Hypertension and diabetes, but not leptin and adiponectin, mediate the relationship between body fat and chronic kidney disease.

PURPOSE: Obesity may promote kidney damage through hemodynamic and hormonal effects. We investigated the association between body mass index (BMI), total body fat (TBF) and chronic kidney disease (CKD) and whether hypertension, diabetes, leptin and adiponectin mediated these associations. METHODS: In this cross-sectional analysis of the Netherlands Epidemiology of Obesity study, 6671 participants (45-65 y) were included. We defined CKD as eGFR <60 ml/min/1.73 m2 and/or moderately increased albuminuria. The percentage of mediation was calculated using general structural equation modeling, adjusted for potential confounding factors age, sex, smoking, ethnicity, physical activity and Dutch healthy diet index. RESULTS: At baseline mean (SD) age was 56 (6), BMI 26.3 (4.4), 44% men, and 4% had CKD. Higher BMI and TBF were associated with 1.08 (95%CI 1.05; 1.11) and 1.05-fold (95%CI 1.02; 1.08) increased odds of CKD, respectively. As adiponectin was not associated with any of the outcomes, it was not studied further as a mediating factor. The association between BMI and CKD was 8.5% (95%CI 0.5; 16.5) mediated by diabetes and 22.3% (95%CI 7.5; 37.2) by hypertension. In addition, the association between TBF and CKD was 9.6% (95%CI -0.4; 19.6) mediated by diabetes and 22.4% (95%CI 4.2; 40.6) by hypertension. We could not confirm mediation by leptin in the association between BMI and CKD (35.6% [95%CI -18.8; 90.3]), nor between TBF and CKD (59.7% [95%CI -7.1; 126.6]). CONCLUSION: Our results suggest that the relations between BMI, TBF and CKD are in part mediated by diabetes and hypertension.

Does 'summative' count? The influence of the awarding of study credits on feedback use and test-taking motivation in medical progress testing.

Despite the increasing implementation of formative assessment in medical education, its' effect on learning behaviour remains questionable. This effect may depend on how students value formative, and summative assessments differently. Informed by Expectancy Value Theory, we compared test preparation, feedback use, and test-taking motivation of medical students who either took a purely formative progress test (formative PT-group) or a progress test that yielded study credits (summative PT-group). In a mixed-methods study design, we triangulated quantitative questionnaire data (n = 264), logging data of an online PT feedback system (n = 618), and qualitative interview data (n = 21) to compare feedback use, and test-taking motivation between the formative PT-group (n = 316), and the summative PT-group (n = 302). Self-reported, and actual feedback consultation was higher in the summative PT-group. Test preparation, and active feedback use were relatively low and similar in both groups. Both quantitative, and qualitative results showed that the motivation to prepare and consult feedback relates to how students value the assessment. In the interview data, a link could be made with goal orientation theory, as performance-oriented students perceived the formative PT as not important due to the lack of study credits. This led to low test-taking effort, and feedback consultation after the formative PT. In contrast, learning-oriented students valued the formative PT, and used it for self-study or self-assessment to gain feedback. Our results indicate that most students are less motivated to put effort in the test, and use feedback when there are no direct consequences. A supportive assessment environment that emphasizes recognition of the value of formative testing is required to motivate students to use feedback for learning.

The safety of a low protein diet in older adults with advanced chronic kidney disease.

BACKGROUND: A low protein diet (LPD) is recommended to patients with advanced chronic kidney disease (CKD), whereas geriatric guidelines recommend a higher amount of protein. The aim of this study was to evaluate the safety of LPD treatment in older adults with advanced CKD. METHODS: The EQUAL study is a prospective, observational study, including patients ≥65 years, incident estimated glomerular filtration rate <20 ml/min/1.73m², in six European countries with follow-up up till six years. Nutritional status was assessed by 7-point subjective global assessment (SGA) every 3-6 months. Prescribed diet (gram protein/kilogram/bodyweight) was recorded on every study visit; measured protein intake was available in three countries. Time to death and decline in nutritional status (SGA decrease by ≥2 points) were analysed using marginal structural models with dynamic inverse probability of treatment and censoring weights. RESULTS: Out of 1738 adults (631 prescribed LPD at any point during follow-up) there were 1319 with repeated SGA measurements of which 267 (20%) declined in SGA ≥ 2 points and 565 (32.5%) died. There was no difference in survival or decline in nutritional status for patients prescribed LPD ≤0.8 g/kg ideal bodyweight (Odds Ratio (OR) for mortality 1.15 (95% Confidence interval (CI) 0.86-1.55) and OR for decline in SGA 1.11 (95% CI 0.74-1.66) in the adjusted models. In patients prescribed LPD <0.6 g/kg ideal bodyweight, the results were similar. There was a significant interaction with LPD and higher age >75 years, lower SGA, and higher comorbidity burden for both mortality and nutritional status decline. CONCLUSIONS: In older adults with CKD approaching end-stage kidney disease, a traditional LPD prescribed and monitored according to routine clinical practice in Europe appears to be safe.

Clinical impact of the Kidney Failure Risk Equation for vascular access planning.

BACKGROUND: Risk-based thresholds for arteriovenous (AV) access creation has been proposed to aid vascular access planning. We aimed to assess the clinical impact of implementing the kidney failure risk equation (KFRE) for vascular access referral. METHODS: 16,102 nephrology-referred chronic kidney disease (CKD) patients from the Swedish Renal Registry 2008-2018 were included. The KFRE was calculated repeatedly, and the timing was identified for when the KFRE risk exceeded several pre-defined thresholds and/or the estimated glomerular filtration rate <15 ml/min/1.73m2 (eGFR15). To assess the utility of the KFRE/eGFR thresholds, cumulative incidence curves of kidney replacement therapy (KRT) or death, and decision-curve analyses were computed at 6, 12 months, and 2 years. The potential impact of using the different thresholds was illustrated by an example from the Swedish access registry. RESULTS: The 12-month specificity for KRT initiation was highest for KFRE>50% 94.5 (95% Confidence interval [CI] 94.3-94.7), followed by KFRE>40% 90.0 (95% CI 89.7-90.3), while sensitivity was highest for KFRE>30% 79.3 (95% CI 78.2-80.3) and eGFR<15 ml/min/1.73m2 81.2 (95% CI 80.2-82.2). The 2-year positive predictive value was 71.5 (95% CI 70.2-72.8), 61.7 (95% CI 60.4-63.0) and 47.2 (95% CI 46.1-48.3) for KFRE>50%, KFRE>40%, and eGFR<15 respectively. Decision curve analyses suggested the largest net benefit for KFRE>40% over two years and KFRE>50% over 12 months when it is important to avoid the harm of possibly unnecessary surgery. In Sweden, 54% of nephrology-referred patients started hemodialysis in a central venous catheter (CVC) of which only 5% had AV access surgery >6 months before initiation. 60% of the CVC patients exceeded KFRE>40% a median of 0.8 years (interquartile range 0.4-1.5) before KRT initiation. CONCLUSIONS: The utility of using KFRE>40% and KFRE>50% is higher compared to the more traditionally used eGFR threshold <15 ml/min/1.73m2 for vascular access planning.

Protein Biomarkers and Major Cardiovascular Events in Older People With Advanced CKD: The European Quality (EQUAL) Study.

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 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 m2. 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. Plain-Language Summary: Kidney disease increases the risk of heart disease, stroke, and other vascular conditions. Blood tests that predict the likelihood of these problems may help to guide treatment, but studies are needed in people with kidney disease. We analyzed blood tests from older people with kidney disease, looking for proteins associated with higher risk of these conditions. Nine proteins were identified, of which 3 showed a strong effect after all other information was considered. This work supports previous research regarding 4 of these proteins and identifies 5 additional proteins that may be associated with higher risk. Further work is needed to confirm our findings and to determine whether these proteins can be used to guide treatment.

FLOW: Flow dysfunction of hemodialysis vascular access: A randomized controlled trial on the effectiveness of surveillance of arteriovenous fistulas and grafts.

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 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.

Prognostic Models in Nephrology: Where Do We Stand and Where Do We Go from Here? Mapping Out the Evidence in a Scoping Review.

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 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.

Exploring Patients' Perceptions About Chronic Kidney Disease and Their Treatment: A Qualitative Study.

BACKGROUND: Unhelpful 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. METHODS: Individual 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. RESULTS: Illness 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. CONCLUSIONS: Several 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.

Health-related quality of life and symptom burden in patients on haemodialysis.

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 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 -5.08-0.32)]. With increasing symptom burden, physical HRQoL declined more in older than in younger patients (ß = -0.287 versus -0.189, respectively; P-value for interaction = .007). For mental HRQoL, this decrease was similar in both age groups (ß = -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.

Accuracy of GFR estimating equations based on creatinine, cystatin C or both in routine care.

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 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-Malmö (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.

The impact of gender on the risk of cardiovascular events in older adults with advanced chronic kidney disease.

Background: Patients with chronic kidney disease (CKD) are at a higher risk of major adverse cardiovascular events (MACE) compared with the general population, but gender differences in this risk, especially in older adults, are not fully known. We aim to identify gender differences in the risk of MACE in older European CKD patients, and explore factors that may explain these differences. Methods: The European Quality study (EQUAL) is a prospective study on stage 4-5 CKD patients, ≥65 years old, not on dialysis, from Germany, Italy, the Netherlands, Poland, Sweden and the UK. Cox regression and cumulative incidence competing risk curves were used to identify gender differences in MACE risks. Mediation analysis was used to identify variables which may explain risk differences between men and women. Results: A total of 417 men out of 1134 (37%) and 185 women out of 602 women (31%) experienced at least one MACE, over a follow-up period of 5 years. Women had an 18% lower risk of first MACE compared with men (hazard ratio 0.82; 95% confidence interval 0.69-0.97; P = .02), which was attenuated after adjusting for pre-existing cardiometabolic comorbidities and cardiovascular risk factors. There were no significant gender differences in the risk of recurrent MACE or fatal MACE. The risk difference in MACE by gender was larger in patients aged 65-75 years, compared with patients over 75 years. Conclusions: In a cohort of older adults with advanced CKD, women had lower risks of MACE. These risk differences were partially explained by pre-existing cardiometabolic comorbidities and cardiovascular risk factors.

The long-term benefits of early intensive therapy in chronic diseases-the legacy effect.

The 'legacy effect' refers to the long-term benefits of intensive therapy that are observed long after the end of clinical trials and trial interventions in chronic diseases such as diabetes, hyperlipidaemia and hypertension. It emphasizes the importance of intensive treatment to prevent long-term complications and mortality. In chronic kidney disease (CKD), the legacy effect is evident in various studies. Long-term nephroprotection in diabetes is well documented in major studies in the early stages of diabetes, such as Diabetes Control and Complications Trial-Epidemiology of Diabetes Interventions and Complications (DCCT-EDIC), UK Prospective Diabetes Study (UKPDS) and Intensified Multifactorial Intervention in Patients with Type 2 Diabetes and Microalbuminuria (STENO-2). These studies highlight the importance of intensive glycaemic control in reducing microvascular complications, including nephropathy, in patients with recently diagnosed type 1 and type 2 diabetes. However, the legacy effect is less evident in patients with long-term, established diabetes. In chronic glomerulonephritis, studies on immunoglobulin A nephropathy showed that early immunosuppressive treatment could have long-term beneficial effects on kidney function in children and adults with CKD. The Frequent Hemodialysis (FH) and the EXerCise Introduction To Enhance Performance in Dialysis (EXCITE) trials indicated that frequent haemodialysis and a personalized walking exercise program could improve clinical outcomes and reduce the long-term risk of death and hospitalization. The legacy effect concept underscores the importance of intensive intervention in chronic diseases, including CKD. This concept has significant implications for public health and warrants in-depth basic and clinical research to be better understood and exploited in clinical practice. However, its limitations should be considered when interpreting long-term observational data collected after a clinical trial. Appropriate study designs are necessary to investigate an unbiased legacy effect.

Considerable Variability Among Transplant Nephrologists in Judging Deceased Donor Kidney Offers.

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 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, calculated 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.

Exploring Fairness in Scholarly Development: Are We Creating Knowledge Storing Zombies or Curious, Creative and Critical Healthcare Professionals?

Scholarly doctors require research knowledge and skills (Ausbildung), as well as an academic mindset, which includes curiosity, creativity, and critical thinking (Bildung). However, in contrast to knowledge and skills, summative assessment of the development of an academic mindset is not so easy in an objective and so-called 'fair' way. As a result, in practice, assessing knowledge and skills tends to dominate in scholarly development. In this perspective, we explore the issues that arise when we give priority to objective assessment of knowledge and skills in scholarly development to safeguard fairness and, consequently, standardize educational procedures and learning pathways. We argue that eventually this approach may even result in hampered development of a true academic mindset and can be considered unfair rather than fair. To solve this, perhaps we should go back to the core business of the university and in the tradition of founder of the modern university Von Humboldt focus on shaping an academic mindset (Bildung). To rebalance Ausbildung and Bildung in academic education, we should go beyond the assumption that objectivity is a prerequisite for achieving fairness in assessment. Shifting the focus from pure objectivity to both objectivity and subjectivity in assessment as well as learning pathways can assist in protecting fairness and, as a result, bring back Bildung to medical education to ensure future doctors to be true scholars.

Dialysis withdrawal and symptoms of anxiety and depression: a prospective cohort study.

BACKGROUND: An important aspect of end-of-life decisions in dialysis patients is elective withdrawal from dialysis therapy. Several studies have shown that clinical factors, such as comorbidity, play a role in dialysis withdrawal. The role of symptoms of anxiety and depression is largely unknown. The. METHODS: A prospective multi-center study has been set up to investigate anxiety and depressive symptoms longitudinally in dialysis patients. Anxiety and depressive symptoms were investigated using the Beck Anxiety Inventory (BAI) and Beck Depression Inventory (BDI) as baseline. Adverse events, including dialysis withdrawal and mortality were registered during follow-up. Multivariable cox proportional hazard models were used with anxiety and depression as the independent variable and dialysis withdrawal as the outcome variable. Models included age, sex, ethnicity and a set of clinical comorbidities. RESULTS: A total of 687 patients were included between 2012 and 2017, with a median follow-up of 3.2 years. A total of 48 patients (7%) withdrew from dialysis therapy, and subsequently deceased. Anxiety and depressive symptoms at baseline showed an association with dialysis withdrawal with hazard ratios of 2.31 (1.09-4.88) for anxiety and 2.56 (1.27-5.15) for depressive symptoms, independent of somatic comorbidities. DISCUSSION: Withdrawal from dialysis therapy is associated with anxiety and depressive symptoms. Dialysis patients with more severe depressive and anxiety symptoms were more vulnerable for dialysis withdrawal. Insight in factors that play a role in dialysis withdrawal could aid patients and clinicians making an informed decision and develop clinical guidelines.

Use of very short answer questions compared to multiple choice questions in undergraduate medical students: An external validation study.

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-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.

Clinical and patient-reported trajectories at end-of-life in older patients with advanced CKD.

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 chronic kidney disease (CKD). METHODS: The EQUAL study is a European observational prospective cohort study with an incident eGFR <20 ml/min per 1.73 m2 and ≥65 years of age. The evolution of each clinical indicator was explored using generalized additive models during the 4 years preceding death. 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 ∼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.

Serum Potassium and Risk of Death or Kidney Replacement Therapy in Older People With CKD Stages 4-5: Eight-Year Follow-up.

RATIONALE & OBJECTIVE: Hypokalemia may accelerate kidney function decline. Both hypo- and hyperkalemia can cause sudden cardiac death. However, little is known about the relationship between serum potassium and death or the occurrence of kidney failure requiring replacement therapy (KRT). We investigated this relationship in older people with chronic kidney disease (CKD) stage 4-5. STUDY DESIGN: Prospective observational cohort study. SETTING & PARTICIPANTS: We followed 1,714 patients (≥65 years old) from the European Quality (EQUAL) study for 8 years from their first estimated glomerular filtration rate (eGFR)<20mL/min/1.73m2 measurement. EXPOSURE: Serum potassium was measured every 3 to 6 months and categorized as≤3.5,>3.5-≤4.0,>4.0-≤4.5,>4.5-≤5.0 (reference),>5.0-≤5.5, >5.5-≤6.0, and>6.0mmol/L. OUTCOME: The combined outcome death before KRT or start of KRT. ANALYTICAL APPROACH: The association between categorical and continuous time-varying potassium and death or KRT start was examined using Cox proportional hazards and restricted cubic spline analyses, adjusted for age, sex, diabetes, cardiovascular disease, renin-angiotensin-aldosterone system (RAAS) inhibition, eGFR, and subjective global assessment (SGA). RESULTS: At baseline, 66% of participants were men, 42% had diabetes, 47% cardiovascular disease, and 54% used RAAS inhibitors. Their mean age was 76±7 (SD) years, mean eGFR was 17±5 (SD) mL/min/1.73m2, and mean SGA was 6.0±1.0 (SD). Over 8 years, 414 (24%) died before starting KRT, and 595 (35%) started KRT. Adjusted hazard ratios for death or KRT according to the potassium categories were 1.6 (95% CI, 1.1-2.3), 1.4 (95% CI, 1.1-1.7), 1.1 (95% CI, 1.0-1.4), 1 (reference), 1.1 (95% CI, 0.9-1.4), 1.8 (95% CI, 1.4-2.3), and 2.2 (95% CI, 1.5-3.3). Hazard ratios were lowest at a potassium of about 4.9mmol/L. LIMITATIONS: Shorter intervals between potassium measurements would have allowed for more precise estimations. CONCLUSIONS: We observed a U-shaped relationship between serum potassium and death or KRT start among patients with incident CKD 4-5, with a nadir risk at a potassium level of 4.9mmol/L. These findings underscore the potential importance of preventing both high and low potassium in patients with CKD 4-5. PLAIN-LANGUAGE SUMMARY: Abnormal potassium blood levels may increase the risk of death or kidney function decline, especially in older people with chronic kidney disease (CKD). We studied 1,714 patients aged≥65 years with advanced CKD from the European Quality (EQUAL) study and followed them for 8 years. We found that both low and high levels of potassium were associated with an increased risk of death or start of kidney replacement therapy, with the lowest risk observed at a potassium level of 4.9 mmol/L. In patients with CKD, the focus is often on preventing high blood potassium. However, this relatively high optimum potassium level stresses the potential importance of also preventing low potassium levels in older patients with advanced CKD.

Association between CKD-MBD and mortality in older patients with advanced CKD-results from the EQUAL study.

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 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 ≥65 years with estimated glomerular filtration rate ≤20 mL/min/1.73 m2 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.