PRE‐dialysis survey on anaemia management

Background. The PRE‐dialysis survey on anaemia management (PRESAM) was designed to assess the care given to pre‐dialysis patients in the 12 months before haemodialysis or peritoneal dialysis, with emphasis on anaemia management. Methods. For this epidemiological study, a retrospective chart review was conducted for patients who started haemodialysis or peritoneal dialysis between 1 August, 1999 and 6 April, 2000. All adult patients who entered one of the 779 participating centres in 21 European countries, Israel or South Africa were included, except for patients who underwent dialysis only during an acute episode. In addition to demographic characteristics, the study examined the prevalence of anaemia, anaemia management including the use of iron supplementation and epoetin, source of referral to the dialysis centre, comorbidities and major clinical events. Results. A total of 4333 new dialysis patients were included in the survey. At the first visit to the dialysis centre, 68% of the patients had a haemoglobin (Hb) concentration ≤11.0 g/dl; Hb concentration was positively correlated with creatinine clearance rate (r=0.43, P<0.01). Patients who received epoetin had a mean Hb concentration of 8.8 g/dl at the start of epoetin treatment, and 96% of these patients had an Hb concentration ≤11.0 g/dl. Only 26.5% of the patients received epoetin before dialysis. The length of time under the care of a nephrologist was associated with meeting the European Best Practice Guidelines (EBPG) target Hb concentration, as well as receiving epoetin. Conclusions. Few pre‐dialysis patients met the EBPG target for Hb concentration, despite regular nephrology car

Comparable Renal Function at 6 Months with Tacrolimus Combined with Fixed-Dose Sirolimus or MMF: Results of a Randomized Multicenter Trial in Renal Transplantation

In a multicenter trial, renal transplant recipients were randomized to tacrolimus with fixed-dose sirolimus (Tac/SRL, N = 318) or tacrolimus with MMF (Tac/MMF, N = 316). Targeted tacrolimus trough levels were lower in the Tac/SRL group after day 14. The primary endpoint was renal function at 6 months using creatinine clearance (Cockcroft-Gault) and was comparable at 66.4 mL/min (SE 1.4) with Tac/SRL and at 65.2mL/min (SE 1.3) with Tac/MMF (completers). Biopsy-confirmed acute rejection was 15.1% (Tac/SRL) and 12.3% (Tac/MMF). In both groups, graft survival was 93% and patient survival was 99.0%. Premature withdrawal due to an adverse event was twice as high in the Tac/SRL group, 15.1% versus 6.3%. Hypercholesterolemia incidence was higher with Tac/SRL (P < .05) while CMV, leukopenia, and diarrhea incidences were higher with Tac/MMF (P < .05). The incidence of any antidiabetic treatment for >30 consecutive days in previously nondiabetic patients was 17.8%, Tac/SRL, and 24.8%, Tac/MMF. Evaluation at 6 months showed comparable renal function using tacrolimus/sirolimus and tacrolimus/MMF regimens

Survival with low- and high-flux dialysis

FUNDING COSMOS is sponsored by the Bone and Mineral Research Unit (Hospital Universitario Central de Asturias), SAFIM (Sociedad Asturiana Fomento Investigaciones O´ seas), the European Renal Association–European Dialysis and Transplant Association, the National Program of I þ D þ I 2008–2011 and Instituto de Salud Carlos III (ISCIII), the ISCIII Retic REDinREN (RD06/0016/1013, RD12/0021/0023 and RD16/ 0009/0017), the ISCIII (ICI14/00107, PI17/00384 and PI20/ 00633), Fondo Europeo de Desarrollo Regional (FEDER), Plan Estatal de I þ D þ I 2013–2016, Plan de Ciencia, Tecnologia e Innovacion 2013–2017 y 2018–2022 del Principado de Asturias (GRUPIN14-028, IDI-2018-000152), Fundacio´n Renal I ´nigo A ~ ´ lvarez de Toledo (FRIAT) and the Spanish Society of Nephrology (Estudio Estrate´gico de la SEN). Logistics (meetings, secretarial help, printing of materials, development of website for data entry, etc.) have been financially supported by AMGEN Europe and FRIAT. The authors are not aware of any additional relationships, funding or financial holdings that might be perceived as affecting the objectivity of this study. COSMOS participating centres: see Supplementary Appendix.Background. Besides advances in haemodialysis (HD), mortality rates are still high. The effect of the different types of HD membranes on survival is still a controversial issue. The aim of this COSMOS (Current management Of Secondary hyperparathyroidism: a Multicentre Observational Study) analysis was to survey, in HD patients, the relationship between the use of conventional low- or high-flux membranes and all-cause and cardiovascular mortality. Methods. COSMOS is a multicentre, open-cohort, 3-year prospective study, designed to evaluate mineral and bone disorders in the European HD population. The present analysis included 5138 HD patients from 20 European countries, 3502 randomly selected at baseline (68.2%), plus 1636 new patients with <1 year on HD (31.8%) recruited to replace patients who died, were transplanted, switched to peritoneal dialysis or lost to follow-up by other reasons. Cox-regression analysis with timedependent variables, propensity score matching and the use of an instrumental variable (facility-level analysis) were used. Results. After adjustments using three different multivariate models, patients treated with high-flux membranes showed a lower all-cause and cardiovascular mortality risks fhazard ratio (HR) = 0.76 [95% confidence interval (CI) 0.61-0.96] and HR = 0.61 (95% CI 0.42-0.87), respectivelyg, that remained significant after matching by propensity score for all-cause mortality (HR = 0.69, 95% CI 0.52-0.93). However, a facility-level analysis showed no association between the case-mix-adjusted facility percentage of patients dialysed with high-flux membranes and all-cause and cardiovascular mortality. Conclusions. High-flux dialysis was associated with a lower relative risk of all-cause and cardiovascular mortality. However, dialysis facilities using these dialysis membranes to a greater extent did not show better survival.publishersversionpublishe

COSMOS: the dialysis scenario of CKD-MBD in Europe

Background Chronic kidney disease-mineral and bone disorders (CKD-MBD) are important complications of CKD5D patients that are associated with mortality. Methods COSMOS is a multicentre, open cohort, prospective, observational 3-year study carried out in haemodialysis patients from 20 European countries during 2005-07. The present article describes the main characteristics of the European dialysis population, the current practice for the prevention, diagnosis and treatment of secondary hyperparathyroidism and the differences across different European regions. Results The haemodialysis population in Europe is an aged population (mean age 64.8 ± 14.2 years) with a high prevalence of diabetes (29.5%) and cardiovascular disease (76.0%), and 28.7% of patients have been on haemodialysis more than 5 years. Patients from the former Eastern countries are younger (59.3 ± 14.3 versus 66.0 ± 13.9), having a lower proportion of diabetics (24.1 versus 30.7%). There were relevant differences in the frequency of measurement of the main CKD-MBD biochemical parameters [Ca, P and parathyroid hormone (PTH)] and the Eastern countries showed a poorer control of these biochemical parameters (K/DOQI and K/DIGO targets). Overall, 48.0% of the haemodialysis patients received active vitamin D treatment. Calcitriol use doubled that of alfacalcidiol in the Mediterranean countries, whereas the opposite was found in the non-Mediterranean countries. The criteria followed to perform parathyroidectomy were different across Europe. In the Mediterranean countries, the level of serum PTH considered to perform parathyroidectomy was higher than in non-Mediterranean countries; as a result, in the latter, more parathyroidectomies were performed in the year previous to inclusion to COSMOS. Conclusions The COSMOS baseline results show important differences across Europe in the management of CKD-MB

Renal replacement therapy in Europe : A summary of the 2011 ERA-EDTA Registry Annual Report

BackgroundThis article provides a summary of the 2011 ERA-EDTA Registry Annual Report (available at www.era-edta-reg.org).MethodsData on renal replacement therapy (RRT) for end-stage renal disease (ESRD) from national and regional renal registries in 30 countries in Europe and bordering the Mediterranean Sea were used. From 27 registries, individual patient data were received, whereas 17 registries contributed data in aggregated form. We present the incidence and prevalence of RRT, and renal transplant rates in 2011. In addition, survival probabilities and expected remaining lifetimes were calculated for those registries providing individual patient data.ResultsThe overall unadjusted incidence rate of RRT in 2011 among all registries reporting to the ERA-EDTA Registry was 117 per million population (pmp) (n = 71.631). Incidence rates varied from 24 pmp in Ukraine to 238 pmp in Turkey. The overall unadjusted prevalence of RRT for ESRD on 31 December 2011 was 692 pmp (n = 425 824). The highest prevalence was reported by Portugal (1662 pmp) and the lowest by Ukraine (131 pmp). Among all registries, a total of 22 814 renal transplantations were performed (37 pmp). The highest overall transplant rate was reported from Spain, Cantabria (81 pmp), whereas the highest rate of living donor transplants was reported from Turkey (39 pmp). For patients who started RRT between 2002 and 2006, the unadjusted 5-year patient survival on RRT was 46.8% [95% confidence interval (CI) 46.6-47.0], and on dialysis 39.3% (95% CI 39.2-39.4). The unadjusted 5-year patient survival after the first renal transplantation performed between 2002 and 2006 was 86.7% (95% CI 86.2-87.2) for kidneys from deceased donors and 94.3% (95% CI 93.6-95.0) for kidneys from living donors.publishersversionPeer reviewe

Renal replacement therapy in Europe: a summary of the 2012 ERA-EDTA Registry Annual Report

BACKGROUND: This article summarizes the 2012 European Renal Association-European Dialysis and Transplant Association Registry Annual Report (available at www.era-edta-reg.org) with a specific focus on older patients (defined as ≥65 years). METHODS: Data provided by 45 national or regional renal registries in 30 countries in Europe and bordering the Mediterranean Sea were used. Individual patient level data were received from 31 renal registries, whereas 14 renal registries contributed data in an aggregated form. The incidence, prevalence and survival probabilities of patients with end-stage renal disease (ESRD) receiving renal replacement therapy (RRT) and renal transplantation rates for 2012 are presented. RESULTS: In 2012, the overall unadjusted incidence rate of patients with ESRD receiving RRT was 109.6 per million population (pmp) (n = 69 035), ranging from 219.9 pmp in Portugal to 24.2 pmp in Montenegro. The proportion of incident patients ≥75 years varied from 15 to 44% between countries. The overall unadjusted prevalence on 31 December 2012 was 716.7 pmp (n = 451 270), ranging from 1670.2 pmp in Portugal to 146.7 pmp in the Ukraine. The proportion of prevalent patients ≥75 years varied from 11 to 32% between countries. The overall renal transplantation rate in 2012 was 28.3 pmp (n = 15 673), with the highest rate seen in the Spanish region of Catalonia. The proportion of patients ≥65 years receiving a transplant ranged from 0 to 35%. Five-year adjusted survival for all RRT patients was 59.7% (95% confidence interval, CI: 59.3-60.0) which fell to 39.3% (95% CI: 38.7-39.9) in patients 65-74 years and 21.3% (95% CI: 20.8-21.9) in patients ≥75 years

The European Renal Association - European Dialysis and Transplant Association Registry Annual Report 2014 : a summary

Background: This article summarizes the European Renal Association - European Dialysis and Transplant Association Registry's 2014 annual report. It describes the epidemiology of renal replacement therapy (RRT) for end-stage renal disease (ESRD) in 2014 within 35 countries. Methods: In 2016, the ERA-EDTA Registry received data on patients who in 2014 where undergoing RRT for ESRD, from 51 national or regional renal registries. Thirty-two registries provided individual patient level data and 19 provided aggregated patient level data. The incidence, prevalence and survival probabilities of these patients were determined. Results: In 2014, 70 953 individuals commenced RRT for ESRD, equating to an overall unadjusted incidence rate of 133 per million population (pmp). The incidence ranged by 10-fold; from 23 pmp in the Ukraine to 237 pmp in Portugal. Of the patients commencing RRT, almost two-thirds were men, over half were aged >= 65 years and a quarter had diabetes mellitus as their primary renal diagnosis. By day 91 of commencing RRT, 81% of patients were receiving haemodialysis. On 31 December 2014, 490 743 individuals were receiving RRT for ESRD, equating to an unadjusted prevalence of 924 pmp. This ranged throughout Europe by more than 10-fold, from 157 pmp in the Ukraine to 1794 pmp in Portugal. In 2014, 19 406 kidney transplantations were performed, equating to an overall unadjusted transplant rate of 36 pmp. Again this varied considerably throughout Europe. For patients commencing RRT during 2005-09, the 5-year-adjusted patient survival probabilities on all RRT modalities was 63.3% (95% confidence interval 63.0-63.6). The expected remaining lifetime of a 20-to 24-year-old patient with ESRD receiving dialysis or living with a kidney transplant was 21.9 and 44.0 years, respectively. This was substantially lower than the 61.8 years of expected remaining lifetime of a 20-year-old patient without ESRD.Peer reviewe

WNT activation by lithium abrogates TP53 mutation associated radiation resistance in medulloblastoma

TP53 mutations confer subgroup specific poor survival for children with medulloblastoma. We hypothesized that WNT activation which is associated with improved survival for such children abrogates TP53 related radioresistance and can be used to sensitize TP53 mutant tumors for radiation. We examined the subgroup-specific role of TP53 mutations in a cohort of 314 patients treated with radiation. TP53 wild-type or mutant human medulloblastoma cell-lines and normal neural stem cells were used to test radioresistance of TP53 mutations and the radiosensitizing effect of WNT activation on tumors and the developing brain. Children with WNT/TP53 mutant medulloblastoma had higher 5-year survival than those with SHH/TP53 mutant tumours (100% and 36.6% +/- 8.7%, respectively (p < 0.001)). Introduction of TP53 mutation into medulloblastoma cells induced radioresistance (survival fractions at 2Gy (SF2) of 89% +/- 2% vs. 57.4% +/- 1.8% (p < 0.01)). In contrast, beta-catenin mutation sensitized TP53 mutant cells to radiation (p < 0.05). Lithium, an activator of the WNT pathway, sensitized TP53 mutant medulloblastoma to radiation (SF2 of 43.5% +/- 1.5% in lithium treated cells vs. 56.6 +/- 3% (p < 0.01)) accompanied by increased number of.H2AX foci. Normal neural stem cells were protected from lithium induced radiation damage (SF2 of 33% +/- 8% for lithium treated cells vs. 27% +/- 3% for untreated controls (p = 0.05). Poor survival of patients with TP53 mutant medulloblastoma may be related to radiation resistance. Since constitutive activation of the WNT pathway by lithium sensitizes TP53 mutant medulloblastoma cells and protect normal neural stem cells from radiation, this oral drug may represent an attractive novel therapy for high-risk medulloblastomas.B.R.A.I.N Child Canada; Cancer Research UK; Brain Tumour Charity; Hungarian Brain Research Program [KTIA_13_NAP-A-V/3]; Janos Bolyai Scholarship of the Hungarian Academy of Sciences [TAMOP-4.2.2. A-11/1/KONV-2012-0025]; German Cancer Aid/Dr. Mildred Scheel Foundation for Cancer Research; Cure Childhood Cancer Foundation; St. Baldrick's Foundation; Southeastern Brain Tumor Foundation; Action Medical Research; [CZ.1.05/2.1.00/03.0101]; [CZ.1.07/2.3.00/20.0183