Adnan Sharif

Mortality after pediatric kidney transplantation in England – a population-based cohort study

The aim of this study was to explore mortality after pediatric kidney transplantation in England over the last decade. We used data from HES to select all kidney transplant procedures performed in England between April 2001 and March 2012. Data linkage analysis was performed with the ONS to identify all deaths occurring among this study cohort. Data for 1189 pediatric recipients were compared to 17 914 adult recipients (number of deaths, 33 vs. 2052, respectively, p < 0.001), with median follow‐up 4.4 yr (interquartile range 2.2–7.3 yr). There was no difference in mortality within the pediatric cohort; age 0–1 (n = 25, patient survival 100.0%), age 2–5 (n = 198, patient survival 96.0%), age 6–12 (n = 359, patient survival 97.5%), and age 13–18 (n = 607, patient survival 97.4%), respectively (p = 0.567). The most common causes of death were renal (n = 8, 24.2%), infection (n = 6, 18.2%), and malignancy (n = 5, 15.2%). All deaths from malignancy were secondary to PTLD. In a fully adjusted Cox regression model, only white ethnicity was significantly associated with risk of pediatric mortality post‐kidney transplantation (hazard ratio 2.7, 95% confidence interval [1.0–7.3], p = 0.047). To conclude, this population‐based cohort study confirms low mortality after pediatric kidney transplantation with short follow‐up.

A survey of South Asian attitudes to organ donation in the United Kingdom.

South Asians in the United Kingdom are overrepresented on the organ transplant waiting list but underrepresented as organ donors. In this study, we surveyed South Asian opinion with regards to organ donation.

Cardiovascular actions of mineralocorticoid receptor antagonists in patients with chronic kidney disease: A systematic review and meta-analysis of randomized trials.

Introduction: The safety and actions of mineralocorticoid receptor antagonists on surrogate markers of cardiovascular disease as well as major patient level cardiovascular end-points in patients with chronic kidney disease are unclear. Methods: MEDLINE, EMBASE, Trip Database, Cochrane Central Register of Controlled Trials, Cochrane Renal Group specialized register, Current Controlled Trials and clinicaltrials.gov were searched for relevant trials. Results: Twenty-nine trials (1581 patients) were included. Overall, mineralocorticoid receptor antagonists lowered both systolic and diastolic blood pressure (–5.24, 95% confidence interval (CI) –8.65, −1.82 mmHg; p=0.003 and −1.96, 95% CI −3.22, –0.69 mmHg; p=0.002 respectively). There were insufficient data to perform a meta-analysis of other cardiovascular effects. However, a systematic review of the studies included suggested a consistent improvement in surrogate markers of cardiovascular disease. Overall, the use of mineralocorticoid receptor antagonists was associated with an increased serum potassium (0.23, 95% CI 0.13, 0.33 mmol/l; p<0.0001) and higher risk ratio (1.76, 95% CI 1.20, 2.57; p=0.001) of hyperkalemia. Data on long-term cardiovascular outcomes and mortality were not available in any of the trials. Conclusions: The long-term effects of mineralocorticoid receptor antagonists on cardiovascular events, mortality and safety need to be established.

Comparing glycaemic benefits of Active Versus passive lifestyle Intervention in kidney Allograft Recipients (CAVIAR): study protocol for a randomised controlled trial

BackgroundLifestyle modification is widely recommended to kidney allograft recipients post transplantation due to the cardiometabolic risks associated with immunosuppression including new-onset diabetes, weight gain and cardiovascular events. However, we have no actual evidence that undertaking lifestyle modification protects from any adverse outcomes post transplantation. The aim of this study is to compare whether a more proactive versus passive interventional approach to modify lifestyle is associated with superior outcomes post kidney transplantation.Methods/designWe designed this prospective, single-centre, open-label, randomised controlled study to compare the efficacy of active versus passive lifestyle intervention for kidney allograft recipients early post transplantation. A total of 130 eligible patients, who are stable, nondiabetic and between 3 and 24xa0months post kidney transplantation, will be recruited. Randomisation is being undertaken by random block permutations into passive (nu2009=u200965, leaflet guidance only) versus active lifestyle modification (nu2009=u200965, supervised intervention) over a 6-month period. Supervised intervention is being facilitated by two dietitians during the 6-month intervention period to provide continuous lifestyle intervention guidance, support and encouragement. Both dietitians are accredited with behavioural intervention skills and will utilise motivational aids to support study recruits randomised to active intervention. The primary outcome is change in abnormal glucose metabolism parameters after 6xa0months of comparing active versus passive lifestyle intervention. Secondary outcomes include changes in a wide array of cardiometabolic parameters, kidney allograft function and patient-reported outcome measures. Long-term tracking of patients via data linkage to electronic patient records and national registries will facilitate long-term comparison of outcomes after active versus passive lifestyle intervention beyond the 6-month intervention period.DiscussionThis is the first randomised controlled study to investigate the benefits of active versus passive lifestyle intervention in kidney allograft recipients for the prevention of abnormal cardiometabolic outcomes. In addition, this is the first example of utilising behaviour therapy intervention post kidney transplantation to achieve clinically beneficial outcomes, which has potential implications on many spheres of post-transplant care.Trial registrationThis study was registered with the Clinical Trials Registry on 27 August 2014 (ClinicalTrials.org Identifier: NCT02233491).

The impact of donor body mass index on outcomes after deceased kidney transplantation - a national population-cohort study

The aim of this study was to determine the effect of donor body mass index (BMI) on deceased donor kidney transplant outcomes. Data were collected from the UK Transplant Registry for all deceased donor kidney transplant recipients between January 2003 and January 2015. Univariable and multivariable analyses were undertaken to assess the impact of donor BMI on a range of outcomes. Donor BMI (kg/m2) was stratified as <18.5 (n = 380), 18.5–25.0 (n = 6890), 25.1–30.0 (n = 6669), 30.1–35.0 (n = 2503) and >35.0 (n = 1148). The prevalence of delayed graft function increased significantly with donor BMI (P < 0.001), with an adjusted odds ratio of 1.38 (95% CI: 1.16–1.63) for the >35.0 vs. 18.5–25.0 groups. However, there was no significant association between donor BMI and 12‐month creatinine (P = 0.550), or patient (P = 0.109) or graft (P = 0.590) survival. In overweight patients, increasing donor BMI was associated with a significant increase in warm ischaemia time and functional warm ischaemia time, by an average of 4.6% (P = 0.043) and 5.2% (P = 0.013) per 10.0 kg/m2. However, rising warm ischaemic time and functional warm ischaemic time was not significantly associated with delayed graft function, 12‐month creatinine levels, graft loss or patient death. In this population cohort study, we identified no significant association between donor BMI and long‐term clinical outcomes in deceased donor kidney transplantation.

Cancer-related outcomes in kidney allograft recipients in England versus New York State: a comparative population-cohort analysis between 2003 and 2013

It is unclear whether cancer‐related epidemiology after kidney transplantation is translatable between countries. In this population‐cohort study, we compared cancer incidence and all‐cause mortality after extracting data for every kidney‐alone transplant procedure performed in England and New York State (NYS) between 2003 and 2013. Data were analyzed for 18,493 and 11,602 adult recipients from England and NYS respectively, with median follow up 6.3 years and 5.5 years respectively (up to December 2014). English patients were more likely to have previous cancer at time of transplantation compared to NYS patients (5.6% vs. 3.5%, P < 0.001). Kidney allograft recipients in England versus NYS had increased cancer incidence (12.3% vs. 5.9%, P < 0.001) but lower all‐cause mortality during the immediate postoperative stay (0.7% vs. 1.0%, P = 0.011), after 30‐days (0.9% vs. 1.8%, P < 0.001) and after 1‐year post‐transplantation (3.0% vs. 5.1%, P < 0.001). However, mortality rates among patients developing post‐transplant cancer were equivalent between the two countries. During the first year of follow up, if patients had an admission with a cancer diagnosis, they were more likely to die in both England (Odds Ratio 4.28 [95% CI: 3.09–5.93], P < 0.001) and NYS (Odds Ratio 2.88 [95% CI: 1.70–4.89], P < 0.001). Kidney allograft recipients in NYS demonstrated higher hazard ratios for developing kidney transplant rejection/failure compared to England on Cox regression analysis. Our analysis demonstrates significant differences in cancer‐related epidemiology between kidney allograft recipients in England versus NYS, suggesting caution in translating post‐transplant cancer epidemiology between countries.

Frailty Intervention Trial iN End-Stage patientS on haemodialysis (FITNESS): study protocol for a randomised controlled trial

BackgroundFrailty is a state of low physiological reserve and multi-systemic dysregulation that leads to susceptibility to external stressors; it is associated with adverse outcomes. North American data suggest that haemodialysis recipients are more likely to be frail than the general population, although data on UK cohorts are lacking. Furthermore, with a multitude of assessment tools, it is difficult for the clinician to ascertain which is most suitable for this population. The FITNESS Study aims to measure the prevalence and outcomes associated with frailty in a large UK haemodialysis cohort to determine the optimum frailty tool as defined by predictive value for mortality/hospitalisation and to conduct a feasibility study exploring a multi-disciplinary clinical intervention to improve frailty among haemodialysis recipients.Methods/designThe study will follow a cohort multiple randomised controlled trial design; the initial cohort study will identify participants to be invited into a subsequent open-label randomised controlled trial. Eligible patients will be identified and recruited from their usual haemodialysis session. They will be invited to complete tasks and questionnaires collecting data on sarcopenia, immunosenescence, mood, cognition, disability, and comorbidity. Fifty pre-frail participants with suitable English proficiency will be randomly selected from this cohort to participate in the randomised controlled trial phase of the study. Further stratified randomisation will occur to assign these 50 participants to active or passive groups. The active group will receive a psychologically supported, patient-centred, multi-disciplinary intervention into frailty, in what we believe to be a first within this patient group. The control group will receive usual haemodialysis standard of care. All participants will be followed up using electronic patient records for outcomes to include hospitalisation and mortality. Primary outcomes for this phase of the study will be feasibility and tolerability of the clinical intervention study.DiscussionThe study will collect data on multiple aspects of frailty allowing for a rich dataset for detailed analysis. We believe this will be the first study to explore a psychologically supported, patient-centred intervention in this patient group.Trial registrationClinicaltrials.gov, NCT03071107. Registered on 6 March 2017.

Ethnicity matching and outcomes after kidney transplantation in the United Kingdom

Background Kidneys from non-white donors have inferior outcomes, but it is unclear if ethnicity matching between donors and recipients achieves better post kidney transplant outcomes. Methods We undertook a retrospective, population cohort study utilising UK Transplant Registry data. The cohort comprised adult, kidney-alone, transplant recipients receiving their first kidney transplant between 2003–2015, with data censored at 1st October 2016. We included 27,970 recipients stratified into white (n = 23,215), black (n = 1,679) and south Asian (n = 3,076) ethnicity, with median post-transplant follow-up of 1,676 days (IQR 716–2,869 days). Unadjusted and adjusted Cox regression survival analyses were performed to investigate ethnicity effect on risk for graft loss and mortality. Results In unadjusted analyses, matched ethnicity between donors-recipients resulted in better outcomes for delayed graft function, one-year creatinine, graft and patient survival but these differed by ethnicity matches. Compared to white-to-white transplants, risk for death-censored graft loss was higher in black-to-black and similar among Asian-to-Asian transplants, but mortality risk was lower for both black-to-black and Asian-to-Asian transplants. In Cox regression models, compared to white donors, we observed higher risk for graft loss with both south Asian (HR 1.38, 95%CI 1.12–1.70, p = 0.003) and black (HR 1.66, 95%CI 1.30–2.11, p<0.001) donated kidneys independent of recipient ethnicity. We observed no mortality difference with south Asian donated kidneys but increased mortality with black donated kidneys (HR 1.68, 95%CI 1.21–2.35, p = 0.002). Matching ethnicities made no significant difference in any Cox regression model. Similar results were observed after stratifying our analysis by living and deceased-donor kidney transplantation. Conclusions Our data confirm inferior outcomes associated with non-white kidney donors for kidney transplant recipients of any ethnicity in a risk-adjusted model for the United Kingdom population. However, contrary to non-renal transplant literature, we did not identify any survival benefits associated with donor-recipient ethnicity matching.

Hypoalbuminaemia at time of surgery is associated with an increased risk for overall graft loss after kidney transplantation: Hypoalbuminaemia and post-transplant outcomes

The aim of this retrospective cohort study was to investigate whether pre‐operative hypoalbuminaemia (<35u2009g/L) is associated with adverse outcomes post‐kidney transplantation.

Mortality risk after cancer diagnosis in kidney transplant recipients: the limitations of analyzing hospital administration data alone

Administrative data are frequently used for epidemiological studies but its usefulness to analyze cancer epidemiology after kidney transplantation is unclear. In this retrospective population‐based cohort study, we identified every adult kidney‐alone transplant performed in England (2003–2014) using administrative data from Hospital Episode Statistics. Results were compared to the hospitalized adult general population in England to calculate standardized incidence and mortality ratios. Data were analyzed for 19,883 kidney allograft recipients, with median follow‐up 6.0 years post‐transplantation. Cancer incidence was more common after kidney transplantation compared to the general population in line with published literature (standardized incidence ratio 2.47, 95% CI: 2.34–2.61). In a Cox proportional hazards model, cancer development was associated with increasing age, recipients of deceased kidneys, frequent readmissions within 12 months post‐transplant and first kidney recipients. All‐cause mortality risk for kidney allograft recipients with new‐onset cancer was significantly higher compared to those remaining cancer‐free (42.0% vs. 10.3%, respectively). However, when comparing mortality risk for kidney allograft recipients to the general population after development of cancer, risk was lower for both cancer‐related (standardized mortality ratio 0.75, 95% CI: 0.71–0.79) and noncancer‐related mortality (standardized mortality ratio 0.90, 95% CI: 0.85–0.95), which contradicts reported literature. Although some plausible explanations are conceivable, our analysis likely reflects the limitations of administrative data for analyzing cancer data. Future studies require record linkage with dedicated cancer registries to acquire more robust and accurate data relating to cancer epidemiology after transplantation.