Inflammation & Infection in renal disease

In patients with chronic kidney disease (CKD) the mortality rate is high. An important contributing factor to the mortality rate is the activated state of the immune system that is seen in CKD, which is also called chronic systemic inflammation. One of the causes of this inflammatory state is immune activation due to bacterial stimulation. Recurrent (bacterial) infections form a repeated stimulus of the immune system, while also bacterial translocation from the gut due to a decreased intestinal barrier function forms a trigger of the immune system.
In the first part of this thesis, we focus on the intestinal barrier in CKD. We evaluate methods to measure the intestinal permeability, and focus on a possible cause and potential therapeutic target: butyrate. Butyrate is an important energy source for colonocytes and is produced through bacterial fermentation of dietary fiber. We evaluate whether a decreased abundance of butyrate producing species actually correlates with an increased intestinal permeability in patients with CKD.
In the second part of this thesis, we focus on the immune response against bacterial infections in CKD. We evaluated the role of a specific type of innate like T-cells, namely Mucosal Associated Invariant T- (MAIT) cells, in the defense against one of the most common infections: urinary tract infection (UTI). We have analyzed the phenotype and function of MAIT cells in the kidney, where they are likely involved in the defense against UTI. Furthermore, we demonstrate that circulating MAIT cells in women with recurrent UTI seem to be functionally impaired.