What is the diagnosis, diagnostics, and treatment for puffy eyes, slight facial edema, and occasional pedal edema with normal creatinine and estimated Glomerular Filtration Rate (eGFR) 6 months ago, normal Kidney, Ureter, and Bladder (KUB) ultrasound, and urinalysis showing moderate renal tubular epithelial cells?

Diagnosis: Likely Early Glomerular Disease (Nephrotic Syndrome or Glomerulonephritis)

The presence of moderate renal tubular epithelial cells (RTECs) on urinalysis combined with periorbital puffiness and pedal edema strongly suggests glomerular pathology requiring immediate quantitative proteinuria assessment and nephrology evaluation, even with previously normal renal function. 1, 2

Immediate Diagnostic Workup Required

Essential Laboratory Tests (Order Immediately)

• Spot urine albumin-to-creatinine ratio (UACR) - this is the preferred initial test for quantifying proteinuria, with abnormal defined as >30 mg/g 3, 1
• 24-hour urine protein collection - gold standard for total protein quantification in suspected glomerulonephritis 3
• Serum creatinine and eGFR - repeat testing needed since last measurement was 6 months ago 3
• Serum albumin - hypoalbuminemia <25 g/L suggests nephrotic syndrome 4
• Complete metabolic panel - assess for electrolyte abnormalities and cholesterol elevation (hyperlipidemia is part of nephrotic syndrome) 3, 4
• Urinalysis with microscopy - specifically examine for dysmorphic red blood cells, red cell casts, and acanthocytes which indicate glomerulonephritis 3, 1

Critical Serologic Studies

• Antineutrophil cytoplasmic antibody (ANCA) testing - MPO and PR3 antibodies to evaluate for ANCA-associated vasculitis, which can present with rapidly progressive glomerulonephritis 3
• Anti-GBM antibodies - to exclude anti-GBM disease 3
• Complement levels (C3, C4) - low levels suggest immune complex-mediated glomerulonephritis 3
• Antinuclear antibody (ANA) and anti-dsDNA - to evaluate for lupus nephritis 3
• Hepatitis B and C serology, HIV testing - secondary causes of glomerular disease 3

Imaging

• Repeat renal ultrasound - while the previous KUB ultrasound was normal, reassess kidney size and corticomedullary differentiation, as early CKD can maintain normal architecture 5

Clinical Significance of Renal Tubular Epithelial Cells

The finding of moderate RTECs is clinically significant and suggests upper urinary tract pathology, particularly glomerular disease. 6 RTECs are shed from the renal tubules and their presence in moderate amounts, combined with edema, indicates active kidney injury beyond simple lower urinary tract processes 6.

Nephrology Referral Criteria (Act on These)

Immediate nephrology referral is warranted if any of the following are present:

• Proteinuria >1,000 mg/24 hours 1
• Red cell casts or >80% dysmorphic RBCs - suggests glomerulonephritis requiring urgent evaluation 1
• eGFR <30 mL/min/1.73 m² 3, 2
• Rapidly declining eGFR - defined as decline >10 mL/min/year 5
• Positive ANCA or anti-GBM antibodies - do not wait for biopsy results before starting treatment if clinical presentation is compatible 3

Kidney Biopsy Indications

Kidney biopsy should be strongly considered and is likely necessary for definitive diagnosis given the constellation of findings 3. Specific indications include:

• Proteinuria with unclear etiology despite serologic workup 3
• Nephrotic-range proteinuria (>3.5 g/day) with hypoalbuminemia 3, 4
• Evidence of glomerulonephritis on urinalysis (dysmorphic RBCs, casts) 3
• Rapidly progressive kidney dysfunction 3

Do not delay biopsy if clinical suspicion is high - the biopsy provides critical information for diagnosis, prognosis, and treatment decisions 3.

Differential Diagnosis Priority List

Most Likely Diagnoses (Based on Presentation)

1. Minimal change disease - most common cause of nephrotic syndrome in adults with sudden onset periorbital edema, can present with normal kidney size and preserved eGFR initially 3, 4

2. Focal segmental glomerulosclerosis (FSGS) - can present with nephrotic syndrome and normal-sized kidneys, particularly in early stages 3, 5

3. Membranous nephropathy - common cause of nephrotic syndrome in adults, presents with edema and proteinuria 3, 4

4. Early diabetic kidney disease - even without known diabetes, screen with HbA1c given family history patterns and that type 2 diabetes can present with CKD at diagnosis 3, 5

5. ANCA-associated vasculitis - can present with rapidly progressive glomerulonephritis and normal kidney size initially 3

Less Likely But Important to Exclude

• IgA nephropathy - typically presents with hematuria but can have proteinuria 3
• Lupus nephritis - check ANA, anti-dsDNA 3
• Drug-induced nephrotic syndrome - obtain detailed medication history including over-the-counter drugs and supplements 7

Immediate Symptomatic Management

Edema Control

• Loop diuretics (furosemide) - start with 20-40 mg daily, titrate based on response 3
• Thiazide diuretics - can be added if loop diuretics alone are insufficient 3
• Sodium restriction - limit to <2 g/day 4
• Monitor daily weights - to assess fluid status 4

Blood Pressure Management

• Target BP <130/80 mmHg (or <125/80 if tolerated) 3
• ACE inhibitor or ARB - initiate if proteinuria is confirmed and BP is elevated, as these reduce proteinuria progression 3
• Monitor serum creatinine and potassium within 1-2 weeks after starting ACE inhibitor/ARB 3

Complications Prevention

• Anticoagulation consideration - if nephrotic syndrome is confirmed (albumin <25 g/L with heavy proteinuria), discuss thromboprophylaxis with nephrology given increased thrombotic risk 4
• Statin therapy - if hyperlipidemia is present (common in nephrotic syndrome) 3
• Infection prophylaxis - patients with nephrotic syndrome have increased infection risk 4

Critical Pitfalls to Avoid

• Do not assume normal creatinine/eGFR from 6 months ago means current kidney function is normal - glomerular diseases can progress rapidly 3, 5
• Do not dismiss RTECs as insignificant - their presence indicates upper urinary tract pathology and warrants full evaluation 6
• Do not delay nephrology referral while awaiting test results if clinical deterioration occurs 3
• Do not start immunosuppression before establishing diagnosis unless ANCA-positive with rapidly progressive disease 3
• Do not discontinue ACE inhibitor/ARB for minor creatinine increases (<30%) in the absence of volume depletion 3

Timeline for Action

• Within 24-48 hours: Complete all laboratory testing including UACR, serum albumin, comprehensive metabolic panel, and serologic studies 1
• Within 1 week: Obtain nephrology consultation if any concerning features present 3, 2
• Within 2 weeks: Complete 24-hour urine collection and repeat imaging if indicated 3
• Kidney biopsy timing: Coordinate with nephrology, typically within 2-4 weeks unless urgent indications present 3