Prevalent Kidney Transplant Recipients Research Articles

#520 Trends in kidney replacement therapy in Central and Eastern Europe—data from the ERA Registry

Abstract Background and Aims Despite huge efforts to accomplish equitable access to high-quality healthcare, large disparities in kidney care delivery remain across Europe. Economic factors are considered to be the driving force behind differences in access to kidney replacement therapy (KRT), with lower access in lower-income countries. There is a sparsity of epidemiological data on KRT in Central and Eastern Europe. Therefore, we aimed to examine time trends in incidence and prevalence of KRT in Central and Eastern Europe from 2010 to 2021. Method We included incidence and prevalence data on patients starting or receiving KRT between the years 2010 and 2021 from 18 Central and Eastern European countries participating in the ERA Registry. Albania, Belarus, Bulgaria, Cyprus, Czech Republic, Latvia, Lithuania, Northern Macedonia, Poland, Russia, Slovakia, Turkey, and Ukraine provided data on aggregated level, whereas Bosnia and Herzegovina, Estonia, Greece, Romania and Serbia provided individual patient data. General population data were reported by the collaborating registries or extracted from Eurostat. Most registries had full coverage of the general population. We expressed incidence and prevalence per million population (pmp) and time trends were studied with Joinpoint regression and expressed as Annual Percentage Changes (APCs). Results Incidence of KRT varied largely across Central and Eastern European countries (Fig. 1). In 2010, it ranged from 23.0 pmp in Ukraine to 190.5 pmp in Greece, and in 2021 from 53.0 pmp in Ukraine to 283.0 pmp in Cyprus. In 7 countries the KRT incidence increased significantly between 2010 and 2021 (APC; 95% CI): Albania (+8%; 5-10%), Cyprus (+6%; 4-9%), Greece (+3%; 3-4%), North Macedonia (+4%; 3-5%), Romania (+3%; 1-5%), Russia (+9%; 7-10%), and Ukraine (+7%; 4-9%). Serbia was the only country in which KRT incidence decreased: from 188.6 pmp in 2010 to 65.9 pmp in 2021 (APC: −8%; −10 to −6%), whereas for other countries KRT incidence remained stable over the study period. Except for the Baltic States, the age of incident KRT patients increased in all countries during the study period, also reflected by a temporal increase in the proportion of patients initiating KRT at ages of 65 years and older. The KRT prevalence also showed large variation across countries, ranging from 123.6 pmp to 1080.0 pmp in 2010 in Ukraine and Greece (Fig. 1). In 2021 it ranged from 303.6 pmp (Ukraine) to 1445.4 pmp (Greece). In all, but five countries (Belarus, Bosnia and Herzegovina, Czech Republic, North Macedonia, and Serbia) the prevalence of KRT increased annually with 2-9% between 2010 and 2021. This increase was mainly driven by an increase in prevalent patients with a functioning kidney transplant. If, however, the period prior to the COVID-19 pandemic was considered (2010 to 2019) there was also an increasing trend in the KRT prevalence for Bosnia and Herzegovina, Czech Republic, and North Macedonia. In all countries, prevalent KRT patients became older during recent years. Conclusion Large variation exists in the number of incident and prevalent patients treated with KRT across Central and Eastern Europe. In the majority of countries the incidence of KRT remained stable between 2010 and 2021, whereas in about one third of countries the incidence of KRT significantly increased. On the other hand, in most countries the number of prevalent KRT patients significantly increased over the study period, especially prior to the COVID-19 pandemic. This increase was mainly driven by an increase in prevalent kidney transplant recipients. Patients on KRT tended to become older in the entire region, reflecting both the aging population, as well as the increasing willingness and capacity to treat elderly patients. Nevertheless, large country variations in the epidemiology of KRT remain and this study is a first important step to define country-specific priorities for the optimization of kidney care and to create further public awareness for kidney diseases in the Central and Eastern European region.

Long-term changes in cardiac remodelling in prevalent kidney graft recipients

BackgroundApproximately 15% of kidney transplant (KT) recipients develop de novo heart failure after KT. There are scarce data reporting the long-term changes in cardiac structure and function among KT recipients. Despite the improvement in renal function, transplant-related complications as well as immunosuppressive therapy could have an impact on cardiac remodelling during follow-up. We aimed to describe the long-term changes in echocardiographic parameters in prevalent KT recipients and identify the clinical and laboratory factors associated with these changes. MethodsA centralised blinded review of two echocardiographic examinations after KT (on average after 17 and 39 months post-KT respectively) was performed among 80 patients (age 50.4 ± 16.2, diabetes 13.8% pre-KT), followed by linear regression to identify clinico-biological factors related to echocardiographic changes. ResultsLeft atrial volume index (LAVI) increased significantly (34.2 ± 10.8 mL/m2vs. 37.6 ± 15.0 mL/m2, annualised delta 3.1 ± 11.4 mL/m2/year; p = 0.034) while left ventricular ejection fraction (LVEF) decreased (62.1 ± 9.0% vs. 59.7 ± 9.9%, annualised delta −2.7 ± 13.6%/year; p = 0.04). Male sex (β = 8.112 ± 2.747; p < 0.01), pre-KT hypertension (β = 9.725 ± 4.156; p < 0.05), graft from expanded criteria donor (β = 3.791 ± 3.587; p < 0.05), and induction by anti-thymocyte globulin (β = 7.920 ± 2.974; p = 0.01) were associated with an increase in LAVI during follow-up. Higher haemoglobin (>12.9 g/dL) at the time of the first echocardiography (β = 6.029 ± 2.967; p < 0.05) and ACEi/ARB therapy (β = 8.306 ± 3.161; p < 0.05) were associated with an increase in LVEF during follow-up. ConclusionThis study confirms the existence of long-term cardiac remodelling after KT despite dialysis cessation, characterised by an increase in LAVI and a decrease in LVEF. A better management of anaemia and using ACEi/ARB therapy may prevent such remodelling.

Immune monitoring of prevalent kidney transplant recipients using Torque Teno Virus: Protocol for a single-centre prospective cohort study

IntroductionKidney transplant recipients (KTRs) suffer from immunosuppression-related adverse events (iRAEs), such as infections and malignancy from chronic immunosuppression, but are also at risk of graft loss from rejection with underimmunosuppression....

A COVID-19 Overview from the Perspective of the Brazilian Kidney Transplantation Program

The Coronavirus disease 2019 (COVID-19) has significantly affected kidney transplantation activities around the world, thus resulting in a substantial decrease in both deceased and living transplants. This study presents a COVID-19 overview from the perspective of the Brazilian kidney transplant program by comparing its differences or similarities with the situations observed in other countries. During the first year of the pandemic, there was a 40% reduction in the number of kidney transplants worldwide. A similar scenario was observed in Brazil, which has the world’s largest public transplantation program. Beyond its effect on transplant activity, COVID-19 has influenced the outcomes of prevalent kidney transplant recipients (KTRs) because the prolonged use of immunosuppressive drugs and comorbidities increase the susceptibility of such patients to severe disease and death. In the pre-vaccination era, almost two-thirds of KTRs required hospitalization, more than 20% required dialysis, and one-third was admitted to the intensive care unit. In the pre-vaccination period in Brazil, 15% and 21% of KTRs died within 28 and 90 days of COVID-19 diagnosis, respectively. Although high vaccination coverage rates have altered the COVID-19 landscape in many populations, persistently low immunogenicity rates following sequential vaccination shots and the absence of targeted treatments for severe cases continue to classify KTRs as highly vulnerable, thus warranting significant concern.

Differences in medication adherence by sex and organ type among adolescent and young adult solid organ transplant recipients.

Identification of differences in medication adherence by sex or organ type may help in planning interventions to optimize outcomes. We compared immunosuppressive medication adherence between males and females, and between kidney, liver and heart transplant recipients. This multicenter study of prevalent kidney, liver and heart transplant recipients 14-25 years assessed adherence 3 times (0, 3, 6 months post-enrollment) with the BAASIS self-report tool. At each visit, participants were classified as adherent if they missed no doses in the prior 4 weeks and non-adherent otherwise. Adherence was also assessed using the coefficient of variation (CV) of tacrolimus trough levels; CV < 30% was classified as adherent. We used multivariable mixed effects logistic regression models adjusted for potential confounders to compare adherence by sex and by organ. Across all visits, males (n=150, median age 20.4 years, IQR 17.2-23.3) had lower odds of self-reported adherence than females (n=120, median age 19.8 years, IQR 17.1-22.7) (OR 0.41, 95% CI 0.21-0.80) but higher odds of adherence by tacrolimus CV (OR 2.50, 95% CI 1.30-4.82). No significant differences in adherence (by self-report or tacrolimus CV) were noted between the 184 kidney, 58 liver, and 28 heart recipients. Females show better self-reported adherence than males but greater variability in tacrolimus levels. Social desirability bias, more common in females than males, may contribute to better self-reported adherence among females. Higher tacrolimus variability among females may reflect biologic differences in tacrolimus metabolism between males and females rather than sex differences in adherence. There were no significant differences in adherence by organ type.

Humoral response after athird and fourth dose of mRNA-based SARS-CoV-2 vaccine in previously seronegative kidney transplant recipients.

Growing evidence shows diminished response to mRNA-based SARS-CoV‑2 vaccination in kidney transplant recipients. We aimed to investigate the seroconversion rate after a3rd and 4th dose of mRNA vaccination in kidney transplant recipients without prior antibody response to two or three vaccination doses.This retrospective study included 324 prevalent kidney transplant recipients of asingle tertiary transplantation center of which 157 remained seronegative, defined as anti-spike-RBD-IgG antibody titer < 7.1 BAU/ml, after two doses of mRNA-based SARS-CoV‑2 vaccination. Maintenance immunosuppression was not changed. The median patient age was 60.6 years (IQR 51.4-68.1 years), 66.9% were male. Positivity for anti-spike-RBD-IgG (≥ 7.1 BAU/ml) was measured 4-5weeks after administration of a3rd and 4th vaccine dose.Seroconversion rates were 63.9% after a3rd dose and 29.3% after a4th dose of vaccine. Cumulative prevalence of seropositivity was 51.5% after 2 doses, 80.5% after 3 doses and 84.2% after 4 doses.In conclusion, seroconversion can be achieved in the majority of the kidney transplant recipients by administrating three or four doses of mRNA vaccine without changing maintenance immunosuppression.

Care processes and structures associated with higher medication adherence in adolescent and young adult transplant recipients.

We aimed to identify care processes and structures that were independently associated with higher medication adherence among young transplant recipients. We conducted a prospective, observational cohort study of 270 prevalent kidney, liver, and heart transplant recipients 14-25years old. Patients were ≥3months post-transplant, ≥2months post-discharge, and followed in one of 14 pediatric or 14 adult transplant programs in Canada. Patients were enrolled between June 2015 and March 2018 and followed for 6months. Adherence was assessed at baseline, 3, and 6months using the BAASIS© self-report tool. Patients were classified as adherent if no doses were missed in the prior 4weeks. Transplant program directors and nurses completed questionnaires regarding care organization and processes. Of the 270 participants, 99 were followed in pediatric programs and 171 in adult programs. Median age was 20.3years, and median time since transplant was 5years. At baseline, 71.5% were adherent. Multivariable mixed effects logistic regression models with program as a random effect identified two program-level factors as independently associated with better adherence: minimum number of prescribed blood draws per year for those >3years post-transplant (per 1 additional) (OR 1.12 [95% CI 1.00, 1.26]; p=.047), and average time nurses spend with patients in clinic (per 5 additional minutes) (OR 1.15 [1.03, 1.29]; p=.017). Program-level factors including protocols with a greater frequency of routine blood testing and more nurse time with patients were associated with better medication adherence. This suggests that interventions at the program level may support better adherence.

Association between serum osteoprotegerin level and mortality in kidney transplant recipients - a prospective observational cohort study.

Paradoxically, higher serum levels of osteoprotegerin (OPG: a vascular calcification inhibitor) have been associated with increased arterial stiffness, risk of cardiovascular disease and all-cause mortality. A few studies reported that post-transplant OPG levels are associated with mortality in kidney transplant (KT) recipients. In this study, this association was assessed in a cohort of prevalent KT recipients, adjusting for previously untested potential confounders, including fibroblast growth factor 23 (FGF23) and interleukin 6 (IL-6). Socio-demographic and clinical parameters, medical and transplant history, and laboratory data were collected from 982 prevalent KT recipients. The association between serum OPG and all-cause mortality over a 6-year follow-up period was examined using Kaplan-Meier survival curves and multivariable-adjusted Cox regression models. Participants with high serum OPG were more likely female, older, deceased donor KT recipients and have more comorbidity, lower eGFR, higher FGF23, higher IL-6, and longer dialysis vintage. Each 1pmol/l higher serum OPG level was associated with a 49% higher risk of mortality (hazard ratio (HR) [95% confidence interval (CI)]: 1.49 [1.40-1.61]). This association persisted after adjusting for confounders (HR [95% CI]: 1.20 [1.10-1.30]). In conclusion, serum OPG was associated with all-cause mortality independent of several novel confounders in prevalent KT recipients.

Impact of Timely Public Health Measures on Kidney Transplantation in Austria during the SARS-CoV-2 Outbreak-A Nationwide Analysis.

SARS-CoV-2 led to considerable morbidity/mortality worldwide and tremendously impacted on daily life. Strict lockdown measures were implemented early to contain the viral outbreak in Austria. Massive changes in organizational structures of healthcare facilities followed with unclear implications on the care of non-COVID-19-affected patients. We studied the nationwide impact of COVID-19 on kidney transplantation in Austria during the first six months of 2020. Concurrent with general lockdown measures, all kidney transplant activity was suspended from 13 March to 9 April. Nevertheless, between January and June, total transplant (p = 0.48) and procured donor organ numbers (p = 0.6) did not differ significantly from earlier years. Ten (0.18%) of 5512 prevalent Austrian kidney transplant recipients were diagnosed with SARS-CoV-2. The case fatality rate (one death; 10%) in renal transplant patients was less than in other countries but higher than in Austria’s general population (2.4%). We conclude that early and strict general lockdown measures imposed by the government allowed an early, however cautious, re-opening of Austrian transplant programs and played a crucial role for the favorable outcomes of SARS-CoV-2 in Austrian kidney transplant patients. Even though it may be uncertain whether similar results may be obtainable in other countries, the findings may support early intervention strategies during similar episodes in the future.

P1655HYPERKALAEMIA IN PREVALENT KIDNEY TRANSPLANT RECIPIENTS

Abstract Background and Aims Hyperkalaemia is a common and life-threatening medical emergency present in up to 10% of acute hospital admissions. End-stage Kidney Disease (ESKD) patients undergoing transplantation are at increased risk of hyperkalaemia, a potentially life-threatening medical emergency. Although the prevalence of hyperkalaemia in ESKD is well described, few studies have assessed the incidence and associations of hyperkalaemia in kidney transplant recipients. We evaluated post-transplant hyperkalaemia in a single centre using a large electronic health record dataset of emergency admissions. Methods Prevalent kidney transplant recipients were identified using ICD-10 codes from a complete Electronic Health Records database of all emergency admissions to Addenbrooke’s Hospital, Cambridge between April 2015 and August 2018. We abstracted demographics, comorbidities, concomitant medications, biochemistry results including all blood potassium values, in-hospital prescribing and admission and discharge dates. Data were summarised as frequency (%), mean± standard deviation (SD) or median with interquartile range (IQR) as appropriate. Categorical variables were compared by Chi-squared test and continuous variables by Student's t-test or Mann–Whitney U-test based on their distribution. Factors associated with developing hyperkalaemia were explored using mixed-effects logistic regression and odds ratios (OR) are reported. Results 421 prevalent kidney transplant recipients were admitted a total of 1,065 times via the Emergency Department and a further 475 times direct to the Transplant ward. 324 (77%) were deceased-donor recipients with 83 (20%) living-donor recipients and 14 (3%) simultaneous pancreas kidney (SPK) recipients. Median age of admitted recipients was 56 (IQR 44-65) years and 87% were of white ethnic origin. Mean serum potassium was 4.56±0.72 mmol/L compared to 4.21±0.61 mmol/L amongst the 170,913 non-kidney transplant patients admitted over the same time period (p&amp;lt;0.001). 376 (89%) recipients were prescribed a calcineurin inhibitor. Hyperkalaemia &amp;gt;5.5mmol/L occurred in 282 (67%) of 421 prevalent kidney transplant recipients with 203 (48%) patients including all SPK recipients experiencing moderate-severe hyperkalaemia (K &amp;gt;=6.0mmol/L). Of these, 110 (39%) received emergency treatment with insulin/dextrose. Potassium concentration immediately (≤ 60 min) pre-treatment was 6.26±0.76 mmol/L. The mean reduction in potassium at 4-hours post treatment was 0.89±0.90 mmol/L. Twenty-five of 110 (23%) patients developed hypoglycaemia (glucose &amp;lt;4mmol/L) within 6 hours of treatment and 37/110 (34%) required retreatment with insulin/dextrose within 24 hours. Kidney transplant recipients were at significantly increased risk of developing hyperkalaemia (OR 19.8, 95% Confidence Interval (CI) 16.2-24.4, p&amp;lt;0.001) compared with all admitted patients and this risk persisted after adjustment for age, sex and co-morbidity (OR 3.6, 2.9-4.5, p&amp;lt;0.001). Associations with hyperkalaemia amongst transplant recipients included receiving a deceased-donor kidney (OR 1.96, 1.13-3.40, p=0.017) and exposure to beta-blockers (OR 2.26, 1.36-3.59, p=0.001) and calcineurin inhibitors (OR 6.39, 2.81-14.5, p&amp;lt;0.001). Conclusion Kidney transplant recipients are at greatly increased risk of developing hyperkalaemia. Recipients who become hyperkalaemic are more likely to have received a deceased-donor transplant and be prescribed beta-blockers and calcineurin inhibitors than those who do not. Insulin/dextrose for hyperkalaemia is associated with hypoglycaemia in almost 1 in 4 recipients treated and re-treatment is required in one third of recipients.

P1666ASSOCIATION OF TACROLIMUS TROUGH LEVEL AND DAILY DOSE RATIO WITH OUTCOMES IN A PROSPECTIVE PREVALENT COHORT OF KIDNEY TRANSPLANT RECIPIENTS

Abstract Background and Aims Tacrolimus is an integral part of the immunosuppressive regimen after solid organ transplantation. Due to its narrow therapeutic window, it requires frequent serum trough level (C0) monitoring and dose adjustment. Both over-and under treatment may have harmful effects regarding overall mortality and graft survival due to increased risk of cardiovascular diseases, malignancies, new onset diabetes and rejection. C0 and total daily dose ratio (CD) has recently been suggested as a potential predictor of worse graft outcome in the early period after transplantation, however, long term prospective studies are lacking. We hypothesized the association between lower CD ratio and increased risk of death with functioning graft (DWFG), graft loss (GL) and overall death (D) in our prospective cohort study. Method Our study included 386 prevalent kidney transplant recipients (205(53%) males, median and IQR age of 47.5 (13.2) years, eGFR 53.5 (22.5) ml/min/1.73m2, time since last transplant 51 (26-79) months) out of a total of 993 enrolled between 2006-2007. Sociodemographic, past medical history, clinical and laboratory data were collected and CD was recorded at baseline and 1 year after the enrollment. The associations between CD and CD2 ratios and above mentioned outcomes were examined using survival models.. Results The median and IQR of CD was 2.1(1.4-3.2) at baseline and 2.0 (1.3-3.0) 1 year later (CD2). There was 46 (11.9%) DWFG, 79 (20.5%) GL and 68 (17.6%) D, respectively. After adjustment for important confounders (age, gender, eGFR, Charlson score, dialysis duration, donor age, rejection), neither CD (DWGL: HR 0.56(0.30-1.03) p=0.06; GL: HR 0.82(0.50-1.36) p=0.46; D: HR 0.79(0.48-1.32) p=0.38) nor CD2 (DWGL: HR 1.12(0.54-2.31) p=0.74; GL: HR 0.76(0.61-1.97) p=0.78; D: HR 1.19(0.64-2.20) p=0.59) found to be predictors of the outcomes. Conclusion CD ratio was not associated with increased risk of death with functioning graft, graft loss or overall death in our prevalent kidney transplant recipients.

MO011A RANDOMISED, DOUBLE-BLIND, PLACEBO-CONTROLLED TRIAL OF VITAMIN K SUPPLEMENTATION TO IMPROVE VASCULAR HEALTH IN KIDNEY TRANSPLANT RECIPIENTS

Abstract Background and Aims Vascular stiffness (VS) and calcification (VC) are markers of cardiovascular disease which are prevalent in kidney transplant recipients (KTR) and associated with subclinical vitamin K deficiency. We tested the hypothesis that vitamin K supplementation would reduce VS and VC in prevalent KTR in the Vitamin K for kidney Transplant Organ Recipients: Investigating vEssel Stiffness (ViKTORIES) trial. Method In a single-centre, phase II, parallel-group, randomised, double-blind, placebo-controlled trial (ISRCTN22012044), KTR were randomised 1:1 to vitamin K (menadiol diphosphate 5mg) or placebo thrice weekly for one year. The primary outcome was between-group difference in VS (ascending aortic distensibility by cardiac magnetic resonance imaging) at 1 year by ANCOVA adjusted for the baseline value, age and duration of end-stage kidney disease. Secondary outcomes included VC (coronary artery calcium score on non-contrast computed tomography), cardiac structure and function (on cardiac magnetic resonance imaging), blood pressure, eGFR, proteinuria and quality of life. All outcomes were assessed by intention-to-treat with secondary per-protocol analyses. Missing data were multiply imputed as a sensitivity analysis for the main outcomes. The trial was conducted in accordance with the Declaration of Helsinki and was approved by the West of Scotland Research Ethics Committee 4 (Ref: 17/WS/0101). The results were combined in a meta-analysis with other published data. Results Ninety participants were randomised to vitamin K (n=45) or placebo (n=45) and included in the analysis. Baseline demographics, clinical history and immunosuppression regimens were similar between groups: mean age 57.6 ± 9.6 years, 70% male, with median time after transplantation 7.8 (IQR 3.5 - 13.9) years. There was no impact of vitamin K versus placebo on VS after 12 months (-0.2 (-0.5 - 0.2) vs. -0.3 (-0.6 - 0.1) x10-3 mmHg-1; p=0.60), nor on VC (184 (52 - 315) vs 44 (-89 - 177) units; p=0.11), nor on any other outcome measure. Medication adherence was very good in both groups (90 vs. 95%; p=0.58). Achieved power was 85%. Serious adverse events were common (vitamin K: 26.7 vs. placebo: 60.0%): all serious adverse events were classified as expected. Multiple imputation of missing data had no impact on results of VS or VC outcomes. Combining these with other published results, vitamin K supplementation has no significant observed effect on VS or VC, though with few available studies for analysis. Conclusion In this heterogeneous cohort of prevalent KTR, vitamin K supplementation did not reduce VS or VC over 1 year. Improving vascular health in patients with established kidney disease is likely to require a multifaceted approach.

The Role of Telemedicine in Kidney Transplantation: Opportunities and Challenges.

Kidney transplantation is the treatment of choice for patients with advanced kidney disease who are medically and surgically fit to undergo the procedure and have reasonable life expectancy. It provides improved survival and quality of life for recipients and overall cost savings to the health care system (1,2). The process of undergoing kidney transplantation involves several phases of care including pretransplant referral and evaluation, waitlist management, and follow-up. In all phases of care, transplant centers interface with candidates and recipients who live across a wide geographic range, with many patients traveling significant distances to a transplant center (3). In the United States, 41,077 candidates were added to the waiting list in 2019 and 23,401 received a transplant. There are approximately 220,000 prevalent kidney transplant recipients and 250 centers actively performing kidney transplants (4). With this continually growing patient population and a limited number of transplant providers, transplant centers are in need of innovative models of health care delivery that ( 1 ) allow them to reach and monitor candidates and recipients, particularly those that live far away; and ( 2 ) improve utilization of transplant center resources. Telemedicine, the practice of medicine using technology to deliver care at a distance, represents an opportunity to do both. The technology used may include telehealth videoconferencing (TVC), the internet, store-and-forward imaging, streaming media, and terrestrial and wireless communication (5). Although telemedicine has been successfully used by numerous specialties, its utilization in the field of kidney transplantation has been lagging. Telemedicine has the potential to affect and improve the delivery of kidney transplant care through the following: ( 1 ) replacing or supplementing in-person visits with virtual visits through TVC, ( 2 ) electronic consultation, and ( 3 ) remote monitoring and provision of education through mobile technology (6). Here we focus on TVC and highlight opportunities for its use …

Eliminating Hepatitis C Virus From a Prevalent Kidney Transplant Recipient Population: A Single-Center Study in Belgium in the Direct-Acting Antivirals Era

BackgroundDirect-acting antivirals (DAAs) have revolutionized the treatment of hepatitis C virus (HCV) infection. Although previous studies have reported positive results with DAAs after kidney transplantation (KT), their impact on the prevalence of HCV viremia (HCVv) in prevalent kidney transplant recipients (KTRs) remains ill defined. MethodsWe retrospectively reviewed the HCV status of all patients followed at Cliniques Universitaires Saint-Luc, Brussels, Belgium, outpatient KT clinic between January 2014 and December 2018. We collected the clinical features of KTRs treated with DAAs during this period and calculated the annual prevalence of HCVv over this period. ResultsOut of 1451 KTRs, 22 (1.52%) had HCVv in 2014 to 2018. From 2014 to 2018, the annual prevalence of HCVv dropped from 1.97% to 0.43%, (P < .001). Fourteen KTRs were treated with DAAs a median of 197 months (range: 5-374) after KT, mostly (79%) in 2017 after reimbursement restrictions of DAAs for KTRs in Belgium were removed. DAA treatment was safe with a sustained virological response rate at 12 weeks after treatment (SVR12) of 93%. Two patients died 14 months (lymphoma, despite SVR12) and 7 months (hepatocarcinoma, no SVR12) after DAAs initiation, respectively. Among HCVv KTRs not treated with DAAs (n = 8), 2 lost their graft, 5 died, and 1 is initiating therapy. The current prevalence of HCVv in the cohort is 0.08%, with a single patient currently on treatment. ConclusionTreatment with DAAs led to a dramatic decrease of HCVv prevalence in this KTR cohort. DAA use was safe and effective. Elimination of HCV is possible at KT clinics.

The Associations of Muscle Strength, Muscle Mass, and Adiposity With Clinical Outcomes and Quality of Life in Prevalent Kidney Transplant Recipients

Sarcopenia, defined as loss of both muscle strength and mass, is associated with inferior clinical outcomes and quality of life (QoL) in chronic kidney disease, but its effects are unknown in kidney transplantation. Obesity confers increased mortality risk and compromises QoL in kidney transplant recipients (KTRs), but the impacts of sarcopenic obesity remain unexplored. This study aimed to evaluate the associations of muscle strength and mass, sarcopenia, and sarcopenic obesity with clinical outcomes and QoL in KTRs. This prospective longitudinal study enrolled 128 KTRs ≥1-year posttransplantation. Low muscle strength (by handgrip strength) and mass (by bioimpedance analysis), and a combination of both (sarcopenia) were defined as<reference cutoffs for corresponding indices. Sarcopenic obesity was defined as sarcopenia combined with fulfillment of ≥2 out of 3 criteria from (1) body mass index ≥30kg/m2, (2) bioimpedance analysis-derived fat mass>reference cutoffs, and (3) waist circumference>World Health Organization cutoffs. Prospective follow-up data on mortality and hospitalization were collected. QoL was evaluated using Medical Outcomes Study Short Form-36 questionnaire. Median follow-up duration was 64 (60-72) months. Low muscle strength was independently associated with the composite endpoint of mortality and hospitalization (hazard ratio=2.45; P=.006), and QoL (physical-related: β=-12.2; P=.04; mental-related: β=-9.9; P=.04). Low muscle mass (β=-8.8; P=.04) and sarcopenia (β=-14.7; P=.03) were associated with physical-related QoL only. No independent associations were found between muscle mass, sarcopenia, and sarcopenic obesity with the composite outcome of mortality and hospitalization. Low muscle strength is common among KTRs, conferring poor prognosis in the medium term. Future research on strength training may prove valuable in improving kidney transplantation outcomes.

The Effects of 12-months of Denosumab on Bone Density in Prevalent Kidney Transplant Recipients

The Effects of 12-months of Denosumab on Bone Density in Prevalent Kidney Transplant Recipients

Association Between Serum Prealbumin Level and Outcomes in Prevalent Kidney Transplant Recipients

Prealbumin, a transport protein mostly synthesized in the liver, is a marker of nutrition. Although decreased prealbumin levels are associated with increased mortality in end-stage kidney disease patients, its association with mortality in kidney transplant recipients remains unknown. We evaluated the association between prealbumin levels and outcomes in kidney transplant recipients. This was a prospective prevalent cohort study. This study included 991 kidney transplant recipients enrolled from December 31, 2006, to December 31, 2007, and followed over a 6-year period. Sociodemographic, past medical history, clinical, and laboratory data were collected at the study entry. Associations between prealbumin levels and death with functioning graft, all-cause mortality, and graft loss were examined using survival models. Serum prealbumin levels showed significant negative correlation with estimated glomerular filtration rate (R=-0.28; P<.001) and high-sensitive C-reactive protein (R=-0.24; P<.001). Each 5mg/dL lower serum prealbumin level was associated with 20% higher risk of death with functioning graft (subdistribution hazard ratio [95% confidence interval]: 1.20 [1.08-1.35]; P=.001), which persisted after multivariable adjustments (subdistribution hazard ratio [95% confidence interval]: 1.13 [1.00-1.28]; P=.039). Qualitatively similar trend was observed in all-cause mortality; however, there was no association between prealbumin levels and graft loss. Lower serum prealbumin level is associated with increased risk of death with functioning graft in prevalent kidney transplant recipients.

Development and validation of PART (Pharmacotherapy Assessment in Renal Transplant Patients) criteria to assess drug-related problems in an outpatient renal transplant population: A cross-sectional study.

Kidney transplant recipients are at risk of pharmacological interactions and adverse drug reactions. Community pharmacists are uniquely poised to detect and intervene in cases of drug‐related problems. The aims of this study were to develop and validate a list of explicit criteria to be used by community pharmacists to assess drug‐related problems in kidney transplant patients, and to assess their frequency and their determinants. First, we used a modified RAND method where a panel of experts established the PART (Pharmacotherapy Assessment in Renal Transplant Patient) criteria. Then, we performed a cross‐sectional study in which we applied the PART criteria to 97 prevalent kidney transplant recipients followed at a single university‐affiliated center. The final list of PART criteria included 70 drug‐related problems and was reliable (kappa: 0.88). An average of 1.2 drug‐related problems per patient was detected when the PART criteria were applied, with 68% of patients having at least 1 problem. This figure was 1.4 per patient using the expert judgment of renal transplant pharmacists who had no access to the PART list. The total number of medications taken was the only factor associated with the number of drug‐related problems (β: 0.27 for an increase of five medications, 95% CI 0.005, 0.547). The PART criteria provide a novel tool for community pharmacists to systematically detect drug‐related problems in kidney transplant recipients.

Association between malnutrition-inflammation score and risk of subsequent self-reported bone fractures in prevalent kidney transplant recipients.

Kidney transplant recipients (KTR) have a 4-fold higher risk of fracture compared to the general population. Chronic inflammation and PEW syndrome are common in KTR and are associated with poor outcomes. We hypothesized that the Malnutrition-Inflammation Score (MIS), a validated measure of PEW, is associated with higher risk of bone fractures in KTR. This prospective cohort study included 839 prevalent KTR from a Central European academic center. MIS, a semiquantitative instrument of PEW, was calculated at the study entry. Self-reported history of fractures was recorded during the 2-year follow-up period. The association between MIS and bone fractures was examined in logistic regression analyses with adjustment for age, gender, eGFR, smoking habits, history of pre-transplant bone fractures, and acute rejection. Mean age was 51 ± 13years, and 56% of patients were males with median (interquartile range) transplant vintage 69 (38-112)months, estimated glomerular filtration rate 55 ± 21ml/min/1.73m2, and calculated MIS 3 (2-4) at enrollment. Fifty-five (7%) patients experienced self-reported bone fractures during the 2-year follow-up period. Higher MIS score showed linear association with increased risk of fracture. Each one-point higher MIS was associated with 23% higher risk of bone fractures (odds ratio (OR) and 95% CI 1.23, 1.12-1.34), which remained significant after multivariable adjustments (OR 1.17, 95% CI 1.06-1.29). The MIS is independently associated with new clinically detected bone fractures in prevalent KTR.

A Randomized Trial of a Multicomponent Intervention to Promote Medication Adherence: The Teen Adherence in Kidney Transplant Effectiveness of Intervention Trial (TAKE-IT)

Poor adherence to immunosuppressive medications is a major cause of premature graft loss among children and young adults. Multicomponent interventions have shown promise but have not been fully evaluated. Unblinded parallel-arm randomized trial to assess the efficacy of a clinic-based adherence-promoting intervention. Prevalent kidney transplant recipients 11 to 24 years of age and 3 or more months posttransplantation at 8 kidney transplantation centers in Canada and the United States (February 2012 to May 2016) were included. Adherence was electronically monitored in all participants during a 3-month run-in, followed by a 12-month intervention. Participants assigned to the TAKE-IT intervention could choose to receive text message, e-mail, and/or visual cue dose reminders and met with a coach at 3-month intervals when adherence data from the prior 3 months were reviewed with the participant. "Action-Focused Problem Solving" was used to address adherence barriers selected as important by the participant. Participants assigned to the control group met with coaches at 3-month intervals but received no feedback about adherence data. The primary outcomes were electronically measured "taking" adherence (the proportion of prescribed doses of immunosuppressive medications taken) and "timing" adherence (the proportion of doses of immunosuppressive medications taken between 1 hour before and 2 hours after the prescribed time of administration) on each day of observation. Secondary outcomes included the standard deviation of tacrolimus trough concentrations, self-reported adherence, acute rejection, and graft failure. 81 patients were assigned to intervention (median age, 15.5 years; 57% male) and 88 to the control group (median age, 15.8 years; 61% male). Electronic adherence data were available for 64 intervention and 74 control participants. Participants in the intervention group had significantly greater odds of taking prescribed medications (OR, 1.66; 95% CI, 1.15-2.39) and taking medications at or near the prescribed time (OR, 1.74; 95% CI, 1.21-2.50) than controls. Lack of electronic adherence data for some participants may have introduced bias. There was low statistical power for clinical outcomes. The multicomponent TAKE-IT intervention resulted in significantly better medication adherence than the control condition. Better medication adherence may result in improved graft outcomes, but this will need to be demonstrated in larger studies. Registered at ClinicalTrials.gov with study number NCT01356277.