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Hematuria DETECTION — presence of an increased number of red blood cells (RBCs) in theurine. Hematuria can either be visible to the naked eye (gross) or apparent only upon urinalysis (microscopic).
Urinary dipstick — The most common screening test. These strips can detect 5 to 10 intact RBCs/µL, which roughly corresponds to a finding on microscopic examination of 2-5 RBCs /HPF from the sediment of a centrifuged 10 to 15 mL urine sample. False-negative in the presence of formalin or high urinary concentration of ascorbic acid. False-positive with alkaline urine (ie, pH greater than 9) or contamination with oxidizing agents used to clean the perineum.
Microscopic examination Sediment of 10 to 15 mL of centrifuged fresh urine. Microscopic hematuria = presence of more than five RBCs per high-power field .
glomerular disease Red cell casts . Protein excretion greater than 100 mg/m2 at a time when there is no gross bleeding. The optimal method is obtaining a first morning sample to determine the protein to creatinine ratio because it excludes orthostatic proteinuria, a normal variant. Red blood cells (RBCs) having a dysmorphic appearance.
Red cell casts
Morphologic study of urinary RBCs By phase-contrast microscope, The presence of more than 30 %dysmorphic RBCs or of more than 5 % of a specific form named an "acanthocyte" is highly suggestive of glomerular hematuria . In nonglomerular hematuria, RBCs with a uniform normal size and shape . Hypercalciuria, can be associated with dysmorphic red blood cells but not red cell casts.
ETIOLOGYBoth benign and serious conditions can cause microscopic hematuria in children. The most common causes of persistent microscopic hematuria include; glomerulopathies hypercalciuria nutcracker syndrome
IgA nephropathyDiagnosed by renal biopsy . mesangial IgA deposits on immunofluorescence study. There is often a history of gross hematuria preceded by an URTI or gastrointestinal illness and usually a negative family history of renal disease.
Alport syndromeClassic Alport syndrome (hereditary nephritis) is a recessive X-linked disorder that is typically seen in males and is often accompanied by high-frequency sensorineural hearing loss, ocular abnormalities including anterior lenticonus, and, over time, progressive renal failure. Heterozygous carrier-females also can have hematuria, but do not have progressive renal disease. The genetic abnormality in these patients involves the gene for the alpha-5 chain of type IV collagen (COL4A5). In addition, there are autosomal recessive and dominant forms of Alport syndrome with mutations in the COL4A3 and COL4A4
Thin basement membrane disease(TBM) TBM, also called benign familial hematuria, is an autosomal dominant condition. Kidney biopsy reveals an isolated thinning of the glomerular basement membrane on electron microscopy. In many cases, TBM disease is the heterozygous form of autosomal recessive Alport syndrome.
Postinfectious glomerulonephritis —hematuria generally resolves within three to six months after the presentation..
Hypercalciuria —defined 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. the prevalence has ranged from as low as 11 % in the Northeast to as high as 35 % in the South. Thus, the association between hypercalciuria and hematuria may be more common in areas where there is a higher prevalence of nephrolithiasis
Nutcracker syndrome — Left renal vein compression between the aorta and proximal superior mesenteric artery, has been suggested as a cause of hematuria in children that is usually asymptomatic but may be associated with left flank pain. Detected by Doppler ultrasonographic assessment of left renal vein diameter and peak velocity. Nutcracker syndrome can also cause orthostatic proteinuria in children . nutcracker syndrome highest in Asia
EVALUATION The diagnostic evaluation depends upon the clinical presentation, which falls into the following three categories:1. Asymptomatic isolated microscopic hematuria2. Asymptomatic microscopic hematuria with proteinuria3. Symptomatic microscopic hematuria
Asymptomatic isolatedmicroscopic hematuria ie, no proteinuria Evaluation including blood pressure and a GUE performed weekly for 2wk. One should ensure that there is no exercise prior to obtaining the urine sample, since vigorous exercise can induce hematuria. 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 every3-6 mo including physical examination with blood pressure measurement and GUE. If the asymptomatic isolated hematuria persists for one year, the following subsequent evaluation should be performed:
Measure urine calcium/creatinine ratio forhypercalciuria.Test parents and siblings for hematuria to detectpossible thin basement membrane disease (autosomaldominant) or hereditary nephritis (mostly X-linkedrecessive).Consider hemoglobin electrophoresis if there is aclinical suspicion for sickle cell trait. PerformDoppler ultrasonography for the "nutcrackersyndrome".
Asymptomatic microscopichematuria and proteinuria The combination of hematuria and proteinuria is associated with a higher risk for significant renal disease. Evaluation ; S cr and proteinuria ( by a 24-hour urine collection or urine protein-to-creatinine ratio on a first morning urine sample) . If protein excretion is >4 mg/m2 /hr or if in a first morning urine specimen, the urine protein-to-creatinine ratio is >0.2 mg protein/mg creatinine in children older than 2 years of age and >0.5 mg protein/mg creatinine in younger children it is likely that there is significant renal disease. If protein excretion is less than the above values, reevaluated in 2-3 WK. 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 asymptomatic isolated microscopic hematuria.
If proteinuria is persistent the patient should be referred for further evaluation.Further assessment should include microscopic examination of the urine by an experienced clinician, serum creatinine, C3, C4, albumin, and complete blood count. ASO titer, streptozyme testing, antinuclear antibody testing, imaging, and renal biopsy.
Symptomatic microscopichematuriaThe evaluation ; The clinical manifestations; may be nonspecific (eg, fever, malaise, weight loss) Extrarenal (eg, rash, purpura, arthritis), 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 Henoch-Schönlein purpura. Renal causes of symptomatic microscopic hematuria include glomerular or interstitial diseases of the kidney, lower urinary tract disease, nephrolithiasis, tumors, and vascular disease. The urinalysis can be helpful in differentiating between glomerular and nonglomerular causes of bleeding
Historical clues Recent trauma.A history of incontinence, dysuria, frequency, orurgency ( suggests UTI).unilateral flank pain that radiates to the groin (acalculus or blood clot).Flank pain without radiation but with fever, dysuria,and frequency and/or urgency ( acute pyelonephritis).History of pharyngitis or impetigo 2-3 wks prior toonset of hematuria( poststreptococcalglomerulonephritis).
Recent upper respiratory (one or two days prior to onset ofhematuria) infection can be associated with IgAnephropathy. A history of predisposing or preexisting clinical conditionssuch as sickle cell disease or trait, a coagulopathy such assevere hemophilia, or deafness (Alport syndrome).A family history of hematuria, kidney disease (eg, Alportsyndrome or thin basement membrane nephropathy), orkidney stones. Exposure to medications that can cause interstitialnephritis, although hematuria is not typically the centralmanifestation in such patients.
Physical examination — 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
Further evaluation Trauma history —CT scan of the abdomen and pelvis. Signs or symptoms of UTI —on urinalysis .include positive dipstick tests for leukocyte esterase and/or nitrite, more than 5 WBC per high-power field and the presence of bacteria on a Gram stain of urine. Adenovirus should be considered as a potential etiology if urinary symptoms and urinalysis suggestive of infection but the culture is negative. Signs or symptoms of perineal/meatal irritation — Supportive care and reassurance.
Signs or symptoms of nephrolithiasis — Renal ultrasonography. Abdominal plain films. 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.
glomerular disease —( proteinuria, RBCcasts, edema, and hypertension ) Evaluation; serum creatinine, CBC, 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.
Indications for renal biopsy 1- Biopsy is not performed for isolated microscopic hematuria.2- Considered if substantial or progressive ; Elevation in the creatinine concentration, Significant proteinuria, Unexplained rise in blood pressure even when the values remain within the normal range. 3- Child with persistent glomerular hematuria, in whom the parents are worried about the diagnosis and prognosis.
4- Child with microscopic hematuria and a family history of kidney failure in early adulthood in a first order relative.5- 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.
Cystoscopy — is rarely indicated for hematuria in children. for bladder mass noted on ultrasound and those with urethral abnormalities due to trauma.