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Urine biochemistry assessment in critically ill patients: controversies and future perspectives

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Abstract

In the past, urine biochemistry was a major tool in acute kidney injury (AKI) management. Classic papers published some decades ago established the values of the urine indices which were thought to distinguish “pre-renal” (functional) AKI attributed to low renal perfusion and “renal” (structural) AKI attributed to acute tubular necrosis (ATN). However, there were a lot of drawbacks and limitations in these studies and some recent articles have questioned the utility of measuring urine electrolytes especially because they do not seem to adequately inform about renal perfusion nor AKI duration (transient vs. persistent). At the same time, the “pre-renal” paradigm has been consistently criticized because hypoperfusion followed by ischemia and ATN does not seem to explain most of the AKI developing in critically ill patients and distinct AKI durations do not seem to be clearly related to different pathophysiological mechanisms or histopathological findings. In this new context, other possible roles for urine biochemistry have emerged. Some studies have suggested standardized changes in the urine electrolyte composition preceding increases in serum creatinine independently of AKI subsequent duration, which might actually be due to intra-renal microcirculatory changes and activation of sodium-retaining mechanisms even in the absence of impaired global renal blood flow. In the present review, the points of controversy regarding urine biochemistry assessment were evaluated as well as future perspectives for its role in AKI monitoring. An alternative approach for the interpretation of measured urine electrolytes is proposed which needs further larger studies to be validated and incorporated in daily ICU practice.

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References

  1. Schrier RW. Diagnostic value of urinary sodium, chloride, urea, and flow. J Am Soc Nephrol. 2011;22(9):1610–3.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. 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(10):1245–54.

    Article  PubMed  Google Scholar 

  3. Miller TR, Anderson RJ, Linas SL, Henrich WL, Berns AS, Gabow PA, Schrier RW. Urinary diagnostic indices in acute renal failure: a prospective study. Ann Intern Med. 1978;89(1):47–50.

    Article  CAS  PubMed  Google Scholar 

  4. Espinel CH. The FENa test. Use in the differential diagnosis of acute renal failure. JAMA. 1976;236(6):579–81.

    Article  CAS  PubMed  Google Scholar 

  5. Bellomo R, Wan L, Langenberg C, May C. Septic acute kidney injury: new concepts. Nephron Exp Nephrol. 2008;109(4):e95–100.

    Article  PubMed  Google Scholar 

  6. Prowle J, Bagshaw SM, Bellomo R. Renal blood flow, fractional excretion of sodium and acute kidney injury: time for a new paradigm? Curr Opin Crit Care. 2012;18(6):585–92.

    Article  PubMed  Google Scholar 

  7. Rosen S, Heyman SN. Difficulties in understanding human “acute tubular necrosis”: limited data and flawed animal models. Kidney Int. 2001;60(4):1220–4.

    Article  CAS  PubMed  Google Scholar 

  8. Langenberg C, Bagshaw SM, May CN, Bellomo R. The histopathology of septic acute kidney injury: a systematic review. Crit Care. 2008;12(2):R38.

    Article  PubMed  PubMed Central  Google Scholar 

  9. Langenberg C, Wan L, Egi M, May CN, Bellomo R. Renal blood flow in experimental septic acute renal failure. Kidney Int. 2006;69(11):1996–2002.

    Article  CAS  PubMed  Google Scholar 

  10. Langenberg C, Wan L, Bagshaw SM, Egi M, May CN, Bellomo R. Urinary biochemistry in experimental septic acute renal failure. Nephrol Dial Transplant. 2006;21(12):3389–97.

    Article  CAS  PubMed  Google Scholar 

  11. Bagshaw SM, Bennett M, Devarajan P, Bellomo R. Urine biochemistry in septic and non-septic acute kidney injury: a prospective observational study. J Crit Care. 2013;28(4):371–8.

    Article  CAS  PubMed  Google Scholar 

  12. Bellomo R, Bagshaw S, Langenberg C, Ronco C. Pre-renal azotemia: a flawed paradigm in critically ill septic patients? Contrib Nephrol. 2007;156:1–9.

    Article  PubMed  Google Scholar 

  13. Bagshaw SM, Langenberg C, Bellomo R. Urinary biochemistry and microscopy in septic acute renal failure: a systematic review. Am J Kidney Dis. 2006;48(5):695–705.

    Article  CAS  PubMed  Google Scholar 

  14. Natalini G, Rosano A, Militano CR, Di Maio A, Ferretti P, Bertelli M, de Giuli F, Bernardini A. Prediction of arterial pressure increase after fluid challenge. BMC Anesthesiol. 2012;12:3.

    Article  PubMed  PubMed Central  Google Scholar 

  15. Zafrani L, Ince C. Microcirculation in acute and chronic kidney diseases. Am J Kidney Dis. 2015;66(6):1083–94.

    Article  PubMed  Google Scholar 

  16. Zafrani L, Payen D, Azoulay E, Ince C. The microcirculation of the septic kidney. Semin Nephrol. 2015;35(1):75–84.

    Article  CAS  PubMed  Google Scholar 

  17. Matejovic M, Ince C, Chawla LS, Blantz R, Molitoris BA, Rosner MH, Okusa MD, Kellum JA, Ronco C, Group AXW. Renal hemodynamics in AKI: in search of new treatment targets. J Am Soc Nephrol. 2016;27(1):49–58.

  18. Vanmassenhove J, Glorieux G, Hoste E, Dhondt A, Vanholder R, Van Biesen W. Urinary output and fractional excretion of sodium and urea as indicators of transient versus intrinsic acute kidney injury during early sepsis. Crit Care. 2013;17(5):R234.

    Article  PubMed  PubMed Central  Google Scholar 

  19. Vanmassenhove J, Glorieux G, Hoste E, Dhondt A, Vanholder R, Van Biesen W. AKI in early sepsis is a continuum from transient AKI without tubular damage over transient AKI with minor tubular damage to intrinsic AKI with severe tubular damage. Int Urol Nephrol. 2014;46(10):2003–8.

    Article  CAS  PubMed  Google Scholar 

  20. Pons B, Lautrette A, Oziel J, Dellamonica J, Vermesch R, Ezingeard E, Mariat C, Bernardin G, Zeni F, Cohen Y, et al. Diagnostic accuracy of early urinary index changes in differentiating transient from persistent acute kidney injury in critically ill patients: multicenter cohort study. Crit Care. 2013;17(2):R56.

    Article  PubMed  PubMed Central  Google Scholar 

  21. Darmon M, Vincent F, Dellamonica J, Schortgen F, Gonzalez F, Das V, Zeni F, Brochard L, Bernardin G, Cohen Y, et al. Diagnostic performance of fractional excretion of urea in the evaluation of critically ill patients with acute kidney injury: a multicenter cohort study. Crit Care. 2011;15(4):R178.

    Article  PubMed  PubMed Central  Google Scholar 

  22. Dewitte A, Biais M, Petit L, Cochard JF, Hilbert G, Combe C, Sztark F. Fractional excretion of urea as a diagnostic index in acute kidney injury in intensive care patients. J Crit Care. 2012;27(5):505–10.

    Article  PubMed  Google Scholar 

  23. Varela CF, Greloni G, Schreck C, Bratti G, Medina A, Marenchino R, Pizarro R, Belziti C, Rosa-Diez G. Assessment of fractional excretion of urea for early diagnosis of cardiac surgery associated acute kidney injury. Ren Fail. 2015;37(10):327–31.

    Article  CAS  PubMed  Google Scholar 

  24. Wlodzimirow KA, Abu-Hanna A, Royakkers AA, Spronk PE, Hofstra LS, Kuiper MA, Schultz MJ, Bouman CS. Transient versus persistent acute kidney injury and the diagnostic performance of fractional excretion of urea in critically ill patients. Nephron Clin Pract. 2014;126(1):8–13.

    Article  CAS  PubMed  Google Scholar 

  25. Perinel S, Vincent F, Lautrette A, Dellamonica J, Mariat C, Zeni F, Cohen Y, Tardy B, Souweine B, Darmon M. Transient and persistent acute kidney injury and the risk of hospital mortality in critically ill patients: results of a multicenter cohort study. Crit Care Med. 2015;43(8):e269–75.

    Article  PubMed  Google Scholar 

  26. Maciel AT, Park M, Macedo E. Physicochemical analysis of blood and urine in the course of acute kidney injury in critically ill patients: a prospective, observational study. BMC Anesthesiol. 2013;13(1):31.

    Article  PubMed  PubMed Central  Google Scholar 

  27. Maciel AT, Nassar AP, Vitorio D. Very transient cases of acute kidney injury in the early postoperative period after cardiac surgery: the relevance of more frequent serum creatinine assessment and concomitant urinary biochemistry evaluation. J Cardiothorac Vasc Anesth. 2016;30(1):56–63.

    Article  CAS  PubMed  Google Scholar 

  28. Maciel AT, Vitório D. Urine biochemistry in the early postoperative period after cardiac surgery: role in acute kidney injury monitoring. Case Rep Crit Care. 2013;2013:103450.

    PubMed  PubMed Central  Google Scholar 

  29. Nejat M, Pickering JW, Devarajan P, Bonventre JV, Edelstein CL, Walker RJ, Endre ZH. Some biomarkers of acute kidney injury are increased in pre-renal acute injury. Kidney Int. 2012;81(12):1254–62.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Bayly WM, Brobst DF, Elfers RS, Reed SM. Serum and urinary biochemistry and enzyme changes in ponies with acute renal failure. Cornell Vet. 1986;76(3):306–16.

    CAS  PubMed  Google Scholar 

  31. Langenberg C, Wan L, Egi M, May CN, Bellomo R. Renal blood flow and function during recovery from experimental septic acute kidney injury. Intensive Care Med. 2007;33(9):1614–8.

    Article  PubMed  Google Scholar 

  32. Jones LW, Weil MH. Water, creatinine and sodium excretion following circulatory shcok wtih renal failure. Am J Med. 1971;51(3):314–8.

    Article  CAS  PubMed  Google Scholar 

  33. Maciel AT, Vitorio D, Salles LD, Park M. Sodium concentration in urine greater than in the plasma: possible biomarker of normal renal function and better outcome in critically ill patients. Anaesth Intensive Care. 2014;42(5):584–91.

    CAS  PubMed  Google Scholar 

  34. Caironi P, Langer T, Taccone P, Bruzzone P, De Chiara S, Vagginelli F, Caspani L, Marenghi C, Gattinoni L. Kidney instant monitoring (K.IN.G): a new analyzer to monitor kidney function. Minerva Anestesiol. 2010;76(5):316–24.

    CAS  PubMed  Google Scholar 

  35. Horpacsy G, Zinsmeyer J, Mebel M. Continuous determination of various enzymes and sodium concentration in urine: a usable method for diagnosis of kidney graft rejection. Eur Urol. 1978;4(5):334–7.

    CAS  PubMed  Google Scholar 

  36. Moviat M, Pickkers P, van der Voort PH, van der Hoeven JG. Acetazolamide-mediated decrease in strong ion difference accounts for the correction of metabolic alkalosis in critically ill patients. Crit Care. 2006;10(1):R14.

    Article  PubMed  PubMed Central  Google Scholar 

  37. Singh D, Shrestha K, Testani JM, Verbrugge FH, Dupont M, Mullens W, Tang WH. Insufficient natriuretic response to continuous intravenous furosemide is associated with poor long-term outcomes in acute decompensated heart failure. J Card Fail. 2014;20(6):392–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  38. Bragadottir G, Redfors B, Ricksten SE. Assessing glomerular filtration rate (GFR) in critically ill patients with acute kidney injury-true GFR versus urinary creatinine clearance and estimating equations. Crit Care. 2013;17(3):R108.

    Article  PubMed  PubMed Central  Google Scholar 

  39. Bihari S, Peake SL, Seppelt I, Williams P, Bersten A. Health GIfG, Group AaNZICSCT: Sodium administration in critically ill patients in Australia and New Zealand: a multicentre point prevalence study. Crit Care Resusc. 2013;15(4):294–300.

    PubMed  Google Scholar 

  40. Bihari S, Peake SL, Prakash S, Saxena M, Campbell V, Bersten A. Sodium balance, not fluid balance, is associated with respiratory dysfunction in mechanically ventilated patients: a prospective, multicentre study. Crit Care Resusc. 2015;17(1):23–8.

    PubMed  Google Scholar 

  41. Maciel AT, Park M. Urine assessment in the critically ill: a matter of both quantity and quality. Rev Bras Ter Intensiva. 2013;25(3):184–5.

    Article  PubMed  PubMed Central  Google Scholar 

  42. Bihari S, Baldwin CE, Bersten AD. Fluid balance does not predict estimated sodium balance in critically ill mechanically ventilated patients. Crit Care Resusc. 2013;15(2):89–96.

    PubMed  Google Scholar 

  43. Besen BA, Gobatto AL, Melro LM, Maciel AT, Park M. Fluid and electrolyte overload in critically ill patients: an overview. World J Crit Care Med. 2015;4(2):116–29.

    Article  PubMed  PubMed Central  Google Scholar 

  44. Sam R, Hart P, Haghighat R, Ing TS. Hypervolemic hypernatremia in patients recovering from acute kidney injury in the intensive care unit. Clin Exp Nephrol. 2012;16(1):136–46.

    Article  PubMed  Google Scholar 

  45. Sarahian S, Pouria MM, Ing TS, Sam R. Hypervolemic hypernatremia is the most common type of hypernatremia in the intensive care unit. Int Urol Nephrol. 2015;47(11):1817–21.

    Article  PubMed  Google Scholar 

  46. Vitorio D, Maciel AT. Acute kidney injury induced by systemic inflammatory response syndrome is an avid and persistent sodium-retaining state. Case Rep Crit Care. 2014;2014:471658.

    PubMed  PubMed Central  Google Scholar 

  47. Vaz AJ. Low fractional excretion of urine sodium in acute renal failure due to sepsis. Arch Intern Med. 1983;143(4):738–9.

    Article  CAS  PubMed  Google Scholar 

  48. Bagshaw SM, Haase M, Haase-Fielitz A, Bennett M, Devarajan P, Bellomo R. A prospective evaluation of urine microscopy in septic and non-septic acute kidney injury. Nephrol Dial Transplant. 2012;27(2):582–8.

    Article  CAS  PubMed  Google Scholar 

  49. Schmidt C, Höcherl K, Schweda F, Kurtz A, Bucher M. Regulation of renal sodium transporters during severe inflammation. J Am Soc Nephrol. 2007;18(4):1072–83.

    Article  CAS  PubMed  Google Scholar 

  50. Schmidt C, Höcherl K, Schweda F, Bucher M. Proinflammatory cytokines cause down-regulation of renal chloride entry pathways during sepsis. Crit Care Med. 2007;35(9):2110–9.

    Article  CAS  PubMed  Google Scholar 

  51. Bellomo R, Wan L, Langenberg C, Ishikawa K, May CN. Septic acute kidney injury: the glomerular arterioles. Contrib Nephrol. 2011;174:98–107.

    Article  PubMed  Google Scholar 

  52. Calzavacca P, May CN, Bellomo R. Glomerular haemodynamics, the renal sympathetic nervous system and sepsis-induced acute kidney injury. Nephrol Dial Transplant. 2014;29(12):2178–84.

    Article  PubMed  Google Scholar 

  53. Singh P, Okusa MD. The role of tubuloglomerular feedback in the pathogenesis of acute kidney injury. Contrib Nephrol. 2011;174:12–21.

    Article  PubMed  Google Scholar 

  54. Belcher JM, Parikh CR, Garcia-Tsao G. Acute kidney injury in patients with cirrhosis: perils and promise. Clin Gastroenterol Hepatol. 2013;11(12):1550–8.

    Article  CAS  PubMed  Google Scholar 

  55. Longhini C, Molino C, Fabbian F. Cardiorenal syndrome: still not a defined entity. Clin Exp Nephrol. 2010;14(1):12–21.

    Article  PubMed  Google Scholar 

  56. Masevicius FD, Tuhay G, Pein MC, Ventrice E, Dubin A. Alterations in urinary strong ion difference in critically ill patients with metabolic acidosis: a prospective observational study. Crit Care Resusc. 2010;12(4):248–54.

    PubMed  Google Scholar 

  57. Pepin 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(4):566–73.

    Article  PubMed  Google Scholar 

  58. 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(6):2223–9.

    Article  CAS  PubMed  Google Scholar 

  59. Bazzano T, Restel TI, Porfirio LC, Souza AS, Silva IS. Renal biomarkers of male and female Wistar rats (Rattus norvegicus) undergoing renal ischemia and reperfusion. Acta Cir Bras. 2015;30(4):277–88.

    Article  PubMed  Google Scholar 

  60. Yang SK, Duan SB, Pan P, Xu XQ, Liu N, Xu J. Preventive effect of pentoxifylline on contrast-induced acute kidney injury in hypercholesterolemic rats. Exp Ther Med. 2015;9(2):384–8.

    CAS  PubMed  Google Scholar 

  61. Malagrino PA, Venturini G, Yogi PS, Dariolli R, Padilha K, Kiers B, Gois TC, da Motta-Leal-Filho JM, Takimura CK, Girardi AC, et al. Catheter-based induction of renal ischemia/reperfusion in swine: description of an experimental model. Physiol Rep. 2014;2(9):e12150.

  62. Maciel AT, Park M, Macedo E. Fractional excretion of potassium in the course of acute kidney injury in critically ill patients: potential monitoring tool? Rev Bras Ter Intensiva. 2014;26(2):143–7.

    Article  PubMed  PubMed Central  Google Scholar 

  63. Lehnhardt A, Kemper MJ. Pathogenesis, diagnosis and management of hyperkalemia. Pediatr Nephrol. 2011;26(3):377–84.

    Article  PubMed  Google Scholar 

  64. Elisaf M, Siamopoulos KC. Fractional excretion of potassium in normal subjects and in patients with hypokalaemia. Postgrad Med J. 1995;71(834):211–2.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  65. Mehta RL, Kellum JA, Shah SV, Molitoris BA, Ronco C, Warnock DG, Levin A. Acute Kidney Injury Network: report of an initiative to improve outcomes in acute kidney injury. Crit Care. 2007;11(2):R31.

    Article  PubMed  PubMed Central  Google Scholar 

  66. Maciel AT, Park M. Early diagnosis of acute kidney injury in a critically ill patient using a combination of blood and urinary physicochemical parameters. Clinics (Sao Paulo). 2012;67(5):525–6.

    Article  PubMed  PubMed Central  Google Scholar 

  67. Gattinoni L, Carlesso E, Cadringher P, Caironi P. Strong ion difference in urine: new perspectives in acid-base assessment. Crit Care. 2006;10(2):137.

    Article  PubMed  PubMed Central  Google Scholar 

  68. Masevicius FD, Vazquez AR, Enrico C, Dubin A. Urinary strong ion difference is a major determinant of plasma chloride concentration changes in postoperative patients. Rev Bras Ter Intensiva. 2013;25(3):197–204.

    Article  PubMed  PubMed Central  Google Scholar 

  69. Moviat M, Terpstra AM, van der Hoeven JG, Pickkers P. Impaired renal function is associated with greater urinary strong ion differences in critically ill patients with metabolic acidosis. J Crit Care. 2012;27(3):255–60.

    Article  CAS  PubMed  Google Scholar 

  70. Macedo E, Bouchard J, Soroko SH, Chertow GM, Himmelfarb J, Ikizler TA, Paganini EP, Mehta RL. Fluid accumulation, recognition and staging of acute kidney injury in critically-ill patients. Crit Care. 2010;14(3):R82.

    Article  PubMed  PubMed Central  Google Scholar 

  71. Maciel AT, Park M, Macedo E. Urinary electrolyte monitoring in critically ill patients: a preliminary observational study. Rev Bras Ter Intensiva. 2012;24(3):236–45.

    Article  PubMed  Google Scholar 

  72. Toledo Maciel A, Vitorio D, Delphino Salles L. Urine sodium profile in the course of septic acute kidney injury: insights relevant for kidney function monitoring. Minerva Anestesiol. 2014;80(4):506–7.

    CAS  PubMed  Google Scholar 

  73. Musso CG, Reynaldi J, Vilas M, De Miguel R, Imperiali N, Algranati L. Fractional excretion of K, Na and Cl following furosemide infusion in healthy, young and very old people. Int Urol Nephrol. 2010;42(1):273–7.

    Article  CAS  PubMed  Google Scholar 

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  1. Imed Research Group, Adult Intensive Care Unit, Hospital São Camilo, Av Pompéia 1178, São Paulo, SP, 05024-000, Brazil

    Alexandre Toledo Maciel & Daniel Vitorio

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  1. Alexandre Toledo Maciel
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Maciel, A.T., Vitorio, D. Urine biochemistry assessment in critically ill patients: controversies and future perspectives. J Clin Monit Comput 31, 539–546 (2017). https://doi.org/10.1007/s10877-016-9871-3

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