The pathogenesis of NS is still unclear. Changes in “podocyte molecules” are considered to be the essence of the development of proteinuria, and changes in the properties of the glomerular capillary filtration barrier caused by the immune response are the primary factors of proteinuria. In the past, most scholars believed that the occurrence of nephrotic syndrome was related to T cells. However, the efficacy of rituximab and other specific B-cell suppressive agents has challenged the T-cell origin hypothesis [
2]. Recently, the discovery of circulating anti-nephrin antibodies has provided further evidence for the autoimmune etiology of minimal change disease (MCD) [
3]. Thromboembolism is a serious complication of NS, and previous studies have found that the incidence of primary nephrotic syndrome (PNS) thrombosis in children is about 2–5% [
4,
5], which is similar to the results of our previous study [
6]. The symptoms of thromboembolism have different manifestations according to the site of occurrence. High-risk pulmonary artery thrombosis often presents with the triad of chest pain, hemoptysis, and dyspnea [
7‐
10]. The most common symptom of intracranial thrombosis is headache. Deep vein thrombosis is a common cause of limb pain, swelling, and difficulty in walking [
11]. Severe costoabdominal pain, costoovertebral angle tenderness, hematuria, proteinuria, and renal dysfunction are the main manifestations of renal vein thrombosis. If bilateral renal vein thrombosis occurs rapidly, it might develop into oliguric acute renal failure [
12,
13]. At present, there is still a lack of standard thrombolytic therapy after thrombosis, and once thromboembolism is formed, the prognosis is often poor; therefore, reasonable preventive anticoagulant therapy is particularly important. In 1884, Virchow first proposed three key factors for thrombosis: A hypercoagulable state, vascular endothelial injury, and hemodynamic factors [
14]. Large amounts of small molecular weight proteins, including coagulation factors IX, XI, and XII, are spilled into the urine because of glomerular permeability changes. At the same time, the concentrations of anticoagulant factors also decrease, including antithrombin III (ATIII), protein C, protein S, and tissue factor pathway inhibitor. In contrast, the concentrations of high molecular weight proteins increase, including coagulation factor I, II, V, VII, VIII, X, Von Willebrand factor (vWF), and fibrinogen. This is because these macromolecule proteins are not easily lost and, as a compensatory mechanism, there is increased hepatic protein synthesis. Under a hypercoagulable state, clotting function is activated and, at the same time, the fibrinolytic system is activated [
5]. In addition, the role of endothelial injury in thrombosis has received increased attention. Endothelial cells mainly play an anticoagulant role under physiological conditions [
15]; however, when the body is in a state of nephropathy, the increase in oxygen free radicals in the body, hyperlipidemia, and the application of glucocorticoids and immunosuppressants can cause endothelial cell damage [
16]. In a injury state, endothelial cells synthesize and release tissue factor, thromboxane A2 (TXA2), plasminogen activator inhibitor 1 (PAI-1), and vWF, which participate in the activation of internal and external coagulation pathways [
17].
A number of observational studies have found that the high risk factors of thrombosis in children with NS mainly include the age of onset (≥ 12 years) [
18,
19], indwelling intravenous catheter [
18,
20‐
22], complicated by infection [
23], persistent severe hypoproteinemia (< 20 g/l) [
22,
24], hyperlipidemia [
20,
21,
25,
26], hyperfibrinogenemia [
19,
22], platelets (Plt) > 300 × 10
9/l [
19,
27], glucocorticoids application [
19,
28], ATIII < 80% [
20,
22,
24], Ddimer > 1 mg/l [
24,
29], and diuretics application [
19,
28]. The occurrence of thrombosis often indicates a poor prognosis, and many cases of disability and even death have been reported in the literature at home and abroad [
30‐
35]. However, the potential adverse reactions to anticoagulants make the prophylactic use of anticoagulants in children with NS controversial.
At present, most clinicians are still cautious about the prophylactic use of anticoagulant drugs in children with PNS, and the 2021 Kidney Disease Improving Global Outcomes (KDIGO) guidelines only proposes the use of anticoagulant drugs in adults with membranous nephropathy. The present study retrospectively analyzed the clinical results of urokinase (UK) application as an anticoagulant drug in the treatment of PNS in children in the Children’s Hospital of Soochow University and Zibo Maternal and Child Health Hospital from 2018 to 2022, aiming to provide guidance for the prevention of thromboembolism in children with PNS.