What is the diagnosis and management for a 22-year-old (twenty-two-year-old) male with a history of anasarca and kidney problems in childhood, presenting with fever and lower extremity edema?

Diagnosis: Relapsed Nephrotic Syndrome with Possible Infection

This 22-year-old male with childhood anasarca and kidney problems presenting with fever and lower extremity edema most likely has relapsed nephrotic syndrome, potentially complicated by infection, and requires immediate evaluation for both conditions.

Diagnostic Approach

Immediate Clinical Assessment

Obtain a focused history and physical examination targeting:

• Volaemia status: assess for signs of hypovolemia (prolonged capillary refill time, tachycardia, hypotension, oliguria) versus fluid overload (ascites, pericardial/pleural effusions) 1
• Infection indicators: document fever pattern, presence of abdominal pain, respiratory symptoms, or urinary symptoms 1
• Growth parameters: current weight compared to baseline, blood pressure 1

First-Line Laboratory Evaluation

Order the following tests immediately:

• Blood biochemistry: complete blood count, sodium, chloride, albumin, magnesium, creatinine, urea, total protein, cholesterol, triglycerides 1
• Urinalysis with microscopy: evaluate for proteinuria, pyuria, bacteriuria, and hematuria 2, 3
• Urine culture with antimicrobial susceptibility testing if urinalysis shows pyuria/bacteriuria 2, 3
• Serum IgG level to assess immunodeficiency risk 1
• C-reactive protein to quantify inflammatory response 1

Imaging Studies

Perform abdominal and pleural ultrasound to assess kidney echogenicity and size, detect ascites, pleural effusions, and rule out thrombosis 1

Differential Diagnosis Priority

Primary Consideration: Relapsed Nephrotic Syndrome with Infection

The childhood history of anasarca and kidney problems strongly suggests congenital or childhood-onset nephrotic syndrome 1. Fever in nephrotic syndrome patients warrants immediate infection workup as these patients have increased susceptibility due to urinary immunoglobulin losses and immunosuppressive therapy 1.

Common infections to exclude:

• Urinary tract infection/pyelonephritis: especially if flank pain or costovertebral angle tenderness present 2, 3
• Peritonitis: particularly spontaneous bacterial peritonitis if ascites present 1
• Cellulitis: given lower extremity edema 1
• Respiratory infections: if pleural effusions or respiratory symptoms 1

Alternative Diagnosis: TAFRO Syndrome

Consider TAFRO syndrome (Thrombocytopenia, Anasarca, Fever, Reticulin fibrosis/Renal dysfunction, Organomegaly) if the patient presents with:

• Thrombocytopenia on complete blood count 4, 5, 6
• Systemic lymphadenopathy on examination or imaging 4, 5
• Severe diuretic-resistant anasarca with only mild proteinuria (<1 g/day) 5
• Elevated inflammatory markers disproportionate to findings 4, 7

TAFRO syndrome typically affects young adults and can present with severe systemic inflammation requiring aggressive immunosuppressive therapy 4, 5, 7.

Management Algorithm

If Infection is Confirmed or Suspected

For urinary tract infection/pyelonephritis:

• Start empirical antibiotics immediately after obtaining urine culture 3, 8
• Outpatient oral therapy: ciprofloxacin 500-750 mg twice daily for 7 days OR levofloxacin 750 mg once daily for 5 days 3, 8
• Hospitalized patients requiring IV therapy: ceftriaxone 1-2 g IV once daily, ciprofloxacin 400 mg IV twice daily, OR levofloxacin 750 mg IV once daily 3, 8
• Reassess within 48-72 hours: 95% of uncomplicated pyelonephritis cases become afebrile within 48 hours of appropriate therapy 2, 3
• If fever persists beyond 72 hours: obtain renal ultrasound to evaluate for complications (obstruction, abscess) 2, 3, 8

For other bacterial infections:

• Initiate appropriate culture-directed or empirical antibiotic therapy based on suspected source 1

If Nephrotic Syndrome Relapse Without Clear Infection

Refer immediately to specialized pediatric or adult nephrology unit for management of relapsed nephrotic syndrome 1

Fluid management approach:

• Assess volaemia clinically before initiating diuretic therapy 1
• For euvolemic or hypervolemic patients: oral furosemide 2-5 mg/kg/day combined with thiazide or amiloride (preferred over spironolactone due to direct ENaC activation by urinary proteases) 1
• Avoid routine albumin infusions unless clinical indicators of hypovolemia present (oliguria, acute kidney injury, prolonged capillary refill, tachycardia, hypotension) 1
• Do NOT base albumin administration on serum albumin levels alone 1

Anti-proteinuric therapy:

• Consider ACE inhibitor or ARB to reduce glomerular protein loss 1

If TAFRO Syndrome is Suspected

Obtain additional diagnostic studies:

• Bone marrow biopsy to evaluate for reticulin fibrosis and megakaryocyte hyperplasia 5, 6, 7
• Lymph node biopsy if lymphadenopathy present 6, 7
• Immature platelet fraction if thrombocytopenia develops 6

Treatment regimen:

• Glucocorticoids plus tocilizumab (IL-6 receptor antagonist) as first-line therapy 5, 9
• Rituximab for tocilizumab-resistant cases 7, 9

Critical Pitfalls to Avoid

• Do NOT delay infection workup in nephrotic syndrome patients with fever, as they are immunocompromised and at high risk for serious bacterial infections 1
• Do NOT perform routine kidney biopsy if genetic nephrotic syndrome is suspected; genetic testing identifies >85% of cases non-invasively 1
• Do NOT administer aggressive IV fluids or saline in nephrotic syndrome patients, as this worsens edema 1
• Do NOT use high-dose furosemide (>6 mg/kg/day) for >1 week due to ototoxicity risk 1
• Do NOT obtain imaging for uncomplicated pyelonephritis unless fever persists >72 hours or clinical deterioration occurs 2, 3
• Do NOT miss TAFRO syndrome by attributing all findings to nephrotic syndrome relapse; check platelet count and look for organomegaly/lymphadenopathy 4, 5, 6