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The Decreased Serum Urea Nitrogen–Creatinine Ratio

The Decreased Serum Urea Nitrogen–Creatinine Ratio Abstract Sometimes, readily available laboratory data can provide valuable hidden information. Such is the case with the serum urea nitrogen–creatinine ratio. A normal ratio is 8:1 to 10:1. It is well known that an elevated ratio is seen in cases of prerenal or postrenal uremia. Less appreciated are the diagnostic possibilities suggested by a decreased serum urea nitrogen–creatinine ratio (ie, <8). Several clinical circumstances can lead to a decreased serum urea nitrogen–creatinine ratio. The following case report highlights the importance of correctly interpreting a serum urea nitrogen–creatinine ratio. Report of a case A 62-year-old woman was admitted to Emory University Hospital, Atlanta, Ga, for evaluation of headaches and lethargy of several weeks' duration. She had been taking prednisone and azathioprine for 312 years for the treatment of chronic autoimmune hepatitis. The physical examination results were normal except for lethargy and mild nuchal rigidity. No stigmata of chronic hepatic failure were present. Admission laboratory tests revealed the following: serum creatinine, 80 µmol/L (0.9 mg/dL); serum urea nitrogen, 3.9 mmol/L (11 mg/dL); serum albumin, 39 g/L; and prothrombin time, 11.5 seconds (international normalized ratio, 1.2). The results of a computed tomography scan of her head were normal, and a lumbar puncture was performed. Cryptococcus neoformans was found in cerebrospinal fluid and blood cultures, and therapy with amphotericin B was started. On hospital day 9, flucytosine was added as adjunctive therapy. On day 11, the serum creatinine level was reported as 442 µmol/L (5 mg/dL) (assay performed on the Kodak Ektachem, Eastman Kodak, Rochester, NY), and the serum urea nitrogen level was 4.6 mmol/L (13 mg/dL). The amphotericin was discontinued because it was considered to be the most likely cause of the elevated creatinine level. After it was noted that the elevation of the creatinine level was not accompanied by an elevation of the serum urea nitrogen level (leading to a decreased serum urea nitrogen–creatinine ratio), chemical interference with the creatinine determination was considered. When the serum creatinine level was determined on day 12 by using the ACA analyzer (Dupoint Instruments, Wilmington, Del), a level of 106 µmol/L (1.2 mg/dL) was obtained, so amphotericin was restarted, and her therapy was completed successfully. Comment Some basic concepts about creatinine and urea physiology and their laboratory measurements are useful in understanding the decreased serum urea nitrogen–creatinine ratio. After being synthesized in the kidneys, small intestine, pancreas, and liver, creatine enters the circulation to be distributed chiefly to muscle cells, which contain 98% of the total body creatine. The body content of creatine is thus proportional to the muscle mass. Creatine is normally released from these muscle deposits at a slow rate. This released creatine is irreversibly and nonenzymatically dehydrated to creatinine, which is then freely filtered at the glomerular level and not substantially reabsorbed. However, the renal tubular cells secrete a small yet important amount of creatinine. The amount of creatinine secreted increases as the glomerular filtration rate decreases. Urea, the major end product of protein and amino acid metabolism, is generated almost exclusively in the liver through the urea cycle and is then freely filtered at the glomerulus and reabsorbed in the renal tubules. A decreased serum urea nitrogen–creatinine ratio may be due to several different mechanisms. Medications and ketone bodies cause chemical interference with the accurate determination of the creatinine level. Rhabdomyolysis results in the increased production of creatinine. Decreased production of the serum urea nitrogen can be caused by the following: (1) hereditary deficiency of urea cycle enzymes, (2) abnormal liver function, and (3) malnutrition. Dialysis results in increased clearance of serum urea nitrogen. Each of these is discussed in the following sections. Chemical interference with accurate creatinine determination The Jaffe reaction, a serum creatinine determination method, colorimetrically measures complexes formed between creatinine and alkaline picrate. Other substances also may produce the same colorimetric reaction with alkaline picrate. Chemicals producing this reaction are referred to as Jaffe chromogens.1 These noncreatinine chromogens, which include glucose, uric acid, acetoacetate, pyruvate, proteins, fructose, and ascorbic acid, can contribute as much as 20% of the colorimetric reaction in plasma or serum and falsely elevate the measured creatinine level, thus decreasing the serum urea nitrogen–creatinine ratio. Several chemicals and medications can spuriously elevate the creatinine level by interfering with the assay. Cephalosporins, especially cefoxitin, may falsely raise creatinine levels by interfering with the Jaffe reaction and causing spurious elevations up to 248 µmol/L (2.8 mg/dL).2 Of the various methods devised to bypass this colorimetric interference, only the Astra autoanalyzer technique (Beckman Instruments, Inc, Fullerton, Calif) and the Ektachem analyzer are widely used. The Astra autoanalyzer technique takes advantage of the differential rate of color development by creatinine compared with noncreatinine chromogens, thus allowing a rate-dependent separation of creatinine from these other substances. Blood levels of methyldopa greater than 9469 µmol/L may interfere with the autoanalyzer technique and elevate the measured creatinine level.3 The Ektachem analyzer is based on the enzymatic reaction of creatinine with imidohydrolase (Kodak Ektachem test method), resulting in the formation of N-methylhydantoin, which is measured by reflectance spectrometry. Flucytosine is well known to interfere with this creatinine determination method and falsely raise the serum creatinine level.4-6 Other chemicals and medication that interfere with the assay are as follows: ascorbic acid barbiturates sulfobromophthalein and phenolsulfonphthalein levodopa ketones7 Certain medications may elevate the serum creatinine by blocking the tubular secretion of creatinine. Cimetidine,8 pyrimethamine,9 and trimethoprim10 compete with creatinine for tubular secretion, and the use of these drugs may elevate serum creatinine levels, leading to a decreased serum urea nitrogen–creatinine ratio. This elevation in the serum creatinine level reflects the decrease in creatinine excretion and does not signify a decrease in the overall glomerular filtration rate.8-10 Acetoacetate interferes with automated creatinine determination methods, albeit to different extents.7 This spurious elevation of the serum creatinine level may be as much as 194 µmol/L (2.2 mg/dL). This artifactual elevation of the serum creatinine level must be remembered to prevent the misconception that the patient has renal failure at the time of the initial evaluation. Although patients with diabetic ketoacidosis may have elevated levels of serum urea nitrogen and creatinine due to depletion of blood volume, an isolated elevation in the serum creatinine level with a decreased serum urea nitrogen–creatinine ratio indicates an error in the creatinine measurement. β-Hydroxybutyrate has no effect on creatinine determination by any method. Increased creatinine production Muscle cells contain 98% of the total body creatine. In the presence of muscle damage, the released creatine is spontaneously dehydrated to creatinine, thus leading to an elevation of the serum creatinine level. Although rhabdomyolysis may lead to acute renal insufficiency, a decreased serum urea nitrogen–creatinine ratio may be the first clue to the diagnosis of rhabdomyolysis, thus allowing for early intervention. Alterations in serum urea nitrogen metabolism The biosynthesis of urea, a process that occurs almost exclusively in the liver, involves 4 enzymes: ornithine carbamoyltransferase, carbamoyl phosphate synthetase, argininosuccinate synthetase, and argininosuccinate lyase. Congenital deficiencies of these enzymes can produce hyperammonemic syndromes and decreased urea synthesis, resulting in a low serum urea nitrogen level. Although most cases are discovered during the neonatal or early childhood period, ornithine carbamoyltransferase deficiency has been diagnosed in adult patients as old as 58 years.11,12 Urea synthesis also may be impaired in hepatic insufficiency. After protein ingestion, the serum concentration of urea is lower in patients with cirrhosis than in healthy persons, and serum levels of urea precursors (ammonia and amino acids) often are increased in patients with cirrhosis. This may be due to subnormal activity of urea cycle enzymes.13-15 The decreased urea synthesis in patients with cirrhosis is compounded by the frequently accompanying malnutrition, which also may decrease the serum urea nitrogen level. Thus, a decreased serum urea nitrogen–creatinine ratio may suggest hepatic insufficiency. Increased serum urea nitrogen clearance The flux of a solute per unit of surface area of a dialysis membrane is proportional to the concentration gradient and inversely proportional to the resistance the solute encounters in its passage from the blood to the dialysate side. This resistance can be considered the sum of the resistance on the blood side, the membrane resistance, and the resistance on the dialysate side. The overall resistance to diffusion also depends on solute size; in general, the higher the molecular weight of a substance, the larger the resistance to diffusion.16 Owing to the lower molecular weight (urea, 60; creatinine, 113) and the higher concentration of urea compared with creatinine, urea dialyzes more efficiently than creatinine, accounting for the decreased serum urea nitrogen–creatinine ratio seen in patients undergoing dialysis. Hemodialysis and peritoneal dialysis create a decreased serum urea nitrogen–creatinine ratio by removing more urea than creatinine, but the effect is greater with hemodialysis. The serum urea nitrogen–creatinine ratio is a well-known diagnostic tool. Conditions such as malnutrition, hepatic disease, and rhabdomyolysis may be recognized by a decreased serum urea nitrogen–creatinine ratio. In addition, understanding other mechanisms that create a decreased serum urea nitrogen–creatinine ratio, such as chemical interference with the methods for creatinine determination or inhibition of tubular secretion by medications, will prevent the clinician from misinterpreting an elevated serum creatinine level as an index of a decreased glomerular filtration rate. Therefore, it is helpful to use the serum urea nitrogen–creatinine ratio and to remember the significance of a decreased ratio. Accepted for publication June 22, 1998. Reprints: Rafael Jurado, MD, Atlanta Veterans Affairs Medical Center, Medical Service (111), 1670 Clairmont Rd, Decatur, GA 30033. References 1. Cook JHG Factors influencing the assay of creatinine. Ann Clin Biochem. 1975;12219- 232Google ScholarCrossref 2. Saah AJKopcj TRDrusano GL Cefoxitin falsely elevates creatinine levels. JAMA. 1982;247205- 206Google ScholarCrossref 3. Myhre ERugstad HEHansen T Clinical pharmacokinetics of methyldopa. Clin Pharmacokinet. 1982;7221- 233Google ScholarCrossref 4. Mitchell EK Flucytosin and false elevation of creatinine level [letter]. Ann Intern Med. 1984;101278Google ScholarCrossref 5. Herrington DDrusaoo GLSmalls UStandiford HC False elevation in serum creatinine levels [letter]. JAMA. 1984;2522962Google ScholarCrossref 6. Kennedy CAGoetz MBMathisen G Artifactual elevation of the serum creatinine in patients receiving flucytosine for cryptococcal meningitis. J Infect Dis. 1989;1601090- 1091Google ScholarCrossref 7. Molitch MERodman EHirsch CADubinsky E Spurious serum creatinine elevations in ketoacidosis. Ann Intern Med. 1980;93280- 281Google ScholarCrossref 8. Larrson RBodemar GKagedal BWalan A The effects of cimetidine on renal function in patients with renal failure. Acta Med Scand. 1980;20827Google ScholarCrossref 9. Berglund F Effect of trimethoprim/sulfamethoxazole on the renal excretion of creatinine in man. J Urol. 1975;114802Google Scholar 10. Opravil MKeusch GLuthy R Pyrimethamine inhibits renal secretion of creatinine. Antimicrob Agents Chemother. 1993;371056Google ScholarCrossref 11. Wilson BEHobbs WNNewmark JJFarrow SJ Rapidly fatal hyperammonemic coma in adults: urea cycle enzyme deficiency. West J Med. 1994;161166- 168Google Scholar 12. Dimagno EPLowe JESnodgrass PLJones JD Ornithine transcarbamylase deficiency: a cause of bizarre behavior in man. N Engl J Med. 1986;315744- 747Google ScholarCrossref 13. Rudman DDiFulco TJGalambos JT Maximal rates of urea excretion and synthesis in normal and cirrhotic subjects. J Clin Invest. 1973;522241Google ScholarCrossref 14. Fisher JEYoshimura NAguirre AJames JHCummings MGAbel RMDeindoerfer F Plasma amino acids in patients with hepatic encephalopathy: effects of amino acid infusions. Am J Surg. 1974;12740- 47Google ScholarCrossref 15. Khatra BSSmith RBMillikan WJ Activities of Krebs-Henseleit enzymes in normal and cirrhotic human liver. J Lab Clin Med. 1974;84708Google Scholar 16. Lazarus JMHakin RM Medical aspects of hemodialysis. Brenner BMRector FCeds The Kidney. 4th ed. Philadelphia, Pa WB Saunders Co1991;Google Scholar http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Archives of Internal Medicine American Medical Association

The Decreased Serum Urea Nitrogen–Creatinine Ratio

Archives of Internal Medicine , Volume 158 (22) – Dec 7, 1998

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American Medical Association
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Copyright © 1998 American Medical Association. All Rights Reserved.
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0003-9926
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1538-3679
DOI
10.1001/archinte.158.22.2509
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Abstract

Abstract Sometimes, readily available laboratory data can provide valuable hidden information. Such is the case with the serum urea nitrogen–creatinine ratio. A normal ratio is 8:1 to 10:1. It is well known that an elevated ratio is seen in cases of prerenal or postrenal uremia. Less appreciated are the diagnostic possibilities suggested by a decreased serum urea nitrogen–creatinine ratio (ie, <8). Several clinical circumstances can lead to a decreased serum urea nitrogen–creatinine ratio. The following case report highlights the importance of correctly interpreting a serum urea nitrogen–creatinine ratio. Report of a case A 62-year-old woman was admitted to Emory University Hospital, Atlanta, Ga, for evaluation of headaches and lethargy of several weeks' duration. She had been taking prednisone and azathioprine for 312 years for the treatment of chronic autoimmune hepatitis. The physical examination results were normal except for lethargy and mild nuchal rigidity. No stigmata of chronic hepatic failure were present. Admission laboratory tests revealed the following: serum creatinine, 80 µmol/L (0.9 mg/dL); serum urea nitrogen, 3.9 mmol/L (11 mg/dL); serum albumin, 39 g/L; and prothrombin time, 11.5 seconds (international normalized ratio, 1.2). The results of a computed tomography scan of her head were normal, and a lumbar puncture was performed. Cryptococcus neoformans was found in cerebrospinal fluid and blood cultures, and therapy with amphotericin B was started. On hospital day 9, flucytosine was added as adjunctive therapy. On day 11, the serum creatinine level was reported as 442 µmol/L (5 mg/dL) (assay performed on the Kodak Ektachem, Eastman Kodak, Rochester, NY), and the serum urea nitrogen level was 4.6 mmol/L (13 mg/dL). The amphotericin was discontinued because it was considered to be the most likely cause of the elevated creatinine level. After it was noted that the elevation of the creatinine level was not accompanied by an elevation of the serum urea nitrogen level (leading to a decreased serum urea nitrogen–creatinine ratio), chemical interference with the creatinine determination was considered. When the serum creatinine level was determined on day 12 by using the ACA analyzer (Dupoint Instruments, Wilmington, Del), a level of 106 µmol/L (1.2 mg/dL) was obtained, so amphotericin was restarted, and her therapy was completed successfully. Comment Some basic concepts about creatinine and urea physiology and their laboratory measurements are useful in understanding the decreased serum urea nitrogen–creatinine ratio. After being synthesized in the kidneys, small intestine, pancreas, and liver, creatine enters the circulation to be distributed chiefly to muscle cells, which contain 98% of the total body creatine. The body content of creatine is thus proportional to the muscle mass. Creatine is normally released from these muscle deposits at a slow rate. This released creatine is irreversibly and nonenzymatically dehydrated to creatinine, which is then freely filtered at the glomerular level and not substantially reabsorbed. However, the renal tubular cells secrete a small yet important amount of creatinine. The amount of creatinine secreted increases as the glomerular filtration rate decreases. Urea, the major end product of protein and amino acid metabolism, is generated almost exclusively in the liver through the urea cycle and is then freely filtered at the glomerulus and reabsorbed in the renal tubules. A decreased serum urea nitrogen–creatinine ratio may be due to several different mechanisms. Medications and ketone bodies cause chemical interference with the accurate determination of the creatinine level. Rhabdomyolysis results in the increased production of creatinine. Decreased production of the serum urea nitrogen can be caused by the following: (1) hereditary deficiency of urea cycle enzymes, (2) abnormal liver function, and (3) malnutrition. Dialysis results in increased clearance of serum urea nitrogen. Each of these is discussed in the following sections. Chemical interference with accurate creatinine determination The Jaffe reaction, a serum creatinine determination method, colorimetrically measures complexes formed between creatinine and alkaline picrate. Other substances also may produce the same colorimetric reaction with alkaline picrate. Chemicals producing this reaction are referred to as Jaffe chromogens.1 These noncreatinine chromogens, which include glucose, uric acid, acetoacetate, pyruvate, proteins, fructose, and ascorbic acid, can contribute as much as 20% of the colorimetric reaction in plasma or serum and falsely elevate the measured creatinine level, thus decreasing the serum urea nitrogen–creatinine ratio. Several chemicals and medications can spuriously elevate the creatinine level by interfering with the assay. Cephalosporins, especially cefoxitin, may falsely raise creatinine levels by interfering with the Jaffe reaction and causing spurious elevations up to 248 µmol/L (2.8 mg/dL).2 Of the various methods devised to bypass this colorimetric interference, only the Astra autoanalyzer technique (Beckman Instruments, Inc, Fullerton, Calif) and the Ektachem analyzer are widely used. The Astra autoanalyzer technique takes advantage of the differential rate of color development by creatinine compared with noncreatinine chromogens, thus allowing a rate-dependent separation of creatinine from these other substances. Blood levels of methyldopa greater than 9469 µmol/L may interfere with the autoanalyzer technique and elevate the measured creatinine level.3 The Ektachem analyzer is based on the enzymatic reaction of creatinine with imidohydrolase (Kodak Ektachem test method), resulting in the formation of N-methylhydantoin, which is measured by reflectance spectrometry. Flucytosine is well known to interfere with this creatinine determination method and falsely raise the serum creatinine level.4-6 Other chemicals and medication that interfere with the assay are as follows: ascorbic acid barbiturates sulfobromophthalein and phenolsulfonphthalein levodopa ketones7 Certain medications may elevate the serum creatinine by blocking the tubular secretion of creatinine. Cimetidine,8 pyrimethamine,9 and trimethoprim10 compete with creatinine for tubular secretion, and the use of these drugs may elevate serum creatinine levels, leading to a decreased serum urea nitrogen–creatinine ratio. This elevation in the serum creatinine level reflects the decrease in creatinine excretion and does not signify a decrease in the overall glomerular filtration rate.8-10 Acetoacetate interferes with automated creatinine determination methods, albeit to different extents.7 This spurious elevation of the serum creatinine level may be as much as 194 µmol/L (2.2 mg/dL). This artifactual elevation of the serum creatinine level must be remembered to prevent the misconception that the patient has renal failure at the time of the initial evaluation. Although patients with diabetic ketoacidosis may have elevated levels of serum urea nitrogen and creatinine due to depletion of blood volume, an isolated elevation in the serum creatinine level with a decreased serum urea nitrogen–creatinine ratio indicates an error in the creatinine measurement. β-Hydroxybutyrate has no effect on creatinine determination by any method. Increased creatinine production Muscle cells contain 98% of the total body creatine. In the presence of muscle damage, the released creatine is spontaneously dehydrated to creatinine, thus leading to an elevation of the serum creatinine level. Although rhabdomyolysis may lead to acute renal insufficiency, a decreased serum urea nitrogen–creatinine ratio may be the first clue to the diagnosis of rhabdomyolysis, thus allowing for early intervention. Alterations in serum urea nitrogen metabolism The biosynthesis of urea, a process that occurs almost exclusively in the liver, involves 4 enzymes: ornithine carbamoyltransferase, carbamoyl phosphate synthetase, argininosuccinate synthetase, and argininosuccinate lyase. Congenital deficiencies of these enzymes can produce hyperammonemic syndromes and decreased urea synthesis, resulting in a low serum urea nitrogen level. Although most cases are discovered during the neonatal or early childhood period, ornithine carbamoyltransferase deficiency has been diagnosed in adult patients as old as 58 years.11,12 Urea synthesis also may be impaired in hepatic insufficiency. After protein ingestion, the serum concentration of urea is lower in patients with cirrhosis than in healthy persons, and serum levels of urea precursors (ammonia and amino acids) often are increased in patients with cirrhosis. This may be due to subnormal activity of urea cycle enzymes.13-15 The decreased urea synthesis in patients with cirrhosis is compounded by the frequently accompanying malnutrition, which also may decrease the serum urea nitrogen level. Thus, a decreased serum urea nitrogen–creatinine ratio may suggest hepatic insufficiency. Increased serum urea nitrogen clearance The flux of a solute per unit of surface area of a dialysis membrane is proportional to the concentration gradient and inversely proportional to the resistance the solute encounters in its passage from the blood to the dialysate side. This resistance can be considered the sum of the resistance on the blood side, the membrane resistance, and the resistance on the dialysate side. The overall resistance to diffusion also depends on solute size; in general, the higher the molecular weight of a substance, the larger the resistance to diffusion.16 Owing to the lower molecular weight (urea, 60; creatinine, 113) and the higher concentration of urea compared with creatinine, urea dialyzes more efficiently than creatinine, accounting for the decreased serum urea nitrogen–creatinine ratio seen in patients undergoing dialysis. Hemodialysis and peritoneal dialysis create a decreased serum urea nitrogen–creatinine ratio by removing more urea than creatinine, but the effect is greater with hemodialysis. The serum urea nitrogen–creatinine ratio is a well-known diagnostic tool. Conditions such as malnutrition, hepatic disease, and rhabdomyolysis may be recognized by a decreased serum urea nitrogen–creatinine ratio. In addition, understanding other mechanisms that create a decreased serum urea nitrogen–creatinine ratio, such as chemical interference with the methods for creatinine determination or inhibition of tubular secretion by medications, will prevent the clinician from misinterpreting an elevated serum creatinine level as an index of a decreased glomerular filtration rate. Therefore, it is helpful to use the serum urea nitrogen–creatinine ratio and to remember the significance of a decreased ratio. Accepted for publication June 22, 1998. Reprints: Rafael Jurado, MD, Atlanta Veterans Affairs Medical Center, Medical Service (111), 1670 Clairmont Rd, Decatur, GA 30033. References 1. Cook JHG Factors influencing the assay of creatinine. Ann Clin Biochem. 1975;12219- 232Google ScholarCrossref 2. Saah AJKopcj TRDrusano GL Cefoxitin falsely elevates creatinine levels. JAMA. 1982;247205- 206Google ScholarCrossref 3. Myhre ERugstad HEHansen T Clinical pharmacokinetics of methyldopa. Clin Pharmacokinet. 1982;7221- 233Google ScholarCrossref 4. Mitchell EK Flucytosin and false elevation of creatinine level [letter]. Ann Intern Med. 1984;101278Google ScholarCrossref 5. Herrington DDrusaoo GLSmalls UStandiford HC False elevation in serum creatinine levels [letter]. JAMA. 1984;2522962Google ScholarCrossref 6. Kennedy CAGoetz MBMathisen G Artifactual elevation of the serum creatinine in patients receiving flucytosine for cryptococcal meningitis. J Infect Dis. 1989;1601090- 1091Google ScholarCrossref 7. Molitch MERodman EHirsch CADubinsky E Spurious serum creatinine elevations in ketoacidosis. Ann Intern Med. 1980;93280- 281Google ScholarCrossref 8. Larrson RBodemar GKagedal BWalan A The effects of cimetidine on renal function in patients with renal failure. Acta Med Scand. 1980;20827Google ScholarCrossref 9. Berglund F Effect of trimethoprim/sulfamethoxazole on the renal excretion of creatinine in man. J Urol. 1975;114802Google Scholar 10. Opravil MKeusch GLuthy R Pyrimethamine inhibits renal secretion of creatinine. Antimicrob Agents Chemother. 1993;371056Google ScholarCrossref 11. Wilson BEHobbs WNNewmark JJFarrow SJ Rapidly fatal hyperammonemic coma in adults: urea cycle enzyme deficiency. West J Med. 1994;161166- 168Google Scholar 12. Dimagno EPLowe JESnodgrass PLJones JD Ornithine transcarbamylase deficiency: a cause of bizarre behavior in man. N Engl J Med. 1986;315744- 747Google ScholarCrossref 13. Rudman DDiFulco TJGalambos JT Maximal rates of urea excretion and synthesis in normal and cirrhotic subjects. J Clin Invest. 1973;522241Google ScholarCrossref 14. Fisher JEYoshimura NAguirre AJames JHCummings MGAbel RMDeindoerfer F Plasma amino acids in patients with hepatic encephalopathy: effects of amino acid infusions. Am J Surg. 1974;12740- 47Google ScholarCrossref 15. Khatra BSSmith RBMillikan WJ Activities of Krebs-Henseleit enzymes in normal and cirrhotic human liver. J Lab Clin Med. 1974;84708Google Scholar 16. Lazarus JMHakin RM Medical aspects of hemodialysis. Brenner BMRector FCeds The Kidney. 4th ed. Philadelphia, Pa WB Saunders Co1991;Google Scholar

Journal

Archives of Internal MedicineAmerican Medical Association

Published: Dec 7, 1998

Keywords: creatinine,nitrogen,urea

References