Although Jaffe's name is synonymous with clinical creatinine testing, his paper only described the principle behind what would later become the enduring method.[4] It was Otto Folin (1867–1934), a Harvard biochemist, who adapted Jaffe's research—abandoning the standard Neubauer reaction of the time—and published several papers using the Jaffe reaction to analyze creatinine levels in both blood and urine.[8][9][10] Folin began using the picric acid procedure in 1901 and included it in his 1916 Lab Manual of Biological Chemistry.[9][11] During his career, Folin modified and improved several quantitative colorimetric procedures, the first of which was for creatinine.[9] He took advantage of technology available at the time, using a Duboscq colorimeter for measurement precision, and is credited for introducing colorimetry into modern biochemical analysis.[9]
It should be noted that Folin's research did not focus on creatinine as a renal function indicator. Since the precursors of creatinine are synthesized in the liver,[2] at this point in history, creatinine was considered indicative of liver function.[4] It was not until 1926 that Poul Kristian Brandt Rehberg suggested creatinine was a significant marker for renal function.