Multimorbidity and the risk of major adverse kidney events: findings from the UK Biobank cohort
Ontology highlight
ABSTRACT: Background
Multimorbidity [the presence of two or more long-term conditions (LTCs)] is associated with a heightened risk of mortality, but little is known about its relationship with the risk of kidney events. Methods
Associations between multimorbidity and major adverse kidney events [MAKE: the need for long-term kidney replacement therapy, doubling of serum creatinine, fall of estimated glomerular filtration rate (eGFR) to <15 mL/min/1.73 m2 or 30% decline in eGFR] were studied in 68 505 participants from the UK Biobank cohort. Participants were enrolled in the study between 2006 and 2010. Associations between LTC counts and MAKE were tested using survival analyses accounting for the competing risk of death. Results
Over a median follow-up period of 12.0 years, 2963 participants had MAKE. There were associations between LTC count categories and the risk of MAKE [one LTC adjusted subhazard ratio (sHR) = 1.29, 95% confidence interval (CI) 1.15–1.45; two LTCs sHR = 1.74 (95% CI 1.55–1.96); and three or more LTCs sHR = 2.41 (95% CI 2.14–2.71)]. This finding was more pronounced when only cardiometabolic LTCs were considered [one LTC sHR = 1.58 (95% CI 1.45–1.73); two LTCs sHR = 3.17 (95% CI 2.80–3.59); and three or more LTCs sHR = 5.24 (95% CI 4.34–6.33)]. Combinations of LTCs associated with MAKE were identified. Diabetes, hypertension and coronary heart disease featured most commonly in high-risk combinations. Conclusions
Multimorbidity, and in particular cardiometabolic multimorbidity, is a risk factor for MAKE. Future research should study groups of patients who are at high risk of progressive kidney disease based on the number and type of LTCs. Graphical Abstract GRAPHICAL ABSTRACT
SUBMITTER: Sullivan M
PROVIDER: S-EPMC8573008 | biostudies-literature |
REPOSITORIES: biostudies-literature
Similar Datasets
Project description:BackgroundMultimorbidity is associated with higher mortality, but the relationship with cancer and cardiovascular mortality is unclear. The influence of demographics and type of condition on the relationship of multimorbidity with mortality remains unknown. We examine the relationship between multimorbidity (number/type) and cause of mortality and the impact of demographic factors on this relationship.MethodsData source: the UK Biobank; 500,769 participants; 37-73 years; 53.7% female. Exposure variables: number and type of long-term conditions (LTCs) (N = 43) at baseline, modelled separately. Cox regression models were used to study the impact of LTCs on all-cause/vascular/cancer mortality during median 7-year follow-up. All-cause mortality regression models were stratified by age/sex/socioeconomic status.ResultsAll-cause mortality is 2.9% (14,348 participants). Of all deaths, 8350 (58.2%) were cancer deaths and 2985 (20.8%) vascular deaths. Dose-response relationship is observed between the increasing number of LTCs and all-cause/cancer/vascular mortality. A strong association is observed between cardiometabolic multimorbidity and all three clinical outcomes; non-cardiometabolic multimorbidity (excluding cancer) is associated with all-cause/vascular mortality. All-cause mortality risk for those with ≥ 4 LTCs was nearly 3 times higher than those with no LTCs (HR 2.79, CI 2.61-2.98); for ≥ 4 cardiometabolic conditions, it was > 3 times higher (HR 3.20, CI 2.56-4.00); and for ≥ 4 non-cardiometabolic conditions (excluding cancer), it was 50% more (HR 1.50, CI 1.36-1.67). For those with ≥ 4 LTCs, morbidity combinations that included cardiometabolic conditions, chronic kidney disease, cancer, epilepsy, chronic obstructive pulmonary disease, depression, osteoporosis and connective tissue disorders had the greatest impact on all-cause mortality. In the stratified model by age/sex, absolute all-cause mortality was higher among the 60-73 age group with an increasing number of LTCs; however, the relative effect size of the increasing number of LTCs on higher mortality risk was larger among those 37-49 years, especially men. While socioeconomic status was a significant predictor of all-cause mortality, mortality risk with increasing number of LTCs remained constant across different socioeconomic gradients.ConclusionsMultimorbidity is associated with higher all-cause/cancer/vascular mortality. Type, as opposed to number, of LTCs may have an important role in understanding the relationship between multimorbidity and mortality. Multimorbidity had a greater relative impact on all-cause mortality in middle-aged as opposed to older populations, particularly males, which deserves exploration.
| S-EPMC6456941 | biostudies-literature
Project description:Aims:To examine the number and type of co-morbid long-term health conditions (LTCs) and their associations with all-cause mortality in an atrial fibrillation (AF) population. Methods and results:Community cohort participants (UK Biobank n?=?502?637) aged 37-73?years were recruited between 2006 and 2010. Self-reported LTCs (n?=?42) identified in people with AF at baseline. All-cause mortality was available for a median follow-up of 7?years (interquartile range 76-93?months). Hazard ratios (HRs) examined associations between number and type of co-morbid LTC and all-cause mortality, adjusting for age, sex, socio-economic status, smoking, and anticoagulation status. Three thousand six hundred fifty-one participants (0.7% of the study population) reported AF; mean age was 61.9?years. The all-cause mortality rate was 6.7% (248 participants) at 7?years. Atrial fibrillation participants with??4 co-morbidities had a six-fold higher risk of mortality compared to participants without any LTC. Co-morbid heart failure was associated with higher risk of mortality [HR 2.96, 95% confidence interval (CI) 1.83-4.80], whereas the presence of co-morbid stroke did not have a significant association. Among non-cardiometabolic conditions, presence of chronic obstructive pulmonary disease (HR 3.31, 95% CI 2.14-5.11) and osteoporosis (HR 3.13, 95% CI 1.63-6.01) was associated with a higher risk of mortality. Conclusion:Survival in middle-aged to older individuals with self-reported AF is strongly correlated with level of multimorbidity. This group should be targeted for interventions to optimize their management, which in turn may potentially reduce the impact of their co-morbidities on survival. Future AF clinical guidelines need to place greater emphasis on the issue of co-morbidity.
| S-EPMC6277149 | biostudies-literature
Project description:BACKGROUND:Sarcopenia, the loss of muscle strength and mass, predicts adverse outcomes and becomes common with age. There is recognition that sarcopenia may occur at younger ages in those with long-term conditions (LTCs) as well as those with multimorbidity (the presence of two or more LTCs), but their relationships have been little explored. Our aims were to describe the prevalence of sarcopenia in UK Biobank, a large sample of men and women aged 40-70 years, and to explore relationships with different categories of LTCs and multimorbidity. METHODS:We used data from 499 046 participants in the baseline of UK Biobank. Our main outcome was probable sarcopenia based on maximum grip strength below sex-specific cut-points. Participants' LTCs were recorded during an interview and categorized against a hierarchy. We used logistic regression to examine the independent associations between each category of LTCs and probable sarcopenia, including adjustment for age, sex, and body mass index. We also examined the association with multimorbidity. RESULTS:Probable sarcopenia had an overall prevalence of 5.3% and increased with age. The categories with the strongest associations with probable sarcopenia were musculoskeletal/trauma [OR 2.17 (95% CI: 2.11, 2.23)], endocrine/diabetes [OR 1.49 (95% CI: 1.45, 1.55)], and neurological/psychiatric [OR 1.39 (95% CI: 1.34, 1.43)] LTCs. Almost half of the sample (44.5%) had multimorbidity, and they were at nearly twice the odds of probable sarcopenia [OR 1.96 (95% CI: 1.91, 2.02)] compared with those without. CONCLUSIONS:We have shown an overall prevalence of 5.3% of probable sarcopenia at ages 40-70 in UK Biobank. The risk of probable sarcopenia was higher in those with some categories of LTCs, suggesting that these groups may stand to benefit from assessment of sarcopenia, during mid-life as well as old age.
| S-EPMC7015236 | biostudies-literature
Project description:BackgroundIt is now well recognised that the risk of severe COVID-19 increases with some long-term conditions (LTCs). However, prior research primarily focuses on individual LTCs and there is a lack of data on the influence of multimorbidity (≥2 LTCs) on the risk of COVID-19. Given the high prevalence of multimorbidity, more detailed understanding of the associations with multimorbidity and COVID-19 would improve risk stratification and help protect those most vulnerable to severe COVID-19. Here we examine the relationships between multimorbidity, polypharmacy (a proxy of multimorbidity), and COVID-19; and how these differ by sociodemographic, lifestyle, and physiological prognostic factors.Methods and findingsWe studied data from UK Biobank (428,199 participants; aged 37-73; recruited 2006-2010) on self-reported LTCs, medications, sociodemographic, lifestyle, and physiological measures which were linked to COVID-19 test data. Poisson regression models examined risk of COVID-19 by multimorbidity/polypharmacy and effect modification by COVID-19 prognostic factors (age/sex/ethnicity/socioeconomic status/smoking/physical activity/BMI/systolic blood pressure/renal function). 4,498 (1.05%) participants were tested; 1,324 (0.31%) tested positive for COVID-19. Compared with no LTCs, relative risk (RR) of COVID-19 in those with 1 LTC was no higher (RR 1.12 (CI 0.96-1.30)), whereas those with ≥2 LTCs had 48% higher risk; RR 1.48 (1.28-1.71). Compared with no cardiometabolic LTCs, having 1 and ≥2 cardiometabolic LTCs had a higher risk of COVID-19; RR 1.28 (1.12-1.46) and 1.77 (1.46-2.15), respectively. Polypharmacy was associated with a dose response higher risk of COVID-19. All prognostic factors were associated with a higher risk of COVID-19 infection in multimorbidity; being non-white, most socioeconomically deprived, BMI ≥40 kg/m2, and reduced renal function were associated with the highest risk of COVID-19 infection: RR 2.81 (2.09-3.78); 2.79 (2.00-3.90); 2.66 (1.88-3.76); 2.13 (1.46-3.12), respectively. No multiplicative interaction between multimorbidity and prognostic factors was identified. Important limitations include the low proportion of UK Biobank participants with COVID-19 test data (1.05%) and UK Biobank participants being more affluent, healthier and less ethnically diverse than the general population.ConclusionsIncreasing multimorbidity, especially cardiometabolic multimorbidity, and polypharmacy are associated with a higher risk of developing COVID-19. Those with multimorbidity and additional factors, such as non-white ethnicity, are at heightened risk of COVID-19.
| S-EPMC7440632 | biostudies-literature
Project description:Background and objectivesMajor adverse kidney events, a composite of death, new kidney replacement therapy, or persistent kidney dysfunction, is a potential patient-centered outcome for clinical trials in sepsis-associated kidney injury. We sought to determine the incidence of major adverse kidney events within 30 days and validate this end point in pediatric sepsis.Design, setting, participants, & measurementsWe conducted a retrospective observational study using the Pediatric Health Information Systems Plus database of patients >6 months to <18 years old with a diagnosis of severe sepsis/septic shock; orders for bacterial blood culture, antibiotics, and at least one fluid bolus on hospital day 0/1; and known hospital disposition between January 2007 and December 2011. The primary outcome was incidence of major adverse kidney events within 30 days. Major adverse kidney events within 30 days were validated against all-cause mortality at hospital discharge, hospital length of stay, total hospital costs, hospital readmission within 30 days and 1 year, and lowest eGFR between 3 months and 1 year after discharge. We reported incidence of major adverse kidney events within 30 days with 95% confidence intervals using robust SEM and used multivariable logistic regression to test the association of major adverse kidney events within 30 days with hospital costs and mortality.ResultsOf 1685 admissions, incidence of major adverse kidney events within 30 days was 9.6% (95% confidence interval, 8.1% to 11.0%), including 4.5% (95% confidence interval, 3.5% to 5.4%) death, 1.7% (95% confidence interval, 1.1% to 2.3%) kidney replacement therapy, and 5.8% (95% confidence interval, 4.7% to 6.9%) persistent kidney dysfunction. Patients with versus without major adverse kidney events within 30 days had higher all-cause mortality at hospital discharge (28% versus 1%; P<0.001), higher total hospital costs ($61,188; interquartile range, $21,272-140,356 versus $28,107; interquartile range, $13,056-72,697; P<0.001), and higher proportion with eGFR<60 ml/min per 1.73 m2 between 3 months and 1 year after discharge (19% versus 4%; P=0.001). Major adverse kidney events within 30 days was not associated with length of stay or readmissions.ConclusionsIn children with sepsis, major adverse kidney events within 30 days are common, feasible to measure, and a promising end point for future clinical trials.
| S-EPMC6500940 | biostudies-literature
Project description:BackgroundAcute kidney injury (AKI) survivors are at increased risk of major adverse kidney events (MAKEs), including chronic kidney disease (CKD), end-stage kidney disease (ESKD) and death. High-risk AKI patients may benefit from specialist follow-up, but factors associated with increased risk have not been reported.MethodsWe conducted a retrospective study of AKI patients admitted to a single centre between 2012 and 2016 who had a baseline estimated glomerular filtration rate (eGFR) >30 mL/min/1.73 m2 and were alive and independent of renal replacement therapy (RRT) at 30 days following discharge. AKI was identified using International Classification of Diseases, Tenth Revision codes and staged according to the Kidney Disease: Improving Global Outcomes criteria. Patients were excluded if they were kidney transplant recipients or if AKI was attributed to intrinsic kidney disease. We performed Cox regression models to examine MAKEs in the first year, defined as the composite of CKD (sustained 25% drop in eGFR), ESKD (requirement for chronic RRT or sustained eGFR <15 mL/min/1.73 m2) or death. We examined secondary outcomes (CKD, ESKD and death) using Cox and competing risk regression analyses.ResultsWe studied 2101 patients (mean ± SD age 69 ± 15 years, baseline eGFR 72 ± 23 mL/min/1.73 m2). Of these, 767 patients (37%) developed at least one MAKE (429 patients developed CKD, 21 patients developed ESKD, 375 patients died). MAKEs occurred more frequently with older age [hazard ratio (HR) 1.16 per decade, 95% confidence interval (CI) 1.10-1.24], greater severity of AKI (Stage 2 HR 1.38, 95% CI 1.16-1.64; Stage 3 HR 1.62, 95% CI 1.31-2.01), higher serum creatinine at discharge (HR 1.04 per 10 µmol/L, 95% CI 1.03-1.06), chronic heart failure (HR 1.41, 95% CI 1.19-1.67), liver disease (HR 1.68, 95% CI 1.39-2.03) and malignancy (non-metastatic HR 1.44, 95% CI 1.14-1.82; metastatic HR 2.26, 95% CI 1.80-2.83). Traditional risk factors (e.g. diabetes and cardiovascular disease) had limited predictive value.ConclusionsMore than a third of AKI patients develop MAKEs within the first year. Clinical variables available at the time of discharge can help identify patients at increased risk of such events.
| S-EPMC7886537 | biostudies-literature
Project description:ObjectiveTo evaluate the association between body composition and subsequent risk of the major gynecologic malignancies.MethodsThis is a prospective analysis of participants from the UK Biobank. We measured baseline body composition and confirmed cancer diagnosis through linkage to cancer and death registries. We evaluated hazard ratios (HRs) and confidence interval (CIs) with COX models adjusting for potential confounders.ResultsWe document 1430 cases of the top three gynecologic malignancies (uterine corpus cancer 847 cases, ovarian cancer 514 cases, and cervical cancer 69 cases) from 245,084 female participants (75,307 were premenopausal and 169,777 were postmenopausal). For premenopausal women, whole body fat-free mass (WBFFM) was associated with an increased risk of uterine corpus cancer (Adjusted HR per unit increase 1.04, 95% CI 1.02-1.06). For postmenopausal women, compared with the first quartile, the fourth quartile of WBFFM and whole body fat mass(WBFM) was associated with 2.16 (95% CI 1.49-3.13) times and 1.89 (95% CI 1.31-2.72) times of increased uterine corpus cancer risk, respectively. Regarding the distribution of body fat mass (FM)/fat-free mass (FFM), FFM distributed in the trunk was associate with increased uterine corpus cancer risk in premenopausal (HR 1.18,95% CI 1.07-1.31) and postmenopausal women (HR 1.13,95% CI 1.09-1.18). Meanwhile, FM/FFM distributed in the limbs present an U-shaped associations with uterine corpus cancer risk. We did not observe any association between aforementioned body composition indices with ovarian or cervical cancer.ConclusionFM is associated with an increased risk of uterine corpus cancer in postmenopausal women. Meanwhile, FFM is found to be a risk factor for uterine corpus cancer in both premenopausal and postmenopausal women. No association of body composition with ovarian or cervical cancer was observed.
| S-EPMC8267135 | biostudies-literature
Project description:ObjectiveThis study aims: (1) to describe the pattern and extent of multimorbidity and polypharmacy in UK Biobank participants with chronic obstructive pulmonary disease (COPD) and (2) to identify which comorbidities are associated with increased risk of adverse drug reactions (ADRs) resulting from polypharmacy.DesignCross-sectional.SettingCommunity cohort.ParticipantsUK Biobank participants comparing self-reported COPD (n=8317) with no COPD (n=494 323).OutcomesMultimorbidity (≥4 conditions) and polypharmacy (≥5 medications) in participants with COPD versus those without. Risk of ADRs (taking ≥3 medications associated with falls, constipation, urinary retention, central nervous system (CNS) depression, bleeding or renal injury) in relation to the presence of COPD and individual comorbidities.ResultsMultimorbidity was more common in participants with COPD than those without (17% vs 4%). Polypharmacy was highly prevalent (52% with COPD taking ≥5 medications vs 18% in those without COPD). Adjusting for age, sex and socioeconomic status, those with COPD were significantly more likely than those without to be prescribed ≥3 medications contributing to falls (OR 2.27, 95% CI 2.13 to 2.42), constipation (OR 3.42, 95% CI 3.10 to 3.77), urinary retention (OR 3.38, 95% CI 2.94 to 3.87), CNS depression (OR 3.75, 95% CI 3.31 to 4.25), bleeding (OR 4.61, 95% CI 3.35 to 6.19) and renal injury (OR 2.22, 95% CI 1.86 to 2.62). Concomitant cardiovascular disease was associated with the greatest risk of taking ≥3 medications associated with falls/renal injury. Concomitant mental health conditions were most strongly associated with medications linked with CNS depression/urinary retention/bleeding.ConclusionsMultimorbidity is common in COPD and associated with high levels of polypharmacy. Co-prescription of drugs with various ADRs is common. Future research should examine the effects on healthcare outcomes of co-prescribing multiple drugs with similar potential ADRs. Clinical guidelines should emphasise assessment of multimorbidity and ADR risk.
| S-EPMC5781016 | biostudies-literature
Project description:PurposeWe aimed to classify individuals with RA and ≥2 additional long-term conditions (LTCs) and describe the association between different LTC classes, number of LTCs and adverse health outcomes.MethodsWe used UK Biobank participants who reported RA (n=5,625) and employed latent class analysis (LCA) to create classes of LTC combinations for those with ≥2 additional LTCs. Cox-proportional hazard and negative binomial regression were used to compare the risk of all-cause mortality, major adverse cardiac events (MACE), and number of emergency hospitalisations over an 11-year follow-up across the different LTC classes and in those with RA plus one additional LTC. Persons with RA without LTCs were the reference group. Analyses were adjusted for demographic characteristics, smoking, BMI, alcohol consumption and physical activity.ResultsA total of 2,566 (46%) participants reported ≥2 LTCs in addition to RA. This involved 1,138 distinct LTC combinations of which 86% were reported by ≤2 individuals. LCA identified 5 morbidity-classes. The distinctive condition in the class with the highest mortality was cancer (class 5; HR 2.66 95%CI (1.91-3.70)). The highest MACE (HR 2.95 95%CI (2.11-4.14)) and emergency hospitalisations (rate ratio 3.01 (2.56-3.54)) were observed in class 3 which comprised asthma, COPD & CHD. There was an increase in mortality, MACE and emergency hospital admissions within each class as the number of LTCs increased.ConclusionsThe risk of adverse health outcomes in RA varied with different patterns of multimorbidity. The pattern of multimorbidity should be considered in risk assessment and formulating management plans in patients with RA.
| S-EPMC9926377 | biostudies-literature
Project description:BackgroundCommencing work at an early age has been linked to various risk factors for coronary heart disease (CHD), such as shift work and intensive job strain. However, the relationship between starting work too early and CHD risk remains largely unclear. We examined the association between age at job initiation and the risk of CHD.MethodsUK Biobank participants aged 38 to 70 years without cardiovascular disease who provided data on their age at job initiation were included. The primary outcome was CHD, which was ascertained using hospital and death records. The hazard ratios (HRs) and 95% confidence interval (CIs) for the association between age at job initiation and CHD were calculated using multivariable Cox regression.ResultsOf the 501,971 participants, 114,418 eligible participants were included in the final analysis. The median age at job initiation was 19.0 years. During the mean follow-up of 12.6 years, 6,130 (5.4%) first CHD events occurred. We observed that age at job initiation was inversely associated with CHD (HR 0.98, 95% CI 0.97-0.99), and the association was potentially J-shaped. The HRs for the < 17-year, 17-18-year, and 19-21-year age groups were 1.29 (95%CI 1.18-1.41), 1.12 (95% CI 1.03-1.22) and 1.05 (95% CI 0.97-1.14), respectively, compared with those of the ≥ 22-year group.ConclusionsAge at job initiation was associated with incident CHD, which was independent of socioeconomic status. Participants who commenced employment before the age of 19 years exhibited a higher risk of developing CHD later in adulthood.
| S-EPMC10614325 | biostudies-literature