Epidemiology of cardiovascular disease in chronic renal disease

Elevated serum phosphate levels have been linked with vascular calcification and mortality among dialysis patients. The relationship between phosphate and mortality has not been explored among patients with chronic kidney disease (CKD). A retrospective cohort study was conducted from eight Veterans Affairs’ Medical Centers located in the Pacific Northwest. CKD was defined by two continuously abnormal outpatient serum creatinine measurements at least 6 mo apart between 1999 and 2002. Patients who received chronic dialysis, those with a present or previous renal transplant, and those without a recent phosphate measurement were excluded. The primary end point was all-cause mortality. Secondary end points were acute myocardial infarction and the combined end point of myocardial infarction plus death. A total of 95,619 veterans with at least one primary care or internal medicine clinic contact from a Northwest VA facility and two or more outpatient measurements of serum creatinine, at least 6 mo apart, between January 1, 1999, and December 31, 2002, were identified. From this eligible population, 7021 patients met our definition of CKD. After exclusions, 6730 CKD patients were available for analysis, and 3490 had a serum phosphate measurement during the previous 18 mo. After adjustment, serum phosphate levels >3.5 mg/dl were associated with a significantly increased risk for death. Mortality risk increased linearly with each subsequent 0.5-mg/dl increase in serum phosphate levels. Elevated serum phosphate levels were independently associated with increased mortality risk among this population of patients with CKD.

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Serum Phosphate Levels and Mortality Risk among People with Chronic Kidney Disease

Context The prevalence of diabetes in the United States has increased. People with diabetes are at risk for diabetic retinopathy. No recent national population-based estimate of the prevalence and severity of diabetic retinopathy exists. Objectives To describe the prevalence and risk factors of diabetic retinopathy among US adults with diabetes aged 40 years and older. Design, Setting, and Participants Analysis of a cross-sectional, nationally representative sample of the National Health and Nutrition Examination Survey 2005-2008 (N = 1006). Diabetes was defined as a self-report of a previous diagnosis of the disease (excluding gestational diabetes mellitus) or glycated hemoglobin A1c of 6.5% or greater. Two fundus photographs were taken of each eye with a digital nonmydriatic camera and were graded using the Airlie House classification scheme and the Early Treatment Diabetic Retinopathy Study severity scale. Prevalence estimates were weighted to represent the civilian, noninstitutionalized US population aged 40 years and older. Main Outcome Measurements Diabetic retinopathy and vision-threatening diabetic retinopathy. Results The estimated prevalence of diabetic retinopathy and vision-threatening diabetic retinopathy was 28.5% (95% confidence interval [CI], 24.9%-32.5%) and 4.4% (95% CI, 3.5%-5.7%) among US adults with diabetes, respectively. Diabetic retinopathy was slightly more prevalent among men than women with diabetes (31.6%; 95% CI, 26.8%-36.8%; vs 25.7%; 95% CI, 21.7%-30.1%; P = .04). Non-Hispanic black individuals had a higher crude prevalence than non-Hispanic white individuals of diabetic retinopathy (38.8%; 95% CI, 31.9%-46.1%; vs 26.4%; 95% CI, 21.4%-32.2%; P = .01) and vision-threatening diabetic retinopathy (9.3%; 95% CI, 5.9%-14.4%; vs 3.2%; 95% CI, 2.0%-5.1%; P = .01). Male sex was independently associated with the presence of diabetic retinopathy (odds ratio [OR], 2.07; 95% CI, 1.39-3.10), as well as higher hemoglobin A1c level (OR, 1.45; 95% CI, 1.20-1.75), longer duration of diabetes (OR, 1.06 per year duration; 95% CI, 1.03-1.10), insulin use (OR, 3.23; 95% CI, 1.99-5.26), and higher systolic blood pressure (OR, 1.03 per mm Hg; 95% CI, 1.02-1.03). Conclusion In a nationally representative sample of US adults with diabetes aged 40 years and older, the prevalence of diabetic retinopathy and vision-threatening diabetic retinopathy was high, especially among Non-Hispanic black individuals.

https://jamanetwork.com/journals/jama/articlepdf/186384/joc05096_649_656.pdf

Prevalence of diabetic retinopathy in the United States, 2005-2008

BACKGROUND\nStatins reduce the incidence of cardiovascular events in persons with type 2 diabetes mellitus. However, the benefit of statins in such patients receiving hemodialysis, who are at high risk for cardiovascular disease and death, has not been examined.\n\n\nMETHODS\nWe conducted a multicenter, randomized, double-blind, prospective study of 1255 subjects with type 2 diabetes mellitus receiving maintenance hemodialysis who were randomly assigned to receive 20 mg of atorvastatin per day or matching placebo. The primary end point was a composite of death from cardiac causes, nonfatal myocardial infarction, and stroke. Secondary end points included death from all causes and all cardiac and cerebrovascular events combined.\n\n\nRESULTS\nAfter four weeks of treatment, the median level of low-density lipoprotein cholesterol was reduced by 42 percent among patients receiving atorvastatin, and among those receiving placebo it was reduced by 1.3 percent. During a median follow-up period of four years, 469 patients (37 percent) reached the primary end point, of whom 226 were assigned to atorvastatin and 243 to placebo (relative risk, 0.92; 95 percent confidence interval, 0.77 to 1.10; P=0.37). Atorvastatin had no significant effect on the individual components of the primary end point, except that the relative risk of fatal stroke among those receiving the drug was 2.03 (95 percent confidence interval, 1.05 to 3.93; P=0.04). Atorvastatin reduced the rate of all cardiac events combined (relative risk, 0.82; 95 percent confidence interval, 0.68 to 0.99; P=0.03, nominally significant) but not all cerebrovascular events combined (relative risk, 1.12; 95 percent confidence interval, 0.81 to 1.55; P=0.49) or total mortality (relative risk, 0.93; 95 percent confidence interval, 0.79 to 1.08; P=0.33).\n\n\nCONCLUSIONS\nAtorvastatin had no statistically significant effect on the composite primary end point of cardiovascular death, nonfatal myocardial infarction, and stroke in patients with diabetes receiving hemodialysis.

Atorvastatin in Patients With Type 2 Diabetes Mellitus Undergoing Hemodialysis

BACKGROUND In clinical practice, there is considerable variation in the timing of the initiation of maintenance dialysis for patients with stage V chronic kidney disease, with a worldwide trend toward early initiation. In this study, conducted at 32 centers in Australia and New Zealand, we examined whether the timing of the initiation of maintenance dialysis influenced survival among patients with chronic kidney disease. METHODS We randomly assigned patients 18 years of age or older with progressive chronic kidney disease and an estimated glomerular filtration rate (GFR) between 10.0 and 15.0 ml per minute per 1.73 m 2 of body-surface area (calculated with the use of the Cockcroft–Gault equation) to planned initiation of dialysis when the estimated GFR was 10.0 to 14.0 ml per minute (early start) or when the estimated GFR was 5.0 to 7.0 ml per minute (late start). The primary outcome was death from any cause. RESULTS Between July 2000 and November 2008, a total of 828 adults (mean age, 60.4 years; 542 men and 286 women; 355 with diabetes) underwent randomization, with a median time to the initiation of dialysis of 1.80 months (95% confidence interval [CI], 1.60 to 2.23) in the early-start group and 7.40 months (95% CI, 6.23 to 8.27) in the late-start group. A total of 75.9% of the patients in the late-start group initiated dialysis when the estimated GFR was above the target of 7.0 ml per minute, owing to the development of symptoms. During a median follow-up period of 3.59 years, 152 of 404 patients in the early-start group (37.6%) and 155 of 424 in the late-start group (36.6%) died (hazard ratio with early initiation, 1.04; 95% CI, 0.83 to 1.30; P = 0.75). There was no significant difference between the groups in the frequency of adverse events (cardiovascular events, infections, or complications of dialysis). CONCLUSIONS In this study, planned early initiation of dialysis in patients with stage V chronic kidney disease was not associated with an improvement in survival or clinical outcomes. (Funded by the National Health and Medical Research Council of Australia and others; Australian New Zealand Clinical Trials Registry number, 12609000266268.)

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A Randomized, Controlled Trial of Early versus Late Initiation of Dialysis

The possibility of indirect linkage between data from the French REIN registry and data from the National Health Data System makes it possible to enhance knowledge of the care pathway of patients with severe kidney disease. Taking an interest in hospitalizations makes it possible to understand the burden of this disease, both for patients, in terms of comorbidities, complications and quality of life but also for society in terms of care load, need for organization of the care offer and costs.Patients on dialysis in 2019 were identified from REIN. The information on hospital stays comes from an extraction of the National Health Data System linked with REIN. The hospitalization rate corresponds to the number of hospital stays over the period, relative to the number of people at risk on dialysis over the period.After excluding dialysis sessions, 36,962 patients had a hospital stay in 2019: 36,738 in medicine, surgery, obstetrics, 2863 in rehabilitation, 531 in home hospitalizations and 201 in psychiatry facilities. This represents a total of 146,743 stays, including 140,372 in medicine, surgery, obstetrics. The hospitalization rate in medicine, surgery, obstetrics is 259 stays for 100 person-years. The reasons vary according to age, type of hospitalization (with or without overnight stays) and mode of discharge (home, death or transfer). The median amounts for a stay vary from €7920 in rehabilitation to €719 in medicine, surgery, obstetrics without overnight stay. Due to the volumes, stays for cardiovascular pathology represent a high total amount over the year. Hospitalizations for infection have significant median costs.The results presented in this article confirm the important place of hospitalization in the trajectory of dialysis patients. Hospitalizations in medicine, surgery, obstetrics represent 96% of hospitalizations. For the first time, this study shows the very low place of hospitalizations in psychiatry and rehabilitation facilities. 

Descriptions des hospitalisations au cours de l’année 2019 des patients dialysés en France

ABSTRACT Background This study was conducted to estimate the direct effect of sex on the proportion of hemodialysis (HD) catheters used at dialysis initiation and to investigate whether predialysis care or socioeconomic status acted as a mediator of the sex effect. Methods Patients who started dialysis between January 1, 2017, and June 30, 2018, in France were included using the data of the Renal Epidemiology and Information Network (REIN) registry. We performed logistic regression to study the association between sex and the proportion of HD catheters used. A mediation analysis with a counterfactual approach was carried out to evaluate whether there was an indirect effect of sex through the proxies of predialysis care {hemoglobin, albumin levels, glomerular filtration rate [GFR] at dialysis initiation} and socioeconomic status. Because an interaction between sex and social deprivation has been identified, we performed a subgroup analysis on deprived and nondeprived patients. Results The study included 16 032 patients, and the sex ratio (male to female) was 10 405:5627. In the multivariable analysis, women were associated with a greater risk of starting dialysis with a catheter {odds ratio [OR], 1.32 [95% confidence interval (CI): 1.23–1.42]}. There was an indirect effect of sex on the proportion of HD catheters through proxies for predialysis care {albuminemia <30 g/L [OR, 1.08 (95% CI: 1.05–1.10)], hemoglobin <11 g/dL [OR, 1.03 (95% CI: 1.02–1.04)], glomerular filtration rate <7 mL/min [OR, 1.05 (95% CI: 1.04–1.07)]}. Among deprived patients, there was no direct effect of sex on catheter proportion. Conclusions Women were associated with a higher risk of starting dialysis through an HD catheter. The effect of sex was mediated by predialysis care, particularly for deprived patients.

Is there sex disparity in vascular access at dialysis initiation in France? A mediation analysis using data from the Renal Epidemiology and Information Network registry

Introduction En 2006 le registre REIN montrait une proportion importante de patients demarrant la dialyse en urgence, associee a un plus mauvais pronostic. Des efforts ont depuis ete faits pour referer les patients plus precocement, afin de diminuer l’incidence et ameliorer le pronostic de la dialyse en urgence. Objectif Comparer les caracteristiques des patients debutant la dialyse en urgence en France metropolitaine entre 2006 et 2012. Patients et methodes L’ensemble des patients majeurs ayant debute l’epuration extrarenale dans les 22 regions de France metropolitaine en 2012 a ete inclus a partir des donnees du registre REIN. Leurs caracteristiques et la survie a 1 an ont ete analysees selon qu’ils debutaient en urgence ou de facon programmee, puis comparees a la meme population en 2006. Resultats En 2012, la dialyse a ete debutee en urgence chez 30,3 % des 8839 patients inclus. Ces patients sont significativement plus comorbides par rapport aux programmes (39 % vs 28,7 % ont ≥ 2 pathologies cardiovasculaires, p  Par rapport a 2006, la proportion de patients debutant en urgence reste stable (29,2 % vs 28,4 % sur les 16 memes regions, p = 0,28). Il y a plus d’insuffisants respiratoires (18 % vs 14,6 %, p = 0,005), et de patients denutris (25 % vs 19,6 %, p   10 mL/min, p = 0,003), et l’usage de l’HDF progresse (11,7 % vs 6,2 %, p  Discussion Malgre les efforts realises, la proportion de patients demarrant en urgence n’a pas baisse entre 2006 et 2012, avec un profil toujours plus comorbide. Conclusion Le demarrage de la dialyse en urgence reste associe a une surmortalite, mais la survie a 1 an s’est nettement amelioree en 6 ans, ce qui semble refleter une meilleure prise en charge, notamment en amont.

État des lieux des patients dialysés en urgence en 2012 : quelle évolution depuis 2006 ?

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 la trajectoire des patients avec une maladie rénale stade 5, les messages clés suivants ont été retenus. En dehors de quelques rares contre-indications absolues ou relatives, à ce jour, il n’existe pas de consensus médical sur les indications d’une modalité de traitement par rapport à une autre, et par conséquent, de recommandations permettant de définir des critères d’orientation des patients en fonction de leurs caractéristiques vers une technique/modalité de traitement. Par ailleurs, les choix des patients et l’évolution de leurs besoins au cours du temps doivent être pris en compte. Ainsi, du fait des limites de chacune de ces modalités, un bon nombre de patients en insuffisance rénale stade 5 traités par suppléance rénale vont transiter entre ces différentes modalités. Depuis de nombreuses années, le registre REIN s’est attaché à représenter les flux de patients entre les différentes modalités de traitement. Afin de mieux connaître puis d’optimiser les trajectoires suivies par les patients arrivés au stade 5 de leur insuffisance rénale chronique, il a été nécessaire de mettre au point des outils permettant de modéliser ces trajectoires complexes où les modalités de traitement sont considérées comme complémentaires. © 2022 Société francophone de néphrologie, dialyse et transplantation. Publié par Elsevier Masson SAS. Tous droits réservés. 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 trajectory of ESKD patients, the following key messages were retained. Apart from a few rare, absolute or relative contraindications, till date, there is no medical consensus on the indications of one treatment modality as compared to another, and therefore, no recommendations allowing defining criteria for guiding patients, based on their characteristics, to a technique/treatment modality. In addition, the patients’ choices and their changing needs over time must be taken into account. Thus, due to the limitations of each of these modalities, a good number of patients with stage 5 renal failure treated with kidney replacement therapy will move between these different modalities. For many years, the REIN registry has endeavoured to represent the patient flows between the different treatment modalities. In order to better understand and then optimise the trajectories followed by patients who have reached stage 5 of their chronic renal failure, it was necessary to develop tools to model these complex trajectories where the treatment modalities are considered as complementary. © 2022 Société francophone de néphrologie, dialyse et transplantation. Published by Elsevier Masson SAS. All rights reserved. 

Trajectoires des patients en suppléance

Multi-state models help predict future numbers of patients requiring specific treatments but these models require exhaustive incidence data. Deriving reliable predictions from repeated-prevalence data would be helpful. A new method to model the number of patients that switch between therapeutic modalities using repeated-prevalence data is presented and illustrated. The parameters and goodness of fit obtained with the new method and repeated-prevalence data were compared to those obtained with the classical method and incidence data. The multi-state model parameters’ confidence intervals obtained with annually collected repeated-prevalence data were wider than those obtained with incidence data and six out of nine pairs of confidence intervals did not overlap. However, most parameters were of the same order of magnitude and the predicted patient distributions among various renal replacement therapies were similar regardless of the type of data used. In the absence of incidence data, a multi-state model can...

Cécile Couchoud

Papers

Descriptions des hospitalisations au cours de l’année 2019 des patients dialysés en France

Is there sex disparity in vascular access at dialysis initiation in France? A mediation analysis using data from the Renal Epidemiology and Information Network registry

État des lieux des patients dialysés en urgence en 2012 : quelle évolution depuis 2006 ?

Trajectoires des patients en suppléance

Using repeated-prevalence data in multi-state modeling of renal replacement therapy