Routine measurement of urea and creatinine in clinical practice

Yosuke Hirakawa
The University of Tokyo Hospital

Routine measurement of urea and creatinine, sensitive indicators of renal function, forms the present-day basis of clinical nephrology. Around 1850, two important events related to measurement of urea and creatinine occurred.

The word “creatinine” was probably first used by Justus von Liebig in 1847 (1). He found the ingredient creatinine in beef tea. Beef tea was a traditional English remedy, made using only beef and salt, not tea leaves. It had previously been known that creatine, the precursor of creatinine, was abundant in animal muscle. Liebig, who established the Justus von Liebig’s Extract of Meat Company, found that the addition of hydrochloric acid to creatine resulted in the production of creatinine. Around this time, creatinine was not used as an indicator of renal function; researchers focused on urea as an indicator of renal function, with Joseph Picard having established the reproducible and sensitive method of urea measurement in 1856. He later found that urea concentration in the renal vein fell from that in the renal artery (3). Around the same time, toxic mechanism came to be accepted as the etiology of uremic syndrome; therefore, the establishment of the urea measurement technique and the discovery of the urea fall in the renal vein led to the concept that urea was the causative substance of uremic syndrome. However, a brave study of urea loading in human patients performed in 1972 revealed that urea itself is not a uremic toxin (4).


  1. Pierre Delanaye (2012). “Serum Creatinine: An Old and Modern Marker of Renal Function” in Pierre Delanaye (ed.) Nephrology and Clinical Chemistry: The Essential Link pp9-20.
  2. Kramer H, Rosas SE, Matsushita K. Beef Tea, Vitality, Creatinine, and the Estimated GFR. Am J Kidney Dis. 2016;67:169-72.
  3. Gabriel Richet. Early history of uremia. Kidney Int 1988;33:1013-5
  4. Johnson WJ, Hagge WW, Wagoner RD, Dinapoli RP, Rosevear JW. Effects of urea loading in patients with far-advanced renal failure. Mayo Clin Proc 1972;47:21-29

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