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DIFFUSE LUNG PROCESS IN A RENAL TRANSPLANT PATIENT

New York Hospital Queens, Flushing, NY

INTRODUCTION: Many etiologies cause diffuse lung processes in renal transplant patients whose diagnostic workup is limited by hypoxia. We discuss a case of diffuse lung infiltrates in a severely hypoxic patient without definite diagnosis after recent hospital discharge. We obtained a proper diagnosis, instituted least invasive therapy, and graduated to invasive ones.

CASE PRESENTATION: A 41 year-old female saturating at 88% on 6L oxygen by nasal cannula (NC) was admitted to the hospital. Patient was recently discharged from another hospital. Past medical history was significant for renal transplant three years ago. Post-transplant, treatment included sirolimus and prednisone. Sirolimus was substituted by tacrolimus a month before current hospitalization. History also includes treated pulmonary tuberculosis (TB) two years prior to current hospitalization.Prior hospitalization records revealed that patient suffered hypoxic respiratory failure, leading to intubation, broad-spectrum drug therapy for possible pneumonia, and pneumocystis pneumonia (PCP) prophylaxis. Radiographic studies revealing bilateral patchy infiltrates were similar to studies done two years prior. Patient underwent fiber-optic bronchoscopy that ruled out tuberculosis and PCP. Patient was extubated to non-invasive ventilation and discharged home with supplementary oxygen. Pre-admission chest CAT scan revealed bilateral extensive ground-glass opacities with "crazy paving" pattern. Admission labs were within normal limits, except elevated H/H (18.4/54.1) and LDH (216). ABG on 100% non-rebreather mask was 7.37/30/89.3 with 97% saturation. Patient underwent lung biopsy via video assisted thoracoscopy (VATS).Lung biopsy showed eosinophilic material filled alveolar spaces, focally dense globules, cholesterol clefts, and clear punched out spaces—consistent with Pulmonary Alveolar Proteinosis (PAP). No PCP or TB was present.Patient treated with four sessions of bronchial lung lavage using 1-1.5L warmed normal saline (NS) in 60mL eliquotes. Each session lasted up to 1.5 hours. She responded with improved oxygenation but with neither radiographic improvement nor correlation with LDH values. The lavages facilitated discharge on 4L NC. Worsening A-a gradient after discharge prompted three sessions of whole lung lavage under general anesthesia using double lumen intubation. Lavages were performed using 10-18L of warmed NS, starting with left lung and followed a week later with two sessions with right lung.Patiently presently requires no supplemental oxygen and follow up chest CAT scan reveals marked improvement in interstitial/alveolar changes.

DISCUSSIONS: Interstitial pneumonias have been associated with sirolimus therapy in renal transplant recipients, and two specific cases of PAP have been reported. In our patient, PAP is likely associated with sirolimus use. The earliest recorded radiographic abnormalities occurred approximately one year into her three year sirolimus use. We are seeking a laboratory to measure presence of anti GM-SCF antibody in lavage fluid, possibly supporting use of novel therapeutic options (nebulized and subcutaneous GM-SCF).Diagnosis was established by VATS biopsy, the gold standard. We treated our patient with fiberoptic bronchoscopic lavage using NS, but the treatment duration was limited by hypoxia and intractable cough. Despite short-term improvement in oxygen saturation, patient showed no physiologic or radiographic improvement. Our patient tolerated whole lung lavage, with optimal oxygenation and perfusion during the procedure, including immediate post-procedure extubation. Patient showed functional, physiologic, and radiographic improvement with each session.

CONCLUSION: PAP remains an enigmatic disease process with unclear reasons for progression in some and resolution without therapy in others. In our experience, bronchoscopic lavage may benefit patients with limited disease, but in cases of extensive lung involvement, whole lung lavage is more beneficial. Our patient currently requires no oxygen supplementation, and her recent chest x-ray shows almost complete resolution of the infiltrates.

DISCLOSURE: Sukriti Singhal, None.

REFERENCES:

1. Seethamraju H, Kaleekal TS, Bag, R. "Pulmonary Toxicity of Sirolimus in Lung Transplant Patients." Chest2003; 124 :101S .[Abstract]
2. Singer SJ, Tiernan R, Sullivan EJ. "Interstitial Pneumonitis Associated with Sirolimus Therapy in Renal-Transplant Recipients" [letter] NEJM2000; 343 :1815 -6.[Free Full Text]