What is the most likely diagnosis and recommended work‑up for a patient presenting with peripheral edema, hypertension, and hematuria?

Acute Glomerulonephritis: Most Likely Diagnosis

A patient presenting with peripheral edema, hypertension, and hematuria most likely has acute glomerulonephritis (GN), and the immediate work-up must include urinalysis with microscopy, serum creatinine, complement levels (C3, C4), and urgent nephrology referral if proteinuria or renal dysfunction is present. 1, 2

Clinical Presentation and Pathophysiology

The classic triad of edema, hypertension, and hematuria defines the nephritic syndrome, which is the hallmark presentation of acute glomerulonephritis. 1, 3 This constellation occurs because:

• Hematuria results from glomerular inflammation allowing red blood cells to leak into the urinary space 2
• Edema develops from sodium and water retention secondary to reduced glomerular filtration 4
• Hypertension is a direct consequence of volume expansion from impaired renal sodium handling 1, 4

The nephritic syndrome carries a poorer prognosis than isolated hematuria and typically indicates significant glomerular injury requiring prompt evaluation. 1

Immediate Diagnostic Work-Up

Essential Initial Testing

Perform these tests immediately—do not wait for nephrology consultation: 5

• Urinalysis with microscopy: Examine for dysmorphic RBCs (>80% suggests glomerular origin), red cell casts (pathognomonic for GN), and degree of proteinuria 6, 1
• Spot urine protein-to-creatinine ratio: Quantify proteinuria; values >0.5 g/g strongly suggest renal parenchymal disease 6
• Serum creatinine and eGFR: Assess renal function; elevation indicates acute kidney injury 5, 7
• Complete metabolic panel: Evaluate electrolytes, BUN, albumin 5
• Complement levels (C3, C4): Low C3 supports post-infectious GN or C3 glomerulopathy; low C3 and C4 suggest lupus nephritis 6
• 12-lead ECG: Screen for left ventricular hypertrophy and cardiac complications of hypertension 5

Critical Urinary Findings That Confirm Glomerular Disease

Red cell casts are pathognomonic for glomerulonephritis—their presence mandates immediate nephrology referral. 6, 1

Dysmorphic RBCs >80% indicate glomerular bleeding and distinguish GN from urologic causes of hematuria. 6, 8

Tea-colored or cola-colored urine is the classic appearance of glomerular hematuria, contrasting with bright red urine from lower urinary tract bleeding. 6

Differential Diagnosis: Most Common Causes

Post-Infectious Glomerulonephritis (PIGN)

The most common cause of acute nephritic syndrome, particularly following streptococcal pharyngitis or skin infection. 1, 4 Key features include:

• Latent period of 1-3 weeks after infection 2
• Low C3 levels (complement consumption is characteristic) 6
• Hypertension and edema are common but normal blood pressure does NOT exclude PIGN 6
• Self-limited course in most cases 4

IgA Nephropathy (Berger Disease)

The most common primary glomerulonephritis worldwide, often presenting with episodic gross hematuria concurrent with or immediately following upper respiratory infections. 8, 2, 4 Typically shows:

• Normal complement levels (distinguishes from PIGN) 2
• Mild-to-moderate proteinuria (though nephrotic-range can occur) 6
• Requires renal biopsy for definitive diagnosis 8, 4

Lupus Nephritis

Consider in patients with systemic symptoms (rash, arthritis, serositis) or known systemic lupus erythematosus. 1, 4 Characterized by:

• Low C3 and C4 levels (distinguishes from PIGN) 6
• Positive ANA and anti-dsDNA antibodies 5
• Variable proteinuria and renal dysfunction 1

ANCA-Associated Vasculitis

Presents with rapidly progressive glomerulonephritis and often systemic manifestations (pulmonary hemorrhage, sinusitis). 2 Features include:

• Positive ANCA (PR3 or MPO antibodies) 5
• Pauci-immune pattern on biopsy (minimal immune deposits) 2
• Requires urgent immunosuppression 2

Mandatory Nephrology Referral Criteria

Refer immediately to nephrology if ANY of the following are present: 6

• Red cell casts or >80% dysmorphic RBCs on urinary microscopy
• Protein-to-creatinine ratio >0.5 g/g (or >500 mg/24 hours)
• Elevated serum creatinine or declining renal function
• Hypertension accompanying hematuria and proteinuria
• Rapidly progressive course (rising creatinine over days to weeks)

Critical Pitfalls to Avoid

Do not assume normal blood pressure excludes glomerulonephritis—hypertension may develop later or be absent in some cases. 6

Do not attribute hematuria to anticoagulation or antiplatelet therapy—these medications may unmask underlying pathology but do not cause glomerular bleeding. 6

Do not skip urinalysis with microscopy—dipstick alone has only 65-99% specificity and cannot identify dysmorphic RBCs or casts. 6

Do not delay nephrology referral while awaiting complement levels or other serologies—the presence of the nephritic triad (edema, hypertension, hematuria) with proteinuria warrants urgent consultation. 6, 1

Do not order CT urography or cystoscopy as initial tests—these are indicated for urologic causes of hematuria, not glomerular disease. Complete the glomerular work-up first; if urologic evaluation is needed, it can be performed after excluding or treating GN. 6

Concurrent Urologic Evaluation Considerations

Even when glomerular disease is suspected, complete urologic evaluation may still be required if: 6

• Patient has high-risk features for malignancy (age >40 years, smoking >30 pack-years, occupational chemical exposure)
• Hematuria persists after treatment of glomerulonephritis
• Imaging reveals structural abnormalities requiring further investigation

However, nephrology evaluation takes priority when the nephritic syndrome is present, as acute GN can lead to irreversible renal damage if treatment is delayed. 1, 2