PhD defence D. (Davide) Bolignano

The number of elderly persons worldwide is forecasted to grow dramatically over the next decades. Hence, future medicine will inevitably face new challenges related to the several, inexorable consequences of aging. The assessment of renal function in the framework of aging is problematic and the question whether renal aging should be considered as a physiological or pathological process remains an open issue. Gender, race, genetic background and other mediators such as oxidative stress, the renin-angiotensin-aldosterone (RAAS) system, impairment of kidney repair capacities and background cardiovascular disease, are all key-players of kidney aging. Whether or not promising dietary and pharmacological approaches targeting some of these factors retard renal senescence and prevent chronic kidney disease (CKD) is currently tested. Indeed, there is an urgent need to identify new prognostic biomarkers for refining outcome prediction in CKD individuals. Pulmonary hypertension (PH), a powerful and independent predictor of death in the general population and in subjects with heart or lung diseases, is highly prevalent also in renal patients and may hold the same prognostic utility for risk stratification and therapeutic management, particularly in persons with early CKD stages. As for the kidney and other organs, senescence is known to impair also physical capacity. In a pilot trial of healthy individuals of various ages, I found increased blood pressure levels after isometric challenge and a strong association between handgrip strength and change in blood pressure levels and aortic stiffness in elderly subjects. This altered vascular hemodynamics may reflect vascular ageing, a prelude to a decline in physical activity and mobility which characterizes the majority of old individuals. Similar to the elderly population, hemodialysis individuals have also a reduced physical activity. In an analysis of the EXCITE (Exercise Introduction to Enhance Performance in Dialysis) trial, a significantly reduced walking capacity predicted a high risk of mortality, cardiovascular events and hospitalizations in dialysis patients; this substantiates the importance of including objective measures of motor fitness in assessing the overall risk profile of dialysis and elderly study populations. In another analysis of the same study, I focused on two groups, who remained outside the trial. Despite several differences in baseline risk factors, an impaired mobility was the sole variable clearly explaining the difference in survival rate between these two sub-populations. Future studies are required to assess whether improving fitness may translate into better clinical outcomes in this high risk population.

The public defence will take place at the Senatehall, 1st floor of the Erasmus Building, Campus Woudestein. The ceremony will begin exactly at 11.30 hrs. In light of the solemn nature of the ceremony, we recommend that you do not take children under the age of 6 to the first part of the ceremony.