What is Nephrotic Syndrome?
Nephrotic syndrome is a clinical kidney disorder defined by the presence of heavy proteinuria (≥3.5 g/day in adults or ≥1.0 g/m²/day in children), hypoalbuminemia (<3.0 g/dL in adults or <2.5 g/dL in children), and edema, commonly accompanied by hypercholesterolemia 1.
Core Diagnostic Criteria
The syndrome results from increased glomerular permeability to proteins, allowing albumin and other proteins to pass into the urine 2. The diagnostic triad consists of:
- Heavy proteinuria: >3.5 g/24 hours in adults (protein:creatinine ratio >300-350 mg/mmol) 3
- Hypoalbuminemia: Serum albumin <3.0 g/dL in adults or <2.5 g/dL in children 1
- Edema: Typically periorbital (morning) or dependent pitting edema (later in day) 3
Hyperlipidemia is frequently present but not required for diagnosis 1.
Underlying Pathophysiology
Nephrotic syndrome develops from pathological injury to renal glomeruli, which can be:
- Primary (idiopathic): Disease specific to the kidneys
- Secondary: Related to systemic disorders such as diabetes mellitus, systemic lupus erythematosus, infections, malignancy, or medications 4
The three most common histologic variants in idiopathic nephrotic syndrome are minimal change disease (MCD), focal segmental glomerulosclerosis (FSGS), and membranous nephropathy 1. The relative frequency varies by age and ethnicity—MCD predominates in children, while membranous nephropathy is most common in white adults and FSGS in populations of African ancestry 3.
Clinical Complications
The syndrome triggers a cascade of complications beyond simple fluid retention 2:
- Thrombotic disease: Urinary loss of anticoagulants and overproduction of coagulation factors create a hypercoagulable state, with renal vein thrombosis occurring in 29% of cases, pulmonary embolism in 17-28%, and deep vein thrombosis in 11% 1
- Infection risk: Hypogammaglobulinemia, loss of complement factors, and immunosuppressive therapy increase susceptibility 5
- Cardiovascular disease: The combination of hypercholesterolemia, hypertension, hypercoagulability, and steroid exposure increases coronary heart disease risk fourfold compared to age-matched controls 1
- Progressive kidney dysfunction: Prolonged proteinuria leads to tubular epithelial cell dysfunction, tubular atrophy, and interstitial fibrosis 5
- Mortality risk: Each 1.0 g/dL decrease in serum albumin increases mortality odds by 137% 1
Prognostic Factors
Proteinuria severity directly predicts outcomes—adults with proteinuria >3.8 g/day have a 35% risk of end-stage renal disease within 2 years, compared to only 4% for those with <2.0 g/day 1. The response of proteinuria to therapy is the main factor predicting prognosis across all histologic variants 1.
Clinical Presentation Patterns
Patients typically present with edema and fatigue without evidence of heart failure or severe liver disease 4. The presentation differs from nephritic syndrome, which is characterized by hematuria, proteinuria, abnormal kidney function, and hypertension, carrying a poorer prognosis 6.