DOI: https://doi.org/10.21203/rs.3.rs-58762/v2
Nephrotic syndrome (NS) was first described in 1827 as the presence of proteinuria of ≥3.5 g/24 hours, albuminemia <3.0 g, peripheral edema, hyperlipidemia, lipiduria, and increased thrombotic risk. Nephrotic syndrome has an incidence of three cases per 100 000 each year in adults. Nephrotic syndrome also has serious complications due to hypercoagulable state in both various venous and arteries which could lead thromboembolic events. The pathophysiology of hypercoagulability in the nephrotic syndrome is due to an imbalance of prothrombotic and antithrombotic factors, as well as impaired thrombolytic activities.
Here we will present 19 years old women who presented to the emergency department complaining of chest pain and shortness of breath for three days. The patient was quickly diagnosed with pulmonary embolism and inferior vena cava thrombosis as a complication of nephrotic syndrome, allowing prompt initiation of anticoagulant therapy. After two weeks of admission, the patient's condition resolved, her laboratory results returned to almost normal and the patient was discharged with Oral Prednisolone, Coumadin, Atorvastatin, and Ramipril. We are aim to determine which is the likely cause of pulmonary embolism in patients with the nephrotic syndrome.
Nephrotic syndrome (NS) was first described in 1827 as the presence of proteinuria of ≥3.5 g/24 hours, albuminemia <3.0 g, peripheral edema, hyperlipidemia, lipiduria, and increased thrombotic risk (1,2). Nephrotic syndrome has an incidence of three cases per 100 000 each year in adults (3). Thromboembolism, including pulmonary embolism, deep venous thrombosis (DVT), renal vein thrombosis, and inferior vena cava thrombosis have been reported as a life-threatening complication of nephrotic syndrome patients(4). Enhanced platelet aggregation and loss of anticoagulant proteins including AT‑III through renal are thought to cause the excessive thrombotic risk in patients with nephrotic syndrome (4,5). Here we present a case of an unusual combination of multiple venous thromboses as the presentation of nephrotic syndrome.
A 19 years old female, previously healthy, nonsmoker, non-diabetic came to the emergency department with a complaint of chest pain and shortness of breath for three days.
She never had a similar incident before. She does not have any history of drug use including oral contraceptive drugs. On examination, the patient looked ill, anxious, tachyapneic, and edematous. On vital signs, her respiratory rate was 23 breath/minute, blood pressure 110/70 mm/hg, pulse 112 bpm, and oxygen saturation was 90%. Head and neck examination were unremarkable. Tachycardia was the only prominent sign of cardiovascular findings. The respiratory evaluation revealed diminished breath sounds in both lungs. Grade 2+ lower limb edema noted during the examination while other systems examination were unremarkable. Laboratory investigations including complete blood count, and serum electrolytes revealed normal range. Regarding the liver function test, AST was 35U/L, ALT was 16U/L, total protein was 4g/dl and Albumin was 1.9g/dl. Total cholesterol was 450mg/dl and lactate dehydrogenase was 639 U/l. HBV, HCV, HIV, RF, and tumor screenings were all in the normal range or negative. The D-dimer (>4μg /ml) and 24-hour urinary protein excretion (10 g) were positive. As there had no obvious predisposing factor for PE, tests for the etiology of the thrombophilic state were ordered. While waiting the results in the emergency, oxygen therapy with high flow nasal cannula was started along with subcutaneous low molecular weight heparin.
Chest x-ray and electrocardiograms were unremarkable. Abdominal ultrasonography detected mild ascites. Computed tomography (CT) angiography of the chest and abdomen revealed thrombus at both right and left pulmonary arteries and inferior vena cava (figure 1-A & B). The patient was admitted for nephrotic syndrome complicated with pulmonary embolism and inferior vena cava thrombosis.
The patient was started on heparin, Ramipril, Methylprednisolone and atorvastatin. Two days later Coumadin tablet was added. After two weeks of hospitalization, the patient symptoms resolved, lower limb edema decreased, proteinuria was not detected and albumin returned to the normal range. The patient was discharged with Oral Prednisolone, Coumadin, Atorvastatin and Ramipril. Close follow up was recommended for the patient. The patient’s six months follow up revealed no complaints and no thrombus on the repeated chest CT angiography (figure-2).
Patients with nephrotic syndrome carry a high risk of both venous and arterial thrombosis(4). Pulmonary embolism, DVT, renal vein thrombosis, and inferior vena cava thrombosis are reported as life-threatening complications of nephrotic syndrome (4,5).
The etiology of NS is divided into primary, which includes focal segmental glomerulosclerosis (FSGS), membranous nephropathy (MN) and minimal change disease (MCD), and secondary to systemic diseases which included diabetes mellitus, systemic lupus erythematosus, multiple myeloma, amyloidosis, and infections (6). The pathophysiology of hypercoagulability in the nephrotic syndrome is due to imbalances of prothrombotic and antithrombotic factors, impaired thrombolytic activity and other important contributing factors such as intravascular volume depletion, the use of diuretics, immobilization, and procoagulant diatheses ( such as protein C and protein S deficiencies) (7).
Hull RPet al reported DVT at the lower limbs as the most common complication of nephrotic syndrome, but also noted thrombosis at renal and pulmonary vessels (6). Our case initially presented with pulmonary embolism as a complication of NS with no previous history of NS which is uncommon.
Similar to the presented case, Peces R et al (8) reported a 42 years old male that presented with multiple venous thromboses and pulmonary artery embolism as a complication of nephrotic syndrome. In our case, pulmonary embolism and inferior vena cava thrombosis were complications of nephrotic syndrome while persistent adequate renal blood flow prevented renal infarction.
Nephrotic syndrome is a risk factor for venous thromboembolism due to increased renal loss of anticoagulant proteins included Anti-thrombin III and increased production of pro-thrombotic factors by the liver. The possible occurrence of PE in a young person with nephrotic syndrome should not be missed. Early diagnosis and management of nephrotic syndrome may prevent the occurrence of venous thromboembolism(VTE).
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Written consent had obtained from the patients.
Competing of interest and Funding:
The authors declare that they have no Competing of interest and funding source.