What is the difference between nephrotic syndrome and nephritic syndrome?

Nephrotic vs Nephritic Syndrome: Key Differences

Nephrotic syndrome is characterized by massive proteinuria (>3.5 g/24h), hypoalbuminemia (<3.0 g/dL), and edema, while nephritic syndrome presents with hematuria, proteinuria (typically less severe), hypertension, and acute kidney dysfunction. 1, 2

Nephrotic Syndrome

Defining Features

• Proteinuria: >3.5 g/24 hours in adults (or spot UPCR ≥2 g/g in children) 1, 3
• Hypoalbuminemia: Serum albumin <3.0 g/dL in adults, ≤2.5 g/dL in children 1, 3
• Edema: Peripheral and periorbital swelling, often most noticeable in the morning 4, 5
• Hyperlipidemia: Frequently present with elevated cholesterol and triglycerides 1, 5

Clinical Presentation

Patients typically present with fatigue and progressive edema without signs of heart failure or severe liver disease 5. The edema is periorbital early in the day and becomes dependent pitting edema later 4. Patients appear cushingoid with fluid retention but lack the acute inflammatory features seen in nephritic syndrome 4, 5.

Common Causes

• Adults (Caucasian): Membranous nephropathy is most common 4, 2
• Adults (African ancestry): Focal segmental glomerulosclerosis predominates 4
• Children: Minimal change disease accounts for the majority of cases 6, 2
• Secondary causes: Diabetes mellitus is the most common systemic disease causing nephrotic syndrome 4, 2

Major Complications

• Thromboembolism: Particularly when albumin <2.9 g/dL, with 29% risk of renal vein thrombosis 1, 3
• Infection: Due to urinary immunoglobulin losses and immunosuppressive therapy 5, 7
• Progressive kidney dysfunction: Proteinuria >3.8 g/day carries 35% risk of ESRD within 2 years 3
• Accelerated cardiovascular disease: Four times greater risk due to severe hyperlipidemia 1

Nephritic Syndrome

Defining Features

• Hematuria: Prominent feature with red blood cells and cellular casts 2
• Proteinuria: Present but typically <3.5 g/24 hours (sub-nephrotic range) 2
• Hypertension: Consistently present due to sodium retention and volume expansion 2
• Acute kidney dysfunction: Elevated creatinine with declining GFR 2
• Edema: Present but less severe than nephrotic syndrome 2

Clinical Presentation

Patients present with acute onset of hypertension, hematuria (often "tea-colored" or "cola-colored" urine), and oliguria 2. The syndrome carries a poorer prognosis compared to nephrotic syndrome due to the inflammatory nature and risk of rapidly progressive glomerulonephritis 2.

Common Causes

• Post-infectious glomerulonephritis: Most common overall, typically following streptococcal infection 2
• IgA nephropathy: Frequent cause of recurrent hematuria with nephritic features 2
• Lupus nephritis: Important secondary cause requiring specific immunosuppression 2

Pathophysiology Distinction

Nephritic syndrome results from inflammatory glomerular injury with disruption of the glomerular basement membrane, allowing red blood cells to pass into urine 2. In contrast, nephrotic syndrome involves podocyte dysfunction and loss of charge selectivity, leading to massive protein leakage without significant inflammation 6, 7.

Critical Diagnostic Approach

For Suspected Nephrotic Syndrome

• Quantify proteinuria: 24-hour urine collection or spot UPCR (>300-350 mg/mmol indicates nephrotic range) 4
• Measure serum albumin: Note assay type (BCG vs BCP) as values differ by ~0.5 g/dL 1, 3
• Assess for secondary causes: Check glucose, ANA, anti-dsDNA, complement levels (C3, C4), hepatitis B/C, HIV serologies 1
• Kidney biopsy: Recommended in adults to determine specific histologic diagnosis and guide immunosuppression 6, 1

For Suspected Nephritic Syndrome

• Urinalysis with microscopy: Look for dysmorphic RBCs and red cell casts 2
• Assess kidney function: Creatinine and GFR to determine severity of acute injury 2
• Complement levels: Low C3 suggests post-infectious GN or lupus nephritis 2
• Serologic testing: ASO titers for post-streptococcal GN, ANA for lupus 2

Common Pitfalls to Avoid

Do not confuse sub-nephrotic proteinuria with hypoalbuminemia as nephrotic syndrome - this suggests a secondary cause requiring different evaluation 1. Conversely, nephrotic-range proteinuria with albumin >3.0 g/dL should prompt investigation for secondary FSGS or early disease 1.

In nephritic syndrome, do not delay treatment while awaiting biopsy results if rapidly progressive glomerulonephritis is suspected, as irreversible kidney damage can occur within days 2. However, in nephrotic syndrome without acute kidney injury, biopsy should ideally be performed before starting immunosuppression to avoid obscuring histologic diagnosis 1.

Thromboembolism risk in nephrotic syndrome is frequently underestimated - consider prophylactic anticoagulation when albumin <2.0-2.5 g/dL with additional risk factors (proteinuria >10 g/day, BMI >35, immobilization) 1. Use warfarin with target INR 2-3, not direct oral anticoagulants, due to unpredictable pharmacokinetics from urinary losses 1.