxter PRISMAFLEX TPE 2000 Hemofilter Set; 100% albumin [5%], 1.5 plasma volume) was started on day 1 postoperatively. A total of 10 sessions of TPE were performed based on daily measurements of anti-A isoagglutinin titers, which reached clearance and stability on day 21 post-LTx (Fig. 2). Maintenance immunosuppression therapy with tacrolimus and prednisone was administered according to protocol. The patient was discharged on day 39 post-LTx and started a pulmonary rehabilitation program. No allograft rejection was observed at the 12-month follow-up. 

Case 3: An 18-year-old female with advanced cystic fibrosis required invasive mechanical ventilation in the ICU due to severe hypercapnic respiratory failure. She experienced cardiopulmonary arrest and relied on peripheral VV-ECMO support for 59 days. Despite being status 0 for 18 days (Fig. 1c), she underwent sequential bilateral ABO-i LTx (donor type B, recipient type O) with veno-arterio-venous ECMO as a bridge and was successfully weaned off on day 19. Complications included post-resuscitation status with cerebral and cerebellar infarcts, hypoxic-ischemic encephalopathy, and focal epilepsy. Primary left lung graft dysfunction and necrotizing pneumonia due to E. coli BLEE (CTX-M) also developed. Broad-spectrum antibiotics were used and percutaneous tracheostomy was performed. Extubation occurred on day 49 after prolonged weaning. Immunotherapy included methylprednisolone, anti-thymocyte globulin and mycophenolate. Conventional membrane TPE (Baxter PRISMAFLEX TPE 2000 Hemofilter Set; 100% fresh frozen plasma, 1 plasmatic volume) was started on day 2 post-op and continued for 6 sessions based on anti-B isoagglutinin titers, which normalized on day 20 post-LTx (Fig. 2). The patient was discharged on day 111 post-LTx. At 5-month follow-up, pulmonary improvement was observed with continued rehabilitation. 

Results