What are the symptoms and treatment of nephrotic syndrome?

Symptoms of Nephrotic Syndrome

Nephrotic syndrome presents with four cardinal features: heavy proteinuria (≥3.5 g/day in adults), hypoalbuminemia (<3.0 g/dL in adults), edema, and hyperlipidemia. 1

Core Clinical Manifestations

Primary Symptoms

• Edema is the most prominent presenting symptom, resulting from decreased oncotic pressure as albumin is lost in urine, causing fluid shift from intravascular to interstitial spaces 1
• Proteinuria of nephrotic range (≥3.5 g/day in adults; ≥1.0 g/m²/day in children) is the defining laboratory feature 1
• Fatigue and generalized weakness are common presenting complaints due to protein loss and metabolic derangements 2
• Foamy urine may be noticed by patients due to high protein content 3

Laboratory Abnormalities

• Hypoalbuminemia (<3.0 g/dL in adults; <2.5 g/dL in children) develops from urinary albumin loss 1
• Hyperlipidemia occurs as a compensatory hepatic response to hypoalbuminemia, with elevated cholesterol and triglycerides 1, 2

Serious Complications That May Present as Symptoms

Thrombotic Events

• Thromboembolism risk is markedly elevated, with 29% prevalence of renal vein thrombosis, 17-28% for pulmonary embolism, and 11% for deep vein thrombosis 4
• Patients may present with symptoms of venous thrombosis, pulmonary embolism, or renal vein thrombosis due to loss of anticoagulant proteins 1

Infectious Complications

• Increased susceptibility to infections, particularly cellulitis and spontaneous bacterial peritonitis in children, due to loss of immunoglobulins and complement factors 4, 1
• Serious bacterial infections can be presenting features, especially in severe cases 5

Cardiovascular Manifestations

• Accelerated coronary heart disease risk is four times greater than age-matched controls due to hypercholesterolemia, hypertension, hypercoagulability, and exposure to atherogenic therapies 4
• Hypertension may develop or worsen as part of the syndrome 5

Renal Dysfunction

• Progressive kidney disease with patients having proteinuria >3.8 g/day carrying a 35% risk of end-stage renal disease within 2 years 4, 1
• Acute kidney injury can occur as a complication 2, 5

Metabolic Derangements

• Vitamin D deficiency develops from urinary loss of vitamin D-binding protein 5
• Hypothyroidism may occur due to loss of thyroid-binding proteins 6
• Hyponatremia can develop, particularly with severe edema 6

Disease-Specific Presentations

Minimal Change Disease

• Typically presents with sudden onset of edema and nephrotic-range proteinuria 1
• More common in children but can occur in adults 1

Focal Segmental Glomerulosclerosis (FSGS)

• Often presents with sudden onset nephrotic syndrome in primary FSGS 1
• May have more gradual onset in secondary forms 4

Membranous Nephropathy

• Usually presents in adults with insidious onset of edema and proteinuria 7
• Higher thrombotic risk compared to other causes 4

Important Clinical Caveats

• Hypoalbuminemia severity correlates with poor prognosis: each 1.0 g/dL decrease in serum albumin increases morbidity odds by 89% and mortality by 137% 4
• Duration and severity of proteinuria are surrogate markers for disease progression and should guide treatment intensity 4
• The absence of signs of serious liver damage or cardiac failure helps distinguish nephrotic syndrome from other causes of edema and hypoalbuminemia 2
• In adults, diabetes mellitus is the most common secondary cause, while focal segmental glomerulosclerosis and membranous nephropathy are the most common primary causes 7