How should I evaluate and manage a patient whose urinalysis shows hematuria (blood), proteinuria, and ketonuria?

Evaluation and Management of Urinalysis Showing Hemoglobin, Protein, and Ketones

Immediate Diagnostic Confirmation

You must first confirm true hematuria with microscopic urinalysis showing ≥3 red blood cells per high-power field (RBC/HPF) before initiating any further workup. 1 Dipstick testing alone has only 65–99% specificity and cannot distinguish between intact red blood cells, free hemoglobin, or myoglobin. 2, 1

• Order a fresh microscopic urinalysis on a properly collected clean-catch midstream specimen to verify the dipstick finding. 2
• If microscopy shows <3 RBCs/HPF, this is a false-positive dipstick result—document as normal and discontinue hematuria workup. 1
• If microscopy shows ≥3 RBCs/HPF, true microscopic hematuria is confirmed and requires risk stratification. 2, 1

Distinguish Glomerular from Urologic Sources

The combination of hematuria + proteinuria + ketonuria requires careful differentiation between glomerular disease and urologic pathology:

Glomerular Indicators (Nephrology Referral)

• Examine urinary sediment for dysmorphic RBCs (>80%) or red cell casts—these are pathognomonic for glomerular bleeding. 2, 3
• Obtain spot urine protein-to-creatinine ratio: values >0.5 g/g strongly suggest renal parenchymal disease. 2, 3
• Measure serum creatinine and eGFR to assess renal function; elevation indicates glomerular involvement. 2, 3
• Tea-colored or cola-colored urine suggests a glomerular source. 2

Urologic Indicators (Urology Referral)

• Predominantly normal-shaped RBCs (>80%) with minimal proteinuria suggest a non-glomerular, urologic origin. 2
• Age >35–40 years, smoking history, or occupational chemical exposure increase pre-test probability of urologic malignancy. 2, 3

Interpret the Ketonuria

Ketonuria is a confounding factor that increases false-positive proteinuria readings on dipstick. 4 The presence of ketones can artificially elevate protein readings, making quantitative testing essential:

• Do not rely on dipstick protein results when ketones are present—obtain a spot urine protein-to-creatinine ratio for accurate quantification. 4
• Ketonuria may indicate metabolic states (starvation, diabetic ketoacidosis, low-carbohydrate diet) unrelated to kidney disease. 5

Critical Pitfall: High Specific Gravity and Hematuria

High specific gravity (≥1.020) combined with hematuria are the strongest predictors of false-positive proteinuria on dipstick. 4 In your patient:

• The presence of both hematuria and ketones places this urinalysis in the "UA+CF" (confounding factors) category, which accounts for 98% of false-positive proteinuria results. 4
• Always confirm proteinuria with albumin-to-creatinine ratio (ACR) or protein-to-creatinine ratio when confounding factors are present. 4

Risk Stratification for Hematuria Workup

If microscopic hematuria is confirmed (≥3 RBC/HPF), stratify by risk:

High-Risk Features (Require Cystoscopy + CT Urography)

• Age ≥60 years (any sex) 2
• Smoking history >30 pack-years 2
• History of gross hematuria (even if self-limited) 2
• Occupational exposure to benzenes, aromatic amines, or industrial chemicals 2
• Irritative voiding symptoms without documented infection 2
• Degree of hematuria >25 RBC/HPF 2

Intermediate-Risk Features (Shared Decision-Making)

• Age 40–59 years (men) or 50–59 years (women) 2
• Smoking history 10–30 pack-years 2
• Hematuria 11–25 RBC/HPF 2

Low-Risk Features (May Defer Extensive Imaging)

• Age <40 years (men) or <50 years (women) 2
• Never smoker or <10 pack-years 2
• Hematuria 3–10 RBC/HPF 2

Recommended Diagnostic Algorithm

Step 1: Laboratory Evaluation (Order Today)

• Microscopic urinalysis with sediment examination for dysmorphic RBCs and casts 2, 3
• Spot urine protein-to-creatinine ratio (not dipstick) 2, 4
• Serum creatinine and eGFR 2, 3
• Urine culture if infection suspected (before antibiotics) 2, 3

Step 2: Determine Source

If glomerular features present (dysmorphic RBCs >80%, red cell casts, protein-to-creatinine ratio >0.5 g/g, elevated creatinine):

• Refer to nephrology urgently for further workup (complement levels, ANA, ANCA, renal biopsy consideration). 2
• Still complete urologic evaluation because malignancy can coexist with glomerular disease. 2

If non-glomerular features (normal-shaped RBCs, minimal proteinuria, normal renal function):

• Refer to urology for cystoscopy and imaging based on risk stratification. 2, 3

Step 3: Imaging and Endoscopy (If Indicated)

• Multiphasic CT urography is preferred for intermediate- and high-risk patients (96% sensitivity, 99% specificity for urothelial malignancy). 2
• Flexible cystoscopy is mandatory for patients ≥40 years with microscopic hematuria or any patient with gross hematuria. 2

Common Pitfalls to Avoid

• Never attribute hematuria to anticoagulant/antiplatelet therapy without completing full workup—these medications may unmask underlying pathology but do not cause hematuria. 2, 3
• Do not rely solely on dipstick proteinuria when confounding factors (ketones, hematuria, high specific gravity) are present—always confirm with quantitative testing. 4
• Do not dismiss hematuria in patients >35–40 years—age alone mandates comprehensive urologic evaluation. 2, 3
• Never ignore gross hematuria, even if self-limited—it carries a 30–40% malignancy risk. 2

Follow-Up Protocol

If initial workup is negative but hematuria persists:

• Repeat urinalysis at 6,12,24, and 36 months with blood pressure monitoring at each visit. 2, 3
• Immediate re-evaluation if gross hematuria develops, microscopic hematuria markedly increases, new urologic symptoms appear, or hypertension/proteinuria/glomerular bleeding emerges. 2, 3
• After two consecutive negative annual urinalyses, further testing is unnecessary. 2