Management of Hematuria with Calcium Oxalate Crystals and Urobilinogen
Confirm true microscopic hematuria (≥3 RBCs/HPF) with microscopic examination, then proceed with complete urologic evaluation including upper tract imaging and cystoscopy to exclude malignancy, while simultaneously investigating metabolic causes of calcium oxalate crystalluria. 1, 2
Immediate Confirmation and Risk Assessment
Verify microscopic hematuria by documenting ≥3 red blood cells per high-power field on at least two of three properly collected clean-catch midstream urine specimens—dipstick results alone are insufficient (specificity only 65-99%) 1, 2
Assess risk factors for malignancy including age >40 years, smoking history (especially >30 pack-years), occupational exposure to benzenes or aromatic amines, history of gross hematuria, irritative voiding symptoms, and history of pelvic irradiation 1, 3
Exclude benign transient causes by ruling out urinary tract infection with urine culture (obtain before antibiotics if possible), menstruation, vigorous exercise, sexual activity, recent trauma, and viral illness 1, 2
Distinguish Glomerular from Non-Glomerular Sources
Examine urinary sediment for dysmorphic RBCs (>80% suggests glomerular disease), red cell casts (pathognomonic for glomerular disease), and degree of proteinuria 1, 3
Measure serum creatinine to assess renal function and identify potential renal parenchymal disease 1, 2
Quantify proteinuria using spot urine protein-to-creatinine ratio (normal <0.2 g/g); significant proteinuria >500 mg/24 hours suggests glomerular disease and warrants nephrology referral in addition to urologic evaluation 1, 3
The presence of normal-appearing RBCs (>80%) with calcium oxalate crystals suggests a non-glomerular, metabolic source rather than glomerular disease 3
Complete Urologic Evaluation for Non-Glomerular Hematuria
This evaluation is mandatory regardless of the presence of calcium oxalate crystals, as malignancy must be excluded:
Multiphasic CT urography is the preferred imaging modality to detect renal cell carcinoma, transitional cell carcinoma, and urolithiasis—includes unenhanced, nephrographic, and excretory phases 1, 3, 2
Cystoscopy is mandatory for all patients ≥40 years old and for younger patients with risk factors (smoking, occupational exposures, irritative voiding symptoms, history of gross hematuria) 1, 3, 2
Voided urine cytology should be obtained in high-risk patients to detect urothelial cancers, particularly high-grade tumors and carcinoma in situ 1, 3
Flexible cystoscopy is preferred over rigid cystoscopy as it causes less pain with equivalent or superior diagnostic accuracy 1, 3
Metabolic Evaluation for Calcium Oxalate Crystalluria
After excluding malignancy, investigate metabolic causes of calcium oxalate crystal formation:
24-hour urine collection to measure volume, pH, and excretion of calcium, phosphorus, magnesium, uric acid, citrate, sodium, oxalate, and creatinine 4
Hypercalciuria (>200 mg/24 hours) is the most common metabolic cause of calcium oxalate stones and can cause isolated microscopic hematuria 4, 5
Hyperuricosuria frequently coexists with hypercalciuria and can cause familial microscopic hematuria with calcium oxalate and uric acid crystals in the sediment 5
Hypocitraturia (reduced urinary citrate) increases calcium oxalate supersaturation and stone risk 4
Measure serum calcium, phosphate, uric acid, and creatinine to identify systemic metabolic abnormalities 4
Significance of Urobilinogen
Positive urobilinogen on urinalysis is typically a normal finding (trace to 1 mg/dL is physiologic) and does not require specific intervention unless markedly elevated
If urobilinogen is significantly elevated, consider hemolysis or hepatobiliary disease, but this is unrelated to the hematuria and calcium oxalate crystals
Treatment Strategy for Metabolic Hematuria
If urologic evaluation is negative and metabolic abnormalities are identified:
Increase fluid intake to achieve urine volume >2.5 L/24 hours to reduce urinary supersaturation 4
Thiazide diuretics to reduce urinary calcium excretion to <200 mg/24 hours if hypercalciuria is present 4, 5
Potassium citrate supplementation if urinary citrate levels are reduced 4
Allopurinol if hyperuricosuria is present 5
Dietary modifications including moderate calcium intake (600-800 mg/day), reduced sodium intake, and oxalate restriction if urinary oxalate is elevated 4
These interventions can lead to complete disappearance of hematuria when metabolic abnormalities are corrected 5
Follow-Up Protocol
Repeat urinalysis at 6,12,24, and 36 months if hematuria persists after negative urologic evaluation 1, 2
Immediate re-evaluation is warranted if gross hematuria develops, significant increase in microscopic hematuria occurs, or new urologic symptoms appear 1, 3
Nephrology referral is indicated if hematuria persists with development of hypertension, proteinuria >500 mg/24 hours, or evidence of glomerular bleeding 1, 2
Consider repeat complete evaluation within 3-5 years for persistent hematuria in high-risk patients 1
Critical Pitfalls to Avoid
Never attribute hematuria solely to calcium oxalate crystals without excluding malignancy—crystalluria is common and does not rule out concurrent urologic cancer 1, 3
Do not defer evaluation due to anticoagulation or antiplatelet therapy—these medications may unmask underlying pathology but do not cause hematuria 1, 3, 2
Do not treat with antibiotics if urine culture is negative—this delays cancer diagnosis and provides false reassurance 3
Do not rely on dipstick alone—always confirm with microscopic examination showing ≥3 RBCs/HPF 1, 3, 2
The finding of >200 pure calcium oxalate monohydrate (whewellite) crystals per cubic millimeter in young children is highly suggestive of primary hyperoxaluria type 1, though specificity is lower in adults 6