The presence and impact of multimorbidity clusters on adverse outcomes across the spectrum of kidney function

Abstract

Background Multimorbidity (the presence of two or more chronic conditions) is common amongst people with chronic kidney disease, but it is unclear which conditions cluster together and if this changes as kidney function declines. We explored which clusters of conditions are associated with different estimated glomerular filtration rates (eGFRs) and studied associations between these clusters and adverse outcomes. Methods Two population-based cohort studies were used: the Stockholm Creatinine Measurements project (SCREAM, Sweden, 2006–2018) and the Secure Anonymised Information Linkage Databank (SAIL, Wales, 2006–2021). We studied participants in SCREAM (404,681 adults) and SAIL (533,362) whose eGFR declined lower than thresholds (90, 75, 60, 45, 30 and 15 mL/min/1.73m2). Clusters based on 27 chronic conditions were identified. We described the most common chronic condition(s) in each cluster and studied their association with adverse outcomes using Cox proportional hazards models (all-cause mortality (ACM) and major adverse cardiovascular events (MACE)). Results Chronic conditions became more common and clustered differently across lower eGFR categories. At eGFR 90, 75, and 60 mL/min/1.73m2, most participants were in large clusters with no prominent conditions. At eGFR 15 and 30 mL/min/1.73m2, clusters involving cardiovascular conditions were larger and were at the highest risk of adverse outcomes. At eGFR 30 mL/min/1.73m2, in the heart failure, peripheral vascular disease and diabetes cluster in SCREAM, ACM hazard ratio (HR) is 2.66 (95% confidence interval (CI) 2.31–3.07) and MACE HR is 4.18 (CI 3.65–4.78); in the heart failure and atrial fibrillation cluster in SAIL, ACM HR is 2.23 (CI 2.04 to 2.44) and MACE HR is 3.43 (CI 3.22–3.64). Chronic pain and depression were common and associated with adverse outcomes when combined with physical conditions. At eGFR 30 mL/min/1.73m2, in the chronic pain, heart failure and myocardial infarction cluster in SCREAM, ACM HR is 2.00 (CI 1.62–2.46) and MACE HR is 4.09 (CI 3.39–4.93); in the depression, chronic pain and stroke cluster in SAIL, ACM HR is 1.38 (CI 1.18–1.61) and MACE HR is 1.58 (CI 1.42–1.76). Conclusions Patterns of multimorbidity and corresponding risk of adverse outcomes varied with declining eGFR. While diabetes and cardiovascular disease are known high-risk conditions, chronic pain and depression emerged as important conditions and associated with adverse outcomes when combined with physical conditions.

Sex-stratified multimorbidity trajectories in UK Biobank cohort identify triage rules for the risk of mortality and hospitalisation in secondary care

“…Recently, association between clusters of multimorbidity patterns within groups of CKD patients and adverse events has been investigated, nding adverse outcomes to be associated with patterns of multimorbidity including known patterns of diabetes and cardiovascular disease, and relatively unknown patterns of pain and depression (Sullivan et al, 2022). Our results support this, showing that there are multimorbidity patterns that should be identi ed at diagnosis of renal failure in order to triage secondary care females and males.…”

Patterns of multimorbidity in primary care electronic health records: A systematic review

“…In such analyses, a disease may belong to more than one pattern, and the use of higher-level categories may hinder the identification of individuals who could benefit from earlier and/or more targeted interventions. For instance, Sullivan et al 58 found that the composition of multimorbidity patterns varied significantly based on the level of kidney dysfunction assessed using the estimated glomerular filtration rate (eGFR), with cardiovascular conditions becoming increasingly prominent at lower eGFR levels. Therefore, careful consideration of accuracy and granularity when defining chronic conditions is important to maintain a balance between disease misclassification and loss of potentially critical information.…”

Prevalence, patterns, and impacts of multimorbidity on adverse clinical outcomes in chronic kidney disease

“…While older people had more multimorbidity burdens, younger patients with CKD were at a higher risk of death from multimorbidity (36, 37). Severe CKD (eGFR <30 ml/min/1.73m 2 ) with clusters of heart failure, peripheral vascular disease, atrial brillation, diabetes, chronic pain, and depression was signi cantly associated with all-cause mortality and major cardiovascular events (32).…”