Determining urea concentration

A key challenge in renal medicine solved

Technical file

Type of innovation: Procedure

Scope: Clinical Analysis

Innovation leader: Grifols i Roig, Josep Antoni

Year: 1924

Period: 1909-1971

Geographical scope: Spain

Economic impact: Low

Level of innovation: Evolutionary

Patent: No

Interdisciplinary connections: -

Diagnosing kidney disease was one of the great medical challenges of the early twentieth century. Clinical analysis of renal function was simply not precise or reliable enough for the job. Improving on existing techniques would not only be good news for sufferers of conditions such as nephritis, but would also help determine the optimal amount of general anesthesia needed for patients prior to surgery.

A key indicator of renal function is the concentration of urea in blood, both in absolute terms and relative to this compound's concentration in urine. Determining both became a top priority for researchers with an interest in renal medicine.

“The automatic cleaning device accurately measured the quantity of urea in blood, as well as in cerebrospinal fluid and urine.”

Overcoming technical shortcomings

Early solutions were problematic. The hypobromite method was not exact and needed a large amount of blood. In contrast, Van Slyke-Cullen's method was very precise, but was somewhat impractical due to the entire apparatus having to be hermetically sealed. Also, the process required a prohibitively large quantity of water.

Dr. Grifols i Roig was also involved in the quest. With characteristic insight and imagination, he adapted the Van Slyke-Cullen mechanism using a modified Electrolux brand automatic cleaning device. The new method was presented to the Academia y Laboratorio de Ciencias Médicas de Cataluña on April 30, 1924.

A winning joint venture

The device had been developed jointly with Dr. K. Helmholz and accurately measured the quantity of urea in blood, as well as in cerebrospinal fluid and urine. Importantly, it overcame the shortcomings of previous approaches. Minimal blood was required, and the method was accurate and easy to put into practice.

The quality of life of the patient was improved and human errors were minimized. The method was published a year later in the German scientific journal Deutsche Medizinische Wochenschrift.


  • Van Slyke, D.D., & Cullen, G.E. (1916). The determination of Urea by the Urease Method. The Journal of Biological Chemistry, 24, 117-122.
  • Grifols-Roig, J.A. (1924). Exposició del mètode a la Permutita de Grífols i Helmholz, per a la investigació minimètrica de la urea en la sang, orina i líquid cefalo-raquidi. Anals de Ciències Mèdiques, 18(1), 444-449.
  • Grifols-Roig, J.A., & Helmholz, K. (1925). Einfache minimetrische Methode zur Bestimmung des Harnstoffs im Blut, in der Spinalflüssigkeit und im Urin mit Hilfe von Permutit. Deutsche Medizinische Wochenschrift, 51(4), 146-147.
  • Ormsby, A.A. (1942). A direct colorimetric method for the determination of urea in blood and urine. The Journal of Biological Chemistry, 146, 595-604.
  • Grifols-Lucas, V. (2009). Amb un suro i un cordill. Vivències d'un empresari de postguerra. Barcelona: Grupo Grifols, S.A.
  • Avellà, R., & Miquel, B. (Eds.). (2015). Cuando un sueño se cumple. Crónica ilustrada de 75 años de Grifols. Barcelona: Grupo Grifols, S.A.