Background: Cardiovascular disease is a major contributor to mortality and morbidity in chronic kidney disease (CKD). Salt and water homeostasis and its management in advanced CKD present a significant clinical challenge. The thesis investigates the compartmental distribution of salt and water both in the steady state and in dynamic conditions induced by fluid removal on haemodialysis (HD). Methodology: In three clinical experimental studies with variable study designs, novel techniques of 23Sodium Magnetic Resonance Imaging and bioimpedance spectroscopy were applied to study salt and water compartmental distribution in pre-dialysis and in HD patients on conventional and extended regimes. Simultaneous measurements of the macro- and microcirculation were performed using blood pressure, pulse wave velocity and sublingual capillaroscopy. Blood samples were taken to measure pro-inflammatory and endothelial biomarkers. In the interventional studies during ultrafiltration (UF), real-time data were collected from continuous online blood volume measurements and interfaced with sessional treatment data records. An online bolus dilution approach was adopted to quantify plasma refill volumes. The Pietribiasi et al. computational transcapillary fluid transport model was applied to study fluid translocation during UF. Results: Salt and water accumulation is abnormally distributed in body fluid compartments in CKD. These abnormal states were strongly linked with inflammatory mediators that can lead to vascular endothelial injury. During UF, absolute refilling rates of 4.3Â±2.0ml/kg/hr remain relatively constant, with oscillations, during a stable HD session. An initial time delay in initiation of refill in the first 30 mins of UF was consistent in 80% of sessions. The refilling patterns observed during UF are unique and deviations from standard fluid transport models can be explained by altered transcapillary permeability factors. Conclusion: Salt and water accumulation in advanced CKD is abnormally distributed and has unique characteristics, both in steady state and in dynamic situations induced by UF. These characteristics can inform future improvements in assessing fluid compartments and in fluid removal strategies.
|Date of Award
|31 Dec 2019
- The University of Manchester
|Paul Brenchley (Supervisor) & Sandip Mitra (Supervisor)