Patients with end-stage renal disease have an approximate eight fold increased mortality rate due to cardiovascular causes as compared with individuals of equal age and sex without renal... Show morePatients with end-stage renal disease have an approximate eight fold increased mortality rate due to cardiovascular causes as compared with individuals of equal age and sex without renal dysfunction. Whereas traditional cardiovascular risk factors (such as smoking, hypertension and obesity) fail to completely explain this surplus in risk, nontraditional risk factors seem of pathophysiological importance. This thesis aimed at studying the impact of an increased inflammatory state and nonthyroidal illness as potential nontraditional cardiovascular risk factors in patients with end-stage renal disease. Show less
Background. An increase in C-reactive protein (CRP) levels during a single haemodialysis (HD) session has been associated with mortality. These associations, however, are difficult to understand... Show moreBackground. An increase in C-reactive protein (CRP) levels during a single haemodialysis (HD) session has been associated with mortality. These associations, however, are difficult to understand from the current understanding of CRP metabolism. Methods. In 190 Swedish haemodialysis (HD) patients from the Mapping of Inflammatory Markers in Chronic Kidney Disease (MIMICK) cohort, CRP was measured before and after a HD session. During follow-up, events of death and censoring were recorded, and hazard ratios were calculated and analysed as a function of CRP variation. Results were replicated in 94 Dutch HD patients from the Netherlands Cooperative Study on the Adequacy of Dialysis (NECOSAD). In this cohort, also correlation and kappa statistics were calculated to assess concordance in CRP changes amid multiple dialysis sessions from the same individuals. Results. In both cohorts, mean CRP values did not increase during a single HD session. In the MIMICK, median (interquartile range) dialysis vintage was 29.0 (14.8-57.0) months. In both crude [hazard ratio (95% confidence interval): 1.008 (0.971-1.047)] and multivariate Cox models [0.996 (0.949-1.046)], no association was observed with mortality. In the NECOSAD, individuals endured 6.0 (6.012.0) months on dialysis. No association was found with mortality neither in a crude [0.961 (0.908-1.018)] nor in an adjusted analysis [0.978 (0.923-1.037)]. Finally, the concordance between changes in different sessions was poor. Conclusions. CRP changes during a single HD session do not associate with mortality, thereby adding to the biological uncertainty concerning the ability of CRP to rise in such a short period. Show less
Background: The long-term effects of perinatal growth and corticosteroid exposure on adrenal steroid concentrations in adults born very preterm are uncertain. Objectives: To examine the effect of... Show moreBackground: The long-term effects of perinatal growth and corticosteroid exposure on adrenal steroid concentrations in adults born very preterm are uncertain. Objectives: To examine the effect of birth weight, early postnatal growth, and pre- and postnatal corticosteroid administration on serum adrenal steroids in 19-year-old subjects born very preterm. Design and methods: Subjects born before 32 weeks of gestation in The Netherlands participating in the Project on Preterm and Small for Gestational Age Infants (POPS) were investigated at 19 years of age. Serum cortisol, DHEA sulfate (DHEAS), and androstenedione (Adione) concentrations were measured in 393 out of 676 eligible subjects, compared with controls, and associated with perinatal growth and pre- and postnatal corticosteroids administration using multiple linear regression analyses. Results: Serum DHEAS and Adione in men and women were higher than in controls. In the multiple regression analyses, birth weight SDS showed a statistically significant negative association with serum DHEAS concentrations in women (beta: -0.865, 95% confidence interval (CI): -1.254 to -0.476) and in men (beta: -0.758, 95% CI: -1.247 to -0.268) and with serum Adione concentrations in women (beta: -0.337, 95% CI: -0.593 to -0.082). Early postnatal weight gain showed no association with any of measured adrenal markers. In women, serum Adione was associated with postnatal dexamethasone exposure (beta: 0.932, 95% CI: 0.022 1.843). Conclusions: Young adults born very preterm show elevated adrenal androgens, particularly when born small for gestational age. Postnatal corticosteroid administration is positively associated with serum Adione in young women. Show less
