Optimising care in chronic kidney disease with risk prediction tools and better hyperkalaemia management

Abstract

Chronic kidney disease (CKD) is a highly prevalent condition worldwide that is associated with major health consequences. Patients with progressive and advanced disease can experience significant multi-system complications as well as an increased risk of end-stage renal disease (ESRD) and mortality. Using data from the Salford Kidney Study, an ongoing observational cohort study of non-dialysis patients with CKD stages 3 to 5, this thesis aimed to explore two major research themes related to optimising CKD care. The first was risk prediction in CKD: the capacity to accurately risk stratify patients in order to enable timely, targeted treatment to those most likely to sustain adverse outcomes. The second concerned better hyperkalaemia management: effectively negating the occurrence of hyperkalaemia can facilitate continuation and optimisation of renin-angiotensin-aldosterone system inhibitors (RAASi), which are well established renoprotective agents. Results chapters 4 to 8 focused on areas in the field of risk prediction. Chapter 4 highlighted the differential impact of risk determinants in different primary renal disease groups with emphasis on ESRD and mortality for those with rapid linear progression and those with stable disease. Those progressing rapidly can be further differentiated with respect to clinical endpoints by their pattern of progression, detailed in chapter 5. Chapter 6 reinforced the need to account for the rate and pattern of CKD progression when attempting to identify novel biomarkers of disease. Risk prediction tools exist such as the Kidney Failure Risk Equation (KFRE), designed to predict the 2- and 5-year risk of ESRD in patients with CKD stages 3-5. Chapter 7 demonstrated that the KFRE is not wholly accurate when used for risk prediction in transplant recipients but does have clinical utility in those with advanced CKD as analysed in chapter 8. This provides compelling evidence for shifting towards risk-based tools to guide decision making in clinical practice. With respect to hyperkalaemia management, chapter 9 emphasised the efficacy of patiromer, a novel potassium binder, in maintaining normokalaemia. This effect was harnessed to successfully up-titrate RAASi dosing in patients with symptomatic heart failure attending a bespoke hyperkalaemia clinic, which was described in chapter 10. Whilst all the studies in this thesis have helped to deepen our understanding in the field of CKD care, the strength of the KFRE for risk prediction in advanced CKD and the real-world experience of the effectiveness of oral potassium binders have emerged as major findings. This will hopefully provide optimism for future research into tackling the heterogeneity and complexity of CKD management so as to improve long-term patient prognosis.

Date of Award	1 Aug 2022
Original language	English
Awarding Institution	The University of Manchester
Supervisor	Philip Kalra (Supervisor) & Darren Green (Supervisor)