Twenty years of the French Renal Epidemiology and Information Network.

Background: The French Renal Epidemiology and Information Network (REIN) is 20 years old. It is not just a national data registry, but rather an epidemiological and informational network serving patients with chronic kidney disease, nephrology teams and health services. Methods: The past 10-year trends of the incidence and prevalence of renal replacement therapy by dialysis or kidney transplantation and waitlist activity are presented. To detect potential significant changes in trends from 2012 and 2021, a Joinpoint regression model was used. Results: The overall incidence of treated end-stage kidney disease (ESKD) was 169 per million population (pmp) in 2021. It was stable despite an increase in the incidence of diabetes. We found a decreasing trend in the proportion of patients starting dialysis in an emergency but an increase in those starting haemodialysis (HD) with a temporary catheter. Peritoneal dialysis decreased by 1.7% each year, whereas home HD, although involving only 1% of dialysis patients, increased by 10% each year. For patients not treated at home, the median time to drive from the patient's home to the dialysis unit was 17 min. The proportion of patients on the transplantation waitlist at the start of dialysis increased from 7% to 12%. Among the 111 263 new ESKD patients from 2012 to 2021, 8% received a first transplant at 1 year and 20% at 5 years. Among kidney transplant recipients, the mean time on the waitlist increased from 13.8 to 22.6 months. Living donor transplants increased in frequency, representing 15% of kidney transplants. Conclusions: Data from the REIN registry allow for the evaluation of needs and provide a planning tool for French authorities. The progressive implementation of automatic data retrieval from dialysis informatics charts might alleviate the burden of data collection. Furthermore, the research activity the REIN engenders, resulting in renewed confidence by health authorities in the dynamism of French nephrology, allows for an optimistic outlook for the REIN.

Chronic Myelomonocytic Leukemia Patients With Lysozyme Nephropathy and Renal Infiltration Display Markers of Severe Disease.

Introduction: Chronic myelomonocytic leukemia (CMML) is a hematologic disorder that is an overlap syndrome between myelodysplastic syndromes and myeloproliferative neoplasms, and can be associated with autoimmune and inflammatory diseases. This study aimed to describe kidney involvement in patients with CMML, their treatments, and outcomes. Methods: We conducted a French and American multicenter retrospective study in 15 centers, identifying patients with CMML with acute kidney injury (AKI), chronic kidney disease (CKD), and urine abnormalities. Results: Sixteen patients (males, n = 14; median age 76.5 years [71.9-83]) developed a kidney disease 6 months [1.6-25.6] after the diagnosis of CMML. At the time of kidney disease diagnosis, median urinary protein-to-creatinine ratio was 2 g/g [1.25-3.4], and median serum creatinine was 2.26 mg/dl [1.46-2.68]. Fourteen patients (87.5%) underwent a kidney biopsy, and the 2 main pathological findings were lysozyme nephropathy (56%) and renal infiltration by the CMML (37.5%). Ten patients received a new treatment following the CMML-associated kidney injury. Among patients with monitored kidney function, and after a median follow-up of 15 months [9.9-34.9], 4 patients had CKD stage 3, 4 had CKD stage 4, 1 had an end-stage kidney disease. In our patient series, 2 patients evolved to an acute myeloid leukemia (AML), and 5 died. Compared with 116 CMML controls, patients who had a kidney involvement had a higher monocyte count (P < 0.001), had more CMML-1 (P = 0.005), were more susceptible to develop an AML (P = 0.02), and were more eligible to receive a specific hematologic treatment, with hydroxyurea, or hypomethylating agents (P < 0.001), but no survival difference was seen between the 2 groups (P = 0.6978). Conclusion: In this cohort of patients with CMML with a kidney injury, the 2 most frequent renal complications were lysozyme-induced nephropathy and renal infiltration by the CMML. Kidney involvement should be closely monitored in patients with CMML.

Heart disease in hemodialysis: physiopathology and therapeutic breakthroughs / Atteintes cardiaques en hémodialyse : physiopathologie et avancées thérapeutiques

Especially exposed to frequent cardiovascular events and its related mortality, some cardiovascular therapies of the hemodialyzed population as well as coronary investigations remain controversial. We have collected data and discussed recent trials and guidelines dedicated to this patient subset.

Tout particulièrement exposé aux complications cardiovasculaires, le sujet dialysé fait l'objet de multiples controverses sur les traitements antihypertenseurs, les anticoagulants, les statines, les explorations et le traitement de la coronaropathie. Nous revenons sur les données récentes sur la physiopathologie et les recommandations pour l'exploration et les traitements à visée cardiovasculaire.

REIN: a tool at the service of vigilance and pharmaco-epidemiology / REIN : un outil au service de la vigilance et de la pharmaco-épidémiologie

On the occasion of the 20th anniversary of the REIN (French Renal Epidemiology and Information Network), a summary work on the contributions of the national French ESKD register was carried out. On the issue of its role in vigilance, the following key messages were retained. The vigilance system consists, among other things, of collecting information that is useful for the surveillance of health products that are drugs for pharmacovigilance, and medical devices for materiovigilance. This includes the reporting of adverse events by health professionals and manufacturers as well as the use of any information concerning the risk of adverse events. Vigilance enables improving and optimising product and patient safety by reducing the risks of adverse events and better understanding the risks and benefits. Using data from the REIN registry, cross-referenced with other external sources, it is possible to conduct post-marketing studies of these products. These studies generate hypotheses, are low-cost and are yet to be confirmed by randomised studies. Following the presentation of a study suggesting an unfavourable role of citrate dialysates on mortality, and thanks to the mobilisation of all the operators of the network, the REIN registry was able to conduct a study in a few months that made it possible to conclude that the use of citric acid in dialysates does not present a risk of excess mortality for the patients. With this example, the REIN registry has shown its adaptability and utility as a vigilance tool.

À l'occasion des 20 ans du REIN (Réseau Epidémiologie et Information en Néphrologie), un travail de synthèse sur les apports du registre a été mené. Sur la question de son rôle dans la vigilance, les messages clés suivants ont été retenus. Le système de vigilance consiste, entre autres, à recueillir des informations utiles à la surveillance des produits de santé que sont, pour la pharmacovigilance, les médicaments et, pour la matériovigilance, les dispositifs médicaux. Cela inclut le signalement d'évènements indésirables par les professionnels de santé et les industriels mais aussi l'exploitation de toute information concernant le risque d'évènements indésirables. La vigilance permet d'améliorer et d'optimiser la sécurité du patient et des produits en réduisant les risques d'évènements indésirables et de mieux appréhender les bénéfices-risques. À l'aide de données du registre REIN, croisées avec d'autres sources externes, il est possible de mener des études après la mise sur le marché de ces produits. Ces études génèrent des hypothèses, sont de faible coût et restent à confirmer par des études randomisées. Suite à la présentation d'une étude suggérant un rôle défavorable des dialysats au citrate sur la mortalité, et grâce à la mobilisation de tous les acteurs du réseau, le registre REIN a pu mener une étude en quelques mois qui a permis de conclure que l'utilisation de l'acide citrique dans les dialysats ne présente pas de risque de surmortalité pour les patients. Par cet exemple, le registre REIN a montré sa capacité d'adaptation et son utilité comme outil au service de la vigilance.

Clinical and Prognostic Factors in Patients with IgG4-Related Kidney Disease.

BACKGROUND: IgG4-related kidney disease is a major manifestation of IgG4-related disease, a systemic fibroinflammatory disorder. However, the clinical and prognostic kidney-related factors in patients with IgG4-related kidney disease are insufficiently defined. METHODS: We conducted an observational cohort study using data from 35 sites in two European countries. Clinical, biologic, imaging, and histopathologic data; treatment modalities; and outcomes were collected from medical records. Logistic regression was performed to identify the possible factors related to an eGFR ≤30 ml/min per 1.73 m 2 at the last follow-up. Cox proportional hazards model was performed to assess the factors associated with the risk of relapse. RESULTS: We studied 101 adult patients with IgG4-related disease with a median follow-up of 24 (11-58) months. Of these, 87 (86%) patients were male, and the median age was 68 (57-76) years. Eighty-three (82%) patients had IgG4-related kidney disease confirmed by kidney biopsy, with all biopsies showing tubulointerstitial involvement and 16 showing glomerular lesions. Ninety (89%) patients were treated with corticosteroids, and 18 (18%) patients received rituximab as first-line therapy. At the last follow-up, the eGFR was below 30 ml/min per 1.73 m 2 in 32% of patients; 34 (34%) patients experienced a relapse, while 12 (13%) patients had died. By Cox survival analysis, the number of organs involved (hazard ratio [HR], 1.26; 95% confidence interval [CI], 1.01 to 1.55) and low C3 and C4 concentrations (HR, 2.31; 95% CI, 1.10 to 4.85) were independently associated with a higher risk of relapse, whereas first-line therapy with rituximab was protective (HR, 0.22; 95% CI, 0.06 to 0.78). At their last follow-up, 19 (19%) patients had an eGFR ≤30 ml/min per 1.73 m 2 . Age (odd ratio [OR], 1.11; 95% CI, 1.03 to 1.20), peak serum creatinine (OR, 2.74; 95% CI, 1.71 to 5.47), and serum IgG4 level ≥5 g/L (OR, 4.46; 95% CI, 1.23 to 19.40) were independently predictive for severe CKD. CONCLUSIONS: IgG4-related kidney disease predominantly affected middle-aged men and manifested as tubulointerstitial nephritis with potential glomerular involvement. Complement consumption and the number of organs involved were associated with a higher relapse rate, whereas first-line therapy with rituximab was associated with lower relapse rate. Patients with high serum IgG4 concentrations (≥5 g/L) had more severe kidney disease.

Diversity of the quality of data collection in a registry: proposal of an analysis approach and application to the REIN register / Diversité de la qualité de recueil des données dans un registre : proposition d'une démarche d'analyse et application au registre REIN

Missing data may lead to bias and loss of information in epidemiological research. In this article, we propose an approach to analyze missing data on comorbidity variables in a register with consideration of the territorialized organization of the collection. To illustrate this approach, we used the national REIN registry as an application case.

Les données manquantes peuvent introduire des biais et des pertes d'informations dans les études épidémiologiques. Dans cet article, nous proposons une démarche d'analyse des données manquantes sur des variables de comorbidités dans un registre, avec prise en compte de l'organisation territorialisée du recueil. Afin d'illustrer cette démarche, nous avons utilisé le registre national du Réseau épidémiologie et information en néphrologie (REIN) comme cas d'application.

Automated adjustment of dialysate sodium by the hemodialysis monitor: Rationale, implementation, and clinical benefits.

Prescribing dialysate sodium is the responsibility of the physician, but there are currently no clear guidelines for this prescription. Furthermore, there is quite frequently a significant difference between prescribed and measured dialysate sodium. Several arguments, both theoretical and experimental, suggest that dialysate sodium should be adjusted individually in such a way as to result in a decreasing sodium profile that takes into account the patient's predialytic natremia. The generalization in clinical routine of this strategy requires the integration into the hemodialysis monitor of software making the machine capable to automatically adjust the dialysate sodium at each session. The only three such softwares that have been integrated into hemodialysis machines for routine clinical use are discussed. All three work with conductivity measurements as a surrogate for sodium concentrations. Although there are only a few publications on the use of these softwares in clinical practice, they appear to result in improved intradialytic tolerance to the dialysis treatment, better control of hypertension, and reduced thirst, leading to decreased interdialytic weight gain.

Trends in Mortality Due to Myocardial Infarction, Stroke, and Pulmonary Embolism in Patients Receiving Dialysis.

Importance: During the past decades, improvements in the prevention and management of myocardial infarction, stroke, and pulmonary embolism have led to a decline in cardiovascular mortality in the general population. However, it is unknown whether patients receiving dialysis have also benefited from these improvements. Objective: To assess the mortality rates for myocardial infarction, stroke, and pulmonary embolism in a large cohort of European patients receiving dialysis compared with the general population. Design, Setting, and Participants: In this cohort study, adult patients who started dialysis between 1998 and 2015 from 11 European countries providing data to the European Renal Association Registry were and followed up for 3 years. Data were analyzed from September 2020 to February 2022. Exposures: Start of dialysis. Main Outcomes and Measures: The age- and sex-standardized mortality rate ratios (SMRs) with 95% CIs were calculated by dividing the mortality rates in patients receiving dialysis by the mortality rates in the general population for 3 equal periods (1998-2003, 2004-2009, and 2010-2015). Results: In total, 220 467 patients receiving dialysis were included in the study. Their median (IQR) age was 68.2 (56.5-76.4) years, and 82 068 patients (37.2%) were female. During follow-up, 83 912 patients died, of whom 7662 (9.1%) died because of myocardial infarction, 5030 (6.0%) died because of stroke, and 435 (0.5%) died because of pulmonary embolism. Between the periods 1998 to 2003 and 2010 to 2015, the SMR of myocardial infarction decreased from 8.1 (95% CI, 7.8-8.3) to 6.8 (95% CI, 6.5-7.1), the SMR of stroke decreased from 7.3 (95% CI, 7.0-7.6) to 5.8 (95% CI, 5.5-6.2), and the SMR of pulmonary embolism decreased from 8.7 (95% CI, 7.6-10.1) to 5.5 (95% CI, 4.5-6.6). Conclusions and Relevance: In this cohort study of patients receiving dialysis, mortality rates for myocardial infarction, stroke, and pulmonary embolism decreased more over time than in the general population.

Vascular access cannulation and haemostasis: a national observational study of French practices.

BACKGROUND: We report the results of an observational study of arteriovenous fistula (AVF) cannulation and haemostasis practices in France. METHODS: The study (sponsored by Brothier Pharmaceutical Inc.) was conducted in 150 dialysis units. Data obtained from 150 supervisory nurses, 1538 nurses and 3588 patients with an AVF were analysed. RESULTS: The nurses reported using rope-ladder, area or buttonhole cannulation techniques in 68, 26 and 6% of cases, respectively. Metal needles were used most frequently (64%), with mainly a diameter of 15 G or 16 G. The needle was introduced with the bevel up in 56% of cases. Compression applied using dressings (in particular, pure calcium alginate dressings) was the method of choice for haemostasis of the puncture sites and was assessed as being strong by most of the nurses and very strong in cases of prolonged bleeding. Most (82%) of the patients reported the use of local anaesthetic before cannulation and 23% reported an allergic skin reaction to the anaesthetic. Bleeding of the puncture sites lasted for >10 min for 48% of the patients and it reappeared between two sessions for 29% of the patients. Whereas the nurses appeared to have a good understanding of AVF, more than half of the patients did not know how to care for it, with 55% requiring more information. CONCLUSIONS: This study underlines the lack of national consensus concerning AVF cannulation practices. It suggests that haemostasis methods of the puncture sites can be improved and it highlights the need to improve patient knowledge.

Recovery of kidney function in patients treated with maintenance dialysis-a report from the ERA-EDTA Registry.

BACKGROUND: Literature on recovery of kidney function (RKF) in patients with end-stage kidney disease treated with maintenance dialysis (i.e. >90 days) is limited. We assessed the incidence of RKF and its associated characteristics in a European cohort of dialysis patients. METHODS: We included adult patients from the European Renal Association-European Dialysis and Transplant Association Registry who started maintenance dialysis in 1997-2016. Sustained RKF was defined as permanent discontinuation of dialysis. Temporary discontinuation of ≥30 days (non-sustained RKF) was also evaluated. Factors associated with RKF adjusted for potential confounders were studied using Cox regression analyses. RESULTS: RKF occurred in 7657 (1.8%) of 440 996 patients, of whom 71% experienced sustained RKF. Approximately 90% of all recoveries occurred within the first 2 years after Day 91 of dialysis. Of patients with non-sustained RKF, 39% restarted kidney replacement therapy within 1 year. Sustained RKF was strongly associated with the following underlying kidney diseases (as registered by the treating physician): tubular necrosis (irreversible) or cortical necrosis {adjusted hazard ratio [aHR] 20.4 [95% confidence interval (CI) 17.9-23.1]}, systemic sclerosis [aHR 18.5 (95% CI 13.8-24.7)] and haemolytic uremic syndrome [aHR 17.3 (95% CI 13.9-21.6)]. Weaker associations were found for haemodialysis as a first dialysis modality [aHR 1.5 (95% CI 1.4-1.6)] and dialysis initiation at an older age [aHR 1.8 (95% CI 1.6-2.0)] or in a more recent time period [aHR 2.4 (95% CI 2.1-2.7)]. CONCLUSIONS: Definitive discontinuation of maintenance dialysis is a rare and not necessarily an early event. Certain clinical characteristics, but mostly the type of underlying kidney disease, are associated with a higher likelihood of RKF.

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.

Prescription patterns of dialysate potassium and potassium binders and survival on haemodialysis-the French Renal Epidemiology and Information Network registry.

BACKGROUND: Management of potassium disorders in patients on haemodialysis (HD) is complex. We studied prescription patterns of dialysate potassium and potassium binders, and their associations with patient survival. METHODS: This national registry-based study included 25 629 incident adult patients alive after 3 months of HD from 2010 through 2013 and followed-up through 31 December 2014. We used Cox proportional hazard models to estimate multiadjusted mortality hazard ratios (HRs) associated with time-dependent exposure to facility-level dialysate potassium concentrations and patient-level potassium binder exposure. RESULTS: Almost all dialysis units used, and generally most often, dialysate potassium concentrations of 2 mmol/L. During this period, use of concentrations <2 mmol/L tended to decrease and those ≥3 mmol/L to increase. In 2014, 9% of units used a single dialysate formula, 41% used two and 50% three or more. The most frequent combinations were 2 and 3 mmol/L (40%), and <2, 2 and 3 mmol/L (37%). Compared with patients on HD in units using only one dialysate formula, those in units using two or three had adjusted mortality HRs of 0.91 [95% confidence interval (CI) 0.82-1.01] and 0.84 (0.75-0.93), respectively. Potassium binders were prescribed for 37% of all patients at baseline. Adjusted mortality HRs associated with doses <4, 4-8 and ≥8 g/day versus none were 1.22 (95% CI 1.04-1.51), 0.6 (0.54-0.66) and 0.25 (0.24-0.33), respectively. CONCLUSIONS: Diversity in facility-level use of dialysate potassium concentrations and potassium binder use at an appropriate dose appear to be associated with better survival in HD patients.

Use of proton pump inhibitors in dialysis patients: a double-edged sword?

Large cohort-based studies have shown that proton pump inhibitors (PPIs) are linked to rare but multiple and varied secondary events when used in the general population. Although clinicians accept the negative effects of PPIs on renal function, there is a lack of available data regarding the potential consequences of their use by dialysis patients in whom the risk of gastrointestinal bleeding is quite high. This review aims to highlight the risks and benefits of PPIs use in dialysis patients. To summarize, the benefit on the reduction of high digestive bleeding seems certain, but without any beneficial impact on overall survival. The impact on quality of life seems to be significant. The data on the occurrence of peritonitis during PPIs treatment are very contradictory. There is evidence regarding the occurrence of hypomagnesaemia in haemodialysis patients with PPIs; which may lead to increase bone fragility. New data show an increased cardiovascular risk and even a risk of death linked to the use of PPIs on dialysis. Several mechanisms of IPP toxicity are advanced to explain these findings.

Low incidence of SARS-CoV-2, risk factors of mortality and the course of illness in the French national cohort of dialysis patients.

The aim of this study was to estimate the incidence of COVID-19 disease in the French national population of dialysis patients, their course of illness and to identify the risk factors associated with mortality. Our study included all patients on dialysis recorded in the French REIN Registry in April 2020. Clinical characteristics at last follow-up and the evolution of COVID-19 illness severity over time were recorded for diagnosed cases (either suspicious clinical symptoms, characteristic signs on the chest scan or a positive reverse transcription polymerase chain reaction) for SARS-CoV-2. A total of 1,621 infected patients were reported on the REIN registry from March 16th, 2020 to May 4th, 2020. Of these, 344 died. The prevalence of COVID-19 patients varied from less than 1% to 10% between regions. The probability of being a case was higher in males, patients with diabetes, those in need of assistance for transfer or treated at a self-care unit. Dialysis at home was associated with a lower probability of being infected as was being a smoker, a former smoker, having an active malignancy, or peripheral vascular disease. Mortality in diagnosed cases (21%) was associated with the same causes as in the general population. Higher age, hypoalbuminemia and the presence of an ischemic heart disease were statistically independently associated with a higher risk of death. Being treated at a selfcare unit was associated with a lower risk. Thus, our study showed a relatively low frequency of COVID-19 among dialysis patients contrary to what might have been assumed.

Effects of the dialysate calcium concentrations and mineral bone disease treatments on mortality in The French Renal Epidemiology and Information Network (REIN) registry.

BACKGROUND: In patients on hemodialysis (HD), the various chemical elements in the dialysate may influence survival rates. In particular, calcium modifies mineral and bone metabolism and the vascular calcification rate. We studied the influence of the dialysate calcium concentration and the treatments prescribed for mineral bone disease (MBD) on survival. METHODS: All patients in REIN having initiated HD from 2010 to 2013 were classified according to their exposure to the different dialysate calcium concentrations in their dialysis unit. Data on the individual patients' treatments for MBD were extracted from the French national health database. Cox proportional hazard models were used to estimate mortality hazard ratios (HR) associated with time-dependent exposure to dialysate calcium concentrations and MBD therapies, adjusted for comorbidities, laboratory and technical data. RESULTS: Dialysate calcium concentration of 1.5 mmol/L was used by 81% of the dialysis centers in 2010 and in 83% in 2014. Most centers were using several formulas in up to 78% for 3 formulas in 2010 to 86% in 2014. In full adjusted Cox survival analyses, the percentage of calcium >1.5 mmol/L and <1.5 mmol/l by center and the number of formula used per center were not associated with survival. Depending on the daily dose used, the MBD therapies were associated with survival improvement for calcium, native vitamin D, active vitamin D, sevelamer, lanthanum and cinacalcet in the second and third tertiles of dose. CONCLUSION: No influence of the dialysate calcium concentration was evidenced on survival whereas all MBD therapies were associated with a survival improvement depending on the daily dose used.

Oxalate nephropathy is a major cause of kidney injury in surgically treated pancreatic adenocarcinoma patients.

BACKGROUND: Despite new therapeutics, the prognosis for pancreatic cancer remains poor. Pancreatic surgery is a therapeutic option in non-metastatic forms. The consequences for renal function are poorly described. METHODS: Patients who underwent surgery for pancreatic cancer between 1 January 2010 and 1 January 2017 and who experienced kidney biopsy in the Pitié-Salpêtrière Hospital were analysed. RESULTS: Two hundred and ninety-four patients had pancreatic surgery during the period of analysis and five of them had a kidney biopsy (mean ± SD 20 months ±13.6 months after surgery) during the post-operative follow-up. Among these patients, three exhibited oxalate nephropathy (ON), indicating that the prevalence of ON in patients with pancreatectomy is at least 1%. ON may be insidious, with chronic renal failure without urinary abnormalities. All patients had a high oxalate-to-creatinine ratio in urine sample. Renal function improved after specific management of ON in two patients. Pancreaticoduodenectomy may represent a higher risk of ON than left pancreatectomy. CONCLUSION: Although rare and underestimated, ON appears to be a real risk after pancreatic resection. Early detection may preserve renal function.