Skip to main content
SpringerLink
Log in

Urea

  • Chapter
  • First Online:
Urea Transporters

Part of the book series: Subcellular Biochemistry ((SCBI,volume 73))

Abstract

Urea is generated by the urea cycle enzymes, which are mainly in the liver but are also ubiquitously expressed at low levels in other tissues. The metabolic process is altered in several conditions such as by diets, hormones, and diseases. Urea is then eliminated through fluids, especially urine. Blood urea nitrogen (BUN) has been utilized to evaluate renal function for decades. New roles for urea in the urinary system, circulation system, respiratory system, digestive system, nervous system, etc., were reported lately, which suggests clinical significance of urea.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 129.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Hardcover Book
USD 169.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  1. Ademola J, Frazier C, Kim SJ, Theaux C, Saudez X (2002) Clinical evaluation of 40 % urea and 12 % ammonium lactate in the treatment of xerosis. Am J Clin Dermatol 3:217–222

    PubMed  Google Scholar 

  2. Albrectsen SR, Thaysen JH (1955) The excretion of urea by the human parotid gland. Scand J Clin Lab Invest 7:231–238

    CAS  PubMed  Google Scholar 

  3. Almdal TP, Egfjord M, Hansen BA, Vilstrup H (1991) Increased hepatic capacity of urea synthesis in acute and chronic uraemia in rats. Clin Nutr 10:206–212

    CAS  PubMed  Google Scholar 

  4. Almdal TP, Vilstrup H (1988) Loss of nitrogen from organs in rats induced by exogenous glucagon. Endocrinology 123:2182–2186

    CAS  PubMed  Google Scholar 

  5. Alvarez Pérez JA, González JJ, Baldonedo RF, Sanz L, Carreño G, Junco A, Rodrı́guez JI, Martı́nez MaD, Jorge JI (2001) Clinical course, treatment, and multivariate analysis of risk factors for pyogenic liver abscess. Am J Surg 181:177–186

    Google Scholar 

  6. Angus DC, Linde-Zwirble WT, Lidicker J, Clermont G, Carcillo J, Pinsky MR (2001) Epidemiology of severe sepsis in the United States: analysis of incidence, outcome, and associated costs of care. Crit Care Med 29:1303–1310

    CAS  PubMed  Google Scholar 

  7. Aokage T, Sato N, Kajimoto K, Asai K, Yumino D, Sakata Y, Keida T, Mizuno K, Tanaka K, Takano T (2011) Baseline blood urea nitrogen as a marker for predicting cardiac events in patients hospitalized for acute heart failure syndrome-beyond other renal variables. Eur Heart J 32:126–127

    Google Scholar 

  8. Aronson D, Hammerman H, Beyar R, Yalonetsky S, Kapeliovich M, Markiewicz W, Goldberg A (2008) Serum blood urea nitrogen and long-term mortality in acute ST-elevation myocardial infarction. Int J Cardiol 127:380–385

    PubMed  Google Scholar 

  9. Aronson D, Mittleman MA, Burger AJ (2004) Elevated blood urea nitrogen level as a predictor of mortality in patients admitted for decompensated heart failure. Am J Med 116:466–473

    CAS  PubMed  Google Scholar 

  10. Atherton J, Spiller R (1994) The urea breath test for Helicobacter pylori. Gut 35:723

    CAS  PubMed Central  PubMed  Google Scholar 

  11. Awad S, Herrod PJ, Palmer R, Carty HM, Abercrombie JF, Brooks A, de Beer T, Mole J, Lobo DN (2012) One- and two-year outcomes and predictors of mortality following emergency laparotomy: a consecutive series from a United Kingdom teaching hospital. World J Surg 36:2060–2067

    PubMed  Google Scholar 

  12. Azar AT, Wahba K, Mohamed AS, Massoud WA (2007) Association between dialysis dose improvement and nutritional status among hemodialysis patients. Am J Nephrol 27:113–119

    PubMed  Google Scholar 

  13. Bacigalupo A, Oneto R, Bruno B, Soracco M, Lamparelli T, Gualandi F, Occhini D, Raiola A, Mordini N, Berisso G (1999) Early predictors of transplant-related mortality (TRM) after allogeneic bone marrow transplants (BMT): blood urea nitrogen (BUN) and bilirubin. Bone Marrow Transplant 24:653–659

    CAS  PubMed  Google Scholar 

  14. Bailey SH, Bull DA, Harpole DH, Rentz JJ, Neumayer LA, Pappas TN, Daley J, Henderson WG, Krasnicka B, Khuri SF (2003) Outcomes after esophagectomy: a ten-year prospective cohort. Ann Thorac Surg 75:217–222

    PubMed  Google Scholar 

  15. Bankir L, Yang B (2012) New insights into urea and glucose handling by the kidney, and the urine concentrating mechanism. Kidney Int 81:1179–1198

    CAS  PubMed  Google Scholar 

  16. Barber T, Viña J, Viña J, Cabo J (1985) Decreased urea synthesis in cafeteria-diet-induced obesity in the rat. Biochem J 230:675–681

    CAS  PubMed Central  PubMed  Google Scholar 

  17. Begum L, Jalil MA, Kobayashi K, Iijima M, Li MX, Yasuda T, Horiuchi M, del Arco A, Satrústegui J, Saheki T (2002) Expression of three mitochondrial solute carriers, citrin, aralar1 and ornithine transporter, in relation to urea cycle in mice. Biochim Biophys Acta 1574:283–292

    CAS  PubMed  Google Scholar 

  18. Beier K, Eppanapally S, Bazick HS, Chang D, Mahadevappa K, Gibbons FK, Christopher KB (2011) Elevation of blood urea nitrogen is predictive of long-term mortality in critically ill patients independent of “normal” creatinine. Crit Care Med 39:305–313

    CAS  PubMed Central  PubMed  Google Scholar 

  19. Bihuniak JD, Simpson CA, Sullivan RR, Caseria DM, Kerstetter JE, Insogna KL (2013) Dietary protein-induced increases in urinary calcium are accompanied by similar increases in urinary nitrogen and urinary urea: a controlled clinical trial. J Acad Nutr Diet 113:447–451

    PubMed  Google Scholar 

  20. Bispo JAM, de Sousa Vieira EE, Silveira L, Fernandes AB (2013) Correlating the amount of urea, creatinine, and glucose in urine from patients with diabetes mellitus and hypertension with the risk of developing renal lesions by means of Raman spectroscopy and principal component analysis. J Biomed Opt 18:87004

    Google Scholar 

  21. Bjerrum K, Vilstrup H, Almdal T, Ostergaard L (1990) No effect of bicarbonate-induced alkalosis on urea synthesis in normal man. Scand J Clin Lab Invest 50:137–141

    CAS  PubMed  Google Scholar 

  22. Blatchford O, Murray WR, Blatchford M (2000) A risk score to predict need for treatment for uppergastrointestinal haemorrhage. Lancet 356:1318–1321

    CAS  PubMed  Google Scholar 

  23. Bliss DZ, Stein TP, Schleifer CR, Settle RG (1996) Supplementation with gum arabic fiber increases fecal nitrogen excretion and lowers serum urea nitrogen concentration in chronic renal failure patients consuming a low-protein diet. Am J Clin Nutr 63:392–398

    CAS  PubMed  Google Scholar 

  24. van den Boogaard M, Schoonhoven L, Maseda E, Plowright C, Jones C, Luetz A, Sackey PV, Jorens PG, Aitken LM, van Haren FM, Donders R, van der Hoeven JG, Pickkers P (2014) Recalibration of the delirium prediction model for ICU patients (PRE-DELIRIC): a multinational observational study. Intensive Care Med 40:361–369

    PubMed  Google Scholar 

  25. Boon L, Blommaart PJ, Meijer AJ, Lamers WH, Schoolwerth A (1994) Acute acidosis inhibits liver amino acid transport: no primary role for the urea cycle in acid–base balance. Am J Physiol Renal Physiol 267:F1015–F1020

    CAS  Google Scholar 

  26. Boon L, Blommaart PJ, Meijer AJ, Lamers WH, Schoolwerth AC (1996) Response of hepatic amino acid consumption to chronic metabolic acidosis. Am J Physiol 271:F198–F202

    CAS  PubMed  Google Scholar 

  27. Brebnor LD, Grimm J, Balinsky JB (1981) Regulation of urea cycle enzymes in transplantable hepatomas and in the livers of tumor-bearing rats and humans. Cancer Res 41:2692–2699

    CAS  PubMed  Google Scholar 

  28. Brosnan JT, Brosnan ME (2002) Hepatic glutaminase—a special role in urea synthesis? Nutrition 18:455–457

    CAS  PubMed  Google Scholar 

  29. Brown RL, Gibson JA, Fenton JC, Snedden W, Clark ML, Sladen GE (1975) Ammonia and urea transport by the excluded human colon. Clin Sci Mol Med 48:279–287

    CAS  PubMed  Google Scholar 

  30. Brzosko S, Szkolka T, Mysliwiec M (2009) Kidney disease is a negative predictor of 30-day survival after acute ischaemic stroke. Nephron Clin Pract 112:c79–c85

    CAS  PubMed  Google Scholar 

  31. Carco P, Canciullo D (1958) Urea excretion through the human salivary glands. Ann Otol Rhinol Laryngol 67:1050–1065

    CAS  PubMed  Google Scholar 

  32. Cardinali LdCC, Rocha GA, Rocha AMC, de Moura SB, de Figueiredo Soares T, Esteves AMB, Nogueira AMMF, Cabral MMDÁ, de Carvalho AST, Bitencourt P (2003) Evaluation of 13C urea breath test and Helicobacter pylori stool antigen test for diagnosis of H. pylori infection in children from a developing country. J Clin Microbiol 41:3334–3335

    Google Scholar 

  33. Carvounis CP, Nisar S, Guro-Razuman S (2002) Significance of the fractional excretion of urea in the differential diagnosis of acute renal failure. Kidney Int 62:2223–2229

    CAS  PubMed  Google Scholar 

  34. Cauthen CA, Lipinski MJ, Abbate A, Appleton D, Nusca A, Varma A, Goudreau E, Cowley MJ, Vetrovec GW (2008) Relation of blood urea nitrogen to long-term mortality in patients with heart failure. Am J Cardiol 101:1643–1647

    CAS  PubMed  Google Scholar 

  35. Cauthen CA, Tong M, Wu Y, Jain A, Tang W (2011) Prognostic importance of serial evaluation of blood urea nitrogen in ambulatory patients with chronic systolic heart failure and preserved renal function. J Card Fail 17:S86

    Google Scholar 

  36. Cederbaum SD, Shaw KN, Spector EB, Verity MA, Snodgrass PJ, Sugarman GI (1979) Hyperargininemia with arginase deficiency. Pediatr Res 13:827–833

    CAS  PubMed  Google Scholar 

  37. Chen CY, Yoshida A, Asakura M, Hasegawa T, Takahama H, Amaki M, Funada A, Asanuma H, Yokoyama H, Kim J, Kanzaki H, Kitakaze M (2012) Serum blood urea nitrogen and plasma brain natriuretic Peptide and low diastolic blood pressure predict cardiovascular morbidity and mortality following discharge in acute decompensated heart failure patients. Circ J 76:2372–2379

    CAS  PubMed  Google Scholar 

  38. Chen C-Y, Lin Y-R, Zhao L-L, Yang W-C, Chang Y-J, Wu H-P (2013) Clinical factors in predicting acute renal failure caused by rhabdomyolysis in the ED. Am J Emerg Med 31:1062

    Google Scholar 

  39. Chey WD, Wong BC (2007) American College of Gastroenterology guideline on the management of Helicobacter pylori infection. Am J Gastroenterol 102:1808–1825

    CAS  PubMed  Google Scholar 

  40. Coltart I, Tranah TH, Shawcross DL (2013) Inflammation and hepatic encephalopathy. Arch Biochem Biophys 536:189–196

    CAS  PubMed  Google Scholar 

  41. Corbello Pereira SR, Darronqui E, Constantin J, da Silva MHdRA, Yamamoto NS, Bracht A (2004) The urea cycle and related pathways in the liver of Walker-256 tumor-bearing rats. Biochim Biophys Acta 1688:187–196

    Google Scholar 

  42. Costell M, O’Connor J-E, Míguez M-P, Grisolía S (1984) Effects of L-carnitine on urea synthesis following acute ammonia intoxication in mice. Biochem Biophys Res Commun 120:726–733

    CAS  PubMed  Google Scholar 

  43. Curthoys NP, Watford M (1995) Regulation of glutaminase activity and glutamine metabolism. Annu Rev Nutr 15:133–159

    CAS  PubMed  Google Scholar 

  44. Cushny AR (1917) The excretion of urea and sugar by the kidney. J Physiol 51:36–44

    CAS  PubMed Central  PubMed  Google Scholar 

  45. Davis PK, Wu G (1998) Compartmentation and kinetics of urea cycle enzymes in porcine enterocytes. Comp Biochem Physiol B: Biochem Mol Biol 119:527–537

    CAS  Google Scholar 

  46. Debongnie J, Pauwels S, Raat A, De Meeus Y, Haot J, Mainguet P (1991) Quantification of Helicobacter pylori infection in gastritis and ulcer disease using a simple and rapid carbon-14-urea breath test. J Nucl Med 32:1192–1198

    CAS  PubMed  Google Scholar 

  47. Dewitte A, Biais M, Petit L, Cochard J-F, Hilbert G, Combe C, Sztark F (2012) Fractional excretion of urea as a diagnostic index in acute kidney injury in intensive care patients. J Crit Care 27:505–510

    PubMed  Google Scholar 

  48. Dimski DS (1994) Ammonia metabolism and the urea cycle: function and clinical implications. J Vet Intern Med 8:73–78

    CAS  PubMed  Google Scholar 

  49. Elewski BE, Haley HR, Robbins CM (2004) The use of 40 % urea cream in the treatment of moccasin tinea pedis. Cutis 73:355–357

    PubMed  Google Scholar 

  50. Emmanuel B (1981) Autoregulation of urea cycle by urea in mammalian species. Comp Biochem Physiol 70A:79–81

    CAS  Google Scholar 

  51. Esteban-Pretel G, Marín MP, Cabezuelo F, Moreno V, Renau-Piqueras J, Timoneda J, Barber T (2010) Vitamin A deficiency increases protein catabolism and induces urea cycle enzymes in rats. J Nutr 140:792–798

    CAS  PubMed  Google Scholar 

  52. Fabjan TH, Hojs R, Tetičkovič E, Balon BP (2007) Ischaemic stroke–impact of renal dysfunction on in-hospital mortality. Eur J Neurol 14:1351–1356

    Google Scholar 

  53. Faisst M, Wellner UF, Utzolino S, Hopt UT, Keck T (2010) Elevated blood urea nitrogen is an independent risk factor of prolonged intensive care unit stay due to acute necrotizing pancreatitis. J Crit Care 25:105–111

    CAS  PubMed  Google Scholar 

  54. Farnebo S, Zettersten EK, Samuelsson A, Tesselaar E, Sjöberg F (2011) Assessment of blood flow changes in human skin by microdialysis urea clearance. Microcirculation 18:198–204

    CAS  PubMed  Google Scholar 

  55. Felker GM, Leimberger JD, Califf RM, Cuffe MS, Massie BM, Adams KF Jr, Gheorghiade M, O’Connor CM (2004) Risk stratification after hospitalization for decompensated heart failure. J Card Fail 10:460–466

    PubMed  Google Scholar 

  56. Fernandez WG, Hung O, Bruno GR, Galea S, Chiang WK (2005) Factors predictive of acute renal failure and need for hemodialysis among ED patients with rhabdomyolysis. Am J Emerg Med 23:1–7

    PubMed  Google Scholar 

  57. Filippatos G, Rossi J, Lloyd-Jones DM, Stough WG, Ouyang J, Shin DD, O’Connor C, Adams KF, Orlandi C, Gheorghiade M (2007) Prognostic value of blood urea nitrogen in patients hospitalized with worsening heart failure: insights from the acute and chronic therapeutic impact of a vasopressin antagonist in chronic heart failure (ACTIV in CHF) study. J Card Fail 13:360–364

    PubMed  Google Scholar 

  58. Fine MJ, Auble TE, Yealy DM, Hanusa BH, Weissfeld LA, Singer DE, Coley CM, Marrie TJ, Kapoor WN (1997) A prediction rule to identify low-risk patients with community-acquired pneumonia. N Engl J Med 336:243–250

    CAS  PubMed  Google Scholar 

  59. Fonarow GC, Adams KF Jr, Abraham WT, Yancy CW, Boscardin WJ (2005) Risk stratification for in-hospital mortality in acutely decompensated heart failure. JAMA 293:572–580

    CAS  PubMed  Google Scholar 

  60. Ginde AA, Rhee SH, Katz ED (2004) Predictors of outcome in geriatric patients with urinary tract infections. J Emerg Med 27:101–108

    PubMed  Google Scholar 

  61. Greisen J, Grofte T, Hansen PO, Jensen TS, Vilstrup H (1999) Acute non-traumatic pain increases the hepatic amino- to urea-N conversion in normal man. J Hepatol 31:647–655

    CAS  PubMed  Google Scholar 

  62. Grofte T, Jensen DS, Gronbaek H, Wolthers T, Jensen SA, Tygstrup N, Vilstrup H (1998) Effects of growth hormone on steroid-induced increase in ability of urea synthesis and urea enzyme mRNA levels. Am J Physiol 275:E79–E86

    CAS  PubMed  Google Scholar 

  63. Grofte T, Wolthers T, Jensen SA, Moller N, Jorgensen J, Tygstrup N, Orskov H, Vilstrup H (1997) Effects of growth hormone and insulin-like growth factor-I singly and in combination on in vivo capacity of urea synthesis, gene expression of urea cycle enzymes, and organ nitrogen contents in rats. Hepatology 25:964–969

    CAS  PubMed  Google Scholar 

  64. Grofte T, Wolthers T, Jorgensen JO, Poulsen PL, Vilstrup H, Moller N (1999) Hepatic amino- to urea-N clearance and forearm amino-N exchange during hypoglycemic and euglycemic hyperinsulinemia in normal man. J Hepatol 30:819–825

    CAS  PubMed  Google Scholar 

  65. Gundpatil DB, Somani BL, Saha TK, Banerjee M (2014) Serum urea: albumin ratio as a prognostic marker in critical patients with non-chronic kidney disease. Indian J Clin Biochem 29:97–100

    CAS  PubMed  Google Scholar 

  66. Hamberg O, Andersen V, Sonne J, Larsen S, Vilstrup H (2001) Urea synthesis in patients with chronic pancreatitis: relation to glucagon secretion and dietary protein intake. Clin Nutr 20:493–501

    CAS  PubMed  Google Scholar 

  67. Hamberg O, Vilstrup H (1994) Regulation of urea synthesis by glucose and glucagon in normal man. Clin Nutr 13:183–191

    CAS  PubMed  Google Scholar 

  68. Hansen BA, Almdal TP, Vilstrup H (1989) Effects of xylitol versus glucose on urea synthesis and alanine metabolism in rats. Clin Nutr 8:109–112

    CAS  PubMed  Google Scholar 

  69. Hansen BA, Krog B, Vilstrup H (1986) Insulin and glucose decreases the capacity of urea-N synthesis in the rat. Scand J Clin Lab Invest 46:599–603

    CAS  PubMed  Google Scholar 

  70. Hartz AJ, Kuhn EM, Kayser KL, Johnson WD (1995) BUN as a risk factor for mortality after coronary artery bypass grafting. Ann Thorac Surg 60:398–404

    CAS  PubMed  Google Scholar 

  71. Havir EA, Tamir H, Ratner S, Warner RC (1965) Biosynthesis of urea XI. Preparation and properties of crystalline argininosuccinase. J Biol Chem 240:3079–3088

    CAS  PubMed  Google Scholar 

  72. Hayase K, Yokogoshi H, Yoshida A (1980) Effect of dietary proteins and amino acid deficiencies on urinary excretion of nitrogen and the urea synthesizing system in rats. J Nutr 110:1327–1337

    CAS  PubMed  Google Scholar 

  73. Heindorff H, Almdal TP, Vilstrup H (1991) Blockade of glucocorticoid receptors prevents the increase in urea synthesis after hysterectomy in rats. Eur J Clin Invest 21:625–630

    CAS  PubMed  Google Scholar 

  74. Heindorff H, Billesbolle P, Pedersen SL, Hansen R, Vilstrup H (1995) Somatostatin prevents the postoperative increases in plasma amino acid clearance and urea synthesis after elective cholecystectomy. Gut 36:766–770

    CAS  PubMed Central  PubMed  Google Scholar 

  75. Hoberman HD, Havir EA, Rochovansky O, Ratner S (1964) Biosynthesis of urea X. Stereospecificity of the argininosuccinase reaction. J Biol Chem 239:3818–3820

    CAS  PubMed  Google Scholar 

  76. Hoppe-Seyler G, Maier K, Schollmeyer P, Frohlich J, Talke H, Gerok W (1975) Studies on urea cycle enzymes in rat liver during acute uraemia. Eur J Clin Invest 5:15–20

    CAS  PubMed  Google Scholar 

  77. Huang Y, Xi Q, Xia S, Wang X, Liu Y, Huang C, Zheng W, Yu S (2014) Development and validation of a prognostic scale for hospitalized patients with terminally ill cancer in China. Support Care Cancer 22:145–152

    PubMed  Google Scholar 

  78. Hummel SL, Ghalib HH, Ratz D, Koelling TM (2013) Risk stratification for death and all-cause hospitalization in heart failure clinic outpatients. Am Heart J 166(895–903):e891

    Google Scholar 

  79. Husson A, Bouazza M, Buquet C, Vaillant R (1983) Hormonal regulation of two urea-cycle enzymes in cultured foetal hepatocytes. Biochem J 216:281–285

    CAS  PubMed Central  PubMed  Google Scholar 

  80. Husson A, Bouazza M, Buquet C, Vaillant R (1985) Role of dexamethasone and insulin on the development of the five urea-cycle enzymes in cultured rat foetal hepatocytes. Biochem J 225:271

    CAS  PubMed Central  PubMed  Google Scholar 

  81. Husson A, Buquet C, Vaillant R (1987) Induction of the five urea-cycle enzymes by glucagon in cultured foetal rat hepatocytes. Differentiation 35:212–218

    CAS  PubMed  Google Scholar 

  82. Häussinger D, Kaiser S, Stehle T, Gerok W (1986) Liver carbonic anhydrase and urea synthesis the effect of diuretics. Biochem Pharmacol 35:3317–3322

    PubMed  Google Scholar 

  83. Indiveri C, Tonazzi A, Stipani I, Palmieri F (1997) The purified and reconstituted ornithine/citrulline carrier from rat liver mitochondria: electrical nature and coupling of the exchange reaction with H+ translocation. Biochem J 327(Pt 2):349–355

    CAS  PubMed Central  PubMed  Google Scholar 

  84. Ivarsen P, Greisen J, Vilstrup H (2001) Acute effects of moderate dehydration on the hepatic conversion of amino nitrogen into urea nitrogen in healthy men. Clin Sci (Lond) 101:339–344

    CAS  Google Scholar 

  85. Jassal MS, Nedeltchev GG, Lee J-H, Choi SW, Atudorei V, Sharp ZD, Deretic V, Timmins GS, Bishai WR (2010) 13C-urea breath test as a novel point-of-care biomarker for tuberculosis treatment and diagnosis. PLoS ONE 5:e12451

    PubMed Central  PubMed  Google Scholar 

  86. Jensen SA, Almdal TP, Vilstrup H (1991) Acute in vivo effects of low ethanol concentration on the capacity of urea synthesis in rats. Alcohol Clin Exp Res 15:90–93

    CAS  PubMed  Google Scholar 

  87. Johnson W, Hagge W, Wagoner R, Dinapoli R, Rosevear J (1972) Effects of urea loading in patients with far-advanced renal failure. Mayo Clin Proc 47:21–29

    CAS  PubMed  Google Scholar 

  88. Jorda A, Gomez M, Cabo J, Grisolia S (1982) Effect of streptozotocin diabetes on some urea cycle enzymes. Biochem Biophys Res Commun 106:37–43

    CAS  PubMed  Google Scholar 

  89. Jorda A, Portoles M, Guasch R, Bernal D, Saez GT (1989) Effect of caffeine on urea biosynthesis and some related processes, ketone bodies, ATP and liver amino acids. Biochem Pharmacol 38:2727–2732

    CAS  PubMed  Google Scholar 

  90. Kafali H, Öksüzler C (2007) Vaginal fluid urea and creatinine in diagnosis of premature rupture of membranes. Arch Gynecol Obstet 275:157–160

    CAS  PubMed  Google Scholar 

  91. Kashiwagura T, Erecińska M, Wilson D (1985) pH dependence of hormonal regulation of gluconeogenesis and urea synthesis from glutamine in suspensions of hepatocytes. J Biol Chem 260:407–414

    CAS  PubMed  Google Scholar 

  92. Klein L, Massie BM, Leimberger JD, O’Connor CM, Pina IL, Adams KF Jr, Califf RM, Gheorghiade M (2008) Admission or changes in renal function during hospitalization for worsening heart failure predict postdischarge survival: results from the outcomes of a prospective trial of intravenous milrinone for exacerbations of chronic heart failure (OPTIME-CHF). Circ Heart fail 1:25–33

    CAS  PubMed  Google Scholar 

  93. Kobayashi K, Sinasac DS, Iijima M, Boright AP, Begum L, Lee JR, Yasuda T, Ikeda S, Hirano R, Terazono H, Crackower MA, Kondo I, Tsui LC, Scherer SW, Saheki T (1999) The gene mutated in adult-onset type II citrullinaemia encodes a putative mitochondrial carrier protein. Nat Genet 22:159–163

    CAS  PubMed  Google Scholar 

  94. Kraus VB, Stabler TV, Kong S, Varju G, McDaniel G (2007) Measurement of synovial fluid volume using urea. Osteoarthritis Cartilage 15:1217–1220

    CAS  PubMed Central  PubMed  Google Scholar 

  95. Krebs HA, Henseleit K (1932) Untersuchungen uber die Harnstoffbildung im Tierkörper. Hoppe-Seyler’s Zeitschrift für physiologische Chemie 210:33–66

    CAS  Google Scholar 

  96. Layton AT, Bankir L (2013) Impacts of active urea secretion into pars recta on urine concentration and urea excretion rate. Physiol Rep 1

    Google Scholar 

  97. Lee DS, Austin PC, Rouleau JL, Liu PP, Naimark D, Tu JV (2003) Predicting mortality among patients hospitalized for heart failure. JAMA 290:2581–2587

    CAS  PubMed  Google Scholar 

  98. Li Z, Yarmush ML, Chan C (2004) Insulin concentration during preconditioning mediates the regulation of urea synthesis during exposure to amino acid-supplemented plasma. Tissue Eng 10:1737–1746

    CAS  PubMed  Google Scholar 

  99. Lim W, Van der Eerden M, Laing R, Boersma W, Karalus N, Town G, Lewis S, Macfarlane J (2003) Defining community acquired pneumonia severity on presentation to hospital: an international derivation and validation study. Thorax 58:377–382

    CAS  PubMed Central  PubMed  Google Scholar 

  100. Lima HN, Cabral NL, Franklin J, Moro CHC, Pecoits-filho R, Goncalves AR (2012) Age dependent impact of estimated glomerular filtration rate on long-term survival after ischaemic stroke. Nephrology 17:725–732

    PubMed  Google Scholar 

  101. Lin HL, Chen CW, Lu CY, Sun LC, Shih YL, Chuang JF, Huang YH, Sheen MC, Wang JY (2012) High preoperative ratio of blood urea nitrogen to creatinine increased mortality in gastrointestinal cancer patients who developed postoperative enteric fistulas. Kaohsiung J Med Sci 28:418–422

    CAS  PubMed  Google Scholar 

  102. Lin LC, Yang JT, Weng HH, Hsiao CT, Lai SL, Fann WC (2011) Predictors of early clinical deterioration after acute ischemic stroke. Am J Emerg Med 29:577–581

    PubMed  Google Scholar 

  103. Listernick R (2013) A 13-year-old boy with elevated BUN and creatinine. Pediatr Ann 42:96–98

    PubMed  Google Scholar 

  104. Liu X, Zhang H, Liang J (2012) Blood urea nitrogen is elevated in patients with non-alcoholic fatty liver disease. Hepatogastroenterology 60:343–345

    Google Scholar 

  105. Longo WE, Virgo KS, Johnson FE, Oprian CA, Vernava AM, Wade TP, Phelan MA, Henderson WG, Daley J, Khuri SF (2000) Risk factors for morbidity and mortality after colectomy for colon cancer. Dis Colon Rectum 43:83–91

    CAS  PubMed  Google Scholar 

  106. Lundsgaard C, Hamberg O, Thomsen OO, Nielsen OH, Vilstrup H (1996) Increased hepatic urea synthesis in patients with active inflammatory bowel disease. J Hepatol 24:587–593

    CAS  PubMed  Google Scholar 

  107. Luria MH, Knoke JD, Margolis RM, Hendricks FH, Kuplic JB (1976) Acute myocardial infarction: prognosis after recovery. Ann Intern Med 85:561–565

    CAS  PubMed  Google Scholar 

  108. Lusty C, Ratner S (1972) Biosynthesis of urea XIV. The quaternary structure of argininosuccinase. J Biol Chem 247:7010–7022

    CAS  PubMed  Google Scholar 

  109. MacWalter RS, Wong SY, Wong KY, Stewart G, Fraser CG, Fraser HW, Ersoy Y, Ogston SA, Chen R (2002) Does renal dysfunction predict mortality after acute stroke? A 7-year follow-up study. Stroke 33:1630–1635

    PubMed  Google Scholar 

  110. Mackinney-Novelo I, Barahona-Garrido J, Castillo-Albarran F, Santiago-Hernandez JJ, Mendez-Sanchez N, Uribe M, Chavez-Tapia N (2012) Clinical course and management of acute hepatitis A infection in adults. Ann Hepatol 11:652–657

    CAS  PubMed  Google Scholar 

  111. Malfertheiner P, Megraud F, O’Morain C, Bazzoli F, El-Omar E, Graham D, Hunt R, Rokkas T, Vakil N, Kuipers EJ (2007) Current concepts in the management of Helicobacter pylori infection: the Maastricht III Consensus Report. Gut 56:772–781

    CAS  PubMed Central  PubMed  Google Scholar 

  112. Manjareeka M, Nanda S (2013) Elevated levels of serum uric acid, creatinine or urea in preeclamptic women. Int J Med Sci Public Health 2:43–47

    Google Scholar 

  113. Marchesini G, Zaccheroni V, Brizi M, Natale S, Forlani G, Bianchi G, Baraldi L, Melchionda N (2001) Systemic prostaglandin E1 infusion and hepatic aminonitrogen to urea nitrogen conversion in patients with type 2 diabetes in poor metabolic control. Metabolism 50:253–258

    CAS  PubMed  Google Scholar 

  114. Mariz J, Santos NC, Afonso H, Rodrigues P, Faria A, Sousa N, Teixeira J (2013) Risk and clinical-outcome indicators of delirium in an emergency department intermediate care unit (EDIMCU): an observational prospective study. BMC Emerg Med 13:2

    PubMed Central  PubMed  Google Scholar 

  115. Marusic M, Majstorovic Barac K, Bilic A, Jurcic D, Gulic S, Grubic Rotkvic P, Bago J (2013) Do gender and age influence the frequency of Helicobacter pylori infection? Wien Klin Wochenschr 125:714–716

    Google Scholar 

  116. Maswoswe SM, Tremblay GC (1989) Biosynthesis of hippurate, urea and pyrimidines in the fatty liver: studies with rats fed orotic acid or a diet deficient in choline and inositol, and with genetically obese (Zucker) rats. J Nutr 119:273–279

    CAS  PubMed  Google Scholar 

  117. Meijer AJ, Lamers WH, Chamuleau R (1990) Nitrogen metabolism and ornithine cycle function. Physiol Rev 70:701–748

    CAS  PubMed  Google Scholar 

  118. Michels VV, Beaudet AL (1978) Arginase deficiency in multiple tissues in argininemia. Clin Genet 13:61–67

    CAS  PubMed  Google Scholar 

  119. Monroy-Torres R, Naves-Sánchez J, Ortega-García JA (2011) Breastfeeding and metabolic indicators in Mexican premature newborns. Rev Invest Clin 64:521–528

    Google Scholar 

  120. Mulrennan S, Tempone SS, Ling ITW, Williams SH, Gan G-C, Murray RJ, Speers DJ (2010) Pandemic influenza (H1N1) 2009 pneumonia: CURB-65 score for predicting severity and nasopharyngeal sampling for diagnosis are unreliable. PLoS ONE 5:e12849

    PubMed Central  PubMed  Google Scholar 

  121. Musch W, Verfaillie L, Decaux G (2006) 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 1:909–914

    CAS  PubMed  Google Scholar 

  122. Nakano K, Kurimoto S, Ashida K (1971) Effect of previous high fat diet on body protein metabolism in rats. J Nutr 101:895–900

    CAS  PubMed  Google Scholar 

  123. Nielsen SS, Grofte T, Gronbaek H, Tygstrup N, Vilstrup H (2007) Opposite effects on regulation of urea synthesis by early and late uraemia in rats. Clin Nutr 26:245–251

    CAS  PubMed  Google Scholar 

  124. Nielsen SS, Grofte T, Tygstrup N, Vilstrup H (2005) Effect of lipopolysaccharide on in vivo and genetic regulation of rat urea synthesis. Liver Int 25:177–183

    CAS  PubMed  Google Scholar 

  125. Nielsen SS, Grofte T, Tygstrup N, Vilstrup H (2007) Cirrhosis and endotoxin decrease urea synthesis in rats. Hepatol Res 37:540–547

    CAS  PubMed  Google Scholar 

  126. Nissim I, Horyn O, Luhovyy B, Lazarow A, Daikhin Y, Yudkoff M (2003) Role of the glutamate dehydrogenase reaction in furnishing aspartate nitrogen for urea synthesis: studies in perfused rat liver with 15 N. Biochem J 376:179–188

    CAS  PubMed Central  PubMed  Google Scholar 

  127. Nullmann H, Pflug MA, Wesemann T, Heppner HJ, Pientka L, Thiem U (2014) External validation of the CURSI criteria (confusion, urea, respiratory rate and shock index) in adults hospitalised for community-acquired pneumonia. BMC Infect Dis 14:39

    PubMed Central  PubMed  Google Scholar 

  128. Núñez J, Núñez E, Miñana G, Bodí V, Fonarow GC, Bertomeu-González V, Palau P, Merlos P, Ventura S, Chorro FJ (2012) Differential mortality association of loop diuretic dosage according to blood urea nitrogen and carbohydrate antigen 125 following a hospitalization for acute heart failure. Eur J Heart Fail 14:974–984

    PubMed Central  PubMed  Google Scholar 

  129. Ostfeld R, Spinelli M, Mookherjee D, Holtzman D, Shoyeb A, Schaefer M, Kawano T, Doddamani S, Spevack D, Duc Y (2010) The association of blood urea nitrogen levels and coronary artery disease. Einstein J Biol Med 25:3–7

    Google Scholar 

  130. Palmieri L, Pardo B, Lasorsa FM, del Arco A, Kobayashi K, Iijima M, Runswick MJ, Walker JE, Saheki T, Satrustegui J, Palmieri F (2001) Citrin and aralar1 are Ca2+-stimulated aspartate/glutamate transporters in mitochondria. EMBO J 20:5060–5069

    CAS  PubMed Central  PubMed  Google Scholar 

  131. Pant C, Madonia P, Minocha A, Manas K, Jordan P, Bass P (2010) Laboratory markers as predictors of mortality in patients with Clostridium difficile infection. J Investig Med 58:43–45

    CAS  PubMed  Google Scholar 

  132. Parsonnet J, Friedman GD, Vandersteen DP, Chang Y, Vogelman JH, Orentreich N, Sibley RK (1991) Helicobacter pylori infection and the risk of gastric carcinoma. N Engl J Med 325:1127–1131

    CAS  PubMed  Google Scholar 

  133. Pellicori P, Carubelli V, Zhang J, Castiello T, Sherwi N, Clark AL, Cleland JG (2013) IVC diameter in patients with chronic heart failure: relationships and prognostic significance. JACC Cardiovasc Imaging 6:16–28

    PubMed  Google Scholar 

  134. Perri F, Clemente R, Pastore M, Quitadamo M, Festa V, Bisceglia M, Bergoli ML, Lauriola G, Leandro G, Ghoos Y (1998) The 13C-urea breath test as a predictor of intragastric bacterial load and severity of Helicobacter pylori gastritis. Scand J Clin Lab Invest 58:19–28

    CAS  PubMed  Google Scholar 

  135. Peter F, Wittekindt C, Finkensieper M, Kiehntopf M, Guntinas-Lichius O (2013) Prognostic impact of pretherapeutic laboratory values in head and neck cancer patients. J Cancer Res Clin Oncol 139:171–178

    PubMed  Google Scholar 

  136. Petrack B, Ratner S (1958) Biosynthesis of urea VII. Reversible formation of argininosuccinic acid. J Biol Chem 233:1494–1500

    CAS  PubMed  Google Scholar 

  137. Petrak J, Myslivcova D, Man P, Cmejla R, Cmejlova J, Vyoral D, Elleder M, Vulpe CD (2007) Proteomic analysis of hepatic iron overload in mice suggests dysregulation of urea cycle, impairment of fatty acid oxidation, and changes in the methylation cycle. Am J Physiol Gastrointest Liver Physiol 292:G1490–G1498

    CAS  PubMed  Google Scholar 

  138. Pigatto P, Bigardi A, Cannistraci C, Picardo M (1996) 10 % urea cream (Laceran) for atopic dermatitis: a clinical and laboratory evaluation. J Dermatolog Treat 7:171–175

    Google Scholar 

  139. de Prost N, Mekontso-Dessap A, Valeyrie-Allanore L, Van Nhieu JT, Duong TA, Chosidow O, Wolkenstein P, Brun-Buisson C, Maitre B (2014) Acute respiratory failure in patients with toxic epidermal necrolysis: clinical features and factors associated with mechanical ventilation. Crit Care Med 42:118–128

    PubMed  Google Scholar 

  140. Putaala J, Haapaniemi E, Gordin D, Liebkind R, Groop P-H, Kaste M, Tatlisumak T (2011) Factors associated with impaired kidney function and its impact on long-term outcome in young ischemic stroke. Stroke 42:2459–2464

    PubMed  Google Scholar 

  141. Rabbani P, Prasad AS (1978) Plasma ammonia and liver ornithine transcarbamoylase activity in zinc-deficient rats. Am J Physiol 235:E203–E206

    CAS  PubMed  Google Scholar 

  142. Rao GN, Cotlier E (1984) Urea cycle enzymes in retina, ciliary body-iris, lens and senile cataracts. Exp Eye Res 39:483–495

    CAS  PubMed  Google Scholar 

  143. Ratner S, Anslow WP, Petrack B (1953) Biosynthesis of urea VI. Enzymatic cleavage of argininosuccinic acid to arginine and fumaric acid. J Biol Chem 204:115–125

    CAS  PubMed  Google Scholar 

  144. Ratner S, Pappas A (1949) Biosynthesis of urea I. Enzymatic mechanism of arginine synthesis from citrulline. J Biol Chem 179:1183–1198

    CAS  PubMed  Google Scholar 

  145. Ratner S, Pappas A (1949) Biosynthesis of urea II. Arginine synthesis from citrulline in liver homogenates. J Biol Chem 179:1199–1212

    CAS  PubMed  Google Scholar 

  146. Ratner S, Petrack B (1951) Biosynthesis of urea III. Further studies on arginine synthesis from citrulline. J Biol Chem 191:693–705

    CAS  PubMed  Google Scholar 

  147. Ratner S, Petrack B (1953) Biosynthesis of urea IV. Further studies on condensation in arginine synthesis from citrulline. J Biol Chem 200:161–174

    CAS  PubMed  Google Scholar 

  148. Ratner S, Petrack B, Rochovansky O (1953) Biosynthesis of urea V. Isolation and properties of argininosuccinic acid. J Biol Chem 204:95–113

    CAS  PubMed  Google Scholar 

  149. Reddi PK, Knox WE, Herzfeld A (1975) Types of arginase in rat tissues. Enzyme 20:305–314

    CAS  PubMed  Google Scholar 

  150. Relles DM, Richards NG, Bloom JP, Kennedy EP, Sauter PK, Leiby BE, Rosato EL, Yeo CJ, Berger AC (2013) Serum blood urea nitrogen and serum albumin on the first postoperative day predict pancreatic fistula and major complications after pancreaticoduodenectomy. J Gastrointest Surg 17:326–331

    PubMed  Google Scholar 

  151. Riegel B, Knafl GJ (2013) Electronically monitored medication adherence predicts hospitalization in heart failure patients. Patient Prefer Adherence 8:1–13

    PubMed Central  PubMed  Google Scholar 

  152. Robles NR, Felix FJ, Fernandez-Berges D, Perez-Castan J, Zaro MJ, Lozano L, Alvarez-Palacios P, Garcia-Trigo A, Tejero V, Morcillo Y, Hidalgo AB (2013) The HUGE formula (hematocrit, urea and gender): association with cardiovascular risk. Eur Rev Med Pharmacol Sci 17:1889–1893

    CAS  PubMed  Google Scholar 

  153. Rochovansky O, Ratner S (1961) Biosynthesis of urea IX. Further studies on mechanism of argininosuccinate synthetase reaction. J Biol Chem 236:2254–2260

    CAS  PubMed  Google Scholar 

  154. Rochovansky O, Ratner S (1967) Biosynthesis of urea XII. Further studies on argininosuccinate synthetase: substrate affinity and mechanism of action. J Biol Chem 242:3839–3849

    CAS  PubMed  Google Scholar 

  155. Ruiz LA, Zalacain R, Capelastegui A, Bilbao A, Gomez A, Uranga A, Espana PP (2014) Bacteremic pneumococcal pneumonia in elderly and very elderly patients: host- and pathogen-related factors, process of care, and outcome. J Gerontol A Biol Sci Med Sci 69:1018–1024

    Google Scholar 

  156. Saheki T, Atsuko U, Hosoya M, Katsunuma T, Ohnishi N, Ozawa A (1980) Comparison of the urea cycle in conventional and germ-free mice. J Biochem 88:1563–1566

    CAS  PubMed  Google Scholar 

  157. Salah K, Kok WE, Eurlings LW, Bettencourt P, Pimenta JM, Metra M, Bayes-Genis A, Verdiani V, Bettari L, Lazzarini V, Damman P, Tijssen JG, Pinto YM (2014) A novel discharge risk model for patients hospitalised for acute decompensated heart failure incorporating N-terminal pro-B-type natriuretic peptide levels: a European collaboration on acute decompensated heart failure: ELAN-HF score. Heart 100:115–125

    CAS  PubMed  Google Scholar 

  158. Saygitov RT, Glezer MG, Semakina SV (2010) Blood urea nitrogen and creatinine levels at admission for mortality risk assessment in patients with acute coronary syndromes. Emerg Med J 27:105–109

    PubMed  Google Scholar 

  159. Schellekens R, Olsder G, Langenberg S, Boer T, Woerdenbag H, Frijlink H, Kosterink J, Stellaard F (2009) Proof-of-concept study on the suitability of 13C-urea as a marker substance for assessment of in vivo behaviour of oral colon-targeted dosage forms. Br J Pharmacol 158:532–540

    CAS  PubMed Central  PubMed  Google Scholar 

  160. Schimke RT (1962) Differential effects of fasting and protein-free diets on levels of urea cycle enzymes in rat liver. J Biol Chem 237:1921–1924

    CAS  PubMed  Google Scholar 

  161. Schimke RT (1963) Studies on factors affecting the levels of urea cycle enzymes in rat liver. J Biol Chem 238:1012–1018

    CAS  PubMed  Google Scholar 

  162. Schmidt-Nielsen B, Sands JA (2001) Urea excretion in white rats and kangaroo rats as influenced by excitement and by diet. J Am Soc Nephrol 12:856–864

    CAS  PubMed  Google Scholar 

  163. Schulze IT, Lusty C, Ratner S (1970) Biosynthesis of urea XIII. Dissociation-association kinetics and equilibria of argininosuccinase. J Biol Chem 245:4534–4543

    CAS  PubMed  Google Scholar 

  164. Schwartz IL, Thaysen JH, Dole VP (1953) Urea excretion in human sweat as a tracer for movement of water within the secreting gland. J Exp Med 97:429–437

    CAS  PubMed Central  PubMed  Google Scholar 

  165. See KC, Phua J, Yip HS, Yeo LL, Lim TK (2013) Identification of concurrent bacterial infection in adult patients with dengue. Am J Trop Med Hyg 89:804–810

    PubMed Central  PubMed  Google Scholar 

  166. Shambaugh G (1977) Urea biosynthesis I. The urea cycle and relationships to the citric acid cycle. Am J Clin Nutr 30:2083–2087

    CAS  PubMed  Google Scholar 

  167. Shemer A, Nathansohn N, Kaplan B, Weiss G, Newman N, Trau H (2000) Treatment of scalp seborrheic dermatitis and psoriasis with an ointment of 40 % urea and 1 % bifonazole. Int J Dermatol 39:532–534

    CAS  PubMed  Google Scholar 

  168. Shenkman HJ, Zareba W, Bisognano JD (2007) Comparison of prognostic significance of amino-terminal pro-brain natriuretic peptide versus blood urea nitrogen for predicting events in patients hospitalized for heart failure. Am J Cardiol 99:1143–1145

    CAS  PubMed  Google Scholar 

  169. Shoobridge JJ, Bultitude MF, Koukounaras J, Royce PL, Corcoran NM (2013) Predicting surgical exploration in renal trauma: assessment and modification of an established nomogram. J Trauma Acute Care Surg 75:819–823

    PubMed  Google Scholar 

  170. Skala I, Mareckova O, Ruzickova J, Blaha J, Strakova M, Reneltova I, Jirka J, Kocandrle V, Zvolankova K (1978) Urea and ammonia excretion into gastric juice in regularly dialyzed patients and patients after renal transplantation. I Dialyzed patients. Czech Med 1:180–190

    CAS  PubMed  Google Scholar 

  171. Slomianski A, Schubert T, Cutler A (1995) 13C Urea breath test to confirm eradication of Helicobacter pylori. Am J Gastroenterol 90:224–226

    CAS  PubMed  Google Scholar 

  172. Smith GL, Shlipak MG, Havranek EP, Foody JM, Masoudi FA, Rathore SS, Krumholz HM (2006) Serum urea nitrogen, creatinine, and estimators of renal function: mortality in older patients with cardiovascular disease. Arch Intern Med 166:1134

    CAS  PubMed  Google Scholar 

  173. Sormani M, Oneto R, Bruno B, Fiorone M, Lamparelli T, Gualandi F, Raiola A, Dominietto A, Van Lint M, Frassoni F (2003) A revised day +7 predictive score for transplant-related mortality: serum cholinesterase, total protein, blood urea nitrogen, gamma glutamyl transferase, donor type and cell dose. Bone Marrow Transplant 32:205–211

    CAS  PubMed  Google Scholar 

  174. Spector DA, Yang Q, Wade JB (2007) High urea and creatinine concentrations and urea transporter B in mammalian urinary tract tissues. Am J Physiol Renal Physiol 292:F467–F474

    CAS  PubMed  Google Scholar 

  175. Spek JW, Bannink A, Gort G, Hendriks WH, Dijkstra J (2012) Effect of sodium chloride intake on urine volume, urinary urea excretion, and milk urea concentration in lactating dairy cattle. J Dairy Sci 95:7288–7298

    CAS  PubMed  Google Scholar 

  176. Stiell IG, Clement CM, Aaron SD, Rowe BH, Perry JJ, Brison RJ, Calder LA, Lang E, Borgundvaag B, Forster AJ, Wells GA (2014) Clinical characteristics associated with adverse events in patients with exacerbation of chronic obstructive pulmonary disease: a prospective cohort study. CMAJ 186:E193–E204

    PubMed Central  PubMed  Google Scholar 

  177. Stosovic M, Stanojevic M, Simic-Ogrizovic S, Jovanovic D, Djukanovic L (2009) Relation between serum urea and mortality of hemodialysis patients. Ren Fail 31:335–340

    CAS  PubMed  Google Scholar 

  178. Sukasem C, Chamnanphon M, Koomdee N, Santon S, Jantararoungtong T, Prommas S, Puangpetch A, Manosuthi W (2014) Pharmacogenetics and clinical biomarkers for subtherapeutic plasma efavirenz concentration in HIV-1 infected Thai adults. Drug Metab Pharmacokinet [Epub ahead of print], PMID: 24477223

    Google Scholar 

  179. Sułowicz W, Walatek B, Sydor A, Ochmański W, Miłkowski A, Szymczakiewicz-Multanowska A, Szumilak D, Kraśniak A, Lonak H, Wojcikiewicz T (2002) Acute renal failure in patients with rhabdomyolysis. Med Sci Monit 8:CR24

    Google Scholar 

  180. Sweileh WM (2008) Predictors of in-hospital mortality after acute stroke: impact of renal dysfunction. Int J Clin Pharmacol Ther 46:637–643

    CAS  PubMed  Google Scholar 

  181. Syed TA, Ahmadpour OA, Ahmad SA, Shamsi S (1998) Management of toenail onychomycosis with 2 % butenafine and 20 % urea cream: a placebo-controlled, double-blind study. J Dermatol 25:648–652

    CAS  PubMed  Google Scholar 

  182. Testani JM, Cappola TP, Brensinger CM, Shannon RP, Kimmel SE (2011) Interaction between loop diuretic-associated mortality and blood urea nitrogen concentration in chronic heart failure. J Am Coll Cardiol 58:375–382

    CAS  PubMed Central  PubMed  Google Scholar 

  183. Thaysen JH, Thorn NA (1954) Excretion of urea, sodium, potassium and chloride in human tears. Am J Physiol 178:160–164

    CAS  PubMed  Google Scholar 

  184. Thomsen KL, Aagaard NK, Gronbæk H, Holst JJ, Jessen N, Frystyk J, Vilstrup H (2011) IL-6 has no acute effect on the regulation of urea synthesis in vivo in rats. Scand J Clin Lab Invest 71:150–156

    CAS  PubMed  Google Scholar 

  185. Thomsen KL, Jessen N, Moller AB, Aagaard NK, Gronbaek H, Holst JJ, Vilstrup H (2013) Regulation of urea synthesis during the acute-phase response in rats. Am J Physiol Gastrointest Liver Physiol 304:G680–G686

    CAS  PubMed  Google Scholar 

  186. Tomomura M, Tomomura A, Musa DAA, Horiuchi M, Takiguchi M, Mori M, Saheki T (1997) Suppressed expression of the urea cycle enzyme genes in the liver of carnitine-deficient juvenile visceral steatosis (JVS) mice in infancy and during starvation in adulthood. J Biochem 121:172–177

    CAS  PubMed  Google Scholar 

  187. Traynor J, Mactier R, Geddes CC, Fox JG (2006) How to measure renal function in clinical practice. BMJ 333:733

    PubMed Central  PubMed  Google Scholar 

  188. Tsagalis G, Akrivos T, Alevizaki M, Manios E, Stamatellopoulos K, Laggouranis A, Vemmos KN (2009) Renal dysfunction in acute stroke: an independent predictor of long-term all combined vascular events and overall mortality. Nephrol Dial Transplant 24:194–200

    PubMed  Google Scholar 

  189. Tuncel A, Keten T, Aslan Y, Kayali M, Erkan A, Koseoglu E, Atan A (2014) Comparison of different scoring systems for outcome prediction in patients with Fournier’s gangrene: Experience with 50 patients. Scand J Urol 48:393–399

    Google Scholar 

  190. Ueda T, Takeyama Y, Yasuda T, Matsumura N, Sawa H, Nakajima T, Ajiki T, Fujino Y, Suzuki Y, Kuroda Y (2007) Simple scoring system for the prediction of the prognosis of severe acute pancreatitis. Surgery 141:51–58

    PubMed  Google Scholar 

  191. Ugarte G, Pino ME, Valenzuela J, Lorca F (1963) Urea cycle enzymatic abnormalities in patients in endogenous hepatic coma. Gastroenterology 45:182–188

    CAS  PubMed  Google Scholar 

  192. Valente MA, Voors AA, Damman K, Van Veldhuisen DJ, Massie BM, O’Connor CM, Metra M, Ponikowski P, Teerlink JR, Cotter G, Davison B, Cleland JG, Givertz MM, Bloomfield DM, Fiuzat M, Dittrich HC, Hillege HL (2014) Diuretic response in acute heart failure: clinical characteristics and prognostic significance. Eur Heart J 35:1284–1293

    Google Scholar 

  193. Valtin H (1966) Sequestration of urea and nonurea solutes in renal tissues of rats with hereditary hypothalamic diabetes insipidus: effect of vasopressin and dehydration on the countercurrent mechanism. J Clin Invest 45:337–345

    CAS  PubMed Central  PubMed  Google Scholar 

  194. Vandenplas Y, Blecker U, Devreker T, Keppens E, Nijs J, Cadranel S, Pipeleers-Marichal M, Goossens A, Lauwers S (1992) Contribution of the 13C-urea breath test to the detection of Helicobacter pylori gastritis in children. Pediatrics 90:608–611

    CAS  PubMed  Google Scholar 

  195. Vilstrup H (1980) Synthesis of urea after stimulation with amino acids: relation to liver function. Gut 21:990–995

    CAS  PubMed Central  PubMed  Google Scholar 

  196. Vilstrup H, Hansen BA, Almdal TP (1990) Glucagon increases hepatic efficacy for urea synthesis. J Hepatol 10:46–50

    CAS  PubMed  Google Scholar 

  197. Waikar SS, Bonventre JV (2006) Can we rely on blood urea nitrogen as a biomarker to determine when to initiate dialysis? Clin J Am Soc Nephrol 1:903–904

    PubMed  Google Scholar 

  198. Walid M (2008) Blood urea nitrogen/creatinine ratio in rhabdomyolysis. Indian J Nephrol 18:173

    CAS  PubMed Central  PubMed  Google Scholar 

  199. Walters M, Wallace K (2010) Urea cycle gene expression is suppressed by PFOA treatment in rats. Toxicol Lett 197:46–50

    CAS  PubMed  Google Scholar 

  200. Waring W, Stephen A, Robinson O, Dow M, Pettie J (2008) Serum urea concentration and the risk of hepatotoxicity after paracetamol overdose. QJM 101:359–363

    CAS  PubMed  Google Scholar 

  201. Warren JR (2006) Helicobacter: the ease and difficulty of a new discovery (nobel lecture). ChemMedChem 1:672–685

    CAS  PubMed  Google Scholar 

  202. Watford M (1993) Hepatic glutaminase expression: relationship to kidney-type glutaminase and to the urea cycle. FASEB J 7:1468–1474

    CAS  PubMed  Google Scholar 

  203. Wilson AH, Kidd AC, Skinner J, Musonda P, Pai Y, Lunt CJ, Butchart C, Soiza RL, Potter JF, Myint PK (2014) A simple 5-point scoring system, NaURSE (Na+, Urea, Respiratory Rate and Shock Index in the Elderly), predicts in-hospital mortality in oldest old. Age Ageing 43:352–357

    Google Scholar 

  204. Winter JM, Cameron JL, Yeo CJ, Alao B, Lillemoe KD, Campbell KA, Schulick RD (2007) Biochemical markers predict morbidity and mortality after pancreaticoduodenectomy. J Am Coll Surg 204:1029–1036

    PubMed  Google Scholar 

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

    CAS  PubMed  Google Scholar 

  206. Wolthers T, Grofte T, Jorgensen JO, Vilstrup H (1997) Growth hormone prevents prednisolone-induced increase in functional hepatic nitrogen clearance in normal man. J Hepatol 27:789–795

    CAS  PubMed  Google Scholar 

  207. Wolthers T, Hamberg O, Grofte T, Vilstrup H (2000) Effects of budesonide and prednisolone on hepatic kinetics for urea synthesis. J Hepatol 33:549–554

    CAS  PubMed  Google Scholar 

  208. Wright FC, Chakraborty A, Helyer L, Moravan V, Selby D (2010) Predictors of survival in patients with non-curative stage IV cancer and malignant bowel obstruction. J Surg Oncol 101:425–429

    CAS  PubMed  Google Scholar 

  209. Wu BU, Bakker OJ, Papachristou GI, Besselink MG, Repas K, van Santvoort HC, Muddana V, Singh VK, Whitcomb DC, Gooszen HG, Banks PA (2011) Blood urea nitrogen in the early assessment of acute pancreatitis: an international validation study. Arch Intern Med 171:669–676

    PubMed  Google Scholar 

  210. Wu BU, Johannes RS, Sun X, Conwell DL, Banks PA (2009) Early changes in blood urea nitrogen predict mortality in acute pancreatitis. Gastroenterology 137:129–135

    CAS  PubMed  Google Scholar 

  211. Wu G, Meininger CJ (1993) Regulation of L-arginine synthesis from L-citrulline by L-glutamine in endothelial cells. Am J Physiol 265:H1965–H1971

    CAS  PubMed  Google Scholar 

  212. Yahalom G, Schwartz R, Schwammenthal Y, Merzeliak O, Toashi M, Orion D, Sela B-A, Tanne D (2009) Chronic kidney disease and clinical outcome in patients with acute stroke. Stroke 40:1296–1303

    PubMed  Google Scholar 

  213. Yamada M, Kubo H, Ishizawa K, Kobayashi S, Shinkawa M, Sasaki H (2005) Increased circulating endothelial progenitor cells in patients with bacterial pneumonia: evidence that bone marrow derived cells contribute to lung repair. Thorax 60:410–413

    CAS  PubMed Central  PubMed  Google Scholar 

  214. Yancy CW, Lopatin M, Stevenson LW, De Marco T, Fonarow GC (2006) Clinical presentation, management, and in-hospital outcomes of patients admitted with acute decompensated heart failure with preserved systolic functionA report from the acute decompensated heart failure national registry (ADHERE) database. J Am Coll Cardiol 47:76–84

    PubMed  Google Scholar 

  215. Yang B, Bankir L (2005) Urea and urine concentrating ability: new insights from studies in mice. Am J Physiol Renal Physiol 288:F881–F896

    CAS  PubMed  Google Scholar 

  216. Yassuda Filho P, Bracht A, Ishii-Iwamoto EL, Lousano SH, Bracht L, Kelmer-Bracht AM (2003) The urea cycle in the liver of arthritic rats. Mol Cell Biochem 243:97–106

    CAS  PubMed  Google Scholar 

  217. Young VR, El-Khoury AE, Raguso CA, Forslund AH, Hambraeus L (2000) Rates of urea production and hydrolysis and leucine oxidation change linearly over widely varying protein intakes in healthy adults. J Nutr 130:761–766

    CAS  PubMed  Google Scholar 

  218. Zar T, Kohn OF, Kaplan AA (2011) Fractional excretion of urea in pre-eclampsia. Iran J Kidney Dis 5:398–403

    PubMed  Google Scholar 

  219. Zevit N, Niv Y, Shirin H, Shamir R (2011) Age and gender differences in urea breath test results. Eur J Clin Invest 41:767–772

    PubMed  Google Scholar 

  220. Zhang Y, Churilov L, Meretoja A, Teo S, Davis SM, Yan B (2013) Elevated urea level is associated with poor clinical outcome and increased mortality post intravenous tissue plasminogen activator in stroke patients. J Neurol Sci 332:110–115

    CAS  PubMed  Google Scholar 

Download references

Acknowledgments

This work was supported by NSFC Grants 30500171, Scientific and Technological Research Program of Chongqing Municipal Education Commission KJ120330 and Scientific and Technological Research Program of Chongqing Yuzhongqu Scientific and Technological Commission 20120202 to JHR.

Author information

Authors and Affiliations

  1. Department of Anatomy and Neuroscience Center, Basic Medical College, Chongqing Medical University, Yixueyuan Road 1, Chongqing, 400016, China

    Hongkai Wang & Jianhua Ran

  2. Department of Pharmacology, School of Basic Medical Sciences, Peking University, Beijing, 100191, China

    Tao Jiang

Authors
  1. Hongkai Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Jianhua Ran
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Tao Jiang
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Jianhua Ran .

Editor information

Editors and Affiliations

  1. School of Basic Medical Sciences, Department of Pharmacology, Peking University, Beijing, China

    Baoxue Yang

  2. Renal Division, Department of Medicine and Department of Physiology, Emory University School of Medicine, Atlanta, Georgia, USA

    Jeff M. Sands

Rights and permissions

Reprints and permissions

Copyright information

© 2014 Springer Science+Business Media Dordrecht

About this chapter

Cite this chapter

Wang, H., Ran, J., Jiang, T. (2014). Urea. In: Yang, B., Sands, J. (eds) Urea Transporters. Subcellular Biochemistry, vol 73. Springer, Dordrecht. https://doi.org/10.1007/978-94-017-9343-8_2

Download citation

Publish with us

Policies and ethics

Search

Navigation