Urol Clin N Am 31 (2004) 559–573 Evaluation of hematuria in children Kevin E.C. Meyers, MBBCh Division of Nephrology, Department of Pediatrics, Children’s Hospital of Philadelphia, University of Pennsylvania School of Medicine, 34th Street and Civic Center Boulevard, Main Building, 2nd Floor, Philadelphia, PA 19104-4399, USA The detection of even microscopic amounts of Nine milliliters is decanted and the sediment blood in a child’s urine alarms the patient, is resuspended and an aliquot examined. The urine parents, and physician, and often prompts the is examined by microscopy by high power field performance of many laboratory studies. Hema- (hpf) that is 400Â magnification. Macroscopic turia is one of the most important signs of renal or hematuria often does not require concentration. bladder disease, but proteinuria is a more impor- Bright-red urine, visible clots, or crystals with tant diagnostic and prognostic finding, except in normal-looking red blood cells (RBCs) suggests the case of calculi or malignancies. Hematuria is bleeding from the urinary tract. Cola-colored almost never a cause of anemia. The physician urine, RBC casts, and deformed (dysmorphic) should ensure that serious conditions are not RBCs suggest glomerular bleeding [4]. An absence overlooked, avoid unnecessary and often expen- of RBCs in the urine with a positive dipstick re- sive laboratory studies, reassure the family, and action suggests hemoglobinuria or myoglobinuria. provide guidelines for additional studies if there is The sensitivity and specificity of the dipstick a change in the child’s course [1]. This article method for detecting blood in the urine vary. provides an approach to the evaluation and When tested on urine samples in which a prede- management of hematuria in a child [2,3]. Many termined amount of blood has been placed, dip- tests have been recommended for the child with sticks have a sensitivity of 100 and a specificity of hematuria, but no consensus exists on a stepwise 99 in detecting one to five RBCs/hpf [5]. This evaluation. Although more research is needed to corresponds to approximately 5 to 10 intact resolve certain controversies in management, the RBCs/lL urine [6]. There is no consensus on the suggested approach aims to detect major or definition of microscopic hematuria, although treatable problems and limit the anxiety, cost, more than 5 to 10 RBCs/hpf is considered and energy required by unnecessary testing. significant [7,8]. The author and others recom- mend that at least two of three urinalyses show microhematuria over 2 to 3 weeks before further Definitions evaluation is performed [3,9]. The American Academy of Pediatrics recommends a screening Macroscopic hematuria is visible to the naked urinalysis at school entry (4–5 years of age) and eye, but microscopic hematuria usually is detected once during adolescence (11–21 years of age) as by a dipstick test during a routine examination. a component of well child–care. Hematuria is confirmed by microscopic examina- tion of the spun urine sediment. Microscopic examination is performed with concentration of Incidence and prevalence the urinary sediment by centrifugation. Ten milli- liters of urine is spun at 2000 rpm for 5 minutes. Pediatricians frequently encounter hematuria in children. Macroscopic hematuria has an esti- mated incidence of 1.3 per 1000 [2]. Microscopic E-mail address: [email protected] hematuria, although more common than gross 0094-0143/04/$ - see front matter Ó 2004 Elsevier Inc. All rights reserved. doi:10.1016/j.ucl.2004.04.015 560 K.E.C. Meyers / Urol Clin N Am 31 (2004) 559–573 hematuria, has a variably reported incidence depending on the definition used for making the Box 1. Causes of hematuria in children diagnosis. The incidence of microscopic hematu- ria in schoolchildren was estimated at 0.41% Glomerular diseases when four urine samples per child were collected Recurrent gross hematuria (IgA and 0.32% in girls and 0.14% in boys when five nephropathy, benign familial consecutive urine specimens were analyzed over 5 hematuria, Alport’s syndrome) years [10,11]. Microscopic hematuria in two or Acute poststreptococcal more urine samples is found in 1% to 2% of glomerulonephritis children 6 to 15 years of age. Membranoproliferative glomerulonephritis Systemic lupus erythematosus Pathophysiology Membranous nephropathy Rapidly progressive Hematuria may originate from the glomeruli, glomerulonephritis renal tubules and interstitium, or urinary tract Henoch-Schonlein purpura (including collecting systems, ureters, bladder, and Goodpasture’s disease urethra) (Boxes 1 and 2). In children, the source of bleeding is more often from glomeruli than from Interstitial and tubular the urinary tract. RBCs cross the glomerular Acute pyelonephritis endothelial-epithelial barrier and enter the capil- Acute interstitial nephritis lary lumen through structural discontinuities in the Tuberculosis capillary wall. These discontinuities seem to be at Hematologic (sickle cell disease, the capillary wall–mesangial cell reflections [12].In coagulopathies von Willebrand’s most cases, proteinuria, RBC casts, and deformed disease, renal vein thrombosis, (dysmorphic) RBCs in the urine accompany he- thrombocytopenia) maturia caused by any of the glomerulonephriti- Urinary tract des. The renal papillae are susceptible to necrotic Bacterial or viral (adenovirus) injury from microthrombi and anoxia in patients infection–related with a hemoglobinopathy or in those exposed to Nephrolithiasis and hypercalciuria toxins. Patients with renal parenchymal lesions Structural anomalies, congenital may have episodes of transient microscopic or anomalies, polycystic kidney macroscopic hematuria during systemic infections disease or after moderate exercise. This may be the result Trauma of renal hemodynamic responses to exercise or Tumors fever by undetermined mechanisms. Exercise Medications (aminoglycosides, Initial evaluation amitryptiline, anticonvulsants, aspirin, chlorpromazine, coumadin, Macroscopic hematuria cyclophosphamide, diuretics, The evaluation of a child with gross hematuria penicillin, thorazine) differs from that of microscopic hematuria (Fig. 1). Macroscopic hematuria of glomerular origin usu- ally is described as brown, tea-colored, or cola- evaluate children with recurrent nonglomerular colored, whereas macroscopic hematuria from the macroscopic hematuria of undetermined origin lower urinary tract (bladder and urethra) is usually because cystoscopy may be warranted. pink or red. Macroscopic hematuria in the absence of significant proteinuria or RBC casts is an Microscopic hematuria indication for a renal and bladder ultrasound to exclude malignancy or cystic renal disease. Re- Microscopic hematuria, defined by more than ferral to a urologist is required when clinical five RBCs/hpf, almost always warrants referral to evaluation and workup indicates that there is a nephrologist rather than an urologist. Figs. 2 a tumor, a structural urogenital abnormality, or and 3 give an approach to the evaluation of an obstructing calculus. A urologist also should asymptomatic and symptomatic microscopic K.E.C. Meyers / Urol Clin N Am 31 (2004) 559–573 561 History Box 2. Causes of asymptomatic isolated microscopic hematuria A history of dysuria, frequency, urgency, or flank or abdominal pain suggests a diagnosis of Common urinary tract infection or nephrolithiasis. Recent Undetermined trauma, strenuous exercise, menstruation, or blad- Benign familial der catheterization may account for transient Idiopathic hypercalciuria hematuria. A sore throat or skin infection within IgA nephropathy the past 2 to 4 weeks directs the evaluation toward Sickle cell trait or anemia postinfectious glomerulonephritis. Drugs and Transplant toxins may cause either hematuria or hemoglobin- uria (Box 5). A careful family history must include Less common questions about hematuria, hearing loss, hyper- Alport nephritis tension, nephrolithiasis, renal diseases, renal cystic Postinfectious glomerulonephritis diseases, hemophilia, sickle cell trait, and dialysis Trauma or transplant. Exercise Nephrolithiasis Physical examination Henoch-Schonlein purpura The presence or absence of hypertension or Uncommon proteinuria helps to decide how extensively to Drugs and toxins pursue the diagnostic evaluation. If the blood Coagulopathy pressure is normal and the patient is passing Ureteropelvic junction obstruction normal amounts of urine, it is unlikely that Focal segmental glomerulosclerosis microscopic hematuria, whatever its cause, war- Membranous glomerulonephritis rants immediate treatment. If the blood pressure is Membranoproliferative elevated, the hematuria requires a more intensive glomerulonephritis diagnostic evaluation. The presence of fever or Lupus nephritis costovertebral angle tenderness may indicate a Hydronephrosis urinary tract infection. An abdominal mass may Pyelonephritis be caused by a tumor, hydronephrosis, multicystic Vascular malformation dysplastic kidney, or polycystic kidney disease. Tuberculosis Macroscopic hematuria with proteinuria suggests Tumor glomerulonephritis. Rashes and arthritis can occur in Henoch-Schonlein purpura and systemic lupus erythematosus. Edema is an important feature of (Adapted from Lieu TA, Grasmeder M, the nephrotic syndrome (Table 1). Kaplan BS. An approach to the evaluation and treatment of microscopic hematuria. Laboratory studies Pediatr Clin North Am 1991;38:579–92.) Only two diagnostic tests are required for a child with microscopic hematuria: (1) a test for proteinuria