Fractional Excretion of Urea in Pediatric Patients with Acute Kidney Injury

Abstract

Objective: Fractional excretion of sodium (FeNa) and fractional excretion of urea (FeU) are used to differentiate prerenal and renal injuries in acute kidney injury (AKI). In this study, we aimed to compare the discriminative power of FeU with FeNa between prerenal and renal azotemia groups as well as among AKI stages according to pRIFLE criteria.

Material and Methods: Laboratory and medical records of 55 pediatric AKI patients who had the measurements of random urine excretions of urea, creatinine and sodium as well as serum urea, creatinine and sodium levels in order to calculate FeU and FeNa values at the time of AKI diagnosis were evaluated retrospectively. Patients were divided into prerenal and renal injury groups according to the clinical findings and laboratory data. Sensitivities and specifities of FeNa and FeU in differentiating prerenal versus renal injury were determined. FeNa and FeU values were compared in patients with different RIFLE stages.

Results: Among 55 pediatric AKI patients 31 were boys, 24 were girls. The mean age at the time of diagnosis was 71.1 ± 83.5 months (min-max: 1-216). When we grouped the patients as having FeU<35% and FeU≥35%, the difference between the numbers of the patients in prerenal and renal groups was significant (p=0.039). The sensitivity and specificity of FeU to determine prerenal vs renal injury were calculated as 50% and 77.1% respectively. When FeNa and FeU were used together (FeNa>1% and FeU>35%) in order to distinguish prerenal and renal injuries the specificity increased to 81% (p=0.020). Mean FeU was significantly different between AKI stages (p=0.022), and was higher in Injury and Failure stages when compared with the Risk stage.

Conclusion: Fractional urea excretion is as important as FeNa in evaluating children with AKI. We recommend to obtain FeU in pediatric AKI in order to differentiate prerenal and renal etiology and to differentiate the severity of the injury according to the AKI stages in order to arrange the treatment.

Keywords

• Acute kidney injury
• Children
• Fractional urea excretion
• pRIFLE

Pediatrik Akut Böbrek Hasarında Fraksiyone Üre Ekskresyonu

Abstract

Amaç: Fraksiyone sodyum ekskresyonu (FeNa) ile fraksiyone üre ekskresyonu (FeU) akut böbrek hasarında prerenal ve renal hasarı ayırt etmek için kullanılmaktadır. Bu çalışmada, FeNa ve FeU değerlerinin prerenal ve renal azotemi grupları ile pRIFLE kriterlerine göre akut böbek hasarı evrelerini ayırdetmedeki gücünü kıyaslamayı amaçladık.

Gereç ve Yöntemler: Akut böbrek hasarı tanısı sırasındaki FeU ve FeNa değerlerini hesaplamak amacıyla spot idrar üre, kreatinin ve sodyum ekskresyonları ile serum üre, kreatinin ve sodyum değerleri elde olunan 55 pediatrik akut böbrek hasarı hastasının laboratuvar ve klinik verileri retrospektif olarak değerlendirildi. Hastalar klinik ve laboratuvar bilgiler ışığında prerenal ve renal hasar grupları olarak ikiye ayrıldı. Prerenal ve renal hasarı ayırt etmede FeNa ve FeU testlerinin sensitivite ve spesifisiteleri hesaplandı. Farklı RIFLE evreleri olan hastalar arasında FeNa ve FeU yüzdeleri kıyaslandı.

Bulgular: Elli beş pediatrik akut böbrek hasarı hastasının 31’i erkek, 24’ü kızdı. Tanı anında ortalama yaş 71.1±83.5 ay (min-max: 1-216)’di. Hastaları FeU değerlerine göre FeU<%35 ve FeU ≥35% olarak iki gruba ayırdığımızda prerenal ve renal gruplardaki hasta sayıları arasındaki fark anlamlıydı (p=0.039). Prerenal ve renal hasar ayırımını belirlemede FeU testinin sensitivitesi %50, spesifisitesi %77.1 olarak hesaplandı. FeNa ve FeU birlikte kullanıldığında (FeNa >%1 ve FeU >%35) spesifisite %81’e yükseldi (p=0.020). FeU ortalaması akut böbrek hasarı evreleri arasında anlamlı olarak farklıydı (p=0.022) ve Risk evresiyle kıyaslandığında Injury ve Failure evrelerinde daha yüksekti.

Sonuç: Fraksiyone üre ekskresyonu, pediatrik akut böbrek hasarı olan çocukların değerlendirilmesinde FeNa kadar önemlidir. Prerenal ve renal hasarı ayırt etmede ve akut böbrek hasarı evrelerine göre böbrek hasarının şiddetinin belirlenmesinde FeU değerinin elde edilmesini öneriyoruz.

Keywords

• Akut böbrek hasarı
• fraksiyone üre ekskresyonu
• pRIFLE

References

1. Fahimi D, Mohajeri S, Hajizadeh N, Madani A, Esfahani ST, Ataei N, et al. Comparison between fractional excretions of urea and sodium in children with acute kidney injury. Pediatr Nephrol 2009;24:2409–12.
2. Schrier RW, Wang W, Poole B, Mitra A. Acute renal failure: definitions, diagnosis, pathogenesis, and therapy. J Clin Invest 2004;114:5–14. Hilton R. Acute renal failure. BMJ 2006;333:786–90.
3. Diskin JB, Walker CB, Oberle MD, Diskin CJ. Use of the Fractional Excretion of Urea in an Azotemic Nonoliguric State: Type 1 Cardiorenal Syndrome. Ther Apher Dial 2018;22:319-24.
4. Pépin MN, Bouchard J, Legault L, Ethier J. Diagnostic Performance of Fractional Excretion of Urea and Fractional Excretion of Sodium in the Evaluations of Patients With Acute Kidney Injury With or Without Diuretic Treatment. Am J Kidney Dis 2007;50:566-53.
5. Akcan-Arikan A, Zappitelli M, Loftis LL, Washburn KK, Jefferson LS, Goldstein SL. Modified RIFLE criteria in critically ill children with acute kidney injury. Kidney Int 2007;71:1028–35.
6. Patidar KR, Kang L, Bajaj JS, Carl D, Sanyal AJ. Fractional excretion of urea: A simple tool for the differential diagnosis of acute kidney injury in cirrhosis. Hepatology 2018;68:224-33.
7. Esson ML, Schrier RW. Diagnosis and treatment of acute tubular necrosis. Ann Intern Med 2002;137:744–52.
8. Fujita H, Shinjoh M, Ishii T, Awazu M. Utility of fractional excretion of urea in the differential diagnosis of acute kidney injury in children. Pediatr Nephrol 2016;31:1349-53.

9. Morgan DB, Carver ME, Payne RB. Plasma creatinine and urea: creatinine ratio in patients with raised plasma urea. Br Med 1977;2:929–32.
10. Steiner RW. Interpreting the fractional excretion of sodium. Am J Med 1984;77:699–702.
11. Diamond JR, Yoburn DC. Nonoliguric acute renal failure associated with a low fractional excretion of sodium. Ann Intern Med 1982;96:597–600.
12. Carvounis CP, Nisar S, Guro-Razuman S. Significance of the fractional excretion of urea in the differential diagnosis of acute renal failure. Kidney Int 2002;62:2223–9.
13. Westhuyzen J, Endre ZH, Reece G, Reith DM, Saltissi D, Morgan TJ. Measurement of tubular enzymuria facilitates early detection of acute renal impairment in the intensive care unit. Nephrol Dial Transplant 2003;18:543-51.
14. Corey HE, Greifer I, Greenstein SM, Tellis V, Spitzer A. The fractional excretion of urea: a new diagnostic test for acute renal allograft rejection. Pediatr Nephrol 1993;7:268–72.
15. Fushimi K, Shichiri M, Marumo F. Decreased fractional excretion of urate as an indicator of prerenal azotemia. Am J Nephrol 1990;10:489–94.
16. Steinhäuslin F, Burnier M, Magnin JL, Munafo A, Buclin T, Diezi J, et al. Fractional excretion of trace lithium and uric acid in acute renal failure. J Am Soc Nephrol 1994; 4:1429–37.
17. Diskin CJ, Stokes TJ, Dansby LM, Radcliff L, Carter TB. Toward the optimal clinical use of the fraction excretion of solutes in oliguric azotemia. Ren Fail 2010;32:1245-54.
18. Kaplan AA, Kohn OF. Fractional excretion of urea as a guide to renal dysfunction. Am J Nephrol 1992;12: 49–54.
19. Brady HR, Brenner BM, Clarkson MR, Lieberthal W. Acute renal failure. In Brenner BM (editor): The Kidney. Philadelphia, WB Saunders, pp 2000; 1201-62.
20. Rose BD, Post TW. Clinical physiology of acid-base and electrolyte disorders. Vol 427, 5th edn. McGraw-Hill, New York 2001;406-9.
21. Musch W, Verfaillie L, Decaux G. Age-related increase in plasma urea level and decrease in fractional urea excretion: clinical application in the syndrome of inappropriate secretion of antidiuretic hormone. Clin J Am Soc Nephrol 2006;1:909–14.
22. Schmidt C, Höcherl K, Bucher M. Cytokinemediated regulation of urea transporters during experimental endotoxemia. Am J Physiol Renal Physiol 2007;292:1479–89.
23. Bardanzellu F, Marcialis MA, Frassetto R, Melis A, Fanos V. Differential diagnosis between syndrome of inappropriate antidiuretic hormone secretion and cerebral/renal salt wasting syndrome in children over 1 year: proposal for a simple algorithm. Pediatr Nephrol 2022:37:1469-78.
24. Stiburkova B, Bleyer AJ. Changes in serum urate and urate excretion with age. Adv Chronic Kidney Dis 2012;19:372-6.