Knut Aukland

Knut Aukland


Knut Aukland Memorial– kidney and interstitial fluid physiologist

Professor emeritus Knut Aukland, University of Bergen, Norway, born 1929 and honorary member of APS, died peacefully January 24, 2014 from Alzheimer’s disease. Aukland was a member of the Norwegian Academy for Science and Letters, and received several prizes for his research, including the Cecil K. Drinkers Award from the International Society of Lymphology for significant contributions towards understanding of lymphatics in health and disease. He made a lifetime contribution to renal physiology, particularly in fields of renal blood flow measurement and regulation and transcapillary fluid balance.

After finishing medical school at University of Bergen, Norway (1954) Knut Aukland spent 4 years in clinical medicine, mainly internal medicine and nephrology. In 1958 he joined Professor Fredrik Kiil in the new Institute for Experimental Medical Research, University of Oslo, and stayed there for 12 years, including a year in the Nephrology Department (1961-1962) and another year with Dr. Robert W Berliner as a Fulbright postdoctoral fellow (1962-1963) at NIH studying renal physiology. Along with collaboration with these excellent aforementioned mentors, Knut also enjoyed working with John Krog, a comparative physiologist with broad interests and exciting ideas.

In 1970 Aukland was appointed professor at the Department of Physiology, University of Bergen, teaching students in medicine, dentistry and science.  There he established a highly-productive group, continuing research on renal circulation and pioneering new directions in transcapillary fluid balance and edema-preventing mechanisms. Related to this research, he spent two sabbatical years (1981-1982 and 1989-1990) at the University of California-Davis, working with Professor Eugene M. Renkin in the Department of Human Physiology. 

After retiring from his professorship in l996, he was awarded a three-year senior research stipendium from the Research Council of Norway. In his opinion, his decades of editorial work, reviewing papers and evaluating grant applications were of high educational value.  That also applied to evaluating doctoral theses and writing classic and comprehensive reviews of interstitial and lymphatic mechanisms regulating interstitial volume in Physiological Reviews and Annual Reviews of Physiology. Still, he claimed his most rewarding activity was to introduce and guide young students and colleagues in experimental physiology. Kidney studies.   At the beginning of his career, Knut Aukland together with Fredrik Kiil studied tubular handling of various ions, including potassium and halogens, using the then new stop-flow technique. Proximal tubular reabsorption of serum protein was demonstrated, while a consistent "secretion" of protein at the level of the collecting ducts still remained unexplained.  By replacing the conventional mannitol diuresis with water or salt diuresis, and by developing a "push-flow technique" Aukland and Kiil were able to decipher the concentrating mechanism.  In retrospect, the demonstration of large water absorption in the apparent absence of antidiuretic hormone was probably their most significant finding. Renal energy expenditure was estimated as O2 uptake, and was related to NaCl reabsorption. In addition, they measured local renal energy turnover as the rate of heat accumulation during 5-10 seconds of circulatory arrest.

In response to the predicted importance of medullary blood flow for the concentrating mechanism, R.W. Berliner came up with the idea to measure local blood flow by recording the washout rate for H2 gas with platinum electrodes implanted in the medulla.  When Aukland joined the project in l962, the team of Berliner, Bower and Aukland, first attempted potentiometric techniques, which were previously used to detect cardiac shunts without success. However, by reducing the resistance of the electrode circuit they achieved a linear system. The team later realized that this was analogous to oxygen polarography, measuring the availability of gas for oxidation at the platinum surface and that a more selective measurement could be obtained with a polarizing voltage of 0.2 V versus a silver electrode.  Unfortunately, the method turned out to be useless for measuring inner medullary blood flow, but rather served to quantify the extremely efficient counter-current exchange of H2 gas.  On the other hand, absolute flow values were obtained in tissues such as myocardium, renal cortex and outer medulla. Subsequently, the method was employed in many organs and tissues in experimental animals as well as in studies of humans. In 1986 the description of the method in Circulation Research was presented as a "Citation Classic" in Current Contents.

Autoregulation of renal blood flow was then studied through development of new techniques. Glomeruli in deep cortex of the rat kidney were made accessible for micropuncture by acute ablation of a part of outer cortex. Glomerular capillary pressure in deep cortex was found similar to that in superficial layers. Interlobular arteries were identified through injection of microspheres. Measurement of pressure in these locations showed that the interlobular arteries are responsible for about 50% of the preglomerular resistance of superficial nephrons, and that they represented the first buffer at alterations in renal arterial pressure (descending autoregulation). These studies as well as the response to sudden reduction of peri-renal pressure strongly suggested a marked myogenic component in the autoregulation mechanism, a conclusion compatible with mathematical models.

Knut Aukland’s most recent effort to study regional functional differences in the kidney consisted of repeatable measurements of local glomerular filtration based on the uptake of the basic polypeptide aprotinin in the proximal convoluted tubules. This technique showed a remarkably uniform response in deep and superficial nephrons to altered arterial pressure, injection of furosemide, and to blocking of prostaglandin and NO formation.  Also vasopressin infusion documented equal changes of GFR in deep and superficial cortical layers, apparently conflicting with the view that the sensitivity to vasopressin is higher in juxtamedullary than in the cortical arterioles. An unexpected finding in these studies was that the concentration of aprotinin in glomerular filtrate was only 65% of that in plasma. While in retrospect, this is an obvious result of the Gibbs-Donnan effect of plasma proteins on the strongly cationic aprotinin, it implied that the interpretation of several previous studies on the renal handling of other charged polypeptides and proteins required revision.

Transcapillary fluid balance studies.  In the early 1970s, Knut Aukland and colleagues began to develop methods to collect interstitial fluid for analysis and to improve methods for measuring interstitial fluid pressure. Inspired by P. F. Scholander’s wick technique and a cadre of young interstitial physiologists (Reed, Wiig, Noddeland and Hargens, on sabbatical from UCSD), Aukland and his team explored blood/interstitial protein and fluid regulation in rats and humans. Micro-methods for estimating albumin and total protein were adapted, and in l971 Aukland and his collaborators constructed a membrane osmometer for 5 µl samples that obviously filled a demand as many of these osmometers are still used in laboratories around the world.

Knowing that wick insertion may cause protein leakage from the capillaries, Aukland’s group spent several years to estimate the consequences of this leakage by estimating its time course, studying protein composition of the wick fluid, priming the fluid with protein solutions, using wicks of various thickness, measuring hydrostatic fluid pressure within the wick during equilibration, testing the effect of anti-inflammatory agents, and comparing wick fluid protein concentration to that of local lymph.

For hydrostatic pressure measurements Aukland’s group simplified the Scholander-Hargens wick catheter method by placing the wick in a hypodermic needle with a sidehole. Still, Aukland and his team believed that the "gold standard" was obtained when they found that pressure could be measured through 2-5 µm thick glass pipettes introduced through the skin, the pressure being measured by the Wiederhielm automatic counter-pressure technique.

Using the techniques mentioned above, Knut Aukland’s group made extensive studies of the rise of interstitial fluid pressure in skin and skeletal muscle as well as the washout of interstitial proteins resulting from increased filtration resulting from increased venous pressure or hypoproteinemia, both responses that tend to counteract excessive capillary filtration. Briefly summarized, it was shown that hydrostatic and oncotic buffering are of about equal importance at normal hydration and during dehydration, while with overhydration and edema formation the oncotic buffering of 8-10 mm Hg greatly exceeds the hydrostatic counter-pressure of only 2-3 mm Hg. Human studies have clarified edema-preventing mechanisms in orthostasis, in nephrotic syndrome, and in heart patients with reduced ejection fraction but without clinical congestive failure.

On a more personal note, we will always remember Knut’s distinctive laugh, his enjoyment being with family, friends and collaborators.  He enjoyed hiking, walks talking about science and fishing the rich Norwegian fjords.  We will always remember these wonderful times with him.

 

Rolf Reed, Helge Wiig and Alan Hargens


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