Hematuria

History

Development of pain with the onset of hematuria usually indicates a lower urinary tract source. Irritative symptoms, such as dysuria, urgency, or frequency, can be seen in bleeding from the bladder from a variety of causes. Although not a typical feature of urinary tract infection (UTI), the most common identifiable cause of gross hematuria is a UTI and is usually accompanied by significant dysuria or abdominal pain, and sometimes fever. Severe and episodic or colicky flank or abdominal pain should raise suspicion for urolithiasis, which may have accompanying dysuria as the stone is being passed. Urinary tract obstruction, such as posterior urethral valves in males or ureteropelvic junction obstruction in either gender, may remain occult until infection or trauma causes hematuria. In the former, the only preceding symptoms may be a male who voids only infrequently, commonly strains to void, or has ongoing urinary incontinence beyond the toddler years. Bleeding from renal tumors is an uncommon cause of gross hematuria in children but should be considered particularly in the setting of associated abdominal pain, a palpable mass, or passing of blood clots.

Gross hematuria due to glomerular disease is rarely accompanied by significant pain, though some may report mild abdominal pain or flank discomfort. An exception is immunoglobulin A (IgA) vasculitis (Henoch-Schönlein purpura [HSP]), a common pediatric systemic vasculitis, which can have variable, including severe, gastrointestinal disease. Clues to underlying glomerular disease may be a recent history of pharyngitis, streptococcal skin infection, or other febrile illnesses, indicating possible acute postinfectious glomerulonephritis. Patients with glomerulonephritis or renal insufficiency may report shortness of breath, edema, or weight gain from fluid retention. They may also have a headache or visual changes secondary to severe hypertension. Abdominal pain, diarrhea, hematochezia, rash, and arthralgias are symptoms indicative of a systemic vasculitis, such as IgA vasculitis (HSP). Recurrent, painless gross hematuria is often seen in young patients with IgA nephropathy in association with concurrent respiratory illness. Recurrent fever, weight loss, alopecia, mouth ulcers, chest pain, fatigue, and arthritis suggest systemic lupus erythematosus (SLE). Hemoptysis or cough is seen in pulmonary-renal syndromes caused by antineutrophil cytoplasmic antibody (ANCA)-associated disease, and on occasion in lupus and HSP.

The patient’s medical history may be most informative. Stressed neonates from birth asphyxia, infection, or volume depletion can develop renal vein thrombus that presents as gross hematuria. Patients with African ancestry should be queried for personal or family history of sickle cell hemoglobinopathy since gross hematuria from renal papillary necrosis can occur in those with sickle cell disease as well as in children with simple sickle cell trait. Medication history can uncover a cause of gross hematuria from drug-induced interstitial nephritis, seen with several antibiotics, anticonvulsants, or nonsteroidal antiinflammatory drugs; the latter can also cause papillary necrosis. Cyclophosphamide can cause a severe hemorrhagic cystitis, which usually has concomitant prominent bladder symptoms.

A history of frequent or severe bleeding from other sites, such as heavy menses, prolonged nosebleeds, hemarthroses, or significant bleeding associated with surgical procedures, suggests an undiagnosed bleeding disorder. Exposure history to tuberculosis should be obtained, as well as a travel history, as parasitic infections such as schistosomiasis of the bladder, uncommon in Western societies, is common in other parts of the world. Questions specific to other potential sources of blood in the urine include those directed at a foreign body from self-instrumentation of the urethra, trauma, sexual abuse, and menstruation. Extreme sports activities such as running a marathon or long-distance cycling can cause gross hematuria.

Review of the family history is important to uncover hereditary nephritis, hereditary cystic kidney disease, or potential benign familial hematuria. A family history of kidney disease leading to end-stage renal failure, especially if in men in multiple generations and if not clearly due to diabetes mellitus, would suggest Alport syndrome, the most common cause of hereditary nephritis. Alport syndrome is predominantly an X-linked recessive disorder that may cause gross hematuria in childhood, although more often it is microscopic. When gross hematuria occurs in Alport syndrome, it is often triggered by any infectious process such as a common cold. The gross hematuria then subsequently clears, but microscopic hematuria is a persistent finding. The early clinical features of hereditary nephritis can be exactly the same as benign familial hematuria but then evolve to develop other features. Early in the course of the disease, there is no associated proteinuria, but that feature develops later, often in childhood as the nephropathy progresses. Hearing loss is a common but variable feature of Alport syndrome that tends to run in affected families. Female family members who are carriers usually have persistent and isolated hematuria that does not progress, but on occasion may develop progressive nephritis.

Benign familial hematuria and familial thin basement membrane nephropathy are also responsible for both microhematuria and gross hematuria. The primary difference in family history that separates benign familial hematuria from progressive hereditary nephritis is that members of sequential generations of the family with benign familial hematuria, either male or female, have persistent isolated hematuria that never progresses to significant renal disease. The genetics of benign familial hematuria due to thin basement membrane nephropathy has been defined and includes gene variants that are identical to those seen in some patients with autosomal recessive forms of progressive hereditary nephritis. Patients with thin basement membrane nephropathy, or benign familial hematuria, may be carriers of genes that cause autosomal recessive Alport syndrome.

Patients with autosomal dominant polycystic kidney disease (ADPKD) may present initially with gross hematuria from spontaneous bleeding into the macrocysts. Because the course of ADPKD can vary widely from one generation to the next, with some members having very mild disease with minimal clinical features until late adulthood, the family history of the disease may not be apparent on presentation. Early onset of hypertension, during youth or young adulthood in a parent of an affected child, may be the only clue to a family member being affected by ADPKD.

Gross hematuria is a presenting complaint in 15% of children with urolithiasis . Kidney stone disease can be familial, and in some cases related to specific genes, as in X-linked recessive nephrolithiasis (Dent disease) or primary hyperoxaluria. Therefore, family history of early-onset nephrolithiasis, especially in siblings, should be sought in children presenting with gross hematuria and symptoms or imaging that indicate kidney stone disease as the cause. A family history of a bleeding disorder such as hemophilia or platelet disorders should be sought.

Physical Examination

The initial focus of the physical examination should be for evidence of systemic disease for which the hematuria is one manifestation, and for potential sequelae of renal disease. Accurate measurement and attention to blood pressure, recognizing age differences in blood pressure, is critical. Hypertension may be the sole feature on physical examination that indicates underlying acute glomerulonephritis, or chronic kidney disease from several causes. The finding of edema in this context is highly suggestive of underlying renal parenchymal disease, either acute or chronic, with likely accompanying renal insufficiency. Poor growth or failure to thrive may indicate chronic renal disease. Pallor, fever, rashes, or musculoskeletal findings suggest systemic vasculitis with renal involvement from diseases such as HSP, SLE, or, less often, ANCA-associated disease. Examination of the abdomen may reveal abdominal or flank masses that could be tumors, cystic kidneys, or urinary obstruction. The most common renal tumor in childhood, typically seen in young children (ages 1–4 years), is Wilms tumor, though other types occur. Hydronephrosis or enlarged cystic kidneys may be palpable. Suprapubic tenderness may indicate bladder infection, stone, or other less common causes of bladder pathology as the source of blood. The genitalia should be inspected for blood at the urethral meatus that suggests a urethral source, tears or lacerations due to abuse or accidents such as from straddle injuries, or to look for a foreign body.

Evaluation