Determining urea concentration

A key challenge in renal medicine solved

Technical file

Innovation leader: Josep Antoni Grífols i Roig

Year: 1924

Period: Origins (1909-1939)

Type of innovation: Technical Procedure

Scope: Clinical analysis

Patent: No

Geographical reach: National

Economic impact:  3-Low

Level of innovation:  2-Evolutionary

Interdisciplinary connections: -

Related innovations: -

One of the great medical challenges of the early twentieth century was diagnosing kidney disease. Clinical analysis of the 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 kidney disease such as nephritis, but also help determine the optimal amount of general anesthetic 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 the same compound's concentration in urine. Determining both became a top priority for researchers with an interest in renal medicine.


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


A winning joint venture

It 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 used, 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.



A solution that combines accuracy with ease of use to help sufferers of kidney disease



  • Van Slyke, D.D., & Cullen, G.E. (1916). The determination of Urea by the Urease Method. The Journal of Biological Chemistry, 24, 117- 122.
  • Grífols 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.
  • Grífols 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.
  • Grífols-Lucas, V. (2009). Amb un suro i un cordill. Vivències d'un empresari de postguerra. Barcelona: Grífols Group, 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.