Physical Performance and Protein-energy Wasting in Chronic Kidney Disease and Nocturnal Hemodialysis

Patients with chronic kidney disease (CKD) have a high risk of developing a poor state of physical performance and malnutrition, called protein-energy wasting (PEW) in nephrology patients. Impaired physical performance and PEW are caused by a diversity of factors, such as symptoms of fatigue, nausea and loss of appetite, at first caused by the kidney disease itself. These symptoms often worsen during CKD progression and persist during dialysis treatment. Although this treatment is of great importance to prolong life, it comes with a high disease burden. Most patients choose incenter hemodialysis (HD) treatment as kidney replacement therapy, where the conventional approach is three or four a week of HD sessions for three to four hours. This approach only partially replaces kidney function and therefore medications and a strict dietary regimen are recommended. Additionally, HD has a catabolic effect which does not support physical condition. Consequently, maintaining an adequate physical condition and preventing PEW poses a considerable challenge for patients with CKD, especially when treated with HD. Therefore, the overall aim of this thesis was to investigate which factors influence the physical and nutritional condition of patients with CKD and patients undergoing HD. It examines the effects of prolonged (nocturnal) dialysis treatment and interventions related to exercise and nutrition. Additionally, the association between NHD treatment and cardiovascular biomarkers is investigated, along with a comparison of methods for calculating protein requirements in HD patients. In this thesis, chapter 2 describes the results of a systematic review and meta-analysis on exercise and nutritional interventions in CKD patients and patients treated with HD, focusing on outcomes of nutritional status, muscle strength, physical performance and QoL. In chapter 3, a systematic review is performed to investigate if conversion from CHD treatment to NHD treatment improves physical performance. In chapter 4 and 5, we describe the design and results of the prospective cohort and multicenter DiapriFIT study, with the aim to investigate if physical performance improves and PEW decreases in patients who change from CHD to NHD, compared to patient continuing their CHD treatment. Also, we measure TnT, NT-proBNP and FGF23 at start of the study and after six and twelve months of NHD treatment (chapter 6). At last, we investigate in chapter 7 different methods to calculate protein intake in hemodialysis patients. This thesis presents several key massages that need to be highlighted:  Integrate diagnostics: simultaneously assess physical performance and PEW in CKD patients, as they are complementary.  Combine assessments: use unified terminology and assessments for the physical and nutritional condition of patients with CKD to eliminate the need for separate diagnostics.  Routine evaluations: integrate regular assessment of physical performance and body composition into standard care for CKD patients, allowing for a more personalized approach.  Supportive approaches: consider NHD as a strategy to improve outcomes for patients with poor physical performance and PEW.  Future research: conduct studies to identify the most effective exercise and nutritional interventions for improving the physical and nutritional status of patients with CKD.