Lupus activity and outcomes in lupus patients undergoing maintenance dialysis.

OBJECTIVES: Lupus activity has long been considered to decline after initiation of maintenance dialysis (MD). This assumption is based on limited historical data. We aimed to describe the natural history of lupus in patients undergoing MD. METHODS: We assembled a national retrospective cohort of lupus patients who started dialysis between 2008 and 2011, included in the REIN registry with a 5-year follow-up. We analysed healthcare consumption from the National Health Data System. We evaluated the proportion of patients 'off-treatment' (i.e. receiving 0-5 mg/d of corticosteroids, without any immunosuppressive therapy) after the start of MD. We describe the cumulative incidences of non-severe and severe lupus flares, cardiovascular events, severe infections, kidney transplantation and survival. RESULTS: We included 137 patients (121 females and 16 males), with a median age of 42 years. The proportion of patients 'off-treatment' at dialysis initiation was 67.7% (95% CI: 61.8, 73.8%), and increased to 76.0% (95% CI: 73.3, 78.8) at 1 year and 83.4% (95% CI: 81.0, 85.9%) at 3 years, with a lower proportion in younger patients. Lupus flares mainly occurred in the first year after MD initiation, and at 12 months 51.6% of patients had presented a non-severe lupus flare and 11.6% a severe lupus flare. In addition, 42.2% (95% CI: 32.9, 50.3%) and 23.7% (95% CI: 16.0, 30.7%) of patients at 12 months had been hospitalized for cardiovascular events or infections, respectively. CONCLUSION: The proportion of lupus patients off-treatment increases after MD initiation, but non-severe and severe lupus flares continue to occur, mainly during the first year. This calls for the continued follow-up of lupus patients by lupus specialists after dialysis initiation.

Effectiveness and safety of direct oral anticoagulants versus vitamin K antagonists in patients on chronic dialysis: a nationwide registry study.

BACKGROUND AND HYPOTHESIS: Clinical trials of direct oral anticoagulants (DOAC) are scarce and inconclusive in patients who are receiving dialysis, for whom DOAC are not labelled in Europe. In a French nationwide registry study of patients on chronic dialysis, we compared the effectiveness and safety of off-label DOAC use vs. approved vitamin K antagonist (VKA). METHODS: Data on patients on dialysis were extracted from the French Renal Epidemiology and Information Network (REIN) registry and merged with data from the French national healthcare system database (Système National des Données de Santé, SNDS). Patients on dialysis who had initiated treatment with an oral anticoagulant between January 1st, 2012, and December 31st, 2020, were eligible for inclusion. The primary safety outcome was the occurrence of major bleeding events and the primary effectiveness outcome was the occurrence of thrombotic events. Using propensity-score-weighted cause-specific Cox regression, we compared the safety and effectiveness outcomes for DOAC and VKA. RESULTS: 8,954 patients received an oral anticoagulant (483 DOAC and 8,471 VKA) for the first time after the initiation of dialysis. Over a median [interquartile range] follow-up period of 1.7 [0.8-3.2] years, 2,567 patients presented a first thromboembolic event and 1,254 patients had a bleeding event. After propensity score adjustment, the risk of a thromboembolic event was significantly lower in patients treated with a DOAC than in patients treated with a VKA (weighted hazard ratio (wHR) [95% confidence interval (CI)]: 0.66 [0.46; 0.94]. A non-significant trend toward a lower risk of major bleeding events was found in DOAC-treated patients, relative to VKA-treated patients (wHR [95%CI]: 0.68 [0.41; 1.12]). The results were consistent across subgroups and in sensitivity analyses. CONCLUSIONS: In a large group of dialysis patients initiating an oral anticoagulant, the off-label use of DOACs was associated with a significantly lower risk of thromboembolic events and a non-significantly lower risk of bleeding, relative to VKA use. This provides reassurance regarding the off-label use of DOACs in people on dialysis.

Lower access to kidney transplantation for women in France is not explained by comorbidities and social deprivation.

BACKGROUND: Access to kidney transplantation (KT) remains challenging for patients with end-stage kidney disease. This study assessed women's access to KT in France by considering comorbidities and neighborhood social deprivation. METHODS: All incident 18-85-year-old patients starting dialysis in France between January 1, 2017 and December 31, 2019 were included. Three outcomes were assessed: (i) access to the KT waiting list after dialysis start, (ii) KT access after waitlisting, and (iii) KT access after dialysis start. Cox and Fine and Gray models were used. Gender-EDI and gender-age interactions were tested and analyses were performed among strata if required. RESULTS: 29,395 patients were included (35% of women). After adjusting for social deprivation and comorbidities, women were less likely to be waitlisted at 1 (adjHR: 0.91 [0.87-0.96]) and 3 years (adjHR: 0.87 [0.84-0.91]) post-dialysis initiation. This disparity concerned mainly ≥60-year-old women (adjHR: 0.76 [0.71-0.82] at 1 year and 0.75 [0.71-0.81] at 3 years). Access to KT, after 2 years of waitlisting was similar between genders. Access to KT was similar between genders at 3 years after dialysis start, but decreased for women after 4 years (adjHR: 0.93 [0.88-0.99]) and longer follow-up (adjHR: 0.90 [0.85-0.96]). CONCLUSIONS: In France, women are less likely to be waitlisted and undergo kidney transplantation. This is driven by the ≥60-year-old group and is not explained by comorbidities or social deprivation level.

Time trends in preemptive kidney transplantation in Europe: an era registry study.

BACKGROUND: Preemptive kidney transplantation has better outcomes when compared to transplantation after dialysis. We aimed to examine trends in preemptive kidney transplantation between 2000 and 2019 in Europe and to provide an overview of associated policies, barriers and initiatives. METHODS: Adult patients from 12 European countries who received a preemptive kidney transplant were included. The representatives of the registries providing these data were questioned on the policies, barriers and initiatives around preemptive kidney transplantation. RESULTS: Between 2000 and 2019, 20 251 adults underwent preemptive kidney transplantation (11 169 from living donors, 8937 from deceased donors). The proportion of first kidney transplantations that were preemptive more than doubled from 7% in 2000 to 18% in 2019, reflecting a similar relative increase for living donor kidney recipients (from 21% to 43%) and deceased donor kidney recipients (from 4% to 11%). Large international differences were found. The increase in preemptive kidney transplantation was observed across all age, sex and primary renal disease groups. Countries had similar criteria for preemptive waitlisting. Barriers mentioned included donor shortage, late referral to the transplant center and long donor or recipient work-up. Suggested initiatives included raising awareness on the possibility of preemptive kidney transplantation, earlier start and shorter work-up time for recipient and living donor. CONCLUSIONS: Over the last two decades the proportion of patients receiving a first kidney transplant preemptively has more than doubled, reflecting a similar relative increase for living and deceased donor kidney recipients.

Evolution of HLA-sensitization according to immunosuppressive therapy management among kidney transplant patients returning to dialysis between 2008 and 2019: A French retrospective study.

BACKGROUND: The optimal management of immunosuppressive therapy (IT) after kidney allograft failure (KAF) remains controversial. Although maintaining IT may reduce HLA-sensitization and improve access to retransplantation, it may also increase the rate of immunosuppression-related complications. The overall impact on patient mortality is unknown. The main objective of this study was to compare the evolution of HLA-sensitization 6 months after KAF according to IT management. METHODS: Individual clinical and health care data were extracted from the French national end-stage kidney disease registry (Renal Epidemiology and Information Network [REIN]) and the French National Health Data system (SNDS), respectively. Patients aged > 18 years returning to dialysis after KAF between January 2008 and December 2019 in Lorraine were included. Patients were classified into two groups, IT continuation or IT discontinuation. HLA-sensitization was defined as an increase in incompatible graft rate (IGR) between KAF and 6 months post-KAF (change to a higher predefined category (0%-5%), (5%-20%), (20%-50%), (50%-85%), (85%-95%), (95%-98%), (98%-100%)). Secondary outcome was patient survival according to IT management. RESULTS: A total of 121 patients were included, 35 (29%) of whom continued IT. HLA-sensitization after KAF tended to be higher in the "IT discontinuation" group (57% vs. 38% in the "IT continuation" group, p = .07). In multivariate analysis, IT continuation was associated with a lower increase in IGR (OR .37, 95% CI [.14; .93]). IT management was not associated with patient mortality. CONCLUSIONS: Continuation of IT after KAF was associated with less change in IGR and was not associated with excess mortality.

Home dialysis: conclusions from a Kidney Disease: Improving Global Outcomes (KDIGO) Controversies Conference.

Home dialysis modalities (home hemodialysis [HD] and peritoneal dialysis [PD]) are associated with greater patient autonomy and treatment satisfaction compared with in-center modalities, yet the level of home-dialysis use worldwide is low. Reasons for limited utilization are context-dependent, informed by local resources, dialysis costs, access to healthcare, health system policies, provider bias or preferences, cultural beliefs, individual lifestyle concerns, potential care-partner time, and financial burdens. In May 2021, KDIGO (Kidney Disease: Improving Global Outcomes) convened a controversies conference on home dialysis, focusing on how modality choice and distribution are determined and strategies to expand home-dialysis use. Participants recognized that expanding use of home dialysis within a given health system requires alignment of policy, fiscal resources, organizational structure, provider incentives, and accountability. Clinical outcomes across all dialysis modalities are largely similar, but for specific clinical measures, one modality may have advantages over another. Therefore, choice among available modalities is preference-sensitive, with consideration of quality of life, life goals, clinical characteristics, family or care-partner support, and living environment. Ideally, individuals, their care-partners, and their healthcare teams will employ shared decision-making in assessing initial and subsequent kidney failure treatment options. To meet this goal, iterative, high-quality education and support for healthcare professionals, patients, and care-partners are priorities. Everyone who faces dialysis should have access to home therapy. Facilitating universal access to home dialysis and expanding utilization requires alignment of policy considerations and resources at the dialysis-center level, with clear leadership from informed and motivated clinical teams.

Social deprivation and kidney failure due to an undiagnosed nephropathy.

BACKGROUND: In France, kidney diseases of undetermined origin account for 5%-20% of all causes of end-stage kidney disease. We investigated the impact of social disadvantage on the lack of aetiological diagnosis of nephropathies. METHODS: Data from patients who started dialysis in France between 1 January 2017 and 30 June 2018 were extracted from the French Renal Epidemiology and Information Network registry. The social deprivation of each individual was estimated by the European Deprivation Index (EDI) defined by the patient's address. Logistic regression was used to perform mediation analysis to study the potential association between social deprivation and unknown nephropathy. RESULTS: Of the 7218 patients included, 1263 (17.5%) had unknown kidney disease. A total of 394 (31.4%) patients in the unknown kidney disease belonged to the most deprived quintile of the EDI [fifth quintile (Q5)], vs 1636 (27.5%) patients in the known kidney disease group. In the multivariate analysis, unknown kidney disease was associated with Q5 (odds ratio 1.40, 95% confidence interval 1.12-1.74, P = .003). Mediation analysis did not identify any variables (e.g. obesity, initiation of dialysis in emergency, number of visits to the general practitioner and nephrologist before initiation of dialysis, date of first nephrology consultation) that mediated the association between social deprivation and nephropathy of unknown origin. CONCLUSIONS: Our results show that, compared with nondeprived subjects, individuals experiencing social deprivation have a higher risk of unknown nephropathy at dialysis initiation. However, mediation analysis did not identify any variables that explained the association between social deprivation and nephropathy of unknown origin.

Arteriovenous access creation and hazards of hospitalization and death in patients starting hemodialysis.

BACKGROUND: Recent evidence suggests overestimation of benefits associated with arteriovenous (AV) fistula versus graft in certain populations. We assessed hazards of all-cause and cause-specific hospitalization and death associated with AV access type in patients who started hemodialysis with a catheter in France, overall and by subgroups of age, sex, and comorbidities. METHODS: From the REIN Registry, we included patients who initiated hemodialysis with a catheter from 2010 through 2018, and identified first-created fistula or graft through the French national health-administrative database. We used joint frailty models to deal with recurrent hospitalizations and potential informative censoring by death, and inverse probability weighting to account for confounding. RESULTS: From the 18 800 patients included (mean age 68 ± 15 years, 35% women), 5% underwent AV graft creation first. Weighted hazard ratio (wHR) of all-cause hospitalization associated with graft was 1.08 (95% CI 1.02 to 1.15), that of vascular access-related hospitalization was 1.43 (95% CI 1.32 to 1.55), and those of cardiovascular- and infection-related hospitalizations were 1.14 (95% CI 1.03 to 1.26) and 1.11 (95% CI 0.97 to 1.28), respectively. Results were consistent for most subgroups, except that the highest hazard of all-cause, cardiovascular-, and infection- related hospitalizations with graft was blunted in patients with comorbidities (i.e. diabetes, wHR 1.01, 95% CI 0.93 -1.10; 1.10, 95% CI 0.96 to 1.26; and 0.94, 95% CI 0.78 to 1.12, respectively). CONCLUSIONS: In patients starting hemodialysis with a catheter, AV graft creation is associated with increased hazard of vascular access-related hospitalizations compared to fistula. This may not be the case for death or other causes of hospitalization.

Cross-validation of comorbidity items in two national databases in a sample of patients with end-stage kidney disease.

BACKGROUND: The use of national medico-administrative databases for epidemiological studies has increased in the last decades. In France, the Healthcare Expenditures and Conditions Mapping (HECM) algorithm has been developed to analyse and monitor the morbidity and economic burden of 58 diseases. We aimed to assess the performance of the HECM in identifying different conditions in patients with end-stage kidney disease (ESKD) using data from the REIN registry (the French National Registry for patients with ESKD). METHODS: We included all patients over 18 years of age who started renal replacement therapy in France in 2018. Five conditions with a similar definition in both databases were included (ESKD, diabetes, human immunodeficiency virus [HIV], coronary insufficiency, and cancer). The performance of each SNDS algorithm was assessed using sensitivity, specificity, positive predictive values (PPVs), negative predictive values (NPVs), and Cohen's kappa coefficient. RESULTS: In total 5,971 patients were included. Among them, 81% were identified as having ESKD in both databases. Diabetes was the condition with the best performance, with a sensitivity, specificity, PPV, NPV, and Kappa coefficient all over 80%. Cancer had the lowest level of agreement with a Kappa coefficient of 51% and a high specificity and high NPV (94% and 95%). The conditions for which the definition in the HECM included disease-specific medications performed better in our study. CONCLUSION: The HECM showed good to very good concordance with the REIN database information overall, with the exception of cancer. Further validation of the HECM tool in other populations should be performed.

A prospective observational study for justification, safety, and efficacy of a third dose of mRNA vaccine in patients receiving maintenance hemodialysis.

The level of protection achieved by the standard two doses of COVID-19 mRNA vaccines in patients receiving maintenance hemodialysis (MHD) remains unclear. To study this we used the French Renal Epidemiology and Information Network (REIN) Registry to compare the incidence and severity of 1474 cases of COVID-19 diagnosed in patients receiving MHD after none, one or two doses of vaccine. Vaccination significantly reduce COVID-19 incidence and severity, but 11% of patients infected after two doses still died. Lack of vaccinal protection in patients naïve for SARS-CoV-2 could be due to defective Tfh response [38% of patients with negative spike-specific CD4+ T-cell interferon gamma release assay] and failure to generate viral neutralizing titers of anti-spike receptor binding domain (RBD) IgGs (63% of patients with titer at or under 997 BAU/ml, defining low/no responders) after two doses of vaccine. To improve protection, a third dose of vaccine was administered to 75 patients [57 low/no responders, 18 high responders after two doses] from the ROMANOV cohort that prospectively enrolled patients receiving MHD vaccinated with BNT162b2 (Pfizer). Tolerance to the third dose was excellent. High responders to two doses did not generate more anti-RBD IgGs after three doses but had more side effects. Importantly, 31 (54%) of low/no responders to two doses reached neutralizing titers of anti-RBD IgGs after three doses. A positive interferon gamma release assay and/or suboptimal titer of anti-RBD IgGs after two doses were the only predictive variables for response to three doses in multivariate analysis. Thus, the standard scheme of vaccination insufficiently protects patients receiving MHD. Anti-RBD IgG and specific CD4+ T-cell response after two doses can guide personalized administration of the third dose, which improves the humoral response of SARS-CoV-2-naïve patients receiving MHD.

Association between kidney retransplantation and survival according to age in the French national cohort of dialysis patients.

The mean age of patients returning to dialysis after a first kidney transplantation (KT) has increased in the past decades. We aimed to assess the association between second KT (2KT) and survival according to age at the time of return to dialysis. Data of 5334 patients registered in the French Renal Epidemiology and Information Network (REIN) (mean age 56.6 ± 13.6 years) who returned to dialysis after a first KT were collected. The association of 2KT with death was assessed using a propensity score-based analysis taking into account baseline and follow-up variables. In relisted patients (3272 patients, 61.3%), retransplantation was associated with better overall survival in comparison with patients who remained in dialysis (adjusted HR 0.75 [0.63-0.89], p = .0009). The survival advantage conferred by retransplantation gradually declined with increasing age (adjusted HR 0.41 [0.24-0.70] in patients <50, HR 0.94 (0.69-1.27) in patients aged 70 or older, p for interaction 0.034 for age considered as a continuous variable). 2KT is associated with better survival as opposed to remaining on dialysis after a first kidney graft failure. Nevertheless, this survival benefit is age dependent and diminishes with increasing age. The risk/benefit ratio should be comprehensively assessed in the oldest patients when relisting is considered.

Switch from Hemodialysis to Peritoneal Dialysis: Does the Time Spent on Hemodialysis Impact Outcomes in Peritoneal Dialysis?

INTRODUCTION: Switch from hemodialysis (HD) to peritoneal dialysis (PD) is unfrequent, but incentive strategies to perform PD can lead to an increase of these transitions. However, data on transitioning from HD to PD are scarce. We hypothesized that time spent on HD before transfer to PD would impact PD outcomes. METHODS: This registry-based, nationwide study analyzed patients transferred from HD to PD. Patients who began HD between January 2008 and December 2016 were included. Cox and Fine and Gray regression models were used to explore the relationship between time spent on HD before PD and outcomes in PD: PD cessation for death or retransfer to HD (composite endpoint); for death; and for retransfer to HD. RESULTS: Over the study period, 1,985 of the 77,587 HD starters (3%) were transferred to PD. The median time spent on HD before transfer to PD was 1.94 months (interquartile range [IQR] 1.02-4.01). The median survival time on PD after this transition was 20 months (IQR 18-21). Time spent on HD before PD was associated with increased risk of death or retransfer to HD (cause-specific hazard ratio [cs-HR] 1.01, 95% confidence interval [CI]: 1-1.02 for a 1-month increase) and death (cs-HR 1.02, 95% CI: 1.01-1.03) but not with retransfer to HD censored on death (cs-HR 1.00, 95% CI: 0.99-1.01). The results were similar when considering competing events. DISCUSSION/CONCLUSION: Switch from HD to PD is rare in France. Time spent on HD before transfer is associated with patient survival but not with retransfer to HD.

Dialysis-network variability in home dialysis use not explained by patient characteristics: a national registry-based cohort study in France.

BACKGROUND: Although associated with better quality of life and potential economic advantages, home dialysis use varies greatly internationally and appears to be underused in many countries. This study aimed to estimate the dialysis-network variability in home dialysis use and identify factors associated with (i) the uptake in home dialysis, (ii) the proportion of time spent on home dialysis and (iii) home dialysis survival (patient and technique). METHODS: All adults ≥18 years old who had dialysis treatment during 2017-2019 in mainland France were included. Mixed-effects regression models were built to explore factors including patient or residence characteristics and dialysis network associated with variation in home dialysis use. RESULTS: During 2017-2019, 7728/78 757 (9.8%) patients underwent dialysis at least once at home for a total of 120 594/1 508 000 (8%) months. The heterogeneity at the dialysis-network level and to a lesser extent the regional level regarding home dialysis uptake or total time spent was marginally explained by patient characteristics or residence and dialysis-network factors. Between-network heterogeneity was less for patient and technique survival. These results were similar when the analysis was restricted to home peritoneal dialysis or home hemodialysis. CONCLUSIONS: Variability between networks in the use of home dialysis was not fully explained by non-modifiable patient and residence characteristics. Our results suggest that to increase home dialysis use in France, one should focus on home dialysis uptake rather than survival. Financial incentives and a quality improvement programme should be implemented at the dialysis-network level to increase home dialysis use.

Implementation of patient-reported outcome measures in a heart transplant recipient registry: First step toward a patient-centered approach.

BACKGROUND: Heart transplantation (HTX) is a well-established treatment for suitable patients with end-stage heart failure, intended to prolong their survival and improve their health-related quality of life (HR-QoL). No international consensus exists, however, about the preferred patient-reported outcomes (PROs) and their measures (PROMs) for heart transplant recipients. The purpose of this study, the first step in a mixed-method investigation, was to review the PROMs developed and used in this population to identify the instruments for measuring HR-QoL and adherence to immunosuppressive medications most appropriate for heart transplant patients. METHODS: This systematic search of the literature in the PubMed database focused on the assessment of PROMs for patients after HTX. We analyzed 66 studies with cross-sectional, 28 with longitudinal, and 2 with mixed-methods designs, as well as 6 literature reviews. RESULTS: These 102 articles used 115 different PROMs, which we categorized as generic HR-QoL instruments (n = 19), domain-specific instruments (n = 71), heart disease-specific instruments (n = 9), and heart transplant-specific instruments (n = 16). They cover different dimensions of HR-QoL and of immunosuppressive-drug experience, with diverse numbers of items, types of scales, and psychometric properties. CONCLUSIONS: Despite the abundance of instruments, PROMs for HTX can be improved to meet other patient expectations (i.e., by including important issues such as coping strategies, employment, social support, sexual relationships, spirituality, and beliefs), while paying attention to ease of use, reliability, validity, and the contribution of new technologies. A qualitative approach will complete our project of developing a patient-centered instrument for HTX patients.

Impact of nephrology care trajectories pre-CKD stage 5 on initiation of kidney replacement therapy in children.

BACKGROUND: To improve pre-emptive kidney transplantation (PKT) in children and limit starting dialysis in an emergency, we aimed to describe nephrology care trajectories pre-CKD stage 5. METHODS: We included all children in France who, between 2010 and 2016, started kidney replacement therapy (KRT): standard dialysis (reference group) and emergency dialysis or PKT. We identified four pre-CKD stage 5 nephrology care trajectories before KRT that were extracted from the national exhaustive medical-administrative database and used logistic regression to explore associations between patient characteristics, care trajectories, and KRT initiation. RESULTS: Six hundred forty-three pediatric patients started KRT in France; 406 started dialysis and 30.5% emergency dialysis. The "optimal" care trajectory encompassed 179 patients, 82.7% with at least 18 months nephrology follow-up. Conversely, the "no care" trajectory encompassed 118 patients with no nephrology follow-up before KRT. The "severe" trajectory encompassed 128 patients; 93% hospitalized more than once a year and 18% in an intensive care unit. Finally, the "irregular" trajectory encompassed 127 patients, 77% and 46% with irregular laboratory monitoring and CKD drug delivery, respectively. With the "optimal" trajectory as the reference, probability of emergency dialysis was higher with the "irregular" and "no care" trajectories (odds ratio 3.02 [95% confidence interval 1.18-7.66] and 26.5 [10.8-64.8], respectively), and PKT was reduced with the "severe" trajectory (0.43 [0.23-0.82]). CONCLUSION: We identified a group of patients with irregular follow-up who may benefit the most from interventions aiming at improving adherence to treatment and earlier diagnosis of their CKD to improve access to PKT. A higher resolution version of the Graphical abstract is available as Supplementary information.

Supplemented ERA-EDTA Registry data evaluated the frequency of dialysis, kidney transplantation, and comprehensive conservative management for patients with kidney failure in Europe.

The aims of this study were to determine the frequency of dialysis and kidney transplantation and to estimate the regularity of comprehensive conservative management (CCM) for patients with kidney failure in Europe. This study uses data from the ERA-EDTA Registry. Additionally, our study included supplemental data from Armenia, Germany, Hungary, Ireland, Kosovo, Luxembourg, Malta, Moldova, Montenegro, Slovenia and additional data from Israel, Italy, Slovakia using other information sources. Through an online survey, responding nephrologists estimated the frequency of CCM (i.e. planned holistic care instead of kidney replacement therapy) in 33 countries. In 2016, the overall incidence of replacement therapy for kidney failure was 132 per million population (pmp), varying from 29 (Ukraine) to 251 pmp (Greece). On 31 December 2016, the overall prevalence of kidney replacement therapy was 985 pmp, ranging from 188 (Ukraine) to 1906 pmp (Portugal). The prevalence of peritoneal dialysis (114 pmp) and home hemodialysis (28 pmp) was highest in Cyprus and Denmark respectively. The kidney transplantation rate was nearly zero in some countries and highest in Spain (64 pmp). In 28 countries with five or more responding nephrologists, the median percentage of candidates for kidney replacement therapy who were offered CCM in 2018 varied between none (Slovakia and Slovenia) and 20% (Finland) whereas the median prevalence of CCM varied between none (Slovenia) and 15% (Hungary). Thus, the substantial differences across Europe in the frequency of kidney replacement therapy and CCM indicate the need for improvement in access to various treatment options for patients with kidney failure.

Effect of age and care organization on sources of variation in kidney transplant waiting list registration.

Despite national guidelines, medical practices and kidney transplant waiting list registration policies may differ from one dialysis/transplant unit to another. Benefit risk assessment variations, especially for elderly patients, have also been described. The aim of this study was to identify sources of variation in early kidney transplant waiting list registration in France. Among 16 842 incident patients during the period 2016-2017, 4386 were registered on the kidney transplant waiting list at the start of, or during the first year after starting, dialysis (26%). We developed various log-linear mixed effect regression models on three levels: patients, dialysis networks, and transplant centers. Variability was expressed as variance from the random intercepts (± standard error). Although patient characteristics have an important impact on the likelihood of registration, the overall magnitude of variability in registration was low and shared by dialysis networks and transplant centers. Between-transplant center variability (0.23 ± 0.08) was 1.8 higher than between-dialysis network variability (0.13 ± 0.004). Older age was associated with a lower probability of registration and greater variability between networks (0.04, 0.20, & 0.93 in the 18-64, 65-74, and 75-84 age groups). Targeted interventions should focus on elderly patients and/or certain regions with greater variability in waiting list access.

Clinical Trial Emulation by Matching Time-dependent Propensity Scores: The Example of Estimating Impact of Kidney Transplantation.

BACKGROUND: No study to our knowledge has examined the use of observational data to emulate a clinical trial whereby patients at the time of kidney transplant proposal are randomly assigned to an awaiting transplantation or transplantation group. The main methodologic issue is definition of the baseline for dialyzed patients assigned to awaiting transplantation, resulting in the inability to use common propensity score-based approaches. We aimed to use time-dependent propensity score to better appraise the benefit of transplantation. METHODS: We studied 23,231 patients included in the French registry and on a transplant waiting list from 2005 to 2016. The main outcome was time to death. By matching on time-dependent propensity score, we obtained 10,646 pairs of recipients (transplantation group) versus comparable patients remaining on dialysis (awaiting transplantation group). RESULTS: The baseline exposure, that is, pseudo-randomization, was matching time. Median follow-up time was 3.5 years. At 10 years' follow-up, the restricted mean survival time was 8.8 years [95% confidence interval (CI) = 8.7, 8.9] in the transplantation group versus 8.2 years (95% CI = 8.1, 8.3) in the awaiting transplantation group. The corresponding life expectancy gain was 6.8 months (95% CI = 5.5, 8.2), and this corresponded to one prevented death at 10 years for 13 transplantations. CONCLUSIONS: Our study has estimated the life expectancy gain due to kidney transplantation. It confirms transplantation as the best treatment for end-stage renal disease. Furthermore, we demonstrated that this simple method should also be considered for estimating marginal effects of time-dependent exposures.

Adverse gastrointestinal events with sodium polystyrene sulphonate and calcium polystyrene sulphonate use in dialysis patients: a nationwide registry study.

INTRODUCTION: Sodium polystyrene sulphonate (SPS) and calcium polystyrene sulphonate (CPS) are commonly used cation-exchange resins for the treatment and control of hyperkalaemia. However, their use (particularly SPS) has been limited by reports of adverse gastrointestinal (GI) events. The safety of these compounds in patients undergoing dialysis requires larger investigation. AIMS: To study the occurrence of adverse GI events (occlusion, perforation, thrombosis/ischaemia) in the periods of SPS or CPS exposition versus the periods without exposition in dialysis patients. METHODS: Dialysis patients were extracted from the French National Registry and merged with the French hospital discharge database (between 2006 and 2017). For our primary analysis, we used patients who had any claim of SPS use (n = 43 771). Time-varying Cox models, negative binomial regression and pre- versus post-treatment average treatment effects. RESULTS: The mean age was 66 ± 15 years, 37% were female and 92% were undergoing haemodialysis. Over a 1-year follow-up, patients on periods with SPS (on-SPS) did not present an increased risk of adverse GI events versus the periods without SPS (off-SPS):  incidence rate (IR) (per 1000 person years) = 7.4 (6.4-8.7) versus 9.5 (8.1-11.0); adjusted hazard ratio (HR) (95% CI) = 0.81 (0.60-1.09), P = 0.17. Patients exposed to SPS did not experience a higher rate of adverse GI events in the year after SPS initiation versus the year before SPS initiation; P-value for parallel trend = 0.87. Patients on-CPS also did not show an increased risk of adverse GI events versus off-CPS: IR (per 1000 py) = 8.6 (5.1-11.9) versus 7.8 (5.1-11.9); adjusted HR (95% CI) = 0.76 (0.31-1.80), P = 0.52. The rates of adverse GI events in the periods on and off exposure were also similar over a follow-up of 5 years. CONCLUSION: Our large, nationwide study shows that the incidence of adverse GI events in patients undergoing dialysis was low and that neither the use of SPS nor CPS was associated with increased GI events risk.

Dialysis dose and mortality in haemodialysis: is higher better?

BACKGROUND: The effect of dialysis dose on mortality remains unsettled. Current guidelines recommend targeting a single-pool Kt/V (spKt/V) at 1.20-1.40 per thrice-weekly dialysis session. However, the optimal dialysis dose remains mostly disputed. METHODS: In a nationwide registry of all incident patients receiving thrice-weekly haemodialysis, 32 283 patients had available data on dialysis dose, estimated by Kt/V and its variants epuration volume per session (Kt) and Kt indexed to body surface area (Kt/A). Survival was analysed with a multivariate Cox model and a concurrent risk model accounting for renal transplantation. A predictive model of Kt in the upper quartile was developed. RESULTS: Regardless of the indicator, a higher dose of dialysis was consistently associated with better survival. The survival differential of Kt was the most discriminating, but marginally, compared with the survival differential according to Kt/V and Kt/A. Patient survival was higher in the upper quartile of Kt (>69 L/session) then deteriorated as the Kt decreased, with a difference in survival between the upper and lower quartile of 23.6% at 5 years. Survival differences across Kt distribution were similar after accounting for kidney transplantation as a competing risk. Predictive factors for Kt in the upper quartile were arteriovenous fistula versus catheters and graft, haemodiafiltration versus haemodialysis, scheduled dialysis start versus emergency start, long weekly dialysis duration and spKt/V measurement versus double-pool equilibrated Kt/V. CONCLUSIONS: Our data confirm the existence of a relationship between dialysis dose and survival that persisted despite correcting for known confounders. A model for predicting a high dose of dialysis is proposed with practical relevance.