Cardiovascular disease and risk management in patients with nephrotic syndrome

Nephrotic syndrome, defined by proteinuria ≥3.5 g/24 hr, hypoalbuminemia, hyperlipidemia, and edema, shows a significantly elevated risk of both arterial and venous thromboembolic complications. Large cohort studies have demonstrated an up to two-fold increase in myocardial infarction and stroke incidence and an eight-fold increase in venous thromboembolism, especially among patients with membranous nephropathy. The increased cardiovascular vulnerability in this population is driven by a constellation of interrelated mechanisms: dyslipidemia, urinary loss of natural anticoagulants alongside increased procoagulant factors and platelet activation, and neurohormonal activation of the renin angiotensin system (RAS) and sympathetic pathways, which then exacerbates hypertension and alters fluid homeostasis. Despite this, commonly used scores to assess cardiovascular risk underestimate the true risk as they lack nephrotic syndrome-specific parameters like proteinuria and hypoalbuminemia. Optimal management therefore requires early recognition and a combined approach of lifestyle modification, including diet, salt restriction, regular exercise, smoking cessation, and tailored pharmacotherapy. This includes lipid control in those at risk, RAS inhibition to reduce blood pressure and proteinuria, targeted anticoagulation for patients with serum albumin below 2.5 g/dL and elevated venous thromboembolism risk as well as low-dose aspirin where arterial thrombosis prophylaxis is indicated. Future research should focus on developing nephrotic syndrome-specific risk prediction models and evaluating the benefit of highly effective therapies such as proprotein convertase subtilisin/kexin type 9 and sodium glucose co-transporter 2 inhibitors in clinical trials. An integrated, multidisciplinary care model involving both nephrology and cardiology is crucial for mitigating the significant cardiovascular burden in this vulnerable patient population.