What is the best course of treatment for a patient with hypertension (high blood pressure), anasarca (generalized edema), and hematuria (blood in urine)?

Acute Nephritic Syndrome: Immediate Diagnostic Workup and Treatment

This clinical triad of hypertension, anasarca, and hematuria is pathognomonic for acute glomerulonephritis until proven otherwise, and requires urgent evaluation for rapidly progressive glomerulonephritis (RPGN) with immediate initiation of RAS blockade and aggressive blood pressure control.

Immediate Diagnostic Priorities

• Obtain urinalysis with microscopy to confirm hematuria and look for red blood cell casts (diagnostic of glomerulonephritis), proteinuria quantification via urine protein-to-creatinine ratio, and assess for nephrotic-range proteinuria (>3 g/day) 1

• Measure serum creatinine and eGFR to establish baseline renal function and determine if acute kidney injury is present, as this will guide medication dosing and urgency of nephrology referral 2

• Check serum electrolytes including potassium before initiating RAS blockade, as hyperkalemia is a contraindication to ACE inhibitors/ARBs 3, 2

• Quantify proteinuria using spot urine protein-to-creatinine ratio, as proteinuria ≥300 mg/g mandates aggressive RAS blockade regardless of blood pressure 1, 4

• Screen for secondary causes including complement levels (C3, C4), ANA, ANCA, anti-GBM antibodies, hepatitis B/C serology, and blood cultures if infection-related glomerulonephritis is suspected 2

Immediate Blood Pressure Management

Target systolic blood pressure to 120-129 mmHg in this patient with proteinuria and presumed glomerulonephritis, as lower targets provide additional renoprotection in proteinuric patients 2, 1

First-Line Therapy: RAS Blockade

• Initiate an ACE inhibitor (lisinopril 10-40 mg daily) or ARB immediately as first-line therapy, as these agents provide blood pressure-independent antiproteinuric effects and are superior to other antihypertensives in reducing proteinuria 1, 4, 3

• Uptitrate to maximum tolerated dose (lisinopril up to 40 mg daily) within 1-2 weeks, as the goal is proteinuria reduction to <1 g/day, not just blood pressure control 4, 1

• Accept up to 30% increase in serum creatinine after ACE inhibitor initiation, which is hemodynamic and expected, not a reason to stop therapy 4

Second-Line: Add Diuretic for Volume Overload

• Add a thiazide-like diuretic (chlorthalidone 12.5-25 mg daily or indapamide 1.25-2.5 mg daily) if blood pressure remains uncontrolled or if eGFR >30 mL/min/1.73m² 2, 1

• Switch to loop diuretic (furosemide 20-80 mg twice daily) if eGFR <30 mL/min/1.73m² or if severe volume overload/anasarca persists, as thiazides are ineffective at low GFR 2

• Aggressive diuresis is essential to resolve anasarca and reduce preload, which will also help lower blood pressure 2

Third-Line: Add Calcium Channel Blocker

• Add a dihydropyridine calcium channel blocker (amlodipine 5-10 mg daily) if blood pressure remains >130/80 mmHg despite RAS blocker plus diuretic 2, 5

• Caution: Amlodipine can cause peripheral edema (and rarely anasarca), which may worsen the clinical picture in a patient already presenting with generalized edema 6, 5

Fourth-Line: Mineralocorticoid Receptor Antagonist

• Add low-dose spironolactone (25-50 mg daily) for resistant proteinuria despite maximum-dose RAS blockade plus diuretic, with careful potassium monitoring (hold if K+ >4.5 mmol/L or eGFR <45 mL/min/1.73m²) 2, 1

Critical Monitoring Parameters

• Monitor urine protein-to-creatinine ratio at 4-6 weeks to assess treatment response—aim for reduction to <1 g/day or at least 30-50% reduction from baseline 1, 4

• Monitor serum creatinine/eGFR at 1-2 weeks after ACE inhibitor initiation—investigate if decline continues beyond 30% increase 4, 1

• Monitor serum potassium at 1-2 weeks after ACE inhibitor initiation and with any dose adjustments, as hyperkalemia is the most common reason for discontinuation 3, 2

• Recheck blood pressure at 2-4 week intervals until target of 120-129 mmHg systolic is achieved 2, 1

Essential Lifestyle Modifications

• Restrict dietary sodium to <2 g/day (<90 mmol/day), as sodium restriction enhances the antiproteinuric effects of RAS blockers and is critical for volume management 1, 4

• Fluid restriction to 1-1.5 L/day if anasarca is severe, to facilitate diuresis 2

• Achieve weight normalization through diet and exercise once acute phase resolves, as obesity independently worsens proteinuria 1

When to Refer to Nephrology Urgently

• Immediate nephrology referral if rapidly rising creatinine (>0.5 mg/dL increase in 1 week), oliguria, or suspicion for RPGN requiring kidney biopsy and possible immunosuppression 4

• Urgent referral within 1-2 weeks if proteinuria >1 g/day persists after 3-6 months of optimized supportive care, as immunosuppression may be needed 4

Common Pitfalls to Avoid

• Do not discontinue ACE inhibitors prematurely due to modest creatinine elevation (up to 30%), as this removes critical renoprotection 4

• Do not combine ACE inhibitor with ARB, as this increases adverse effects without additional benefit in most patients 2

• Do not use amlodipine as first-line therapy in a patient presenting with anasarca, as calcium channel blockers can worsen peripheral edema 6, 5

• Do not delay diuretic therapy in a patient with anasarca—aggressive volume management is essential 2