Introduction: It is assumed that identification and correction of asymptomatic stenoses in the vascular access circuit will prevent thrombosis that would require urgent intervention to continue... Show moreIntroduction: It is assumed that identification and correction of asymptomatic stenoses in the vascular access circuit will prevent thrombosis that would require urgent intervention to continue hemodialysis treatment. However, the evidence base for this assumption is limited. Recent international clinical practice guidelines reach different conclusions on the use of surveillance for vascular access flow dysfunction and recommend further research to inform clinical practice.Methods: The FLOW trial is a double-blind, multicenter, randomized controlled trial with a 1:1 individual participant treatment allocation ratio over two study arms. In the intervention group, only symptomatic vascular access stenoses detected by clinical monitoring are treated, whereas in the comparison group asymptomatic stenoses detected by surveillance using monthly dilution flow measurements are treated as well. Hemodialysis patients with a functional arteriovenous vascular access are enrolled. The primary outcome is the access-related intervention rate that will be analyzed using a general linear model with Poisson distribution. Secondary outcomes include patient satisfaction, access-related serious adverse events, and quality of the surveillance process. A cost effectiveness analysis and budget impact analysis will also be conducted. The study requires 828 patient-years of follow-up in 417 participants to detect a difference of 0.25 access-related interventions per year between study groups.Discussion: As one of the largest randomized controlled trials assessing the clinical impact of vascular access surveillance using a strong double-blinded study design, we believe the FLOW trial will provide much-needed evidence to improve vascular access care for hemodialysis patients. Show less
Milders, J.; Ramspek, C.L.; Janse, R.J.; Bos, W.J.W.; Rotmans, J.I.; Dekker, F.W.; Diepen, M. van 2023
Prognostic models can strongly support individualized care provision and well-informed shared decision making. There has been an upsurge of prognostic research in the field of nephrology, but the... Show morePrognostic models can strongly support individualized care provision and well-informed shared decision making. There has been an upsurge of prognostic research in the field of nephrology, but the uptake of prognostic models in clinical practice remains limited. Therefore, we map out the research field of prognostic models for kidney patients and provide directions on how to proceed from here. We performed a scoping review of studies developing, validating, or updating a prognostic model for patients with CKD. We searched all published models in PubMed and Embase and report predicted outcomes, methodological quality, and validation and/or updating efforts. We found 602 studies, of which 30.1% concerned CKD populations, 31.6% dialysis populations, and 38.4% kidney transplantation populations. The most frequently predicted outcomes were mortality (n=129), kidney disease progression (n=75), and kidney graft survival (n=54). Most studies provided discrimination measures (80.4%), but much less showed calibration results (43.4%). Of the 415 development studies, 28.0% did not perform any validation and 57.6% performed only internal validation. Moreover, only 111 models (26.7%) were externally validated either in the development study itself or in an independent external validation study. Finally, in 45.8% of development studies no useable version of the model was reported. To conclude, many prognostic models have been developed for patients with CKD, mainly for outcomes related to kidney disease progression and patient/graft survival. To bridge the gap between prediction research and kidney patient care, patient-reported outcomes, methodological rigor, complete reporting of prognostic models, external validation, updating, and impact assessment urgently need more attention. Show less
Rationale & Objective: Cardiovascular disease is the leading cause of morbidity and mortality in chronic kidney disease (CKD). We investigated 184 inflammatory and cardiovascular proteins to... Show moreRationale & Objective: Cardiovascular disease is the leading cause of morbidity and mortality in chronic kidney disease (CKD). We investigated 184 inflammatory and cardiovascular proteins to determine their potential as biomarkers for major cardiovascular events (MACEs).Study Design: The European Quality (EQUAL) is an observational cohort study that enrolled people aged >= 65 years with an estimated glomerular filtration rate <= 20 mL/min/1.73 m(2).Setting & Participants: Recruited participants were split into the discovery (n = 611) and replication cohorts (n = 292).Exposure: Levels of 184 blood proteins were measured at the baseline visit, and each protein was analyzed individually.Outcome: MACE.Analytical Approach: Cox proportional hazard models adjusted for age, sex, estimated glomerular filtration rate, previous MACE, and country were used to determine the risk of MACE. Proteins with false discovery rate adjusted P values of <0.05 in the discovery cohort were tested in the replication cohort. Sensitivity analyses were performed by adjusting for traditional risk factors, CKD-specific risk factors, and level of proteinuria and segregating atherosclerotic and nonatherosclerotic MACE.Results: During a median follow-up of 2.9 years, 349 people (39%) experienced a MACE. Forty-eight proteins were associated with MACE in the discovery cohort; 9 of these were reproduced in the replication cohort. Three of these proteins maintained a strong association with MACE after adjustment for traditional and CKD-specific risk factors and proteinuria. Tenascin (TNC), fibroblast growth factor-23 (FGF-23), and V-set and immunoglobulin domain-containing protein 2 (VSIG2) were associated with both atherosclerotic and nonatherosclerotic MACE. All replicated proteins except carbonic anhydrase 1 and carbonic anhydrase 3 were associated with nonatherosclerotic MACE.Limitations: Single protein concentration measurements and limited follow-up time.Conclusions: Our findings corroborate previously reported relationships between FGF-23, vascular cell adhesion protein-1, TNC, and placental growth factor with cardiovascular outcomes in CKD. We identify 5 proteins not previously linked with MACE in CKD that may be targets for future therapies. Show less
Background New equations to estimate glomerular filtration rate based on creatinine (eGFRcr), cystatin C (eGFRcys) or both (eGFRcr-cys) have been developed by the Chronic Kidney Disease... Show moreBackground New equations to estimate glomerular filtration rate based on creatinine (eGFRcr), cystatin C (eGFRcys) or both (eGFRcr-cys) have been developed by the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) and the European Kidney Function Consortium (EKFC). There is a need to evaluate the performance of these equations in diverse European settings to inform implementation decisions, especially among people with key comorbid conditions.Methods We performed a cross-sectional study including 6174 adults referred for single-point plasma clearance of iohexol in Stockholm, Sweden, with 9579 concurrent measurements of creatinine and cystatin C. We assessed the performance of the CKD-EPI 2009/2012/2021, EKFC 2021/2023, revised Lund-Malmo (RLM) 2011 and Caucasian, Asian, Pediatric and Adult (CAPA) 2014 equations against measured GFR (mGFR).Results Mean age was 56 years, median mGFR was 62 mL/min/1.73 m2 and 40% were female. Comorbid conditions were common: cardiovascular disease (30%), liver disease (28%), diabetes (26%) and cancer (26%). All eGFRcr-cys equations had small bias and P30 (the percentage of estimated values within 30% of mGFR) close to 90%, and performed better than eGFRcr or eGFRcys equations. Among eGFRcr equations, CKD-EPI 2009 and CKD-EPI 2021 showed larger bias and lower P30 than EKFC 2021 and RLM. There were no meaningful differences in performance across eGFRcys equations. Findings were consistent across comorbid conditions, and eGFRcr-cys equations showed good performance in patients with liver disease, cancer and heart failure.Conclusions In conclusion, eGFRcr-cys equations performed best, with minimal variation among equations in this Swedish cohort. The lower performance of CKD-EPI eGFRcr equations compared with EKFC and RLM may reflect differences in population characteristics and mGFR methods. Implementing eGFRcr equations will require a trade-off between accuracy and uniformity across regions.Graphical Abstract Show less
Introduction: Transplant clinicians may disagree on whether or not to accept a deceased donor kidney offer. We investigated the interobserver variability between transplant nephrologists regarding... Show moreIntroduction: Transplant clinicians may disagree on whether or not to accept a deceased donor kidney offer. We investigated the interobserver variability between transplant nephrologists regarding organ acceptance and whether the use of a prediction model impacted their decisions. Methods: We developed an observational online survey with 6 real-life cases of deceased donor kidneys offered to a waitlisted recipient. Per case, nephrologists were asked to estimate the risk of adverse outcome and whether they would accept the offer for this patient, or for a patient of their own choice, and how certain they felt. These questions were repeated after revealing the risk of adverse outcome, calcu-lated by a validated prediction model. Results: Sixty Dutch nephrologists completed the survey. The intraclass correlation coefficient of their estimated risk of adverse outcome was poor (0.20, 95% confidence interval [CI] 0.08-0.62). Interobserver agreement of the decision on whether or not to accept the kidney offer was also poor (Fleiss kappa 0.13, 95% CI 0.129-0.130). The acceptance rate before and after providing the outcome of the prediction model was significantly influenced in 2 of 6 cases. Acceptance rates varied considerably among transplant centers. Conclusion: In this study, the estimated risk of adverse outcome and subsequent decision to accept a suboptimal donor kidney varied greatly among transplant nephrologists. The use of a prediction model could influence this decision and may enhance nephrologists' certainty about their decision. Show less
Oevelen, M. van; Bonenkamp, A.A.; Sluijs, A.V. van der; Bos, W.J.W.; Douma, C.E.; Buren, M. van; ... ; DOMESTICO Study Grp 2023
Background. Patients on haemodialysis (HD) generally experience poor health-related quality of life (HRQoL) and a broad range of physical and mental symptoms, but it is unknown whether this differs... Show moreBackground. Patients on haemodialysis (HD) generally experience poor health-related quality of life (HRQoL) and a broad range of physical and mental symptoms, but it is unknown whether this differs between younger and older patients. We aimed to describe the trajectories of HRQoL and symptom burden of patients <70 and >= 70 years old and to assess the impact of symptom burden on HRQoL.Methods. In incident Dutch HD patients, HRQoL and symptoms were measured with the 12-item Short Form Health Survey and Dialysis Symptom Index. We used linear mixed models for examining the trajectories of HRQoL and symptom burden during the first year of dialysis and linear regression for the impact of symptom burden on HRQoL.Results. In 774 patients, the trajectories of physical HRQoL, mental HRQoL and symptom burden were stable during the first year of dialysis. Compared with patients <70 years of age, patients >= 70 years reported similar physical HRQoL {mean difference -0.61 [95% confidence interval (CI) -1.86-0.63]}, better mental HRQoL [1.77 (95% CI 0.54-3.01)] and lower symptom burden [-2.38 (95% CI -5.080.32)]. With increasing symptom burden, physical HRQoL declined more in older than in younger patients (beta= -0.287 versus -0.189, respectively; P-value for interaction =.007). For mental HRQoL, this decrease was similar in both age groups (beta = -0.295 versus -0.288, P =.847).Conclusion. Older HD patients generally experience a better mental HRQoL and a (non-statistically significant) lower symptom burden compared with younger patients. Their physical HRQoL declines more rapidly with increasing symptom burden. Show less
Wijk, E.V. van; Janse, R.J.; Ruijter, B.N.; Rohling, J.H.T.; Kraan, J. van der; Crobach, S.; ... ; Langers, A.M.J. 2023
Multiple choice questions (MCQs) offer high reliability and easy machine-marking, but allow for cueing and stimulate recognition-based learning. Very short answer questions (VSAQs), which are open... Show moreMultiple choice questions (MCQs) offer high reliability and easy machine-marking, but allow for cueing and stimulate recognition-based learning. Very short answer questions (VSAQs), which are open-ended questions requiring a very short answer, may circumvent these limitations. Although VSAQ use in medical assessment increases, almost all research on reliability and validity of VSAQs in medical education has been performed by a single research group with extensive experience in the development of VSAQs. Therefore, we aimed to validate previous findings about VSAQ reliability, discrimination, and acceptability in undergraduate medical students and teachers with limited experience in VSAQs development. To validate the results presented in previous studies, we partially replicated a previous study and extended results on student experiences. Dutch undergraduate medical students (n = 375) were randomized to VSAQs first and MCQs second or vice versa in a formative exam in two courses, to determine reliability, discrimination, and cueing. Acceptability for teachers (i.e., VSAQ review time) was determined in the summative exam. Reliability (Cronbach's & alpha;) was 0.74 for VSAQs and 0.57 for MCQs in one course. In the other course, Cronbach's & alpha; was 0.87 for VSAQs and 0.83 for MCQs. Discrimination (average R-ir) was 0.27 vs. 0.17 and 0.43 vs. 0.39 for VSAQs vs. MCQs, respectively. Reviewing time of one VSAQ for the entire student cohort was & PLUSMN;2 minutes on average. Positive cueing occurred more in MCQs than in VSAQs (20% vs. 4% and 20.8% vs. 8.3% of questions per person in both courses). This study validates the positive results regarding VSAQs reliability, discrimination, and acceptability in undergraduate medical students. Furthermore, we demonstrate that VSAQ use is reliable among teachers with limited experience in writing and marking VSAQs. The short learning curve for teachers, favourable marking time and applicability regardless of the topic suggest that VSAQs might also be valuable beyond medical assessment. Show less
Wijk, E.V. van; Janse, R.J.; Ruijter, B.N.; Rohling, J.H.T.; Kraan, J. van der; Crobach S.; ... ; Langers, A.M.J. 2023
Multiple choice questions (MCQs) offer high reliability and easy machine-marking, but allow for cueing and stimulate recognition-based learning. Very short answer questions (VSAQs), which are open... Show moreMultiple choice questions (MCQs) offer high reliability and easy machine-marking, but allow for cueing and stimulate recognition-based learning. Very short answer questions (VSAQs), which are open-ended questions requiring a very short answer, may circumvent these limitations. Although VSAQ use in medical assessment increases, almost all research on reliability and validity of VSAQs in medical education has been performed by a single research group with extensive experience in the development of VSAQs. Therefore, we aimed to validate previous findings about VSAQ reliability, discrimination, and acceptability in undergraduate medical students and teachers with limited experience in VSAQs development. To validate the results presented in previous studies, we partially replicated a previous study and extended results on student experiences. Dutch undergraduate medical students (n = 375) were randomized to VSAQs first and MCQs second or vice versa in a formative exam in two courses, to determine reliability, discrimination, and cueing. Acceptability for teachers (i.e., VSAQ review time) was determined in the summative exam. Reliability (Cronbach's α) was 0.74 for VSAQs and 0.57 for MCQs in one course. In the other course, Cronbach's α was 0.87 for VSAQs and 0.83 for MCQs. Discrimination (average Rir) was 0.27 vs. 0.17 and 0.43 vs. 0.39 for VSAQs vs. MCQs, respectively. Reviewing time of one VSAQ for the entire student cohort was ±2 minutes on average. Positive cueing occurred more in MCQs than in VSAQs (20% vs. 4% and 20.8% vs. 8.3% of questions per person in both courses). This study validates the positive results regarding VSAQs reliability, discrimination, and acceptability in undergraduate medical students. Furthermore, we demonstrate that VSAQ use is reliable among teachers with limited experience in writing and marking VSAQs. The short learning curve for teachers, favourable marking time and applicability regardless of the topic suggest that VSAQs might also be valuable beyond medical assessment. Show less
Background Cystatin C is recommended as a confirmatory test to eGFR when more precise estimates are needed for clinical decision making. Although eGFR on the basis of both creatinine and cystatin ... Show moreBackground Cystatin C is recommended as a confirmatory test to eGFR when more precise estimates are needed for clinical decision making. Although eGFR on the basis of both creatinine and cystatin (eGFR(cr-cys)) is the most accurate estimate in research studies, it is uncertain whether this is true in real-world settings, particularly when there are large discordances between eGFR based on creatinine (eGFR(cr)) and that based on cystatin C (eGFR(cys))Methods We included 6185 adults referred for measured GFR (mGFR) using plasma clearance of iohexol in Stockholm, Sweden, who had 9404 concurrent measurements of creatinine, cystatin C, and iohexol clearance. The performance of eGFR(cr), eGFR(cys), and eGFR(cr-cys) was assessed against mGFR with median bias, P-30, and correct classification of GFR categories. We stratified analyses within three categories: eGFR(cys) at least 20% lower than eGFR(cr) (eGFR(cys)eGFR(cr)).Results eGFR(cr) and eGFR(cys) were similar in 4226 (45%) samples, and among these samples all three estimating equations performed similarly. By contrast, eGFR(cr-cys) was much more accurate in cases of discordance. For example, when eGFR(cys)eGFR(cr) (8% of samples), the median biases were -4.5, 8.4, and 1.4 ml/min per 1.73m(2). The findings were consistent among individuals with cardiovascular disease, heart failure, diabetes mellitus, liver disease, and cancer.Conclusions When eGFR(cr) and eGFR(cys) are highly discordant in clinical practice, eGFR(cr-cys) is more accurate than either eGFR(cr) or eGFR(cys). Show less
Magagnoli, L.; Cozzolino, M.; Caskey, F.J.; Evans, M.; Torino, C.; Porto, G.; ... ; Jager, K.J. 2023
Background Chronic kidney disease-mineral and bone disorder (CKD-MBD) is a common complication of CKD; it is associated with higher mortality in dialysis patients, while its impact in non-dialysis... Show moreBackground Chronic kidney disease-mineral and bone disorder (CKD-MBD) is a common complication of CKD; it is associated with higher mortality in dialysis patients, while its impact in non-dialysis patients remains mostly unknown. We investigated the associations between parathyroid hormone (PTH), phosphate and calcium (and their interactions), and all-cause, cardiovascular (CV) and non-CV mortality in older non-dialysis patients with advanced CKD. Methods We used data from the European Quality study, which includes patients aged & GE;65 years with estimated glomerular filtration rate & LE;20 mL/min/1.73 m(2) from six European countries. Sequentially adjusted Cox models were used to assess the association between baseline and time-dependent CKD-MBD biomarkers and all-cause, CV and non-CV mortality. Effect modification between biomarkers was also assessed. Results In 1294 patients, the prevalence of CKD-MBD at baseline was 94%. Both PTH [adjusted hazard ratio (aHR) 1.12, 95% confidence interval (CI) 1.03-1.23, P = .01] and phosphate (aHR 1.35, 95% CI 1.00-1.84, P = .05), but not calcium (aHR 1.11, 95% CI 0.57-2.17, P = .76), were associated with all-cause mortality. Calcium was not independently associated with mortality, but modified the effect of phosphate, with the highest mortality risk found in patients with both hypercalcemia and hyperphosphatemia. PTH level was associated with CV mortality, but not with non-CV mortality, whereas phosphate was associated with both CV and non-CV mortality in most models. Conclusions CKD-MBD is very common in older non-dialysis patients with advanced CKD. PTH and phosphate are independently associated with all-cause mortality in this population. While PTH level is only associated with CV mortality, phosphate seems to be associated with both CV and non-CV mortality. Show less
Meuleman, Y.; Bent, Y. van der; Gentenaar, L.; Caskey, F.J.; Bart, H.A.J.; Konijn, W.S.; ... ; Dekker, F.W. 2023
BackgroundUnhelpful illness perceptions can be changed by means of interventions and can lead to improved outcomes. However, little is known about illness perceptions in patients with chronic... Show moreBackgroundUnhelpful illness perceptions can be changed by means of interventions and can lead to improved outcomes. However, little is known about illness perceptions in patients with chronic kidney disease (CKD) prior to kidney failure, and no tools exist in nephrology care to identify and support patients with unhelpful illness perceptions. Therefore, this study aims to: (1) identify meaningful and modifiable illness perceptions in patients with CKD prior to kidney failure; and (2) explore needs and requirements for identifying and supporting patients with unhelpful illness perceptions in nephrology care from patients' and healthcare professionals' perspectives.MethodsIndividual semi-structured interviews were conducted with purposive heterogeneous samples of Dutch patients with CKD (n = 17) and professionals (n = 10). Transcripts were analysed using a hybrid inductive and deductive approach: identified themes from the thematic analysis were hereafter organized according to Common-Sense Model of Self-Regulation principles.ResultsIllness perceptions considered most meaningful are related to the seriousness (illness identity, consequences, emotional response and illness concern) and manageability (illness coherence, personal control and treatment control) of CKD. Over time, patients developed more unhelpful seriousness-related illness perceptions and more helpful manageability-related illness perceptions, caused by: CKD diagnosis, disease progression, healthcare support and approaching kidney replacement therapy. Implementing tools to identify and discuss patients' illness perceptions was considered important, after which support for patients with unhelpful illness perceptions should be offered. Special attention should be paid towards structurally embedding psychosocial educational support for patients and caregivers to deal with CKD-related symptoms, consequences, emotions and concerns about the future.ConclusionsSeveral meaningful and modifiable illness perceptions do not change for the better by means of nephrology care. This underlines the need to identify and openly discuss illness perceptions and to support patients with unhelpful illness perceptions. Future studies should investigate whether implementing illness perception-based tools will indeed improve outcomes in CKD. Show less
BACKGROUND & AIMS: Recent pancreatic cancer surveil-lance programs of high-risk individuals have reported improved outcomes. This study assessed to what extent outcomes of pancreatic ductal... Show moreBACKGROUND & AIMS: Recent pancreatic cancer surveil-lance programs of high-risk individuals have reported improved outcomes. This study assessed to what extent outcomes of pancreatic ductal adenocarcinoma (PDAC) patients with a CDKN2A/p16 pathogenic variant diagnosed under surveillance are better as compared with patients with PDAC diagnosed outside surveillance.METHODS: In a pro-pensity score matched cohort using data from the Netherlands Cancer Registry, we compared resectability, stage, and survival between patients diagnosed under sur-veillance with non-surveillance patients with PDAC. Survival analyses were adjusted for potential effects of lead time.RESULTS: Between January 2000 and December 2020, 43,762 patients with PDAC were identified from the Netherlands Cancer Registry. Thirty-one patients with PDAC under surveillance were matched in a 1:5 ratio with 155 non surveillance patients based on age at diagnosis, sex, year diagnosis, and tumor location. Outside surveillance, 5.8% of the patients had stage I cancer, as compared with 38.7% of surveillance patients with PDAC (odds ratio [OR], 0.09; 95% confidence interval [CI], 0.04-0.19). In total, 18.7% of non surveillance patients vs 71.0% of surveillance patients un- derwent a surgical resection (OR, 10.62; 95% CI, 4.56-26.63). Patients in surveillance had a better prognosis, reflected by 5-year survival of 32.4% and a median overall survival of 26.8 months vs 4.3% 5-year survival and 5.2 months median overall survival in non-surveillance patients (hazard ratio, 0.31; 95% CI 0.19-0.50). For all adjusted lead times, survival remained significantly longer in surveillance patients than non-surveillance patients.CONCLUSION: Surveillance for PDAC in carriers of a CDKN2A/p16 pathogenic variant results in earlier detection, increased resectability, and improved survival as compared with non-surveillance patients with PDAC. Show less
Wang, Y.M.; Boog, P. van der; Hemmelder, M.H.; Dekker, F.W.; Vries, A. de; Meuleman, Y. 2023
The purpose of our article is to investigate the impact of symptom experience on health related quality of life (HRQOL) in kidney transplant recipients (KTRs) and whether illness perceptions... Show moreThe purpose of our article is to investigate the impact of symptom experience on health related quality of life (HRQOL) in kidney transplant recipients (KTRs) and whether illness perceptions mediated this impact. Symptom experience, illness perceptions, and HRQOL were measured at transplantation and 6 weeks after transplantation in KTRs in an ongoing Dutch cohort study. Multivariable linear regression models were used for the analysis. 90 KTRs were analyzed. Fatigue and lack of energy were the most prevalent and burdensome symptoms at transplantation. Mental HRQOL at 6 weeks after transplantation was comparable to that of the general Dutch population (mean [standard deviation, SD]: 49.9 [10.7]) versus 50.2 [9.2]), while physical HRQOL was significantly lower (38.9 [9.1] versus 50.6 [9.2]). Experiencing more symptoms was associated with lower physical and mental HRQOL, and the corresponding HRQOL reduced by -0.15 (95%CI, -0.31; 0.02) and -0.23 (95%CI, -0.42; -0.04) with each additional symptom. The identified mediation effect suggests that worse symptom experiences could cause more unhelpful illness perceptions and consequently lead to lower HRQOL. Illness perceptions may explain the negative impact of symptom experience on HRQOL. Future studies at later stages after kidney transplantation are needed to further explore the mediation effect of illness perceptions and guide clinical practice to improve HRQOL. Show less
Veltkamp, D.M.J.; Wang, Y.M.; Meuleman, Y.; Dekker, F.W.; Michels, W.M.; Boog, P.J.M. van der; Vries, A.P.J. de 2023
Background Health-related quality of life (HRQOL) is an increasingly important patient-reported outcome in kidney transplant recipients (KTRs). This study explored relationships between symptom... Show moreBackground Health-related quality of life (HRQOL) is an increasingly important patient-reported outcome in kidney transplant recipients (KTRs). This study explored relationships between symptom prevalence and burden with HRQOL, and age and gender differences in symptom experience. Methods Eligible Dutch KTRs transplanted in Leiden University Medical Center were invited for this cross-sectional study. HRQOL, and occurrence and burden of 62 symptoms were measured using validated questionnaires. Univariate and multivariate regression analysis were used for investigating the associations of symptom experience with mental and physical HRQOL, and differences in symptom experience between genders and KTRs of diverse age groups. Results A total of 631 KTRs were analyzed; the mean (standard deviation) age was 61.3 (11.3) years, and 62% were male. The median (interquartile range) number of symptoms was 14 (7-22), with a burden of 20 (8-37; range 0-244). Per extra symptom, physical and mental HRQOL decreased [-0.41 (-0.50; -0.31) and -0.51 (-0.59; -0.42), respectively, P < .001]. Most occurring symptoms were bruises, tiredness, lack of energy, urge to urinate at night and dry skin. Sexual problems were considered most burdensome. Female KTRs reported more symptoms than men. Amongst others, younger KTRs experienced more (18-50 > 50-65 >= 65 years) feelings of depression and both female and younger KTRs reported higher symptom prevalence concerning changes in physical appearance. Conclusion KRTs' symptom experience differed depending on gender and age, highlighting the need to develop tailored treatment strategies to reduce symptom experience and subsequently improve HRQOL. Show less
Rooij, E.N.M. de; Meuleman, Y.; Fijter, J.W. de; Jager, K.J.; Chesnaye, N.C.; Evans, M.; ... ; EQUAL Study Investigators 2022
Background and objectives For older patients with kidney failure, lowering symptom burden may be more important than prolonging life. Dialysis initiation may affect individual kidney failure... Show moreBackground and objectives For older patients with kidney failure, lowering symptom burden may be more important than prolonging life. Dialysis initiation may affect individual kidney failure-related symptoms differently, but the change in symptoms before and after start of dialysis has not been studied. Therefore, we investigated the course of total and individual symptom number and burden before and after starting dialysis in older patients.Design, setting, participants, & measurements The European Quality (EQUAL) study is an ongoing, prospective, multicenter study in patients >= 65 years with an incident eGFR <= 20 ml/min per 1.73 m(2) . Using the dialysis symptom index (DSI), 30 symptoms were assessed every 3-6 months between 2012 and 2021. Scores for symptom number range from zero to 30 and, for burden, from zero to 150, with higher scores indicating more severity. Using mixed effects models, we studied symptoms during the year preceding and the year after dialysis initiation.Results We included 456 incident patients on dialysis who filled out at least one DSI during the year before or after dialysis. At dialysis initiation, mean (SD) participant age was 76 (6) years, 75% were men, mean (SD) eGFR was 8 (3) ml/min per 1.73 m(2), 44% had diabetes, and 46% had cardiovascular disease. In the year before dialysis initiation, symptom number increased +3.6 (95% confidence interval [95% CI], +2.5 to +4.6) and symptom burden increased +13.3 (95% CI, +9.5 to +17.0). In the year after, symptom number changed -0.9 (95% CI, -3.4 to +1.5) and burden decreased -5.9 (95% CI, -14.9 to -3.0). At dialysis initiation, "fatigue," "decreased interest in sex," and "difficulty becoming sexually aroused" had the highest prevalence of 81%, 69%, and 68%, respectively, with a burden of 2.7, 2.4, and 2.3, respectively. "Fatigue" somewhat improved after dialysis initiation, whereas the prevalence and burden of sexual symptoms further increased.Conclusions Symptom burden worsened considerably before and stabilized after dialysis initiation. "Fatigue," "decreased interest in sex," and "difficulty becoming sexually aroused" were considered most burdensome, of which only "fatigue" somewhat improved after dialysis initiation. Show less
Objectives: Patient-reported outcome measures (PROMs) provide insight into patients' experienced health and needs, and can improve patient-professional communication. However, little is known about... Show moreObjectives: Patient-reported outcome measures (PROMs) provide insight into patients' experienced health and needs, and can improve patient-professional communication. However, little is known about how to discuss PROM results. This study aimed to provide in-depth knowledge of patients' and healthcare professionals' experiences with and perspectives on discussing PROM results as part of routine dialysis care..Design: A qualitative study was performed using an interpretive description approach. Individual semistructured interviews were conducted with 22 patients and healthcare professionals. Interviews focused on general and specific situations (eg, addressing sensitive topics or when no medical treatment is available). Interviews were transcribed verbatim and analysed inductively using thematic analysis. Setting: Participants were purposively sampled from eight dialysis centres across the Netherlands.ParticipantsInterviews were conducted with 10 patients receiving dialysis treatment and 12 healthcare professionals (nephrologists and nurses). Results: Patients and healthcare professionals provided practical guidance for optimal discussion about PROM results. First, patients and healthcare professionals emphasised that PROM results should always be discussed and indicated how to create a suitable setting, adequately prepare, deal with time constraints and use PROMs as a tool for personalised holistic consultations. Second, patients should actively participate and healthcare professionals should take a guiding role. A trusting patient-professional relationship was considered a prerequisite and patient-professional interaction was described as a collaboration in which both contribute their knowledge, experiences and ideas. Third, follow-up after discussing PROM results was considered important, including evaluations and actions (eg, symptom management) structurally embedded into the multidisciplinary treatment process. These general themes also applied to the specific situations, for example: results should also be discussed when no medical treatment is available. Though, healthcare professionals were expected to take more initiative and a leading role when discussing sensitive topics. Conclusions: This study provides insight into how to organise and conduct conversations about PROM results and lays the foundation for training healthcare professionals to optimally discuss PROM results in routine nephrology care. Further research is needed to provide guidance on follow-up actions in response to specific PROM results. Show less
PURPOSE: Pancreatic cancer surveillance in high-risk individuals may lead to detection of pancreatic ductal adenocarcinoma (PDAC) at an earlier stage and with improved survival. This study... Show morePURPOSE: Pancreatic cancer surveillance in high-risk individuals may lead to detection of pancreatic ductal adenocarcinoma (PDAC) at an earlier stage and with improved survival. This study evaluated the yield and outcomes of 20 years of prospective surveillance in a large cohort of individuals with germline pathogenic variants (PVs) in CDKN2A. METHODS: Prospectively collected data were analyzed from individuals participating in pancreatic cancer surveillance. Surveillance consisted of annual magnetic resonance imaging with magnetic resonance cholangiopancreatography and optional endoscopic ultrasound. RESULTS: Three hundred forty-seven germline PV carriers participated in surveillance and were followed for a median of 5.6 (interquartile range 2.3-9.9) years. A total of 36 cases of PDAC were diagnosed in 31 (8.9%) patients at a median age of 60.4 (interquartile range 51.3-64.1) years. The cumulative incidence of primary PDAC was 20.7% by age 70 years. Five carriers (5 of 31; 16.1%) were diagnosed with a second primary PDAC. Thirty (83.3%) of 36 PDACs were considered resectable at the time of imaging. Twelve cases (12 of 36; 33.3%) presented with stage I disease. The median survival after diagnosis of primary PDAC was 26.8 months, and the 5-year survival rate was 32.4% (95% CI, 19.1 to 54.8). Individuals with primary PDAC who underwent resection (22 of 31; 71.0%) had an overall 5-year survival rate of 44.1% (95% CI, 27.2 to 71.3). Nine (2.6%; 9 of 347) individuals underwent surgery for a suspected malignant lesion, which proved to not be PDAC, and this included five lesions with low-grade dysplasia. CONCLUSION: This long-term surveillance study demonstrates a high incidence of PDAC in carriers of a PV in CDKN2A. This provides evidence that surveillance in such a high-risk population leads to detection of early-stage PDAC with improved resectability and survival. Show less
PURPOSEPancreatic cancer surveillance in high-risk individuals may lead to detection of pancreatic ductal adenocarcinoma (PDAC) at an earlier stage and with improved survival. This study evaluated... Show morePURPOSEPancreatic cancer surveillance in high-risk individuals may lead to detection of pancreatic ductal adenocarcinoma (PDAC) at an earlier stage and with improved survival. This study evaluated the yield and outcomes of 20 years of prospective surveillance in a large cohort of individuals with germline pathogenic variants (PVs) in CDKN2A.METHODSProspectively collected data were analyzed from individuals participating in pancreatic cancer surveillance. Surveillance consisted of annual magnetic resonance imaging with magnetic resonance cholangiopancreatography and optional endoscopic ultrasound.RESULTSThree hundred forty-seven germline PV carriers participated in surveillance and were followed for a median of 5.6 (interquartile range 2.3-9.9) years. A total of 36 cases of PDAC were diagnosed in 31 (8.9%) patients at a median age of 60.4 (interquartile range 51.3-64.1) years. The cumulative incidence of primary PDAC was 20.7% by age 70 years. Five carriers (5 of 31; 16.1%) were diagnosed with a second primary PDAC. Thirty (83.3%) of 36 PDACs were considered resectable at the time of imaging. Twelve cases (12 of 36; 33.3%) presented with stage I disease. The median survival after diagnosis of primary PDAC was 26.8 months, and the 5-year survival rate was 32.4% (95% CI, 19.1 to 54.8). Individuals with primary PDAC who underwent resection (22 of 31; 71.0%) had an overall 5-year survival rate of 44.1% (95% CI, 27.2 to 71.3). Nine (2.6%; 9 of 347) individuals underwent surgery for a suspected malignant lesion, which proved to not be PDAC, and this included five lesions with low-grade dysplasia.CONCLUSIONThis long-term surveillance study demonstrates a high incidence of PDAC in carriers of a PV in CDKN2A. This provides evidence that surveillance in such a high-risk population leads to detection of early-stage PDAC with improved resectability and survival. 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
Background Trimethylamine N-oxide (TMAO), a metabolite from red meat and fish consumption, plays a role in promoting cardiovascular events. However, data regarding TMAO and its impact on clinical... Show moreBackground Trimethylamine N-oxide (TMAO), a metabolite from red meat and fish consumption, plays a role in promoting cardiovascular events. However, data regarding TMAO and its impact on clinical outcomes are inconclusive, possibly due to its undetermined dietary source. Objectives We hypothesized that circulating TMAO derived from fish intake might cause less harm compared with red meat sources by examining the concomitant level of 3-carboxy-4-methyl-5-propyl-2-furanpropionate (CMPF), a known biomarker of fish intake, and investigated the association between TMAO, CMPF, and outcomes. Methods Patients were recruited from the European QUALity (EQUAL) Study on treatment in advanced chronic kidney disease among individuals aged >= 65 y whose estimated glomerular filtration rate (eGFR) had dropped for the first time to <= 20 mL/min per 1.73 m(2) during the last 6 mo. The association between TMAO, CMPF, and outcomes including all-cause mortality and kidney replacement therapy (KRT) was assessed among 737 patients. Patients were further stratified by median cutoffs of TMAO and CMPF, suggesting high/low red meat and fish intake. Results During a median of 39 mo of follow-up, 232 patients died. Higher TMAO was independently associated with an increased risk of all-cause mortality (multivariable HR: 1.46; 95% CI: 1.17, 1.83). Higher CMPF was associated with a reduced risk of both all-cause mortality (HR: 0.79; 95% CI: 0.71, 0.89) and KRT (HR: 0.80; 95% CI: 0.71, 0.90), independently of TMAO and other clinically relevant confounders. In comparison to patients with low TMAO and CMPF, patients with low TMAO and high CMPF had reduced risk of all-cause mortality (adjusted HR: 0.49; 95% CI: 0.31, 0.73), whereas those with high TMAO and high CMPF showed no association across adjusted models. Conclusions High CMPF conferred an independent role in health benefits and might even counteract the unfavorable association between TMAO and outcomes. Whether higher circulating CMPF concentrations are due to fish consumption, and/or if CMPF is a protective factor, remains to be verified. Show less
