Odd E. Hanssen and the Hanssen method for measurement of single-nephron glomerular filtration rate

In the middle of the twentieth century, the suspicion that deep and superfi cial nephrons might serve different functions created a demand for measurem ent of single-nephron glomerular filtration rate (SNGFR). Rather unexpected ly, the answer came from Odd E. Hanssen (1917-1964), a Norwegian physician working on his own in the Department of Pathological Anatomy, University of Oslo, with minimal support and no interaction with renal physiologists. In 1963, after nearly 10 years of work, he presented the ferrocyanide method, allowing simultaneous estimates of SNGFR in a large number of nephrons in all layers of the kidney. This review first describes his early visions of the method and the elaborate and extremely time-consuming studies in mice t o verify the technique. As a byproduct came valuable information on the rel ationship between nephron size and SNGFR, glomerular intermittency, and the emptying of the tubules on filtration stop. Hanssen died from a cerebral h emorrhage in 1964, and for several years the method seemed entirely forgott en. Fortunately, Andrew Baines took up the use of ferrocyanide in 1963-1964 while working on his thesis in Toronto, but his first publication came in 1969 from Saclay, France, in collaboration with Christian de Rouffignac. Mo difications allowing determination of absolute SNGFR were worked out by de Rouffignac and by Jaime Coehlo in New York. Thereafter, the "Hanssen method " spread rapidly, and in the early 1980s about 50 reports had been publishe d from 17 laboratories in 9 countries. The distribution of SNGFR in mammals , birds, and fish was described, as well as the response to water and salt loads, vasoactive substances, hormones, varying perfusion pressure, blood l oss, etc. Finally, after mentioning two recent methods inspired by the Hans sen technique but using other filtration markers, the review concludes that most of our present knowledge on SNGFR distribution and regulation has bee n obtained by the method developed by Hanssen 40 years ago.