What are the presentation, diagnostic work‑up, and management for nephritic syndrome in a patient of any age presenting with sudden hematuria, mild proteinuria, hypertension, edema, and declining renal function?

Nephritic Syndrome: Presentation, Diagnosis, and Management

Clinical Presentation

Nephritic syndrome presents with hematuria, mild proteinuria (typically <3.5 g/24h), hypertension, edema, and declining renal function—a constellation that distinguishes it from nephrotic syndrome's heavy proteinuria and hypoalbuminemia. 1

Key Clinical Features

• Hematuria with dysmorphic RBCs: >80% dysmorphic red blood cells on urine microscopy indicates glomerular bleeding 2, 3
• Red cell casts: Pathognomonic for glomerulonephritis 2, 3
• Proteinuria: Usually <3.0 g/24 hours, distinguishing it from nephrotic syndrome 1
• Hypertension: Commonly present and requires aggressive management 1
• Edema: Typically mild to moderate 1
• Declining GFR: Progressive renal dysfunction is characteristic and portends worse prognosis 1

Diagnostic Work-Up

Initial Laboratory Assessment

Obtain comprehensive serologic evaluation to identify the underlying cause and assess disease severity:

• Complete blood count with differential and platelets 2
• Renal function panel: Serum creatinine, BUN, electrolytes, and calculate eGFR 2, 3
• Urinalysis with microscopy: Quantify RBCs, identify dysmorphic RBCs and red cell casts 2, 3
• Quantitative proteinuria: First morning spot urine protein-to-creatinine ratio (UPCR) or 24-hour urine collection 2, 4
• Serum albumin: To differentiate from nephrotic syndrome (typically >3.0 g/dL in nephritic syndrome) 2

Etiologic Evaluation

Screen for common causes of nephritic syndrome systematically:

• Complement levels (C3, C4): Low C3 suggests post-infectious glomerulonephritis or lupus nephritis 4, 3, 5
• Autoimmune serologies: ANA, anti-dsDNA for systemic lupus erythematosus 2, 3
• Infectious workup: Hepatitis B and C serologies, HIV testing, throat culture or anti-streptolysin O titer for post-streptococcal GN 2, 5
• ANCA testing: If vasculitis suspected (MPO-ANCA, PR3-ANCA) 2

Imaging

• Renal ultrasound: First-line imaging to assess kidney size, echogenicity, and structural abnormalities 4, 3
• Enlarged echogenic kidneys suggest acute glomerulonephritis 3

Kidney Biopsy Indications

Kidney biopsy is the gold standard for diagnosis and should be performed within the first month of presentation, ideally before initiating immunosuppressive therapy. 2

Biopsy is indicated for:

• All adults with nephritic syndrome to establish specific diagnosis 2
• Children ≥12 years with nephritic features 2
• Children <12 years who are steroid-resistant or have atypical features 4
• Rapidly progressive glomerulonephritis (RPGN) with rising creatinine 6

Technical requirements:

• Minimum 8-10 glomeruli for light microscopy (H&E, PAS, Masson's trichrome, silver stain) 2
• Immunofluorescence for IgG, C3, IgA, IgM, C1q, κ and λ light chains 2
• Electron microscopy to detect proliferative lesions and assess podocyte changes 2

Management

Supportive Care (First-Line for All Patients)

Blood Pressure Control:

• Target systolic BP <120 mmHg in adults using standardized office measurement 6
• ACE inhibitors or ARBs as first-line agents at maximally tolerated doses 6
• Caution: Hold ACEi/ARB during volume depletion or intercurrent illness 6
• Monitor for up to 30% increase in creatinine (acceptable and stable) 6
• Discontinue if progressive renal dysfunction or refractory hyperkalemia develops 6

Edema Management:

• Dietary sodium restriction: <2.0 g/day (<90 mmol/day) 6
• Loop diuretics (furosemide) as preferred agents 6
• Combination diuretic therapy for resistant edema: Add thiazide-like diuretics or amiloride for synergistic effect 6
• Monitor for hypokalemia, hyponatremia, and volume depletion 6

Proteinuria Reduction:

• Uptitrate ACEi/ARB to maximally tolerated dose even without hypertension 6
• Target proteinuria <1 g/day where achievable 6
• Use potassium-wasting diuretics or potassium binders to allow continued RAS blockade if hyperkalemia develops 6

Metabolic Management:

• Treat metabolic acidosis if serum bicarbonate <22 mmol/L 6
• Lifestyle modifications: Weight normalization, smoking cessation, regular exercise 6

Disease-Specific Immunosuppression

The specific immunosuppressive regimen depends on the underlying histologic diagnosis:

Post-Infectious Glomerulonephritis:

• Primarily supportive care; immunosuppression generally not indicated 1, 5
• Treat underlying infection if still present 5
• Monitor for resolution (typically 6-8 weeks) 5

IgA Nephropathy (Most Common Cause in Adolescents/Adults):

• High-dose glucocorticoids for patients with persistent proteinuria >1 g/day despite maximal supportive care and eGFR >30 mL/min/1.73m² 6
• Prednisone dosing per KDIGO guidelines (individualized based on risk stratification) 6
• Caution: Assess contraindications including obesity, metabolic syndrome, latent infections (TB, HIV, HBV, HCV) 6

Rapidly Progressive Glomerulonephritis (RPGN) with Crescents:

• Urgent treatment required for >50% crescents with declining GFR 6
• Cyclophosphamide plus high-dose glucocorticoids per ANCA-vasculitis protocols 6
• Consider plasma exchange for severe cases with pulmonary hemorrhage or dialysis-dependent AKI 6

Lupus Nephritis:

• Treat according to specific lupus nephritis guidelines based on ISN/RPS class 6
• Typically requires combination immunosuppression (mycophenolate or cyclophosphamide plus glucocorticoids) 6

Monitoring Strategy

Close follow-up is essential given the progressive nature of nephritic syndrome:

• Initial phase (first 2-4 months): Monitor every 2-4 weeks for renal function, proteinuria, blood pressure 2
• Maintenance phase: Every 3-6 months once stable 2, 4
• Laboratory monitoring: Serial creatinine, UPCR, electrolytes, albumin 4, 3
• Adjust ACEi/ARB and diuretics based on volume status and renal function 6

Infection Prophylaxis During Immunosuppression

Implement prophylaxis when using immunosuppressive therapy:

• Pneumococcal vaccine for all patients with glomerulonephritis 6
• Influenza vaccine annually for patients and household contacts 6
• Trimethoprim-sulfamethoxazole prophylaxis for patients on high-dose prednisone, rituximab, or cyclophosphamide 6
• Screen for latent infections (TB, HBV, HCV, HIV) before initiating immunosuppression 6

Common Pitfalls and Caveats

Avoid starting ACEi/ARB in patients with abrupt-onset nephrotic syndrome or minimal change disease, as these can precipitate acute kidney injury. 6

Do not delay kidney biopsy in adults or atypical pediatric presentations—histologic diagnosis is essential for appropriate immunosuppressive therapy selection 2

Recognize that nephritic syndrome carries a poorer prognosis than nephrotic syndrome due to progressive renal dysfunction; aggressive blood pressure control and proteinuria reduction are critical 1

Distinguish post-infectious GN from IgA nephropathy: Post-infectious GN typically shows low C3 with recent streptococcal infection and resolves spontaneously, while IgA nephropathy has normal complement and requires long-term management 6, 1, 5

In adolescents with gross hematuria, consider IgA nephropathy first—it is the most common cause in this age group and often leads to unnecessary urologic procedures if not recognized early 3, 7