Interview with Prof F. Kokot

 

Prof F. Kokot
Department of Nephrology
Silesian University, School of Medicine
Katowice, Poland

 

Prof Zoccali: Although you have several scientific interests, your focus has always been the endocrine system and its relationship with renal failure. Could you tell us how did you fall in love with nephro-endocrinology?

Prof Kokot: My love with nephro-endocrinology started already during my medical studies when I learned that from more than 150 l of glomerular filtrate only about 1% is finally excreted as urine. From these data I concluded that humoral factors (and not only activity of the autonomous nervous system) must be involved in the reabsorption process of such a large volume of primary glomerular filtrate. My love with nephrology deepened during my work for 7 years as junior and senior assistant in the Department of Pharmacology where I studied the influence of artificial hibernation on renal GFR, RBF and diuresis. Results of this study became the basis of my doctorate thesis, which I defended in 1957. Parallel to my work in Pharmacology I worked as a volunteer in the III Department of Internal Medicine headed at that time by a brilliant scientist Prof Dr Gibinski. In 1957, my Chief of the Department of Pharmacology was replaced by a new man with whom I could not find a common language. Sticking to the polish proverb, "that it is better to lose with a bright man, than to gain with a stupid one", I divorced with my beloved pharmacology and decided to work only in the Dep. of Internal Medicine. Very soon I became Head of the clinical laboratory, which I supervised up to the end of my active professional life (2000). Of cause I continued my studies on water-electrolyte disturbances in chronic cardiac failure especially examining the role of aldosterone in the pathogenesis of cardiac oedema. In 1958-1959 I worked with Prof R. Mach in Geneva (Clinique Therapeutique Universitaire) where I learned a lot on humoral factors regulating the exocrine function of the kidney. In the early 60s it became evident that the kidney is not only an exocrine organ but also an important endocrine one, and target for different hormones involved in the regulation of blood pressure, and of different biochemical pathways involved in the maintenance of the human homeostasis (in the broad sense of this term). In order to get instruments for studying the endocrine function of the kidneys in different pathological states and the relationship between renal function and function of classical endocrine organs it became mandatory to develop contemporary methods for the estimation of different hormones in nanomol or even femtomol concentrations. For this purpose we produced antibodies for the assessment of more than 15 hormones and elaborated appropriate radioimmunoassays, which were used not only for scientific but also diagnostic purposes. By this way we became independent from the import of very expensive kits from Western European countries and could essentially broaden our scientific activity. As in 1974 I was nominated Director of the Dep. of Nephrology, all my laboratory capacity was used for solving nephro-endocrinological problems (functioning of the endocrine system in acute and chronic renal failure, active renal stone disease and arterial hypertensive, erythropoietin secretion and renal function etc.)


Prof Zoccali: I think that before the fall of the Berlin wall it must have been very difficult for you to remain a productive and worldwide respected clinical investigator. How did you manage to build up a solid research group and to remain in close contact with your western colleagues?

Prof Kokot: The partial answer to this question is presented in point 1. After mastering the methodology of antibody production for assessment of different hormones and elaboration of my own radioimmunoassays the only difficulty was to get money for the purchase of a y- and ß-counter. This difficulty was overcome by my boss, who was a recognized scientist not only in Poland and found connections to get the necessary money in hot currency. Being the head of a modern laboratory and working with dedicated collaborators it was possible to be in good competition even with western nephrology. By presenting our studies at different international congresses I made friendship with nephrologists all over the world who opened their laboratories to my colleagues, while over 20 fellows from eastern European countries were trained in my department. 15 of my collaborators were trained in the USA (4) or Western European countries (11) for 1-2 years. These colleagues essentially contributed to our scientific potential. In addition I was elected council member of the ERA-EDTA for (in total) 9 years, which allowed me to have tough contacts with first line nephrologists from all over the world.


Prof Zoccali: Who are the colleagues that gave inspiration to your research work and ideas?

Prof Kokot: The flywheel of my scientific inspiration was my first boss, Prof K. Gibinski, who more than 50 years ago prophesied the face of medicine in 2000. My contribution to nephrology was that I met (or rather selected) dedicated and loyal collaborators who were bright, hardworking and willing to realize my scientific projects. The mottos I followed scrupulously during all my life were, "not to demand from my collaborators more than from myself" and "to accept successes of my fellow-nephrologists with humbleness and dignity".


Prof Zoccali: In the eighties you published several papers on endogenous opioids in renal failure. Do you believe that this research field was perhaps abandoned too early, before it could impact on treatment of at least some uremic complications?

Prof Kokot: The answer to this question is difficult for three reasons: I° the kidneys don’t seem to be a main site of opioid action, II° the role of opioids in the pathogenesis of uraemic toxicity is difficult to assess by measuring blood levels of opioids (blood is not the main site of opioids action) and III° the main site of opioid action is the CNS which is barely accessible for studies in human beings. In conclusion, I expect that only methodological progress will contribute to a better understanding of the role of opioids in the pathogenesis and treatment of uraemic toxicity.


Prof Zoccali: In Katowice you founded an excellent school of nephrology and mentored several successful Polish nephrologists. Could you tell us how did you melt clinical and research work in your academic unit?

Prof Kokot: Don’t think that I am conceited saying that only by working hard in concert with intelligent and dedicated collaborators it was possible to create a harmoniously performing orchestra. This orchestra comprised 76 doctors. By dividing my published scientific output by 76 I should rather be ashamed to have done so little.


Prof Zoccali: Which future do you foresee for nephro-endocrinology in the era of genomic medicine?

Prof Kokot: I expect that gene therapy will not enter practical nephrology during the next forthcoming 5-10 years although it seems likely that "titrated" expression of the EPO-gene in human cells (e.g. hepatocytes), of uraemic patients could revolutionize treatment of uremic anaemia. It seems likely that pluripotential or "mature" stem cell respectively will enrich therapy of different nephropathies, and contribute to nephroendocrinology.


Prof Zoccali: Which is the scientific paper that had the greatest impact on your scientific projects?

Prof Kokot: I think it was the paper of Thurau K., Schnermann J.: "The sodium concentration in the macula dense cells as a regulating factor for glomerular filtration (micropuncture experiments)." Klin Wochenschr, 1965, 43, 410-413 (in German). In this paper the existence of the tubular- glomerular feedback was elegantly proven. The results of this paper were of fundamental impact on our studies on the importance of the RAA system in essential and secondary forms of arterial hypertension, in preeclampsia and acute and chronic renal failure respectively.


Prof Zoccali: Research in nephrology in western countries is on the rise. Which are presently the main problems for Renal Physicians in Poland and western countries for pursuing clinical and basic research on kidney diseases?

Prof Kokot: Two problems deprive Polish (and I assume also western) nephrologists of their sleep:
These are:
1) diabetic nephropathy (which is really becoming a worldwide catastrophe) and
2) uraemic vasculopathy (macro- and micro-)
Both problems are subject of pathogenetic and therapeutic studies, but unfortunately until now, results of clinical relevance are very moderate.


Prof Zoccali: Which is your favorite hobby?

Prof Kokot: I do everything to be mentally and physically fit (unfortunately not with the best success). Aging, like apoptosis, can only be retarded.