Pediatric Nephrology

, Volume 7, Issue 3, pp 268–272 | Cite as

The fractional excretion of urea: a new diagnostic test for acute renal allograft rejection

  • Howard E. Corey
  • Ira Greiter
  • Stuart M. Greenstein
  • Vivian Tellis
  • Adrian Spitzer
Original Article


Fractional excretion of fsodium (FENa) has been used in the diagnosis of acute renal allograft failure on the assumption that poor allograft perfusion should result in a low FENa. However, many patient receive medications which affect the active transport of Na+ and thus FENa. In contrast, the fractional excretion of urea (FEurea) is mostly dependent on passive forces and is therefore less influenced by drug therapy. To test the hypothesis that FEurea might be more useful than FENa in evaluating graft failure, we compared FEurea with FENa during 79 episodes of acute renal allograft dysfunction due to acute rejection (AR), cyclosporine nephrotoxicity (CsA-Nx), viral infection, or bacterial infection in 32 children and young adults with renal transplants. There was no significant difference between groups in FENa. However, FEurea was significantly lower (P<0.05) in patients with CsA-Nx (32.6±1.9%) and viral infection (32.9±3.2%) than those with AR (45.1±1.7%) or bacterial infection (38.9±2.5%). FEurea was < 35% in 20 of 28 (71.4%) episodes of CsA-Nx and 8 of 11 (72.2%) of viral infection, but only 5 of 36 (13.9%) of AR (P<0.05). FEurea was also measured during stable graft function, 7–14 days prior to allograft dysfunction. CsA-Nx was associated with a 30.5±8.3% decrease in FEurea. FEurea did not change in patients with AR. Based on these findings, we present an algorithm to aid in the differential diagnosis of acute renal allograft failure.

Key words

Transplantation Rejection Fractional excretion Urea 


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  1. 1.
    Espinel CH (1976) The FENa test: use in the differential diagnosis of acute renal failure. JAMA 236: 579–581PubMedGoogle Scholar
  2. 2.
    Hong CD, Kappor BS, First MR, Pollack VE, Alexander JW (1979) Fractional excretion of sodium after renal transplantation. Kidney Int 16: 167–178PubMedGoogle Scholar
  3. 3.
    Shabtai M, Anaise D, Miller F, Oster ZH, Atkins H, Waltzer WC, Yland MJ, Rapaport FT (1989) The predictive value of renal cortical perfusion indices during acute allograft rejection crisis. Transplant Proc 21: 1881–1900Google Scholar
  4. 4.
    Chan MK, Wong KK, Cheng KP, Li MK (1988) Clinical prevalence and significance of electrolyte disorders in cyclosporine A-treated patients. Transplant Proc 20: 705–708PubMedGoogle Scholar
  5. 5.
    Dieperink H, Leyssac PP, Kemp E, Starklint H, Frandsen NE, Tvende N, Moller J, Buchler Frederiksen P, Rossing N (1987) Nephrotoxicity of cyclosporin A in humans: effects on glomerular filtration and tubular reabsorption rates. Eur J Clin Invest 17: 493–496PubMedGoogle Scholar
  6. 6.
    Morales JM, Andres A, Prieto C, Ruilope LM, Alcazar A, Oliet A, Praga M, Rodicio JL (1987) Fractional excretion of sodium represents an index of cyclosporine nephrotoxicity in the early post-transplant period. Transplant Proc 19: 4005–4007PubMedGoogle Scholar
  7. 7.
    Morales JM, Andres A, Alcazar JM, Prieto I, de Tueste D, Ruilope LM, Rodicio JL (1988) Usefulness of the fractional excretion of sodium as index of cyclosporine nephrotoxicity in renal transplantation. Transplant Proc 20: 691–699PubMedGoogle Scholar
  8. 8.
    Shah BV, Hong CD, First MR (1990) Effect of cyclosporine on fractional excretion of sodium in renal transplant patients. Clin Transplant 4: 102–107Google Scholar
  9. 9.
    Tonnesen AS, Hammer RW, Weinmann EJ (1983) Cyclosporine and sodium and potassium excretion in the rat. Transplant Proc 15: 2730–2735Google Scholar
  10. 10.
    Kaplan AA, Kohn OF (1990) The fractional excretion of urea to evaluate renal, dysfunction (abstract). J Am Soc Nephrol 1: 335Google Scholar
  11. 11.
    Hanley JA, McNeil BJ (1982) Meaning and use of the area under a receiver operating characteristic (ROC) curve. Radiology 143: 29–36PubMedGoogle Scholar
  12. 12.
    Kudo LH, Van Baak AA, Rocha AS (1990) Effect of furosemide on water and urea transport in cortical and inner medullary collecting duct. Kidney Int 37: 1248–1255PubMedGoogle Scholar
  13. 13.
    Armsen T, Reinhart HW (1991) Transtubular movement of urea at different degrees of water diuresis. Pflugers Arch 326: 270–280Google Scholar
  14. 14.
    Larson TS, Jamison RL (1989) Renal excretion of urea. In: Massry SG, Glassock RJ (eds) Textbook of nephrology. Williams and Wilkins, Baltimore, pp. 85–87Google Scholar
  15. 15.
    Morgan T, Berliner RW (1968) The permeability of the loop of Henle, vasa recta, and collecting duct to water, urea, and sodium. Am J Physiol 215: 108–115PubMedGoogle Scholar
  16. 16.
    Stephenson JL (1972) Concentration of urine in a central core model of the renal counterflow system. Kidney Int 2: 85–94PubMedGoogle Scholar
  17. 17.
    Sands JM, Nonoguchi H, Knepper MA (1987) Vasopressin effects urea and H2O transport in inner medulalary collecting duct segments. Am J Physiol 253: F823-F832PubMedGoogle Scholar
  18. 18.
    Curtis JJ, Luke RG, Dubovsky E, Diethelm AG, Whelchel JD, Jones P (1986) Cyclosporin-A in therapeutic doses increases renal allograft vascular resistance. Lancet II: 477–479Google Scholar
  19. 19.
    Curtis JJ, Laskow DA (1988) Cyclosporine-induced nephrotoxicity: pathophysiology of reduced blood flow. Transplant Proc 20: 540–543PubMedGoogle Scholar
  20. 20.
    Kaskel FJ, Devarajan R, Arbeit LA, Partin JS, Moore LC (1987) Cyclosporine nephrotoxicity: sodium excretion, autoregulation and angiotensin II. Am J Physiol 252: F733-F742PubMedGoogle Scholar
  21. 21.
    Kaskel FJ, Devarajan P, Arbeit LA, Moore LC (1988) Effects of cyclosporine on renal hemodynamics and autoregulation in rats. Transplant Proc 20: 603–609Google Scholar
  22. 22.
    Murray BM, Paller MS, Ferris TF (1985) Effect of cyclosporine administration on renal hemodynamics in conscious rat. Kidney Int 28: 767–774PubMedGoogle Scholar
  23. 23.
    Sabatini M, De Nicola, Uccello F, Russo D, Conte G, Dal Canton A, Andreucci VE (1990) Absence of acute nephrotoxicity with low doses of cyclosporin: experimental study in the rat. Nephrol Dial Transplant 5: 69–74Google Scholar
  24. 24.
    Barros EJG, Boim MA, Ajzen H, Ramos OL, Schor N (1987) Glomerular hemodynamics and hormonal participation on cyclosporine nephrotoxicity. Kidney Int 32: 19–25PubMedGoogle Scholar
  25. 25.
    Whelchel JD, Delaney VB, O'Brian D, Ling B, Fekete P (1988) Efficacy and cost of the various test used in the diagnosis of rejection in cadaveric renal transplant recipients (abstract). Kidney Int 35: 526Google Scholar
  26. 26.
    Winchester JF, Gelfand MC, Foegh ML, Helfrich GB, Schreiner GE (1983) Early indicators of renal allograft rejection. Kidney Int 24: S34-S40Google Scholar
  27. 27.
    Gray W, Derek R, Richardson A, Hughes D, Fuggle S, Dunhill M, Higgins R, McWhinnie D, Morris PJ (1992) A prospective randomized, blind comparison of three biopsy technique in the management of patients after renal transplantation. Transplantation 566: 1126–1232Google Scholar

Copyright information

© IPNA 1993

Authors and Affiliations

  • Howard E. Corey
    • 1
  • Ira Greiter
    • 1
  • Stuart M. Greenstein
    • 2
  • Vivian Tellis
    • 2
  • Adrian Spitzer
    • 1
  1. 1.Department of PediatricsAlbert Einstein College of Medicine/Montefiore Medical CenterNew YorkUSA
  2. 2.Department of SurgeryAlbert Einstein College of Medicine/Montefiore Medical CenterNew YorkUSA

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