What is the appropriate workup for a patient with hematuria, proteinuria, and bilirubinuria, with a past medical history (PMH) of obesity and hypercholesterolemia (high cholesterol), and normal serum bilirubin, who is currently undergoing a 5-day fast and has a normal Hemoglobin A1c (HbA1c)?

Workup for Hematuria, Proteinuria, and Bilirubinuria in a Fasting Patient

The bilirubinuria is almost certainly a false positive related to the 5-day fast and can be disregarded given the normal serum bilirubin; focus your workup on confirming and quantifying the proteinuria and hematuria to determine if glomerular disease is present. 1

Immediate Next Steps

1. Confirm and Quantify the Proteinuria

• Obtain a spot urine protein-to-creatinine ratio (UPCR) using a first morning void to accurately quantify proteinuria, as dipstick readings are qualitative and can be falsely elevated by concentrated urine during fasting 1
• Normal UPCR is <200 mg/g; values ≥200 mg/g indicate significant proteinuria requiring further evaluation 1
• Do not rely on the single dipstick reading alone – quantitative confirmation is mandatory before proceeding with extensive workup 1

2. Characterize the Hematuria

• Examine the urine sediment microscopically to differentiate glomerular from non-glomerular bleeding 2
• Look specifically for dysmorphic red blood cells and red blood cell casts, which indicate glomerular disease 3, 2
• Eumorphic (normal-shaped) RBCs suggest lower urinary tract bleeding rather than glomerular pathology 2

3. Address the Fasting Context

• The bilirubinuria with normal serum bilirubin is likely spurious – prolonged fasting can cause ketonuria and concentrated urine that may interfere with dipstick readings 1
• Repeat the urinalysis after the patient resumes normal eating to confirm persistence of findings 1
• Vigorous exercise and dehydration from fasting can cause transient proteinuria, so retest after adequate hydration 1

Risk Stratification Based on Initial Results

If UPCR is 200-1000 mg/g (0.2-1.0 g/day):

• Check serum creatinine and calculate eGFR to assess baseline kidney function 4
• Measure blood pressure – target <130/80 mmHg if proteinuria confirmed 4
• Initiate conservative management for 3-6 months before considering more invasive workup: ACE inhibitor or ARB therapy, sodium restriction <2 g/day, and blood pressure optimization 4
• Monitor with repeat UPCR every 3 months 1

If UPCR is >1000 mg/g (>1.0 g/day):

• Immediate nephrology referral is indicated for likely glomerular disease 1, 5
• Target blood pressure <125/75 mmHg with ACE inhibitor or ARB as first-line therapy 4
• Obtain additional labs: serum albumin, lipid panel, complement levels (C3, C4), ANA, anti-dsDNA, ANCA, hepatitis B and C serologies, HIV testing 4
• Kidney biopsy will likely be necessary to determine the specific glomerular disease and guide immunosuppressive therapy 4, 1

If UPCR is >3500 mg/g (nephrotic range):

• This is a medical urgency requiring immediate nephrology consultation due to high risk for thrombotic complications and progressive kidney disease 1
• Consider 24-hour urine collection to precisely confirm nephrotic syndrome (>3.5 g/day) for thromboprophylaxis decisions 1

Essential Laboratory Workup

Basic Metabolic Panel

• Serum creatinine and eGFR to assess kidney function 4
• Electrolytes, particularly potassium before starting ACE inhibitor/ARB 4
• Serum albumin to assess for nephrotic syndrome 4

Exclude Secondary Causes of Glomerular Disease

• Fasting glucose and repeat HbA1c – although current A1c is normal, obesity is a risk factor for undiagnosed diabetes 4
• Lipid panel – hypercholesterolemia can be both a cause and consequence of glomerular disease 4
• Rule out infection-related glomerulonephritis: HIV, hepatitis B surface antigen, hepatitis C antibody 4
• Consider checking complement levels (C3, C4) and autoimmune serologies (ANA, anti-dsDNA, ANCA) if proteinuria is significant 4

Urine Studies Beyond Dipstick

• Urine culture to exclude urinary tract infection, which can cause transient proteinuria and hematuria 5
• Microscopic examination of urine sediment for casts, crystals, and RBC morphology 3, 2
• Urine calcium-to-creatinine ratio if gross hematuria present to evaluate for hypercalciuria 2

Imaging Considerations

• Renal ultrasound is reasonable to assess kidney size, echogenicity, and exclude structural abnormalities or masses 2
• CT imaging is not indicated unless there is gross hematuria, flank pain, or concern for nephrolithiasis or malignancy 5, 2
• Avoid contrast-enhanced studies until kidney function is confirmed to be normal 5

Critical Pitfalls to Avoid

Do Not Ignore the Obesity Context

• Obesity-related glomerular disease (secondary FSGS) is a real consideration in this patient with BMI suggesting obesity 4
• The combination of obesity, hypercholesterolemia, and proteinuria may indicate adaptive/hyperfiltration injury rather than primary glomerular disease 4
• Conservative management with weight loss, BP control, and RAS blockade should be the initial approach before considering immunosuppression 4

Do Not Start ACE Inhibitors/ARBs Prematurely

• If nephrotic syndrome is suspected, do not start ACE inhibitors or ARBs immediately – these can cause acute kidney injury in patients with minimal change disease presenting with abrupt-onset nephrotic syndrome 4
• Wait for nephrology evaluation if proteinuria is nephrotic-range 4

Do Not Pursue Genetic Testing Routinely

• Genetic testing for hereditary nephropathies is not indicated without a positive family history of kidney disease or very early onset disease 4

Do Not Delay Nephrology Referral

• Refer immediately if any of the following: UPCR >1000 mg/g despite 3-6 months conservative therapy, eGFR <30 mL/min/1.73 m², active urinary sediment with dysmorphic RBCs or RBC casts, or nephrotic syndrome 1, 5

Follow-Up Timeline

• Repeat urinalysis and UPCR in 1-2 weeks after resuming normal diet to confirm persistence 1
• If proteinuria confirmed and <1 g/day, recheck every 3 months during conservative management 1
• Monitor serum creatinine and potassium 1-2 weeks after starting ACE inhibitor or ARB to detect hyperkalemia or acute kidney injury 4, 5
• Annual screening for proteinuria should continue given risk factors of obesity and hypercholesterolemia 1