Nephritic vs Nephrotic Syndrome: Diagnostic and Treatment Differences
Key Distinguishing Features
Nephrotic syndrome is characterized by heavy proteinuria (>3.5 g/24 hours), hypoalbuminemia (<3.0 g/dL), peripheral edema, and often hyperlipidemia, while nephritic syndrome presents with hematuria, proteinuria (typically less severe), hypertension, and abnormal kidney function with a generally poorer prognosis. 1
Nephrotic Syndrome Clinical Presentation
- Proteinuria >3.0-3.5 g/24 hours (or protein:creatinine ratio >300-350 mg/mmol) 2, 1
- Serum albumin <3.0 g/dL 2, 1
- Peripheral edema (periorbital in morning, dependent pitting later in day) 2
- Hyperlipidemia and increased thrombotic risk 2, 1
- Selective proteinuria in many cases, particularly minimal change disease 3
- Absence of significant hematuria, hypertension, or renal insufficiency in primary forms 3
Nephritic Syndrome Clinical Presentation
- Hematuria (often macroscopic) as predominant feature 3, 1
- Proteinuria present but typically less than nephrotic range 1
- Hypertension (often marked) 3, 1
- Abnormal kidney function/renal insufficiency 3, 1
- Acute nephritic onset possible 3
- Decreased plasma C3 levels in many cases 3
- Poorly selective proteinuria 3
Diagnostic Approach
When to Perform Renal Biopsy
In children with suspected nephrotic syndrome, empiric glucocorticoid therapy should be initiated without biopsy if the presentation is typical (age <12 years, no nephritic features); biopsy is only indicated if steroid-resistant or atypical features present. 4
In adults with nephrotic syndrome, kidney biopsy is typically indicated for diagnosis, with the notable exception of patients with positive anti-phospholipase A2 receptor antibodies, which is diagnostic of membranous nephropathy. 4
Biopsy Indications in Nephrotic Syndrome:
- Clinical features suggesting diffuse glomerular lesions (acute nephritic onset, moderate nephrotic syndrome, macroscopic hematuria, marked hypertension, renal insufficiency, poorly selective proteinuria, decreased C3) 3
- Steroid resistance demonstrated in children 3
- All adults except those with positive anti-PLA2R antibodies 4
- Atypical presentations in any age group 4
Biopsy Indications in Nephritic Syndrome:
- Renal biopsy may be indicated for differentiation of nephritic and nephrotic syndromes when clinical presentation is unclear 5
- Biopsy helps guide immunosuppressive therapy decisions 5
Laboratory Evaluation
- Quantitative proteinuria measurement (24-hour urine protein, PCR, or ACR) 2
- Serum albumin and lipid levels 4
- Urinalysis with microscopy for casts, RBCs, and epithelial cells 5
- Serum creatinine and BUN 5
- Complete blood count 5
- Complement levels (C3, C4) particularly in nephritic presentations 3
- Anti-PLA2R antibodies in adults with suspected membranous nephropathy 4
Common Etiologies
Nephrotic Syndrome
- Children: Minimal change disease (most common), focal segmental glomerulosclerosis 4, 3
- White adults: Membranous nephropathy (most common) 2
- African ancestry populations: Focal segmental glomerulosclerosis (most common) 2
- Secondary causes: Diabetes mellitus (most common systemic cause), amyloidosis, SLE, hematologic malignancies, infections 2, 4
Nephritic Syndrome
Treatment Approaches
Nephrotic Syndrome Treatment
For primary nephrotic syndrome in children <12 years, initiate prednisone 60 mg/m²/day (or 2 mg/kg/day, maximum 60 mg) until remission, then 40 mg/m² on alternate days for 4 weeks. 5
For adults with primary FSGS, high-dose oral glucocorticoids (prednisone 1 mg/kg/day, maximum 80 mg, or 2 mg/kg alternate-day, maximum 120 mg) should be given for minimum 4 weeks, continuing up to maximum 16 weeks as tolerated or until complete remission. 5
Glucocorticoid Therapy Details:
- Continue initial high-dose until complete remission achieved or maximum 16 weeks, whichever earlier 5
- Taper slowly over 6 months after achieving complete remission 5
- Total treatment duration ≥6 months for responders 5
- Glucocorticoids indicated for idiopathic nephrotic syndrome only, NOT for secondary FSGS 5, 6
Alternative Immunosuppression:
- Calcineurin inhibitors (cyclosporine, tacrolimus) as first-line for patients with contraindications to glucocorticoids (uncontrolled diabetes, psychiatric conditions, severe osteoporosis) 5
- Rituximab for steroid-resistant or frequently relapsing disease 4
- Mycophenolate mofetil as alternative agent 7
Supportive Care (All Nephrotic Patients):
- ACE inhibitors or ARBs for proteinuria reduction and blood pressure control (target ≤125/80 mmHg) 6
- Dietary sodium restriction 4
- Statin therapy for hyperlipidemia and cardiovascular risk reduction 6
- Thromboembolism prophylaxis for high-risk patients, particularly membranous nephropathy 4
- Edema management with diuretics as needed 4
Secondary FSGS (e.g., Diabetes) Treatment
Immunosuppressive therapy should NOT be used for secondary FSGS; treatment focuses on ACE inhibitors/ARBs, aggressive blood pressure control (≤125/80 mmHg), statins, sodium restriction, and weight loss in obese patients. 5, 6
Nephritic Syndrome Treatment
Treatment for nephritic syndrome is disease-specific and typically requires immunosuppressive therapy targeting the underlying glomerulonephritis, with non-specific measures including blood pressure control, proteinuria reduction, and edema management. 1
- Hypertension control is critical 1
- Proteinuria reduction with ACE inhibitors/ARBs 1
- Disease-modifying immunosuppression based on specific diagnosis 1
Critical Pitfalls to Avoid
Diagnostic Pitfalls:
- Misdiagnosing secondary FSGS as primary FSGS leads to inappropriate immunosuppressive therapy with significant risks 6
- Performing unnecessary biopsies in children with typical minimal change disease presentation 3
- Failing to test for anti-PLA2R antibodies in adults before proceeding to biopsy 4
- Inadequate assessment for secondary causes before initiating immunosuppression 5
Treatment Pitfalls:
- Using immunosuppression for secondary FSGS (particularly diabetic nephropathy) provides no benefit and causes harm 5, 6
- Inadequate dosing of ACE inhibitors/ARBs in supportive care 6
- Stopping glucocorticoids too early in responders (need ≥6 months total) 5
- Continuing high-dose glucocorticoids beyond 16 weeks in non-responders 5
- Failing to provide thromboembolism prophylaxis in high-risk nephrotic patients 4
Prognosis Differences
Nephritic syndrome carries a poorer prognosis than nephrotic syndrome, with greater risk of progressive kidney function decline. 1