Nephritic Syndrome: Work-up and Management
Initial Diagnostic Work-up
Immediately obtain urinalysis with microscopy to confirm hematuria (dysmorphic RBCs, RBC casts), quantify proteinuria with spot urine protein-to-creatinine ratio (typically <3.5 g/day in nephritic syndrome), measure serum creatinine and eGFR to assess renal function, and check serum albumin to distinguish from nephrotic syndrome. 1, 2
Essential Laboratory Evaluation
- Confirm the nephritic pattern: Hematuria with RBC casts, subnephrotic proteinuria (<3.5 g/24h), elevated creatinine, and oliguria distinguish nephritic from nephrotic syndrome 1, 3
- Screen for post-infectious causes: Anti-streptolysin O (ASO) titer, anti-DNase B, throat/skin cultures for Group A beta-hemolytic streptococcus—post-streptococcal glomerulonephritis is the most common cause in children and remains prevalent in adults 4, 2
- Assess complement levels: Low C3 with normal C4 suggests post-infectious GN or membranoproliferative GN; low C3 and C4 suggest lupus nephritis 1, 5
- Evaluate for systemic disease: ANA, anti-dsDNA, ANCA panel, anti-GBM antibodies, hepatitis B/C, HIV serology to identify secondary causes 6, 1
Indications for Renal Biopsy
Perform kidney biopsy when there is rapidly progressive renal failure (doubling of serum creatinine over 1-2 months), atypical disease progression, diagnostic uncertainty, or features suggesting crescentic glomerulonephritis, as these require urgent immunosuppressive therapy. 7, 4, 2
- Biopsy is not routinely needed for classic post-streptococcal GN with typical presentation and improving course 4, 2
- Delayed resolution, severe renal failure at onset, progressive renal failure, or systemic features (rash, arthritis, fever) mandate biopsy 2, 3
Immediate Management Priorities
Blood Pressure Control
Target systolic blood pressure <120 mmHg using standardized office measurements in adults; in children, target 24-hour mean arterial pressure at 50th percentile for age, sex, and height by ambulatory monitoring. 7, 6
- Initiate ACE inhibitor or ARB and uptitrate to maximally tolerated dose as first-line therapy for both hypertension and proteinuria 7, 6
- Critical caveat: Do NOT start ACE inhibitors/ARBs in patients with abrupt onset nephritic syndrome or acute kidney injury, as these can worsen AKI, particularly in minimal change disease 7
- Add additional antihypertensive agents as needed to achieve target BP 6, 8
Volume and Edema Management
Restrict dietary sodium to <2.0 g/day (<90 mmol/day) immediately—this is synergistic with all other therapies and essential for controlling hypertension and edema. 7, 6, 8
- Start loop diuretics (furosemide) as first-line diuretic therapy for edema control 7, 6
- For resistant edema, combine loop diuretics with mechanistically different diuretics (thiazides, amiloride, or spironolactone) for synergistic effect 7, 6
- Monitor for hypokalemia with loop/thiazide diuretics and hyperkalemia with potassium-sparing agents, especially when combined with ACE inhibitors/ARBs 7
Proteinuria Management
Uptitrate ACE inhibitor or ARB to maximum FDA-approved daily dose (not just the dose that controls BP) for optimal antiproteinuric effect, targeting proteinuria <1 g/day. 7, 9
- Monitor serum creatinine and potassium every 2-4 weeks initially; accept up to 30% stable increase in creatinine but discontinue if kidney function continues to worsen or refractory hyperkalemia develops 7, 9, 8
- Use potassium-wasting diuretics and/or potassium-binding agents to normalize serum potassium, allowing continued RAS blockade 7, 8
- If proteinuria persists despite maximized ACE inhibitor/ARB, add mineralocorticoid receptor antagonist (spironolactone 25-50 mg daily) with careful potassium monitoring 7, 9, 8
Disease-Specific Immunosuppressive Therapy
Post-Streptococcal Glomerulonephritis
Immunosuppressive therapy is NOT indicated for uncomplicated post-streptococcal GN—treatment consists solely of supportive care with diuretics and antihypertensives. 4, 2
- Most patients make full recovery with supportive care alone 4, 2
- Antibiotics do not alter the course of established disease but may prevent spread to contacts 4
Rapidly Progressive/Crescentic Glomerulonephritis
Immunosuppressive therapy is essential and must be initiated urgently in crescentic GN to modify outcome—delay significantly worsens prognosis. 2, 3
- High-dose corticosteroids (methylprednisolone 500-1000 mg IV daily for 3 days, then oral prednisone 1 mg/kg/day) are first-line 2
- Add cyclophosphamide or other immunosuppressants based on underlying etiology (ANCA-associated, anti-GBM, lupus) 2
- Consider plasmapheresis for anti-GBM disease or severe ANCA-associated vasculitis 2
Critical Patient Counseling
Counsel patients to hold ACE inhibitors/ARBs and diuretics during intercurrent illness or any situation with risk for volume depletion ("sick day rules") to prevent acute kidney injury. 7, 8
Monitoring Strategy and Follow-up
Assess proteinuria, kidney function (serum creatinine, eGFR), and blood pressure regularly to evaluate treatment response; target proteinuria reduction of ≥25% by 3 months and ≥50% by 6 months. 6, 9, 8
- For post-streptococcal GN, monitor for persistent proteinuria, hypertension, and progression to chronic kidney disease requiring long-term follow-up 4
- A 40% or greater decline in eGFR from baseline over 2-3 years suggests treatment failure 6
- End-stage renal failure develops in 16% of nephritic syndrome patients overall, with worse prognosis in rapidly progressive GN, focal segmental glomerulosclerosis, and autoimmune diseases (>20% progress to ESRD) 3
Additional Supportive Measures
- Lifestyle modifications: Normalize weight, stop smoking, exercise regularly 7
- Infection prevention: Administer pneumococcal and influenza vaccines 6
- Cardiovascular risk management: Consider statin therapy for persistent dyslipidemia, particularly with additional cardiovascular risk factors 7, 6, 8
- Thromboembolism prevention: Full anticoagulation for documented thromboembolic events; consider prophylactic anticoagulation when risk exceeds bleeding risk 6