Fractional excretion of urea in a pediatric population
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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. Abstract

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Fractional Excretion of Urea in a Pediatric Population

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Fractional excretion of urea in a pediatric population

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


Fractional excretion of urea in a pediatric population

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.


Background fe na vs fe urea

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 <1% and ARF is associated with FENa >1%.

    • 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 > 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


Background urea transporters

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


Physiology of urea excretion

Intravascular

Volume Status

Vasopressin

Concentration

Urea Channel

Expression

Urea

Excretion

Pre-Renal

Azotemia

dry

high

high

low

Acute Renal

Failure

volume

overload

low

low

high

Physiology of Urea Excretion


Fractional excretion of urea in a pediatric population

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.


Fractional excretion of urea in a pediatric population

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.


Patient characteristics

Pre-Renal

Euvolemic

ARF

DKA

Infant

(2 wk - 6 mo)

2

3

0

0

Toddler

(6 mo - 3 yr)

4

4

0

0

Pediatric

(3 -18 yr)

12

13

3

4

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.


Results toddler age group

Results: Toddler Age Group

Age

FE Na

FE Urea

Euvolemic

n=4

1.8 ± 0.6

66.4 ± 24.9

1.73 ± 1.58

Pre-Renal

n=4

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.


Chi square analysis toddler age group

Chi-Square Analysis(Toddler Age Group)

FE Urea

FE Na

≤ 35 %

> 35%

> 1.0 %

≤ 1.0 %

Pre-Renal

3

1

4

0

Euvolemic

0

4

2

2

p = 0.005

p = 0.46


Results pediatric age group

Results: Pediatric Age Group

Age

FE Na

FE Urea

Euvolemic

n=12

10.0 ± 3.4

51.1 ± 12.2

1.10 ± 0.67

Pre-Renal

n=13

9.2 ± 3.2

p = 0.52

33.2 ± 13.8

p = 0.002

0.33 ± 0.33

p = 0.001

ARF

n=3

16.3 ± 2.6

41.4 ± 17.5

p = 0.34

2.35 ± 2.15

p = 0.003

DKA

n=4

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.


Chi square analysis pediatric age group

Chi-Square Analysis(Pediatric Age Group)

FE Urea

FE Na

≤ 35 %

> 35%

> 1.0 %

≤ 1.0 %

Pre-Renal

8

5

13

0

Euvolemic

0

12

6

6

p = 0.001

p = 0.004


Conclusions

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 Chairman’s Fund for Resident Research, University of Chicago, Department of Pediatrics.


Fractional excretion of urea in a pediatric population

References

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