Hematuria

Hematuria, defined as the presence of red blood cells (RBCs) in the urine, can be a concerning finding for pediatric patients, their parents, and healthcare providers.

Hematuria serves as an important indicator of various underlying causes, each with its own level of clinical significance.

While different definitions have been proposed, hematuria is most commonly defined as the presence of more than 5 RBCs per high-power field in an un-centrifuged midstream urine collection.

Hematuria can manifest in two main forms: macroscopic (gross) and microscopic. Macroscopic hematuria is visible to the naked eye and may appear "red" or "pink" due to lower urinary tract issues or "brown" or "tea" colored as a result of the oxidation of heme pigments in the urine.

In normal physiological conditions, hematuria is a rare occurrence. The tightly woven structure of the glomerular basement membrane typically prevents blood from entering the urinary collecting system. However, when this barrier is breached, the flexible cell membrane of RBCs allows them to pass through and enter the urinary system.

It's important to note that hematuria itself is almost never the cause of anemia.

Microscopic examination plays a crucial role in diagnosis. It involves concentrating the urinary sediment through centrifugation. Typically, 10 milliliters of urine are spun at 2000 rpm for 5 minutes, with 9 ml decanted. The resulting sediment is resuspended and examined under high-power microscopy (400× magnification).

Macroscopic hematuria has an estimated incidence of 1.3 per 1000.

Microscopic hematuria, although more common than gross hematuria, has a variably reported incidence depending on the definition used for making the diagnosis.

Microscopic hematuria in two or more urine samples is found in 1% to 2% of children 6 to 15 years of age.

Hematuria may originate from different areas in the urinary system, including:

• Glomeruli
• Renal tubules and interstitium
• Urinary tract (including collecting systems, ureters, bladder, and urethra)

In children, bleeding is more commonly associated with glomerular sources rather than the urinary tract itself.

Red blood cells (RBCs) cross the glomerular endothelial-epithelial barrier and enter the capillary lumen through structural discontinuities in the capillary wall.

In most cases, hematuria caused by glomerulonephritides is accompanied by additional findings in the urine, such as proteinuria, RBC casts, and dysmorphic RBCs.

The renal papillae can be vulnerable to necrotic injury, particularly in patients with hemoglobinopathies or exposure to toxins, leading to microthrombi and anoxia.

Patients with renal parenchymal lesions may experience episodes of transient microscopic or macroscopic hematuria during systemic infections or after moderate exercise.

• Glomerular Diseases:
  • Recurrent gross hematuria (IgA nephropathy, benign familial hematuria, Alport’s syndrome)
  • Acute poststreptococcal glomerulonephritis
  • Membranoproliferative glomerulonephritis
  • Systemic lupus erythematosus
  • Membranous nephropathy
  • Rapidly progressive glomerulonephritis
  • Henoch-Schonlein purpura
  • Goodpasture’s disease
• Medications:
  • Aminoglycosides
  • Amitriptyline
  • Anticonvulsants
  • Aspirin
  • Chlorpromazine
  • Coumadin
  • Thorazine
  • Cyclophosphamide
  • Diuretics
  • Penicillin
• Interstitial and Tubular:
  • Acute pyelonephritis
  • Acute interstitial nephritis
  • Tuberculosis
  • Hematologic (sickle cell disease, coagulopathies, von Willebrand’s disease, renal vein thrombosis, thrombocytopenia)
  • Urinary tract bacterial or viral (adenovirus) infection–related
  • Nephrolithiasis and hypercalciuria
• Structural Anomalies:
  • Congenital anomalies
  • Polycystic kidney disease
• Others:
  • Trauma
  • Tumors
  • Exercise

Causes of Asymptomatic Isolated Microscopic Hematuria

• Common:
  • Benign familial
  • Idiopathic hypercalciuria
  • IgA nephropathy
  • Sickle cell trait or anemia
  • Transplant
• Less Common:
  • Alport nephritis
  • Postinfectious glomerulonephritis
  • Trauma
  • Exercise
  • Nephrolithiasis
  • Henoch-Schonlein purpura
• Uncommon:
  • Drugs and toxins
  • Coagulopathy
  • Ureteropelvic junction obstruction
  • Focal segmental glomerulosclerosis
  • Membranous glomerulonephritis
  • Membranoproliferative glomerulonephritis
  • Lupus nephritis
  • Hydronephrosis
  • Pyelonephritis
  • Vascular malformation
  • Tuberculosis
  • Tumor

• Macroscopic hematuria of glomerular origin usually is described as brown, tea-colored, or cola-colored.
• Macroscopic hematuria from the lower urinary tract (bladder and urethra) is usually pink or red.
• Macroscopic hematuria in the absence of significant proteinuria or RBC casts is an indication for a renal and bladder ultrasound to exclude malignancy or cystic renal disease.
• Most children with isolated microscopic hematuria do not have a treatable or serious cause for hematuria and do not require an extensive evaluation.
• The presence of hematuria must be confirmed by microscopic examination of spun sediment of urine because other substances besides blood can produce red or brown urine or give a false positive dipstick test for blood.

When evaluating a child with hematuria, a comprehensive history is essential. Consider asking the following questions:

Symptoms:

• Ask about symptoms like dysuria (painful urination), urinary frequency, urgency, or flank and abdominal pain. These symptoms may suggest a urinary tract infection or nephrolithiasis.

Potential Triggers:

• Explore recent events or activities that may be related to hematuria, such as trauma, strenuous exercise, menstruation (in females), or bladder catheterization.

Infections:

• Probe for any recent illnesses, such as a sore throat or skin infection within the past 2 to 4 weeks. This information can guide the evaluation toward postinfectious glomerulonephritis, which is a possible cause of hematuria.

Medications and Toxins:

• Ask about any medications the child is taking or potential exposure to toxins. Some drugs and toxins can cause either hematuria or hemoglobinuria.

Family History:

• Obtain a detailed family history, including questions about a family history of hematuria, hearing loss, hypertension, nephrolithiasis, renal diseases, renal cystic diseases, hemophilia, sickle cell trait, and any history of dialysis or transplant in the family.

During the physical examination of a child with hematuria, consider the following:

Blood Pressure and Proteinuria:

• Assess the blood pressure. The presence or absence of hypertension and proteinuria will help determine the extent of the diagnostic evaluation.
• If the blood pressure is normal and the patient is passing normal amounts of urine, it is less likely that microscopic hematuria, regardless of its cause, requires immediate treatment.
• If the blood pressure is elevated, a more comprehensive diagnostic evaluation is necessary.

Abdominal Examination:

• Perform an abdominal examination to check for the presence of any abdominal mass. An abdominal mass may be caused by various conditions, including tumors, hydronephrosis, multicystic dysplastic kidney, or polycystic kidney disease.

Signs of Glomerulonephritis:

• Macroscopic hematuria accompanied by proteinuria suggests glomerulonephritis as a potential cause.

Other Signs and Symptoms:

• Look for additional signs and symptoms that could provide diagnostic clues:
  • Rashes and arthritis may be indicative of conditions like Henoch-Schonlein purpura and systemic lupus erythematosus.
  • Edema is an important feature of the nephrotic syndrome.

When evaluating a child with hematuria, specific laboratory studies are essential:

• For microscopic hematuria, perform the following diagnostic tests:
  • Test for proteinuria.
  • Microscopic examination of the urine for RBCs and RBC casts.
• If the child has macroscopic hematuria, additional investigations are necessary, including:
  • Urine culture to check for infection.
  • Renal imaging using ultrasound.
• Proteinuria may be present regardless of the cause of bleeding. However, it typically does not exceed 2+ (100 mg/dL) when the sole source of protein is from the blood, especially in cases of microscopic hematuria.
• Patients with 1+ to 2+ proteinuria should be evaluated for orthostatic (postural) proteinuria.
• If a patient exhibits more than 2+ proteinuria, further investigation is required to assess for glomerulonephritis and nephrotic syndrome.
• RBC casts, when present in urine, serve as a highly specific marker for glomerulonephritis.

Macroscopic hematuria requires immediate evaluation to rule out potentially life-threatening causes. The following steps are crucial:

• Perform a urinalysis to confirm the presence of red blood cells (RBCs) and to check for casts and crystals.
• In some cases, diagnosis of Schistosoma hematobium is possible by detecting ova in the urine of a child with unexplained macroscopic hematuria.
• Painful macroscopic hematuria is typically caused by infections, calculi (stones), or urologic conditions.
• Glomerular causes of hematuria are usually painless.
• The most common glomerular causes of gross hematuria in children include poststreptococcal glomerulonephritis and IgA nephropathy.
• IgA nephropathy can lead to recurrent macroscopic hematuria with flank or abdominal pain and may be preceded by an upper respiratory tract infection.
• If a child presents with fever, dysuria, and flank pain, with or without voiding symptoms, it suggests a urinary tract infection, which is the most common cause of gross hematuria in children seen in an emergency room.
• A family history of renal calculi or severe renal colic with gross hematuria indicates a potential diagnosis of urinary calculi.
• Hypercalciuria can lead to recurrent macroscopic or microscopic hematuria even in the absence of visible calculi on imaging studies.
• If no apparent cause is found for macroscopic hematuria based on history, physical examination, and initial studies, consider differential diagnoses such as hypercalciuria, sickle cell trait, thin basement membrane disease, calculi, and vascular or bladder pathology.
• Repeat the dipstick and microscopic urinalysis twice within a 2-week period after the initial specimen. If hematuria resolves, further tests may not be necessary.
• If hematuria persists, with more than five RBCs/hpf and no evidence of hypertension, oliguria, or proteinuria on at least two of three consecutive samples, consider determining the serum creatinine concentration.
• Consider renal ultrasonography as a screening test because it is noninvasive and provides information on the presence or absence of stones, tumors, hydronephrosis, structural anomalies, renal parenchymal dysplasia, medical renal disease, bladder inflammation, bladder polyps, and posterior urethral valves.
• The utility of renal ultrasonography for evaluating an asymptomatic child with microscopic hematuria remains unproven.

In summary, the causes of both gross and microscopic hematuria in children encompass a wide spectrum of kidney and urinary tract pathology. A thorough history, detailed physical examination, and targeted laboratory investigations can often shed light on the underlying cause of hematuria.

These assessments can either provide reassurance to the clinician regarding the appropriateness of conservative management or prompt them to consider a referral to a subspecialty care provider for further evaluation and management.