Correspondence

More on Case 7-2006

N Engl J Med 2006; 355:1502-1503October 5, 2006

Article

To the Editor:

Schmitt et al., in their letter to the editor (June 22 issue),1 suggest that Takayesu et al. were incorrect in their assessment that a serum creatinine level of 3.8 mg per deciliter was caused by ingestion of ethylene glycol because it would take at least 3 days to reach such an elevated level. I am currently treating a 25-year-old patient with previously documented normal renal function who presented with a serum creatinine level of 3.7 mg per deciliter 8 hours after ingesting ethylene glycol. Although Schmitt et al. are correct that the accumulation of creatinine often lags behind changes in the glomerular filtration rate (GFR), their mistake is in equating the serum creatinine level with the GFR.2 Only serendipity makes the measurement of creatinine useful, because the tubular secretion of 20% of creatinine is counterbalanced by a 20% overestimation of the serum creatinine level as a result of the interference of noncreatinine chromogens. There are many substances, including pyruvate3 and keto acids,3 that act as chromogens and can disrupt the serendipitous balance, whereas other organic acids can interfere with creatinine secretion.4 Not all the organic acid metabolites of ethylene glycol have been identified, but increased levels of pyruvate result from the increase in lactate acid after the ingestion of ethylene glycol.5

Charles J. Diskin, M.D.
Auburn University, Opelika, AL 36801
hndt512@bellsouth.net

5 References

1. 1

   Case 7-2006: a man with altered mental status and acute renal failure. N Engl J Med 2006;354:2727-2729
   Full Text | Web of Science | Medline

2. 2

   Diskin CJ. Creatinine and GFR: an imperfect marriage of convenience. Nephrol Dial Transplant (in press).
   

3. 3

   Chasson AL, Grady HJ, Stanley MA. Determination of creatinine by means of automatic chemical analysis. Tech Bull Regist Med Technol 1960;30:207-212
   Medline

4. 4

   Deguchi T, Takemoto M, Uehara N, Lindup WE, Suenaga A, Otagiri M. Renal clearance of endogenous hippurate correlates with expression levels of renal organic anion transporters in uremic rats. J Pharmacol Exp Ther 2005;314:932-938
   CrossRef | Web of Science | Medline

5. 5

   Gabow PA, Clay K, Sullivan JB, Lepoff R. Organic acids in ethylene glycol intoxication. Ann Intern Med 1986;105:16-20
   Web of Science | Medline

Author/Editor Response

Diskin makes a valid and constructive point in that there are limitations in using creatinine values as a substitute for the GFR. They are not necessarily equivalent to the GFR for various reasons, such as the inhibition of creatinine secretion, an increase in creatinine production, and analytical inaccuracies caused by interference from noncreatinine chromogens with the commonly used alkaline picrate method of Jaffe.1,2 Yet, if acute kidney failure is the only underlying reason for an increase in creatinine, an increase to 3.8 mg per deciliter is unlikely within only a few hours. If one were to obstruct both ureters in a 70-kg man in steady state who makes approximately 1200 mg of creatinine per day, the GFR would essentially be 0, because the volume of distribution of creatinine is equal to the total body water; in this case, 1200 mg of creatinine per 42 liters of total body water would result in a maximal increase in the creatinine level of 2.8 mg per deciliter in 24 hours.

Roland Schmitt, M.D.
Xiaolei Zhu, M.D., Ph.D.
Shuta Ishibe, M.D.
Yale University School of Medicine, New Haven, CT 06520
roland.schmitt@yale.edu

2 References

1. 1

   Doolan PD, Alpen EL, Theil GB. A clinical appraisal of the plasma concentration and endogenous clearance of creatinine. Am J Med 1962;32:65-79
   CrossRef | Web of Science | Medline

2. 2

   Molitch ME, Rodman E, Hirsch CA, Dubinsky E. Spurious serum creatinine elevations in ketoacidosis. Ann Intern Med 1980;93:280-281
   Web of Science | Medline

Citing Articles (2)

Citing Articles

1. 1

   Anthe S. Zandvliet, Jan H. M. Schellens, Christian Dittrich, Jantien Wanders, Jos H. Beijnen, Alwin D. R. Huitema. (2008) Population pharmacokinetic and pharmacodynamic analysis to support treatment optimization of combination chemotherapy with indisulam and carboplatin. British Journal of Clinical Pharmacology 66:4, 485-497
   CrossRef

2. 2

   C Dittrich, A S Zandvliet, M Gneist, A D R Huitema, A A J King, J Wanders. (2007) A phase I and pharmacokinetic study of indisulam in combination with carboplatin. British Journal of Cancer 96:4, 559-566
   CrossRef