The identification of the glomeruli as the source of bleeding is important. Patients with clear evidence of glomerular hematuria do not need to be evaluated for potentially serious urologic disease.

Signs of glomerular bleeding include red cell casts (essentially pathognomonic for glomerular disease), protein excretion exceeding 500 mg/day at a time when there

A three-tube test may help locate the source of bleeding in selected cases. This test involves the collection and comparative evaluation of three different specimens of roughly equal volume: the first few mL; a midstream sample; and the last few mL.

• A urethral lesion is most likely if the hematuria primarily occurs in the first sample, whereas

• A lesion near the bladder trigone is most likely with terminal hematuria.

• Renal, ureteric, and diffuse bladder lesions result in equivalent degrees of hematuria in each of the three specimens.

Glomerular versus nonglomerular

Extraglomerular Glomerular

Color (if macroscopic) Red or pink Red, smoky brown, or "coca cola"

Clots May be present Absent

Protenuria <500 mg/day May be >500 mg/day

RBC morphology Normal Dysmorphic

RBC casts Absent May be present

Persistent Glomerular Hematuria

Although any glomerular disease may be associated with hematuria, most patients also have other signs such as proteinuria, red cell casts, or renal insufficiency. When persistent hematuria is the only manifestation of glomerular disease, one of three disorders is most likely:

• IgA nephropathy, in which there is often gross hematuria but a negative family history of renal disease;

• Hereditary nephritis, in which gross hematuria can also occur in association with a positive family history of renal failure; and

• Thin basement membrane disease (also called benign familial hematuria), in which gross hematuria is unusual and the family history may be positive for microscopic hematuria but not for renal failure

One of these three conditions is present in more than one-half of adults with isolated hematuria and a negative radiologic and cystoscopic evaluation.

• A patient with episodes of gross hematuria but a negative family history is most likely to have IgA nephropathy.

• A patient with only persistent microscopic hematuria and the finding of hematuria but not renal failure in family members is most likely to have thin basement membrane disease.

• A patient with a family history of renal failure and in some cases deafness probably has hereditary nephritis.

The relative frequency of these disorders also varies with the population that is studied.

The definitive diagnosis can be established only by renal biopsy. This is usually not indicated, however, since the likelihood of finding a treatable disease in isolated glomerular hematuria is very low. Hereditary nephritis is generally diagnosed from the family history of renal failure, and thin basement membrane disease typically has a benign course.

Although IgA nephropathy may progress to renal failure, patients with this disorder who have only isolated hematuria have a benign prognosis if they do not have any of the signs of more advanced disease, such as persistent protein excretion above 1 g/day, edema, hypertension, or renal insufficiency. Furthermore, there is no proven effective treatment for IgA nephropathy. Periodic monitoring of the urinalysis, renal function, and protein excretion is sufficient in most cases. However, biopsy should be considered if there is evidence of progressive disease as manifested by an elevation in the plasma creatinine concentration, increasing protein excretion, or an otherwise unexplained rise in blood pressure.

Postinfectious glomerulonephritis (see below) and exercise also can induce isolated glomerular bleeding; however, the hematuria in these settings is typically transient, not persistent as in the above disorders.

Patients with glomerular hematuria should be referred to a nephrologist; they are likely to be more experienced at examining urine sediment and can make a decision regarding the need for renal biopsy.

Hematuria following an upper respiratory infection

There are three major causes of glomerular hematuria after a URI:

• IgA nephropathy

• Poststreptococcal glomerulonephritis and a

• Nonspecific mesangioproliferative glomerulonephritis

All other glomerular diseases can also cause hematuria, although there is usually not as clear an association to a recent infection.

IgA Nephropathy

IgA nephropathy is probably the most common cause of glomerulonephritis. Patients with this disorder often have recurrent episodes of gross hematuria, beginning 1 to 3 days after a URI. The urine color typically returns to normal within a few days, although microscopic hematuria may persist indefinitely in patients with chronic disease.

Poststreptococcal Glomerulonephritis

Poststreptococcal glomerulonephritis is induced by infection with specific nephritogenic strains of group A, ß-hemolytic streptococci ( type 12 and type 49). This can occur in sporadic cases or during an epidemic. The incidence of clinically detectable glomerulonephritis in children infected during an epidemic is about 5 to 10 percent with pharyngitis and 25 percent with skin infections. Younger children below the age of 7 appear to be at highest risk.

The clinical presentation can vary from asymptomatic, microscopic hematuria to the full-blown acute nephritic syndrome, characterized by red to brown urine, proteinuria (which can reach the nephrotic range), edema, hypertension, and acute renal failure. Although the presentation may be similar to that seen with IgA nephropathy, the following can be used to differentiate between these disorders. Renal biopsy is not required in most cases.

• The latent period from infection to hematuria in poststreptococcal glomerulonephritis averages 10 days with pharyngitis (and 21 days with impetigo) versus less than 5 days in IgA nephropathy.

• Recurrent episodes of gross hematuria are common in IgA nephropathy but rare in poststreptococcal glomerulonephritis.

• Throat culture and serologic tests (including low complement levels) should be positive in poststreptococcal glomerulonephritis following a URI.

• Poststreptococcal glomerulonephritis gradually resolves after the infection has cleared, with renal function beginning to improve within 1 to 2 weeks, complement levels normalizing within 6 weeks, and the hematuria disappearing within 6 months. In comparison, persistent microscopic hematuria is common in IgA nephropathy.

Nonspecific mesangioproliferative glomerulonephritis

Some patients with a nonstreptococcal URI will have microscopic hematuria, often with red cell casts. These abnormalities, will not be detected unless a urinalysis is performed and typically resolve within two to seven months. Some patients, however, have persistent microscopic hematuria and, on renal biopsy, a nonspecific mesangial proliferative glomerulonephritis. The prognosis in this setting is almost always benign.

Transient or persistent non glomerular hematuria

In the absence of other signs and symptoms, it is reasonable to repeat an abnormal urinalysis in a few days to determine if hematuria is transient or persistent.

Transient microscopic hematuria is a common problem in young adults. Hematuria is seen in 39 percent of men on at least one occasion and 16 percent on two or more occasions. Hematuria has also been found in up to 13 percent of postmenopausal women. No obvious etiology can be identified in most cases. Fever, infection, trauma, and exercise are potential causes of transient hematuria.

An important exception is in older patients in whom even transient hematuria carries an appreciable risk of malignancy (assuming no evidence of glomerular bleeding). In this population, the presence of more than 5