Assessment of kidney health: implications for living kidney donors and beyond

This thesis focusses on assessment of kidney health by investigating different aspects of living kidney donation. In the first part, we found that exact measurement of kidney function (“measured GFR: mGFR”) in all potential donors does not result in acceptation of more kidney donors compared to estimation of kidney function (“estimated GFR: eGFR”). Therefore, eGFR will be sufficient for the decision to accept a potential donor in the majority of donor candidates. Moreover, we showed that the CKD-EPI equation for eGFR based on both plasma creatinine and cystatin C, instead of either one of these markers, most accurately and precisely estimates GFR in donor candidates. For the prediction of post-donation GFR, we developed a new equation.During the transplantation procedure, biopsies are taken from the donor kidney. For part two of this thesis, we studied the density of capillaries in relation to pre- and post-donation kidney function. In healthy kidneys, there seems to be no relation between capillary density and kidney function.Shortly after donation, the remaining kidney compensates for the loss of functioning kidney mass. Previously it has been thought that this compensatory response could be harmful over time, resulting in poor long-term outcomes. However, we found that more compensation predicts better, instead of worse, long-term outcomes in living kidney donors

Myelin imaging:past, present, and beyond

In multiple sclerosis (MS) patients, the myelin sheath, which is the protective layer covering nerves, gets damaged. For monitoring of the progression of myelin damage and its repair an accurate direct measurement of myelin density is needed. In this thesis, we show the performances, pitfalls, and practical applications of myelin imaging methods for objectively measuring myelin density. [11C]MeDAS PET scanning is such a method. We demonstrated that [11C]MeDAS PET is a promising method for measuring myelin density as its signal in the brain, spinal cord, and MS lesions corresponded well with the physiological distribution of myelin. Furthermore, with [11C]MeDAS PET a decrease in myelin density within white matter lesions in MS patients over time could be detected. In addition, we used advanced diffusion MRI techniques and showed it enabled MS lesion characterization beyond traditional measures. Advanced analysis of brain networks with diagnostic MRI revealed some deterioration of brain regions involved in motor function. We also found that advanced statistical analyses applied to MRI data could be used to discriminate different MS subtypes