The Presence and Impact of Multimorbidity Clusters on Adverse Outcomes Across the Spectrum of Kidney Function

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/1.73m). 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/1.73m, most participants were in large clusters with no prominent conditions. At eGFR 15 and 30 mL/min/1.73m, clusters involving cardiovascular conditions were larger and were at the highest risk of adverse outcomes. At eGFR 30 mL/min/1.73m, 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/1.73m, 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.