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.Peer reviewe

Disruption of PTH Receptor 1 in T Cells Protects against PTH-Induced Bone Loss

Hyperparathyroidism in humans and continuous parathyroid hormone (cPTH) treatment in mice cause bone loss by regulating the production of RANKL and OPG by stromal cells (SCs) and osteoblasts (OBs). Recently, it has been reported that T cells are required for cPTH to induce bone loss as the binding of the T cell costimulatory molecule CD40L to SC receptor CD40 augments SC sensitivity to cPTH. However it is unknown whether direct PTH stimulation of T cells is required for cPTH to induce bone loss, and whether T cells contribute to the bone catabolic activity of PTH with mechanisms other than induction of CD40 signaling in SCs.Here we show that silencing of PTH receptor 1 (PPR) in T cells blocks the bone loss and the osteoclastic expansion induced by cPTH, thus demonstrating that PPR signaling in T cells is central for PTH-induced reduction of bone mass. Mechanistic studies revealed that PTH activation of the T cell PPR stimulates T cell production of the osteoclastogenic cytokine tumor necrosis factor alpha (TNF). Attesting to the relevance of this effect, disruption of T cell TNF production prevents PTH-induced bone loss. We also show that a novel mechanism by which TNF mediates PTH induced osteoclast formation is upregulation of CD40 expression in SCs, which increases their RANKL/OPG production ratio.These findings demonstrate that PPR signaling in T cells plays an essential role in PTH induced bone loss by promoting T cell production of TNF. A previously unknown effect of TNF is to increase SC expression of CD40, which in turn increases SC osteoclastogenic activity by upregulating their RANKL/OPG production ratio. PPR-dependent stimulation of TNF production by T cells and the resulting TNF regulation of CD40 signaling in SCs are potential new therapeutic targets for the bone loss of hyperparathyroidism

Assessment of urea removal in haemodialysis and the impact of the European Best Practice Guidelines.

Background. Dialysis adequacy, assessed by urea kinetics, is an important determinant of patient outcome, and is therefore an important clinical performance indicator. In this perspective, renal registry data may be useful to compare practices across countries. To serve that purpose available data should be comparable and preferably collected using a standardized procedure. The aim of this study, initiated by the European Renal Association-European Dialysis and Transplantation Association (ERA-EDTA) QUality European STudies (QUEST) initiative, was to make an inventory of the different methods used to determine urea kinetic measurements in the light of the European Best Practice Guidelines. Methods. Via their national and regional registries, European haemodialysis centres were invited to complete a questionnaire regarding their practice of measuring dialysis adequacy. Results. Fourteen regional or national registries among 51 sent back 255 questionnaires. Great variability in the methodology to assess Kt/V was observed. The urea reduction ratio (URR) was used alone by 37% (in association 46%) of dialysis centres, spKt/V by 25% (35%) and online clearance by 4% (12%), whereas only 10% (13%) used eKt/V, as recommended by EBPG. Forty percent of centres measured urea removal less than once a month, 6% of which never measured urea removal and 9% only every 6 months or less frequently. Conclusion. Despite the fact that the use of URR is not recommended by EBPG, it was the most commonly used indicator to measure urea removal, whereas eKt/V was only used by a small minority of centres. This study allowed us to point out the need to standardize definitions and procedures and to develop an effective plan for implementation of the guideline

Conservative care in Europe--nephrologists' experience with the decision not to start renal replacement therapy.

BACKGROUND: For some patients with end-stage renal disease (ESRD), providing conservative care until death may be an acceptable alternative for renal replacement therapy (RRT). We aimed to estimate the occurrence of conservative care in Europe and evaluated opinions about which factors nephrologists consider important in their decision not to offer RRT. METHODS: With a web-based survey sent to nephrologists in 11 European countries, we inquired how often RRT was not started in 2009 and how specific factors would influence the nephrologists' decision to provide conservative care. We compared subgroups by nephrologist and facility characteristics using chi-square tests and Mann-Whitney U tests. RESULTS: We received 433 responses. Nephrologists decided to offer conservative care in 10% of their patients [interquartile range (IQR) 5-20%]. An additional 5% (IQR 2-10%) of the patients chose conservative care as they refused when nephrologists intended to start RRT. Patient preference (93%), severe clinical conditions (93%), vascular dementia (84%) and low physical functional status (75%) were considered extremely or quite important in the nephrologists' decision to provide conservative care. Nephrologists from countries with a low incidence of RRT, not-for-profit centres and public centres more often scored these factors as extremely or quite important than their counterparts from high-incidence countries, for-profit centres and private centres. CONCLUSIONS: Nephrologists estimated conservative care was provided to up to 15% of their patients in 2009. The presence of severe clinical conditions, vascular dementia and a low physical functional status are important factors in the decision-making not to start RRT. Patient preference was considered as a very important factor, confirming the importance of extensive patient education and shared decision-making

Factors influencing the decision to start renal replacement therapy: results of a survey among European nephrologists.

BACKGROUND: Little is known about the criteria nephrologists use in the decision of when to start renal replacement therapy (RRT) in early referred adult patients. We evaluated opinions of European nephrologists on the decision for when to start RRT. STUDY DESIGN: European web-based survey. PREDICTORS: Patient presentations described as uncomplicated patients, patients with unfavorable clinical and unfavorable social conditions, or patients with specific clinical, social, and logistical factors. SETTING & PARTICIPANTS: Nephrologists from 11 European countries. OUTCOMES & MEASUREMENTS: We studied opinions of European nephrologists about the influence of clinical, social, and logistical factors on decision making regarding when to start RRT, reflecting practices in place in 2009. Questions included target levels of kidney function at the start of RRT and factors accelerating or postponing RRT initiation. Using linear regression, we studied determinants of target estimated glomerular filtration rate (eGFR) at the start of RRT. RESULTS: We received 433 completed surveys. The median target eGFR selected to start RRT in uncomplicated patients was 10.0 (25th-75th percentile, 8.0-10.0) mL/min/1.73 m(2). Level of excretory kidney function was considered the most important factor in decision making regarding uncomplicated patients (selected by 54% of respondents); in patients with unfavorable clinical versus social conditions, this factor was selected by 24% versus 32%, respectively. Acute clinical factors such as life-threatening hyperkalemia refractory to medical therapy (100%) and uremic pericarditis (98%) elicited a preference for an immediate start, whereas patient preference (69%) and vascular dementia (66%) postponed the start. Higher target eGFRs were reported by respondents from high- versus low-RRT-incidence countries (10.4 [95% CI, 9.9-10.9] vs 9.1 mL/min/1.73 m(2)) and from for-profit versus not-for-profit centers (10.1 [95% CI, 9.5-10.7] vs 9.5 mL/min/1.73 m(2)). LIMITATIONS: We were unable to calculate the exact response rate and examined opinions rather than practice for 433 nephrologists. CONCLUSIONS: Only for uncomplicated patients did half the nephrologists consider excretory kidney function as the most important factor. Future studies should assess the weight of each factor affecting decision making