Ellipro scores of donor epitope specific HLA antibodies are not associated with kidney graft survival.

In kidney transplantation, donor HLA antibodies are a risk factor for graft loss. Accessibility of donor eplets for HLA antibodies is predicted by the ElliPro score. The clinical usefulness of those scores in relation to transplant outcome is unknown. In a large Dutch kidney transplant cohort, Ellipro scores of pretransplant donor antibodies that can be assigned to known eplets (donor epitope specific HLA antibodies [DESAs]) were compared between early graft failure and long surviving deceased donor transplants. We did not observe a significant Ellipro score difference between the two cohorts, nor significant differences in graft survival between transplants with DESAs having high versus low total Ellipro scores. We conclude that Ellipro scores cannot be used to identify DESAs associated with early versus late kidney graft loss in deceased donor transplants.

Determination of the clinical relevance of donor epitope-specific HLA-antibodies in kidney transplantation.

In kidney transplantation, survival rates are still partly impaired due to the deleterious effects of donor specific HLA antibodies (DSA). However, not all luminex-defined DSA appear to be clinically relevant. Further analysis of DSA recognizing polymorphic amino acid configurations, called eplets or functional epitopes, might improve the discrimination between clinically relevant vs. irrelevant HLA antibodies. To evaluate which donor epitope-specific HLA antibodies (DESAs) are clinically important in kidney graft survival, relevant and irrelevant DESAs were discerned in a Dutch cohort of 4690 patients using Kaplan-Meier analysis and tested in a cox proportional hazard (CPH) model including nonimmunological variables. Pre-transplant DESAs were detected in 439 patients (9.4%). The presence of certain clinically relevant DESAs was significantly associated with increased risk on graft loss in deceased donor transplantations (p < 0.0001). The antibodies recognized six epitopes of HLA Class I, 3 of HLA-DR, and 1 of HLA-DQ, and most antibodies were directed to HLA-B (47%). Fifty-three patients (69.7%) had DESA against one donor epitope (range 1-5). Long-term graft survival rate in patients with clinically relevant DESA was 32%, rendering DESA a superior parameter to classical DSA (60%). In the CPH model, the hazard ratio (95% CI) of clinically relevant DESAs was 2.45 (1.84-3.25) in deceased donation, and 2.22 (1.25-3.95) in living donation. In conclusion, the developed model shows the deleterious effect of clinically relevant DESAs on graft outcome which outperformed traditional DSA-based risk analysis on antigen level.

Responsiveness and minimal important change of seven PROMIS computerized adaptive tests (CAT) in patients with advanced chronic kidney disease.

BACKGROUND: The Patient-Reported Outcomes Measurement Information System (PROMIS®) has the potential to harmonize the measurement of health-related quality of life (HRQL) across medical conditions. We evaluated responsiveness and minimal important change (MIC) of seven Dutch-Flemish PROMIS computerized adaptive tests (CAT) in Dutch patients with advanced chronic kidney disease (CKD). METHODS: CKD patients (eGFR < 30 ml/min.1.73m2) completed at baseline and after 6 months seven PROMIS CATs (assessing physical function, pain interference, fatigue, sleep disturbance, anxiety, depression, and ability to participate in social roles and activities), Short Form Health Survey 12 (SF-12), PROMIS Pain Intensity single item, Dialysis Symptom Index (DSI), and Global Rating Scales (GRS) of change. Responsiveness was assessed by testing predefined hypotheses about expected correlations among measures, area under the ROC Curve, and effect sizes. MIC was determined with predictive modelling. RESULTS: 207 patients were included; 186 (90%) completed the follow-up. Most results were in accordance with expectations (70-91% of hypotheses confirmed), with some exceptions for PROMIS Anxiety and Ability to Participate (60% and 42% of hypotheses confirmed, respectively). For PROMIS Anxiety and Depression correlations with the GRS were too low (0.04 and 0.20, respectively) to calculate a MIC. MIC values, representing minimal important deterioration, ranged from 0.4 to 2.5 T-score points for the other domains. CONCLUSION: We found sufficient responsiveness of PROMIS CATs Physical Function, Fatigue, Sleep Disturbance, and Depression. The results for PROMIS CATs Pain Interference were almost sufficient, but some results for Anxiety and Ability to Participate in Social Roles and Activities were not as expected. Reported MIC values should be interpreted with caution because most patients did not change.

Technique failure in peritoneal dialysis: Modifiable causes and patient-specific risk factors.

BACKGROUND: Technique survival is a core outcome for peritoneal dialysis (PD), according to Standardized Outcomes in Nephrology-Peritoneal Dialysis. This study aimed to identify modifiable causes and risk factors of technique failure in a large Dutch cohort using standardised definitions. METHODS: Patients who participated in the retrospective Dutch nOcturnal and hoME dialysis Study To Improve Clinical Outcomes cohort study and started PD between 2012 and 2016 were included and followed until 1 January 2017. The primary outcome was technique failure, defined as transfer to in-centre haemodialysis for ≥ 30 days or death. Death-censored technique failure was analysed as secondary outcome. Cox regression models and competing risk models were used to assess the association between potential risk factors and technique failure. RESULTS: A total of 695 patients were included, of whom 318 experienced technique failure during follow-up. Technique failure rate in the first year was 29%, while the death-censored technique failure rate was 23%. Infections were the most common modifiable cause for technique failure, accounting for 20% of all causes during the entire follow-up. Leakage and catheter problems were important causes within the first 6 months of PD treatment (both accounting for 15%). APD use was associated with a lower risk of technique failure (hazard ratio 0.66, 95% confidence interval 0.53-0.83). CONCLUSION: Infections, leakage and catheter problems were important modifiable causes for technique failure. As the first-year death-censored technique failure rate remains high, future studies should focus on infection prevention and catheter access to improve technique survival.

Validity and reliability of the Patient-Reported Outcomes Measurement Information System (PROMIS®) using computerized adaptive testing in patients with advanced chronic kidney disease.

BACKGROUND: The Patient-Reported Outcomes Measurement Information System (PROMIS®) has been recommended for computerized adaptive testing (CAT) of health-related quality of life. This study compared the content, validity, and reliability of seven PROMIS CATs to the 12-item Short-Form Health Survey (SF-12) in patients with advanced chronic kidney disease. METHODS: Adult patients with chronic kidney disease and an estimated glomerular filtration rate under 30 mL/min/1.73 m2 who were not receiving dialysis treatment completed seven PROMIS CATs (assessing physical function, pain interference, fatigue, sleep disturbance, anxiety, depression, and the ability to participate in social roles and activities), the SF-12, and the PROMIS Pain Intensity single item and Dialysis Symptom Index at inclusion and 2 weeks. A content comparison was performed between PROMIS CATs and the SF-12. Construct validity of PROMIS CATs was assessed using Pearson's correlations. We assessed the test-retest reliability of all patient-reported outcome measures by calculating the intraclass correlation coefficient and minimal detectable change. RESULTS: In total, 207 patients participated in the study. A median of 45 items (10 minutes) were completed for PROMIS CATs. All PROMIS CATs showed evidence of sufficient construct validity. PROMIS CATs, most SF-12 domains and summary scores, and Dialysis Symptom Index showed sufficient test-retest reliability (intraclass correlation coefficient ≥ 0.70). PROMIS CATs had a lower minimal detectable change compared with the SF-12 (range, 5.7-7.4 compared with 11.3-21.7 across domains, respectively). CONCLUSION: PROMIS CATs showed sufficient construct validity and test-retest reliability in patients with advanced chronic kidney disease. PROMIS CATs required more items but showed better reliability than the SF-12. Future research is needed to investigate the feasibility of PROMIS CATs for routine nephrology care.

Long-term peridialytic blood pressure changes are related to mortality.

BACKGROUND: In chronic haemodialysis (HD) patients, the relationship between long-term peridialytic blood pressure (BP) changes and mortality has not been investigated. METHODS: To evaluate whether long-term changes in peridialytic BP are related to mortality and whether treatment with HD or haemodiafiltration (HDF) differs in this respect, the combined individual participant data of three randomized controlled trials comparing HD with HDF were used. Time-varying Cox regression and joint models were applied. RESULTS: During a median follow-up of 2.94 years, 609 of 2011 patients died. As for pre-dialytic systolic BP (pre-SBP), a severe decline (≥21 mmHg) in the preceding 6 months was independently related to increased mortality [hazard ratio (HR) 1.61, P = .01] when compared with a moderate increase. Likewise, a severe decline in post-dialytic diastolic BP (DBP) was associated with increased mortality (adjusted HR 1.96, P < .0005). In contrast, joint models showed that every 5-mmHg increase in pre-SBP and post-DBP during total follow-up was related to reduced mortality (adjusted HR 0.97, P = .01 and 0.94, P = .03, respectively). No interaction was observed between BP changes and treatment modality. CONCLUSION: Severe declines in pre-SBP and post-DBP in the preceding 6 months were independently related to mortality. Therefore peridialytic BP values should be interpreted in the context of their changes and not solely as an absolute value.

Discussing results of patient-reported outcome measures (PROMs) between patients and healthcare professionals in routine dialysis care: a qualitative study.

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 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. PARTICIPANTS: Interviews 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.

Reconsidering the Edelman equation: impact of plasma sodium concentration, edema and body weight.

BACKGROUND: Guidelines recommend treatment of dysnatremias to be guided by formulas based on the Edelman equation. This equation describes the relation between plasma sodium concentration and exchangeable cations. However, this formula does not take into account clinical parameters that have recently been associated with local tissue sodium accumulation, which occurs without concurrent water retention. We investigated to what extent such clinical factors affect the Edelman equation and dysnatremia treatment. METHODS: We performed a post-hoc analysis with original data of the Edelman study. Linear regression was used to examine the effect of age, sex, weight, edema, total body water (TBW) and heart and kidney failure on the Edelman equation. With attenuated correction, we corrected for measurement errors of both variables. Using piecewise regression, we analyzed whether the Edelman association differs for different plasma sodium concentrations. RESULTS: Data was available for 82 patients; 57 males and 25 females with a mean (SD) age of 57 (15) years. The slope of the Edelman equation was significantly affected by weight (p=0.01) and edema (p=0.03). Also, below and above plasma sodium levels of 133 mmol/L the slope of the Edelman equation was significantly different (1.25 x0025vs 0.58x0025, p<0.01). CONCLUSION: Edelman's equation's coefficients are significantly affected by weight, edema and plasma sodium, possibly reflecting differences in tissue sodium accumulation capacity. The performance of Edelman-based formulas in clinical settings may be improved by taking these clinical characteristics into account.

Symptom dimensions of anxiety and depression in patients receiving peritoneal dialysis compared to haemodialysis.

BACKGROUND: Differences in symptom burden, treatment satisfaction and autonomy between patients receiving peritoneal dialysis and haemodialysis could be reflected by a difference in symptom dimensions of anxiety and depression. The aim of this study is to assess differences in prevalence and symptom dimensions of anxiety and depression between patients receiving peritoneal dialysis and haemodialysis. METHODS: Baseline data from the Depression Related Factors and Outcomes in Dialysis Patients With Various Ethnicities and Races Study were used. Symptoms of anxiety and depression were measured with the Beck Anxiety Inventory and Beck Depression Inventory- second edition. Linear and logistic regression models were used to compare anxiety and depression total scores and somatic and subjective/cognitive symptom dimension scores between patients receiving peritoneal dialysis and haemodialysis, adjusted for potential confounders. RESULTS: In total, 84 patients receiving peritoneal dialysis and 601 patients receiving haemodialysis were included. Clinically significant symptoms of anxiety and depression were present in respectively 22% and 43% of the patients, with no differences between dialysis modality. Both modalities scored high on the somatic symptom dimensions and on individual somatic items. Almost all patients reported symptoms related to loss of energy and sleep. CONCLUSION: No differences in symptom dimensions of anxiety and depression were found between patients receiving peritoneal dialysis and haemodialysis. The high prevalence of somatic symptom dimensions in both groups underscores the possible interaction between somatic and psychiatric symptoms in dialysis patients and the need for early recognition and treatment of symptoms of anxiety and depression regardless of treatment modalities.

Comorbidity is not associated with dialysis modality choice in patients with end-stage kidney disease.

AIM: Over the past years the proportion of home dialysis patients has decreased in the Netherlands. In addition, the home dialysis use varies significantly among centres. It is unclear whether this is the result of differences in comorbidity, or other factors. Our aim was to investigate the association between comorbidity and dialysis modality choice. METHODS: The multi-centre DOMESTICO cohort study collected comorbidity data of patients who started dialysis in 35 Dutch centres from 2012 to 2016. Comorbidity was assessed by the Charlson comorbidity index. Home dialysis was defined as any peritoneal dialysis or home haemodialysis treatment during follow-up. Multivariable logistic regression analysis was used to assess the association between comorbidity and dialysis modality, with a mixed model approach to adjust for clustering of patients within dialysis centres. RESULTS: A total of 1358 patients were included, of whom 628 were treated with home dialysis. In crude mixed model analyses, the probability of receiving home dialysis was lower when comorbidity score was higher: having a high comorbidity score resulted in an odds ratio of 0.74 (95% CI 0.54-1.00) when compared with patients without comorbidities. After adjustments for age, sex, ethnic background, body mass index and dialysis vintage, there was no association between comorbidity and home dialysis. CONCLUSION: Comorbidity was not significantly associated with home dialysis choice, after adjustment for several confounding factors including age and body mass index. Future studies should aim at unravelling the centre-specific characteristics that probably play a role in dialysis modality choice.

Differences in hospitalisation between peritoneal dialysis and haemodialysis patients.

BACKGROUND: Dialysis is associated with frequent hospitalisations. Studies comparing hospitalisations between peritoneal dialysis (PD) and haemodialysis (HD) report conflicting results and mostly analyse data of patients that remain on their initial dialysis modality. This cohort study compares hospitalisations between PD and HD patients taking into account transitions between modalities. METHODS: The Dutch nOcturnal and hoME dialysis Study To Improve Clinical Outcomes collected hospitalisation data of patients who started dialysis between 2012 and 2017. Primary outcome was hospitalisation rate, analysed with a multi-state model that attributed each hospitalisation to the current dialysis modality. RESULTS: In total, 695 patients (252 PD, 443 HD) treated in 31 Dutch hospitals were included. The crude hospitalisation rate for PD was 2.3 ( ± 5.0) and for HD 1.4 ( ± 3.2) hospitalisations per patient-year. The adjusted hazard ratio for hospitalisation rate was 1.1 (95%CI 1.02-1.3) for PD compared with HD. The risk for first hospitalisation was 1.3 times (95%CI 1.1-1.6) higher for PD compared with HD during the first year after dialysis initiation. The number of hospitalisations and number of hospital days per patient-year were significantly higher for PD. The most common causes of PD and HD hospitalisations were peritonitis (23%) and vascular access-related problems (33%). CONCLUSION: PD was associated with higher hospitalisation rate, higher risk for first hospitalisation and higher number of hospitalisations compared with HD. Since the PD hospitalisations were mainly caused by peritonitis, more attention to infection prevention is necessary for reducing the number of hospitalisations in the future.

Itching in dialysis patients: impact on health-related quality of life and interactions with sleep problems and psychological symptoms-results from the RENINE/PROMs registry.

BACKGROUND: Itching (pruritus) is common in dialysis patients, but little is known about its impact on health-related quality of life (HRQOL), sleep problems and psychological symptoms. This study investigates the impact of itching in dialysis patients by looking into the persistence of itching, the effect of itching on the course of HRQOL and the combined effect of itching with sleep problems and with psychological symptoms on HRQOL. METHODS: Data were obtained from the RENINE/PROMs registry and included 2978 dialysis patients who completed patient-reported outcome measures between 2018 and 2020. Itching, sleep problems and psychological symptoms were assessed with the Dialysis Symptom Index (DSI) and HRQOL with the 12-item Short Form Health Survey. Effects of itching on HRQOL and interactions with sleep problems and psychological symptoms were investigated cross-sectionally and longitudinally using linear regression and linear mixed models. RESULTS: Half of the patients experienced itching and in 70% of them, itching was persistent. Itching was associated with a lower physical and mental HRQOL {-3.35 [95% confidence interval (CI) -4.12 to -2.59) and -3.79 [95% CI -4.56 to -3.03]}. HRQOL remained stable during 2 years and trajectories did not differ between patients with or without itching. Sleep problems (70% versus 52%) and psychological symptoms (36% versus 19%) were more common in patients with itching. These symptoms had an additional negative effect on HRQOL but did not interact with itching. CONCLUSIONS: The persistence of itching, its impact on HRQOL over time and the additional effect on HRQOL of sleep problems and psychological symptoms emphasize the need for recognition and effective treatment of itching to reduce symptom burden and improve HRQOL.

Nocturnal Hemodialysis Leads to Improvement in Physical Performance in Comparison with Conventional Hemodialysis.

End-stage kidney disease patients treated with conventional hemodialysis (CHD) are known to have impaired physical performance and protein-energy wasting (PEW). Nocturnal hemodialysis (NHD) was shown to improve clinical outcomes, but the evidence is limited on physical performance and PEW. We investigate whether NHD improves physical performance and PEW. This prospective, multicenter, non-randomized cohort study compared patients who changed from CHD (2−4 times/week 3−5 h) to NHD (2−3 times/week 7−8 h), with patients who continued CHD. The primary outcome was physical performance at 3, 6 and 12 months, assessed with the short physical performance battery (SPPB). Secondary outcomes were a 6-minute walk test (6MWT), physical activity monitor, handgrip muscle strength, KDQOL-SF physical component score (PCS) and LAPAQ physical activity questionnaire. PEW was assessed with a dietary record, dual-energy X-ray absorptiometry, bioelectrical impedance spectroscopy and subjective global assessment (SGA). Linear mixed models were used to analyze the differences between groups. This study included 33 patients on CHD and 32 who converted to NHD (mean age 55 ± 15.3). No significant difference was found in the SPPB after 1-year of NHD compared to CHD (+0.24, [95% confidence interval −0.51 to 0.99], p = 0.53). Scores of 6MWT, PCS and SGA improved (+54.3 [95%CI 7.78 to 100.8], p = 0.02; +5.61 [−0.51 to 10.7], p = 0.03; +0.71 [0.36 to 1.05], p < 0.001; resp.) in NHD patients, no changes were found in other parameters. We conclude that NHD patients did not experience an improved SPPB score compared to CHD patients; they did obtain an improved walking distance and self-reported PCS as well as SGA after 1-year of NHD, which might be related to the younger age of these patients.

Trends in home dialysis use differ among age categories in past two decades: A Dutch registry study.

BACKGROUND: Although the number of patients with end-stage kidney disease is growing, the number of patients who perform dialysis at home has decreased during the past two decades. The aim of this study was to explore time trends in the use of home dialysis in the Netherlands. METHODS: Dialysis episodes of patients who started dialysis treatment were studied using Dutch registry data (RENINE). The uptake of home dialysis between 1997 through 2016 was evaluated in time periods of 5 years. Home dialysis was defined as start with peritoneal dialysis or home haemodialysis, or transfer to either within 2 years of dialysis initiation. All analyses were stratified for age categories. Mixed model logistic regression analysis was used to adjust for clustering at patient level. RESULTS: A total of 33 340 dialysis episodes in 31 569 patients were evaluated. Mean age at dialysis initiation increased from 62.5 ± 14.0 to 65.5 ± 14.5 years in in-centre haemodialysis patients, whereas it increased from 51.9 ± 15.1 to 62.5 ± 14.6 years in home dialysis patients. In patients <65 years, the uptake of home dialysis was significantly lower during each 5-year period compared with the previous period, whereas kidney transplantation occurred more often. In patients ≥65 years, the incidence of home dialysis remained constant, whereas mortality decreased. CONCLUSIONS: In patients <65 years, the overall use of home dialysis declined consistently over the past 20 years. The age of home dialysis patients increased more rapidly than that of in-centre dialysis patients. These developments have a significant impact on the organization of home dialysis.

T-Cell Epitopes Shared Between Immunizing HLA and Donor HLA Associate With Graft Failure After Kidney Transplantation.

CD4+ T-helper cells play an important role in alloimmune reactions following transplantation by stimulating humoral as well as cellular responses, which might lead to failure of the allograft. CD4+ memory T-helper cells from a previous immunizing event can potentially be reactivated by exposure to HLA mismatches that share T-cell epitopes with the initial immunizing HLA. Consequently, reactivity of CD4+ memory T-helper cells toward T-cell epitopes that are shared between immunizing HLA and donor HLA could increase the risk of alloimmunity following transplantation, thus affecting transplant outcome. In this study, the amount of T-cell epitopes shared between immunizing and donor HLA was used as a surrogate marker to evaluate the effect of donor-reactive CD4+ memory T-helper cells on the 10-year risk of death-censored kidney graft failure in 190 donor/recipient combinations using the PIRCHE-II algorithm. The T-cell epitopes of the initial theoretical immunizing HLA and the donor HLA were estimated and the number of shared PIRCHE-II epitopes was calculated. We show that the natural logarithm-transformed PIRCHE-II overlap score, or Shared T-cell EPitopes (STEP) score, significantly associates with the 10-year risk of death-censored kidney graft failure, suggesting that the presence of pre-transplant donor-reactive CD4+ memory T-helper cells might be a strong indicator for the risk of graft failure following kidney transplantation.

Key elements in selection of pre-dialysis patients for home dialysis.

BACKGROUND: Most pre-dialysis patients are medically eligible for home dialysis, and home dialysis has several advantages over incentre dialysis. However, accurately selecting patients for home dialysis appears to be difficult, since uptake of home dialysis remains low. The aim of this study was to investigate which medical or psychosocial elements contribute most to the selection of patients eligible for home dialysis. METHODS: All patients from a Dutch teaching hospital, who received treatment modality education and subsequently started dialysis treatment, were included. The pre-dialysis programme consisted of questionnaires for the patient, nephrologist and social worker, followed by an assessment of eligibility for home dialysis by a multidisciplinary team. Clinimetric assessment and logistic regression were used to identify domains and questions associated with home dialysis treatment. RESULTS: A total of 135 patients were included, of whom 40 were treated with home dialysis and 95 with incentre haemodialysis. The key elements associated with long-term home dialysis treatment were part of the domains 'suitability of the housing', 'self-care', 'social support' and 'patient capacity', with adjusted odds ratios ranging from 0.13 for negative to 18.3 for positive associations. CONCLUSION: The assessment of contraindications by a nephrologist followed by the assessment of possibilities by a social worker or dialysis nurse who investigates four key elements, ideally during a home visit, and subsequent detailed education offered by specialized nurses is an optimal way to select patients for home dialysis.

Routinely measuring symptom burden and health-related quality of life in dialysis patients: first results from the Dutch registry of patient-reported outcome measures.

BACKGROUND: The use of patient-reported outcome measures (PROMs) is becoming increasingly important in healthcare. However, incorporation of PROMs into routine nephrological care is challenging. This study describes the first experience with PROMs in Dutch routine dialysis care. METHODS: A pilot study was conducted in dialysis patients in 16 centres. Patients were invited to complete PROMs at baseline and 3 and 6 months. PROMs consisted of the 12-item short-form and Dialysis Symptom Index to assess health-related quality of life (HRQoL) and symptom burden. Response rates, HRQoL and symptom burden scores were analysed. Qualitative research methods were used to gain insight into patients' views on using PROMs in clinical practice. RESULTS: In total, 512 patients (36%) completed 908 PROMs (24%) across three time points. Response rates varied from 6 to 70% among centres. Mean scores for physical and mental HRQoL were 35.6 [standard deviation (SD) 10.2] and 47.7 (SD 10.6), respectively. Patients experienced on average 10.8 (SD 6.1) symptoms with a symptom burden score of 30.7 (SD 22.0). Only 1-3% of the variation in PROM scores can be explained by differences between centres. Patients perceived discussing their HRQoL and symptom scores as insightful and valuable. Individual feedback on results was considered crucial. CONCLUSIONS: The first results show low average response rates with high variability among centres. Dialysis patients experienced a high symptom burden and poor HRQoL. Using PROMs at the individual patient level is suitable and may improve patient-professional communication and shared decision making. Further research is needed to investigate how the collection and the use of PROMs can be successfully integrated into routine care to improve healthcare quality and outcomes.

The Impact of COVID-19 on the mental health of dialysis patients.

BACKGROUND: Studies have shown increased anxiety, depression, and stress levels among different populations during the coronavirus disease 2019 (COVID-19) pandemic. However, the impact of the pandemic on the mental health of dialysis patients remains unknown. The aim of this study was to investigate the mental health of dialysis patients during the COVID-19 pandemic compared to the period preceding the pandemic. METHODS: Data originate from the ongoing multicentre observational Dutch nOcturnal and hoME dialysis Study To Improve Clinical Outcomes (DOMESTICO). Patients who filled in a health-related quality of life (HRQoL) questionnaire during the pandemic and six to three months prior were included. The mean difference in Mental Component Summary (MCS) score of the Short Form 12 (SF-12) was analysed with multilevel linear regression. A McNemar test was used to compare presence of mental health-related symptoms during and prior to the COVID-19 pandemic. RESULTS: A total of 177 patients were included. The mean MCS score prior to COVID-19 was 48.08 ± 10.15, and 49.00 ± 10.04 during the COVID-19 pandemic. The adjusted mean MCS score was 0.93 point (95% CI - 0.57 to 2.42) higher during the COVID-19 pandemic than during the period prior to the pandemic. Furthermore, no difference in the presence of the following mental health-related symptoms was found during the COVID-19 pandemic: feeling anxious, feeling sad, worrying, feeling nervous, trouble falling asleep, and trouble staying asleep. CONCLUSIONS: The mental health of dialysis patients appears to be unaffected by the COVID-19 pandemic. Dialysis patients may be better able to cope with the pandemic, since they have high resilience and are less impacted by social distancing measures. TRIAL REGISTRATION NUMBER: Netherlands Trial Register NL6519, date of registration: 22 August 2017.

Clinical presentation and long-term follow-up of dopamine beta hydroxylase deficiency.

Dopamine beta hydroxylase (DBH) deficiency is an extremely rare autosomal recessive disorder with severe orthostatic hypotension, that can be treated with L-threo-3,4-dihydroxyphenylserine (L-DOPS). We aimed to summarize clinical, biochemical, and genetic data of all world-wide reported patients with DBH-deficiency, and to present detailed new data on long-term follow-up of a relatively large Dutch cohort. We retrospectively describe 10 patients from a Dutch cohort and 15 additional patients from the literature. We identified 25 patients (15 females) from 20 families. Ten patients were diagnosed in the Netherlands. Duration of follow-up of Dutch patients ranged from 1 to 21 years (median 13 years). All patients had severe orthostatic hypotension. Severely decreased or absent (nor)epinephrine, and increased dopamine plasma concentrations were found in 24/25 patients. Impaired kidney function and anemia were present in all Dutch patients, hypomagnesaemia in 5 out of 10. Clinically, all patients responded very well to L-DOPS, with marked reduction of orthostatic complaints. However, orthostatic hypotension remained present, and kidney function, anemia, and hypomagnesaemia only partially improved. Plasma norepinephrine increased and became detectable, while epinephrine remained undetectable in most patients. We confirm the core clinical characteristics of DBH-deficiency and the pathognomonic profile of catecholamines in body fluids. Impaired renal function, anemia, and hypomagnesaemia can be part of the clinical presentation. The subjective response to L-DOPS treatment is excellent and sustained, although the neurotransmitter profile in plasma does not normalize completely. Furthermore, orthostatic hypotension as well as renal function, anemia, and hypomagnesaemia improve only partially.