Healthcare is shifting towards a more person-centred approach, aiming at a personalised treatment that fits the patient’s preferences and needs. The use of patient-reported outcome measures (PROMs... Show moreHealthcare is shifting towards a more person-centred approach, aiming at a personalised treatment that fits the patient’s preferences and needs. The use of patient-reported outcome measures (PROMs) to systematically assess outcomes such as health-related quality of life and symptom burden can facilitate the process of adapting to what is important to the patient. But, how to integrate PROMs into a routine care setting and how to use PROMs to achieve this personalised treatment? This dissertation provides insight into and practical knowledge of the implementation and use of PROMs in routine nephrology care. Research was performed within the different steps for implementation of PROMs into routine care, including the selection of PROMs, pilot testing PROMs, and nationwide implementation and use of PROMs, using a broad variety of quantitative and qualitative research methods. The use of PROMs was investigated both at individual patient level and at population level, with the potential to facilitate personalised treatment and evaluation of healthcare quality. Patients and healthcare professionals considered the PROM-results relevant additional information in routine practice, complementary to traditional clinical measures. In addition, discussing individual PROM results proved to be of great added value and directly applicable in routine care. Show less
In part 1 of the thesis Predicting Outcomes in Patients with Kidney Disease, key differences between etiological and prediction research are explored and it is shown that observational research... Show moreIn part 1 of the thesis Predicting Outcomes in Patients with Kidney Disease, key differences between etiological and prediction research are explored and it is shown that observational research often conflates etiology and prediction which leads to incorrect causal conclusions. A framework for the external validation of prognostic models is provided and it is shown how competing events can be dealt with when externally validating a time-to-event prognostic model. These results are applicable to many clinical research fields, including nephrology as exemplified in part 2. Within the six applied chapters in part 2, prediction models for various adverse outcomes in patients with advanced kidney disease are identified, validated and developed. The thesis provides a broad overview of prognostic model applications in patients with chronic kidney disease, including comprehensive external validation studies for kidney failure prediction models, mortality prediction models and graft failure prediction models. Models to predict mortality on conservative care and dialysis and models to predict adverse outcomes after kidney transplantation were developed and validated. These results may improve shared decision-making processes and individualized medicine for patients with kidney disease. Show less
This thesis investigates the effectiveness and safety of treatments in patients with cardiovascular and kidney disease. Routinely collected healthcare data provide an immense opportunity to... Show moreThis thesis investigates the effectiveness and safety of treatments in patients with cardiovascular and kidney disease. Routinely collected healthcare data provide an immense opportunity to investigate such questions in populations underrepresented in clinical trials, such as patients with advanced chronic kidney disease (CKD).The first part of this thesis deals with how to appropriately use routinely collected data to answer causal questions. It illustrates what study designs eliminate commonly occurring biases, namely immortal time and prevalent user bias, and how to use propensity scores to correctly adjust for confounding in the setting of time-fixed and time-varying treatments.The second part investigates the effectiveness and safety of various treatments. For instance, the effectiveness of beta-blockers in patients with heart failure and advanced CKD is investigated. Renin-angiotensin system inhibitors (RASi) are an especially widely used medication class in CKD patients. The relationship between the magnitude of renal function decline - which is commonly observed after initiation of these drugs - with mortality and cardiorenal outcomes is investigated. In addition, comparative effectiveness study of RASi and calcium channel blockers among patients with advanced CKD is performed. In the last two chapters, a target trial is explicitly emulated to investigate the effect of stopping or continuing RASi and the optimal timing to start dialysis in patients with advanced chronic kidney disease. Show less
The main objective of this thesis was to determine the value of dialysis and conservative care for older patients with advanced chronic kidney disease. To do so, we compared a combination of... Show moreThe main objective of this thesis was to determine the value of dialysis and conservative care for older patients with advanced chronic kidney disease. To do so, we compared a combination of patient-relevant outcomes and treatment costs in a cohort of older patients (≥70 years old) who chose either dialysis or conservative care after a shared decision-making process. Overall, we observed that older patients who chose dialysis lived longer compared with older patients who chose conservative care. There was, however, little or no significant survival advantage in patients aged ≥80 years old and patients aged ≥70 years old with severe comorbidity who chose dialysis over conservative care, while similar outcomes on quality of life and symptoms were observed between both patient groups, and lower treatment burden and treatment costs were observed in patients who chose conservative care. Therefore, we conclude that conservative care is a viable treatment alternative to dialysis in selected older patients. In clinical practice, conservative care needs to become available and openly discussed as one of the possible treatment pathways for advanced chronic kidney disease in older patients. Moreover, a shift towards a person-centered process of shared decision-making is needed that aims to focus on all that matters to the patient as person, in order to come to a treatment plan that fits best with the patient. Show less
As the population is aging worldwide, and in spite of all preventive efforts, age-related diseases are increasingly prevalent, such as cardiovascular diseases and cognitive impairment. Different... Show moreAs the population is aging worldwide, and in spite of all preventive efforts, age-related diseases are increasingly prevalent, such as cardiovascular diseases and cognitive impairment. Different vascular risk factors, both the ‘traditional’ modifiable factors, such as hypertension or diabetes, and non-modifiable factors, such as age or gender, can lead to different kind of intertwined micro- and macrovascular diseases in various or multiple simultaneous organs. There is a growing need for knowledge regarding the interplay between different (co)morbidities, the relation of (co)morbidities with the various underlying pathophysiological mechanisms and treatment options of these (co)morbidities. Therefore, the aims of this thesis were to identify patients at high cardiovascular risk and to optimize treatment for these patients. We further unravelled the complexity of various interacting (poly) vascular diseases, ultimately leading to an increased risk of not only cognitive impairment, but also MACE including death. Identification of these patients and better understanding of the interplay and underlying mechanisms of these diseases is the first step towards preventive strategies. Treating these high risk patients can be a therapeutic challenge, but there is growing knowledge regarding both established and evolving therapies to optimize efficacy and efficiency. Show less
This thesis encompasses the role of various (modifiable) risk factors on the progression of chronic kidney disease, especially in study cohorts with a high baseline cardiovascular risk. We describe... Show moreThis thesis encompasses the role of various (modifiable) risk factors on the progression of chronic kidney disease, especially in study cohorts with a high baseline cardiovascular risk. We describe the influence of cardiovascular risk factors, for example obesity, diabetes and smoking, lifestyle factors like dietary protein intake, and cholesterol-lowering medication on the rate of kidney function decline. We concluded that patients with diabetes, hypertension, obesity or who smoke, have more rapid kidney function decline, and having more of these risk factors combined incrementally increases the rate of decline. On the other hand, a low-protein diet and use of cholesterol-lowering drugs were associated with slower kidney function decline. Additionally, birth weight in relation to kidney function at middle-age was explored, by three different approaches including Mendelian randomization using genetic data. Furthermore, we assessed the possible role of novel biomarkers in predicting acute kidney injury after cardiac surgery, which is also a well-known risk factor for chronic kidney disease. Finally, we describe the survival benefit of a simultaneous pancreas-kidney transplantation over a kidney transplantation alone, in type 1 diabetes patients with end-stage renal disease, using data of all Dutch type 1 diabetes patients with end-stage renal disease over the past 30 years. Show less
Chronic kidney disease (CKD) is a worldwide growing epidemic associated with an increased risk of cardiovascular morbidity and mortality. Heart failure is particularly frequent among patients... Show moreChronic kidney disease (CKD) is a worldwide growing epidemic associated with an increased risk of cardiovascular morbidity and mortality. Heart failure is particularly frequent among patients with CKD. Pressure and volume overload and non-hemodynamic factors associated with CKD induce left ventricular (LV) hypertrophy, reduce capillary density and increase myocardial fibrosis that lead to LV diastolic and systolic dysfunction. These processes have been proposed as important determinants of increased mortality in this population. The aim of this thesis was to evaluate cardiac mechanics using two-dimensional (speckle tracking) echocardiography and coronary computed tomography angiography in patients with CKD to define the prevalence and prognostic implications of cardiovascular diseases. In pre-dialysis and dialysis patients with preserved LV ejection fraction (LVEF), assessment of left ventricular global longitudinal strain (LV GLS) helps to identify patients with higher rates of heart failure hospitalization and all-cause mortality. When LVEF has already declined, patients within the lowest quartile of LV GLS showed worse prognosis compared to the other groups. The burden of cardiovascular diseases in patients with CKD is high and thorough assessment of cardiac mechanics with (advanced) echocardiographic techniques and coronary CTA helps in identifying patients with worse prognosis, who would potentially benefit of early treatment. Show less
This thesis aimed to provide insight in quality of life (QOL) as an outcome in pre-dialysis patients by investigating appropriate ways to measure this construct and by investigating factors... Show moreThis thesis aimed to provide insight in quality of life (QOL) as an outcome in pre-dialysis patients by investigating appropriate ways to measure this construct and by investigating factors affecting QOL. The second aim was to increase the understanding of the different associations between several cardiovascular risk factors and traditional outcomes in pre-dialysis and dialysis patients. In elderly pre-dialysis patients symptoms have a substantial impact on QOL. The effect of symptoms on a relevant outcome measure indicates symptoms which in turn affect other important outcomes, should have a more prominent role in clinical decision making. An appropriate way to measure the construct QOL in pre-dialysis patients with a short questionnaire is by using the SF-12. No association between dyslipidemia and start of dialysis in pre-dialysis patients was found. In pre-dialysis patients, both dual RAS blockade and single ACEi-use were associated with a lower risk of RRT or death, as compared with no RAS blockade. There is no association between vitamin K antagonist use and rate of renal function decline or time until start of dialysis in the pre-dialysis population. Vitamin K-antagonist use compared to no vitamin K-antagonist use is associated with an increased all-cause mortality risk in dialysis patients. Show less
