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Proper adjustment for confounding is essential when estimating the effects of treatments or risk factors on health outcomes in observational data. To this end, various statistical methods have been developed. In the past couple of years, the use of propensity scores (PSs) to control for confounding has increased. Proper understanding of this method is necessary to critically appraise research in which it is applied. In this article, we provide an overview of PS methods, explaining their concept, advantages and possible disadvantages. Furthermore, the use of PS matching, PS adjustment and PS weighting is illustrated using data from the Netherlands Cooperative Study on the Adequacy of Dialysis (NECOSAD) cohort of dialysis patients., (© The Author(s) 2018. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved.)

Background: Survival among dialysis patients with diabetes mellitus (DM) is inferior to survival of non-diabetic dialysis patients, probably due to the higher prevalence of diabetes-related comorbid conditions. One could hypothesize that these comorbid conditions also contribute to a decreased survival after amputation in diabetic patients compared with non-diabetic patients on dialysis., Methods: Data were collected from the Netherlands Cooperative Study on the Adequacy of Dialysis, a multicentre, prospective cohort study in which new patients with end-stage renal disease were monitored until transplantation or death. Amputation rates (incident cases) were calculated in patients with and without DM. The primary endpoint was all-cause survival after first amputation during dialysis therapy in diabetic patients compared with non-diabetic dialysis patients with an amputation. This was formally assessed using interaction analysis (Poisson regression)., Results: During follow-up (mean duration 2.9 years), 50 of the 413 diabetic patients had a new amputation (12.1%), compared with 20 of 1553 non-diabetic patients (1.2%). Amputation rates/1000 person-years were 47.9 [95% confidence interval (CI) 36.3-63.2] and 4.1 (95% CI 2.7-6.4), respectively, for diabetic patients and non-diabetic patients. Amputation increased mortality risk more than 4-fold in patients without diabetes [hazard ratio (HR) 4.6 (95% CI 2.8-7.6)] as well as in patients with diabetes [HR 4.6 (95% CI 3.3-6.4)]. No formal interaction between diabetes and amputation was found (P = 0.12)., Conclusions: Amputation in dialysis patients is associated with a 4-fold increased mortality risk; this mortality risk was similar for diabetes and non-diabetes patients. Importantly, the risk for amputation is 10-fold higher in DM compared with non-diabetic dialysis patients., (© The Author(s) 2019. Published by Oxford University Press on behalf of ERA-EDTA.)

Background and Objectives: Data from observational and interventional studies provide discordant results regarding the relationship between creatinine increase after renin-angiotensin system inhibition (RASi) and adverse outcomes. We compared health outcomes among patients with different categories of increase in creatinine upon initiation of RASi in a large population-based cohort., Design, Setting, Participants, & Measurements: We performed a retrospective analysis of the Stockholm CREAtinine Measurements database, which contains complete information on diagnoses, medication dispensation claims, and laboratory test results for all Stockholm citizens accessing health care. Included were 31,951 adults initiating RASi during 2007-2011 with available pre- and postinitiation creatinine monitoring. Multivariable Cox regression was used to compare mortality, cardiovascular and ESKD events among individuals with different ranges of creatinine increases within 2 months after starting treatment., Results: In a median follow-up of 3.5 years, acute increases in creatinine were associated with mortality (3202 events) in a graded manner: compared with creatinine increases <10%, a 10%-19% increase showed an adjusted hazard ratio (HR) of 1.15 (95% confidence interval [95% CI], 1.05 to 1.27); HR 1.22 (95% CI, 1.07 to 1.40) for 20%-29%; HR 1.55 (95% CI, 1.36 to 1.77) for ≥30%. Similar graded associations were present for heart failure (2275 events, P <0.001) and ESKD (52 events; P <0.001), and, less consistently, myocardial infarction (842 events, P= 0.25). Results were robust across subgroups, among continuing users, when patients with decreases in creatinine were excluded from the reference group, and after accounting for death as a competing risk., Conclusions: Among real-world monitored adults, increases in creatinine (>10%) after initiation of RASi are associated with worse health outcomes. These results do not address the issue of discontinuation of RASi when plasma creatinine increases but do suggest that patients with increases in creatinine have higher subsequent risk of cardiovascular and kidney outcomes., (Copyright © 2019 by the American Society of Nephrology.)

Objectives: The medical field is facing a physician-scientist shortage. Medical schools could contribute to developing physician-scientists by stimulating student involvement in research. Studies have examined motivation for research as a key parameter of success. However, previous studies did not investigate if students act on their self-reported motivation. The aim of this study is to examine if motivation for research of medical students is related to actual research involvement. Furthermore, this study distinguishes intrinsic (IM) and extrinsic motivation (EM) for research and aims to investigate if a type of motivation matters in the relation between research motivation and involvement., Design and Setting: Prospective cohort study in which students were surveyed at the start of medical school and reported IM and EM for research, self-efficacy, perceptions of research and curiosity on a 7-point Likert scale. One year later, students involved in research were identified. Logistic regression was used to examine influences of IM and EM on research involvement., Participants: All undergraduate medical students starting at one medical school in the Netherlands in 2016. In total, 315 out of 316 students participated (99.7%), of whom 55 became involved in research (17.5%)., Main Outcome Measure: Research involvement, which was operationalised as the enrolment of students in the research-based honours programme or the involvement of students in voluntary research activities outside of the regular curriculum., Results: Students with higher levels of IM were more often involved in research (OR 3.4; 95% CI 2.08 to 5.61), also after adjusting for gender, age, extracurricular high school activities, self-efficacy, perceptions and curiosity (OR 2.5; 95% CI 1.35 to 4.78). Higher levels of EM increased the odds of research involvement (OR 1.4; 95% CI 0.96 to 2.11). However, the effect of EM disappeared after adjusting for the above-mentioned factors (OR 1.05; 95% CI 0.67 to 1.63). Furthermore, the effect of IM remained after adjusting for EM, whereas the effect of EM disappeared after adjusting for IM., Conclusions: Our findings suggest that the type of motivation matters and IM influences research involvement. Therefore, IM could be targeted to stimulate research involvement and could be seen as the first step towards success in fostering the physician-scientist workforce., Competing Interests: Competing interests: No, there are no competing interests for any author., (© Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Bleeding risk scores have been created to identify patients with an increased bleeding risk, which could also be useful in dialysis patients. However, the predictive performances of these bleeding risk scores in dialysis patients are unknown. Therefore, the aim of this study was to validate existing bleeding risk scores in dialysis patients., Methods: A cohort of 1745 incident dialysis patients was prospectively followed for 3 years during which bleeding events were registered. We evaluated the discriminative performance of the Hypertension, Abnormal kidney and liver function, Stroke, Bleeding, Labile INR, Elderly and Drugs or alcohol (HASBLED), the AnTicoagulation and Risk factors In Atrial fibrillation (ATRIA), the Hepatic or kidney disease, Ethanol abuse, Malignancy, Older age, Reduced platelet count or Reduced platelet function, Hypertension, Anaemia, Genetic factors, Excessive fall risk and Stroke (HEMORR2HAGES) and the Outcomes Registry for Better Informed Treatment (ORBIT) bleeding risk scores by calculating C-statistics with 95% confidence intervals (CI). In addition, calibration was evaluated by comparing predicted and observed risks., Results: Of the 1745 dialysis patients, 183 patients had a bleeding event, corresponding to an incidence rate of 5.23/100 person-years. The HASBLED [C-statistic of 0.58 (95% CI 0.54-0.62)], ATRIA [C-statistic of 0.55 (95% CI 0.51-0.60)], HEMORR2HAGES [C-statistic of 0.56 (95% CI 0.52-0.61)] and ORBIT [C-statistic of 0.56 (95% CI 0.52-0.61)] risk scores had poor discriminative performances in dialysis patients. Furthermore, the calibration analyses showed that patients with a low risk of bleeding according to the HASBLED, ATRIA, HEMORR2HAGES and ORBIT bleeding risk scores had higher incidence rates for bleeding in our cohort than predicted., Conclusions: The HASBLED, ATRIA, HEMORR2HAGES and ORBIT bleeding risk scores had poor predictive abilities in dialysis patients. Therefore, these bleeding risk scores may not be useful in this population., (© The Author(s) 2019. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved.)

Background: Chronic kidney disease (CKD) is frequently accompanied by thyroid hormone dysfunction. It is currently unclear whether these alterations are the cause or consequence of CKD. This study aimed at studying the effect of thyroid hormone alterations on renal function in cross-sectional and longitudinal analyses in individuals from all adult age groups., Methods: Individual participant data (IPD) from 16 independent cohorts having measured thyroid stimulating hormone, free thyroxine levels and creatinine levels were included. Thyroid hormone status was defined using clinical cut-off values. Estimated glomerular filtration rates (eGFR) were calculated by means of the four-variable Modification of Diet in Renal Disease (MDRD) formula. For this IPD meta-analysis, eGFR at baseline and eGFR change during follow-up were computed by fitting linear regression models and linear mixed models in each cohort separately. Effect estimates were pooled using random effects models., Results: A total of 72 856 individuals from 16 different cohorts were included. At baseline, individuals with overt hypothyroidism (n = 704) and subclinical hypothyroidism (n = 3356) had a average (95% confidence interval) -4.07 (-6.37 to -1.78) and -2.40 (-3.78 to -1.02) mL/min/1.73 m2 lower eGFR as compared with euthyroid subjects (n = 66 542). In (subclinical) hyperthyroid subjects (n = 2254), average eGFR was 3.01 (1.50-4.52) mL/min/1.73 m2 higher. During 329 713 patient years of follow-up, eGFR did not decline more rapidly in individuals with low thyroid function compared with individuals with normal thyroid function., Conclusions: Low thyroid function is not associated with a deterioration of renal function. The cross-sectional association may be explained by renal dysfunction causing thyroid hormone alterations., (© The Author(s) 2018. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved.)

The 2024 Kidney Disease: Improving Global Outcomes (KDIGO) guidelines for chronic kidney disease (CKD) evaluation and management bring important updates, particularly for European laboratories. These guidelines emphasize the need for harmonization in CKD testing, promoting the use of regional equations. In Europe, the European Kidney Function Consortium (EKFC) equation is particularly suited for European populations, particularly compared to the CKD-EPI 2021 race-free equation. A significant focus is placed on the combined use of creatinine and cystatin C to estimate glomerular filtration rate (eGFRcr-cys), improving diagnostic accuracy. In situations where eGFR may be inaccurate or clinically insufficient, the guidelines encourage the use of measured GFR (mGFR) through exogenous markers like iohexol. These guidelines emphasize the need to standardize creatinine and cystatin C measurements, ensure traceability to international reference materials, and adopt harmonized reporting practices. The recommendations also highlight the importance of incorporating risk prediction models, such as the Kidney Failure Risk Equation (KFRE), into routine clinical practice to better tailor patient care. This article provides a European perspective on how these KDIGO updates should be implemented in clinical laboratories to enhance CKD diagnosis and management, ensuring consistency across the continent., (© 2024 Walter de Gruyter GmbH, Berlin/Boston.)

Background: Chronic kidney disease (CKD) is associated with increased mortality. Individual mortality prediction could be of interest to improve individual clinical outcomes. Using an independent regional dataset, the aim of the present study was to externally validate the recently published 2-year all-cause mortality prediction tool developed using machine learning., Methods: A validation dataset of stage 4 or 5 CKD outpatients was used. External validation performance of the prediction tool at the optimal cutoff-point was assessed by the area under the receiver operating characteristic curve (AUC-ROC), accuracy, sensitivity, and specificity. A survival analysis was then performed using the Kaplan-Meier method., Results: Data of 527 outpatients with stage 4 or 5 CKD were analyzed. During the 2 years of follow-up, 91 patients died and 436 survived. Compared to the learning dataset, patients in the validation dataset were significantly younger, and the ratio of deceased patients in the validation dataset was significantly lower. The performance of the prediction tool at the optimal cutoff-point was: AUC-ROC = 0.72, accuracy = 63.6%, sensitivity = 72.5%, and specificity = 61.7%. The survival curves of the predicted survived and the predicted deceased groups were significantly different (p < 0.001)., Conclusion: The 2-year all-cause mortality prediction tool for patients with stage 4 or 5 CKD showed satisfactory discriminatory capacity with emphasis on sensitivity. The proposed prediction tool appears to be of clinical interest for further development., Competing Interests: Declarations. Conflict of interest: Authors have no conflict of interest to disclose. Ethical approval and informed consent: The study was carried out in accordance with the French law on retrospective studies of data recorded in the hospital system. The physician in charge of the patient had access to the patient’s name and address. A request to use the patient's data was sent to the patient’s address. The information letter sent was reviewed and validated by the local ethics committee. The patient or the patient’s family (if the patient is deceased) had one month to express their opposition to the use of their personal data. This study was approved on July 28, 2022 by the institutional review board of the Hospices Civils de Lyon (Comité Scientifique et Ethique des Hospices Civils de Lyon; number 22 835) and declared to the national data protection commission (Commission Nationale de l’Informatique et des Libertés; number 22 5835). Our research uses only retrospective data from stage 4-5 CKD patients treated at the Hospices Civils de Lyon. Our research was approved by the local ethics committee. Details of ethical considerations have been provided in the ethical considerations section., (© 2024. The Author(s) under exclusive licence to Italian Society of Nephrology.)

A randomised controlled trial (RCT) and a series of case studies were used to determine the impact of two variants of an intervention (a professional development programme) aimed at improving primary school science teachers' subject and pedagogic content knowledge, and enhancing their subject leadership ability. Ninety-six schools were randomly assigned to full or partial treatment groups or a 'business-as-usual' control group. Quantitative data were collected from teachers and pupils through an assessment of scientific knowledge based on standardised assessment items. Qualitative data were collected through interviews and lesson observation initially in thirty case study schools. There were three data collection points: pre- and post-intervention, and one year later. [Guskey, T. (1986). Staff development and the process of teacher change. Educational Researcher , 15 (5), 5-12.] Levels of Professional Development Evaluation model was used as the analysis framework. The quantitative data from the teachers' subject knowledge assessment indicated neither the full nor the partial training programmes had a statistically significant impact on teachers' performance. In contrast, the qualitative data suggested that many teachers in the full treatment group believed that their subject knowledge had improved and reported increased confidence in their teaching of science. Lesson observations provided corroborating evidence of change in teachers' practice, and some modest evidence of wider change in schools. There was no statistically significant improvement in pupil performance in subject knowledge assessments when teachers had participated in the intervention. In the context of research methods, the study suggests that a mixed-methods approach to evaluation is likely to yield a more rounded and nuanced picture of the overall impact of an intervention.

Objective: Patients undergoing chronic dialysis often display sustained elevations of inflammation markers and also have a high prevalence of depressive symptoms. Although multiple studies demonstrated cross-sectional associations between inflammation markers and depressive symptoms in this patient group, longitudinal associations have not been examined. We therefore investigated whether longitudinal associations exist between inflammation markers and depressive symptoms in chronic dialysis patients., Methods: Data of three consecutive measurements of an observational, prospective cohort study among chronic dialysis patients were used. At baseline, 6-month, and 12-month follow-up, patients completed the Beck Depression Inventory, and inflammation markers (high-sensitivity C-reactive protein [HsCRP], interleukin (IL)-1β, IL-6, IL-10, and tumor necrosis factor α) were measured. We examined cross-sectional associations between inflammation markers and depressive symptoms using linear regression models. The longitudinal association between inflammation and depressive symptoms was assessed using a linear mixed model analyses., Results: A total of 513 patients were included. Cross-sectional associations were found between HsCRP and depressive symptoms at baseline (β = 0.9, confidence interval [CI] = 0.4-1.4) and 6-month follow-up (β = 1.1, CI = 0.3-2.0), and between IL-1β and depressive symptoms at 6-month follow-up (β = 1.3, CI = 0.8-1.8) and 12-month follow-up (β = 1.2, CI = 0.4-1.9). Inflammation makers (HsCRP, IL-6, IL-1β, IL-10, and tumor necrosis factor α) at baseline were not associated with depressive symptoms at follow-up and vice versa., Conclusions: We confirmed the presence of cross-sectional associations between inflammation markers and depressive symptoms in chronic dialysis patients, but with our longitudinal data, we found no longitudinal associations. This supports an associative instead of a causal relationship between inflammation and depressive symptoms.

Background: An easy-to-use prediction model for long-term renal patient survival based on only four predictors [age, primary renal disease, sex and therapy at 90 days after the start of renal replacement therapy (RRT)] has been developed in The Netherlands. To assess the usability of this model for use in Europe, we externally validated the model in 10 European countries., Methods: Data from the European Renal Association-European Dialysis and Transplant Association (ERA-EDTA) Registry were used. Ten countries that reported individual patient data to the registry on patients starting RRT in the period 1995-2005 were included. Patients <16  years of age and/or with missing predictor variable data were excluded. The external validation of the prediction model was evaluated for the 10- (primary endpoint), 5- and 3-year survival predictions by assessing the calibration and discrimination outcomes., Results: We used a data set of 136 304 patients from 10 countries. The calibration in the large and calibration plots for 10 deciles of predicted survival probabilities showed average differences of 1.5, 3.2 and 3.4% in observed versus predicted 10-, 5- and 3-year survival, with some small variation on the country level. The concordance index, indicating the discriminatory power of the model, was 0.71 in the complete ERA-EDTA Registry cohort and varied according to country level between 0.70 and 0.75., Conclusions: A prediction model for long-term renal patient survival developed in a single country, based on only four easily available variables, has a comparably adequate performance in a wide range of other European countries.

Objective: To evaluate the performance of five cardiovascular disease (CVD) risk scores developed in diabetes populations and compare their performance to QRISK2., Research Design and Methods: A cohort of people diagnosed with type 2 diabetes between 2004 and 2016 was identified from the Scottish national diabetes register. CVD events were identified using linked hospital and death records. Five-year risk of CVD was estimated using each of QRISK2, ADVANCE (Action in Diabetes and Vascular disease: preterAx and diamicroN-MR Controlled Evaluation), Cardiovascular Health Study (CHS), New Zealand Diabetes Cohort Study (NZ DCS), Fremantle Diabetes Study, and Swedish National Diabetes Register (NDR) risk scores. Discrimination and calibration were assessed using the Harrell C statistic and calibration plots, respectively., Results: The external validation cohort consisted of 181,399 people with type 2 diabetes and no history of CVD. There were 14,081 incident CVD events within 5 years of follow-up. The 5-year observed risk of CVD was 9.7% (95% CI 9.6, 9.9). C statistics varied between 0.66 and 0.67 for all risk scores. QRISK2 overestimated risk, classifying 87% to be at high risk for developing CVD within 5 years; ADVANCE underestimated risk, and the Swedish NDR risk score calibrated well to observed risk., Conclusions: None of the risk scores performed well among people with newly diagnosed type 2 diabetes. Using these risk scores to predict 5-year CVD risk in this population may not be appropriate., (© 2018 by the American Diabetes Association.)

Disturbances in calcium metabolism are common in individuals with chronic kidney disease (CKD), but whether they are associated with subsequent kidney function decline is less clear. In a CKD 3-5 cohort of 15,755 adult citizens of Stockholm with creatinine tests taken during 2006-2011 and concurrent calcium testing at cohort entry, we investigated the association between baseline serum calcium and the subsequent change in estimated glomerular filtration rate (eGFR, by CKD-EPI) decline using linear mixed models. Mean (SD) baseline corrected serum calcium was 9.6 (0.5) mg/dL. Mean (95%-confidence interval [CI]) eGFR decline was -0.82 (-0.90; -0.74) mL/min/1.73 m 2 /year. In advanced CKD stages, higher baseline serum calcium was associated with less rapid kidney function decline. The adjusted change (95%-CI) in eGFR decline associated with each mg/dL increase in baseline serum calcium was -0.10 (-0.28; 0.26), 0.39 (0.07; 0.71), 0.34 (-0.02; 0.70) and 0.68 (0.36; 1.00) mL/min/1.73 m 2 /year for individuals in CKD stage 3a, 3b, 4, and 5, respectively. In a subgroup of patients using vitamin D supplements, the association between baseline serum calcium and CKD progression was eliminated, especially in CKD stage 3b and 4. To conclude, in individuals with CKD stage 3b to 5, lower baseline corrected serum calcium, rather than higher baseline serum calcium, associated with a more rapid CKD progression. Lower serum corrected calcium seems to be indicative for vitamin D deficiency.

Globally the number of patients on renal replacement therapy (RRT) is rising. Dyslipidemia is a potential modifiable cardiovascular risk factor, but its effect on risk of RRT or death in pre-dialysis patients is unclear. The aim of this study was to assess the association between dyslipidemia and risk of RRT or death among patients with CKD stage 4-5 receiving specialized pre-dialysis care, an often under represented group in clinical trials. Of the 502 incident pre-dialysis patients (>18 y) in the Dutch PREPARE-2 study, lipid levels were available in 284 patients and imputed for the other patients. During follow up 376 (75%) patients started RRT and 47 (9%) patients died. Dyslipidemia was defined as total cholesterol ≥5.00 mmol/L, LDL cholesterol ≥2.50 mmol/L, HDL cholesterol <1.00 mmol/L, HDL/LDL ratio <0.4, or triglycerides (TG) ≥2.25 mmol/L, and was present in 181 patients and absent in 93 patients. After multivariable adjustment Cox regression analyses showed a HR (95% CI) for the combined endpoint for dyslipidemia of 1.12 (0.85-1.47), and for high LDL of 1.20 (0.89-1.61). All other HRs were smaller. In conclusion, we did not find an association between dyslipidemia or the separate lipid levels and RRT or death in CKD patients on specialized pre-dialysis care.

Objective: Possibly, different biochemical parameters are involved in the development of depressive symptoms in white and non-white dialysis patients. We examined whether the association between inflammation and depressive symptoms and between tryptophan and depressive symptoms differs between white and non-white dialysis patients and whether the association between inflammation and depressive symptoms is mediated by tryptophan degradation along the kynurenine pathway in both groups., Method: Depressive symptoms were measured with the BDI-II. HsCRP, IL-1β, IL-6, IL-10, and TNFα and tryptophan and its degradation products kynurenine and 3-hydroxykynurenine were measured in 270 white and 220 non-white patients., Results: The presence of depressive symptoms was significantly higher in non-white patients (51%) than in white patients (37%) (P<0.01). Among white patients, HsCRP was significantly associated with depressive symptoms (β=0.6 (95% CI: 0.1-1.2)). Among non-white patients, significant associations with depressive symptoms were found for both HsCRP (β=1.0 (95% CI: 0.1-2.0)) and IL-6 (β=2.6 (95% CI: 0.8-4.4)). Tryptophan levels were only significantly associated with depressive symptoms in non-white patients (β=-0.3 (95% CI: -0.4--0.1)). Tryptophan degradation along the kynurenine pathway did not mediate the association between inflammatory markers and depressive symptoms in either group., Conclusion: Our results indicate that for white and non-white dialysis patients different biochemical parameters are associated with depressive symptoms., (Copyright © 2017. Published by Elsevier Inc.)

Current guidelines on hypertension treatment in chronic kidney disease (CKD) patients discourage combined angiotensin-converting enzyme inhibitor (ACEi) and angiotensin II receptor blocker (ARB) use due to the risk of an increased kidney function decline. However, dual compared to single renin-angiotensin system (RAS) blockade may have more efficacy with regard to hypertension and proteinuria. Among incident predialysis patients (CKD 4-5), we compared dual with no or single RAS blockade regarding kidney function decline and risk of renal replacement therapy (RRT) or death. In a multicenter cohort study, 495 incident predialysis patients (>18 years) were included between 2004 and 2011 and followed until RRT, death, or October 2016. At baseline, patients were divided into four categories: nonuser, single or dual user of ACEi and/or ARB. Cox models were used to estimate the hazard ratio for the combined end point RRT or death. Differences in decline of kidney function among the four drug groups were compared with a linear mixed model. A total of 119 patients were nonusers, 164 ACEi users, 133 ARB users, and 79 dual RAS users. Compared to nonusers, the multivariable adjusted hazard ratio (95% confidence interval) for the combined end point was 0.75 (0.65 to 0.86) for ACEi users, 0.87 (0.76 to 1.00) for ARB users, and 0.79 (0.67 to 0.94) for dual RAS users. The average annual decline in kidney function did not differ among the four groups. We observed in predialysis patients that compared to no RAS blockade, both dual RAS blockade and single ACEi use were associated with about 20%-25% lower risk of RRT or death, without difference in kidney function decline., (Copyright © 2017 American Society of Hypertension. Published by Elsevier Inc. All rights reserved.)

Background: Among chronic dialysis patients, associations have been found between inflammatory markers and depressive symptoms. In this population, no studies have examined the mechanism linking the association between inflammatory markers and depressive symptoms. We examined whether the association between inflammatory markers and depressive symptoms is mediated by tryptophan (TRP) degradation along the kynurenine (KYN) pathway., Methods: The data are part of an observational, prospective cohort study in five urban dialysis centres in The Netherlands. Depressive symptoms were determined with the Beck Depression Inventory. Peripheral blood was collected before dialysis to measure inflammatory markers [high sensitivity C-reactive protein (HsCRP), interleukin (IL)-1β, IL-6, IL-10 and tumour necrosis factor-α (TNF-α)], TRP, KYN and 3-hydroxykynurenine. The KYN/TRP ratio was used as a measure of TRP degradation. The association between inflammatory markers and depressive symptoms was determined using linear regression analysis and adjusted for the KYN/TRP ratio., Results: In total, 490 chronic dialysis patients were included. HsCRP [ β = 3.8; confidence interval (CI): 1.0-6.6], IL-6 ( β = 9.1; CI: 4.0-14.1) and TNF-α ( β = 1.3; CI: 0.9-1.7) were associated with the KYN/TRP ratio. We found significant associations between HsCRP ( β = 0.8; CI: 0.3-1.3) and IL-6 ( β = 1.2; CI: 0.3-2.2) levels and depressive symptoms. However, this association was not attenuated after adjustment for the KYN/TRP ratio. Also, no significant associations were found between the KYN/TRP ratio and depressive symptoms., Conclusion: The association between inflammatory markers and depressive symptoms in chronic dialysis patients was not mediated by TRP degradation along the KYN pathway., (© The Author 2016. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved.)

While developing prediction models has become quite popular both in nephrology and in medicine in general, most models have not been implemented in clinical practice on a larger scale. This should be no surprise, as the majority of published models has been shown to be poorly reported and often developed using inappropriate methods. The main problems identified relate to either using too few candidate predictors (based on univariable P < 0.05) or too many (for the number of events), resulting in poorly performing prediction models. Guidelines on how to develop and test a prediction model all stress the importance of external validation to test discrimination and calibration in other populations, as prediction models usually perform less well in new subjects. However, external validity has not often been tested for prediction models in renal patients. Moreover, impact studies showing improved clinical outcomes when using a prediction model in routine clinical practice have been reported rarely. By and large, notwithstanding a few notable exceptions like the kidney failure risk equation prediction model, most models have not been validated externally or are at best inadequately reported, preventing them from be used in clinical practice. Therefore, we recommend researchers to spend more energy on validation and assessing the impact of existing models, instead of merely developing more models that will most likely never be used in clinical practice as well., (© The Author 2017. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved.)

For the presentation of risk, both relative and absolute measures can be used. The relative risk is most often used, especially in studies showing the effects of a treatment. Relative risks have the appealing feature of summarizing two numbers (the risk in one group and the risk in the other) into one. However, this feature also represents their major weakness, that the underlying absolute risks are concealed and readers tend to overestimate the effect when it is presented in relative terms. In many situations, the absolute risk gives a better representation of the actual situation and also from the patient's point of view absolute risks often give more relevant information. In this article, we explain the concepts of both relative and absolute risk measures. Using examples from nephrology literature we illustrate that unless ratio measures are reported with the underlying absolute risks, readers cannot judge the clinical relevance of the effect. We therefore recommend to report both the relative risk and the absolute risk with their 95% confidence intervals, as together they provide a complete picture of the effect and its implications., (© The Author 2017. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved.)

Prediction research is a distinct field of epidemiologic research, which should be clearly separated from aetiological research. Both prediction and aetiology make use of multivariable modelling, but the underlying research aim and interpretation of results are very different. Aetiology aims at uncovering the causal effect of a specific risk factor on an outcome, adjusting for confounding factors that are selected based on pre-existing knowledge of causal relations. In contrast, prediction aims at accurately predicting the risk of an outcome using multiple predictors collectively, where the final prediction model is usually based on statistically significant, but not necessarily causal, associations in the data at hand.In both scientific and clinical practice, however, the two are often confused, resulting in poor-quality publications with limited interpretability and applicability. A major problem is the frequently encountered aetiological interpretation of prediction results, where individual variables in a prediction model are attributed causal meaning. This article stresses the differences in use and interpretation of aetiological and prediction studies, and gives examples of common pitfalls., (© The Author 2017. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved.)

The presence of tumor-infiltrating immune cells is associated with longer survival and a better response to immunotherapy in early-stage melanoma, but a comprehensive study of the in situ immune microenvironment in stage IV melanoma has not been performed. We investigated the combined influence of a series of immune factors on survival and response to adoptive cell transfer (ACT) in stage IV melanoma patients. Metastases of 73 stage IV melanoma patients, 17 of which were treated with ACT, were studied with respect to the number and functional phenotype of lymphocytes and myeloid cells as well as for expression of galectins-1, -3, and -9. Single factors associated with better survival were identified using Kaplan-Meier curves and multivariate Cox regression analyses, and those factors were used for interaction analyses. The results were validated using The Cancer Genome Atlas database. We identified four parameters that were associated with a better survival: CD8 + T cells, galectin-9 + dendritic cells (DC)/DC-like macrophages, a high M1/M2 macrophage ratio, and the expression of galectin-3 by tumor cells. The presence of at least three of these parameters formed an independent positive prognostic factor for long-term survival. Patients displaying this four-parameter signature were found exclusively among patients responding to ACT and were the ones with sustained clinical benefit. Cancer Immunol Res; 5(2); 170-9. ©2017 AACR., (©2017 American Association for Cancer Research.)

Background: Monitoring of renal function is important in patients with chronic kidney disease progressing towards end-stage renal failure, both for timing the start of renal replacement therapy and for determining the prognosis on dialysis. Thus far, studies on associations between estimated glomerular filtration rate (eGFR) measurements in the pre-dialysis stage and mortality on dialysis have shown no or even inverse relations, which may result from the poor validity of serum creatinine-based estimation equations for renal function in pre-dialysis patients. As decline in renal function may be better reflected by the mean of the measured creatinine and urea clearance based on 24-h urine collections (mGFR by C Cr-U ), we hypothesize that in patients with low kidney function, a fast mGFR decline is a risk factor for mortality on dialysis, in contrast to a fast eGFR decline., Methods: For 197 individuals, included from the multicentre NECOSAD cohort, pre-dialysis annual decline of mGFR and eGFR was estimated with linear regression, and classified according to KDOQI as fast (>4 mL/min/1.73 m 2 /year) or slow (≤4 mL/min/1.73 m 2 /year). Cox regression was used to adjust for potential confounders., Results: Patients with a fast mGFR decline had an increased risk of mortality on dialysis: crude hazard ratio (HR) 1.84 (95% confidence interval: 1.13-2.98), adjusted HR 1.94 (1.11-3.36). In contrast, no association was found between a fast eGFR decline in the pre-dialysis phase and mortality on dialysis: crude HR 1.20 (0.75-1.89), adjusted HR 1.14 (0.67-1.94)., Conclusions: This study demonstrates the importance of mGFR decline (by C Cr-U ) as opposed to eGFR decline in patients with low kidney function, and gives incentive for repeated mGFR measurements in patients on pre-dialysis care., (© The Author 2016. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved.)

Survival of expanded criteria donor (ECD) kidneys and their recipients has not been thoroughly evaluated in Europe. Therefore, we compared the outcome of ECD and non-ECD kidney transplantations in a Dutch cohort, stratifying by age and diabetes. In all first Dutch kidney transplants in recipients ≥18 years between 1995 and 2005, both relative risks (hazard ratios, HR) and adjusted absolute risk differences (RD) for ECD kidney transplantation were analysed. In 3062 transplantations [recipient age 49.0 (12.8) years; 20% ECD], ECD kidney transplantation was associated with graft failure including death [HR 1.62 (1.44-1.82)]. The adjusted HR was lower in recipients ≥60 years of age [1.32 (1.07-1.63)] than in recipients 40-59 years [1.71 (1.44-2.02) P = 0.12 for comparison with ≥60 years] and recipients 18-39 years [1.92 (1.42-2.62) P = 0.03 for comparison with ≥60 years]. RDs showed a similar pattern. In diabetics, the risks for graft failure and death were higher than in the nondiabetics. ECD kidney grafts have a poorer prognosis than non-ECD grafts, especially in younger recipients (<60 years), and diabetic recipients. Further studies and ethical discussions should reveal whether ECD kidneys should preferentially be allocated to specific subgroups, such as elderly and nondiabetic individuals., (© 2016 Steunstichting ESOT.)

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., (© 2023. The Author(s).)

Purpose of Review: The integration of risk prediction in managing chronic kidney disease (CKD) is universally considered a key point of routine clinical practice to guide time-sensitive choices, such as dialysis access planning or counseling on kidney transplant options. Several prognostic models have been developed and validated to provide individualized evaluation of kidney failure risk in CKD patients. This review aims to analyze the current evidence on existing predictive models and evaluate the different advantages and disadvantages of these tools., Recent Findings: Since Tangri et al. introduced the Kidney Failure Risk Equation in 2011, the nephrological scientific community focused its interest in enhancing available algorithms and finding new prognostic equations. Although current models can predict kidney failure with high discrimination, different questions remain unsolved. Thus, this field is open to new possibilities and discoveries., Summary: Accurately informing patients of their prognoses can result in tailored therapy with important clinical and psychological implications. Over the last 5 years, the number of disease-modifying therapeutic options has considerably increased, providing possibilities to not only prevent the kidney failure onset in patients with advanced CKD but also delay progression from early stages in at-risk individuals., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Diabetes mellitus is a frequent cause of the need for renal replacement therapy (RRT). Historically, RRT was started earlier in patients with diabetes, in an attempt to prevent complications of uraemia and diabetes. We did a systematic review to find support for this earlier start of dialysis in patients with versus without diabetes., Methods: The MEDLINE, EMBASE and CENTRAL databases were searched for articles about the timing of dialysis initiation in (subgroups of) patients with diabetes and CKD Stage 5., Results: A total of 340 papers were screened and 11 papers were selected to be reviewed. Only three studies showed data of at least one subgroup of patients with diabetes. Two observational studies concluded that start of dialysis with a higher estimated glomerular filtration rate (eGFR) is beneficial with regard to survival, one did not find a difference and six observational studies concluded that start of dialysis with a lower eGFR is associated with better survival in patients with diabetes. The effect of timing of initiation of dialysis did not differ between patients with versus without diabetes. Lastly, one randomized controlled trial (two papers) reported that there was no difference in survival between start at higher versus lower eGFR overall and a P-value for the interaction with diabetes of P = 0.63, indicating no difference between patients with versus without diabetes with regard to the timing of start of dialysis and subsequent mortality on dialysis., Conclusions: There is no difference between early (eGFR) and late (lower eGFR) start of RRT with regard to mortality in patients with versus without diabetes. RRT should thus be initiated based on the same criteria in all patients, irrespective of the presence or absence of diabetes., (© The Author 2016. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved.)