Epidemiologic transition: a key to understanding global health
by Ron LaPorte, Graduate School of Public Health, University of Pittsburgh, PA, USA

The epidemiological transition is one of the most profound theories of global health. It was published by Omran in the early 1970’s. The argument was simple but extremely persuasive. For those who read the work for the fi rst time, one does not see global health the same anymore. The concept brings together, fertility, mortality, and population growth on the front head, which is typically called the demographic transition. The second part is the epidemiologic transition where he shows in example after example that as the SES increases there is a decline in infectious diseases. With decline there is a steady increase in Non-Communicable diseases in a very systematic manner. First one sees an increase in dental cavities, then a few years later trauma. Following this diabetes; then an increase in CHD, and following this cancer. The evidence suggests that kidney disease chases after the rise in obesity and diabetes. This has been elegantly shown in almost all countries after WWII. The power of this observation is that we need to start to think about the “evolution” of diseases in populations, and systems of disease, rather than focusing on individual diseases such as Kidney, diabetes cancer. By doing this we will have much greater ability to predict the future patterns of disease. Moreover, the examination of the underlying structure will tell us as to what is the “drivers” of disease. Thus our prevention efforts will focus on multiple diseases and be much more cost effective.

The long way to achieving tolerance in renal transplantation
by Fred Fändrich, Dept. of General and Thoracic Surgery, University of Kiel, Germany

Tolerance can still be considered the ultimate goal in transplantation medicine. Current tolerance protocols aim at achieving donor-specific tolerance by clonal deletion via mixed chimerism induction or, alternatively, via induction of peripheral tolerance by stimulating the expansion of “regulatory T-cells”. Regulatory T cells (Tregs) have reached centre-stage in immune tolerance research and their role for preventing autoimmunity or generating transplantation tolerance is now undisputed. However, little is known about their induction, biology and mechanisms of action. In order to use Tregs to approach the ultimate goal of dominant transplantation tolerance, it is of utmost importance to reliably generate donor-antigen-primed regulatory lymphocytes which are able to modify the host´s immune
response selectively in a donor-specific fashion and will sustain stable tolerance in an allogeneic setting. The major focus of this project will investigate the possibility to generate donor-derived monocytes which, upon in vitro modifi cation with M-CSF and γ-IFN, will be able to induce so-called regulatory T lymphocytes, by definition CD4+, Foxp3+, CD25+ cells after a short-term co-culturing procedure. The efficacy of these regulatory cells in a clinical tolerance study was presented.

A new unifying hypothesis for human hypertension
by Richard Johnson, University of Florida, Gainesville, FL, USA

Essential hypertension was originally described as hypertension occurring in the absence of clinical renal disease. However, the importance of the kidney was rediscovered by Guyton and others when they showed that most hypertension involves a physiologic defect in sodium excretion. Studies by our group and others have recently demonstrated that this physiological defect likely develops from stimuli that cause renal vasoconstriction. During the initial stage the renal vasoconstriction is not associated with any structural vascular disease, and this is observed most commonly in early or borderline hypertension, is characterized
by salt-resistance, normal or only slightly depressed GFR, with relatively normal renal autoregulation. Over time renal arteriolar disease develops and which can then drive the hypertension independent of the initiating stimulus. This phase is characterized by salt-sensitivity, blunted renal autoregulation, and an increased risk for the development of microalbuminuria, albuminuria, and progressive renal disease.
While polygenic factors and a congenital reduction in nephron number are likely involved in this pathway, recent studies suggest neither can account for more than 20% of the cases. Rather, the epidemic increase in blood pressure, as well as metabolic syndrome and renal disease, appears to be driven by dietary changes associated with Westernization. We presented evidence that this may be due to the dramatic increase in fructose intake, resulting in a rise in serum uric acid with engagement of this pathway.