Privat-docent thesis

Optimizing the medical management of patients with chronic kidney disease and end-stage renal disease

ContributorsMavrakanas, Thomas
Defense date2018

Chronic kidney disease (CKD) prevalence is high and constantly increasing over the last years across the world. CKD is associated with higher incidence of cardiovascular disease, as well as premature mortality. There is an urgent unmet need for more data on novel treatment strategies that may prevent further renal function decline and appropriately treat cardiovascular complications in patients with CKD. Cardiac and renal interactions remain complex and poorly understood. As we show in the first publication, there is significant overlap between acute kidney injury or acutely decompensated heart failure and progression of chronic kidney disease or congestive heart failure. Involvement of both organs portends worse clinical outcomes. In the ESRD population, hemodialysis itself probably exerts detrimental effects on heart function through worsening myocardial perfusion that seems to be caused by excessive ultrafiltration rates, as we show in the second publication. The third article summarizes available clinical evidence and suggests beneficial effects of mineralocorticoid receptor antagonists, spironolactone or eplerenone, when added to an angiotensin converting enzyme inhibitor or an angiotensin receptor blocker in patients with diabetic nephropathy. Although albuminuria that was examined in this study is a surrogate marker for hard renal outcomes, further blockade of renin-angiotensin-aldosterone system looks promising, at least in patients with diabetes mellitus. Atrial fibrillation is a common problem in CKD and is associated with significant morbidity. It has recently been shown that vitamin K antagonists may not be as effective in this population and there is increasing interest on direct oral anticoagulants in CKD. The fourth article examines the pharmacokinetics of apixaban in patients on hemodialysis. This article demonstrates that steady state levels are far higher than levels obtained after a single dose of the drug and may be supratherapeutic with the full dose (5 mg twice daily). Furthermore, it shows that apixaban is not removed by hemodialysis. The fifth article examines platelet reactivity in stable outpatients with cardiovascular disease and CKD. In contrast to what has been shown in patients undergoing percutaneous coronary intervention, CKD is not associated with higher platelet reactivity or lower antiplatelet drug responsiveness in stable outpatients. Furthermore, there is no interaction between CKD status and high platelet reactivity for major adverse cardiovascular events in this population.

Citation (ISO format)
MAVRAKANAS, Thomas. Optimizing the medical management of patients with chronic kidney disease and end-stage renal disease. 2018. doi: 10.13097/archive-ouverte/unige:116612
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