This thesis aimed to identify possible risks associated with erythropoiesis-simulating agent (ESA) use. First, trends in anemia management are described, showing less ESA use in Swedish patients... Show moreThis thesis aimed to identify possible risks associated with erythropoiesis-simulating agent (ESA) use. First, trends in anemia management are described, showing less ESA use in Swedish patients with chronic kidney disease (CKD) and less ESA-treated patients had a hemoglobin above 12 g/dL. Furthermore it is shown that ESA- treated pre-dialysis patients in the Netherlands received more antihypertensive agents than patients without ESA, confirming the hypertensive effect of ESA. However, no relevant difference in routinely measured blood pressure was observed between patients with and without ESA treatment, thus the hypertensive effect of ESAs could be controlled in clinical practice. In addition, no excess of thrombotic events was shown in ESA-treated dialysis patients compared to patients without ESA treatment. In contrast, a higher risk of cardiovascular events with ESA use was indicated in Danish patients with multiple myeloma and myelodyslastic syndrome. Also, with two analytical approaches, a harmful effect of high ESA doses on mortality was indicated in Dutch dialysis patients. Last, it was shown that ESA resistance was associated with mortality in both hemodialysis and peritoneal dialysis patients. To conclude, treatment with high ESA doses was associated with a higher risk of mortality, but the mechanism is largely unknown. Show less
Chronic kidney disease (CKD) is a progressive disease associated with increased morbidity and mortality. Different therapeutic interventions in the course of CKD are shown to be effective in... Show moreChronic kidney disease (CKD) is a progressive disease associated with increased morbidity and mortality. Different therapeutic interventions in the course of CKD are shown to be effective in slowing or preventing disease progression. This thesis focused on the progression of CKD from pre-dialysis to dialysis. The main conclusions of this thesis are: A positive first-degree family medical history of diabetes mellitus and cardiovascular disease is associated with increased mortality in the first year of pre-dialysis care, but not with decline of kidney function. Second, increased serum phosphorus levels, but not serum calcium levels, are associated with a shorter dialysis-free survival in the first two years of pre-dialysis care. Furthermore, increased phosphorus levels at start of pre-dialysis care are associated with the rate of decline of kidney function. Third, late referral to pre-dialysis care is associated with increased mortality in the first year of dialysis. Fourth, the decline of kidney function is constant in the period of one year before dialysis initiation until two to four months of dialysis therapy. After that period, the rate of decline of kidney function decreases. Finally, in contrast to common believe, in dialysis patients, cardiovascular and noncardiovascular mortality are equally increased. Show less
Assessing metabolic risk in dialysis patients, three main aspects are important: a) the pathophysiologic effects of metabolic disturbances as known from the general population are unlikely to... Show moreAssessing metabolic risk in dialysis patients, three main aspects are important: a) the pathophysiologic effects of metabolic disturbances as known from the general population are unlikely to completely reverse once patients reach dialysis. b) Specific additional problems related to chronic kidney disease, in particular protein-energy wasting, may act as “competing risk”, overshadow effects and interfere in various hormonal regulations. c) In advanced chronic kidney disease, the pattern and composition of risk is changing. The aim of this thesis is to 1) Detect specific effects of metabolic alterations in dialysis patients 2) Provide explanations for conflicting results in the literature 3) Provide a rationale for novel interventions. In this thesis, the metabolic status of dialysis patients is adressed and its consequences for the decline in residual kidney function, cardiovascular events and survival. The metabolic status includes alterations in nutritional and hormonal status, focussing on: lipid metabolism, diabetes mellitus type 2, obesity, the role of adipokines, specific effects of protein-energy wasting, and Vitamin D status with the clinical consequences. The investigations are performed in two large cohorts of dialysis patients, the 4D and NECOSAD studies (The German Diabetes and Dialysis Study and The Netherlands Cooperative Study on the Adequacy of Dialysis). Show less
