Time trends in preemptive kidney transplantation in Europe: an era registry study.

BACKGROUND: Preemptive kidney transplantation has better outcomes when compared to transplantation after dialysis. We aimed to examine trends in preemptive kidney transplantation between 2000 and 2019 in Europe and to provide an overview of associated policies, barriers and initiatives. METHODS: Adult patients from 12 European countries who received a preemptive kidney transplant were included. The representatives of the registries providing these data were questioned on the policies, barriers and initiatives around preemptive kidney transplantation. RESULTS: Between 2000 and 2019, 20 251 adults underwent preemptive kidney transplantation (11 169 from living donors, 8937 from deceased donors). The proportion of first kidney transplantations that were preemptive more than doubled from 7% in 2000 to 18% in 2019, reflecting a similar relative increase for living donor kidney recipients (from 21% to 43%) and deceased donor kidney recipients (from 4% to 11%). Large international differences were found. The increase in preemptive kidney transplantation was observed across all age, sex and primary renal disease groups. Countries had similar criteria for preemptive waitlisting. Barriers mentioned included donor shortage, late referral to the transplant center and long donor or recipient work-up. Suggested initiatives included raising awareness on the possibility of preemptive kidney transplantation, earlier start and shorter work-up time for recipient and living donor. CONCLUSIONS: Over the last two decades the proportion of patients receiving a first kidney transplant preemptively has more than doubled, reflecting a similar relative increase for living and deceased donor kidney recipients.

The ERA Registry Annual Report 2021: a summary.

Background: The European Renal Association (ERA) Registry collects data on kidney replacement therapy (KRT) in patients with end-stage kidney disease (ESKD). This paper is a summary of the ERA Registry Annual Report 2021, including a comparison across treatment modalities. Methods: Data was collected from 54 national and regional registries from 36 countries, of which 35 registries from 18 countries contributed individual patient data and 19 registries from 19 countries contributed aggregated data. Using this data, incidence and prevalence of KRT, kidney transplantation rates, survival probabilities and expected remaining lifetimes were calculated. Result: In 2021, 533.2 million people in the general population were covered by the ERA Registry. The incidence of KRT was 145 per million population (pmp). In incident patients, 55% were 65 years or older, 64% were male, and the most common primary renal disease (PRD) was diabetes (22%). The prevalence of KRT was 1040 pmp. In prevalent patients, 47% were 65 years or older, 62% were male, and the most common PRDs were diabetes and glomerulonephritis/sclerosis (both 16%). On 31 December 2021, 56% of patients received haemodialysis, 5% received peritoneal dialysis, and 39% were living with a functioning graft. The kidney transplantation rate in 2021 was 37 pmp, a majority coming from deceased donors (66%). For patients initiating KRT between 2012-2016, 5-year survival probability was 52%. Compared to the general population, life expectancy was 65% and 68% shorter for males and females receiving dialysis, and 40% and 43% shorter for males and females living with a functioning graft.

A comparison of the epidemiology of kidney replacement therapy between Europe and the United States: 2021 data of the ERA Registry and the USRDS.

BACKGROUND AND HYPOTHESIS: This paper compares the most recent data on the incidence and prevalence of kidney replacement therapy (KRT), kidney transplantation rates, and mortality on KRT from Europe to those from the United States (US), including comparisons of treatment modalities (haemodialysis (HD), peritoneal dialysis (PD), and kidney transplantation (KTx)). METHODS: Data were derived from the annual reports of the European Renal Association (ERA) Registry and the United States Renal Data System (USRDS). The European data include information from national and regional renal registries providing the ERA Registry with individual patient data. Additional analyses were performed to present results for all participating European countries together. RESULTS: In 2021, the KRT incidence in the US (409.7 per million population (pmp)) was almost 3-fold higher than in Europe (144.4 pmp). Despite the substantial difference in KRT incidence, approximately the same proportion of patients initiated HD (Europe: 82%, US: 84%), PD (14%; 13% respectively), or underwent pre-emptive KTx (4%; 3% respectively). The KRT prevalence in the US (2436.1 pmp) was 2-fold higher than in Europe (1187.8 pmp). Within Europe, approximately half of all prevalent patients were living with a functioning graft (47%), while in the US, this was one third (32%). The number of kidney transplantations performed was almost twice as high in the US (77.0 pmp) compared to Europe (41.6 pmp). The mortality of patients receiving KRT was 1.6-fold higher in the US (157.3 per 1000 patient years) compared to Europe (98.7 per 1000 patient years). CONCLUSIONS: The US had a much higher KRT incidence, prevalence, and mortality compared to Europe, and despite a higher kidney transplantation rate, a lower proportion of prevalent patients with a functioning graft.

Incidence and outcomes of kidney replacement therapy for end-stage kidney disease due to primary glomerular disease in Europe: findings from the ERA Registry.

BACKGROUND AND HYPOTHESIS: Primary glomerular disease (PGD) is a major cause of end-stage kidney disease (ESKD) leading to kidney replacement therapy (KRT). We aimed to describe incidence (trends) in individuals starting KRT for ESKD due to PGD and to examine their survival and causes of death. METHODS: We used data from the European Renal Association (ERA) Registry on 69 854 patients who started KRT for ESKD due to PGD between 2000 and 2019. ERA primary renal disease codes were used to define six PGD subgroups. We examined age and sex standardized incidence, trend of the incidence, and survival. RESULTS: The standardized incidence of KRT for ESKD due to PGD was 16.6 per million population (pmp), ranging from 8.6 pmp in Serbia to 20.0 pmp in France. IgA nephropathy (IgAN) and focal segmental glomerulosclerosis (FSGS) had the highest incidence of 4.6 pmp and 2.6 pmp, respectively. Histologically non-examined PGDs represented over 50% of cases in Serbia, Bosnia and Herzegovina, and Romania and were also common in Greece, Estonia, Belgium, and Sweden. The incidence declined from 18.6 pmp in 2000 to 14.5 pmp in 2013, after which it stabilized. All PGD subgroups had five-year survival probabilities above 50%, with crescentic glomerulonephritis having the highest risk of death (adjusted hazard ratio: 1.8 [95% confidence interval: 1.6-1.9]) compared with IgAN. Cardiovascular disease was the most common cause of death (33.9%). CONCLUSION: The incidence of KRT for ESKD due to PGD showed large differences between countries and was highest and increasing for IgAN and FSGS. Lack of kidney biopsy facilities in some countries may have affected accurate assignment of the cause of ESKD. The recognition of the incidence and outcomes of KRT among different PGD subgroups may contribute to a more individualized patient care approach.

International comparison and time trends of first kidney transplant recipient characteristics across Europe: an ERA Registry study.

BACKGROUND: The aim of this study was to provide an overview of age, sex and primary renal disease (PRD) distribution among first kidney transplant recipients across Europe. METHOD: The European Renal Association (ERA) Registry database was used to obtain data on patients aged 20 years or older receiving their first kidney transplant between 2010 and 2019 from 12 European countries. The numbers and percentages of recipients in each age, sex and PRD group were calculated by country, donor type and year. RESULTS: In total, 99 543 adults received a first kidney transplant. Overall, 23% of the recipients were 65 years or older, 36% were female, and 21% had glomerulonephritis and 15% diabetes mellitus as PRD. Compared with deceased donor kidney transplant recipients, living donor kidney transplant recipients were less often 65 years or older (13% versus 26%), more often had glomerulonephritis (25% versus 20%) and less often diabetes mellitus (8% versus 17%) as PRD. We found large international differences, which were most prominent for age and PRD and less prominent for sex. Over time, the largest change in recipient characteristics was observed for the percentage of recipients aged 65 years or older, increasing from 18% in 2010 to 28% in 2019 for all countries combined with a similar trend in most countries. CONCLUSION: We observed large differences for age and PRD distribution between recipients of living and deceased donor kidneys and between European countries. Over time, the percentage of older first kidney transplant recipients increased.

The impact of gender on the risk of cardiovascular events in older adults with advanced chronic kidney disease.

Background: Patients with chronic kidney disease (CKD) are at a higher risk of major adverse cardiovascular events (MACE) compared with the general population, but gender differences in this risk, especially in older adults, are not fully known. We aim to identify gender differences in the risk of MACE in older European CKD patients, and explore factors that may explain these differences. Methods: The European Quality study (EQUAL) is a prospective study on stage 4-5 CKD patients, ≥65 years old, not on dialysis, from Germany, Italy, the Netherlands, Poland, Sweden and the UK. Cox regression and cumulative incidence competing risk curves were used to identify gender differences in MACE risks. Mediation analysis was used to identify variables which may explain risk differences between men and women. Results: A total of 417 men out of 1134 (37%) and 185 women out of 602 women (31%) experienced at least one MACE, over a follow-up period of 5 years. Women had an 18% lower risk of first MACE compared with men (hazard ratio 0.82; 95% confidence interval 0.69-0.97; P = .02), which was attenuated after adjusting for pre-existing cardiometabolic comorbidities and cardiovascular risk factors. There were no significant gender differences in the risk of recurrent MACE or fatal MACE. The risk difference in MACE by gender was larger in patients aged 65-75 years, compared with patients over 75 years. Conclusions: In a cohort of older adults with advanced CKD, women had lower risks of MACE. These risk differences were partially explained by pre-existing cardiometabolic comorbidities and cardiovascular risk factors.

The long-term benefits of early intensive therapy in chronic diseases-the legacy effect.

The 'legacy effect' refers to the long-term benefits of intensive therapy that are observed long after the end of clinical trials and trial interventions in chronic diseases such as diabetes, hyperlipidaemia and hypertension. It emphasizes the importance of intensive treatment to prevent long-term complications and mortality. In chronic kidney disease (CKD), the legacy effect is evident in various studies. Long-term nephroprotection in diabetes is well documented in major studies in the early stages of diabetes, such as Diabetes Control and Complications Trial-Epidemiology of Diabetes Interventions and Complications (DCCT-EDIC), UK Prospective Diabetes Study (UKPDS) and Intensified Multifactorial Intervention in Patients with Type 2 Diabetes and Microalbuminuria (STENO-2). These studies highlight the importance of intensive glycaemic control in reducing microvascular complications, including nephropathy, in patients with recently diagnosed type 1 and type 2 diabetes. However, the legacy effect is less evident in patients with long-term, established diabetes. In chronic glomerulonephritis, studies on immunoglobulin A nephropathy showed that early immunosuppressive treatment could have long-term beneficial effects on kidney function in children and adults with CKD. The Frequent Hemodialysis (FH) and the EXerCise Introduction To Enhance Performance in Dialysis (EXCITE) trials indicated that frequent haemodialysis and a personalized walking exercise program could improve clinical outcomes and reduce the long-term risk of death and hospitalization. The legacy effect concept underscores the importance of intensive intervention in chronic diseases, including CKD. This concept has significant implications for public health and warrants in-depth basic and clinical research to be better understood and exploited in clinical practice. However, its limitations should be considered when interpreting long-term observational data collected after a clinical trial. Appropriate study designs are necessary to investigate an unbiased legacy effect.

The ERA Registry Annual Report 2020: a summary.

Background: The European Renal Association (ERA) Registry collects data on kidney replacement therapy (KRT) in patients with ESKD. This paper is a summary of the ERA Registry Annual Report 2020, also including comparisons among primary renal disease (PRD) groups. Methods: Data were collected from 52 national and regional registries from 34 European countries and countries bordering the Mediterranean Sea: 35 registries from 18 countries providing individual level data and 17 registries from 17 countries providing aggregated data. Using this data, KRT incidence and prevalence, kidney transplantation rates, expected remaining lifetimes and survival probabilities were calculated. Results: A general population of 654.9 million people was covered by the ERA Registry in 2020. The overall incidence of KRT was 128 per million population (p.m.p.). In incident KRT patients, 54% were older than 65 years, 63% were men and the most common PRD was diabetes mellitus (21%). Regarding initial treatment modality in incident patients, 85% received haemodialysis (HD), 11% received peritoneal dialysis (PD) and 4% received a pre-emptive kidney transplant. On 31 December 2020, the prevalence of KRT was 931 p.m.p. In prevalent patients, 45% were older than 65 years, 60% were men and glomerulonephritis was the most common PRD (18%). Of these patients, 58% were on HD, 5% on PD and 37% were living with a kidney transplant. The overall kidney transplantation rate in 2020 was 28 p.m.p., with a majority of kidney grafts from deceased donors (71%). The unadjusted 5-year survival, based on incident dialysis patient from 2011-15, was 41.8%. For patients having received a deceased donor transplant, the unadjusted 5-year survival probability was 86.2% and for patients having received a living donor transplant it was 94.4%. When comparing data by PRD group, differences were found regarding the distribution of age groups, sex and treatment modality received.

Trends in kidney transplantation rate across Europe: study from the ERA Registry.

BACKGROUND: The aim of this study was to identify trends in total, deceased donor (DD) and living donor (LD) kidney transplantation (KT) rates in European countries. METHODS: The European Renal Association (ERA) Registry and the Global Observatory on Donation and Transplantation (GODT) databases were used to obtain the number of KTs in individual European countries between 2010 and 2018. General population counts were obtained from Eurostat or the national bureaus of statistics. The KT rate per million population (p.m.p.) and the average annual percentage change (APC) were calculated. RESULTS: The total KT rate in the 40 participating countries increased with 1.9% annually  [95%  confidence  interval  (CI) 1.5, 2.2] from 29.6 p.m.p. in 2010 to 34.7 p.m.p. in 2018, reflecting an increase of 3.4 p.m.p. in the DD-KT rate (from 21.6 p.m.p. to 25.0 p.m.p.; APC 1.9%; 95% CI 1.3, 2.4) and of 1.5 p.m.p. in the LD-KT rate (from 8.1 p.m.p. to 9.6 p.m.p.; APC 1.6%; 95% CI 1.0, 2.3). The trends in KT rate varied widely across European countries. An East-West gradient was observed for DD-KT rate, with Western European countries performing more KTs. In addition, most countries performed fewer LD-KTs. In 2018, Spain had the highest DD-KT rate (64.6 p.m.p.) and Turkey the highest LD-KT rate (37.0 p.m.p.). CONCLUSIONS: The total KT rate increased due to a rise in the KT rate from DDs and to a lesser extent from LDs, with large differences between individual European countries.

Factors influencing kidney transplantation rates: a study from the ERA Registry.

BACKGROUND: Large international differences exist in kidney transplantation (KT) rates. We aimed to investigate which factors may explain the total, deceased donor and living donor KT rates over the last decade. METHODS: KT experts from 39 European countries completed the Kidney Transplantation Rate Survey on measures and barriers and their potential effect on the KT rate in their country. In the analyses, countries were divided into low, middle and high KT rate countries based on the KT rate at the start of study period in 2010. RESULTS: Experts from low KT rate countries reported more frequently that they had taken measures regarding staff, equipment and facilities to increase the total KT rate compared with middle and high KT rate countries. For donor type-specific KT, the largest international differences in measures taken were reported for deceased donor KT, with middle and high KT rate countries taking more measures, such as the use of expanded criteria donor kidneys, the presence of transplantation coordinators and (inter)national exchange of donor kidneys. Once a measure was taken, experts' opinion on its success was similar across the low, middle and high KT rate countries. Experts from low KT rate countries more often reported potential barriers, such as patients' lack of knowledge and distrust in the healthcare system. CONCLUSIONS: Particularly in low KT rate countries, the KT rate might be stimulated by optimizing staff, equipment and facilities. In addition, all countries may benefit from measures specific to deceased and living donors.

Increasing numbers and improved overall survival of patients on kidney replacement therapy over the last decade in Europe: an ERA Registry study.

BACKGROUND: The aim of this study was to describe the trends in the incidence, prevalence and survival of patients on kidney replacement therapy (KRT) for end-stage kidney disease (ESKD) across Europe from 2008 to 2017. METHODS: Data from renal registries in 9 countries and 16 regions that provided individual patient data to the ERA Registry from 2008 to 2017 were included. These registries cover 34% of the general population in Europe. Crude and standardized incidence and prevalence per million population (pmp) were determined. Trends over time were studied using Joinpoint regression. Survival probabilities were estimated using Kaplan-Meier analysis and hazard ratios (HRs) using Cox regression analysis. RESULTS: The standardized incidence of KRT was stable [annual percentage change (APC): -1.48 (-3.15; 0.21)] from 2008 (146.0 pmp) to 2011 (141.6 pmp), followed by a slight increase [APC: 1.01 (0.43; 1.60)] to 148.0 pmp in 2017, although trends in incidence varied across countries. This increase was primarily due to a rise in the incidence of KRT in men older than 65 years. Moreover, as a cause of kidney failure, diabetes mellitus is increasing. The standardized prevalence increased from 2008 (990.0 pmp) to 2017 (1166.8 pmp) [APC: 1.82 (1.75; 1.89)]. Patient survival on KRT improved in the time period 2011-13 compared with 2008-[adjusted HR: 0.94 (0.93; 0.95)]. CONCLUSION: This study showed an overall increase in the incidence and prevalence of KRT for ESKD as well as an increase in the KRT patient survival over the last decade in Europe.

Pregnancy after living kidney donation, a systematic review of the available evidence, and a review of the current guidance.

Understanding and communicating the risk of pregnancy complications post-living kidney donation is imperative as the majority of living kidney donors (LKD) are women of childbearing age. We aimed to identify all original research articles examining complications in post-donation pregnancies and compared the quality and consistency of related guidelines. We searched Embase, MEDLINE, PubMed, society webpages, and guideline registries for English-language publications published up until December 18, 2020. Ninety-three articles were screened from which 16 studies were identified, with a total of 1399 post-donation pregnancies. The outcome of interest, post-donation pregnancy complications, was not calculable, and only a narrative synthesis of the evidence was possible. The absolute risk of pre-eclampsia increased from ~1%-3% pre-donation (lower than the general population) to ~4%-10% post-donation (comparable to the general population). The risks of adverse fetal and neonatal outcomes were no different between post-donation and pre-donation pregnancies. Guidelines and consensus statements were consistent in stating the need to inform LKDs of their post-donation pregnancy risk, however, the depth and scope of this guidance were variable. While the absolute risk of pregnancy complications remains low post-donation, a concerted effort is required to better identify and individualize risk in these women, such that consent to donation is truly informed.

Chronic prescription of antidepressant medication in patients with chronic kidney disease with and without kidney replacement therapy compared with matched controls in the Dutch general population.

Background: Chronic kidney disease (CKD) is associated with a higher prevalence of depression, neuropathic pain and insomnia. These conditions are often treated pharmaceutically. In this study we aimed to determine the prevalence of chronic antidepressant use among CKD patients with and without kidney replacement therapy (KRT). Methods: By using the Dutch health claims database, we were able to determine the prevalence, type and dosage of chronic antidepressant prescriptions in patients with CKD Stage G4/G5 without KRT (n = 14 905), patients on dialysis (n = 3872) and patients living on a functioning graft (n = 8796) and compared these to age-, sex- and socio-economic status (SES)-matched controls from the general population. Results: Our data show that the prevalence of chronic antidepressant prescription is 5.6%, 5.3% and 4.2% in CKD Stage G4/G5, dialysis and kidney transplant patients, respectively, which is significantly higher than in matched controls. Although our data revealed more prescriptions in female patients and in the age category 45-64 years, our data did not show any association between antidepressant prescriptions and SES. Selective serotonin reuptake inhibitors were the most prescribed drugs in all patient groups and controls. Tricyclic antidepressants were more often used in patients compared with controls. Conclusion: This nationwide analysis revealed that chronic antidepressant prescription in the Netherlands is higher in CKD patients with and without KRT than in controls, higher in middle-aged patients and women, unrelated to socio-economic status and lower than chronic use reported in other countries.

The ERA Registry Annual Report 2019: summary and age comparisons.

BACKGROUND: Data on renal replacement therapy (RRT) for end-stage renal disease were collected by the European Renal Association (ERA) Registry via national and regional renal registries in Europe and countries bordering the Mediterranean Sea. This article provides a summary of the 2019 ERA Registry Annual Report, including data from 34 countries and additional age comparisons. METHODS: Individual patient data for 2019 were provided by 35 registries and aggregated data by 17 registries. Using these data, the incidence and prevalence of RRT, the kidney transplantation activity and the survival probabilities were calculated. RESULTS: In 2019, a general population of 680.8 million people was covered by the ERA Registry. Overall, the incidence of RRT was 132 per million population (p.m.p.). Of these patients, 62% were men, 54% were ≥65 years of age and 21% had diabetes mellitus as primary renal disease (PRD), and 84% had haemodialysis (HD), 11% had peritoneal dialysis (PD) and 5% had pre-emptive kidney transplantation as an initial treatment modality. The overall prevalence of RRT on 31 December 2019 was 893 p.m.p., with 58% of patients on HD, 5% on PD and 37% living with a kidney transplant. The overall kidney transplant rate was 35 p.m.p. and 29% of the kidney grafts were from a living donor. The unadjusted 5-year survival probability was 42.3% for patients commencing dialysis, 86.6% for recipients of deceased donor grafts and 94.4% for recipients of living donor grafts in the period 2010-14. When comparing age categories, there were substantial differences in the distribution of PRD, treatment modality and kidney donor type, and in the survival probabilities.

Translational research in nephrology: prognosis.

Translational research aims at reducing the gap between the results of studies focused on diagnosis, prognosis and therapy, and every day clinical practice. Prognosis is an essential component of clinical medicine. It aims at estimating the risk of adverse health outcomes in individuals, conditional to their clinical and non-clinical characteristics. There are three fundamental steps in prognostic research: development studies, in which the researcher identifies predictors, assigns the weights to each predictor, and assesses the model's accuracy through calibration, discrimination and risk reclassification; validation studies, in which investigators test the model's accuracy in an independent cohort of individuals; and impact studies, in which researchers evaluate whether the use of a prognostic model by clinicians improves their decision-making and patient outcome. This article aims at clarifying how to reduce the disconnection between the promises of prognostic research and the delivery of better individual health.

An introduction to inverse probability of treatment weighting in observational research.

In this article we introduce the concept of inverse probability of treatment weighting (IPTW) and describe how this method can be applied to adjust for measured confounding in observational research, illustrated by a clinical example from nephrology. IPTW involves two main steps. First, the probability-or propensity-of being exposed to the risk factor or intervention of interest is calculated, given an individual's characteristics (i.e. propensity score). Second, weights are calculated as the inverse of the propensity score. The application of these weights to the study population creates a pseudopopulation in which confounders are equally distributed across exposed and unexposed groups. We also elaborate on how weighting can be applied in longitudinal studies to deal with informative censoring and time-dependent confounding in the setting of treatment-confounder feedback.

Patient-reported factors influencing the choice of their kidney replacement treatment modality.

BACKGROUND: Access to various kidney replacement therapy (KRT) modalities for patients with end-stage kidney disease differs substantially within Europe. METHODS: European adults on KRT filled out an online or paper-based survey about factors influencing and experiences with modality choice (e.g. information provision, decision-making and reasons for choice) between November 2017 and January 2019. We compared countries with low, middle and high gross domestic product (GDP). RESULTS: In total, 7820 patients [mean age 59 years, 56% male, 63% on centre haemodialysis (CHD)] from 38 countries participated. Twenty-five percent had received no information on the different modalities, and only 23% received information >12 months before KRT initiation. Patients were not informed about home haemodialysis (HHD) (42%) and comprehensive conservative management (33%). Besides nephrologists, nurses more frequently provided information in high-GDP countries, whereas physicians other than nephrologists did so in low-GDP countries. Patients from low-GDP countries reported later information provision, less information about other modalities than CHD and lower satisfaction with information. The majority of modality decisions were made involving both patient and nephrologist. Patients reported subjective (e.g. quality of life and fears) and objective reasons (e.g. costs and availability of treatments) for modality choice. Patients had good experiences with all modalities, but experiences were better for HHD and kidney transplantation and in middle- and high-GDP countries. CONCLUSION: Our results suggest European differences in patient-reported factors influencing KRT modality choice, possibly caused by disparities in availability of KRT modalities, different healthcare systems and varying patient preferences. Availability of home dialysis and kidney transplantation should be optimized.