Fractional Excretion of Urea in a Pediatric Population

1
Fractional Excretion of Urea in a Pediatric
Population

• Neal B. Blatt, Amy McCammond, Jennifer L. Liedel,
  and Madelyn D. Kahana
• University of Chicago
• June 8, 2005

2
Abstract Despite advancements in medical care,
acute renal failure (ARF) remains a serious
medical condition. ARF is characterized by
elevation of serum blood urea nitrogen (BUN) and
creatinine with a fall in urine output. These
clinical measurements are not specific to ARF,
and can also be associated with prerenal azotemia
(PRA). It is critical to distinguish between
these two clinical entities because their
treatment is very different. ARF is treated with
volume restriction and supportive care whereas
PRA can require aggressive intravenous hydration
to restore perfusion to the kidney. Over the
past 50 years, medicine has searched for a
reliable index to distinguish between ARF and
PRA. In adults, the fractional excretion of urea
(FEUr) has been proposed as an index that can
reliably distinguish between these two
conditions. Since there is no data on FEUr in
children, this study determined FEUr in 53
children seen within the University of Chicago
Hospital system. After obtaining informed
consent, a urine sample from each patient was
collected and analyzed for the concentrations of
urea, sodium and creatinine. The children were
separated into three categories based on clinical
assessment 1. euvolemic (normal controls), 2.
pre-renal (intravascularly dehydrated), or 3.
ARF. The distribution of FEUr was significantly
different between children who were euvolemic vs.
pre-renal (age 6 mo - 3yr, p 0.041 age 3 -18
yr, p 0.002). Interestingly, we also observed
that FEUr was significantly elevated in children
with diabetic ketoacidosis relative to other
pre-renal states (p 0.001). These studies
suggest FEUr may be a useful clinical tool in
children as well as adults, and justify further
investigations.
3
Background(FE Na vs. FE Urea)

• No reliable index exists to distinguish ARF and
  PRA
• The fractional excretion of sodium (FENa) was the
  first marker described to help distinguish
  between ARF and PRA.
• In an intact kidney, less than 1 of the filtered
  sodium is excreted.
• With damage to the normal tubular resorptive
  mechanisms, as seen in ARF, FENa is in excess of
  1.
• PRA is associated with FENa of lt1 and ARF is
  associated with FENa gt1.
• The use of FENa is complicated by concurrent use
  of loop diuretics which act by altering salt
  handling in the kidney, and making FENa
  unreliable
• Fractional Excretion of Urea (FEUr) proposed as
  new index to distinguish ARF and PRA
• FEUr 35 is associated with PRA and FEUr gt 50
  associated with ARF
• FEUr not affected by loop diuretics
• No prior studies of FEUr in children exist
• Renal function in children develops over first
  several years of life

4
Background(Urea Transporters)

• Membrane spanning proteins located in collecting
  ducts of kidney
• Co-localize with aquaporins in kidney
• Expression positively regulated by vasopressin
  (ADH)
• Expression unaffected by loop diuretics
• Provide molecular framework to understand
  behavior of FEUr

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Physiology of Urea Excretion
6
Methods Enrollment and Sample Collection The
study protocol, design, and consent forms were
approved by the University of Chicago Hospital's
Institutional Review Board under protocol 13679B.
Potential study subjects were identified by their
primary treating physician, who then contacted
study personnel to obtain informed consent. The
only prerequisite for enrollment in the study was
that a serum sodium, urea, and creatinine be
drawn as part of routine medical care for the
child. After enrollment, a urine sample was
analyzed for the concentrations of sodium, urea,
and creatinine in the University of Chicago
Hospitals lab using standard protocols. Urine
samples were only used if they were collected
within several hours of the serum
measurements. Study Design Based on the
development of kidney function, children were
recruited into one of three age groups infant (2
weeks through 6 months), toddler (6 months
through 3 years), or pediatric (3 to 18 years).
Within an age group, each child was placed into
one of three categories based on the clinical
assessment of the study personnel and primary
treating physicians. These categories reflected
the patient's volume status and diagnosis
euvolemic (normal controls), pre-renal
(intravascularly dehydrated), or ARF. Samples
were excluded from the analysis if (1) the
patient was diagnosed with diabetes insipidus
(2) the urine creatinine concentration within the
sample was less than 10 mg/dL or (3) the patient
had underlying renal impairment (from a
congenital anomaly or toxic ingestion). Using
these criteria, eight (out of a total of 53)
children were excluded from the analysis.
7
Methods Data Analysis The fractional
excretions of both sodium and urea were
calculated using the formula below.
Urine conc (x) Serum Creatinine
Fractional Excretion (x)
100 Serum
conc (x) Urine Creatinine Statistical
analysis was performed using the student's t-test
(2-tailed) and chi-square tests.
8
Patient Characteristics
Note The values above represent the number of
patients in each category and include a total of
25 male and 20 female subjects.
9
Results Toddler Age Group
Age
FE Urea
FE Na
Euvolemic n4
1.8 0.6
66.4 24.9
1.73 1.58
Pre-Renal n4
1.3 0.5 p 0.24
33.9 2.7 p 0.041
0.61 0.82 p 0.26
All values reported are mean SD. p values
reported for pre-renal patients are compared to
euvolemic patients.
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Chi-Square Analysis(Toddler Age Group)
FE Urea
FE Na
35
gt 35
1.0
gt 1.0
Pre-Renal
3
1
4
0
Euvolemic
0
4
2
2
p 0.005
p 0.46
11
Results Pediatric Age Group
Age
FE Urea
FE Na
Euvolemic n12
10.0 3.4
51.1 12.2
1.10 0.67
Pre-Renal n13
9.2 3.2 p 0.52
33.2 13.8 p 0.002
0.33 0.33 p 0.001
ARF n3
16.3 2.6
41.4 17.5 p 0.34
2.35 2.15 p 0.003
DKA n4
14.1 3.2
76.0 31.3 p 0.001
2.07 1.72 p 0.007
All values reported are mean SD. Reported p
values for pre-renal patients are referenced to
euvolemic patients. All other p values reported
are compared to pre-renal patients.
12
Chi-Square Analysis(Pediatric Age Group)
FE Urea
FE Na
35
gt 35
1.0
gt 1.0
Pre-Renal
8
5
13
0
Euvolemic
0
12
6
6
p 0.001
p 0.004
13
Conclusions

• FE Urea distinguishes pre-renal states from
  euvolemic states in both the toddler and
  pediatric age groups
• FE Urea behaves distinctly in diabetic
  ketoacidosis
• At the current level of recruitment, the study
  cannot
• discuss the behavior of FE Urea in children with
  ARF
• discuss the behavior of FE Urea in infants less
  than 6 mo old
• determine the sensitivity and specificity for FE
  Urea in children
• The data justifies further study of the
  usefulness of FE Urea in children

Acknowledgement This study was funded by a grant
from the Chairmans Fund for Resident Research,
University of Chicago, Department of Pediatrics.
14
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