The Health Burden Experienced by Patients with Chronic Kidney Disease: Quality of Life and Cancers

Abstract

Chronic kidney disease (CKD) is a leading public health problem affecting almost 700 million people globally and is the 12th leading cause of death worldwide.1 The increasing burden of CKD across the globe parallels the increase in ageing populations and the growing prevalence of vascular comorbid conditions like diabetes and hypertension. CKD is associated with increased morbidity and mortality, with patients experiencing an increased risk of death from related conditions such as heart disease and cancers. In 2017, CKD alone resulted in 1.2 million deaths universally.1 Additionally, 1.4 million deaths from cardiovascular disease were attributed to impaired kidney function. CKD is associated with multiple comorbidities which adversely impacts on the life of affected persons and results in reduced quality of life (QoL) compared to the general population,2 with a trend for the lowest QoL experienced by those with kidney failure requiring dialysis.3 Utilities are the numerical value attached to the strength of an individual's preference for specific health-related outcomes. Utility is measured on a 0 to 1 scale, where 0 represents death and 1 represents full health.3 While previous studies have assessed QoL measures in CKD, few have examined domain-specific data in detail across a wide spectrum of CKD stages. Knowledge of factors that negatively affect QoL in CKD may help inform the development of targeted interventions and health policies to help improve QoL in this population. Impaired kidney function is an independent risk factor for cardiovascular disease and all cause mortality, particularly in those with kidney failure requiring dialysis. Kidney transplantation remains the treatment of choice for most patients with kidney failure and is associated with improved survival and QoL compared with treatment with dialysis. However, kidney transplantation is associated with an increased risk of multiple complications through exposure to chronic immunosuppression, with cancer now the leading cause of death in this population.4 Although clinical practice guidelines recommend age and sex-specific screening for potential kidney transplant recipients, cancers ensuing early post-transplant may occur. The incidence and clinical outcomes of these cancers remain uncertain. Knowledge of the epidemiology of these cancers and their risk factors for adverse outcomes will help identify those patients at high risk for developing early cancers post-transplant and facilitate appropriate interventions such as targeted cancer screening in this at-risk population. The aims of this thesis are two-fold. Firstly, we aimed to compare the overall and domain specific QoL in a large cohort of patients with different stages of CKD (stage 3-5, dialysis and kidney transplant recipients) and determine the factors associated with reduced QoL. Secondly, we aimed to compare the burden, frequency, type, stages of cancers and risk of mortality with cancer that occurred early (12 months) after kidney transplantation. Chapter 1 describes and quantifies the disease burden of patients with kidney disease. Chapter 2 reports the QoL experienced by people with CKD, across a broad spectrum of CKD stages and explores overall and domain-specific QoL measures and factors associated with decrements in QoL. Chapter 3 reports the burden of early cancers (occurring <12 months) after kidney transplantation and describes the types, stages, frequency of these cancers, explores mortality associated with early cancers and factors associated with mortality from these cancers. Chapter 4 focusses on discussions related to quality of life in CKD and early posttransplant cancers and future steps on improving care for this group of patients. This thesis generated original insights into the QoL experienced by patients across a broad spectrum of CKD, the factors associated with poor QoL and highlights the need for novel social and medical interventions to support this vulnerable group. This work also provides insight into the burden of early cancers experienced by kidney transplant recipients, which in turn leads to increased morbidity and mortality and emphasizes the need for development of screening and treatment approaches to help improve outcomes in this population