Background and aims: There is an ongoing need to recognize early kidney injury and its progression in structural chronic pathologies. The proteins NGAL, IGFBP7, TIMP2, KIM-1, CXCL9, TGF-beta 1,... Show moreBackground and aims: There is an ongoing need to recognize early kidney injury and its progression in structural chronic pathologies. The proteins NGAL, IGFBP7, TIMP2, KIM-1, CXCL9, TGF-beta 1, SLC22A2, nephrin, cubilin and uromodulin have been proposed as early kidney injury biomarkers. To guide clinical interpretation, their urinary concentrations should be accompanied by reference intervals, which we here establish in a representative Dutch middle-aged population. Materials and Methods: The 24-h urine samples from 1443 Caucasian middle-aged men and women, were analyzed for the biomarkers by quantitative LC-MS/MS. Biomarker excretion per 24-h were calculated, and urine creatinine and osmolality were measured for dilution normalization. This population was characterized by demographic and anthropometric parameters, comorbid conditions, and conventional kidney function measures. Results: NGAL, IGFBP7, TIMP2, KIM-1 and uromodulin could be quantified in this population, whereas nephrin, SLC22A2 and CXCL9 were below their detection limits. Urine creatinine and osmolality ( r= -were correlated to urine volume (r = -0.71; -0.74) and to IGFBP7 (r = 0.73; 0.71) and TIMP2 (r = 0.71; 0.69). Crude and normalized biomarker concentrations were affected by sex, but not by age, BMI, smoking, kidney function or common comorbid conditions. The reference intervals (men; women) were 18-108; 21-131 pmol IGFBP7/mmol creatinine, 1- 63; 4-224 pmol NGAL/mmol creatinine, 7-48; 7- 59 pmol TIMP2/mmol creatinine, <1-9; <1-12 pmol KIM-1/mmol creatinine and 0.1-1.2; 0.1-1.7 mg uromodulin/mmol creatinine. Conclusion: We present dilution-normalized and sex-stratified urinary reference intervals of kidney injury biomarkers in a middle-aged Caucasian population. Show less
In the area of paediatric cardiac intensive care many questions remain unanswered. The professionals taking care of these children should always aim to look for new insights, knowledge and... Show moreIn the area of paediatric cardiac intensive care many questions remain unanswered. The professionals taking care of these children should always aim to look for new insights, knowledge and scientific progress. Clinical studies, such as those presented in this thesis can sometimesanswer a question, but more often give direction for further research. And until we have sound scientific evidence, the paediatric (cardiac) intensivist will have to deliver postoperative care based on the available pathophysiological and pharmacological knowledge, their own clinical experience, sound judgment and common sense.Be amazed. Wonder. Search. And most importantly, be critical of what you think youknow. Show less
Prolactinoma are treated with dopamine agonists, which are effective in reducing prolactin and tumor size. Studies reporting clinical and radiological outcome are scarce. The study described in... Show moreProlactinoma are treated with dopamine agonists, which are effective in reducing prolactin and tumor size. Studies reporting clinical and radiological outcome are scarce. The study described in chapter 2, assesses long-term outcome in patients treated with dopamine agonists for macroprolactinoma. An increased risk of cardiac valve disease has been reported in patients treated with cabergoline for Parkinson__s disease. Stimulation of serotonin receptors on cardiac valves by dopamine agonists results in fibrotic changes. The study described in chapter 3, assesses prevalence of valve regurgitation in patients treated for prolactinomas. Many patients with pituitary diseases suffer from decreased quality of life. Although prolactinomas present with emotional disturbances, quality of life has not been assessed in these patients. The study described in chapter 4, assesses quality of life in patients treated for microprolactinomas using four health-related questionnaires. The study described in chapter 5 compares quality of life, adjusted for age and gender, of patients after treatment for different pituitary adenomas. Malignant prolactinoma is rare manifestation, diagnosed at moment metastasis occur. The study described in chapter 6 evaluates history of patient with malignant prolactinoma, and provides an overview of radiological and histological characteristics and treatment of all cases with malignant prolactinomas published in literature. Show less
