Nephrotic Syndrome Causes and Management

Primary Causes of Nephrotic Syndrome

Nephrotic syndrome is primarily caused by three major histologic variants: minimal change disease, focal segmental glomerulosclerosis (FSGS), and membranous nephropathy, with the relative frequency varying by age and ethnicity 1
Immunoglobulin and complement-mediated glomerular diseases with an MPGN pattern can also cause nephrotic syndrome 1

Various infectious agents can trigger infection-related glomerulonephritis leading to nephrotic syndrome 1
Solid tumors can be associated with paraneoplastic glomerular disease 1
Cancer therapies, including targeted agents and immunotherapies, may cause podocytopathies 1
Anti-angiogenesis drugs are associated with proteinuria and lesions such as minimal change disease/FSGS 1
Immune checkpoint inhibitors can cause nephrotic syndrome 1

Primary T-cell disorders may be responsible for minimal change disease and FSGS, with a proposed T-cell-driven circulating factor that interferes with glomerular permeability to albumin 1
Membranous nephropathy has been definitively proven to be an autoimmune disease 1
The 2021 KDIGO guidelines propose a classification of FSGS to help differentiate between primary FSGS (which may respond to immunosuppression) and secondary forms (which typically don't) 2

In primary FSGS with nephrotic syndrome, immunosuppression has been shown to improve proteinuria and slow progression to ESRD 3
Patients with proteinuria >3.8 g/day have a 35% risk of end-stage renal disease within 2 years if left untreated 1
Complications of nephrotic syndrome include hyperlipidemia, venous thromboembolism, increased risk of infection, and accelerated coronary heart disease 1