What is the appropriate workup for a patient with a history of Focal Segmental Glomerulosclerosis (FSGS) presenting with flank pain?

Workup for Flank Pain in a Patient with FSGS History

In a patient with FSGS presenting with flank pain, prioritize imaging with non-contrast CT abdomen/pelvis to rule out nephrolithiasis, followed by evaluation for secondary causes of FSGS and complications of chronic kidney disease, while avoiding the assumption that flank pain is always stone-related.

Initial Imaging Approach

Non-contrast CT abdomen/pelvis is the reference standard for evaluating flank pain, with sensitivity as high as 97% for detecting urolithiasis 1. This should be your first-line imaging modality because:

• Kidney stone disease is the most common cause of acute flank pain requiring imaging evaluation 1
• FSGS patients may develop stones as a complication of nephrotic syndrome or its treatment 2
• Non-contrast CT can identify alternative diagnoses beyond stones 3

Alternative imaging if CT is contraindicated:

• Renal ultrasound combined with plain radiography has 79-90% sensitivity for clinically significant stones 1
• Ultrasound alone can assess for hydronephrosis and complications 1
• Color Doppler with twinkling artifact improves sensitivity for small stones (<5mm) up to 99%, though false-positive rates reach 60% 1

Critical Differential Diagnoses to Exclude

Do not anchor on nephrolithiasis as the only diagnosis. Flank pain with hematuria in kidney disease patients can represent:

Page Kidney (Subcapsular Hematoma)

• Presents identically to nephrolithiasis with flank pain and hematuria 4
• Causes secondary hypertension through renal parenchymal compression 4
• Requires CT with contrast (CTA) if initial non-contrast CT shows unexpected findings 4
• Treatment involves hypertension management with ACE inhibitors, not stone management 4

FSGS-Related Complications

• Renal vein thrombosis: 29% risk in nephrotic syndrome due to loss of anticoagulant proteins 2
• Infection/abscess: Increased susceptibility from immunoglobulin loss 2
• Progressive kidney disease: Patients with proteinuria >3.8g/day have 35% risk of ESRD within 2 years 2

Essential Clinical History Elements

Obtain these specific details to guide workup:

FSGS Classification History

• Primary vs. secondary FSGS: This distinction is critical because secondary FSGS does not respond to immunosuppression and has different complications 1, 5
• Genetic testing results: 11-24% of steroid-resistant FSGS has genetic causes 1, 2
• Current proteinuria level: Nephrotic-range (≥3.5g/day) vs. non-nephrotic 2, 5
• Serum albumin: Secondary FSGS typically maintains albumin >3.0 g/dL despite proteinuria 5

Secondary FSGS Risk Factors

• HIV status: Well-established viral cause of secondary FSGS 5
• Medication exposure: Interferon, lithium, bisphosphonates, anabolic steroids cause direct podocyte toxicity 5
• Diabetes and hypertension: Cause hyperfiltration injury leading to secondary FSGS 5, 6
• Obesity: Causes hyperfiltration-mediated FSGS 5
• History of prematurity: Associated with reduced nephron endowment 2, 5

Stone Risk Assessment

• Prior stone episodes: If known stone disease, non-contrast CT remains appropriate but consider reduced-dose protocols 1
• Immunosuppression history: Corticosteroids and calcineurin inhibitors affect stone risk 1, 2
• Thromboprophylaxis status: Anticoagulation may increase bleeding risk 2

Laboratory Workup

Order these tests concurrently with imaging:

• Urinalysis with microscopy: Distinguish hematuria patterns (glomerular vs. non-glomerular) 3
• Urine protein-to-creatinine ratio: Assess current disease activity 2
• Serum creatinine and eGFR: Evaluate for acute kidney injury vs. chronic progression 6
• Serum albumin: Helps distinguish primary from secondary FSGS 5
• Complete blood count: Assess for infection or anemia 2
• Blood pressure measurement: Page kidney and FSGS complications cause hypertension 4, 6

When to Add Contrast-Enhanced Imaging

CT abdomen/pelvis with IV contrast is indicated if:

• Initial non-contrast CT shows unexpected findings (mass, hematoma, abscess) 1, 4
• Clinical suspicion for renal vein thrombosis (acute flank pain with sudden proteinuria increase) 2
• Concern for infection/perinephric abscess in immunosuppressed patients 1

Note: Contrast-enhanced CT changes management in only 2-3% of suspected stone cases but is essential for alternative diagnoses 1

Common Pitfalls to Avoid

• Assuming all flank pain is stones: Page kidney, renal vein thrombosis, and infections present identically 4, 2
• Failing to distinguish primary from secondary FSGS: This leads to inappropriate immunosuppressive therapy with significant toxicity 1, 5
• Missing genetic FSGS: Genetic testing should be performed in steroid-resistant cases, as these patients don't benefit from immunosuppression 1, 2
• Overlooking medication-induced causes: Bisphosphonates, lithium, and other drugs cause secondary FSGS requiring drug discontinuation, not immunosuppression 5
• Inadequate evaluation of new hypertension: May indicate Page kidney or disease progression requiring specific management 4, 6

Management Based on Findings

If Nephrolithiasis Confirmed

• Stone size and location guide intervention vs. conservative management 1
• Optimize FSGS management: Ensure adequate RAS blockade and consider SGLT2 inhibitors if eGFR ≥20 mL/min/1.73m² 2

If Alternative Diagnosis Found

• Page kidney: ACE inhibitor therapy, monitor blood pressure 4
• Renal vein thrombosis: Anticoagulation (balance against bleeding risk) 2
• Secondary FSGS cause identified: Address underlying cause (HIV treatment, medication discontinuation, weight loss) rather than immunosuppression 5, 6

If No Acute Cause Identified

• Re-evaluate FSGS classification and consider genetic testing if not previously done 1, 2
• Optimize conservative management: RAS inhibition, blood pressure control ≤125/80 mmHg, sodium restriction 6
• Consider disease progression: Persistent proteinuria >3.8g/day indicates high ESRD risk requiring nephrology follow-up 2