Hematuria

The presence of blood in the urine can be categorized as gross (seen with the naked eye) or microscopic (seen on dipstick analysis and urine microscopy); it is often seen in isolation but can be seen in conjunction with proteinuria.

Classification

• Gross/macroscopic hematuria: blood in the urine is visible to the naked eye

  • Etiologies include:

    • trauma

    • pseudohematuria due to pigments/dyes (e.g., from food or medication)

    • bladder irritation (hemorrhagic cystitis)

    • urinary tract infection (UTI)/infection (most common cause)

    • nephrolithiasis

    • glomerular disease (glomerulonephritis)

    • nutcracker syndrome (a vascular anomaly in which left renal vein is compressed, leading to gross hematuria and sometimes flank pain)

  • In one retrospective review of 158 patients who presented to a pediatric emergency department (ED) for gross hematuria, half had an identifiable cause and half of those with an underlying identifiable cause had UTI.

• Microscopic hematuria: blood in the urine is only noted on microscopic analysis

  • Etiologies include:

    • acute infection

    • hypercalciuria

    • nephrolithiasis

    • glomerulonephritis (including postinfectious)

    • IgA nephropathy

    • Alport syndrome

    • thin basement membrane nephropathy

Evaluation

• A thorough history and physical exam can provide clues to the underlying etiology.

  • History of exercise/trauma may reveal source of gross hematuria.

  • Symptoms of unilateral flank pain and renal colic may signify nephrolithiasis.

  • Dysuria, fevers, increased frequency of urination, or incontinence may signify UTI.

  • Terminal hematuria (gross hematuria at the end of the urinary stream) is almost always due to an extrarenal (ureter or bladder) source of bleeding.

  • Exposure to medications (e.g., phenazopyridine, cyclophosphamide, rifampin) may explain finding of gross hematuria.

  • Family history of hematuria or progressive deafness suggests thin basement membrane syndrome or Alport syndrome.

  • Recurrent episodes of gross hematuria marked by persistent microscopic hematuria is commonly seen in IgA nephropathy.

  • History of skin infection or sore throat should prompt evaluation for post-infectious glomerulonephritis.

• If urinalysis produces a positive dipstick, also check protein.

• Urine microscopy

  • If sample is centrifuged:

    • supernatant red + dipstick positive = myoglobinuria/hemoglobinuria (aka “blood without blood”)

    • supernatant red + dipstick negative = nonblood/dyes/medications/porphyria

    • pellet red = hematuria

• Serum laboratory tests

  • Conduct initial screening with basic metabolic panel (BMP), plasma complement (C3 and C4), albumin, antistreptolysin O (ASO), and antinuclear antibodies (ANA)/anti-double-stranded DNA (dsDNA).

  • If clinical history is significant for acute glomerulonephritis, consider antineutrophil cytoplasmic antibodies (ANCA), glomerular basement membrane (GBM), and other autoimmune antibodies.

• Urine laboratory tests

  • calcium-to-creatinine ratio and protein-to-creatinine ratio.

  • urine culture if symptoms are concerning for UTI

  • some viral infections (e.g., adenovirus) can also lead to gross hematuria

• Imaging

  • ultrasound, CT, or MRI if there is concern for nutcracker syndrome

Management

Nephrolithiasis: Patients with nephrolithiasis typically require serial ultrasounds and referral to Urology for management of stone burden.

• CT may be required to further characterize the stone burden prior to removal. A metabolic workup, including 24-hour urine collection, is then necessary to address the patient’s risk of forming new stones.

• Dietary approaches to prevent stones include increasing liquid intake/hydration, limiting salt intake, and alkalinizing the urine with citrate.

• Other approaches include a thiazide diuretic to limit calcium excretion in the urine.

• Consider genetic testing for monogenic causes of nephrolithiasis that currently explain up to 16% of urinary stone disease in pediatric patients.

IgA nephropathy:

• Patients with isolated microscopic hematuria due to IgA nephropathy or thin basement membrane nephropathy typically only require monitoring for CKD progression with blood pressure and urine checks.

• Although asymptomatic, these patients are at higher risk for ESKD than the general population.

• For rarer causes (e.g., nutcracker syndrome), consider referral to a specialist (vascular surgeon) at a tertiary care center.