Chapter 513 Upper Urinary Tract Causes of Hematuria
513.6 Vascular Abnormalities
Hemangiomas, hemangiolymphangiomas, angiomyomas, and arteriovenous malformations of the kidneys and lower urinary tract are rare causes of hematuria. They can manifest with microscopic hematuria or gross hematuria with clots. Cutaneous vascular malformations, when present, can offer a clue to these underlying causes of hematuria. Renal colic can develop if the upper tract is involved. The diagnosis may be confirmed by angiography or endoscopy.
Unilateral bleeding of varicose veins of the left ureter, resulting from compression of the left renal vein between the aorta and superior mesenteric artery (mesoaortic compression), is referred to as the nutcracker syndrome. Patients with this syndrome typically present with persistent microscopic hematuria (occasionally, recurrent gross hematuria) that may be accompanied by proteinuria, lower abdominal pain, flank pain, or orthostatic hypotension. Diagnosis is confirmed by Doppler ultrasonography, CT, phlebography of the left renal vein, or magnetic resonance angiography.
Guthrie SO, Rhodes M, Janco R, et al. An infant with Kassbach-Merritt syndrome with associated renal hematoma and intussusception. J Perinatol. 2005;25:143-145.
Pratap A, Tiwari A, Pandey SR, et al. Giant cavernous hemangiolymphangioma of the bladder without cutaneous hemangiomatosis causing massive hematuria in a child. J Pediatr Urol. 2007;3:326-329.
Wang L, Yi L, Liu Z, et al. Diagnosis and surgical treatment of nutcracker syndrome: a single-center experience. Urology. 2009;73:871-876.
513.7 Renal Vein Thrombosis
Renal vein thrombosis (RVT) occurs in 2 distinct clinical situations. In newborns and infants, RVT is commonly associated with asphyxia, dehydration, shock, sepsis, congenital hypercoagulable states, and maternal diabetes. In older children, RVT is seen in patients with nephrotic syndrome, cyanotic heart disease, inherited hypercoagulable states, and sepsis and following kidney transplantation and following exposure to angiographic contrast agents.
RVT begins in the intrarenal venous circulation and can spread to the main renal vein and inferior vena cava. Thrombus formation is mediated by endothelial cell injury resulting from hypoxia, endotoxin, or contrast media. Other contributing factors include hypercoagulability from either nephrotic syndrome or mutations in genes that encode clotting factors (i.e., factor V Leiden deficiency); hypovolemia and diminished vascular blood flow associated with septic shock, dehydration, or nephrotic syndrome; and intravascular sludging caused by polycythemia.
The development of RVT is usually heralded by the sudden onset of gross hematuria and unilateral or bilateral flank masses. Patients can also present with microscopic hematuria, flank pain, hypertension, or oliguria. RVT is usually unilateral. Bilateral RVT results in acute kidney failure.
The diagnosis of RVT is suggested by the development of hematuria and flank masses in a patient with predisposing clinical factors. Patients can also have a microangiopathic hemolytic anemia and thrombocytopenia. Ultrasonography shows marked enlargement, and radionuclide studies reveal little or no renal function in the affected kidney(s). Doppler flow studies of the inferior vena cava and renal vein confirm the diagnosis. Contrast studies should be avoided to minimize the risk of further vascular damage.
The differential diagnosis of RVT includes other causes of hematuria that are associated with microangiopathic hemolytic anemia or enlargement of the kidneys. These include hemolytic-uremic syndrome, hydronephrosis, polycystic kidney disease, Wilms tumor, abscess, or hematoma. All patients should be evaluated for congenital and acquired hypercoagulable states.
The primary treatment of RVT consists of supportive care, including correction of fluid and electrolyte imbalance and treatment of renal insufficiency. Treatment with anticoagulation (heparin) or thrombolytic agents including streptokinase, urokinase, or recombinant tissue plasminogen activator is common but remains controversial. Patients with thrombosis of the inferior vena cava can require surgical thrombectomy. Children with severe hypertension refractory to antihypertensive medications can require nephrectomy.
Perinatal mortality from RVT has decreased significantly over the past 20 yr. Partial or complete renal atrophy is a common sequela of RVT in the neonate, leading to renal insufficiency, renal tubular dysfunction, and systemic hypertension. These complications are also seen in older children, although recovery of renal function is common in children with RVT resulting from nephrotic syndrome or cyanotic heart disease with correction of the underlying etiology.
Goldenberg NA. Long-term outcomes of venous thrombosis in children. Curr Opin Hematol. 2005;12:370-376.
Lau KK, Stoffman JM, Williams S, et al. Neonatal renal vein thrombosis: review of the English-language literature between 1992 and 2006. Pediatrics. 2007;120:e1278-e1284.
Messinger Y, Sheaffer JW, Mrozek J, et al. Renal outcome of neonatal renal venous thrombosis: review of 28 patients and effectiveness of fibrinolytics and heparin in 10 patients. Pediatrics. 2006;118:e1478-e1484.
513.8 Idiopathic Hypercalciuria
Idiopathic hypercalciuria, which may be inherited as an autosomal dominant disorder, can manifest as recurrent gross hematuria, persistent microscopic hematuria, dysuria, or abdominal pain in the absence of stone formation. Hypercalciuria can also accompany conditions resulting in hypercalcemia, such as hyperparathyroidism, vitamin D intoxication, immobilization, and sarcoidosis. Hypercalciuria may be associated with Cushing syndrome, corticosteroid therapy, tubular dysfunction secondary to Fanconi syndrome (Wilson disease, oculocerebrorenal syndrome), Williams syndrome, distal renal tubular acidosis, or Bartter syndrome. Hypercalciuria may also be seen in patients with Dent disease, which is an X-linked form of nephrolithiasis associated with hypophosphatemic rickets. Although microcrystal formation and consequent tissue irritation are believed to mediate symptoms, the precise mechanism by which hypercalciuria causes hematuria or dysuria is unknown.
Hypercalciuria is diagnosed by a 24-hr urinary calcium excretion >4 mg/kg. A screening test for hypercalciuria in patients who cannot collect a timed urine specimen may be performed on a random urine specimen by measuring the calcium and creatinine concentrations. A spot urine calcium:creatinine ratio (mg/dL:mg/dL) >0.2 suggests hypercalciuria in an older child. Normal ratios may be as high as 0.8 in infants <7 mo of age.
Left untreated, hypercalciuria leads to nephrolithiasis in approximately 15% of cases. Idiopathic hypercalciuria has been identified as a risk factor in 40% of children with kidney stones, and low urinary citrate level has been associated as a risk factor in approximately 38% of this group. Oral thiazide diuretics can normalize urinary calcium excretion by stimulating calcium reabsorption in the proximal and distal tubule. Such therapy can lead to resolution of gross hematuria or dysuria and can prevent nephrolithiasis. The precise indications for thiazide treatment remain controversial.
In patients with persistent gross hematuria or dysuria, therapy is initiated with hydrochlorothiazide at a dose of 1-2 mg/kg/24 hr as a single morning dose. The dose is titrated upward until the 24-hr urinary calcium excretion is <4 mg/kg and clinical manifestations resolve. After 1 yr of treatment, hydrochlorothiazide is usually discontinued but may be resumed if gross hematuria, nephrolithiasis, or dysuria recurs. During hydrochlorothiazide therapy, the serum potassium level should be monitored periodically to avoid hypokalemia. Potassium citrate at a dose of 1 mEq/kg/24 hr may also be beneficial, particularly in patients with low urinary citrate excretion and symptomatic dysuria.
Sodium restriction is important because calcium excretion parallels sodium excretion. Importantly, dietary calcium restriction is not recommended (except in children with massive calcium intake >250% of RDA by dietary history) because calcium is a critical requirement for growth and no evidence supports a relationship between decreased calcium intake and decreased urinary calcium levels. Reduced bone mineral density with evidence of bone resorption has been described in patients with hypercalciuria. In such patients, dietary calcium restriction is particularly contraindicated. Small-scale studies seem to support a role for bisphosphonate therapy, which leads to a reduction in urinary calcium excretion and improvement in bone mineral density. Controlled studies are necessary to establish a clear role for such therapy.
Freundlich M, Alon US. Bisphosphonates in children with hypercalciuria and reduced bone mineral density. Pediatr Nephrol. 2008;23:2215-2220.
Kari JA, Farouq M, Alshaya HO. Familial hypomagnesemia with hypercalciuria and nephrocalcinosis. Pediatr Nephrol. 2003;18:506-510.
Knohl SJ, Scheinman SJ. Inherited hypercalciuric syndromes: Dent’s disease (CLC-5) and familial hypomagnesemia with hypercalciuria (paracellin-1). Semin Nephrol. 2004;24:55-60.
Magen D, Adler L, Mandel H, et al. Autosomal recessive renal proximal tubulopathy and hypercalciuria: a new syndrome. Am J Kidney Dis. 2004;43:600-606.
Polito C, LaManna A, Cioce F, et al. Clinical presentation and natural course of idiopathic hypercalciuria in children. Pediatr Nephrol. 2000;15:211-214.
So NP, Osorio AV, Simon SD, et al. Normal urinary calcium/creatinine ratios in African-American and Caucasian children. Pediatr Nephrol. 2001;16:133-139.
Spivacow FR, Negri AL, del Valle EE, et al. Metabolic risk factors in children with kidney stone disease. Pediatr Nephrol. 2008;23:1129-1133.