Multimorbidity patterns, polypharmacy and their association with liver and kidney abnormalities in people over 65 years of age: a longitudinal study

Abstract

Background: The implementation of individual clinical practice guidelines in patients with multimorbidity often results in polypharmacy. Our aim was to analyse medication use according to longitudinal multimorbidity patterns (MP) and determine during a 5-year period (2012-16) which MP are associated with abnormal liver and kidney function in primary care patients over 65 years of age living in Catalonia.Methods: Design: Longitudinal study (years 2012 to 2016) based on the electronic health records contained in Information System for Research in Primary Care database of the Catalan Institute of Health (SIDIAP). Variables: age, sex, MP, medication and polypharmacy (drug exposure obtained from the Pharmacy Invoice Registry). Medicines were classified in accordance with the Anatomical Therapeutic Chemical Classification System (ATC). Glomerular filtration rate was used to determine abnormal kidney function, and serum levels of alkaline phosphatase, alanine transaminase and gamma-glutamyl transpeptidase were used to diagnose abnormal liver function. Statistics: For medication use in MP, we calculated annual mean packages of each drug in each MP, and observed/expected ratios were obtained by dividing mean packages in the cluster by mean packages of the same drug in the overall population. Logistic regression models were fitted to estimate the association between MP at baseline and abnormal kidney and liver function tests during follow up.Results: 916,619 patients were included, and 743,827 completed the follow up. We identified one polypharmacy profile per MP, and concluded that the most prescribed drugs in each pattern corresponded to the diseases overrepresented in that specific MP. The median of drugs ranged from 3 (Cluster 1 - Non-Specific) to 8 (Cluster 10 - Multisystem Pattern). Abnormal kidney function was most commonly observed in the Cluster 4 - Cardio-Circulatory and Renal (Odds Ratio [OR] 2.19; Confidence interval [CI] 95% 2.15-2.23) and Cluster 3 - Minority Metabolic Autoimmune-Inflammatory (OR 2.16; CI 95% 2.12-2.20) MP. A higher risk of abnormal liver function was observed in the Cluster 8 - Digestive (OR 3.39; CI 95% 3.30-3.49), and Cluster 4 - Cardio-Circulatory and Renal (OR 1.96; CI 95% 1.91-2.02) MP.Conclusions: A higher risk of abnormal kidney and liver function was observed in specific MP. The long-term characterisation of MP and polypharmacy illustrates the burden of chronic multimorbidity and polypharmacy in the elderly population.

Effectiveness and Safety of PD-1 Inhibitor Monotherapy for Elderly Patients with Advanced Non-Small Cell Lung Cancer: A Real-World Exploratory Study

“…Among them, the elderly patients with lung cancer also increase dramatically. Unfortunately, the increase in age is concomitant with decreased body fat rate, decline in liver and kidney function, and other physical conditions [24]. All these factors based on age could compromise the absorption, metabolism, and excretion of PD-1/PD-L1 inhibitors [25].…”

The interplay between kidney function and multimorbidity: A scoping review

“…Twelve studies examined the coexistence and interactions of CKD with other chronic diseases, nine of which conducted cluster analysis, and three used network analysis [16][17][18][19][20][21][22][23][24] . The studies were from Europe (k = 7), North America (k = 3), and Asia (k = 1).…”

“…We identified ten studies that looked at the association between multimorbidity (including CKD) and negative health outcomes (Table 2) 22,23,[33][34][35][36][37][38][39][40] . The studies were conducted among multimorbid populations in Europe (k = 7), USA (k = 1) and Asia (k = 1).…”

“…We did not identify any longitudinal study that assessed the relationship between kidney function and future multimorbidity burden/trajectories. However, we identified three studies that looked at the association between multimorbidity and the evolution of kidney function 23,29,32 . The studies were conducted in Europe (k = 2) and Asia (k = 1), and operationalized multimorbidity as the count of chronic diseases (k = 2) and as patterns of chronic diseases (k = 1).…”

“…The dose-response relationship between the number of long-term conditions and MAKE was more pronounced when only cardiometabolic multimorbidity was considered. Villen et al used data on 60 chronic disease groups from Spanish electronic health registers to group individuals into multimorbidity patterns, and observed their kidney function evolution over a 5-year period 23 . There were significant differences in the risk of incident kidney function impairment (defined as reductions in eGFR below 60 mL/min/1.73 m 2 ) across the ten identified patterns, with the highest risk observed occurring multimorbidity combinations in the UK Biobank cohort, the dyad of CKD and diabetes was associated with the highest risk of severe SARS-CoV-2 infection (defined as death or hospitalization due to COVID-19) 37 .…”