Evaluation of microscopic hematuria in children

INTRODUCTION — Microscopic hematuria is a common finding in children. There is a long list of causes of microscopic hematuria, most of which are benign, especially in children with isolated asymptomatic microscopic hematuria. The challenge that faces the clinician is to identify the child in whom hematuria is caused by significant underlying disease and avoid unnecessary testing in those individuals with a benign condition.

The etiology and evaluation of microscopic hematuria in children will be reviewed here. The evaluation of children with gross hematuria is discussed separately. (See "Evaluation of gross hematuria in children".)

DETECTION — Hematuria is defined by the presence of an increased number of red blood cells (RBCs) in the urine. Hematuria can either be visible to the naked eye (gross) or apparent only upon urinalysis (microscopic). Microscopic hematuria may be discovered as an incidental finding on an urinalysis prompted by urinary or other symptoms.

Urinary dipstick — The most common screening test for hematuria is the urinary dipstick test for blood. Dipsticks for hemoglobin are as sensitive as the urine sediment examination, but result in more false-positive tests. In comparison, false-negative dipstick tests are unusual; as a result, a negative dipstick reliably excludes abnormal hematuria.

The reagent strip that detects blood utilizes hydrogen peroxide, which catalyzes a chemical reaction between hemoglobin (or myoglobin) and the chromogen tetramethylbenzidine. Different shades of blue-green are produced according to the concentration of hemoglobin in the urine sample. These strips can detect 5 to 10 intact RBCs/microL, which roughly corresponds to a finding on microscopic examination of two to five RBCs per high-power field from the sediment of a centrifuged 10 to 15 mL urine sample.

False-negative results can occur in the presence of formalin (used in preservatives) or high urinary concentration of ascorbic acid (vitamin C). False-positive results may occur with alkaline urine (ie, pH greater than 9) or contamination with oxidizing agents used to clean the perineum.

Microscopic examination — A positive dipstick for hematuria is confirmed by a microscopic examination of the sediment of 10 to 15 mL of centrifuged fresh urine. Microscopic hematuria is defined as the presence of more than five RBCs per high-power field (40x magnification) [1,2].

The microscopic examination is the gold standard for the detection of microscopic hematuria. The procedures for obtaining and processing urine samples in children are reviewed separately. (See "Urine collection techniques in infants and children with suspected urinary tract infection".)

Glomerular versus nonglomerular bleeding — Urinalysis including microscopic examination may identify a potential site of bleeding (glomerular versus nonglomerular) and aid in determining the underlying cause. The identification of the glomeruli as the source of blood is important both prognostically and to optimize the subsequent diagnostic evaluation.

Signs of glomerular bleeding in children with microscopic hematuria include the following (table 1):

●Red cell casts (pathognomonic for glomerular disease) (picture 1).

●Protein excretion greater than 100 mg/m² at a time when there is no gross bleeding. It is optimal to obtain a first morning sample to determine the protein to creatinine ratio because it excludes orthostatic proteinuria, a normal variant. (See "Evaluation of proteinuria in children", section on 'Measurement of urinary protein'.)

●RBCs having a dysmorphic appearance [3].

Although helpful if present, the absence of these findings does not exclude glomerular disease.

Morphologic study of urinary RBCs, particularly with a phase-contrast microscope, may be helpful in distinguishing glomerular from nonglomerular bleeding. The presence of more than 30 percent dysmorphic RBCs or of more than 5 percent of a specific form named an "acanthocyte" is highly suggestive of glomerular hematuria (picture 2 and picture 3). However, confident identification of such cells requires expertise in urinalysis. (See "Etiology and evaluation of hematuria in adults", section on 'Glomerular versus nonglomerular bleeding'.)

In nonglomerular hematuria, microscopic examination demonstrates urinary RBCs with a uniform normal size and shape (picture 4). However, hypercalciuria, a nonglomerular cause of hematuria, can be associated with dysmorphic RBCs, but not red cell casts.

EPIDEMIOLOGY — Several population-based studies of unselected school-age children have shown that the prevalence rate for microscopic hematuria detected in a single urine sample is 3 to 4 percent, which falls to 1 percent or less for two or more positive samples [4-6]. Among the 1 percent of children with two or more positive urines for hematuria, only one-third have persistent hematuria, defined as a positive repeat test after six months [4,5].

The combination of hematuria and proteinuria is less common, with a prevalence rate of less than 0.7 percent in unselected school-age children in a single urine sample [4,5].

ETIOLOGY — Microscopic hematuria in children can be persistent or transient in nature.

Persistent hematuria — The most common causes of persistent microscopic hematuria include glomerulopathies, hypercalciuria, and nutcracker syndrome [1]. (See "Isolated and persistent glomerular hematuria in adults".)

The hematuria in these disorders persists for variable periods. The causes of transient hematuria are different. (See 'Transient hematuria' below.)

IgA nephropathy — Immunoglobulin A (IgA) nephropathy is diagnosed by kidney biopsy with mesangial IgA deposits on immunofluorescence study (picture 5 and picture 6). Patients often have persistent microscopic hematuria with episodes of gross hematuria that is precipitated by an upper respiratory tract or gastrointestinal illness. There is typically a negative family history of kidney disease. (See "IgA nephropathy: Clinical features and diagnosis".)

Alport syndrome — Alport syndrome is a hereditary disorder often associated with high-frequency sensorineural hearing loss (SNHL), ocular abnormalities (eg, anterior lenticonus), and progressive kidney failure (picture 7A-B). The genetic abnormality in these patients involves the genes coding for type IV collagen. Classic X-linked Alport syndrome typically affects males. Hemizygous carrier females can also have hematuria, but less frequently have progressive kidney disease. There are also autosomal recessive and dominant forms which affect both males and females. (See "Clinical manifestations, diagnosis, and treatment of Alport syndrome (hereditary nephritis)" and "Genetics, pathogenesis, and pathology of Alport syndrome (hereditary nephritis)".)

Thin basement membrane disease — We usually discover thin basement membrane (TBM) disease, also called benign familial hematuria, in affected children when hematuria is detected in a first-degree family member during evaluation. Often, we make the diagnosis in children with a family history of hematuria and no history of progressive kidney disease.

Although rarely indicated, kidney biopsy reveals an isolated thinning of the glomerular basement membrane (GBM) on electron microscopy (picture 8).

TBM disease is an autosomal dominant condition involving genes for type IV collagen. In many cases, it is the heterozygous form of autosomal recessive Alport syndrome. At our institution, children with TBM disease undergo genetic screening, as there is a high likelihood that these children have pathogenic variants in the genes for type IV collagen. This approach is supported by a study of 97 children with persistent microscopic hematuria, 28 (29 percent) of whom were found to have pathogenic or likely pathogenic variants in type IV collagen genes [7]. (See "Thin basement membrane nephropathy (benign familial hematuria)".)

Poststreptococcal glomerulonephritis — Although the clinical presentation of poststreptococcal glomerulonephritis varies from asymptomatic, microscopic hematuria to the full-blown acute nephritic syndrome, asymptomatic microscopic hematuria is the most common clinical finding. There is usually an antecedent history of a group A beta-hemolytic streptococcal (GAS) skin or throat infection. The diagnosis is based on transient lowering of complement C3 levels +/- positivity of anti-factor B antibodies [8]. Hematuria generally resolves within three to six months after the presentation. (See "Poststreptococcal glomerulonephritis".)

Hypercalciuria — Hypercalciuria, defined in children as a urine calcium/creatinine ratio >0.2 (mg/mg) in children older than six years of age, has been associated with asymptomatic microscopic hematuria. In studies performed in the United States, the prevalence has ranged from as low as 11 percent in the northeast [9] to as high as 35 percent in the south [10,11]. Thus, the association between hypercalciuria and hematuria may be more common in areas where there is a higher prevalence of nephrolithiasis. (See "Kidney stones in children: Clinical features and diagnosis".)

Nephrolithiasis and nephrocalcinosis — Children with nephrolithiasis typically present with abdominal pain and gross hematuria. However, asymptomatic patients with nephrolithiasis and nephrocalcinosis occasionally will present with microscopic hematuria. (See "Kidney stones in children: Clinical features and diagnosis" and "Nephrocalcinosis in neonates" and "Nephrocalcinosis".)

Nutcracker syndrome — Nutcracker syndrome results from the compression of the left renal vein between the aorta and proximal superior mesenteric artery. It is detected by Doppler ultrasonographic assessment of left renal vein diameter and peak velocity or by computer tomography [12-14]. In addition, nutcracker syndrome can be associated with a ratio >0.6 between the aortomesenteric angle (the angle between the aorta and the superior mesenteric artery) in upright and supine positions.

Nutcracker syndrome often presents in children with asymptomatic hematuria, but may be associated with left flank pain [12,13,15]. Nutcracker syndrome can also cause orthostatic proteinuria in children (image 1 and image 2). These findings are supported by a systematic review of 423 children with nutcracker syndrome and a mean age of 12 years, which reported hematuria as the most common presenting symptom (55.5%), followed by proteinuria (49.9%) [16]. Flank pain was only detected in 19.1% of patients. Another systematic review of 159 patients ≤17 years of age with nutcracker syndrome reported that two-thirds of the patients were asymptomatic [17]. A left-sided varicocele was noted in one-third of affected boys. (See "Orthostatic (postural) proteinuria", section on 'Left renal vein entrapment'.)

These patients are usually managed conservatively with a focus on weight gain to increase retroperitoneal fat, which leads to decompression of the left renal vein due to a change in the position of the left kidney [16]. If symptoms of significant left flank pain persist, reported interventions include endovascular stenting or open surgery with left renal vein transposition but repeated interventions may be necessary [18,19].

Transient hematuria — The distribution of causes of transient hematuria is much larger and includes urinary tract infection (UTI) (which is typically accompanied by dysuria and pyuria), trauma, fever, and exercise. The supporting data are presented separately in the adult section (table 2). (See "Etiology and evaluation of hematuria in adults", section on 'Transient or persistent hematuria' and "Exercise-induced hematuria".)

EVALUATION — The diagnostic evaluation depends upon the clinical presentation, which falls into the following three clinical settings:

●Asymptomatic isolated microscopic hematuria

●Asymptomatic microscopic hematuria with proteinuria

●Symptomatic microscopic hematuria

Asymptomatic isolated microscopic hematuria — Asymptomatic isolated microscopic hematuria is the most common presentation of microscopic hematuria. It is usually transient and is generally not associated with significant clinical disease. As a result, our approach starts with initial observation with repeated examination and urinalyses to determine if there is persistent hematuria (algorithm 1).(See 'Epidemiology' above.)

This approach is supported by the landmark 1979 study of an unselected population of 8954 children who were screened for hematuria. Among the 28 patients (0.3 percent) with two or more urine samples that tested positive for blood, extensive evaluation was performed including kidney biopsy and intravenous pyelogram [5]. A cause was found in only five: two with immunoglobulin A (IgA) nephropathy, one with thin basement membrane (TBM) disease, and two with uretero-pelvic stenosis.

In addition, retrospective reviews of patients referred to tertiary centers for evaluation of asymptomatic isolated microscopic hematuria demonstrated standard laboratory and imaging evaluations were unnecessary, as they typically failed to detect any abnormality. This was illustrated by the following two observations:

●In a study of 325 children, serum creatinine and electrolyte concentrations were normal in all 254 patients who were tested [9]. No clinically significant findings were detected in the 283 patients who underwent ultrasonography. Hypercalciuria was present in 11 percent of the 263 patients whose urine was tested for urinary calcium/creatinine ratio. (See 'Etiology' above.)

●In another series of 342 children, evaluation included complete blood count, urinalysis, serum creatinine, complement component 3 (C3), and ultrasonography or intravenous pyelography [20]. No diagnosis was made in 80 percent of patients. Among those with positive findings, the most common was hypercalciuria in the absence of stone disease in 16 percent of the total group.

These findings have led to recommendations for observation of children with asymptomatic microscopic hematuria with normal physical examinations. Extensive diagnostic evaluation including laboratory testing is reserved only in children with proteinuria, hypertension, or gross hematuria [9,20,21].

The following is our recommended approach to children with asymptomatic isolated microscopic hematuria based upon the available literature (algorithm 1) [1,2,4,5,9,22]:

●Evaluation including blood pressure measurement and a urinalysis should be performed weekly for two weeks. One should ensure that there is no exercise prior to obtaining the urine sample, since vigorous exercise can induce hematuria. A thorough evaluation should be undertaken only if the patient becomes symptomatic or develops hypertension, gross hematuria, or proteinuria. (See "Exercise-induced hematuria" and 'Symptomatic microscopic hematuria' below and 'Asymptomatic microscopic hematuria and proteinuria' below and "Evaluation of gross hematuria in children".)

●If isolated hematuria persists, obtain a urine culture. If the culture is positive, treat with appropriate antibiotics.

●If the patient remains asymptomatic and the urine culture is negative, continue to observe the patient every three to six months including physical examination with blood pressure measurement and urinalysis.

●If the asymptomatic isolated hematuria persists for one year, the following subsequent evaluation should be performed:

•Measure urine calcium/creatinine ratio for hypercalciuria. Hypercalciuria, defined as a urine calcium/creatinine ratio >0.2 (mg/mg), has been associated with asymptomatic microscopic hematuria. (See 'Etiology' above.)

There is disagreement as to whether children with hypercalciuria have an increased likelihood of a family history of nephrolithiasis and whether hypercalciuria leads to kidney stones [9-11]. Although lowering urinary calcium excretion with a thiazide diuretic can lead to resolution of the hematuria [11], there is at present no consensus on the further evaluation or treatment of children with isolated microscopic hematuria who have hypercalciuria.

•Test parents and siblings for hematuria to detect possible thin basement membrane disease (autosomal dominant) or hereditary nephritis (mostly X-linked recessive). (See "Thin basement membrane nephropathy (benign familial hematuria)" and "Genetics, pathogenesis, and pathology of Alport syndrome (hereditary nephritis)".)

•Perform hemoglobin analysis if there is a clinical suspicion for sickle cell trait. (See "Sickle cell trait", section on 'Appropriate laboratory testing' and "Sickle cell trait", section on 'Urologic and kidney disease'.)

•Perform Doppler ultrasonography for the nutcracker syndrome. This study should only be performed by clinicians with expertise in detecting this abnormality.

Asymptomatic microscopic hematuria and proteinuria — The combination of hematuria and proteinuria is significantly less common than either isolated proteinuria or hematuria. Although asymptomatic hematuria with proteinuria has a prevalence rate of less than 0.7 percent in unselected school-age children, it is associated with a higher risk for significant kidney disease [2,4,5,23].

Evaluation of these patients starts with measurement of serum creatinine and quantification of proteinuria by calculation of the urine protein-to-creatinine ratio (UPCR) on a first morning urine sample (algorithm 2) (calculator 1). Alternatively, proteinuria can be quantified with a 24-hour urine collection. We prefer the UPCR to the 24-hour urine collection, as it is easier to obtain in children and it correlates well with the 24-hour values [24]. (See "Evaluation of proteinuria in children".)

●If in a first morning urine specimen the UPCR is >0.2 mg protein/mg creatinine in children older than two years of age and >0.5 mg protein/mg creatinine in younger children, or if protein excretion is >4 mg/m² per hour, the patient should be referred to a pediatric nephrologist (or a clinician with expertise in the care of children with kidney disease) since it is likely that there is significant kidney disease.

●If protein excretion is less than the above values, the patient should be reevaluated in two to three weeks.

•If the hematuria and proteinuria have resolved, no further evaluation is needed.

•If there is only asymptomatic microscopic hematuria, the patient is monitored in the same fashion as those described above with asymptomatic isolated microscopic hematuria.

•If proteinuria is persistent, the patient should be referred to a pediatric nephrologist (or a clinician with expertise in the care of children with kidney disease) for further evaluation.

Patients with significant proteinuria or an elevated serum creatinine at baseline, or persistent proteinuria at follow-up should be referred to a pediatric nephrologist (or a clinician with expertise in the care of children with kidney disease) because they are likely to have kidney disease.

Further assessment includes:

●Microscopic examination of the urine by an experienced clinician to determine if there are other diagnostic elements, such as red cell casts (eg, glomerular disease) or pyuria (eg, infection)

●Lab evaluation:

•Serum creatinine to evaluate kidney function

•Complement studies (C3, C4) – Abnormally low levels may be present in patients with poststreptococcal glomerulonephritis or lupus nephritis (see "Poststreptococcal glomerulonephritis", section on 'Complement' and "Childhood-onset systemic lupus erythematosus (SLE): Clinical manifestations and diagnosis", section on 'Laboratory findings').

•Serum albumin – Hypoalbuminemia may be indicative of nephrotic syndrome in a child with underlying glomerular disease (see "Glomerular disease: Evaluation in children", section on 'Urinalysis and urinary protein').

•Complete blood count – Anemia may be indicative of an underlying systematic condition such as systemic lupus erythematous (SLE).

•Antistreptolysin O (ASO) titer, streptozyme testing if considering poststreptococcal glomerulonephritis (see "Poststreptococcal glomerulonephritis", section on 'Serology').

•Antinuclear antibody testing if there is a clinical suspicion for SLE (see "Childhood-onset systemic lupus erythematosus (SLE): Clinical manifestations and diagnosis", section on 'Laboratory findings').

●Imaging studies that may detect asymptomatic nephrocalcinosis or nutcracker syndrome

●Kidney biopsy is considered if there is evidence of substantial or progressive disease to diagnose underlying kidney disease (eg, glomerulonephritis) (see 'Indications for kidney biopsy' below)

Symptomatic microscopic hematuria — The evaluation of symptomatic microscopic hematuria is directed by the patient's symptoms and clinical findings (algorithm 3). This category is the most challenging because it encompasses a wide range of diseases with varying clinical presentations [1,22]. The clinical manifestations may be nonspecific (eg, fever, malaise, weight loss), extrarenal (eg, rash, purpura, arthritis), or related to kidney disease (eg, edema, hypertension, dysuria, oliguria).

The presence of nonspecific or extrarenal manifestations suggests a systemic process such as lupus nephritis or IgA vasculitis (Henoch-Schönlein purpura). Kidney causes of symptomatic microscopic hematuria include glomerular or interstitial diseases of the kidney, lower urinary tract disease, nephrolithiasis, tumors, and vascular disease.

The diagnosis may be evident and straightforward from the history and physical examination. The urinalysis can be helpful in differentiating between glomerular and nonglomerular causes of bleeding. (See 'Glomerular versus nonglomerular bleeding' above.)

Historical clues — There are often clues from the history that point towards a specific diagnosis. (See 'Etiology' above.)

●Recent trauma.

●A history of new onset of incontinence, dysuria, frequency, or urgency suggests urinary tract infection (UTI). (See "Urinary tract infections in infants and children older than one month: Clinical features and diagnosis", section on 'Older children'.)

●A history of unilateral flank pain that radiates to the groin suggests obstruction caused by a calculus or blood clot. In comparison, flank pain without radiation but with fever, dysuria, and frequency and/or urgency is suggestive of acute pyelonephritis. (See "Urinary tract infections in infants and children older than one month: Clinical features and diagnosis", section on 'Older children'.)

●A history of pharyngitis or impetigo (two or three weeks prior to onset of hematuria) suggests poststreptococcal glomerulonephritis, although a recent upper respiratory (one or two days prior to onset of hematuria) infection can be associated with IgA nephropathy. (See "Glomerular disease: Evaluation and differential diagnosis in adults".)

●A history of predisposing or preexisting clinical conditions such as sickle cell disease or trait, a coagulopathy such as severe hemophilia, or deafness (Alport syndrome).

●A family history of hematuria, kidney disease (eg, Alport syndrome or TBM nephropathy), or kidney stones. (See "Isolated and persistent glomerular hematuria in adults".)

●Exposure to medications that can cause interstitial nephritis, although hematuria is not typically the central manifestation in such patients. (See "Clinical manifestations and diagnosis of acute interstitial nephritis", section on 'Drugs'.)

Physical examination — The physical examination should include measurement of blood pressure, assessment for edema and recent weight gain, close skin examination (eg, purpura), direct visualization of the genitals (looking for penile urethral meatal erosion or female introitus pathology), and evaluation for abdominal discomfort or masses (eg, Wilms tumor).

Urinalysis — Examination of the urine may suggest an underlying etiology and potential site of bleeding (glomerular versus extraglomerular). Glomerular causes of symptomatic hematuria include IgA nephropathy, Alport syndrome, and postinfectious glomerulonephritis. (See 'Glomerular versus nonglomerular bleeding' above and 'Etiology' above and "Etiology and evaluation of hematuria in adults", section on 'Glomerular versus nonglomerular bleeding'.)

Further evaluation — Based upon the history, physical examination, and urinalysis, a preliminary diagnosis will be made in the majority of cases and will guide further evaluation and/or intervention (algorithm 3).

●Trauma history – Obtain a computed tomography (CT) scan of the abdomen and pelvis to determine the source of blood.

●Signs or symptoms of UTI – Additional findings on urinalysis suggestive of a UTI include positive dipstick tests for leukocyte esterase and/or nitrite, more than five white blood cells per high-power field (spun urine), and the presence of bacteria on a Gram stain of unspun urine.

An appropriately collected urine culture is obtained. If the culture is positive, treat appropriately and repeat urinalysis after the infection has cleared.

Adenovirus should be considered as a potential etiology if urinary symptoms and urinalysis are suggestive of infection but the culture is negative [22,23].

●Signs or symptoms of perineal/meatal irritation – Supportive care and reassurance to the child and family that there is no other concerning cause for hematuria.

●Signs or symptoms of nephrolithiasis – The evaluation begins with imaging. Kidney ultrasonography is the preferred modality in children. Abdominal plain films may be useful in identification of radiopaque stones, but will miss radiolucent uric acid stones, small stones, or stones overlying bony structures, and will not detect obstruction.

Spiral CT scan is the most sensitive imaging modality. However, because of concerns related to radiation exposure, it is not typically the initial test in young children as it is in adolescents and adults. Consultation with radiology may be warranted in younger children to determine the risk-to-benefit ratio of the test. (See "Kidney stones in adults: Diagnosis and acute management of suspected nephrolithiasis".)

●Signs or symptoms suggestive of glomerular disease – Manifestations such as proteinuria, red blood cell (RBC) casts, edema, and hypertension suggest a glomerular source for the hematuria. The evaluation includes serum creatinine, complete blood count, C3, C4, and serum albumin. Other tests to consider based upon the history and the physical examination include ASO titer, streptozyme testing, and antinuclear antibody testing. Such patients should be referred to a pediatric nephrologist (or a clinician with expertise in the care of children with kidney disease).

Indications for kidney biopsy — A kidney biopsy is not usually performed for isolated microscopic hematuria. However, biopsy should be considered if there is evidence of substantial or progressive disease as manifested by an elevation in the creatinine concentration, significant proteinuria, or an otherwise unexplained rise in blood pressure even when the values remain within the normal range. Biopsy also may be considered in the child with persistent glomerular hematuria, in whom the parents are worried about the diagnosis and prognosis. In addition, a kidney biopsy may be considered in a child with microscopic hematuria and a family history of kidney failure in early adulthood in a first-order relative.

Patients with clear evidence of poststreptococcal glomerulonephritis represent an exception to these general recommendations, since gradual spontaneous recovery is the rule, although proteinuria may gradually return to normal over many years. (See "Poststreptococcal glomerulonephritis".)

The value of kidney biopsy with different hematuria presentations was evaluated in a report of Korean children with an abnormal urinalysis detected by school screening: 289 patients with persistent isolated microscopic hematuria (≥6 RBCs per high-power field in a centrifuged sample for more than six months) and 163 patients with microscopic hematuria and proteinuria underwent kidney biopsy [23].

●In children with isolated microscopic hematuria, biopsy results demonstrated normal biopsy, TBM disease, and IgA nephropathy in 47, 34, and 16 percent of cases, respectively.

●In children with microscopic hematuria and proteinuria, biopsy results demonstrated normal findings, TBM disease, and IgA nephropathy in 25, 18, and 46 percent of the cases, respectively. Other findings included mesangial proliferative glomerulonephritis (3 percent), poststreptococcal glomerulonephritis (3 percent), Alport syndrome (2 percent), and focal segmental glomerulosclerosis (FSGS) (2 percent).

These results demonstrate that kidney biopsy findings in most cases of isolated microscopic hematuria are normal or are consistent with TBM disease, a benign condition. Although a significant number of patients with isolated microscopic hematuria had IgA nephropathy, these patients have a minimal risk of disease progression as long as they do not develop proteinuria. In contrast, patients with persistent hematuria and proteinuria are more likely to have significant kidney disease. (See "Thin basement membrane nephropathy (benign familial hematuria)" and "IgA nephropathy: Treatment and prognosis".)

Cystoscopy — Cystoscopy is rarely indicated for hematuria in children. It should be reserved for the rare child with a bladder mass noted on ultrasound and for those with urethral abnormalities due to trauma [25]. Hematuria in adolescence has not been associated with urothelial or kidney cell carcinoma.

SOCIETY GUIDELINE LINKS — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Pediatric hematuria".)

INFORMATION FOR PATIENTS — UpToDate offers two types of patient education materials, "The Basics" and "Beyond the Basics." The Basics patient education pieces are written in plain language, at the 5^th to 6^th grade reading level, and they answer the four or five key questions a patient might have about a given condition. These articles are best for patients who want a general overview and who prefer short, easy-to-read materials. Beyond the Basics patient education pieces are longer, more sophisticated, and more detailed. These articles are written at the 10^th to 12^th grade reading level and are best for patients who want in-depth information and are comfortable with some medical jargon.

Here are the patient education articles that are relevant to this topic. We encourage you to print or e-mail these topics to your patients. (You can also locate patient education articles on a variety of subjects by searching on "patient info" and the keyword(s) of interest.)

●Basics topic (see "Patient education: Blood in the urine (hematuria) in children (The Basics)")

●Beyond the Basics topics (see "Patient education: Blood in the urine (hematuria) in children (Beyond the Basics)")

SUMMARY AND RECOMMENDATIONS

●Detection – Three to four percent of normal school-age children have a positive urinary dipstick test for blood, which is the most common screening test for hematuria. Microscopic hematuria is confirmed by microscopic examination. Hematuria is defined as 5 to 10 intact red blood cells (RBCs)/microL, which corresponds to a finding on microscopic examination of two to five RBCs per high-power field of the sediment of a 10 to 15 mL centrifuged urine sample. (See 'Detection' above and 'Epidemiology' above.)

●Glomerular versus nonglomerular bleeding – The presence of red cell casts, proteinuria, and/or dysmorphic RBCs (by an experienced observer) indicates a glomerular source of bleeding. (See 'Glomerular versus nonglomerular bleeding' above.)

●Etiology – Both benign and serious conditions can cause microscopic hematuria in children. The most common causes of persistent microscopic hematuria beyond six months are immunoglobulin A (IgA) nephropathy and thin basement membrane (TBM) disease. Less frequent causes of microscopic hematuria include hereditary nephritis (Alport syndrome), hypercalciuria, urinary tract infection (UTI), and nutcracker syndrome. (See 'Etiology' above.)

●Evaluation – The evaluation depends upon the clinical presentation, which falls into three categories:

•Asymptomatic isolated microscopic hematuria – This is the most common presentation of microscopic hematuria. It is usually transient and is generally not associated with significant clinical disease. As a result, our approach starts with initial observation with repeated examination and urinalyses (algorithm 1). If hematuria persists, subsequent evaluation includes a urine culture, measurement of urine calcium/creatinine ratio, and testing of parents and siblings for hematuria. More extensive evaluation is warranted if, during the period of observation, symptoms, hypertension, proteinuria, or gross hematuria develops. (See 'Asymptomatic isolated microscopic hematuria' above.)

•Asymptomatic microscopic hematuria with proteinuria – Patients with asymptomatic microscopic hematuria and a urine protein-to-creatinine ratio >0.2 mg protein/mg creatinine in children older than two years of age and >0.5 mg protein/mg creatinine in younger children, or a urinary protein excretion greater than 4 mg/m² per hour, should be referred to a pediatric nephrologist (or a clinician with expertise in the care of children with kidney disease) since it is likely that there is significant kidney disease. If protein excretion is less than the above values, the patient should be reevaluated in two to three weeks (algorithm 2). (See 'Asymptomatic microscopic hematuria and proteinuria' above.)

•Symptomatic microscopic hematuria – The evaluation of patients with symptomatic microscopic hematuria encompasses a wide range of diseases with varying clinical presentations. Assessment is directed by patients’ symptoms, clinical findings, and urinalysis (algorithm 3). (See 'Symptomatic microscopic hematuria' above.)