title: Interrogating disease clusters, multimorbidity and adverse outcomes in chronic kidney disease
Creators: name: Sullivan, Michael K.
Publisher: name: University of Glasgow
Year: 2023

description: Background Chronic kidney disease (CKD) is common amongst adults and it often co-exists with other chronic conditions. Compared to people with normal kidney function, people with CKD are at increased risk of kidney-specific outcomes like the need for dialysis, and other outcomes like cardiovascular events. As people age, chronic conditions including CKD become more common, and the risk of adverse outcomes increases. However, little is known about the ways in which CKD and multimorbidity relate to the risk of adverse outcomes. Multimorbidity is the presence of two or more chronic conditions in an individual. It affects more than half of people over the age of 65 and it is closely linked to frailty, socioeconomic deprivation, and reduced quality of life. However, it is not known if the associations between multimorbidity and adverse outcomes are dependent on particular combinations, or “clusters” of conditions. Methods and Results The overall hypothesis was that multimorbidity and clusters of chronic conditions are associated with adverse outcomes in populations with CKD. A systematic review and meta-analysis was followed by four quantitative studies. Four datasets were used: 1. UK Biobank: a prospective research study. 2. The Secure Anonymised Information Linkage Databank (SAIL): a primary care database for the population of Wales. 3. The Stockholm Creatinine Measurement project (SCREAM): a routine care database for the population of Stockholm, Sweden. 4. The International Severe Acute Respiratory and emerging Infection Consortium study (ISARIC): a prospective cohort study of patients hospitalised with COVID-19 in the UK. Associations between risk factors and adverse outcomes were studied. The main risk factors studied were the number of chronic conditions, type of chronic conditions, and combinations of conditions. The adverse outcomes were: mortality, hospitalisation, cardiovascular events, acute kidney injury, and major adverse kidney events. Finally, clustering statistical techniques were used to identify clusters of conditions and the associations between clusters and adverse outcomes were scrutinised. The research questions and the respective results were: 1. What are the associations between multimorbidity, CKD, and risk of adverse outcomes? A systematic review showed that amongst patients with CKD, there are associations between multimorbidity and mortality. However, most studies were in patients with advanced CKD and there was a paucity of research involving mild to moderate CKD or adverse outcomes other than mortality. 2. What are the associations between multimorbidity and risk of major adverse kidney events? The risk of major adverse kidney events increases as the number of chronic conditions increases, even amongst people with normal kidney function at baseline. Specific combinations of conditions are at particularly high risk, especially those including cardiometabolic conditions. 3. What are the associations between multimorbidity, CKD, and risk of hospitalisations? Multimorbidity is associated with an increased risk of emergency hospitalisations and the risk of hospitalisation is particularly high when CKD is one of the chronic conditions. Patients with CKD plus multiple cardiometabolic conditions, conditions affecting multiple systems of the body, and physical and mental health conditions are at heightened risk of hospitalisation. 4. What are the risk factors for acute kidney injury in COVID-19 and what is the association with mortality? Amongst patients hospitalised with COVID-19, risk factors for acute kidney injury are chronic conditions such as CKD and diabetes mellitus, black ethnicity, and severe COVID-19 illness on admission. AKI rates reduced as the pandemic progressed, but AKI remained a key risk factor for mortality. 5. Amongst patients with CKD, what clusters of chronic conditions are associated with the highest risk of adverse outcomes? Cardiovascular conditions cluster together, particularly in advanced CKD. Chronic pain and depression are important components of multimorbidity, and when combined with cardiometabolic conditions, are associated with adverse outcomes. The management of people with multimorbidity may be targeted based on clusters of conditions refined by kidney function. Conclusion Multimorbidity is common amongst people with CKD and it is an important risk factor for adverse outcomes. The risk of kidney events, cardiovascular events, hospitalisation, and mortality increases with the number of chronic conditions and with specific combinations of conditions. People with multiple cardiometabolic conditions are particularly likely to experience these adverse outcomes and these conditions cluster together amongst people with advanced CKD.