Hematuria

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Practice Essentials

Generally, hematuria is defined as the presence of 5 or more red blood cells (RBCs) per high-power field in 3 of 3 consecutive centrifuged specimens obtained at least 1 week apart. Hematuria can be either gross (ie, overtly bloody, smoky, or tea-colored urine) or microscopic. It may also be either symptomatic or asymptomatic, either transient or persistent, and either isolated or associated with proteinuria and other urinary abnormalities. See the image below.



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Microscopy of urinary sediment. Typical appearance in non-glomerular hematuria: RBCs are uniform in size and shape but show two populations of cells b....

Signs and symptoms

The first step in the evaluation of hematuria consists of a detailed history and a thorough physical examination. Efforts should be made to distinguish glomerular causes from extraglomerular ones, as follows:

Physical examination should include the following:

The following findings help distinguish between glomerular and nonglomerular hematuria:

See Clinical Presentation for more detail.

Diagnosis

The laboratory tests ordered for the evaluation of hematuria must be based on the clinical history and the physical examination. Tests that may be helpful include the following:

The following imaging studies may be helpful:

IV urography rarely contributes additional information in the evaluation of hematuria and result in unnecessary exposure to ionizing radiation.

A kidney biopsy is rarely indicated in the evaluation of isolated asymptomatic hematuria. Relative indications for performing a kidney biopsy in patients with hematuria are as follows:

In most patients, a renal biopsy either is normal or reveals minor changes, such as thin glomerular basement membranes, focal glomerulonephritis, or mild mesangial hypercellularity. In a minority of patients, histologic findings, together with historical or serologic data, may point to specific conditions.

Patients with hematuria may be categorized into:

See Workup for more detail.

Management

General principles of treatment are as follows:

See Treatment and Medication for more detail.

Guidelines on hematuria from the American College of Physicians (ACP) advises that clinicians should include gross hematuria in their routine review of systems and specifically ask all patients with microscopic hematuria about any history of gross hematuria.[1, 2]

The ACP also recommend that[1, 2] :

Background

Hematuria is one of the most common urinary findings that result in children presenting to pediatric nephrologists. Generally, hematuria is defined as the presence of 5 or more RBCs per high-power field in 3 of 3 consecutive centrifuged specimens obtained at least 1 week apart. In the office setting, a positive reaction on the urine dipstick test is usually the first indication of the presence of hematuria. Hematuria can be gross (ie, the urine is overtly bloody, smoky, or tea colored) or microscopic. It may be symptomatic or asymptomatic, transient or persistent, and either isolated or associated with proteinuria and other urinary abnormalities. The role of the primary care physician in the management of a child with hematuria includes the following:

Pathophysiology

The etiology and pathophysiology of hematuria vary. For instance, hematuria of glomerular origin may be the result of a structural disruption in the integrity of glomerular basement membrane caused by inflammatory or immunologic processes.{ref38-INVALID REFERENCE} Chemicals may cause toxic disruptions of the renal tubules, whereas calculi may cause mechanical erosion of mucosal surfaces in the genitourinary tract, resulting in hematuria.

Frequency

United States

The prevalence of gross hematuria in children is estimated to be 0.13%. In more than half of the cases (56%) this is due to an easily identifiable cause. The most common cause appears to be cystitis (20-25%). Asymptomatic microscopic hematuria is, on the average, 10-fold as prevalent as gross hematuria (1.5%, range 0.4-4.1%, depending on the criteria used to define hematuria). With repeated evaluations, the prevalence of asymptomatic microscopic hematuria decreases to less than 0.5%, supporting the notion that most cases of hematuria in children are transient. The incidence of simultaneous hematuria and proteinuria is estimated to be only 0.06%, but their coexistence signals significant renal disease.

Mortality/Morbidity

In general, children with isolated asymptomatic microscopic hematuria tend to do well, whereas those with associated findings (eg, hypertension, proteinuria, abnormal serum creatinine levels) are more likely to have serious problems. Because hematuria is the end result of various processes, the morbidity and mortality rates of the condition depend on the primary process that initiated it.

Race

The incidence of hematuria in specific racial groups is determined by the primary cause. For example, idiopathic hypercalciuria is infrequent in black and Asian children, but relatively common in whites. Conversely, hematuria caused by sickle cell disease is more common in blacks and lhispanics than in whites.

Sex

Sex may predispose a child to specific diseases that manifest as hematuria. For example, the sex-linked form of Alport syndrome has a male preponderance, whereas lupus nephritis tend to be more common in adolescent girls.

A 2017 American College of Obstetricians and Gynecologists Committee Opinion on Asymptomatic Microscopic Hematuria in Women concluded that the patient’s sex should influence the differential diagnosis as asymptomatic microscopic hematuria in women is less likely to be associated with urinary tract malignancy than in men. The risk of urinary tract malignancy is ≤ 0.5% in low-risk, never-smoking women younger than 50 years of age without gross hematuria and with fewer than 25 red blood cells per high-power field.[3]

Age

Prevalence of certain conditions varies with age.[4] For instance, Wilms tumors are more frequent in children of preschool age, whereas acute postinfectious glomerulonephritis is more frequent in the school-aged population. In adults, hematuria is often a sign of malignancy of the genitourinary tract (eg, renal cell carcinoma, bladder tumors, prostatic tumors). These conditions are rare in children.

History

The first step in the evaluation of hematuria is a detailed review of the history and a thorough physical examination.

The presence or absence of hypertension or proteinuria helps to decide how extensively to pursue the diagnostic evaluation. The initial evaluation should be directed toward important and potentially life-threatening causes of hematuria in any child who has any of the following in addition to hematuria: hypertension, edema oliguria, significant proteinuria (more than 500 mg per 24 hours), or RBC casts. An attempt should be made to distinguish glomerular causes of hematuria from extraglomerular ones, as this helps in prioritizing the investigations.

Physical

In the general physical examination, the most important step is to measure the blood pressure (with an appropriate-sized cuff) and evaluate for the presence of periorbital puffiness or peripheral edema.[6, 7]

Causes

Hematuria can be of glomerular or nonglomerular origin. Brown-colored urine, RBC casts, and dysmorphic (small deformed, misshapen, sometimes fragmented) RBCs and proteinuria are suggestive of glomerular hematuria. Reddish or pink urine, passage of blood clots, and eumorphic (normal sized, biconcavely shaped) erythrocytes are suggestive of a nonglomerular bleeding site.

Potential causes of hematuria in children include the following:

Laboratory Studies

The laboratory tests ordered for the evaluation of hematuria must be based on the clinical history and the physical examination. Identification of a glomerular and extraglomerular etiology of hematuria based on a good history and urine examination can help the physician to avoid requesting tests that may be unnecessary.

Imaging Studies

The following imaging studies are indicated[9] :

Procedures

A kidney biopsy is rarely indicated in the evaluation of isolated asymptomatic hematuria. Most studies reveal minimal histopathological abnormalities in such children. In a survey of pediatric nephrologists in North America, only 5% of responders indicated that they would perform a kidney biopsy on a child with asymptomatic hematuria. The main reasons for performing a biopsy in that survey were academic interest, parental pressure for a diagnosis, and concern for future economic impact on the child. On the other hand, the simultaneous presence of proteinuria, elevated serum creatinine, hypertension, a suspicious clinical history, or other imaging/laboratory abnormalities may justify a kidney biopsy.

Thus, relative indications for performing a kidney biopsy in patients with hematuria are as follows:

Cystoscopy is not generally required in children with nonglomerular hematuria. The only indication is a suspicious bladder mass revealed on ultrasonography.

Skin biopsy with immunostaining for the α5(IV) chain is particularly useful when suspicion of X-linked Alport syndrome is high.

Histologic Findings

In most patients, a renal biopsy is either normal or reveals minor changes, such as thin glomerular basement membranes, focal glomerulonephritis, or mild mesangial hypercellularity. In a minority of patients, histologic findings, together with historical or serologic data, may point to specific conditions.

Table. Histologic Findings



View Table

See Table

A comprehensive physical examination and a detailed history are indispensable to the evaluation of hematuria.

Staging

Categorizing patients with hematuria into one of the following groups is helpful:

Other Tests

A retrospective cohort study looked to identify clinical and nonclinical factors associated with the evaluation of patients with newly diagnosed hematuria. The study found that patients with hematuria rarely underwent complete evaluation for bladder cancer such as the American Urological Association recommended cystoscopy and abdomino-pelvic imaging for patients 35 years or older.[12]  

Medical Care

Asymptomatic (isolated) hematuria generally does not require treatment. In conditions associated with abnormal clinical, laboratory, or imaging studies, treatment may be necessary, as appropriate, with the primary diagnosis.

Surgical Care

Surgical intervention may be necessary in certain anatomical abnormalities, such as ureteropelvic junction obstruction, tumor, or significant urolithiasis.

Consultations

Consultations are required in patients with urinary tract anomalies and in some patients with systemic diseases (eg, bleeding disorders, collagen vascular diseases, sickle cell nephropathy).

Referral to a urologist is required when clinical evaluation and workup indicates a tumor, a structural urogenital abnormality, or an obstructing calculus.

Diet

Dietary modification is usually not indicated except for children who may have a tendency to develop hypertension or edema as a result of their primary disease process (eg, nephritis). In these patients, a low sodium diet may be helpful. In addition, a diet containing the recommended daily amount (RDA) for calcium plus a low-salt diet may be beneficial in children with hypercalciuria and hematuria.

Activity

Activities of a child with asymptomatic, isolated hematuria should not be restricted. However, these children and their parents should be informed that strenuous exercise may aggravate hematuria. Restrictions in physical activities may be indicated in children with severe hypertension or cardiovascular disease.

Medication Summary

Hematuria is a sign and not a disease. Therapy should be directed at the process causing hematuria.

Further Outpatient Care

Patients with persistent microscopic hematuria should be monitored at 6-month to 12-month intervals for the appearance of signs or symptoms indicative of progressive renal disease. Prominent among them are proteinuria, hypertension, and a decrease in renal function.

Prognosis

The prognosis of patients with asymptomatic isolated hematuria is good. The ultimate prognosis for the various conditions associated with hematuria depends on the primary medical condition that caused the hematuria in the first place.

Patient Education

Inform children and their parents that strenuous exercise may aggravate hematuria; however, hematuria by itself should not prevent the child from participating in sports. Despite the sometimes alarming intensity or persistence of hematuria, parents must be informed that, by itself, hematuria rarely causes anemia.

For excellent patient education resources, visit Medscape Reference's patient education article Blood in the Urine.

How is hematuria defined?What is the focus of clinical history for the evaluation of hematuria?What is included in the physical exam to evaluate hematuria?Which lab tests are performed in the workup of hematuria?Which imaging studies are performed in the workup of hematuria?What is the role of biopsy in the workup of hematuria?How is hematuria categorized?How is hematuria treated?What are the ACP treatment guidelines for hematuria?What is hematuria?What is the pathophysiology of hematuria?What is the prevalence of hematuria?What is the mortality and morbidity associated with hematuria?What are the racial predilections of hematuria?What are the sexual predilections of hematuria?Which age groups have the highest prevalence of hematuria?Which clinical history findings are characteristic of hematuria?Which physical findings are characteristic of hematuria?What causes hematuria?Which conditions are associated with hematuria in children?What are the differential diagnoses for Hematuria?What is the role of lab testing in the workup of hematuria?What is the role of imaging studies in the workup of hematuria?When is a kidney biopsy indicated in the workup of hematuria?What is the role of cystoscopy in the workup of hematuria?What is the role of skin biopsy in the workup of hematuria?Which histologic findings are characteristic of hematuria?What is microscopic hematuria with clinical symptoms?What is asymptomatic microscopic hematuria with proteinuria?What is asymptomatic microscopic (isolated) hematuria?What is gross hematuria?What are the AUA recommendations for additional screening following a diagnosis of hematuria?How is asymptomatic microscopic (isolated) hematuria treated?When is surgery indicated in the treatment of hematuria?Which specialist consultations are beneficial to patients with hematuria?Which dietary modifications are used in the treatment of hematuria?Which activity modifications are used in the treatment of hematuria?What is the role of medications in the treatment of hematuria?What is included in the long-term monitoring of hematuria?What is the prognosis of hematuria?What is included in patient education about hematuria?

Author

Sanjeev Gulati, MD, MBBS, DNB(Peds), DM, DNB(Neph), FIPN(Australia), FICN, FRCPC(Canada), Additional Professor, Department of Nephrology, Sanjay Gandhi Post Graduate Institute of Medical Sciences; Senior Consultant in Pediatric Nephrology and Additional Director, Department of Nephrology and Transplant Medicine, Fortis Institute of Renal Sciences Transplantation, India

Disclosure: Nothing to disclose.

Coauthor(s)

Deogracias Pena, MD, Medical Director of Dialysis, Medical Director of Pediatric Nephrology and Transplantation, Cook Children's Medical Center; Clinical Associate Professor, Texas Tech University Health Sciences Center, Paul L Foster School of Medicine; Medical Director of Pediatric Nephrology, Florida Hospital for Children

Disclosure: Nothing to disclose.

Specialty Editors

Mary L Windle, PharmD, Adjunct Associate Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Nothing to disclose.

Adrian Spitzer, MD, Clinical Professor Emeritus, Department of Pediatrics, Albert Einstein College of Medicine

Disclosure: Nothing to disclose.

Chief Editor

Craig B Langman, MD, The Isaac A Abt, MD, Professor of Kidney Diseases, Northwestern University, The Feinberg School of Medicine; Division Head of Kidney Diseases, The Ann and Robert H Lurie Children's Hospital of Chicago

Disclosure: Received income in an amount equal to or greater than $250 from: Alexion Pharmaceuticals; Horizon Pharmaceuticals); ; Dicerna, Jannsen Pharmaceuticals.

Additional Contributors

Richard Neiberger, MD, PhD, Director of Pediatric Renal Stone Disease Clinic, Associate Professor, Department of Pediatrics, Division of Nephrology, University of Florida College of Medicine and Shands Hospital

Disclosure: Nothing to disclose.

References

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Microscopy of urinary sediment. Typical appearance in non-glomerular hematuria: RBCs are uniform in size and shape but show two populations of cells because a small number have lost their hemoglobin pigment.

Microscopy of urinary sediment. Typical appearance in non-glomerular hematuria: RBCs are uniform in size and shape but show two populations of cells because a small number have lost their hemoglobin pigment.

Microscopy of urinary sediment. Typical appearance of RBCs in glomerular hematuria: RBCs are small and vary in size, shape, and hemoglobin content.

Microscopy of urinary sediment. A cast containing numerous erythrocytes, indicating glomerulonephritis.

Approach to hematuria.

Nonglomerular hematuria.

Approach to hematuria.

Nonglomerular hematuria.

Microscopy of urinary sediment. Typical appearance in non-glomerular hematuria: RBCs are uniform in size and shape but show two populations of cells because a small number have lost their hemoglobin pigment.

Microscopy of urinary sediment. Typical appearance of RBCs in glomerular hematuria: RBCs are small and vary in size, shape, and hemoglobin content.

Microscopy of urinary sediment. A cast containing numerous erythrocytes, indicating glomerulonephritis.

Condition Histology History Laboratory Data
Systemic lupus erythematosusMild glomerulitis, proliferative changes, immune complex deposition, crescents, immunoglobulin depositionHematuria, proteinuria, hypertension, joint pains, rashesAbnormal C3, C4, ANA, and dsDNA levels; anemia; thrombocytopenia
IgA nephropathyIgA deposition in the mesangium, glomerular sclerosis, proliferative changes, crescents in severe casesGross, intermittent, painless hematuriaNo specific changes, although increased serum



IgA levels observed in some patients



Henoch-Schönlein purpuraSame as IgA nephropathyPurpura, joint pains, abdominal pain, hematuriaNo specific laboratory data
Alport syndromeSome thinning of basement membranes, "basket weave" changes in the glomerular basement



membrane on electron microscopy



Sensorineural hearing loss, corneal abnormalities, hematuria, renal failureNo specific changes
Thin basement membrane diseaseAverage glomerular basement membranes reported to be 100-200 nm in children in this conditionPersistent microscopic or gross hematuria, significant family historyNo specific changes
Mesangiocapillary glomerulonephritisGlomerular lobulations, thickening of the mesangial matrix and glomerular basement membranes, crescentsHematuria, proteinuria, hypertensionC3 levels possibly abnormal