Temporal trends in the quality of deceased donor kidneys and kidney transplant outcomes in Europe: an analysis by the ERA-EDTA Registry.

BACKGROUND: We investigated 10-year trends in deceased donor kidney quality expressed as the kidney donor risk index (KDRI) and subsequent effects on survival outcomes in a European transplant population. METHODS: Time trends in the crude and standardized KDRI between 2005 and 2015 by recipient age, sex, diabetic status and country were examined in 24 177 adult kidney transplant recipients in seven European countries. We determined 5-year patient and graft survival probabilities and the risk of death and graft loss by transplant cohort (Cohort 1: 2005-06, Cohort 2: 2007-08, Cohort 3: 2009-10) and KDRI quintile. RESULTS: The median crude KDRI increased by 1.3% annually, from 1.31 [interquartile range (IQR) 1.08-1.63] in 2005 to 1.47 (IQR 1.16-1.90) in 2015. This increase, i.e. lower kidney quality, was driven predominantly by increases in donor age, hypertension and donation after circulatory death. With time, the gap between the median standardized KDRI in the youngest (18-44 years) and oldest (>65 years) recipients widened. There was no difference in the median standardized KDRI by recipient sex. The median standardized KDRI was highest in Austria, the Netherlands and the Basque Country (Spain). Within each transplant cohort, the 5-year patient and graft survival probability were higher for the lowest KDRIs. There was no difference in the patient and graft survival outcomes across transplant cohorts, however, over time the survival probabilities for the highest KDRIs improved. CONCLUSIONS: The overall quality of deceased donor kidneys transplanted between 2005 and 2015 has decreased and varies between age groups and countries. Overall patient and graft outcomes remain unchanged.

Impact of cardiovascular risk stratification strategies in kidney transplantation over time.

BACKGROUND: Kidney transplant recipients exhibit a dramatically increased cardiovascular (CV) risk. In 2007, Austrian centres implemented a consensus of comprehensive CV screening programme prior to kidney transplantation (KT). The consensus placed a particular emphasis on screening for coronary artery disease (CAD) with cardiac computed tomography (CT) or coronary angiography (CAG) in patients with diabetes mellitus, known CAD or those having multiple conventional CV risk factors. Here, we investigate if this affected risk stratification and post-transplant CV outcomes. METHODS: In a retrospective chart review, we evaluated 551 KTs performed from 2003 to 2015 in our centre. Patients were categorized into three groups: KT before (2003-07), directly after (2008-11) and 5 years after (2012-15) implementation of the consensus. We analysed clinical characteristics, the rate of cardiac CTs and CAGs prior to KT as well as major adverse cardiac events (MACEs) during a 2-year follow-up after KT. RESULTS: The three study groups showed a homogeneous distribution of comorbidities and age. Significantly more cardiac CTs (13.6% versus 10.2% versus 44.8%; P = 0.002) and CAGs (39.6% versus 43.9% versus 56.2%; P = 0.003) were performed after the consensus. Coronary interventions were performed during 42 out of 260 CAGs (16.2%), the cumulative 2-year MACE incidence was 8.7%. Regarding MACE occurrence, no significant difference between the three groups was found. CONCLUSION: CV risk stratification has become more rigorous and invasive after the implementation of the consensus; however, this was not associated with an improvement in CV outcome.

Exclusion of pregnancy in dialysis patients: diagnostic performance of human chorionic gonadotropin.

BACKGROUND: A positive pregnancy test in acute or chronically ill patients has implications for the use of potentially mutagenic or teratogenic products in urgent medical therapies such as the use of chemotherapies or therapies with immunosuppressants, for anesthesia, and for time-sensitive indications like urgent surgery or organ Transplantation. Despite a lack of evidence, it is currently believed that human chorionic gonadotropin serum concentrations are always elevated in female dialysis patients even without pregnancy. It is also believed that human chorionic gonadotropin cannot be used to confirm or exclude pregnancy. METHODS: Human chorionic gonadotropin was examined in female dialysis patients (18-50 years of age), and was classified as positive above 5 mlU/ml. In addition, fertility status was determined. For an enhanced index test, the cut-off of 5 mIU/ml was used for potentially fertile patients and 14 mIU/ml for infertile patients to calculate diagnostic test accuracy. The ideal cut-off for human chorionic gonadotropin was estimated using Liu's method with bootstrapped 95% confidence intervals. Predictors of human chorionic gonadotropin increase were analyzed using multivariable linear regression. RESULTS: Among 71 women, two (2.8%) were pregnant, 46 (64.8%) potentially fertile, and 23 (32.4%) infertile. We observed human chorionic gonadotropin concentrations > 5 mIU/ml in 10 patients, which had a sensitivity of 100% (95% confidence interval: 100 to 100), a specificity of 86% (95% confidence interval: 77 to 94), a positive predictive value of 17% (95% confidence interval: 8 to 25) and a negative predictive value of 100% (95% confidence interval: 100 to 100) for the diagnosis of pregnancy. Using a cut-off > 14 mIU/ml for infertile patients or the exclusion of infertile patients increased specificity to 93% or 98%, respectively. The ideal cut-off was 25 mIU/ml (95% confidence interval: 17 to 33). Pregnancy and potential fertility, but not age, were independent predictors of human chorionic gonadotropin. CONCLUSION: Human chorionic gonadotropin is elevated > 5mIU/ml in 14.5% of non-pregnant dialysis patients of child-bearing age. In potentially fertile women, this cut-off can be used to exclude pregnancy. In case of an unknown fertility status, the ideal human chorionic gonadotropin cut-off was 25 mIU/ml.

Sex-specific analysis of haemodialysis prevalence, practices and mortality over time: the Austrian Dialysis Registry from 1965 to 2014.

BACKGROUND: Despite a higher prevalence of chronic kidney disease among women, more men than women start renal replacement therapy (RRT). We hypothesized that gender differences in health care access exist and therefore aimed at determining whether characteristics and outcomes of haemodialysis patients over time differ by sex. METHODS: We studied all 28 323 adults who began haemodialysis during 1965-2014 in the Austrian Dialysis Registry, analysing trends in patient characteristics by sex and decade with mortality (via Cox regression), which was compared with the mortality of the Austrian general population. RESULTS: More men than women started haemodialysis (60.1% men versus 39.9% women overall), with minor differences among decades and age groups. The male:female mortality rate ratio in the general population ranged from 1.2 to 2.4 for age groups >18 years and in haemodialysis patients ranged from 0.80 to 1.3 (closer to 1 than in the general population, but consistently >1 in Decades 3-5). In recent decades, diabetes and hypertension replaced glomerulonephritis as the primary cause of end-stage renal disease in both men and women. Interaction analyses showed the mortality risk associated with haemodialysis access (only recorded in Decade 5) was significantly lower for men than for women. CONCLUSIONS: The male:female mortality rate ratio and the proportion of women starting haemodialysis were remarkably stable, which does not support the hypothesis of gender differences in health care/haemodialysis access or could imply that such differences might have persisted over decades. Future research should expand to other countries and other forms of RRT.

Changes in co-morbidity pattern in patients starting renal replacement therapy in Europe-data from the ERA-EDTA Registry.

Background: Patients starting renal replacement therapy (RRT) for end-stage renal disease often present with one or more co-morbidities. This study explored the prevalence of co-morbidities in patients who started RRT in Europe during the period from 2005 to 2014. Methods: Using data from patients aged 20 years or older from all 11 national or regional registries providing co-morbidity data to the European Renal Association - European Dialysis and Transplant Association Registry, we examined the prevalence of the following co-morbidities: diabetes mellitus (DM) (primary renal disease and/or co-morbidity), ischaemic heart disease (IHD), congestive heart failure (CHF), peripheral vascular disease (PVD), cerebrovascular disease (CVD) and malignancy. Results: Overall, 70% of 7578 patients who initiated RRT in 2014 presented with at least one co-morbidity: 39.0% presented with DM, 25.0% with IHD, 22.3% with CHF, 17.7% with PVD, 16.4% with malignancy and 15.5% with CVD. These percentages differed substantially between countries. Co-morbidities were more common in men than in women, in older patients than in younger patients, and in patients on haemodialysis at Day 91 when compared with patients on peritoneal dialysis. Between 2005 and 2014 the prevalence of DM and malignancy increased over time, whereas the prevalence of IHD and PVD declined. Conclusions: More than two-thirds of patients initiating RRT in Europe have at least one co-morbidity. With the rising age at the start of RRT over the last decade, there have been changes in the co-morbidity pattern: the prevalence of cardiovascular co-morbidities decreased, while the prevalence of DM and malignancy increased.

Kidney transplant outcomes from older deceased donors: a paired kidney analysis by the European Renal Association-European Dialysis and Transplant Association Registry.

As the median age of deceased kidney donors rises, updated knowledge of transplant outcomes from older deceased donors in differing donor-recipient age groups is required. Using ERA-EDTA Registry data we determined survival outcomes of kidney allografts donated from the same older deceased donor (55-70 years), and transplanted into one recipient younger and one recipient of similar age to the donor. The recipient pairs were divided into two groups: group 1; younger (median age: 52 years) and older (60 years) and group 2; younger (41 years) and older (60 years). A total of 1410 adults were transplanted during 2000-2007. Compared to the older recipients, the mean number of functioning graft years at 10 years was 6 months longer in the group 1 and group 2 younger recipients (P < 0.001). Ten-year graft survival was 54% and 40% for the group 1 younger and older recipients, and 60% and 49% for the group 2 younger and older recipients. Paired Cox regression analyses showed a lower risk of graft failure (group 1 younger; adjusted relative risk [RRa]:0.57, 95% CI:0.41-0.79, and group 2 younger; RRa:0.63, 95% CI:0.47-0.85) in younger recipients. Outcomes from older deceased donor allografts transplanted into differing donor-recipient age groups are better than previously reported. These allografts remain a valuable transplant resource, particularly for similar-aged recipients.

Lifetime risk of renal replacement therapy in Europe: a population-based study using data from the ERA-EDTA Registry.

Background: Upcoming KDIGO guidelines for the evaluation of living kidney donors are expected to move towards a personal risk-based evaluation of potential donors. We present the age and sex-specific lifetime risk of renal replacement therapy (RRT) for end-stage renal disease in 10 European countries. Methods: We defined lifetime risk of RRT as the cumulative incidence of RRT up to age 90 years. We obtained RRT incidence rates per million population by 5-year age groups and sex using data from the European Renal Association-European Dialysis and Transplant Association (ERA-EDTA) Registry, and used these to estimate the cumulative incidence of RRT, adjusting for competing mortality risk. Results: Lifetime risk of RRT varied from 0.44% to 2.05% at age 20 years and from 0.17% to 1.59% at age 70 years across countries, and was twice as high in men as in women. Lifetime RRT risk decreased with age, ranging from an average of 0.77% to 0.44% in 20- to- 70-year-old women, and from 1.45% to 0.96% in 20- to- 70-year-old men. The lifetime risk of RRT increased slightly over the past decade, more so in men than in women. However, it appears to have stabilized or even decreased slightly in more recent years. Conclusions: The lifetime risk of RRT decreased with age, was lower in women as compared with men of equal age and varied considerably throughout Europe. Given the substantial differences in lifetime risk of RRT between the USA and Europe, country-specific estimates should be used in the evaluation and communication of the risk of RRT for potential living kidney donors.

Trends in dialysis modality choice and related patient survival in the ERA-EDTA Registry over a 20-year period.

BACKGROUND: Although previous studies suggest similar patient survival for peritoneal dialysis (PD) and haemodialysis (HD), PD use has decreased worldwide. We aimed to study trends in the choice of first dialysis modality and relate these to variation in patient and technique survival and kidney transplant rates in Europe over the last 20 years. METHODS: We used data from 196 076 patients within the European Renal Association-European Dialysis and Transplant Association (ERA-EDTA) Registry who started renal replacement therapy (RRT) between 1993 and 2012. Trends in the incidence rate and prevalence on Day 91 after commencing RRT were quantified with Joinpoint regression. Crude and adjusted hazard ratios (HRs) for 5-year dialysis patient and technique survival were calculated using Cox regression. Analyses were repeated using propensity score matching to control for confounding by indication. RESULTS: PD prevalence dropped since 2007 and HD prevalence stabilized since 2009. Incidence rates of PD and HD decreased from 2000 and 2009, respectively, while the incidence of kidney transplantation increased from 1993 onwards. Similar 5-year patient survival for PD versus HD patients was found in 1993-97 [adjusted HR: 1.02, 95% confidence interval (95% CI): 0.98-1.06], while survival was higher for PD patients in 2003-07 (HR: 0.91, 95% CI: 0.88-0.95). Both PD (HR: 0.95, 95% CI: 0.91-1.00) and HD technique survival (HR: 0.93, 95% CI: 0.87-0.99) improved in 2003-07 compared with 1993-97. CONCLUSIONS: Although initiating RRT on PD was associated with favourable patient survival when compared with starting on HD treatment, PD was often not selected as initial dialysis modality. Over time, we observed a significant decline in PD use and a stabilization in HD use. These observations were explained by the lower incidence rate of PD and HD and the increase in pre-emptive transplantation.

The changing trends and outcomes in renal replacement therapy: data from the ERA-EDTA Registry.

BACKGROUND: This study examines the time trends in incidence, prevalence, patient and kidney allograft survival and causes of death (COD) in patients receiving renal replacement therapy (RRT) in Europe. METHODS: Eighteen national or regional renal registries providing data to the European Renal Association-European Dialysis and Transplant Association Registry between 1998 and 2011 were included. Incidence and prevalence time trends between 2001 and 2011 were studied with Joinpoint and Poisson regression. Patient and kidney allograft survival and COD between 1998 and 2011 were analysed using Kaplan-Meier and competing risk methods and Cox regression. RESULTS: From 2001 to 2008, the adjusted incidence of RRT rose by 1.1% (95% CI: 0.6, 1.7) annually to 131 per million population (pmp). During 2008-2011, the adjusted incidence fell by 2.2% (95% CI: -4.2, -0.2) annually to 125 pmp. This decline occurred predominantly in patients aged 45-64 years, 65-74 years and in the primary renal diseases diabetes mellitus type 1 and 2, renovascular disease and glomerulonephritis. Between 2001 and 2011, the overall adjusted prevalence increased from 724 to 1032 pmp (+3.3% annually, 95% CI: 2.8, 3.8). The adjusted 5-year patient survival on RRT improved between 1998-2002 and 2003-2007 [adjusted hazard ratio (HRa) 0.85, 95% CI: 0.84, 0.86]. Comparing these time periods, the risk of cardiovascular deaths fell by 25% (HRa 0.75, 95% CI: 0.74, 0.77). However the risk of malignant death rose by 9% (HRa 1.09, 95% CI: 1.03, 1.16) in patients ≥65 years. CONCLUSION: This European study shows a declining RRT incidence, particularly in patients aged 45-64 years, 65-74 years and secondary to diabetic nephropathy. Encouragingly, the adjusted RRT patient survival continues to improve. The risk of cardiovascular death has decreased, though the risk of death from malignancy has increased in the older population.

Diabetes-related end-stage renal disease in Austria 1965-2013.

BACKGROUND: Diabetic kidney disease (DKD) is the leading cause of end-stage renal disease (ESRD) in Austria, accounting for a high burden of morbidity and mortality. In this nationwide study, we aimed to evaluate the incidence and fate of patients with DKD-ESRD over time. METHODS: Data (collected annually) from the Austrian Dialysis- and Transplant Registry were analysed for the development of ESRD due to DKD from 1965 to 2013. RESULTS: Over 48 years, 8322 and 22 975 patients with ESRD due to diabetes and non-diabetes, respectively, entered dialysis. While DKD-ESRD-patients were not dialysed until 1974, in 1975 seven type 1- and one type 2-diabetics started dialysis (1.06 per million population-PMP). In the mid-eighties, DKD-ESRD-patients increasingly were accepted for dialysis (1986: 14.53 PMP, 1996: 31.16 PMP). After a peak incidence of 415 diabetic ESRD-patients in 2006 (50.19 PMP), numbers decreased continuously thereafter (2013: 299 patients, 35.73 PMP). Mean age at start of dialysis increased over time and was lower in type 1- and higher in type 2- compared with non-diabetic patients. Five-year-survival-probability in two diabetic ESRD-cohorts, starting in 2007/08 and 10 years earlier was calculated. Five-year-survival was 28% in 1997/98 and 37.5% in 2007/08. Adjusted relative risk reduction was 33% (HR 0.67, CI 95% 0.57-0.78; P < 0.001). CONCLUSION: Despite a growing prevalence of diabetes, the incidence of diabetic ESRD has decreased after 2006. Five-year-survival-probability has improved over 10 years. Multifactorial therapeutic interventions may have resulted in this improvement.

Use of vascular access for haemodialysis in Europe: a report from the ERA-EDTA Registry.

BACKGROUND: Although arteriovenous fistulas (AVFs) are actively promoted, their use at the start of haemodialysis (HD) seems to be decreasing worldwide. In this paper, we describe recent trends in incidence and prevalence of vascular access types in Europe from 2005 to 2009 and their relationship with patient characteristics and survival. METHODS: Ten European renal registries participating in the ERA-EDTA Registry provided data on incidence (n = 13,044) and/or prevalence (n = 75,715) of vascular access types. We used logistic regression to assess which factors influence the likelihood to be treated with an AVF rather than another type. RESULTS: The use of AVFs at the start of HD showed a significant decreasing trend from 42% in 2005 to 32% in 2009 (P < 0.0001), while the use of central venous catheters (CVCs) increased from 58 to 68% (P < 0.0001). A similar evolution pattern was observed for the prevalence; use of AVFs decreased from 66 to 62% and use of CVCs increased from 28 to 32%. There was a large international variation in the use of the different vascular access types. Female patients [adjusted odds ratio: 0.84, 95% confidence interval (CI): 0.78-0.90] and those ≥80 years (0.77, 95% CI: 0.67-0.90) were least likely to start HD with an AVF. CONCLUSION: In Europe, there is a decreasing trend in the use of AVFs and an increasing trend in the use of CVCs at the start and after the start of HD. We cannot explain all between-country variations we found, and more research is needed to clarify how healthcare around vascular access is organized in Europe.

Use of phosphate-binding agents is associated with a lower risk of mortality.

Hyperphosphatemia has been associated with higher mortality risk in CKD 5 patients receiving dialysis. Here, we determined the association between the use of single and combined phosphate-binding agents and survival in 6797 patients of the COSMOS study: a 3-year follow-up, multicenter, open-cohort, observational prospective study carried out in 227 dialysis centers from 20 European countries. Patient phosphate-binding agent prescriptions (time-varying) and the case-mix-adjusted facility percentage of phosphate-binding agent prescriptions (instrumental variable) were used as predictors of the relative all-cause and cardiovascular mortality using Cox proportional hazard regression models. Three different multivariate models that included up to 24 variables were used for adjustments. After multivariate analysis, patients prescribed phosphate-binding agents showed a 29 and 22% lower all-cause and cardiovascular mortality risk, respectively. The survival advantage of phosphate-binding agent prescription remained statistically significant after propensity score matching analysis. A decrease of 8% in the relative risk of mortality was found for every 10% increase in the case-mix-adjusted facility prescription of phosphate-binding agents. All single and combined therapies with phosphate-binding agents, except aluminum salts, showed a beneficial association with survival. The findings made in the present association study need to be confirmed by randomized controlled trials to prove the observed beneficial effect of phosphate-binding agents on mortality.

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-MBD.

Time trend in access to the waiting list and renal transplantation: a comparison of four European countries.

BACKGROUND: To examine the time trend and international differences in access to the waiting list and renal transplantation of patients with end-stage kidney disease. METHODS: We included all patients (n = 30 961) from Austria, Norway, the Netherlands and Scotland who started renal replacement therapy (RRT) between 1995 and 2003 with their kidney transplant waiting list data (until 31 December 2005) and follow-up data on RRT and mortality (until 31 December 2007). The outcome measure was access to the waiting list within 2 years and to a first renal transplant within 4 years from the start of RRT, expressed as incidence per million age-related population (p.m.a.r.p.) per year. To estimate trends over time, mean percentage annual change (MPAC) and 95% confidence interval (CI) were calculated. RESULTS: In each country, the number of patients starting RRT > 65 years increased significantly over time, whereas the number of renal transplants did not increase to the same extent. Only in Norway were almost all patients on the waiting list transplanted within 4 years of RRT start if they were < 65 years. In patients who started RRT > 65 years, the access to renal transplantation was high in Norway (49 p.m.a.r.p.) and low in Austria ( < 26 p.m.a.r.p.), the Netherlands and Scotland (both < 10 p.m.a.r.p.) but increased significantly in Austria (MPAC = 9.8%; 95% CI = 3.9-16.9) and the Netherlands (MPAC = 9.0%; 95% CI = 3.2-15.0). CONCLUSION: Only in Norway, virtually all patients on the waiting list < 65 years received a transplant within 4 years after the start of RRT and, remarkably, also most of those > 65 years of age.

The effect of timing of the first kidney transplantation on survival in children initiating renal replacement therapy.

BACKGROUND: Controversy exists concerning the timing of the first kidney transplantation for children who need to start renal replacement therapy (RRT). Our aim was to estimate the effect of timing of the first transplantation on patient survival in children, for the first time also taking into account the mortality on dialysis before transplantation. METHODS: We included 2091 patients who started RRT between the age of 3 and 18 years in the period 1988-2007, from 13 European renal registries. A multistate model was used to simulate patient survival assuming (i) pre-emptive transplantation, (ii) transplantation after 1 or 2 years on dialysis and (iii) remaining on dialysis. RESULTS: Over the 20-year period, the highest 8-year survival probabilities were achieved in children transplanted pre-emptively {living donor (LD): 95.9% [95% confidence interval (CI): 93.1-98.8], deceased donor (DD): 95.3% (95% CI: 90.9-99.9)} rather than after 2 years of dialysis [LD: 94.2% (95% CI: 91.6-96.8), DD: 93.4% (95% CI: 91.0-95.9)], although these differences were not statistically significant. CONCLUSIONS: Even after taking mortality on dialysis into account, the potentially negative effect of postponing transplantation for 1 or 2 years was relatively small and not statistically significant. Therefore, if pre-emptive transplantation is not possible, starting RRT with a short period of dialysis and receiving a transplant thereafter seems an acceptable alternative from the perspective of patient survival.

New primary renal diagnosis codes for the ERA-EDTA.

The European Renal Association-European Dialysis and Transplant Association (ERA-EDTA) Registry has produced a new set of primary renal diagnosis (PRD) codes that are intended for use by affiliated registries. It is designed specifically for use in renal centres and registries but is aligned with international coding standards supported by the WHO (International Classification of Diseases) and the International Health Terminology Standards Development Organization (SNOMED Clinical Terms). It is available as supplementary material to this paper and free on the internet for non-commercial, clinical, quality improvement and research use, and by agreement with the ERA-EDTA Registry for use by commercial organizations. Conversion between the old and the new PRD codes is possible. The new codes are very flexible and will be actively managed to keep them up-to-date and to ensure that renal medicine can remain at the forefront of the electronic revolution in medicine, epidemiology research and the use of decision support systems to improve the care of patients.

Hemoglobin variability after renal transplantation is associated with mortality.

Anemia is a common problem after renal transplantation. Therefore, the patients are treated with erythropoietin stimulating agents (ESAs). The varying response to treatment contributes to hemoglobin variability, which might be associated with mortality. We conducted a retrospective cohort study of first kidney allograft recipients between 1990 and 2008 represented in the Austrian Transplant Registry. We included 1441 patients of whom 683 received ESAs at any time after transplantation. Cox regression with cubic splines and linear estimates and the purposeful selection algorithm of covariables were used. The measure of variability was the moving standard deviation computed at three monthly intervals for the entire graft life. The hazard ratio (HR) of mortality and graft loss in the spline models increased with hemoglobin variability. The linear HR for mortality was 2.35 (95% confidence interval 1.75-3.17, P<0.001) and functional graft loss 2.45 (1.76-3.40, P<0.001). In an adjusted Cox model (ESA use, hemoglobin, age, diabetes, days on dialysis, eGFR, biopsy confirmed acute rejection and year of transplantation), hemoglobin variability was associated with mortality (HR: 2.11; 1.51-2.94; P<0.001). No association with functional graft loss could be detected (HR: 1.34; 0.93-1.93; P=0.121). These findings suggest that hemoglobin variability is associated with mortality of renal allograft recipients.

Cost-effectiveness analysis of renal replacement therapy in Austria.

BACKGROUND: Providing renal replacement therapy (RRT) for end-stage renal disease patients is resource intensive. Despite growing financial pressure in health care systems worldwide, cost-effectiveness studies of RRT modalities are scarce. METHODS: We developed a Markov model of costs, quality of life and survival to compare three different assignment strategies to chronic RRT in Europe. RESULTS: Mean annual treatment costs for haemodialysis were €43,600 during the first 12 months, €40,000 between 13 and 24 months and €40,600 beyond 25 months after initiation of treatment. Mean annual treatment costs for peritoneal dialysis were €25,900 during the first 12 months, €15,300 between 13 and 24 months and €20,500 beyond 25 months. Mean annual therapy costs for a kidney transplantation during the first 12 months were €50,900 from a living donor, €51,000 from a deceased donor, €17,200 between 13 and 24 months and €12,900 beyond 25 months after engraftment. Over the next 10 years in Austria with a population of 8 million people, increased assignment to peritoneal dialysis of 20% incident patients saved €26 million with a discount rate of 3% and gained 839 quality-adjusted life years (QALYs); additionally, increasing renal transplants to 10% from live donations saved €38 million discounted and gained 2242 QALYs. CONCLUSIONS: Live donor renal transplantation is cost effective and associated with increase in QALYs. Therefore, preemptive live kidney transplantation should be promoted from a fiscal as well as medical point of view.

Sex Differences in Kidney Transplantation: Austria and the United States, 1978-2018.

BACKGROUND: Systematic analyses about sex differences in wait-listing and kidney transplantation after dialysis initiation are scarce. We aimed at identifying sex-specific disparities along the path of kidney disease treatment, comparing two countries with distinctive health care systems, the US and Austria, over time. METHODS: We analyzed subjects who initiated dialysis from 1979-2018, in observational cohort studies from the US and Austria. We used Cox regression to model male-to-female cause-specific hazard ratios (csHRs, 95% confidence intervals) for transitions along the consecutive states dialysis initiation, wait-listing, kidney transplantation and death, adjusted for age and stratified by country and decade of dialysis initiation. RESULTS: Among 3,053,206 US and 36,608 Austrian patients starting dialysis, men had higher chances to enter the wait-list, which however decreased over time [male-to-female csHRs for wait-listing, 1978-1987: US 1.94 (1.71, 2.20), AUT 1.61 (1.20, 2.17); 2008-2018: US 1.35 (1.32, 1.38), AUT 1.11 (0.94, 1.32)]. Once wait-listed, the advantage of the men became smaller, but persisted in the US [male-to-female csHR for transplantation after wait-listing, 2008-2018: 1.08 (1.05, 1.11)]. The greatest disparity between men and women occurred in older age groups in both countries [male-to-female csHR for wait-listing after dialysis, adjusted to 75% age quantile, 2008-2018: US 1.83 (1.74, 1.92), AUT 1.48 (1.02, 2.13)]. Male-to-female csHRs for death were close to one, but higher after transplantation than after dialysis. CONCLUSIONS: We found evidence for sex disparities in both countries. Historically, men in the US and Austria had 90%, respectively, 60% higher chances of being wait-listed for kidney transplantation, although these gaps decreased over time. Efforts should be continued to render kidney transplantation equally accessible for both sexes, especially for older women.

Association of ESA hypo-responsiveness and haemoglobin variability with mortality in haemodialysis patients.

BACKGROUND: Anaemia is a common complication in dialysis patients. In most cases, it is treated with erythropoietin-stimulating agents (ESA). It is not entirely clear whether the variability of haemoglobin caused by changing ESA response is associated with increased mortality. Therefore, we conducted a retrospective cohort study to evaluate ESA responsiveness and haemoglobin variability in association with mortality. METHODS: We used the Austrian dialysis and transplant registry, and identified 932 patients who were on maintenance haemodialysis in the years 2005-08 with recorded weekly ESA doses and haemoglobin concentrations. ESA response was defined as a positive regression slope over the observation period. Cox regression analysis with spline functions and purposeful variable selection algorithms were used. RESULTS: Adjusted Cox regression analysis showed an increased mortality risk in subjects with wide ranges of haemoglobin variability (from <10 to >12 g/dL) (HR = 2.38, 95% CI 1.20-4.71, P = 0.013). Furthermore, patients that never reached haemoglobin levels >10 g/dL despite ESA therapy exhibited the highest risk of mortality (HR = 6.37, 95% CI 2.15-18.82, P < 0.001). ESA hypo-responsiveness was associated with increased risk of mortality in the low as well as high haemoglobin ranges [HR = 2.06, 95% CI 1.49-2.86 at haemoglobin of 9.5 g/dL and HR = 1.64, 95% CI 0.68-3.92 at 13.5 g/dL both vs. 11 g/dL (reference)]. ESA dose equivalents >16,000 units per week were associated with increased mortality in ESA responders (HR = 1.30, 95% CI 1.02-1.64). However, in hypo-responders, mortality is not associated with ESA dose (HR = 1.02, 95% CI 0.87-1.20) [both at weekly ESA dose of 20,000 units vs. 16,000 (reference)]. CONCLUSIONS: These findings suggest that the risk of mortality of haemodialysis patients requiring ESA therapy is lowest if the haemoglobin concentration is stably maintained in the range between 10 and 12 g/dL with weekly ESA dose equivalents <16,000 units.