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
Neal B. Blatt, Amy McCammond, Jennifer L. Liedel, and Madelyn D. Kahana
University of Chicago
June 8, 2005
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.
highPhysiology of Urea Excretion
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.
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.
(2 wk - 6 mo)
(6 mo - 3 yr)
(3 -18 yr)
Note: The values above represent the number of patients in each category and include a total of 25 male and 20 female subjects.
1.8 ± 0.6
66.4 ± 24.9
1.73 ± 1.58
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.
≤ 35 %
> 1.0 %
≤ 1.0 %
p = 0.005
p = 0.46
10.0 ± 3.4
51.1 ± 12.2
1.10 ± 0.67
9.2 ± 3.2
p = 0.52
33.2 ± 13.8
p = 0.002
0.33 ± 0.33
p = 0.001
16.3 ± 2.6
41.4 ± 17.5
p = 0.34
2.35 ± 2.15
p = 0.003
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.
≤ 35 %
> 1.0 %
≤ 1.0 %
p = 0.001
p = 0.004
Acknowledgement: This study was funded by a grant from the Chairman’s Fund for Resident Research, University of Chicago, Department of Pediatrics.
Baum M. 2003. Development of renal function. In Rudolph's Pediatrics. C. D. Rudolph, A. M. Rudolph, M. K. Hostetter, G. Lister, and N. J. Siegel, eds. McGraw-Hill, New York, p. 1632-1638.
Canton AD, Fuiano G, Conte G, Terribile M, Sabbatini M, Cianciaruso B, and Andreucci VE. 1985. Mechanism of increased plasma urea after direutic therapy in uraemic patients. Clin. Sci. 68:255-261.
Carvounis CP, Nisar S, and Guro-Razuman S. 2002. Significance of the fractional excretion of urea in the differential diagnosis of acute renal failure. Kidney Int. 62:2223-2229.
Espinel CH, and Gregory AW. 1980. Differential diagnosis of acute renal failure. Clin. Nephrol. 13:73-77.
Espinel CH. 1976. The FENa Test. Use in the differential diagnosis of acute renal failure. J. A. M. A. 236:579-581.
Kaplan AA, and Kohn OF. 1992. Fractional excretion of urea as a guide to renal dysfunction. Am. J. Nephrol. 12:49-54.
Miller TR, Anderson RJ, Linas SL, Henrich WL, Berns AS, Gabow PA, and Schrier RW. 1978. Urinary diagnostic indices in acute renal failure. A prospective study. Ann. Intern. Med. 89:47-50.
Nanji AJ. 1981. Increase fractional excretion of sodium in prerenal azotemia: need for careful interpretation. Clin. Chem. 27:1314- 1315.
Nielsen S, Frokiaer J, Marples D, Kwon TH, Agre P, and Knepper M. 2002. Aquaporins in the kidney: from molecules to medicine. Physiol Rev 82:205-244.
Rubin MI, Bruck E, Rapoport M, Snively M, McKay H, and Baumler A. 1949. Maturation of renal function in childhood: clearance studies. J. Clin. Invest. 28:1144-1162.
Sands JM. 2003. Molecular Mechanisms of Urea Transport. J. Membrane Biol. 191:149-163.
Schrier RW, Wang W, Poole B, and Mitra A. 2004. Acute renal failure: definitions, diagnosis, pathogenesis, and therapy. J. Clin. Invest. 114:5-14.
West JR, Smith HW, and Chasis H. 1948. Glomerular filtration rate, effective renal blood flow, and maximal tubular excretory capacity in infancy. J. Pediatr. 32:10-18.