Matthew Robb

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

Introduction There 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 to kidney and kidney–pancreas transplantation across the UK and to optimise organ allocation to maximise the benefit and cost-effectiveness of transplantation. Methods and analysis 6844 patients aged 18–75 years starting dialysis and/or receiving a transplant together with matched patients active on the transplant list from all 72 UK renal units were recruited between November 2011 and March 2013 and will be followed for at least 3 years. The outcomes of interest include patient survival, access to the transplant list, receipt of a transplant, patient-reported outcome measures (PROMs) including quality of life, treatment satisfaction, well-being and health status on different forms of renal replacement therapy. Sociodemographic and clinical data were prospectively collected from case notes and from interviews with patients and local clinical teams. Qualitative process exploration with clinical staff will help identify unit-specific factors that influence access to renal transplantation. A health economic analysis will explore costs and outcomes associated with alternative approaches to organ allocation. The study will deliver: (1) an understanding of patient and unit-specific factors influencing access to renal transplantation in the UK, informing potential changes to practices and policies to optimise outcomes and reduce intercentre variability; (2) a patient-survival probability model to standardise access to the renal transplant list and (3) an understanding of PROMs and health economic impact of kidney and kidney–pancreas transplantation to inform the development of a more sophisticated and fairer organ allocation algorithm. Ethics and dissemination The protocol has been independently peer reviewed by National Institute for Health Research (NIHR) and approved by the East of England Research Ethics Committee. The results will be published in peer-reviewed journals and presented at conferences.

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.

UK Renal Registry 19th Annual Report: Chapter 11 Centre Variation in Access to Kidney Transplantation (2010-2015)

. Patients treated at non-transplanting renal centres were less likely to be wait listed for transplantation compared to patients treated at transplanting renal centres (OR 0.78, 95% CI 0.72–0.85). . Patients treated at non-transplanting renal centres were less likely to receive a transplant from a donor after cardiac death or living kidney donor compared to patients treated at a transplanting renal centre (OR 0.79, 95% CI 0.71–0.89).

Donors With Immune Thrombocytopenia: Do They Pose a Risk to Transplant Recipients?

Transplant‐mediated alloimmune thrombocytopenia (TMAT) from donors with immune thrombocytopenia (ITP) can result in significant bleeding complications in the recipient. The risk to a recipient of TMAT if they receive an organ from a donor with ITP is unknown. The outcomes of recipients of organs from deceased donors with ITP recorded in the UK Transplant Registry between 2000 and 2015 were reviewed. Twenty‐one deceased organ donors had a predonation diagnosis of ITP. These donors were significantly more likely to have died from intracranial hemorrhage than were all other deceased organ donors (85% vs. 57%, p < 0.001). Organs from donors with ITP resulted in 49 organ transplants (31 kidney, 14 liver, four heart), with only one case of TMAT, which occurred in a liver transplant recipient and resulted in death from bleeding complications 18 days posttransplantation. The recipient of a kidney from the same organ donor was not affected. Unadjusted 5‐year patient and graft survival was significantly worse for liver transplant recipients from donors with ITP compared with liver transplant recipients from donors without ITP (64% vs. 85%, p = 0.012). Organs from donors with ITP may be considered for transplantation, but livers should be used with caution.

Transplantation of organs from deceased donors with meningitis and encephalitis: a UK registry analysis

Deceased organ donors, where the cause of death is meningitis or encephalitis, are a potential concern because of the risks of transmission of a potentially fatal infection to recipients.

Predicting patient survival after deceased donor kidney transplantation using flexible parametric modelling

BackgroundThe influence of donor and recipient factors on outcomes following kidney transplantation is commonly analysed using Cox regression models, but this approach is not useful for predicting long-term survival beyond observed data. We demonstrate the application of a flexible parametric approach to fit a model that can be extrapolated for the purpose of predicting mean patient survival. The primary motivation for this analysis is to develop a predictive model to estimate post-transplant survival based on individual patient characteristics to inform the design of alternative approaches to allocating deceased donor kidneys to those on the transplant waiting list in the United Kingdom.MethodsWe analysed data from over 12,000 recipients of deceased donor kidney or combined kidney and pancreas transplants between 2003 and 2012. We fitted a flexible parametric model incorporating restricted cubic splines to characterise the baseline hazard function and explored a range of covariates including recipient, donor and transplant-related factors.ResultsMultivariable analysis showed the risk of death increased with recipient and donor age, diabetic nephropathy as the recipient’s primary renal diagnosis and donor hypertension. The risk of death was lower in female recipients, patients with polycystic kidney disease and recipients of pre-emptive transplants. The final model was used to extrapolate survival curves in order to calculate mean survival times for patients with specific characteristics.ConclusionThe use of flexible parametric modelling techniques allowed us to address some of the limitations of both the Cox regression approach and of standard parametric models when the goal is to predict long-term survival.

Predicting humoral alloimmunity from differences in donor-recipient HLA surface electrostatic potential

In transplantation, development of humoral alloimmunity against donor HLA is a major cause of organ transplant failure but our ability to assess the immunological risk associated with a potential donor-recipient HLA combination is limited. We hypothesised that the capacity of donor HLA to induce a specific alloantibody response depends on their structural and physicochemical dissimilarity compared to recipient HLA. To test this hypothesis, we first developed a novel computational scoring system that enables quantitative assessment of surface electrostatic potential differences between donor and recipient HLA molecules at the tertiary structure level (electrostatic mismatch score-three dimensional; EMS-3D). We then examined humoral alloimmune responses in healthy females subjected to a standardised injection of donor lymphocytes from their male partner. This analysis showed a strong association between the EMS-3D of donor HLA and donor-specific alloantibody development; this relationship was strongest for HLA-DQ alloantigens. In the clinical transplantation setting, the immunogenic potential of HLA-DRB1 and -DQ mismatches expressed on donor kidneys, as assessed by their EMS-3D, was an independent predictor of development of donor-specific alloantibody after graft failure. Collectively, these findings demonstrate the translational potential of our approach to improve immunological risk assessment and to decrease the burden of humoral alloimmunity in organ transplantation.

Transplantation of Kidneys from DCD and DBD Donors who Died after Ligature Asphyxiation: the UK Experience

Introduction Kidneys from donors who die after ligature asphyxiation are often used for transplantation but there is concern that the hypoxic injury following ligature asphyxiation may be associated with inferior transplant outcomes, particularly when kidneys incur additional ischaemic injury during donation after circulatory death (DCD). Materials and Methods The UK transplant registry was used to identify all donors who died secondary to ligature asphyxiation from 1/1/2003-1/1/2017 through manual review of the free text entries in deceased organ donor forms. Survival analysis, cox proportional hazards regression and logistic regression models were used to determine the effect that both donation after brain stem death (DBD) and DCD donors who died after ligature asphyxiation had on renal transplant outcomes. Results Over the 14-year study period, 2.7% (n=521) of all potential UK organ donors died secondary to ligature asphyxiation. Nearly all were a result of attempted suicide by hanging (98.7%). Of this number 409 (78.5%) proceeded to donate kidneys for transplantation, of which 192 (46.9%) were DBD donors and 217 (53.1%) were DCD donors. Both DBD and DCD kidney donors who died from ligature asphyxiation were significantly younger, a greater proportion were male, and had markedly lower levels of hypertension and cardiac disease than donors who died from causes other than ligature asphyxiation. Donors who died following ligature asphyxiation provided kidneys for 650 kidney only transplants. 12-month eGFR was significantly better for those who received kidneys from donors who died from ligature asphyxiation (both DCD and DBD). After adjustment for both donor and recipient factors using multivariate linear regression, receiving a kidney from a donor who died following ligature asphyxiation was not an independent predictor of better 12-month eGFR (p=0.625). Recipients of kidneys from donors who died following ligature asphyxiation (both DCD and DBD) had significantly better unadjusted 5-year patient and death censored graft survival. After adjusting for the differences in donor and recipient characteristics, donor ligature asphyxiation was not an independent predictor of 1 and 5 year patient survival or 1 year death censored graft survival. However, it was an independent predictor of good 5 year death censored graft survival (HR 0.712 (0.513-0.990), p=0.042)). Figure. No caption available. Figure. No caption available. Discussion Organ donors who die following ligature asphyxiation represent a relatively small but important proportion of the overall deceased donor population. The findings from the present analysis show that use of kidneys from both DBD and DCD donors who died following ligature asphyxiation result in excellent transplant outcomes. Conclusions In view of the above, increased consideration should be given to the use of kidneys from potential donors following ligature asphyxiation. The National Institute of Health Research, Blood and Transplant Research Unit (NIHR BTRU) on Organ Donation and Transplantation at the University of Cambridge in collaboration with Newcastle University and in partnership funded this research with NHS Blood and Transplant (NHSBT).

Chapter 9 Centre Variation in Access to Kidney Transplantation (2011–2013 incident cohort)

. Patients of non-White ethnicity had an equal chance of transplant wait-listing within two years of starting renal replacement therapy (OR 1.03, 95% CI 0.93– 1.14). This represents an improvement in equity of access to the kidney transplant waiting list compared to findings from 2008–2010. Once on the transplant waiting list, non-White patients had a 60% lower chance of receiving a kidney transplant of any type within two years (OR 0.40, 95% CI 0.35–0.45). . Compared to men, women had a 17% lower chance of being activated on the kidney transplant waiting list within two years of starting renal replacement therapy (OR 0.83, 95% CI 0.76–0.90). Once on the transplant waiting list, women had a 15% lower chance of receiving a kidney transplant of any type within two years (OR 0.85, 95% CI 0.76–0.96).