Dark Urine - Case 20-1: 1-Day-Old Boy
I. History of Present Illness
A 36-week gestation newborn boy was admitted to the neonatal intensive care unit
due to tachypnea and hypoglycemia. Poor variability of fetal heart tones and
nonprogression of labor had complicated the delivery, and a cesarean section
was performed. Meconium was noted at delivery, but the baby was vigorous, with
Apgar scores of 8 at 1 minute and 9 at 5 minutes. However, he was noted to have
significant edema, with the lower extremities being more affected than the
upper extremities or face. He also had bilateral hydroceles. The infant was
admitted to the intensive care nursery for monitoring of serum glucose and for
evaluation of the edema. During the first 24 hours life, he had persistent
tachypnea and required supplemental oxygen. He was also noted to have
hypertension and intermittent frank hematuria.
II. Past Medical History
The mother was an 18-year-old primigravida woman. Her laboratory values were
normal, including a negative rapid plasma reagin test, immunity to rubella,
negative hepatitis B status, and a negative screening test for group B
Streptococcus. The pregnancy had been complicated by gestational diabetes that was controlled
with diet. Pregnancy-induced hypertension led to a decision to induce labor at
36 weeks
' gestation. The mother had no history of ethanol, drug, or cigarette use during
the pregnancy and no history of sexually transmitted diseases. The baby
's family history was significant for a paternal uncle with type 1 diabetes and a
half brother who died from a brain tumor at the age of 5 years.
III. Physical Examination
T, 37°C; RR, 100 rpm; HR, 148 bpm; BP, 116/69 mm Hg
Weight, 4.5 kg
The general examination was most notable for marked tachypnea, but the infant
was alert. He had facial edema, especially of the eyelids. His ears were
externally normal, his nares patent, and his palate intact. Cardiac examination
revealed normal first and second heart sounds (S1 and S2, respectively) without
gallop or murmur. Retractions marked the infant
's increased respiratory effort, but there was no nasal flaring or grunting, and
the lung fields were clear to auscultation. Abdominal examination revealed a
mass on the right side. He had bilateral hydroceles, and there was pitting
edema of all extremities, although it was worse in the lower extremities. He
had slightly decreased tone but a strong suck and a symmetric Moro reflex.
IV. Diagnostic Studies
The white blood cell (WBC) count was 16,100 cells/mm3, with 14% band forms, 14% segmented neutrophils, 54% lymphocytes, and 10%
monocytes. The hemoglobin was 16.7 g/dL, and the platelet count was 89,000
cells/mm
3. The infant's blood type was A negative, and a Coombs test was negative. Serum electrolytes
were normal except for a slightly elevated sodium concentration of 147 mEq/L.
Liver function tests showed the following: total bilirubin, 9.9 mg/dL (all
unconjugated); alanine aminotransferase (ALT), 79 U/L; aspartate
aminotransferase (AST), 101 U/L; alkaline phosphatase, 220 U/L; and
γ-glutamyltransferase (GGT), 93 U/L. The albumin concentration was 2.5 mg/dL. An
arterial blood gas analysis in room air showed pH, 7.34; carbon dioxide tension
(PaCO
2), 41 mm Hg; and oxygen tension (PaO2), 63 mm Hg. Urinalysis revealed a specific gravity of 1.015, 3+ protein, and
blood. Microscopy showed 21 to 50 red blood cells per high-power field.
V. Course of Illness
An abdominal ultrasound study revealed the cause of hematuria.
Discussion: Case 20-1
I. Differential Diagnosis
Frank hematuria is an uncommon finding in the neonatal period. As noted earlier,
urate crystals can give a pinkish hue to an infant
's urine, but this is not usually confused with frank blood. The infant was not
exposed to any medications that would give an unusual color to the urine.
Microscopic urinalysis provides a quick mechanism to differentiate red blood
cells from free hemoglobin or myoglobin. In this case, microscopy indicated
that the clinical impression of frank blood was correct. Catheters or
suprapubic taps used to obtain urine can result in minor trauma, but they do
not usually cause frank hematuria. The remaining constellation of physical
findings in this infant directed concern to the kidney. Edema indicates fluid
overload, and a palpable abdominal mass could indicate an enlarged kidney or
tumor. Although Wilms tumor can manifest as hematuria and an abdominal mass, it
would be unlikely to do so this early. Renal vein thrombosis is a rare but
known entity in infants; it usually is seen in the setting of a hypercoagulable
state, such as infection, maternal diabetes, or hyperviscosity syndrome.
Coagulation disorders do not generally present with isolated hematuria.
Bleeding from intravenous catheter sites or other procedures would be expected.
Congenital kidney anomalies may rarely manifest with hematuria, but they would
not commonly make an infant appear ill. Urate crystals and colonization with
S. marcescens are causes of urine color change that are asymptomatic.
II. Diagnosis
An ultrasound study was obtained to evaluate the possible abdominal mass. A 2-cm
clot was seen in the inferior vena cava (IVC) that extended into the right
renal vein with enlargement of the right kidney. There was documented flow to
and from both kidneys, and collateral circulation provided some flow around the
IVC clot.
The diagnosis was renal vein thrombosis, with the predisposing condition being
maternal diabetes.
Captopril was initiated to manage the hypertension, and a hypercoagulation
evaluation included antithrombin III levels, protein C and S levels, factor V
Leiden mutation screen, and anti-cardiolipin antibodies. These studies were
ultimately normal. Urokinase was administered for 3 days via an intravenous
catheter in the leg. There was no change in the size of the clot, so a heparin
infusion was started and continued for 10 days. The size of the IVC clot
decreased, with resolution of the patient
's edema. The patient was eventually discharged receiving subcutaneous injections
of low-molecular-weight heparin and oral captopril.
III. Incidence and Epidemiology
Thrombotic events are rare in infants, and most are related to the presence of a
central venous catheter. In the Canadian and International Registry of Neonatal
Thrombosis, 21 cases of renal vein thrombosis, 39 cases of thrombosis of other
veins, and 33 arterial thrombotic events were reported from 85 neonatal
intensive care units over a 3-year period. Approximately 90% of cases not
involving the renal veins were associated with central venous catheters. The
cases of renal vein thrombosis were spontaneous, so it appears that this should
be considered a separate entity. A nationwide survey in Germany from 1992 to
1994 indicated the incidence of symptomatic renal vein thrombosis to be 2.2 per
100,000 live births. The incidence is higher among premature infants, and most
cases appear to occur within the first month of life. Some cases appear to
begin
in utero and can be detected within hours to days after birth.
Renal vein thrombosis is associated with disorders that lead to decreased renal
blood flow or increased blood viscosity. Associated conditions include
asphyxia, cyanotic heart disease, polycythemia, maternal diabetes, sepsis, and
shock. In this instance, the likely etiology was being an infant of a diabetic
mother.
There is growing evidence that infants with spontaneous abdominal thrombosis are
at significant risk for having a congenital hypercoagulable state. A study in
Frankfurt, Germany, found factor V mutations, protein C deficiency,
anti-thrombin deficiency, and methylene tetrahydrofolate reductase (MTHFR)
mutation in a prospective study of infants younger than 1 year old who
presented with symptomatic abdominal clots. Thirteen infants with renal vein
thrombosis were identified, and they were found to have an odds ratio of 10.9
for having at least one prothrombotic risk factor.
IV. Clinical Presentation
This infant demonstrated many of the symptoms and physical findings associated
with renal vein thrombosis. Obstruction of venous flow can lead to enlargement
of the kidney and a palpable abdominal mass. In this case, there was associated
obstruction of the IVC, which can lead to cool, mottled, and edematous lower
extremities. Renal function is often impaired, leading to diffuse edema and
sometimes hypertension. Frank blood, as in this case, should also prompt
consideration of thrombosis. Some infants with renal vein thrombosis have
bilateral involvement, so evaluation should not be limited to one side.
Thrombocytopenia during a thrombotic process results from platelet consumption.
V. Diagnostic Approach
Ultrasonography. Ultrasound is by far the most common procedure, because it is readily available
and noninvasive. In addition to assessing renal vein blood flow, enlargement
and increased echogenicity of the involved kidney may be seen. There are,
however, concerns about the sensitivity of ultrasound for looking at flow in
small veins such as those in an infant. A negative ultrasound study in the
setting of strong clinical suspicion should not be considered completely
reassuring.
Contrast angiography. Angiography has been used infrequently but may be helpful if the diagnosis is
uncertain.
Hypercoagulable evaluation. Consideration should also be given to evaluating the infant for a
hypercoagulable predisposition. The number of known genetic mutations affecting
proteins involved in the coagulation cascade continues to grow. As a result,
consultation with a hematologist is recommended to screen for appropriate
disorders and to determine the appropriate time for evaluation. Active
thrombosis can lead to consumption of many factors and give false results.
Evaluation should include determination of factor V mutations, protein C and
protein S levels, anti-thrombin activity, anti-cardiolipin antibodies, and
homocysteine levels. A hematologist may recommend additional studies.
VI. Treatment
As with diagnostic studies, there is limited information about appropriate
treatment for renal vein thrombosis. In the past, renal vein thrombosis was
frequently fatal, and recovery of renal function was unusual in those patients
who did survive. There are no recent studies evaluating the long-term morbidity
associated with renal vein thrombosis. In the Canadian and International
Registry of Neonatal Thrombosis, 62% of infants with renal vein thrombosis were
treated with supportive care only. The majority of the remaining infants were
treated with heparin infusions, as in this case. Many infants with
catheter-related clots have been treated with thrombolytic therapy such as
tissue plasminogen activator or urokinase, but there is very little information
about their utility in renal vein thrombosis. Low-molecular-weight heparin is a
relatively new drug available as a subcutaneous injection. It is likely to be
useful for outpatient care because of the ease of administration and the low
occurrence of bleeding complications. However, its use also is extrapolated
from treatment experience with other thrombotic events.
Other management strategies depend on the predisposing condition. Sepsis needs
to be considered and evaluated with appropriate cultures and antibiotic
coverage. Polycythemia needs to be assessed and an exchange transfusion
performed if it is determined to be the cause of the clot. Dehydration should
be promptly treated with intravenous fluids, and symptoms of shock need to be
managed with appropriate fluid resuscitation and pressor support. If congenital
heart disease is suspected, it should be evaluated with a hyperoxia test and
echocardiogram.
Lastly, symptoms resulting from the thrombosis itself need to be managed. Renal
function should be evaluated periodically, and resolution of the clot should be
monitored by ultrasonography. In this case, persistent hypertension was managed
with captopril. Survival usually depends on the severity of illness caused by
the underlying condition. Long-term consequences of renal vein thrombosis are
decreased glomerular flow rate, systemic hypertension, and tubular dysfunction
causing impaired urinary concentrating ability and phosphaturia with rickets.
VII. References
1. Bokenkamp A, von Kries R, Nowak-Gottl U, et al. Neonatal renal venous
thrombosis in Germany between 1992 and 1994: epidemiology, treatment and
outcome.
Eur J Pediatr 2000;159:44–48.
2. Brion LP, Berstein J, Spitzer A. Kidney and urinary tract. In: Fanaroff AA,
Martin RJ, eds.
Neonatal-perinatal medicine: diseases of the fetus and infant, 6th ed. St. Louis: Mosby, 1997:1564–1636.
3. Heller C, Schobess R, Kurnik K, et al. Abdominal venous thrombosis in
neonates and infants: role of prothrombotic risk factors
—a multicentre case-control study. Br J Haematol 2000;111:534–539.
4. Monagle P, Michelson AD, Bovill E, et al. Antithrombotic therapy in
children.
Chest 2001;119:s344–s370.
5. Schmidt B, Andrew M. Neonatal thrombosis: report of a prospective Canadian
and international registry.
Pediatrics 1995;96:939–944.
6. Tulassay T, Seri I, Evans J. Renal vascular disease in the newborn. In:
Taeusch HW, Ballard RA.
Avery's diseases of the newborn, 7th ed. Philadelphia: WB Saunders, 1998:1177–1187.
7. Tunnessen WW Jr. Signs and symptoms in pediatrics, 3rd ed. Philadelphia: Lippincott Williams & Wilkins, 1999.
Book Source Details
- Book Title: Pediatric Complaints and Diagnostic Dilemmas
- Author(s): Samir S Shah MD; Stephen Ludwig MD
- Year of Publication: 2003
- Copyright Details: Pediatric Complaints and Diagnostic Dilemmas, Copyright © 2003 Lippincott Williams & Wilkins.
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Copyright Details: Pediatric Complaints and Diagnostic Dilemmas, Copyright © 2008 Williams & Wilkins.
More About Causes of Darkened urine
» Next page: Dark Urine - Case 20-2: 15-Year-Old Boy (Pediatric Complaints and Diagnostic Dilemmas)
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