Diagnosis of left ventricular diastolic dysfunction in the setting of acute changes in loading conditions

International audienceINTRODUCTION: Conventional pulsed wave Doppler parameters are known to be preload dependent, whereas newly proposed Doppler indices may be less influenced by variations in loading conditions. The aim of the present study was to evaluate the effects of haemodialysis-induced preload reduction on both conventional and new Doppler parameters for the assessment of left ventricular (LV) diastolic function. METHODS: This prospective observational study was conducted in a medical-surgical intensive care unit (ICU) and nephrology department of a teaching hospital. In total, 37 haemodialysis patients with end-stage renal disease (age [mean +/- standard deviation]: 52 +/- 13 years) and eight ventilated ICU patients with acute renal failure receiving vasopressor therapy (age 57 +/- 16 years; Simplified Acute Physiology Score II 51 +/- 17) were studied. Echocardiography was performed before and after haemodialysis. Conventional pulsed wave Doppler indices of LV diastolic function as well as new Doppler indices, including Doppler tissue imaging early diastolic velocities (E' wave) of the septal and lateral portions of the mitral annulus, and propagation velocity of LV inflow at early diastole (Vp) were measured and compared before and after ultrafiltration. RESULTS: The volume of ultrafiltration was greater in haemodialysis patients than in ICU patients (3.0 +/- 1.1 l versus 1.9 +/- 0.9 l; P = 0.005). All conventional pulsed wave Doppler parameters were altered by haemodialysis. In haemodialysis patients, E' velocity decreased after ultrafiltration when measured at the septal mitral annulus (7.1 +/- 2.5 cm/s versus 5.9 +/- 1.7 cm/s; P = 0.0003), but not at its lateral portion (8.9 +/- 3.1 cm/s versus 8.3 +/- 2.6 cm/s; P = 0.37), whereas no significant variation was observed in ICU patients. Vp decreased uniformly after ultrafiltration, the difference being significant only in haemodialysis patients (45 +/- 11 cm/s versus 41 +/- 13 cm/s; P = 0.04). Although of less magnitude, ultrafiltration-induced variations in Doppler parameters were also observed in haemodialysis patients with altered LV systolic function. CONCLUSION: In contrast to other Doppler parameters, Doppler tissue imaging E' maximal velocity measured at the lateral mitral annulus represents an index of LV diastolic function that is relatively insensitive to abrupt and marked preload reduction

A clinical score to predict 6-month prognosis in elderly patients starting dialysis for end-stage renal disease.

International audienceThis simple clinical score effectively predicts short-term prognosis among elderly patients starting dialysis. It should help to illuminate clinical decision making, but cannot be used to withhold dialysis. It ought to only be used by nephrologists to facilitate the discussion with the patients and their families

Description des caractéristiques, des projets de soins et du devenir des patients de plus 75 ans présentant une insuffisance rénale sévère (DFGe ≤ 20 mL/min/1,73 m2) : phase pilote du projet PSPA [Description of characteristics, therapeutic project and outcome of patients older than 75 years with eGFR below 20mL/min/1.73m(2): PSPA pilot study.]

International audienceIn France, the incidence of dialysis patients is increasing in people over 75 years and represents 40% of incident patients. In these elderly patients with many comorbidities, the benefit of dialysis in terms of survival and quality of life remains controversial. Using data from REIN, determinants of early mortality were identified and a prognostic score was provided. This approach must now be adapted to elderly with end stage renal failure (ESRF) not on dialysis for which we have little data on their clinical characteristics, therapeutic projects and outcome. We report the results of a pilot study and the prospective study protocol that resulted. In four French nephrology department, 76 patients were studied with a mean age of 83±5 years, with a MDRD estimated GFR (abbreviated MDRD) of 16±4mL/min/1.73m(2). These patients were different from the population on dialysis recorded in REIN. This pilot study has shown the feasibility of a prospective study on a larger scale, which aims to build a valuable tool for decision making in elderly patients with ESRF not yet on dialysis

Low performance of prognostic tools for predicting dialysis in elderly people with advanced CKD

International audienceIntroduction Clinical decision-making about care plans can be difficult for very elderly people with advanced chronic kidney disease (CKD). Current guidelines propose the use of prognostic tools predicting end stage renal disease (ESRD) to assist in a patient-centered shared decision-making approach. Our objective was to evaluate the existing risk model scores predicting ESRD, from data collected for a French prospective multicenter cohort of mainly octogenarians with advanced CKD. Methods We performed a rapid review to identify the risk model scores predicting ESRD developed from CKD patient cohorts and evaluated them with data from a prospective multicenter French cohort of elderly (> 75 years) patients with advanced CKD (estimated glomerular filtration rate [eGFR] < 20 mL/min/1.75m(2)), followed up for 5 years. We evaluated these scores (in absolute risk) for discrimination, calibration and the Brier score. For scores using the same time frame, we made a joint calibration curve and compared areas under the curve (AUCs). Results The PSPA cohort included 573 patients; their mean age was 83 years and their median eGFR was 13 mL/min/1.73 m(2). At the end of follow-up, 414 had died and 287 had started renal replacement therapy (RRT). Our rapid review found 12 scores that predicted renal replacement therapy. Five were evaluated: the TANGRI 4-variable, DRAWZ, MARKS, GRAMS, and LANDRAY scores. No score performed well in the PSPA cohort: AUCs ranged from 0.57 to 0.65, and Briers scores from 0.18 to 0.25. Conclusions The low predictiveness for ESRD of the scores tested in a cohort of octogenarian patients with advanced CKD underlines the need to develop new tools for this population. Graphic abstrac

Treatment plans and outcomes in elderly patients reaching advanced chronic kidney disease

International audienceBackground - Elderly patients with advanced chronic kidney disease require accurate outcome descriptions to make treatment decisions. Methods - The PSPA [Parcours de soins des personnes âgées (Treatment pathways for elderly patients)] prospective multicentre cohort study included 573 such patients with a median age of 82 [interquartile range (IQR) 79-86] years and a median estimated glomerular filtration rate of 14 (IQR 11-17) mL/min/1.73 m2 and studied their 5-year outcomes according to the dialysis component of their treatment plans. Results - Mean follow-up for the overall cohort was 34.5 ± 21 months and the 5-year survival rate was 27%. During follow-up, 288 (50%) patients started dialysis and 237 (42%) died before dialysis. At baseline, the four possible dialysis plans were dialysis when needed (38%), stable without mention of a dialysis plan (40%) and dialysis specifically excluded by the patient's (9%) or nephrologist's decision (12%). These baseline plans were associated with death and dialysis start. Follow-up plans were those decided during the study period: dialysis when needed for 47%, stable without mention of a dialysis plan for 20% and dialysis excluded at any time for 32%. For the subgroup of patients who started dialysis, those whose follow-up plan was dialysis started under better conditions than those who had stable or no dialysis follow-up plans before starting. However, survival afterwards did not differ significantly. Conclusions - These findings indicate that nephrology care should accommodate changes over time in older patients' treatment preferences and plans concerning dialysis. These changes are associated with whether, when and how these patients initiate dialysis but are not necessarily associated with post-dialysis survival

Retinoic acid receptor subtype-specific transcriptotypes in the early zebrafish embryo

Retinoic acid (RA) controls many aspects of embryonic development by binding to specific receptors (retinoic acid receptors [RARs]) that regulate complex transcriptional networks. Three different RAR subtypes are present in vertebrates and play both common and specific roles in transducing RA signaling. Specific activities of each receptor subtype can be correlated with its exclusive expression pattern, whereas shared activities between different subtypes are generally assimilated to functional redundancy. However, the question remains whether some subtype-specific activity still exists in regions or organs coexpressing multiple RAR subtypes. We tackled this issue at the transcriptional level using early zebrafish embryo as a model. Using morpholino knockdown, we specifically invalidated the zebrafish endogenous RAR subtypes in an in vivo context. After building up a list of RA-responsive genes in the zebrafish gastrula through a whole-transcriptome analysis, we compared this panel of genes with those that still respond to RA in embryos lacking one or another RAR subtype. Our work reveals that RAR subtypes do not have fully redundant functions at the transcriptional level but can transduce RA signal in a subtype-specific fashion. As a result, we define RAR subtype-specific transcriptotypes that correspond to repertoires of genes activated by different RAR subtypes. Finally, we found genes of the RA pathway (cyp26a1, raraa) the regulation of which by RA is highly robust and can even resist the knockdown of all RARs. This suggests that RA-responsive genes are differentially sensitive to alterations in the RA pathway and, in particular, cyp26a1 and raraa are under a high pressure to maintain signaling integrity

Vers une extension du registre REIN aux patients avec une maladie rénale chronique au stade 5 non traités par dialyse ou greffe ? Étude pilote

International audienceTo date, it is important to know more about the population of CKD stage 5 patients in order to better understand the practices of access to renal replacement therapy (RRT) or conservative treatment and to anticipate future needs. In April 2015, at the instigation of the Scientific Committee of REIN, a working group was formed to reflect on the opportunity and feasibility of a data collection on these patients. Between September 2017 and March 2018, 21 participating centers included 390 patients over a period of at least one month. The data collected included the patient's living conditions, level of study, mode of referral, clinical data and the therapeutic project. The median age at baseline was 71.4years (IQR: 58.4-80.4), 39.9% were diabetic. The median eGFR was 12mL/min/1.73m2 (IQR: 9-14). At inclusion, 77% of the patients were already followed in nephrology, 11% had been referred by a general practitioner. For the majority of patients included (81%), there was a RRT project. In 10% of cases, there was a project of conservative care, in 5% of cases the project was not yet decided and in 7% the project had not been yet discussed. At the latest news (median time 4.0months), 35% of patients were dialyzed, 9 (2%) have been pre-emptively transplanted, 25 (6%) died, 210 (54%) were still with a CKD stage 5. Our pilot study has shown the feasibility and interest of setting up such a data collection. Such a registry will provide important public health information regarding the demographic of nephrologists and advanced practices nurses. At the local level, this information will help the department to organize themselves to set-up pre-RRT information, implementation of care pathway nurses and multidisciplinary meetings for difficult cases. However, our pilot study shows that to ensure the completeness of the collection, the tracking upstream or downstream of nephrology consultations for eligible patients is essential and therefore requires dedicated human time on site

The clinical status and survival in elderly dialysis: example of the oldest region of France.

International audienceBACKGROUND: The number of elderly (>=75 years) patients with end-stage renal disease (ESRD) has increased markedly, including in the Limousin region, which has the oldest population in France. We retrospectively compared outcomes in elderly and non-elderly ESRD patients who started dialysis during two time periods. METHODS: Baseline clinical characteristics, care, and survival rates were assessed in 557 ESRD patients aged >=75 and =75 years, respectively. Dialysis was started in 2002--2004 and 2005--2007 by 197 and 146 patients =75 years, respectively. Median age (73.4 years [interquartile range [IQR] 61.7-79.5 years] vs 69.5 years [IQR 57.4-77.4 years] p = 0.001) and the proportion aged >=75 years (44.7% vs 32.8%, p = 0.004) were significantly higher in 2005--2007 than in 2002--2004. Improved initial status during 2005--2007 was observed only in patients >=75 years, with a decrease in some co-morbidities, improved walking and better preparation for dialysis. Mortality rates were significantly lower in 2005--2007 than in 2002--2004 (hazard ratio 0.81, 95% confidence interval 0.69-0.95; p = 0.008), with the difference due to factors associated with clinical status and care. CONCLUSIONS: Improved initial clinical status and better preparation for dialysis, accompanied by increased survival, were observed for patients >=75 years who started dialysis more recently, perhaps because of early referral to a nephrologist