Hematuria or haematuria is defined as the presence of blood or red blood cells in the urine. "Gross hematuria" occurs when urine appears red, brown, or tea-colored due to the presence of blood. Hematuria may also be subtle and only detectable with a microscope or laboratory test. Blood that enters and mixes with the urine can come from any location within the urinary system, including the kidney, ureter, urinary bladder, urethra, and in men, the prostate. Common causes of hematuria include urinary tract infection (UTI), kidney stones, viral illness, trauma, bladder cancer, and exercise. These causes are grouped into glomerular and non-glomerular causes, depending on the involvement of the glomerulus of the kidney. But not all red urine is hematuria. Other substances such as certain medications and some foods (e.g. blackberries, beets, food dyes) can cause urine to appear red. Menstruation in women may also cause the appearance of hematuria and may result in a positive urine dipstick test for hematuria. A urine dipstick test may also give an incorrect positive result for hematuria if there are other substances in the urine such as myoglobin, a protein excreted into urine during rhabdomyolysis. A positive urine dipstick test should be confirmed with microscopy, where hematuria is defined by three or more red blood cells per high power field. When hematuria is detected, a thorough history and physical examination with appropriate further evaluation (e.g., laboratory testing) can help determine the underlying cause.
Differential diagnosis Hematuria can be classified according to visibility, anatomical origin, and timing of blood during urination. In terms of visibility, hematuria can be visible to the naked eye (termed gross hematuria) and may appear red or brown (sometimes referred to as tea-colored), or it can be microscopic (i.e., not visible but detected with a microscope or laboratory test). Microscopic hematuria is present when there are three or more red blood cells per high power field. In terms of the anatomical origin, blood or red blood cells can enter and mix with urine at multiple anatomical sites within the urinary system, including the kidney, ureter, urinary bladder, and urethra, and in men, the prostate. Additionally menstruation in women may cause the appearance of hematuria and may result in a positive urine dipstick test for hematuria. The causes corresponding to these anatomic locations can be divided into glomerular and non-glomerular causes, referring to the involvement of the glomerulus of the kidney. Non-glomerular causes can be further subdivided into upper urinary tract and lower urinary tract causes. In terms of the timing during urination, hematuria can be initial, total, or terminal, meaning blood can appear in the urine at the onset, midstream, or later. If it appears soon after the onset of urination, a distal site is suggested. Hematuria that occurs throughout urination suggests that bleeding is occurring above the level of the bladder. A longer delay suggests a more proximal lesion.
Many causes may present as either visible hematuria or microscopic hematuria, and so the differential diagnosis is frequently organized based on glomerular and non-glomerular causes.
Glomerular hematuria
Hematuria due to a glomerular source commonly presents as dysmorphic red blood cells (misshapen red blood cells) or red cell casts (small tubular structures made up of red blood cell components) on urine microscopy. This occurs due to the red blood cells being deformed as they pass through the glomerular capillaries into the renal tubules and eventually into the urinary system. Normally red blood cells should never pass from the glomerular capillary into the renal tubule, and this is always a pathological process. Glomerular causes include: IgA nephropathy Thin glomerular basement membrane disease Hereditary nephritis (Alport's disease) Hemolytic uremic syndrome Postinfectious glomerulonephritis (group A β-hemolytic streptococcus pyogenes) Membranoproliferative glomerulonephritis Lupus nephritis Henoch–Schönlein purpura Nephritic syndrome Nephrotic syndrome Polycystic kidney disease Idiopathic hematuria
Non-glomerular hematuria Visible blood clots in the urine indicate a non-glomerular cause. Non-glomerular causes include: Urinary tract infections, such as pyelonephritis, cystitis, prostatitis, and urethritis Kidney stones Cancers, such as renal cell carcinoma and bladder cancer (particularly transitional cell carcinoma), and in men, prostate cancer Urinary tract strictures Benign prostatic hyperplasia Renal papillary necrosis Trauma or damage to the lining of the urinary tract Intense exercise Increased tendency to bleed due to acquired or genetic conditions (e.g. sickle cell disease or vitamin K deficiency bleeding) or certain medications (e.g. blood thinners)
Mimickers of hematuria
Pigmenturia Not all red or brown urine is caused by hematuria. Other substances such as certain medications and certain foods can cause urine to appear red.
Medications that may cause urine to appear red include: Phenazopyridine Nitrofurantoin Doxorubicin Rifampicin
Foods that may cause urine to appear red include: Blackberries Food dyes. Beets Rhubarb Fava beans
False positive urine dipstick A urine dipstick may be falsely positive for hematuria due to other substances in the urine. While the urine dipstick test is able to recognize heme in red blood cells, it also identifies free hemoglobin and myoglobin. Free hemoglobin may be found in the urine resulting from hemolysis, and myoglobin may be found in the urine resulting from rhabdomyolysis (muscle breakdown). Thus, a positive dipstick test does not necessarily indicate hematuria; rather, microscopy of the urine showing three of more red blood cells per high power field confirms hematuria.
Menstruation In women, menstruation may cause the appearance of hematuria and may result in a urine dipstick test positive for hematuria. Menstruation can be ruled out as a cause of hematuria by inquiring about menstruation history and ensuring the urine specimen is collected without menstrual blood.
In children Common causes of hematuria in children are: Fever Strenuous exercise Acute nephritis Congenital abnormalities: Non-vascular: ureteropelvic junction obstruction, posterior urethral valves, urethral prolapse, urethral diverticulum and multicystic dysplastic kidney Vascular: arteriovenous malformations, hereditary hemorrhagic telangiectasias, renal vein thrombosis in newborns. Urinary stones. Coagulation disorders. Mechanical trauma: masturbation, foreign body. Nephritic syndrome: IgA nephropathy, Post-streptococcal glomerulonephritis, Benign familial hematuria, Alport syndrome. Sickle cell trait or disease.
Evaluation The evaluation of hematuria is dependent upon the visibility of the blood in the urine (i.e. visible/gross vs microscopic hematuria). Visible hematuria must be investigated, as it may be due to a pathological cause. In those with visible hematuria, urological cancer (most frequently bladder or kidney cancer) is discovered in 20–25%. Hematuria alone without accompanying symptoms should be raise suspicion of malignancy of the urinary tract until proven otherwise. The initial evaluation of patients presenting with signs and symptoms that are consistent of hematuria include assessment of hemodynamic status, underlying cause of hematuria, and ensuring urinary drainage. These steps include assessment of the patient's heart rate, blood pressure, a physician exam taken by a healthcare professional, and blood work to ensure the patient's hemodynamic status is adequate. It is important to obtain a detailed history from the patient (i.e. recreational, occupational, and medication exposures) as this information can be helpful in suggesting a cause of hematuria. The physical exam can also be helpful in identifying a cause of the hematuria as certain signs found on the physical exam can suggest specific causes of the hematuria. In the event the initial evaluation of hematuria does not reveal an underlying cause then evaluation by a physician who specializes in Urology may proceed. This medical evaluation may consist of, but is not limited too, a history and physical exam taken by healthcare personnel, laboratory studies (i.e. blood work), cystoscopy, and specialized imaging procedures (i.e. CT or MRI).
Visible hematuria The first step in evaluation of red or brown colored urine is to confirm true hematuria with urinalysis and urine microscopy, where hematuria is defined by three of more red blood cells per high power field. Although a urine dipstick test may be used, it can give false positive or false negative results. In gathering information, it is important to inquire about recent trauma, urologic procedures, menses, and culture-documented urinary tract infection. If any of these are present, it is appropriate to repeat a urinalysis with urine microscopy in 1 to 2 weeks or after treatment of the infection. If the results of the urinalysis and urine microscopy reveal a glomerular origin of hematuria (indicated by proteinuria or red blood cell casts), consultation with a nephrologist should be made. If the results of the urinalysis indicate a non-glomerular origin, a microbiological culture of the urine should be performed, if it has not been done already. If the culture is positive (indicating a bladder infection), urinalysis and urine microscopy should be repeated following treatment to confirm resolution of the hematuria. If the culture is negative or if hematuria persists after treatment, CT urogram or renal ultrasound and cystoscopy should be performed. Hemodynamic stability should be monitored and a complete blood count should be ordered to assess for anemia.
Microscopic hematuria