Case Presentation: A 21-year-old female with a past medical history of nephrotic syndrome, due to membranous nephropathy, presented to the emergency department (ED) with symptoms of left sided flank pain and shortness of breath. The patient was previously seen in the ED with similar symptoms 2 weeks prior and was diagnosed with pneumonia and discharged on antibiotics. She then returned to the ED with worsening symptoms despite antibiotic completion. Upon initial evaluation, the patient had a temperature of 101.2 °F, heart rate of 125 beats/min, blood pressure of 142/76 mm Hg, and pulse oxygen saturation of 96 on 2L nasal cannula. On physical exam lower extremity edema was noted. Complete blood count, liver enzymes, renal function test, N-terminal pro-brain natriuretic peptide (NT-proBNP), and cardiac troponin were unremarkable. However, urine protein to creatinine ratio was 9 g/day, albumin and total plasma protein were low, and low-density lipoprotein and total cholesterol were high. Echocardiography and lower extremity venous ultrasound were normal. Electrocardiogram was significant for sinus tachycardia. Chest radiograph showed left basilar pneumonia and antibiotic treatment was begun. However, due to the patient’s history of nephrotic syndrome, clinical presentation, hypoxemia, and tachycardia, pulmonary embolism (PE) was suspected. Computed tomography pulmonary angiogram (CTA) was done which was positive for bilateral thromboemboli seen primarily in the right and left lower lobe pulmonary artery branches. The risk stratification for this patient was low-risk, however simplified PE severity index score was 1. The patient was started on anticoagulation therapy with apixaban and discharged from the hospital 8 days later with continuation of anticoagulation and Losartan for proteinuria.
Discussion: Nephrotic syndrome is characterized by proteinuria, hypoalbuminemia, hyperlipidemia, and edema, which were all present in this patient. The combination of albumin and anticoagulant protein loss in urine, increased fibrinogen and coagulation factors, and systemic inflammation causing endothelial dysfunction, predisposes patients with nephrotic syndrome to venous thromboembolism (VTE). PE is an example of VTE which is a life-threatening complication in nephrotic syndrome. Thus, it is important to consider PE in these patients who present with any symptoms and/or clinical features of PE. Non-specific symptoms can mask signs of PE and some patients may be asymptomatic. The estimated prevalence of asymptomatic PE in patients with nephrotic syndrome ranges from 12-30% (1, 2). This young patient’s generalized symptoms were initially attributed to pneumonia, however considering the hypercoagulable state and clinical features such as tachycardia and hypoxemia, PE was diagnosed. Although nephrotic syndrome is known to be a hypercoagulable state, few reports of PE secondary to nephrotic syndrome have been noted in literature. Consequently, the diagnosis of PE in this patient population may be delayed or missed due to atypical presentations. Studies have shown the risk of thrombosis is significantly higher with albumin concentration of < 2.8 g.dL and anticoagulation should be considered in these patients (3).
Conclusions: PE is a common but frequently overlooked complication in nephrotic syndrome. Patients with atypical presentations should still be considered for PE especially in the setting of hypoalbuminemia due to its high mortality/morbidity if not diagnosed and treated promptly.