What is the differential diagnosis for a 10-year-old boy presenting with acute onset of dark-colored urine and slightly decreased urine output, normal blood pressure, and a significantly elevated urine protein-to-creatinine ratio, with complement (C3) levels pending?

Differential Diagnosis for Dark Urine and Decreased Output in a 10-Year-Old Boy

The most likely differential diagnoses in this 10-year-old boy with dark urine, slightly decreased output, normal blood pressure, and markedly elevated urine protein-creatinine ratio (15 mg/mg) are post-infectious glomerulonephritis, C3 glomerulopathy, IgA nephropathy, and less likely but important to exclude, nephrotic syndrome variants with acute kidney injury.

Primary Glomerular Disease Considerations

Post-Infectious Glomerulonephritis (PIGN)

• PIGN is the most common cause of acute glomerulonephritis in children, typically presenting 1-3 weeks after streptococcal pharyngitis or 3-6 weeks after skin infection with dark ("tea-colored" or "cola-colored") urine, hematuria, and variable proteinuria 1.
• The presentation with dark urine and decreased output in a child strongly suggests glomerular disease, particularly when accompanied by significant proteinuria 1.
• Low C3 levels (which are pending in this case) would strongly support PIGN, as complement consumption is characteristic of this condition 2.
• Normal blood pressure does NOT exclude PIGN, though hypertension is common and may develop as the disease progresses 2.

C3 Glomerulopathy (C3G)

• C3G should be high on the differential given the markedly elevated protein-creatinine ratio of 15 mg/mg, which indicates nephrotic-range proteinuria (>200 mg/mmol or approximately >2 mg/mg) 3.
• C3G is characterized by dysregulation of the alternative complement pathway and presents with variable combinations of hematuria, proteinuria (often nephrotic-range), and renal impairment 4, 5.
• The pending C3 level is critical: persistently low C3 with normal C4 suggests C3G, while low C3 and C4 suggest lupus or other causes 2.
• C3G can present acutely with dark urine and is associated with membranoproliferative glomerulonephritis (MPGN) pattern on biopsy 5.

IgA Nephropathy

• IgA nephropathy commonly presents in children and adolescents with episodic gross hematuria (dark or "tea-colored" urine) often concurrent with or immediately following upper respiratory infections 1.
• The protein-creatinine ratio of 15 mg/mg is unusually high for typical IgA nephropathy, which more commonly presents with mild-to-moderate proteinuria, though nephrotic-range proteinuria can occur 2.
• C3 levels are typically normal in IgA nephropathy, which would help differentiate it from PIGN and C3G once results are available 2.

Secondary Considerations

Nephrotic Syndrome with Acute Presentation

• A protein-creatinine ratio of 15 mg/mg represents severe nephrotic-range proteinuria (normal <0.2 g/g or <200 mg/g; nephrotic range ≥200 mg/mmol or ≥2000 mg/g) 2, 3.
• While classic nephrotic syndrome (minimal change disease, FSGS) typically presents with edema and hypoalbuminemia rather than dark urine, secondary causes or atypical presentations must be considered 3.
• The combination of dark urine (suggesting hematuria) with massive proteinuria points more toward proliferative glomerulonephritis than pure nephrotic syndrome 1.

Acute Tubular Necrosis (ATN) - Less Likely

• While hyaline casts may be present in early ATN 6, the clinical presentation with dark urine and massive proteinuria is not typical for ATN.
• ATN would be expected if there were a clear precipitating event (nephrotoxin exposure, severe dehydration, sepsis), which is not mentioned 6.

Critical Diagnostic Workup Required

Immediate Laboratory Evaluation

• Complete urinalysis with microscopy is essential to examine for dysmorphic RBCs (>80% suggests glomerular disease), red blood cell casts (pathognomonic for glomerulonephritis), and other cellular elements 2, 1.
• Serum creatinine, BUN, and electrolytes to assess renal function and determine if acute kidney injury is present 2, 7.
• Complete blood count to evaluate for anemia and assess for systemic disease 7.
• Serum albumin and total protein to determine if nephrotic syndrome is present (albumin <25 g/L) 3.
• Complement levels (C3, C4) - already pending, but critical for differentiating PIGN (low C3, normal C4) from C3G (persistently low C3) from lupus (low C3 and C4) 2.

Additional Serologic Testing

• Anti-streptolysin O (ASO) titer and anti-DNase B to evaluate for recent streptococcal infection supporting PIGN 1.
• Antinuclear antibody (ANA) and anti-dsDNA if systemic lupus erythematosus is suspected, particularly if C3 and C4 are both low 1.
• ANCA testing if vasculitis is suspected, though less common in this age group 2.

Imaging

• Renal ultrasound to evaluate kidney size, echogenicity, and structural abnormalities (enlarged echogenic kidneys suggest acute glomerulonephritis) 1.

Clinical Pearls and Pitfalls

Key Diagnostic Clues

• The combination of dark urine + massive proteinuria (15 mg/mg) + pending low C3 = think proliferative glomerulonephritis (PIGN or C3G most likely) 2, 1.
• Normal blood pressure does NOT exclude glomerulonephritis - hypertension may develop later or be absent in some cases 2.
• Tea-colored or cola-colored urine strongly suggests glomerular bleeding rather than lower urinary tract pathology 1.

Common Pitfalls to Avoid

• Do not attribute the dark urine to dehydration or exercise without confirming microscopic hematuria - these benign causes would not explain the massive proteinuria 6, 1.
• Do not delay nephrology referral - the combination of significant proteinuria (>200 mg/g), likely hematuria (dark urine), and possible declining renal function mandates specialist evaluation 2.
• Antibiotic therapy should not be initiated for presumed UTI without confirming infection, as this presentation is much more consistent with glomerulonephritis than infection 1.

Nephrology Referral Indications

• Immediate nephrology referral is indicated for this patient given: persistent significant proteinuria (protein-creatinine ratio 15 mg/mg), likely presence of red cell casts or dysmorphic RBCs (pending microscopy), and possible elevated creatinine or declining renal function 2, 1.
• Renal biopsy may be necessary for definitive diagnosis, particularly if C3G, atypical PIGN, or other chronic glomerular disease is suspected 2, 1.