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Hematuria

Abstract

Hematuria is the presence of red blood cells in the urine. Visible hematuria, also known as gross hematuria, is easily identified, as it causes red or brown discoloration of the urine. Microscopic hematuria is invisible to the naked eye and is often found incidentally on urinalysis or urine dipstick. Any part of the kidneys or urinary tract (ureters, urinary bladder, prostate, and urethra) can leak blood into the urine. The causes of hematuria are broad, ranging from urinary tract infection to kidney stones to bladder cancer.

Microscopic hematuria is found regularly on routine urinalysis, with a prevalence between 0.18% and 37%. Some studies have shown increased incidence with age and female sex, but others did not show a correlation. In many people, no specific cause is found. Cancer of the kidney, prostate, bladder, or testes is found in 5% of people with microscopic hematuria and up to 40% of those with visible hematuria. Hematuria is common in pediatric populations, with a prevalence of 0.5-2%.

Certain substances can mimic hematuria either by discoloring the urine or by causing a false positive on urine dipstick. Causes of a false positive urine dipstick include hemoglobin (in absence of red blood cells), semen, myoglobin, porphyrins, betanin (after eating beets), and drugs (such as rifampicin, phenazopyridine, and sulphonamides). Substances that mimic hematuria by causing red or brown discoloration of the urine include drugs (such as sulfonamides, quinine, rifampin, phenytoin), betanin, and menses.

Causes | Visible blood

Visible hematuria causes brown or red discoloration of the urine that is visible to the naked eye. It can be painful or painless.

Causes | Visible blood | Painless

The most worrisome cause of painless, visible blood in the urine is kidney or bladder cancer, especially in a person wth risk factors such as male sex, age over 35, history of smoking, chronic bladder inflammation, and occupational exposures (to aromatic amines and aniline dyes) Between 80-90% of people with bladder cancer initially presented with visible hematuria.

Other causes include

- Exercise-induced hematuria–occurs in up to 30% of long distance runners and often resolves a few days after running cessation

Causes | Visible blood | Children

Greater than 50% of cases of visible hematuria in children have an identifiable cause. Common causes of visible hematuria in pediatric populations are:

- urinary tract infection

- perineal or urethral irritation

- congenital abnormalities–

- Non-vascular—ureteropelvic junction obstruction, posterior urethral valves, urethral prolapse, urethral diverticula, multicystic dysplastic kidney

- Vascular—arteriovenous malformations, hereditary hemorrhagic telangiectasias, renal vascular thromboses

- trauma

- acute nephritis—characterized by visible hematuria, white blood cells in the urine, and a transient decline in renal function, commonly caused by medications

- coagulopathy

- kidney stones

- IgA nephropathy–suspected in a child with dark urine and recent upper respiratory infection

- Post-streptococcal glomerulonephritis–suspected in a child with dark brown urine following recent streptoccocal pharyngitis or impetigo

Causes | Non visible blood

Microscopic hematuria does not discolor the urine and is thus found incidentally on urinalysis or light microscopy. It is defined as greater than three red blood cells per high powered field. In many of these cases, no source or cause is found. Any part of the kidneys or urinary system can cause microscopic hematuria. Causes can be separated into glomerular, arising from the filtering system of the kidney, and non-glomerular, arising from the kidney (outside the glomerulus), ureters, urinary bladder, prostate, or urethra.

Causes | Non visible blood | Glomerular

Inflammation of or injury to the glomeruli can cause leakage of red blood cells, resulting in misshapen cells and red blood cell casts in the urine. Glomerular bleeding is frequently accompanied by proteinuria, or leakage of protein into the urine.

Common causes include

- IgA nephropathy

- Hereditary nephritis (Alport's disease)

- Benign familiar hematuria

- Glomerulonephritis–a group of inflammatory diseases of the glomeruli, leading to hematuria, hypertension, and peripheral edema

Causes | Non visible blood | Children

In many cases of asymptomatic microscopic hematuria without proteinuria, no etiology is found. Common causes of microscopic hematuria in pediatric populations include:

- hypercalciuria–suspected in a child with family history of kidney stones; can be asymptomatic or can cause painful urination

- benign familial hematuria–a genetic disorder causing persistent microscopic hematuria

- IgA nephropathy

- sickle cell trait or disease

- Alport syndrome–a genetic disorder causing recurrent microscopic hematuria with proteinuria, hearing loss, and progressive kidney failure

Diagnosis

Sometimes the cause of hematuria can be determined based on the medical history and urine testing. This is especially true for people ages less than 35, in whom the risk of cancer is low. It is imperative to ascertain key risk factors such as smoking, occupational exposures to benzene, history of recent weight loss and/or history of urologic disorders such as benign enlargement of the prostate or recurrent kidney stones to help with risk stratification. The two most common causes of hematuria are related to kidney stones causing obstruction or infection of the prostate or bladder. Additionally, athletes with vigorous exercise regimens may sometimes have either visible or microscopic hematuria.

The first step in evaluation of Hematuria is to perform a urine dipstick to assess for blood in the urine, followed by a urinalysis with microscopic evaluation for confirmation. If hematuria is present, and is associated with acute onset of unilateral flank pain, it is generally indicative of a presence of a kidney stone and evaluation should be done with a non-contrast CT scan of the abdomen/pelvis. If hematuria is associated fever, pain with urination, urinary frequency or presence of white blood cells in the urine; it is highly suggestive of a urinary tract infection and additional work-up with urine cultures should be done to further evaluate. If neither of these features are present, the next step is to separate the evaluation into visible vs microscopic hematuria.

Diagnosis | Visible

For people with visible hematuria and evidence of blood clots, further imaging with an abdominal CT scan should be done and an urgent referral to a urologist made. Otherwise, the next step involves determining if source of bleeding is glomerular in nature as evidenced by presence of inappropriately shaped/dysmorphic red blood cells, presence of protein in the urine, new or worsening hypertension or swelling. If source is glomerular patients should be referred to a nephrologist for further evaluation. Non-glomerular source of bleeding will usually require further work-up by a urologist.

Diagnosis | Microscopic

In people with microscopic hematuria, it is important to rule out any possible confounders such as menstruation in women, possible presence of semen in sample or recent rigorous exercise. In menstruating women, tests should be repeated during non-bleeding parts of their cycles. In individuals with history of recent rigorous exercise, urinalysis should be repeated 4–6 weeks following cessation of exercise. All women of child-bearing age should undergo a pregnancy test, and if positive should receive an ultrasound of their kidneys and bladder with further invasive diagnostic work-up deferred until completion of pregnancy.

If diagnostic work-up has been unyielding so far or the aforementioned risk factors are present, it is important to begin a thorough work-up for possible malignancy especially of the bladder and kidney by referring to a Urologist to look at the urethra and bladder with a cystoscopy and also performing additional imaging using CT urography, which provides a thorough view of the complete urinary system.

For individuals with persistent hematuria with no immediate identifiable cause, urinalysis should be repeated once a year, and if it is negative for 2 years then you can stop repeating the tests. However, if it is positive for 3 years, repeat anatomic evaluation should be done.

Management

Management of hematuria is aimed at treating secondary causes of hematuria. If hematuria is a result of a UTI, treatment with antibiotics is usually initiated and urine testing repeated after 6 weeks. If hematuria is secondary to a kidney stone, then management depends on the size of the kidney stone. If the stone is small enough, usually less than 1 cm, then conservative management with analgesics and fluid hydration may be sufficient, however stones that are too bid may require removal by a urologist. Another common cause of hematuria is benign enlargement of the prostate (BPH), treatment is aimed at reducing the size of the bladder with medications like finasteride and symptomatic management with drugs like terazonsin or tamsulosin.

For people with exercise induced hematuria, management is conservative and involves cessation of strenuous activities and keeping hydrated. If the cause of hematuria is a result of malignancy, treatment and management depends on the type and stage of cancer and can involve chemotherapy, radiation or surgical resection of the tumor or organ involved.