Transplant Outcome Measures Research Articles

Propensity Score and Instrumental Variable Techniques in Observational Transplantation Studies: An Overview and Worked Example Relating to Pre-Transplant Cardiac Screening.

Inferring causality from observational studies is difficult due to inherent differences in patient characteristics between treated and untreated groups. The randomised controlled trial is the gold standard study design as the random allocation of individuals to treatment and control arms should result in an equal distribution of known and unknown prognostic factors at baseline. However, it is not always ethically or practically possible to perform such a study in the field of transplantation. Propensity score and instrumental variable techniques have theoretical advantages over conventional multivariable regression methods and are increasingly being used within observational studies to reduce the risk of confounding bias. An understanding of these techniques is required to critically appraise the literature. We provide an overview of propensity score and instrumental variable techniques for transplant clinicians, describing their principles, assumptions, strengths, and weaknesses. We discuss the different patient populations included in analyses and how to interpret results. We illustrate these points using data from the Access to Transplant and Transplant Outcome Measures study examining the association between pre-transplant cardiac screening in kidney transplant recipients and post-transplant cardiac events.

Changes in quality of life (QoL) and other patient-reported outcome measures (PROMs) in living-donor and deceased-donor kidney transplant recipients and those awaiting transplantation in the UK ATTOM programme: a longitudinal cohort questionnaire survey with additional qualitative interviews

ObjectiveTo examine quality of life (QoL) and other patient-reported outcome measures (PROMs) in kidney transplant recipients and those awaiting transplantation.DesignLongitudinal cohort questionnaire surveys and qualitative semi-structured interviews using thematic analysis...

Do routine hospital data accurately record comorbidity in advanced kidney disease populations? A record linkage cohort study

BackgroundRoutine healthcare datasets capturing clinical and administrative information are increasingly being used to examine health outcomes. The accuracy of such data is not clearly defined. We examine the accuracy of diagnosis recording in individuals with advanced chronic kidney disease using a routine healthcare dataset in England with comparison to information collected by trained research nurses.MethodsWe linked records from the Access to Transplant and Transplant Outcome Measures study to the Hospital Episode Statistics dataset. International Classification of Diseases (ICD-10) and Office for Population Censuses and Surveys Classification of Interventions and Procedures (OPCS-4) codes were used to identify medical conditions from hospital data. The sensitivity, specificity, positive and negative predictive values were calculated for a range of diagnoses.ResultsComorbidity information was available in 96% of individuals prior to starting kidney replacement therapy. There was variation in the accuracy of individual medical conditions identified from the routine healthcare dataset. Sensitivity and positive predictive values ranged from 97.7 and 90.4% for diabetes and 82.6 and 82.9% for ischaemic heart disease to 44.2 and 28.4% for liver disease.ConclusionsRoutine healthcare datasets accurately capture certain conditions in an advanced chronic kidney disease population. They have potential for use within clinical and epidemiological research studies but are unlikely to be sufficient as a single resource for identifying a full spectrum of comorbidities.

A propensity score–matched analysis indicates screening for asymptomatic coronary artery disease does not predict cardiac events in kidney transplant recipients

Screening for asymptomatic coronary artery disease prior to kidney transplantation aims to reduce peri- and post-operative cardiac events. It is uncertain if this is achieved. Here, we investigated whether pre-transplant screening with a stress test or coronary angiogram associated with any difference in major adverse cardiac events (MACE) up to five years post-transplantation. We examined a national prospective cohort recruited to the Access to Transplant and Transplant Outcome Measures study who received a kidney transplant between 2011-2017, and linked patient demographics and details of cardiac screening investigations to outcome data extracted from the Hospital Episode Statistics dataset and United Kingdom Renal Registry. Propensity score matched groups were analyzed using Kaplan-Meier and Cox survival analyses. Overall, 2572 individuals were transplanted in 18 centers; 51% underwent screening and the proportion undergoing screening by center ranged from 5-100%. The incidence of MACE at 90 days, one and five years was 0.9%, 2.1% and 9.4% respectively. After propensity score matching based on the presence or absence of screening, 1760 individuals were examined (880 each in screened and unscreened groups). There was no statistically significant association between screening and MACE at 90 days (hazard ratio 0.80, 95% Confidence Interval 0.31-2.05), one year (1.12, 0.51-2.47) or five years (1.31, 0.86-1.99). Age, male sex and history of ischemic heart disease were associated with MACE. Thus, there is no association between screening for asymptomatic coronary artery disease and MACE up to five years post-transplant. Practices involving unselected screening of transplant recipients should be reviewed.

Changes in quality of life, health status and other patient-reported outcomes following simultaneous pancreas and kidney transplantation (SPKT): a quantitative and qualitative analysis within a UK-wide programme.

We examined quality of life (QoL) and other patient-reported outcome measures (PROMs) in 95 simultaneous pancreas and kidney transplant (SPKT) recipients and 41 patients wait-listed for SPKT recruited to the UK Access to Transplantation and Transplant Outcome Measures (ATTOM) programme. Wait-listed patients transplanted within 12months of recruitment (n=22) were followed 12months post-transplant and compared with those still wait-listed (n=19) to examine pre- to post-transplant changes. Qualitative interviews with ten SPKT recipients 12months post-transplant were analysed thematically. Cross-sectional analyses showed several better 12-month outcomes for SPKT recipients compared with those still wait-listed, a trend to better health utilities but no difference in diabetes-specific QoL or diabetes treatment satisfaction. Pre- to post-transplant, SPKT recipients showed improved treatment satisfaction, well-being, self-reported health, generic QoL and less negative impact on renal-specific QoL (ps<0.05). Health utility values were better overall in transplant recipients and neither these nor diabetes-specific QoL changed significantly in either group. Pre-emptive transplant advantages seen in 12-month cross-sectional analyses disappeared when controlling for baseline values. Qualitative findings indicated diabetes complications, self-imposed blood glucose monitoring and dietary restrictions continued to impact QoL negatively post-transplant. Unrealistic expectations of SPKT caused some disappointment. Measuring condition-specific PROMs over time will help in demonstrating the benefits and limitations of SPKT.

Recipient Comorbidity and Survival Outcomes After Kidney Transplantation: A UK-wide Prospective Cohort Study.

Comorbidity is increasingly common in kidney transplant recipients, yet the implications for transplant outcomes are not fully understood. We analyzed the relationship between recipient comorbidity and survival outcomes in a UK-wide prospective cohort study-Access to Transplantation and Transplant Outcome Measures (ATTOM). A total of 2100 adult kidney transplant recipients were recruited from all 23 UK transplant centers between 2011 and 2013. Data on 15 comorbidities were collected at the time of transplantation. Multivariable Cox regression models were used to analyze the relationship between comorbidity and 2-year graft survival, patient survival, and transplant survival (earliest of graft failure or patient death) for deceased-donor kidney transplant (DDKT) recipients (n = 1288) and living-donor kidney transplant (LDKT) recipients (n = 812). For DDKT recipients, peripheral vascular disease (hazard ratio [HR] 3.04, 95% confidence interval [CI]: 1.37-6.74; P = 0.006) and obesity (HR 2.27, 95% CI: 1.27-4.06; P = 0.006) were independent risk factors for graft loss, while heart failure (HR 3.77, 95% CI: 1.79-7.95; P = 0.0005), cerebrovascular disease (HR 3.45, 95% CI: 1.72-6.92; P = 0.0005), and chronic liver disease (HR 4.36, 95% CI: 1.29-14.71; P = 0.018) were associated with an increased risk of mortality. For LDKT recipients, heart failure (HR 3.83, 95% CI: 1.15-12.81; P = 0.029) and diabetes (HR 2.23, 95% CI: 1.03-4.81; P = 0.042) were associated with poorer transplant survival. The key comorbidities that predict poorer 2-year survival outcomes after kidney transplantation have been identified in this large prospective cohort study. The findings will facilitate assessment of individual patient risks and evidence-based decision making.

P1660ACCESS TO KIDNEY TRANSPLANTATION IN THE UK CHINESE POPULATION: A UK RENAL REGISTRY ANALYSIS

Abstract Background and Aims Previous UK Renal Registry (UKRR) analyses and the Access to Transplantation and Transplant Outcome Measures (ATTOM) study have shown ethnic disparity in access to kidney transplants in the UK, but access to transplantation for the UK Chinese population has not been investigated In this UKRR analysis, we compared the likelihood of kidney transplantation between the UK White and UK Chinese renal populations, aiming to investigate whether there was evidence of ethnic disparity in access to kidney transplantation for this specific ethnic group. Method Data on all adult patients &amp;gt;=18 years who started renal replacement therapy (RRT) between 1/1/97 and 31/12/16 were extracted from the UKRR. Patients with ethnicity recorded as anything other than “Chinese” or “White” were excluded from analysis. Patients with ethnicity data missing were also excluded. Patients aged &amp;gt;= 75 years at the start of RRT were excluded because of the high prevalence of comorbidity which decreases the likelihood of transplantation and the very small proportion of patients receiving a kidney transplant in the UK in this age group. Socioeconomic status (SES) was measured using country-specific Index of Multiple Deprivation (IMD) quintiles derived from patient postcodes (1= most deprived, 5= least deprived). The independent variable of interest was Chinese ethnicity (Chinese vs White). Multivariable logistic regression models were used to investigate the relationship between Chinese ethnicity and being listed on the deceased donor transplant waiting list i) at start of RRT ii) 2 years after start of RRT iii) pre-emptive kidney transplantation, iv) kidney transplantation at 3 years after start of RRT, and v) living-donor kidney transplantation. The models were run unadjusted and then adjusted for the confounders, specified a priori, age, sex, primary renal disease and SES. Odds ratios (ORs) with 95% confidence intervals (CIs) were calculated using robust standard errors to account for clustering by renal centre. Results The dataset comprised of 92,857 incident RRT patients. 0.5% (n=501) were of Chinese ethnicity, 76% (n=70,575) were White. The findings of the multivariable logistic regression analyses are presented in Table 1. Even after adjustment for potential confounders UK Chinese patients had lower odds of being waitlisted at the start of RRT (OR 0.71, [95% CI 0.54-0.94]) but were more likely to be waitlisted at 2 years (OR 1.28, [95% CI 1.02-1.61]) compared to White patients. UK Chinese individuals were also less likely to receive a pre-emptive kidney transplant (OR 0.47, [95% CI 0.29-0.78]), less likely to be transplanted within 3 years of starting RRT (OR 0.69, [95% CI 0.52-0.92]) or have a living-donor kidney transplant(LDKT) (OR 0.39, [95% CI 0.26-0.59]) compared to White patients. Conclusion This is the first study that has shown that UK Chinese renal patients are less likely to have the opportunity to receive a living or deceased kidney transplant. Future research needs to test whether later presentation or more rapid progression of renal disease could explain these observations. The higher odds of transplant listing at 2 years suggests fitness for transplantation is not a significant barrier. The reasons why this ethnic group are less likely to receive a LDKT is also not well understood. Understanding whether these disparities reflect modifiable policy, health system or donor/recipient level barriers will help ensure equitable access to transplantation.

Inequity in Access to Transplantation in the United Kingdom.

Despite the presence of a universal health care system, it is unclear if there is intercenter variation in access to kidney transplantation in the United Kingdom. This study aims to assess whether equity exists in access to kidney transplantation in the United Kingdom after adjustment for patient-specific factors and center practice patterns. In this prospective, observational cohort study including all 71 United Kingdom kidney centers, incident RRT patients recruited between November 2011 and March 2013 as part of the Access to Transplantation and Transplant Outcome Measures study were analyzed to assess preemptive listing (n=2676) and listing within 2 years of starting dialysis (n=1970) by center. Seven hundred and six participants (26%) were listed preemptively, whereas 585 (30%) were listed within 2 years of commencing dialysis. The interquartile range across centers was 6%-33% for preemptive listing and 25%-40% for listing after starting dialysis. Patient factors, including increasing age, most comorbidities, body mass index >35 kg/m2, and lower socioeconomic status, were associated with a lower likelihood of being listed and accounted for 89% and 97% of measured intercenter variation for preemptive listing and listing within 2 years of starting dialysis, respectively. Asian (odds ratio, 0.49; 95% confidence interval, 0.33 to 0.72) and Black (odds ratio, 0.43; 95% confidence interval, 0.26 to 0.71) participants were both associated with reduced access to preemptive listing; however Asian participants were associated with a higher likelihood of being listed after starting dialysis (odds ratio, 1.42; 95% confidence interval, 1.12 to 1.79). As for center factors, being registered at a transplanting center (odds ratio, 3.1; 95% confidence interval, 2.36 to 4.07) and a universal approach to discussing transplantation (odds ratio, 1.4; 95% confidence interval, 1.08 to 1.78) were associated with higher preemptive listing, whereas using a written protocol was associated negatively with listing within 2 years of starting dialysis (odds ratio, 0.7; 95% confidence interval, 0.58 to 0.9). Patient case mix accounts for most of the intercenter variation seen in access to transplantation in the United Kingdom, with practice patterns also contributing some variation. Socioeconomic inequity exists despite having a universal health care system.

Assessing Consensus Between UK Renal Clinicians on Listing for Kidney Transplantation: A Modified Delphi Study.

It is well recognized that there is significant variation between centers in access to kidney transplantation. In the absence of high-grade evidence, it is unclear whether variation is due to patient case mix, other center factors, or individual clinician decisions. This study sought consensus between UK clinicians on factors that should influence access to kidney transplantation. As part of the Access to Transplantation and Transplant Outcome Measures project, consultant nephrologists and transplant surgeons in 71 centers were invited to participate in a Delphi study involving 2 rounds. During rounds 1 and 2, participants rated their agreement to 29 statements covering 8 topics regarding kidney transplantation. A stakeholder meeting was used to discuss statements of interest after the 2 rounds. In total, 122 nephrologists and 16 transplant surgeons from 45 units participated in rounds 1 and 2. After 2 rounds, 12 of 29 statements reached consensus. Fifty people participated in the stakeholder meeting. After the stakeholder meeting, a further 4 statements reached agreement. Of the 8 topics covered, consensus was reached in 6: use of a transplant protocol, patient age, body mass index, patient compliance with treatment, cardiac workup, and use of multidisciplinary meetings. Consensus was not reached on screening for malignancy and use of peripheral Doppler studies. The Delphi process identified factors upon which clinicians agreed and areas where consensus could not be achieved. The findings should inform national guidelines to support decision making in the absence of high quality evidence and to guide areas that warrant future research.

Education, health literacy, and inequity in access to transplantation: findings from the ATTOM cohort study

BackgroundThe optimal treatment for most people with kidney failure is kidney transplantation, but donor organs are limited. The pathway to living-donor or deceased-donor kidney transplantation entails multiple clinician–patient interactions, likely to require adequate health literacy. The Access to Transplant and Transplant Outcome Measures (ATTOM) study identified inequity in access to transplantation by educational level. We tested the hypothesis that low health literacy promotes inequity by acting as a mediator between reduced education and transplantation. MethodsThe ATTOM cohort study recruited incident dialysis patients aged 18–75 years, who were able to provide informed consent, from all 72 kidney units in the UK from Dec 1, 2011, to Sept 30, 2013]. This mediation analysis concerned the exposure (no educational qualifications vs any), prospective outcomes (time to being added to the deceased-donor transplant waiting list and time to living-donor transplantation, censored at 2 years), the mediator (health literacy as judged by Single Item Literacy Screener, a validated, self-reported health literacy screening measure) and covariates (age, ethnicity, and comorbidity by Charlson index). Effect sizes were calculated for education on health literacy, health literacy on being added to the transplant waiting list and living-donor transplantation, and for education on being added to the waiting list and living-donor transplantation, all adjusted for the covariates. These effect sizes were used to calculate the total effect of education on being added to the transplant list and transplantation and the indirect effect mediated by health literacy. Weibull Accelerated Failure Time models were used. Ethics approval was given by Cambridge Research Ethics Committee. Findings2463 patients were included. The total effect of low educational level was to increase the time to being added to the transplant waiting list by 22% (time to event ratio 1·22, 95% CI 1·02–1·48) and time to living donor transplant by 47% (1·47, 1·04–2·08). The indirect effect mediated by health literacy accounted for 35% and 30%, respectively. InterpretationOur findings show that health literacy mediates a substantial proportion of the effect of low educational level on reduced access to the deceased-donor transplant waiting list and to living donor transplantation. Interventions to improve equity of transplantation should account for the health literacy skills needed for patients to take part in shared decision making. FundingATTOM was funded under National Institute for Health Research Programme Grants for Applied Research (RP-PG-0109-10116).

Estimating Health-State Utility Values in Kidney Transplant Recipients and Waiting-List Patients Using the EQ-5D-5L.

ObjectivesTo report health-state utility values measured using the five-level EuroQol five-dimensional questionnaire (EQ-5D-5L) in a large sample of patients with end-stage renal disease and to explore how these values vary in relation to patient characteristics and treatment factors.MethodsAs part of the prospective observational study entitled “Access to Transplantation and Transplant Outcome Measures,” we captured information on patient characteristics and treatment factors in a cohort of incident kidney transplant recipients and a cohort of prevalent patients on the transplant waiting list in the United Kingdom. We assessed patients’ health status using the EQ-5D-5L and conducted multivariable regression analyses of index scores.ResultsEQ-5D-5L responses were available for 512 transplant recipients and 1704 waiting-list patients. Mean index scores were higher in transplant recipients at 6 months after transplant surgery (0.83) compared with patients on the waiting list (0.77). In combined regression analyses, a primary renal diagnosis of diabetes was associated with the largest decrement in utility scores. When separate regression models were fitted to each cohort, female gender and Asian ethnicity were associated with lower utility scores among waiting-list patients but not among transplant recipients. Among waiting-list patients, longer time spent on dialysis was also associated with poorer utility scores. When comorbidities were included, the presence of mental illness resulted in a utility decrement of 0.12 in both cohorts.ConclusionsThis study provides new insights into variations in health-state utility values from a single source that can be used to inform cost-effectiveness evaluations in patients with end-stage renal disease.

Barriers to living donor kidney transplantation in the United Kingdom: a national observational study.

ABSTRACT Background. Living donor kidney transplantation (LDKT) provides more timely access to transplantation and better clinical outcomes than deceased donor kidney transplantation (DDKT). This study investigated disparities in the utilization of LDKT in the UK. Methods. A total of 2055 adults undergoing kidney transplantation between November 2011 and March 2013 were prospectively recruited from all 23 UK transplant centres as part of the Access to Transplantation and Transplant Outcome Measures (ATTOM) study. Recipient variables independently associated with receipt of LDKT versus DDKT were identified. Results. Of the 2055 patients, 807 (39.3%) received LDKT and 1248 (60.7%) received DDKT. Multivariable modelling demonstrated a significant reduction in the likelihood of LDKT for older age {odds ratio [OR] 0.11 [95% confidence interval (CI) 0.08–0.17], P < 0.0001 for 65–75 years versus 18–34 years}; Asian ethnicity [OR 0.55 (95% CI 0.39–0.77), P = 0.0006 versus White]; Black ethnicity [OR 0.64 (95% CI 0.42–0.99), P = 0.047 versus White]; divorced, separated or widowed [OR 0.63 (95% CI 0.46–0.88), P = 0.030 versus married]; no qualifications [OR 0.55 (95% CI 0.42–0.74), P < 0.0001 versus higher education qualifications]; no car ownership [OR 0.51 (95% CI 0.37–0.72), P = 0.0001] and no home ownership [OR 0.65 (95% CI 0.85–0.79), P = 0.002]. The odds of LDKT varied significantly between countries in the UK. Conclusions. Among patients undergoing kidney transplantation in the UK, there are significant age, ethnic, socio-economic and geographic disparities in the utilization of LDKT. Further work is needed to explore the potential for targeted interventions to improve equity in living donor transplantation.

Limited health literacy in advanced kidney disease

Limited health literacy may reduce the ability of patients with advanced kidney disease to understand their disease and treatment and take part in shared decision making. In dialysis and transplant patients, limited health literacy has been associated with low socioeconomic status, comorbidity, and mortality. Here, we investigated the prevalence and associations of limited health literacy using data from the United Kingdom-wide Access to Transplantation and Transplant Outcome Measures (ATTOM) program. Incident dialysis, incident transplant, and transplant wait-listed patients ages 18 to 75 were recruited from 2011 to 2013 and data were collected from patient questionnaires and case notes. A score >2 in the Single-Item Literacy Screener was used to define limited health literacy. Univariate and multivariate analyses were performed to identify patient factors associated with limited health literacy. We studied 6842 patients, 2621 were incident dialysis, 1959 were wait-listed, and 2262 were incident transplant. Limited health literacy prevalence was 20%, 15%, and 12% in each group, respectively. Limited health literacy was independently associated with low socioeconomic status, poor English fluency, and comorbidity. However, transplant wait-listing, preemptive transplantation, and live-donor transplantation were associated with increasing health literacy.

Access to Transplantation and Transplant Outcome Measures (ATTOM): study protocol of a UK wide, in-depth, prospective cohort analysis

IntroductionThere is significant intercentre variability in access to renal transplantation in the UK due to poorly understood factors. The overarching aims of this study are to improve equity of access...

How to enhance patient experiences of decision-making about kidney transplantation?

In this issue of NDT, Calestani et al. [1] report the results of a qualitative study in the UK. The authors interviewed 53 chronic kidney disease (CKD) stage 5 patients about their views on the transplant-listing procedure in their dialysis unit. The interviews focused on the information that patients received on transplantation and the listing assessment process. The study is part of the Access to Transplant and Transplant Outcome Measures (ATTOM) project, which aims to identify patient-specific and service delivery factors that may influence access to transplantation. Besides showing that the provision of information varied in type and purpose across UK renal units, the authors found that patients perceived the information to be suboptimal in terms of its completeness, comprehensiveness and timing. Although Calestani and colleagues are the first to explore the utility of information to support transplant-listing decisions, the pattern of their findings is consistent with several previous studies concluding that patient information for renal replacement therapy (RRT) decisions leaves room for improvement [2–7]. In order to enhance patients’ experiences of decision-making, health care services need to provide accurate and complete information to ensure patients’ treatment preferences are informed. Patient decision aids are information-based interventions informed by clinical evidence and psychological sciences, which help patients make more effective decisions between treatments [8]. Their components usually include: accurate information about all options and their consequences; a structure to enhance understanding of the treatment decision, without bias; guidance to help people evaluate, and trade-off, their values about treatments in the context of their lives [9]. For many treatment decisions, there are decision aids available [10]; some have been designed to guide CKD stage 5 patients’ choice of RRT type [11–15]. Although most of them included transplantation as one of the options, only one specifically compared living versus deceased donation [15]; none of them discussed the choice of whether to transplant pre-emptively or not. The findings from Calestani et al. seem to indicate that patient decision aids are not yet successfully integrated within renal services in the UK. First, participants reported that the information on transplantation and listing was either too extensive or given too quickly [1]. Especially if information is given verbally during consultations, patients need to attend to, process, store and recall the information in order to clarify their understanding. In addition, when asked to collaborate in decision-making, patients have to evaluate the treatments and consequences and assign importance to them, ask questions and formulate a set of preferences. Patient decision aids usually have a written component that acts as an aide-memoire. Having the information written down contributes to people being able to recall and reason about the options in accordance with their values and allows them to talk about the decision with others. Secondly, Calestani et al. found that not every participant had been offered all treatment options equally. When it came to discussing pre-emptive transplantation, patients reported experiences ranging from their health care team being very positive about this option to some not being offered this alternative at all. The authors suggest that these findings reflect variation in unit-level characteristics by emphasizing that transplant units were more positive about pre-emptive transplantation than non-transplant units. There is a tendency for patient information to focus on engaging with local service delivery or disease management rather than on unbiased decision-making between options [2, 16]. A previous study in the UK explored reasons for between-centre differences in the