From the Guidelines
Nephrotic syndrome is primarily caused by damage to the glomeruli, which are the tiny filtering units in the kidneys, resulting from various diseases and conditions, including minimal change disease, focal segmental glomerulosclerosis, membranous nephropathy, and diabetic nephropathy, as well as systemic diseases and certain infections 1. The damage to the glomeruli allows proteins, particularly albumin, to leak from the blood into the urine, resulting in proteinuria, hypoalbuminemia, edema, and hyperlipidemia.
Common Causes of Nephrotic Syndrome
- Minimal change disease (especially in children)
- Focal segmental glomerulosclerosis
- Membranous nephropathy
- Diabetic nephropathy
- Systemic diseases like lupus, amyloidosis, and certain infections such as HIV, hepatitis B and C
- Medications like NSAIDs, certain antibiotics, and chemotherapy drugs The underlying mechanism involves damage to the glomerular filtration barrier, particularly the podocytes and their slit diaphragms, which normally prevent protein leakage.
Classification of FSGS
A novel classification system divides patients with FSGS into 4 subclasses:
- Primary FSGS, which is typically immunologically mediated and responsive to treatment with immunosuppression
- Genetic FSGS
- Secondary FSGS, which is mediated by viral injury, medication-related injury, or adaptive changes
- FSGS of undetermined cause (FSGS-UC) 1 Treatment depends on identifying and addressing the underlying cause, often involving immunosuppressive medications, diuretics, ACE inhibitors or ARBs, and supportive care to manage symptoms and complications. It is essential to work up for secondary causes in patients with non–nephrotic-range proteinuria or with nephrotic-range proteinuria but albumin > 3.0 g/dL, and to consider history of prematurity as a potential etiology for those with secondary FSGS due to reduced nephron number 1.
From the Research
Causes of Nephrotic Syndrome
- Nephrotic syndrome (NS) can be caused by various primary and secondary conditions, including idiopathic minimal change disease and focal segmental glomerulosclerosis (FSGS) in children, and FSGS and membranous nephropathy (MN) in adults 2
- Secondary causes of NS include diabetes, amyloidosis, systemic lupus erythematosus, hematologic malignancies, and infections 2
- In patients with kidney disease, NS can lead to several complications, including progressive kidney dysfunction, and can be associated with increased risk of mortality and kidney dysfunction 3
Specific Causes and Associations
- Minimal change disease (MCD) is a common cause of NS in children and can also be associated with systemic lupus erythematosus (SLE) 4, 5
- SLE can present with nephrotic syndrome due to MCD, and the association between MCD and SLE may not be a coincidence 5
- Diabetes mellitus (DM) and SLE can both cause kidney involvement and lead to NS, generating diagnostic and therapeutic problems 6
Pathophysiology and Consequences
- Proteinuria in NS can lead to the formation of cellular or fibrous crescents, tubular atrophy, and interstitial fibrosis, and can also cause overload and dysfunction of tubular epithelial cells 3
- Hypoalbuminemia and dyslipidemia can increase the risk of mortality, kidney dysfunction, and atherosclerotic complications, and can contribute to vascular thrombosis 3