Post COVID-19 condition imposes significant burden in patients with advanced chronic kidney disease: A nested case-control study.

BACKGROUND: The burden of post COVID-19 condition (PCC) is not well studied in patients with advanced kidney disease. METHODS: A large prospective cohort of SARS-CoV-2 vaccinated patients with chronic kidney disease stages G4-G5 (CKD G4/5), on dialysis, and kidney transplant recipients (KTR) were included. Antibody levels were determined after vaccination. Presence of long-lasting symptoms was assessed in patients with and without prior COVID-19 and compared using logistic regression. In patients with prior COVID-19, PCC was defined according to the WHO definition. RESULTS: Two hundred sixteen CKD G4/5 patients, 375 dialysis patients, and 2005 KTR were included. Long-lasting symptoms were reported in 204/853 (24%) patients with prior COVID-19 and in 297/1743 (17%) patients without prior COVID-19 (aOR: 1.45 (1.17-1.78)], P < 0.001). PCC was prevalent in 29% of CKD G4/5 patients, 21% of dialysis patients, and 24% of KTR. In addition, 69% of patients with PCC reported (very) high symptom burden. Odds of PCC was lower per 10-fold increase in antibody level after vaccination (aOR 0.82 [0.70-0.96], P = 0.01) and higher in case of COVID-19 related hospital admission (aOR 4.64 [2.61-8.25], P = 0.003). CONCLUSIONS: CKD G4/5 patients, dialysis patients, and KTR are at risk for PCC with high symptom burden after SARS-CoV-2 vaccination, especially if antibody levels are low and in case of hospitalization due to COVID-19.

Cost-effectiveness of home-based screening of the general population for albuminuria to prevent progression of cardiovascular and kidney disease.

Background: Chronic kidney disease (CKD) is often detected late, leading to substantial health loss and high treatment costs. Screening the general population for albuminuria identifies individuals at high risk of kidney events and cardiovascular disease (CVD) who may benefit from early start of preventive interventions. Previous studies on the cost-effectiveness of albuminuria population screening were inconclusive, but were based on survey or cohort data rather than an implementation study, modelled screening as performed by general practitioners rather than home-based screening, and often included only benefits with respect to kidney events. We evaluated the cost-effectiveness of home-based general population screening for increased albuminuria based on real-world data obtained from a prospective implementation study taking into account prevention of CKD as well as CVD events. Methods: We developed an individual-level simulation model to compare home-based screening using a urine collection device with usual care (no home-based screening) in individuals of the general population aged 45-80, based on the THOMAS study (Towards HOMe-based Albuminuria Screening). Cost-effectiveness was assessed from the Dutch healthcare perspective with a lifetime horizon. The costs of the screening process and benefits of preventing CKD progression (dialysis and kidney transplantation) and CVD events (non-fatal myocardial infarction, non-fatal stroke, fatal CVD event) were reflected. Albuminuria detection led to treatment of identified risk factors. The model subsequently simulated CKD progression, the occurrence of CVD events, and death. The risks of experiencing CVD events were calculated using the SCORE2 CKD risk prediction model and individual-level data from the THOMAS study. Relative treatment effectiveness, quality of life scores, resource use, and cost inputs were obtained from literature. Model outcomes were the number of CKD and CVD-related events, total costs, quality-adjusted life years (QALYs), and the incremental cost-effectiveness ratio (ICER) per QALY gained by screening versus usual care. All results were obtained through probabilistic analysis. Findings: The absolute difference between screening versus usual care in lifetime probability of dialysis, kidney transplantation, non-fatal myocardial infarction, non-fatal stroke, and fatal CVD events were 0.2%, 0.05%, 0.6%, 0.6%, and 0.2%, respectively. This led to relative decreases compared to usual care in lifetime incidence of these events of 10.7%, 11.1%, 5.1%, 4.1%, and 1.6%, respectively. The incremental costs and QALYs of screening were €1607 and 0.17 QALY, respectively, which led to a corresponding ICER of €9225/QALY. The probability of screening being cost-effective for the Dutch willingness-to-pay threshold for preventive population screening of €20,000/QALY was 95.0%. Implementing the screening in the subgroup of 45-64 years old reduced the ICER (€7946/QALY), whereas implementing screening in the subgroup of 65-80 years old increased the ICER (€10,310/QALY). A scenario analysis assuming treatment optimization in all individuals with newly diagnosed risk factors or known risk factors not within target range reduced the ICER to €7083/QALY, resulting from the incremental costs and QALY gain of €2145 and 0.30, respectively. Interpretation: Home-based screening for increased albuminuria to prevent CVD and CKD events is likely cost-effective. More health benefits can be obtained by screening younger individuals and better optimization of care in individuals identified with newly diagnosed or known risk factors outside target range. Funding: Dutch Kidney Foundation, Top Sector Life Sciences & Health of the Dutch Ministry of Economic Affairs.

Incidence and outcomes of kidney replacement therapy for end-stage kidney disease due to primary glomerular disease in Europe: findings from the ERA Registry.

BACKGROUND AND HYPOTHESIS: Primary glomerular disease (PGD) is a major cause of end-stage kidney disease (ESKD) leading to kidney replacement therapy (KRT). We aimed to describe incidence (trends) in individuals starting KRT for ESKD due to PGD and to examine their survival and causes of death. METHODS: We used data from the European Renal Association (ERA) Registry on 69 854 patients who started KRT for ESKD due to PGD between 2000 and 2019. ERA primary renal disease codes were used to define six PGD subgroups. We examined age and sex standardized incidence, trend of the incidence, and survival. RESULTS: The standardized incidence of KRT for ESKD due to PGD was 16.6 per million population (pmp), ranging from 8.6 pmp in Serbia to 20.0 pmp in France. IgA nephropathy (IgAN) and focal segmental glomerulosclerosis (FSGS) had the highest incidence of 4.6 pmp and 2.6 pmp, respectively. Histologically non-examined PGDs represented over 50% of cases in Serbia, Bosnia and Herzegovina, and Romania and were also common in Greece, Estonia, Belgium, and Sweden. The incidence declined from 18.6 pmp in 2000 to 14.5 pmp in 2013, after which it stabilized. All PGD subgroups had five-year survival probabilities above 50%, with crescentic glomerulonephritis having the highest risk of death (adjusted hazard ratio: 1.8 [95% confidence interval: 1.6-1.9]) compared with IgAN. Cardiovascular disease was the most common cause of death (33.9%). CONCLUSION: The incidence of KRT for ESKD due to PGD showed large differences between countries and was highest and increasing for IgAN and FSGS. Lack of kidney biopsy facilities in some countries may have affected accurate assignment of the cause of ESKD. The recognition of the incidence and outcomes of KRT among different PGD subgroups may contribute to a more individualized patient care approach.

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.

Incidence and Severity of COVID-19 in Relation to Anti-Receptor-Binding Domain IgG Antibody Level after COVID-19 Vaccination in Kidney Transplant Recipients.

Kidney transplant recipients (KTRs) elicit an impaired immune response after COVID-19 vaccination; however, the exact clinical impact remains unclear. We therefore analyse the relationship between antibody levels after vaccination and the risk of COVID-19 in a large cohort of KTRs. All KTRs living in the Netherlands were invited to send a blood sample 28 days after their second COVID-19 vaccination for measurement of their IgG antibodies against the receptor-binding domain of the SARS-CoV-2 spike protein (anti-RBD IgG). Information on COVID-19 was collected from the moment the blood sample was obtained until 6 months thereafter. Multivariable Cox and logistic regression analyses were performed to analyse which factors affected the occurrence and severity (i.e., hospitalization and/or death) of COVID-19. In total, 12,159 KTRs were approached, of whom 2885 were included in the analyses. Among those, 1578 (54.7%) became seropositive (i.e., anti-RBD IgG level >50 BAU/mL). Seropositivity was associated with a lower risk for COVID-19, also after adjusting for multiple confounders, including socio-economic status and adherence to COVID-19 restrictions (HR 0.37 (0.19-0.47), p = 0.005). When studied on a continuous scale, we observed a log-linear relationship between antibody level and the risk for COVID-19 (HR 0.52 (0.31-0.89), p = 0.02). Similar results were found for COVID-19 severity. In conclusion, antibody level after COVID-19 vaccination is associated in a log-linear manner with the occurrence and severity of COVID-19 in KTRs. This implies that if future vaccinations are indicated, the aim should be to reach for as high an antibody level as possible and not only seropositivity to protect this vulnerable patient group from disease.

Differences in mental health status during the COVID-19 pandemic between patients undergoing in-center hemodialysis and peritoneal dialysis.

BACKGROUND: The mental health of dialysis patients during the COVID-19 pandemic may have been modulated by dialysis modality. Studies comparing mental health of in-center hemodialysis and peritoneal dialysis patients during the first 2 years of the pandemic are lacking. METHODS: We conducted repeated cross-sectional and multivariable regression analyses to compare the mental health of in-center hemodialysis and peritoneal dialysis patients from March 2019 until August 2021 using data from the Dutch nOcturnal and hoME dialysis Study To Improve Clinical Outcomes. The study period was divided into one pre-pandemic and six 3-month pandemic periods (period 1-period 6). Mental health was assessed with the Mental Component Summary score of the 12-item Short Form health survey and mental symptoms of the Dialysis Symptom Index. RESULTS: We included 1274 patients (968 on in-center hemodialysis and 306 on peritoneal dialysis). Mental Component Summary scores did not differ between in-center hemodialysis and peritoneal dialysis patients. In contrast, in-center hemodialysis patients more often reported nervousness during period 3 (27% vs 15%, P = 0.04), irritability and anxiety during period 3 (31% vs 18%, P = 0.03, 26% vs. 9%, P = 0.002, respectively) and period 4 (34% vs 22%, P = 0.04, 22% vs 11%, P = 0.03, respectively), and sadness in period 4 (38% vs 26%, P = 0.04) and period 5 (37% vs 22%, P = 0.009). Dialysis modality was independently associated with mental symptoms. CONCLUSIONS: In-center hemodialysis patients more often experienced mental symptoms compared to peritoneal dialysis patients from September 2020 to June 2021, which corresponds to the second lockdown of the COVID-19 pandemic. Mental health-related quality-of-life did not differ between in-center hemodialysis and peritoneal dialysis patients. TRIAL REGISTRATION NUMBER: Netherlands Trial Register NL6519, date of registration: 22 August, 2017.

Participation rate and yield of two home-based screening methods to detect increased albuminuria in the general population in the Netherlands (THOMAS): a prospective, randomised, open-label implementation study.

BACKGROUND: Chronic kidney disease (CKD) has a rising global prevalence and is expected to become the fifth leading cause of death by 2030. Increased albuminuria defines the early stages of CKD and is among the strongest risk factors for progressive CKD and cardiovascular disease. The value of population screening for albuminuria to detect CKD in an early phase has yet to be studied. We aimed to evaluate the effectiveness of two home-based albuminuria population screening methods. METHODS: Towards Home-based Albuminuria Screening (THOMAS) was a prospective, randomised, open-label implementation study that invited Dutch adults aged 45-80 years for albuminuria screening. Individuals were randomly assigned (1:1) to screening by applying either a urine collection device (UCD) that was sent by post to a central laboratory for measurement of the albumin-to-creatinine ratio (ACR) by immunoturbidimetry or to screening via a smartphone application that measures the ACR with a dipstick method at home. Randomisation was done with a four-block method via a web-based system and was stratified by age, sex, and socioeconomic status. If two or more individuals per household were invited to participate, these individuals were randomly assigned to the same group. In case of confirmed increased albuminuria at home, participants were invited for an elaborate screening in a regional hospital (Amphia Hospital, Breda, Netherlands) for CKD and cardiovascular risk factors. When abnormalities were found, participants were referred to their general practitioner for treatment. The primary outcomes were the participation rate and yield of the home-based screening and elaborate screening. Participation rate was assessed in the intention-to-screen population (ie, all participants who were invited for the home-based screening or elaborate screening). Yield was assessed in the per-protocol population (ie, all individuals who participated in the home-based screening or elaborate screening). An exploratory analysis assessed the sensitivity and specificity of both home-based screening methods. To this end, an additional quantitative ACR test was performed among people participating in the elaborate screening, and a substudy was performed among participants with a first negative home-based screening test, who were invited for an additional test. The study is registered with ClinicalTrials.gov, NCT04295889. FINDINGS: 15 074 participants were enrolled between Nov 14, 2019, and March 19, 2021. 7552 (50·1%) were randomly assigned to home-based albuminuria screening by the UCD method and 7522 (49·9%) were assigned to albuminuria screening by the smartphone application method. The participation rate of the home-based screening was 4484 (59·4% [95% CI 58·3-60·5]) of the 7552 invited individuals for the UCD method and 3336 (44·3% [43·2-45·5]) of 7522 invited individuals for the smartphone application method (p<0·0001). Increased ACR was confirmed by home-based testing in 150 (3·3% [95% CI 2·9-3·9]) of 4484 individuals for the UCD method and 171 (5·1% [4·4-5·9]) of 3336 indivduals for the smartphone application method. 124 (82·7% [95% CI 75·8-87·9]) of 150 individuals assigned to the UCD method and 142 (83·0% [76·7-87·9]) of 171 participants assigned to the smartphone application method attended the elaborate screening. Sensitivity to detect increased ACR was 96·6% (95% CI 91·5-99·1) for the UCD method and 98·1% (89·9-99·9) for the smartphone application method, and specificity was 97·3% (94·7-98·8) for the UCD method and 67·9% (62·0-73·3) for the smartphone application method, indicating that the test characteristics of only the UCD method were sufficient for screening. Albuminuria, hypertension, hypercholesterolaemia, and decreased kidney function were newly diagnosed in 77 (62·1%), 44 (35·5%), 30 (24·2%), and 27 (21·8%) of 124 participants for the UCD method, respectively. Of the 124 participants assigned to the UCD method who completed elaborate screening, 111 (89·5%) were referred to their general practitioner for treatment because of newly diagnosed CKD or cardiovascular disease risk factors or known risk factors outside the target range. INTERPRETATION: Home-based screening of the general population for increased ACR using a UCD had a high participation rate and correctly identified individuals with increased albuminuria and yet unknown or known but outside target range CKD and cardiovascular risk factors. By contrast, the smartphone application method had a lower at-home participation rate than the UCD method and the test specificity was too low to accurately assess individuals for risk factors during the elaborate screening. The UCD screening strategy could allow for an early start of treatment to prevent progressive kidney function loss and cardiovascular disease in patients with CKD. FUNDING: Dutch Kidney Foundation, Top Sector Life Sciences & Health of the Dutch Ministry of Economic Affairs.

Adherence to preventive measures after SARS-CoV-2 vaccination and after awareness of antibody response in kidney transplant recipients in the Netherlands: a nationwide questionnaire study.

Background: Kidney transplant recipients (KTRs) were advised to tightly adhere to government recommendations to curb the spread of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) because of a high risk of morbidity and mortality and decreased immunogenicity after vaccination. The aim of this study was to analyse the change in adherence to preventive measures after vaccination and awareness of antibody response, and to evaluate its effectiveness. Methods: In this large-scale, national questionnaire study, questionnaires were sent to 3531 KTRs enrolled in the Dutch RECOVAC studies, retrospectively asking for adherence to nine preventive measures on a 5-point Likert scale before and after SARS-CoV-2 vaccination and after awareness of antibody response. Blood samples were collected 28 days after the second vaccination. Antibody response was categorised as non-responder (≤50 BAU/mL), low-responder (>50 ≤ 300 BAU/mL) or high-responder (>300 BAU/mL), and shared with participants as a correlate of protection. Participants of whom demographics on sex and age, blood samples and completed questionnaires were available, were included. Our study took place between February 2021 and January 2022. The primary outcome of adherence before and after vaccination was assessed between August and October 2021 and compared via the Wilcoxon signed rank sum test. Logistic regression analysis was performed to estimate the association between antibody response and non-adherence, and adherence on acquiring SARS-CoV-2 infection. This study is registered at ClinicalTrials.gov (NCT04841785). Findings: In 2939 KTRs (83%) who completed the first questionnaire on adherence to preventive measures, adherence was higher before than after vaccination (4.56, IQR 4.11-4.78 and 4.22, IQR 3.67-4.67, p < 0.001). Adherence after awareness of antibody response was analysed in 2399 KTRs (82%) of whom also blood samples were available, containing 949 non-responders, 500 low-responders and 950 high-responders. Compared to non-responders, low- and high-responders reported higher non-adherence. Higher adherence was associated with lower infection rates before and after vaccination (OR 0.67 [0.51-0.91], p = 0.008 and OR 0.48 [0.28-0.86], p = 0.010). Interpretation: Adherence decreased after SARS-CoV-2 vaccination and in KTRs who were aware of a subsequent antibody response compared with those without. Preventive measures in this vulnerable group seem to be effective, regardless of vaccination status. This study starts a debate on sharing antibody results with the patient and future studies should elucidate whether decreased adherence in antibody responders is justified, also in view of future pandemics. Funding: The Netherlands Organization for Health Research and Development and the Dutch Kidney Foundation.

Understanding Health-Related Quality of Life in Kidney Transplant Recipients: The Role of Symptom Experience and Illness Perceptions.

The purpose of our article is to investigate the impact of symptom experience on health related quality of life (HRQOL) in kidney transplant recipients (KTRs) and whether illness perceptions mediated this impact. Symptom experience, illness perceptions, and HRQOL were measured at transplantation and 6 weeks after transplantation in KTRs in an ongoing Dutch cohort study. Multivariable linear regression models were used for the analysis. 90 KTRs were analyzed. Fatigue and lack of energy were the most prevalent and burdensome symptoms at transplantation. Mental HRQOL at 6 weeks after transplantation was comparable to that of the general Dutch population (mean [standard deviation, SD]: 49.9 [10.7]) versus 50.2 [9.2]), while physical HRQOL was significantly lower (38.9 [9.1] versus 50.6 [9.2]). Experiencing more symptoms was associated with lower physical and mental HRQOL, and the corresponding HRQOL reduced by -0.15 (95%CI, -0.31; 0.02) and -0.23 (95%CI, -0.42; -0.04) with each additional symptom. The identified mediation effect suggests that worse symptom experiences could cause more unhelpful illness perceptions and consequently lead to lower HRQOL. Illness perceptions may explain the negative impact of symptom experience on HRQOL. Future studies at later stages after kidney transplantation are needed to further explore the mediation effect of illness perceptions and guide clinical practice to improve HRQOL.

Facing the challenges of PROM implementation in Dutch dialysis care: Patients' and professionals' perspectives.

BACKGROUND: Patient Reported Outcome Measures (PROMs) are increasingly used in routine clinical practice to facilitate patients in sharing and discussing health-related topics with their clinician. This study focuses on the implementation experiences of healthcare professionals and patients during the early implementation phase of the newly developed Dutch set of dialysis PROMs and aims to understand the process of early implementation of PROMs from the users' perspectives. METHODS: This is a qualitative study among healthcare professionals (physicians and nursing staff: n = 13) and patients (n = 14) of which 12 were receiving haemodialysis and 2 peritoneal dialysis. Semi-structured interviews were used to understand the barriers and facilitators that both professionals and patients encounter when starting to implement PROMs. RESULTS: The early PROM implementation process is influenced by a variety of factors that we divided into barriers and facilitators. We identified four barriers: patient´s indifference to PROMs, scepticism on the benefits of aggregated PROM data, the limited treatment options open to doctors and organizational issues such as mergers, organizational problems and renovations. We also describe four facilitators: professional involvement and patient support, a growing understanding of the use of PROMs during the implementation, quick gains from using PROMs such as receiving instant feedback and a clear ambition on patient care such as a shared view on patient involvement and management support. CONCLUSIONS: In this qualitative study carried out during the early implementation phase of the Dutch dialysis PROM set, we found that patients did not yet consider the PROM set to be a useful additional tool to share information with their doctor. This was despite the professionals' primary reason for using PROMs being to improve patient-doctor communication. Furthermore, the perceived lack of intervention options was frustrating for some of the professionals. We found that nurses could be important enablers of further implementation because of their intensive relationship with dialysis patients.

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.

Strategies to prevent SARS-CoV-2 transmission in hemodialysis centres across Europe-lessons for the future.

Background: Early reports on the pandemic nature of coronavirus disease 2019 (COVID-19) directed the nephrology community to develop infection prevention and control (IPC) guidance. We aimed to make an inventory of strategies that dialysis centres followed to prevent infection with COVID-19 in the first pandemic wave. Methods: We analyzed IPC measures taken by hemodialysis centres treating patients presenting with COVID-19 between 1 March 2020 and 31 July 2020 and that completed the European Renal Association COVID-19 Database centre questionnaire. Additionally, we made an inventory of guidelines published in European countries to prevent spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in dialysis centres. Results: Data from 73 dialysis units located in and bordering Europe were analyzed. All participating centres implemented IPC measures to mitigate the impact of SARS-CoV-2 during the first pandemic wave. Measures mentioned most often included triage with questions before entering the dialysis ward, measuring body temperature, hand disinfection, masking for all patients and staff, and personal protective equipment for staff members. These measures were also recommended in most of the 14 guidelines that were identified in the inventory of national guidelines and were also scored as being among the most important measures by the authors of this paper. Heterogeneity existed between centres and national guidelines regarding the minimal distance between dialysis chairs and recommendations regarding isolation and cohorting. Conclusions: Although variation existed, measures to prevent transmission of SARS-CoV-2 were relatively similar across centres and national guidelines. Further research is needed to assess causal relationships between measures taken and spread of SARS-CoV-2.

Impact of immunosuppressive treatment and type of SARS-CoV-2 vaccine on antibody levels after three vaccinations in patients with chronic kidney disease or kidney replacement therapy.

Background: Patients with chronic kidney disease (CKD) or kidney replacement therapy demonstrate lower antibody levels after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccination compared with healthy controls. In a prospective cohort, we analysed the impact of immunosuppressive treatment and type of vaccine on antibody levels after three SARS-CoV-2 vaccinations. Methods: Control subjects (n = 186), patients with CKD G4/5 (n = 400), dialysis patients (n = 480) and kidney transplant recipients (KTR) (n = 2468) were vaccinated with either mRNA-1273 (Moderna), BNT162b2 (Pfizer-BioNTech) or AZD1222 (Oxford/AstraZeneca) in the Dutch SARS-CoV-2 vaccination programme. Third vaccination data were available in a subgroup of patients (n = 1829). Blood samples and questionnaires were obtained 1 month after the second and third vaccination. Primary endpoint was the antibody level in relation to immunosuppressive treatment and type of vaccine. Secondary endpoint was occurrence of adverse events after vaccination. Results: Antibody levels after two and three vaccinations were lower in patients with CKD G4/5 and dialysis patients with immunosuppressive treatment compared with patients without immunosuppressive treatment. After two vaccinations, we observed lower antibody levels in KTR using mycophenolate mofetil (MMF) compared with KTR not using MMF [20 binding antibody unit (BAU)/mL (3-113) vs 340 BAU/mL (50-1492), P < .001]. Seroconversion was observed in 35% of KTR using MMF, compared with 75% of KTR not using MMF. Of the KTR who used MMF and did not seroconvert, eventually 46% seroconverted after a third vaccination. mRNA-1273 induces higher antibody levels as well as a higher frequency of adverse events compared with BNT162b2 in all patient groups. Conclusions: Immunosuppressive treatment adversely affects the antibody levels after SARS-CoV-2 vaccination in patients with CKD G4/5, dialysis patients and KTR. mRNA-1273 vaccine induces a higher antibody level and higher frequency of adverse events.

Outcomes of COVID-19 in peritoneal dialysis patients: A report by the European Renal Association COVID-19 Database.

BACKGROUND: The clinical course of COVID-19 in peritoneal dialysis (PD) patients has so far only been analysed in relatively small, often single-centre case series. Therefore, we studied patient- and disease-related characteristics and outcomes of COVID-19 in a larger European cohort of PD patients. METHODS: We used data from the European Renal Association COVID-19 Database (ERACODA) on PD and haemodialysis (HD) patients with COVID-19 (presentation between February 2020 and April 2021). Hazard ratios (HR) for mortality at 3 months were calculated using Cox proportional-hazards regression. In addition, we examined functional and mental health status among survivors at this time point as determined by their treating physician. RESULTS: Of 216 PD patients with COVID-19, 80 (37%) were not hospitalised and 136 (63%) were hospitalised, of whom 19 (8.8%) were admitted to an intensive care unit. Mortality at 3 months for these subgroups was 18%, 40%, and 37%, respectively (p = 0.0031). Compared with HD patients, PD patients had higher mortality (crude HR: 1.49; 95% CI: 1.33-1.66), even when adjusted for patient characteristics and disease severity (adjusted HR: 1.56; 95% CI: 1.39-1.75). Follow-up data on 67 of 146 patients who survived COVID-19 showed functional recovery to pre-COVID-19 levels in 52 (78%) and mental recovery in 58 patients (87%) at 3 months after the COVID-19 diagnosis. CONCLUSION: The mortality rate in the first 3 months after presentation with COVID-19 is high, especially among PD patients who were hospitalised. PD patients with COVID-19 had a higher mortality risk than HD patients. The majority of surviving patients recovered both functionally and mentally from COVID-19 within 3 months.

Effect of residual kidney function and dialysis adequacy on chronic pruritus in dialysis patients.

BACKGROUND: Chronic kidney disease-associated pruritus (CKD-aP) is common in dialysis patients, and is associated with lower quality of life and increased risk of death. We investigated the association between residual estimated glomerular filtration rate (eGFR), dialysis adequacy or serum phosphate level and CKD-aP in incident dialysis patients. METHODS: A total of 1256 incident hemodialysis (HD) and 670 peritoneal dialysis (PD) patients (>18 years) from the Netherlands Cooperative Study on the Adequacy of Dialysis (NECOSAD) study were included (1997-2007) and followed until death, transplantation or a maximum of 10 years. CKD-aP was measured using a single item of the Kidney Disease Quality of Life Instrument-36. The associations were studied by logistic and linear regression analyses, adjusted for potential baseline confounders. RESULTS: At baseline mean (standard deviation) age was 60 (16) years, 62% were men and median (interquartile range) residual eGFR was 3.4 (1.7; 5.3) mL/min/1.73 m2. The prevalence of CKD-aP (∼70%) was similar in HD and PD. It was observed that 12 months after starting dialysis (after multivariable adjustment) each 1 mL/min/1.73 m2 higher residual eGFR, one unit higher total weekly Kt/V, or 1 mmol/L lower serum phosphate level was associated with lower burden of CKD-aP in HD and PD patients of -0.05 (95% CI -0.09; -0.02) and -0.09 (95% CI -0.13; -0.05), -0.15 (95% CI -0.26; -0.05) and -0.35 (95% CI -0.54; -0.16), and of -0.34 (95%CI: -0.51; -0.17) and -0.45 (95%CI: -0.71; -0.19), respectively. We found no association between dialysis Kt/V and CKD-aP. CONCLUSIONS: Higher residual eGFR and lower serum phosphate level, but not the dialysis dose, were related with lower burden of CKD-aP in dialysis patients.

Preparing European Nephrology for the next pandemic: lessons from the ERACODA collaboration.

Owing to the vulnerability of patients with chronic kidney disease to infectious diseases, the coronavirus disease 2019 (COVID-19) pandemic has been particularly devastating for the nephrology community. Unfortunately, the possibility of future COVID-19 waves or outbreaks of other infectious diseases with pandemic potential cannot be ruled out. The nephrology community made tremendous efforts to contain the consequences of the COVID-19 pandemic. Despite this, the COVID-19 pandemic has highlighted several shortcomings in our response to the pandemic and has taught us important lessons that can be utilized to improve our preparedness for any future health crises of a similar nature. In this article we draw lessons from the European Renal Association COVID-19 Database (ERACODA) project, a pan-European collaboration initiated in March 2020 to understand the prognosis of COVID-19 in patients on kidney function replacement therapy. We discuss the challenges faced in generating timely and robust evidence for informed management of patients with kidney disease and give recommendations for our preparedness for the next pandemic in Europe. Limited collaboration, the absence of common data architecture and the sub-optimal quality of available data posed challenges in our response to COVID-19. Aligning different research initiatives, strengthening electronic health records, and involving experts in study design and data analysis will be important in our response to the next pandemic. The European Renal Association may take a leading role in aligning research initiatives via its engagement with other scientific societies, national registries, administrators and researchers.

Protocol for a randomized study assessing the feasibility of home-based albuminuria screening among the general population: The THOMAS study.

BACKGROUND: Chronic kidney disease (CKD) is a rising public health problem that may progress to kidney failure, requiring kidney replacement therapy. It is also associated with an increased incidence of cardiovascular disease (CVD). Because of its asymptomatic nature, CKD is often detected in a late stage. Population screening for albuminuria could allow early detection of people with CKD who may benefit from preventive treatment. In case such screening is performed in a general practitioner (GP) setting, this will result in relatively high costs. Home-based screening might be an effective and cost-effective alternative. AIM: The THOMAS study (Towards HOMe-based Albuminuria Screening) is designed to prospectively investigate two methods for home-based population screening for increased albuminuria to detect yet undiagnosed CKD and risk factors for progression and CVD. METHODS: This investigator initiated, randomized population-based study will include 15.000 individuals aged 45-80 years, who will be randomly assigned to be invited for a home-based screening test for albuminuria with a more conventional urine collection device or an innovative smartphone application. If the test result is positive upon confirmation (i.e., elevated albuminuria), participants are invited to a central screening facility for an elaborate screening for CKD and CVD risk factors. Participants are referred to their GP for appropriate treatment, if abnormalities are found. Primary endpoints are the participation rate, yield, and cost-effectiveness of the home-based screening and elaborate screening. CONCLUSIONS: The THOMAS study will evaluate the effectiveness and cost-effectiveness of home-based albuminuria screening in the general population for the early detection of CKD and CVD risk factors. It will provide insight into the willingness to participate in population screening for CKD and into the compliance of the general population to a corresponding screening protocol and compliance to participate. Thus, it may help to develop an attractive novel screening strategy for the early detection of CKD. TRIAL REGISTRATION: ClinicalTrials.gov, registration number NCT04295889, registered 05 March 2020. https://www.google.com/search?client=firefox-b-d&q=NCT04295889.

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.

Predictors of Nonseroconversion to SARS-CoV-2 Vaccination in Kidney Transplant Recipients.

Kidney transplant recipients (KTRs) are still at risk of severe COVID-19 disease after SARS­CoV­2 vaccination, especially when they have limited antibody formation. Our aim was to understand the factors that may limit their humoral response. Methods: Our data are derived from KTRs who were enrolled in the Dutch Renal Patients COVID-19 Vaccination consortium, using a discovery cohort and 2 external validation cohorts. Included in the discovery (N = 1804) and first validation (N = 288) cohorts were participants who received 2 doses of the mRNA-1273 vaccine. The second validation cohort consisted of KTRs who subsequently received a third dose of any SARS-CoV-2 vaccine (N = 1401). All participants had no history of SARS-CoV-2 infection. A multivariable logistic prediction model was built using stepwise backward regression analysis with nonseroconversion as the outcome. Results: The discovery cohort comprised 836 (46.3%) KTRs, the first validation cohort 124 (43.1%) KTRs, and the second validation cohort 358 (25.6%) KTRs who did not seroconvert. In the final multivariable model' 12 factors remained predictive for nonseroconversion: use of mycophenolate mofetil/mycophenolic acid (MMF/MPA); chronic lung disease, heart failure, and diabetes; increased age; shorter time after transplantation; lower body mass index; lower kidney function; no alcohol consumption; ≥2 transplantations; and no use of mammalian target of rapamycin inhibitors or calcineurin inhibitors. The area under the curve was 0.77 (95% confidence interval [CI], 0.74-0.79) in the discovery cohort after adjustment for optimism, 0.81 (95% CI, 0.76-0.86) in the first validation cohort, and 0.67 (95% CI, 0.64-0.71) in the second validation cohort. The strongest predictor was the use of MMF/MPA, with a dose-dependent unfavorable effect, which remained after 3 vaccinations. Conclusions: In a large sample of KTRs, we identify a selection of KTRs at high risk of nonseroconversion after SARS-CoV-2 vaccination. Modulation of MMF/MPA treatment before vaccination may help to optimize vaccine response in these KTRs. This model contributes to future considerations on alternative vaccination strategies.