BackgroundAn important aspect of end-of-life decisions in dialysis patients is elective withdrawal from dialysis therapy. Several studies have shown that clinical factors, such as comorbidity, play... Show moreBackgroundAn important aspect of end-of-life decisions in dialysis patients is elective withdrawal from dialysis therapy. Several studies have shown that clinical factors, such as comorbidity, play a role in dialysis withdrawal. The role of symptoms of anxiety and depression is largely unknown. The.MethodsA prospective multi-center study has been set up to investigate anxiety and depressive symptoms longitudinally in dialysis patients. Anxiety and depressive symptoms were investigated using the Beck Anxiety Inventory (BAI) and Beck Depression Inventory (BDI) as baseline. Adverse events, including dialysis withdrawal and mortality were registered during follow-up. Multivariable cox proportional hazard models were used with anxiety and depression as the independent variable and dialysis withdrawal as the outcome variable. Models included age, sex, ethnicity and a set of clinical comorbidities.ResultsA total of 687 patients were included between 2012 and 2017, with a median follow-up of 3.2 years. A total of 48 patients (7%) withdrew from dialysis therapy, and subsequently deceased. Anxiety and depressive symptoms at baseline showed an association with dialysis withdrawal with hazard ratios of 2.31 (1.09-4.88) for anxiety and 2.56 (1.27-5.15) for depressive symptoms, independent of somatic comorbidities.DiscussionWithdrawal from dialysis therapy is associated with anxiety and depressive symptoms. Dialysis patients with more severe depressive and anxiety symptoms were more vulnerable for dialysis withdrawal. Insight in factors that play a role in dialysis withdrawal could aid patients and clinicians making an informed decision and develop clinical guidelines. Show less
Background:The long-term effects of schistosomiasis on the glomerulus may contribute to the development of chronic kidney disease. This study aimed to investigate baseline Schistosoma mansoni-Circu... Show moreBackground:The long-term effects of schistosomiasis on the glomerulus may contribute to the development of chronic kidney disease. This study aimed to investigate baseline Schistosoma mansoni-Circulating Anodic Antigen (CAA) levels and their association with kidney biomarkers related to podocyte injury and inflammation in long-term follow-up after praziquantel (PZQ) treatment.Methods:Schistosoma infection was diagnosed by detecting CAA in urine using a quantitative assay based on lateral flow using luminescent up-converting phosphor reporter particles. A cutoff threshold of 0.1 pg/mL CAA was used to diagnose Schistosoma infection (baseline) in a low-prevalence area in Ceará, Northeast, Brazil. Two groups were included: CAA-positive and CAA-negative individuals, both of which received a single dose of PZQ at baseline. Urinary samples from 55 individuals were evaluated before (baseline) and at 1, 2, and 3 years after PZQ treatment. At all time points, kidney biomarkers were quantified in urine and adjusted for urinary creatinine levels.Results:CAA-positive patients had increased baseline albuminuria and proteinuria and showed greater associations between kidney biomarkers. CAA levels correlated only with Vascular Endothelial Growth Factor (VEGF) (podocyte injury) levels. Increasing trends were observed for malondialdehyde (oxidative stress), monocyte chemoattractant protein-1 (inflammation marker), and VEGF. In the follow-up analysis, no relevant differences were observed in kidney biomarkers between the groups and different periods.Conclusions:S. mansoni-infected individuals presented subclinical signs of glomerular damage that may reflect podocyte injury. However, no causal effect on long-term renal function was observed after PZQ treatment. Show less
The main objectives of this thesis were to investigate the association between kidney disease and venous and arterial thrombosis and to provide insight in the mechanism of the association between... Show moreThe main objectives of this thesis were to investigate the association between kidney disease and venous and arterial thrombosis and to provide insight in the mechanism of the association between kidney disease and thrombosis. Furthermore, the mortality risks for hemodialysis patients with catheter, fistula and graft vascular accesses were investigated. Our studies showed that kidney disease was associated with an increased risk of venous thrombosis. We showed that patients with chronic kidney disease stages 1__3 (early stages) had an almost 2-fold increased risk of venous thrombosis as compared with subjects without chronic kidney disease. We also showed that patients with a severely decreased kidney function (estimated glomerular filtration rate <30 ml/min) had a 6-fold increased risk of venous thrombosis as compared with persons with a normal kidney function. Furthermore, it was shown that dialysis patients have increased risks of myocardial infarction and ischemic stroke. Dialysis patients with a catheter had increased mortality risks as compared with dialysis patients with an arteriovenous access (fistula or graft). An important mechanism for the increased thrombosis risk in patients with a kidney disease could be hypercoagulability (increased factor VIII and von Willebrand factor levels). 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
Primary IgA nephropathy (IgAN) is the most common form of primary glomerulonephritis world wide and leads to end stage renal disease in 30-50% of patients. The hallmark of IgAN is the deposition... Show morePrimary IgA nephropathy (IgAN) is the most common form of primary glomerulonephritis world wide and leads to end stage renal disease in 30-50% of patients. The hallmark of IgAN is the deposition of IgA1 in the mesangial area of the kidney. Since the inflammatory response which leads to progressive renal disease, is triggered and sustained by the deposition of IgA in the renal mesangium, it is important to determine by which mechanisms binding to mesangial cells (MC) occurs. Most likely both the intrinsic renal features, as well as circulating factors, such as structural alterations in serum IgA molecules are thought to be involved in the pathogenesis of IgAN. In this thesis we concentrated on two aspects. First identify and further characterize the IgA binding receptors potentially playing a role in IgA nephropathy, including FcRI/CD89, Fc/µR. Furthermore, we characterized the different molecular forms of IgA with special attention to the specific glycosylation patterns. Finally, we found a clear deposition of SIgA in the glomeruli of IgA nephropathy patients. Altogether, the data presented in this thesis support a role for SIgA in the pathogenesis of a subpopulation of IgAN patients. Show less
