Background We explore longitudinal trajectories of clinical indicators, patient-reported outcomes, and hospitalizations, in the years preceding death in a population of older patients with advanced... Show moreBackground We explore longitudinal trajectories of clinical indicators, patient-reported outcomes, and hospitalizations, in the years preceding death in a population of older patients with advanced chronic kidney disease (CKD). Methods The EQUAL study is a European observational prospective cohort study with an incident eGFR Results We included 661 decedents with a median time to death of 2.0 years (IQR 0.9-3.2). During the years preceding death, eGFR, Subjective Global Assessment score, and blood pressure declined, with accelerations seen at 6 months preceding death. Serum hemoglobin, hematocrit, cholesterol, calcium, albumin, and sodium values declined slowly during follow-up, with accelerations observed between 6 and 12 months preceding death. Physical and mental quality of life declined linearly throughout follow-up. The number of reported symptoms was stable up to 2 years prior to death, with an acceleration observed at 1 year prior to death. The rate of hospitalization was stable at around one hospitalization per person year, increasing exponentially at 6 months preceding death. Conclusions We identified clinically relevant physiological accelerations in patient trajectories that began similar to 6 to 12 months prior to death, which are likely multifactorial in nature, but correlate with a surge in hospitalizations. Further research should focus on how to effectively use this knowledge to inform patient and family expectations, to benefit the planning of (end-of-life) care, and to establish clinical alert systems. Show less
Ramspek, C.L.; Boekee, R.; Evans, M.; Heimburger, O.; Snead, C.M.; Caskey, F.J.; ... ; EQUAL Study Investigators 2022
Introduction: Predicting the timing and occurrence of kidney replacement therapy (KRT), cardiovascular events, and death among patients with advanced chronic kidney disease (CKD) is clinically... Show moreIntroduction: Predicting the timing and occurrence of kidney replacement therapy (KRT), cardiovascular events, and death among patients with advanced chronic kidney disease (CKD) is clinically useful and relevant. We aimed to externally validate a recently developed CKD G4thorn risk calculator for these outcomes and to assess its potential clinical impact in guiding vascular access placement.Methods: We included 1517 patients from the European Quality (EQUAL) study, a European multicentre prospective cohort study of nephrology-referred advanced CKD patients aged $65 years. Model performance was assessed based on discrimination and calibration. Potential clinical utility for timing of referral for vascular access placement was studied with diagnostic measures and decision curve analysis (DCA).Results: The model showed a good discrimination for KRT and "death after KRT," with 2-year concordance (C) statistics of 0.74 and 0.76, respectively. Discrimination for cardiovascular events (2-year C-statistic: 0.70) and overall death (2-year C-statistic: 0.61) was poorer. Calibration was fairly accurate. Decision curves illustrated that using the model to guide vascular access referral would generally lead to less unused arteriovenous fistulas (AVFs) than following estimated glomerular filtration rate (eGFR) thresholds.Conclusion: This study shows moderate to good predictive performance of the model in an older cohort of nephrology-referred patients with advanced CKD. Using the model to guide referral for vascular access placement has potential in combating unnecessary vascular surgeries. Show less
Maarse, B.C.E.; Chesnaye, N.C.; Schouten, R.; Michels, W.M.; Bos, W.J.W.; Szymczak, M.; ... ; EQUAL Study Investigators 2022
Background Prospective cohort studies are challenging to deliver, with one of the main difficulties lying in retention of participants. The need to socially distance during the COVID-19 pandemic... Show moreBackground Prospective cohort studies are challenging to deliver, with one of the main difficulties lying in retention of participants. The need to socially distance during the COVID-19 pandemic has added to this challenge. The pre-COVID-19 adaptation of the European Quality (EQUAL) study in the UK to a remote form of follow-up for efficiency provides lessons for those who are considering changing their study design. Methods The EQUAL study is an international prospective cohort study of patients >= 65 years of age with advanced chronic kidney disease. Initially, patients were invited to complete a questionnaire (SF-36, Dialysis Symptom Index and Renal Treatment Satisfaction Questionnaire) at research clinics every 3-6 months, known as "traditional follow-up" (TFU). In 2018, all living patients were invited to switch to "efficient follow-up" (EFU), which used an abbreviated questionnaire consisting of SF-12 and Dialysis Symptom Index. These were administered centrally by post. Response rates were calculated using returned questionnaires as a proportion of surviving invitees, and error rates presented as the average percentage of unanswered questions or unclear answers, of total questions in returned questionnaires. Response and error rates were calculated 6-monthly in TFU to allow comparisons with EFU. Results Of the 504 patients initially recruited, 236 were still alive at the time of conversion to EFU; 111 of these (47%) consented to the change in follow-up. In those who consented, median TFU was 34 months, ranging from 0 to 42 months. Their response rates fell steadily from 88% (98/111) at month 0 of TFU, to 20% (3/15) at month 42. The response rate for the first EFU questionnaire was 60% (59/99) of those alive from TFU. With this improvement in response rates, the first EFU also lowered errors to baseline levels seen in early follow-up, after having almost trebled throughout traditional follow-up. Conclusions Overall, this study demonstrates that administration of shorter follow-up questionnaires by post rather than in person does not negatively impact patient response or error rates. These results may be reassuring for researchers who are trying to limit face-to-face contact with patients during the COVID-19 pandemic. Show less
BACKGROUND Cardiac troponin T (cTnT) is associated with mortality in chronic kidney disease (CKD). However, the association between longitudinal cTnT measurements and survival has not previously... Show moreBACKGROUND Cardiac troponin T (cTnT) is associated with mortality in chronic kidney disease (CKD). However, the association between longitudinal cTnT measurements and survival has not previously been assessed. OBJECTIVES This study determined whether various parameterizations of longitudinal cTnT measurements were associated with patient survival in the older population with advanced CKD. METHODS The EQUAL (European QUALity) study is an observational prospective cohort study that includes subjects with stage 4-5 CKD aged $65 years and not on dialysis. The study includes 176 participants in Sweden, where longitudinal information of cTnT was collected. The study uses joint models for longitudinal and time-to-event data to assess the longitudinal association between cTnT and survival. RESULTS There were 927 cTnT measurements (median 6 per patient) collected over a median follow-up of 2.4 years. The overall 5-year survival was 57% (95% CI: 46%-69%). Longitudinally measured cTnT was associated with mortality risk, with every SD increase in cTnT, at any time point, associated with a 3.3-fold increase in mortality risk (HR: 3.3; 95% CI: 2.5-4.6). The slope of the cTnT trajectory was also associated with increased mortality risk (HR: 3.2; 95% CI: 2.06.0), as was the area under the cTnT trajectory (HR: 4.2; 95% CI: 2.6-7.2), which reflected the cumulative cTnT exposure. CONCLUSIONS Longitudinally measured cTnT is independently associated with mortality risk in older patients with stage 4 and 5 CKD, which suggests that monitoring patients with cTnT could be a valuable tool for the identification of subjects with a high mortality risk. (J Am Coll Cardiol 2022;79:327-336) (c) 2022 by the American College of Cardiology Foundation. Show less
Maarse, B.C.E.; Chesnaye, N.C.; Schouten, R.; Michels, W.M.; Bos, W.J.W.; Szymczak, M.; ... ; EQUAL Study Investigators 2022
Background: Depressive symptoms are associated with adverse clinical outcomes in patients with end-stage kidney disease; however, few small studies have examined this association in patients with... Show moreBackground: Depressive symptoms are associated with adverse clinical outcomes in patients with end-stage kidney disease; however, few small studies have examined this association in patients with earlier phases of chronic kidney disease (CKD). We studied associations between baseline depressive symptoms and clinical outcomes in older patients with advanced CKD and examined whether these associations differed depending on sex. Methods: CKD patients (>= 65 years; estimated glomerular filtration rate <= 20 mL/min/1.73 m(2)) were included from a European multicentre prospective cohort between 2012 and 2019. Depressive symptoms were measured by the five-item Mental Health Inventory (cut-off <= 70; 0-100 scale). Cox proportional hazard analysis was used to study associations between depressive symptoms and time to dialysis initiation, all-cause mortality and these outcomes combined. A joint model was used to study the association between depressive symptoms and kidney function over time. Analyses were adjusted for potential baseline confounders. Results: Overall kidney function decline in 1326 patients was -0.12 mL/min/1.73 m(2)/month. A total of 515 patients showed depressive symptoms. No significant association was found between depressive symptoms and kidney function over time (P = 0.08). Unlike women, men with depressive symptoms had an increased mortality rate compared with those without symptoms [adjusted hazard ratio 1.41 (95% confidence interval 1.03-1.93)]. Depressive symptoms were not significantly associated with a higher hazard of dialysis initiation, or with the combined outcome (i.e. dialysis initiation and all-cause mortality). Conclusions: There was no significant association between depressive symptoms at baseline and decline in kidney function over time in older patients with advanced CKD. Depressive symptoms at baseline were associated with a higher mortality rate in men. Show less
Background-People with reduced glomerular filtration rate (GFR) often have elevated cardiac troponin T (cTnT) levels. It remains unclear how cTnT levels develop over time in those with chronic... Show moreBackground-People with reduced glomerular filtration rate (GFR) often have elevated cardiac troponin T (cTnT) levels. It remains unclear how cTnT levels develop over time in those with chronic kidney disease (CKD). The aim of this study was to prospectively study the association between cTnT and GFR over time in older advanced-stage CKD patients not on dialysis.Methods and Results-The EQUAL (European Quality Study) study is an observational prospective cohort study in stage 4 to 5 CKD patients aged >= 65 years not on dialysis (incident estimated GFR, <20 mL/min/1.73 m(2)). The EQUAL cohort used for the purpose of this study includes 171 patients followed in Sweden between April 2012 and December 2018. We used linear mixed models, adjusted for important groups of confounders, to investigate the effect of both measured GFR and estimated GFR on high-sensitivity cTnT (hs-cTnT) trajectory over 4 years. Almost all patients had at least 1 hs-cTnT measurement elevated above the 99th percentile of the general reference population (<= 14 ng/L). On average, hs-cTnT increased by 16%/year (95% CI, 13-19; P<0.0001). Each 15 mL/min/1.73 m(2) lower mean estimated GFR was associated with a 23% (95% CI, 14-31; P<0.0001) higher baseline hs-cTnT and 9% (95% CI, 5-13%; P<0.0001) steeper increase in hs-cTnT. The effect of estimated GFR on hs-cTnT trajectory was somewhat lower than a previous myocardial infarction (15%), but higher than presence of diabetes mellitus (4%) and male sex (5%).Conclusions-In CKD patients, hs-cTnT increases over time as renal function decreases. Lower CKD stage (each 15 mL/min/1.73 m2 lower) is independently associated with a steeper hs-cTnT increase over time in the same range as other established cardiovascular risk factors. Show less
Luijtgaarden, M.W.M. van de; Caskey, F.J.; Wanner, C.; Chesnaye, N.C.; Postorino, M.; Janmaat, C.J.; ... ; EQUAL Study Investigators 2019
Background The epidemiology and prognosis of chronic kidney disease (CKD) differ by sex. We aimed to compare symptom prevalence and the clinical state in women and men of >= 65years of age with... Show moreBackground The epidemiology and prognosis of chronic kidney disease (CKD) differ by sex. We aimed to compare symptom prevalence and the clinical state in women and men of >= 65years of age with advanced CKD receiving routine nephrology care.Methods The European QUALity study on treatment in advanced chronic kidney disease (EQUAL) study follows patients from six European countries of >= 65years of age years whose estimated glomerular filtration rate (eGFR) dropped to <= 20mL/min/1.73m(2) for the first time during the last 6 months. The Dialysis Symptom Index was used to assess the prevalence and severity of 33 uraemic symptoms. Data on the clinical state at baseline were collected from medical records. Prevalence was standardized using the age distribution of women as the reference.Results The results in women (n=512) and men (n=967) did not differ with age (77.0 versus 75.7years) or eGFR (19.0 versus 18.5). The median number of symptoms was 14 [interquartile range (IQR) 9-19] in women, and 11 (IQR 7-16) in men. Women most frequently reported fatigue {39% [95% confidence interval (CI) 34-45]} and bone/joint pain [37% (95% CI 32-42)] as severe symptoms, whereas more men reported difficulty in becoming sexually aroused [32% (95% CI 28-35)] and a decreased interest in sex [31% (95% CI 28-35)]. Anaemia [73% (95% CI 69-77) versus 85% (95% CI 82-87)] was less common in women than in men, as were smoking history and cardiovascular comorbidity. However, a diagnosis of liver disease other than cirrhosis, psychiatric disease and mild malnutrition were more common among women.Conclusions Women in secondary care with an incident eGFR <= 20mL/min/1.73m(2) reported a higher symptom burden, while their clinical state was considered similar or even more favourable as compared with men. Show less
Bilo, H.; Coentrao, L.; Couchoud, C.; Covic, A.; Sutter, J. de; Drechsler, C.; ... ; ERBP Methods Support Team 2015
Background. An increase in C-reactive protein (CRP) levels during a single haemodialysis (HD) session has been associated with mortality. These associations, however, are difficult to understand... Show moreBackground. An increase in C-reactive protein (CRP) levels during a single haemodialysis (HD) session has been associated with mortality. These associations, however, are difficult to understand from the current understanding of CRP metabolism. Methods. In 190 Swedish haemodialysis (HD) patients from the Mapping of Inflammatory Markers in Chronic Kidney Disease (MIMICK) cohort, CRP was measured before and after a HD session. During follow-up, events of death and censoring were recorded, and hazard ratios were calculated and analysed as a function of CRP variation. Results were replicated in 94 Dutch HD patients from the Netherlands Cooperative Study on the Adequacy of Dialysis (NECOSAD). In this cohort, also correlation and kappa statistics were calculated to assess concordance in CRP changes amid multiple dialysis sessions from the same individuals. Results. In both cohorts, mean CRP values did not increase during a single HD session. In the MIMICK, median (interquartile range) dialysis vintage was 29.0 (14.8-57.0) months. In both crude [hazard ratio (95% confidence interval): 1.008 (0.971-1.047)] and multivariate Cox models [0.996 (0.949-1.046)], no association was observed with mortality. In the NECOSAD, individuals endured 6.0 (6.012.0) months on dialysis. No association was found with mortality neither in a crude [0.961 (0.908-1.018)] nor in an adjusted analysis [0.978 (0.923-1.037)]. Finally, the concordance between changes in different sessions was poor. Conclusions. CRP changes during a single HD session do not associate with mortality, thereby adding to the biological uncertainty concerning the ability of CRP to rise in such a short period. Show less
