Defining Priorities for Future Research:Results of the UK Kidney Transplant Priority Setting Partnership

It has been suggested that the research priorities of those funding and performing research in transplantation may differ from those of end service users such as patients, carers and healthcare professionals involved in day-to-day care. The Kidney Transplant Priority Setting Partnership (PSP) was established with the aim of involving all stakeholders in prioritising future research in the field.The PSP methodology is as outlined by the James Lind Alliance. An initial survey collected unanswered research questions from patients, carers and clinicians. Duplicate and out-of-scope topics were excluded and the existing literature searched to identify topics answered by current evidence. An interim prioritisation survey asked patients and professionals to score the importance of the remaining questions to create a ranked long-list. These were considered at a final consensus workshop using a modified nominal group technique to agree a final top ten.The initial survey identified 497 questions from 183 respondents, covering all aspects of transplantation from assessment through to long-term follow-up. These were grouped into 90 unanswered "indicative" questions. The interim prioritisation survey received 256 responses (34.8% patients/carers, 10.9% donors and 54.3% professionals), resulting in a ranked list of 25 questions that were considered during the final workshop. Participants agreed a top ten priorities for future research that included optimisation of immunosuppression (improved monitoring, choice of regimen, personalisation), prevention of sensitisation and transplanting the sensitised patient, management of antibody-mediated rejection, long-term risks to live donors, methods of organ preservation, induction of tolerance and bioengineering of organs. There was evidence that patient and carer involvement had a significant impact on shaping the final priorities.The final list of priorities relates to all stages of the transplant process, including access to transplantation, living donation, organ preservation, post-transplant care and management of the failing transplant. This list of priorities will provide an invaluable resource for researchers and funders to direct future activity

Proportion and Characteristics of US Adults Who May Be Eligible From Additional Blood Pressure Lowering Based on Absolute Risk

BACKGROUND The Systolic Blood Pressure Intervention Trial (SPRINT) and the Heart Outcomes Prevention Evaluation 3 (HOPE-3) trial demonstrated the merits of blood pressure (BP) lowering to reduce cardiovascular events in intermediate to high cardiovascular risk adults. However, the population impact of an absolute risk-based strategy for BP lowering remains unclear. METHODS We examined 3 treatment thresholds using the National Health and Nutrition Examination Survey. First, the JNC8 guideline was used to determine treatment goals. Second, adults with a systolic BP (SBP) of 130 mm Hg and high cardiovascular risk (based on eligibility for SPRINT) were considered eligible for additional BP lowering. Finally, we combined the treatment threshold for high-risk adults with an SBP treatment threshold of 140 mm Hg for intermediate-risk adults that met the eligibility criteria for HOPE-3. RESULTS Under the JNC8 guideline, 78.0% of adults ≥50 years were at target while 22.0% were eligible for additional BP lowering. If an SBP treatment threshold of 130 mm Hg was used for adults at high cardiovascular risk, 31.1% would be eligible for additional BP lowering (an increase of 8.1 million). If an SBP threshold of 140 mm Hg was additionally used for adults at intermediate risk, 31.4% of adults would be eligible for BP lowering (an increase of 8.3 million). The proportion of adults eligible for BP lowering with established coronary artery disease decreased with the risk-based strategies. CONCLUSION An absolute risk treatment strategy would modestly increase the proportion of adults eligible for BP lowering

Proportion and Characteristics of US Adults Who May Be Eligible From Additional Blood Pressure Lowering Based on Absolute Risk

BACKGROUND The Systolic Blood Pressure Intervention Trial (SPRINT) and the Heart Outcomes Prevention Evaluation 3 (HOPE-3) trial demonstrated the merits of blood pressure (BP) lowering to reduce cardiovascular events in intermediate to high cardiovascular risk adults. However, the population impact of an absolute risk-based strategy for BP lowering remains unclear. METHODS We examined 3 treatment thresholds using the National Health and Nutrition Examination Survey. First, the JNC8 guideline was used to determine treatment goals. Second, adults with a systolic BP (SBP) of 130 mm Hg and high cardiovascular risk (based on eligibility for SPRINT) were considered eligible for additional BP lowering. Finally, we combined the treatment threshold for high-risk adults with an SBP treatment threshold of 140 mm Hg for intermediate-risk adults that met the eligibility criteria for HOPE-3. RESULTS Under the JNC8 guideline, 78.0% of adults ≥50 years were at target while 22.0% were eligible for additional BP lowering. If an SBP treatment threshold of 130 mm Hg was used for adults at high cardiovascular risk, 31.1% would be eligible for additional BP lowering (an increase of 8.1 million). If an SBP threshold of 140 mm Hg was additionally used for adults at intermediate risk, 31.4% of adults would be eligible for BP lowering (an increase of 8.3 million). The proportion of adults eligible for BP lowering with established coronary artery disease decreased with the risk-based strategies. CONCLUSION An absolute risk treatment strategy would modestly increase the proportion of adults eligible for BP lowering

Donor-recipient weight and sex mismatch and the risk of graft loss in renal transplantation.

Background and objectives Relatively smaller kidney donor to recipient size is proposed to result in higher graft loss due to nephron underdosing and hyperfiltration injury, but the potentially additive effect of sex and weight mismatch has not been explored in detail. The purpose of this study was to determine if concurrent donor and recipient absolute weight and sex mismatch was associated with graft loss in a cohort of deceased donor kidney transplant recipients. Design, setting, participants, and measurements The association of kidney donor and recipient absolute weight and sex difference with death-censored graft loss was explored using a cohort of United States deceased donor recipients between 2000-2014 through the Scientific Registry of Transplants Recipients (SRTR). Donor-recipient sex pairings (male donor-male recipient; female donor-female recipient; male donor-female recipient; female donor-male recipient) were further stratified by donor and recipient absolute weight difference (>30 kg or 10-30 kg (donor recipient) or Results 21,261 of 115,124 kidney transplant recipients developed death-censored graft failure, (median graft survival time was 3.8 years, Q1-Q3 0.0-14.8 years). After multivariable adjustment, the highest relative hazards for graft failure were observed for female recipients of male donor kidneys and male recipients of female donor kidneys in situations where the recipient was >30 kg larger than donor (HR 1.50 95% CI [1.32-1.70], HR 1.35 95% CI [1.25-1.45], respectively). Conclusions A concurrent mismatch in donor-recipient weight (donor<recipient) and donor-recipient sex is associated with a higher risk of death-censored graft loss in kidney transplantation.</p

Donor-recipient weight and sex mismatch and the risk of graft loss in renal transplantation.

Background and objectives Relatively smaller kidney donor to recipient size is proposed to result in higher graft loss due to nephron underdosing and hyperfiltration injury, but the potentially additive effect of sex and weight mismatch has not been explored in detail. The purpose of this study was to determine if concurrent donor and recipient absolute weight and sex mismatch was associated with graft loss in a cohort of deceased donor kidney transplant recipients. Design, setting, participants, and measurements The association of kidney donor and recipient absolute weight and sex difference with death-censored graft loss was explored using a cohort of United States deceased donor recipients between 2000-2014 through the Scientific Registry of Transplants Recipients (SRTR). Donor-recipient sex pairings (male donor-male recipient; female donor-female recipient; male donor-female recipient; female donor-male recipient) were further stratified by donor and recipient absolute weight difference (&gt;30 kg or 10-30 kg (donor &lt; recipient; donor &gt; recipient) or &lt;10 kg (donor = recipient)) resulting in 20 weight and sex pairings. Time to death-censored graft loss for each pairing was evaluated using multivariable Cox Proportional Hazards models adjusting for donor, immunological, surgical and recipient predictors of graft loss compared to the reference group of male donor-male recipients with no weight mismatch (&lt;10 kg difference). Results 21,261 of 115,124 kidney transplant recipients developed death-censored graft failure, (median graft survival time was 3.8 years, Q1-Q3 0.0-14.8 years). After multivariable adjustment, the highest relative hazards for graft failure were observed for female recipients of male donor kidneys and male recipients of female donor kidneys in situations where the recipient was &gt;30 kg larger than donor (HR 1.50 95% CI [1.32-1.70], HR 1.35 95% CI [1.25-1.45], respectively). Conclusions A concurrent mismatch in donor-recipient weight (donor</p