Challenges in Diagnosis and Management: A Rare Case of Antithymocyte Globulin Induced Noncardiogenic Pulmonary Edema in Renal Transplant Recipient

Dear Editor, A 32-year-old female, a diagnosed case of thrombotic microangiopathy-induced chronic renal failure, on dialysis, was posted for live donor renal transplant. She was hypertensive for 1 year taking tablets amlodipine 5 mg BD, prazosin 5 mg BD, metoprolol succinate 25 mg OD, and torsemide 20 mg. The preoperative evaluation showed normal electrocardiogram, and 2-dimensional echocardiography (2D ECHO) revealed 40% ejection fraction (EF), global left ventricular (LV) hypokinesia, and LV hypertrophy (LVH). Her preoperative vitals showed heart rate of 103/min, blood pressure of 134/98 mmHg, and room air saturation of 100%. A day before surgery, she underwent plasmapheresis followed by dialysis. On the day of surgery, antithymocyte globulin (ATG) infusion was started, and within 1 h of infusion, she developed tachypnea and SpO2 dropped to 84%–86%. Auscultation revealed bilateral coarse crepitations. ATG was stopped immediately, she was put on oxygen mask, and intravenous (IV) injection of frusemide 40 mg and injection hydrocortisone 100 mg were given. She was then shifted to the intensive care unit (ICU) for further evaluation and management. Fresh 2D ECHO showed EF of 30%, global LV hypokinesia, dilated left atrium and ventricle, severe mitral and tricuspid regurgitation, severe pulmonary arterial hypertension, and mild concentric LVH. Her chest X-ray showed bilateral pulmonary opacities [Figure 1]. The cardiac enzymes were as follows creatine kinase-myoglobin binding (CK-MB) 13.20 U/L, troponin-I - 15.70 ug/L, and N-terminal pro brain natriuretic peptide (NT-pro BNP) >35,000. Patient’s dyspnea relieved after IV injection of furosemide, and her oxygen saturation also improved to 96%. She underwent dialysis and was monitored in the ICU for 4 days. During her stay in ICU, she underwent dialysis and plasmapheresis. She was also doing spirometry and chest physiotherapy. The surgery was rescheduled after six days and this time instead of ATG, injection tacrolimus and mycophenolate mofetil were given for immunosuppresion. The surgery was uneventful, and the patient was shifted to ICU after extubation.Figure 1: X-ray Chest showing prominent bronchovascular markingsThe present patient was completely asymptomatic till she received IV injection of ATG. Within an hour of the injection, she developed acute-onset tachypnea with hypoxemia, bilateral crepitations on auscultation, and bilateral pulmonary infiltrates on chest X-ray pointed out toward the development of pulmonary edema (PE). The cause of the PE could be cardiogenic or noncardiogenic. This patient was a case of chronic kidney disease on dialysis with LV dysfunction. Such patients can develop cardiogenic PE if fluid overloaded.[1] Furthermore, her NT-Pro BNP was fairly raised. Hence, the first impression was of cardiogenic PE. However, it was observed that this episode occurred immediately after injection of ATG. Hence, the possibility of ATG to be a contributing factor cannot be denied. Upon literature search, we found out that there are cases where ATG has caused acute respiratory distress syndrome, serum sickness, and also serious complications such as noncardiogenic PE (NCPE).[2,3] ATG is basically a polyclonal antibody that is often used as an induction therapy for immunosuppression in renal transplant patients to prevent or treat acute rejection, particularly where risk of rejection is high.[4] It acts by depleting T cells.[4] The mechanism behind ATG-associated NCPE is observed to be due to the immune reaction and complement activation, leading to increased permeability of pulmonary capillaries and leakage of fluid into the alveoli. The points against favor of cardiogenic PE were: (1) she underwent dialysis a day prior and did not receive any IV fluid therapy, (2) during the period of 4 months when she was undergoing twice weekly dialysis, she never developed PE, (3) six days later, she underwent uneventful surgery when ATG was omitted, and (4) other features of cardiogenic PE such as raised jugular venous pressure and cough were absent. The definitive diagnosis of NCPE requires calculating the pulmonary capillary wedge pressure, with an anticipated value of <18 mmHg. However, in our particular case, this diagnostic procedure was not conducted. The other proposed cause was that ATG can cause cytokine release, leading to tachycardia, tachypnea, nausea, hypotension, and rash. The inflammatory reaction along with tachycardia can itself aggravate the already compromised heart, leading to cardiogenic PE.[2] However, there is no definitive investigation to find out the exact cause, but our case report does emphasize on cautious use of ATG, especially in cardiac patients undergoing renal transplant. This letter is to make aware of cautious use of ATG and to consider safer alternative options. Declaration of patient consent The authors certify that patient consent has been taken for participation in the study and for publication of clinical details and images. Patients understand that the names, initials would not be published, and all standard protocols will be followed to conceal their identity. Financial support and sponsorship Nil. Conflicts of interest There are no conflicts of interest.