New NICE Interventional procedures guidance [IPG609] Robot-assisted kidney transplant

New NICE Interventional procedures guidance [IPG609] Robot-assisted kidney transplant
Published date: April 2018, Next review: April 2021


Evidence-based recommendations on robot-assisted kidney transplant in adults. This involves the surgeon using a robot to help with a kidney transplant.


Read full guidance at  https://www.nice.org.uk/guidance/ipg609

UHCW publication: gastric acid-reducing drugs following renal transplantation

Do stop me now: gastric acid-reducing drugs following renal transplantation

I Held, R Pyart J Kidney Care 2018 Jan 3(1):6-13

Abstract

Proton pump inhibitors (PPIs) can counteract the risk of gastrointestinal bleeds, but can also be harmful. University Hospitals Coventry and Warwickshire NHS Trust's renal transplant drug protocol recommends that patients take omeprazole if they have a history of peptic ulcers or indigestion. Ines Held and Rhodri Pyart share the findings of two audits on PPIs in renal transplant patients.

Full text available with UHCW Openathens login at https://www.magonlinelibrary.com/doi/10.12968/jokc.2018.3.1.6

SaBTO microbiological safety guidelines 2017

Guidance from the Department of Health and Social Care on the microbiological safety of human organs, tissues and cells used in transplantation.

Infographic: Meniscal transplantation is beneficial at one year

Bone Joint J. 2018 Jan;100-B(1):64-65. doi: 10.1302/0301-620X.100B1.BJJ-2017-1478.
UHCW Research: Smith NA, Wright, D, Spalding, T, Hutchinson, C and Thompson, P

A pilot randomized trial of meniscal allograft transplantation versus personalized physiotherapy for patients with a symptomatic meniscal deficient knee compartment

Bone Joint J. 2018 Jan;100-B(1):56-63. doi: 10.1302/0301-620X.100B1.BJJ-2017-0918.R1.

Meniscal allograft transplantation is undertaken to improve pain and function in patients with a symptomatic meniscal deficient knee compartment. While case series have shown improvements in patient reported outcome measures (PROMs), its efficacy has not been rigorously evaluated. This study aimed to compare PROMs in patients having meniscal transplantation with those having personalized physiotherapy at 12 months.

UHCW Research: Smith NA, Wright, D, Spalding, T and Thompson, P

Artificial heart implantation as a bridge to transplantation for end-stage refractory biventricular heart failure [IPG602]

New interventional procedures guidance from NICE.  This involves replacing the 2 lower chambers of the heart with a mechanical device to improve circulation until heart transplantation.

Current evidence on the safety and efficacy of total artificial heart implantation as a bridge to transplantation for end-stage refractory biventricular heart failure is limited in quality and quantity. Therefore, this procedure should only be used with special arrangements for clinical governance, consent and audit or research.

Clinicians wishing to do total artificial heart implantation as a bridge to transplantation for end-stage refractory biventricular heart failure should:

• Inform the clinical governance leads in their NHS trusts.
• Ensure that patients understand the uncertainty about the procedure's safety and provide them with clear written information. In addition, the use of NICE's information for the public is recommended.
• Audit and review clinical outcomes of all patients having total artificial heart implantation as a bridge to transplantation for end-stage refractory biventricular heart failure (see section 6.3).
• Clinicians should enter details about all patients having total artificial heart implantation as a bridge to transplantation for end-stage refractory biventricular heart failure onto an appropriate registry and review local clinical outcomes.
• Patient selection should be done by a multidisciplinary team experienced in managing end-stage refractory biventricular heart failure in patients needing a heart transplant, for whom a donor organ is not expected to be available before their own heart fails completely.
• This technically challenging procedure should only be done in centres specialising in heart transplantation. Only cardiothoracic surgeons with specific expertise and training in inserting the device should carry it out.

Introducing 'opt-out' consent for organ and tissue donation in England

This DH consultation seeks views on proposed plans to make it easier for people to give consent to be an organ donor.

The consultation is specifically seeking input on how much input families have in deceased relative's donation decisions, whether exemptions to opting out is needed and how these proposals may affect certain groups depending on age, disability, race or faith. The consultation closes on 6 March 2018.

Immunosuppressive therapy for kidney transplant in children and young people [TA482]

New:  Technology Appraisal Guidance

Evidence-based recommendations  on immunosuppressive therapies for preventing kidney rejection in children and young people. The therapies are basiliximab (Simulect), immediate-release tacrolimus (Adoport, Capexion, Modigraf, Prograf, Tacni, Vivadex), mycophenolate mofetil (Cellcept and non-branded versions), rabbit anti-human thymocyte immunoglobulin (Thymoglobuline), prolonged-release tacrolimus (Advagraf, Envarsus), mycophenolate sodium (Myfortic, Ceptava), sirolimus (Rapamune), everolimus (Certican) and belatacept (Nulojix).

This guidance makes recommendations on using basiliximab, rabbit anti-human thymocyte immunoglobulin, tacrolimus (immediate-release and prolonged-release), mycophenolate mofetil, mycophenolate sodium, sirolimus, everolimus and belatacept after kidney transplant in children and young people. The recommendations apply only to the initial immunosuppressive therapy (induction and maintenance therapy) started around the time of kidney transplant.

It was outside the scope of the appraisal to make recommendations on using azathioprine or corticosteroids after kidney transplant in children and young people.
Under an exceptional directive from the Department of Health, the appraisal committee was allowed to make recommendations about using drugs outside the terms of their marketing authorisations if there was compelling evidence of their safety and effectiveness.

Immunosuppressive therapy for kidney transplant in children and young people [TA481]

New Guidance from NICE:

Evidence-based recommendations on immunosuppressive therapies for preventing kidney rejection in children and young people. The therapies are basiliximab (Simulect), immediate-release tacrolimus (Adoport, Capexion, Modigraf, Prograf, Tacni, Vivadex), mycophenolate mofetil (Cellcept and non-branded versions), rabbit anti-human thymocyte immunoglobulin (Thymoglobuline), prolonged-release tacrolimus (Advagraf, Envarsus), mycophenolate sodium (Myfortic, Ceptava), sirolimus (Rapamune), everolimus (Certican) and belatacept (Nulojix).

This guidance makes recommendations on using basiliximab, rabbit anti-human thymocyte immunoglobulin, tacrolimus (immediate-release and prolonged-release), mycophenolate mofetil, mycophenolate sodium, sirolimus, everolimus and belatacept after kidney transplant in children and young people. The recommendations apply only to the initial immunosuppressive therapy (induction and maintenance therapy) started around the time of kidney transplant.
It was outside the scope of the appraisal to make recommendations on using azathioprine or corticosteroids after kidney transplant in children and young people.
Under an exceptional directive from the Department of Health, the appraisal committee was allowed to make recommendations about using drugs outside the terms of their marketing authorisations if there was compelling evidence of their safety and effectiveness.

Immunosuppressive therapy for kidney transplant in adults

New Guidance from NICE:

Evidence-based recommendations on immunosuppressive therapies for preventing kidney rejection in children and young people. The therapies are basiliximab (Simulect), immediate-release tacrolimus (Adoport, Capexion, Modigraf, Prograf, Tacni, Vivadex), mycophenolate mofetil (Cellcept and non-branded versions), rabbit anti-human thymocyte immunoglobulin (Thymoglobuline), prolonged-release tacrolimus (Advagraf, Envarsus), mycophenolate sodium (Myfortic, Ceptava), sirolimus (Rapamune), everolimus (Certican) and belatacept (Nulojix).

This guidance makes recommendations on using basiliximab, rabbit anti-human thymocyte immunoglobulin, tacrolimus (immediate-release and prolonged-release), mycophenolate mofetil, mycophenolate sodium, sirolimus, everolimus and belatacept after kidney transplant in children and young people. The recommendations apply only to the initial immunosuppressive therapy (induction and maintenance therapy) started around the time of kidney transplant.
It was outside the scope of the appraisal to make recommendations on using azathioprine or corticosteroids after kidney transplant in children and young people.
Under an exceptional directive from the Department of Health, the appraisal committee was allowed to make recommendations about using drugs outside the terms of their marketing authorisations if there was compelling evidence of their safety and effectiveness.

Kidney retransplantation from HLA incompatible living donors: a single centre study of 3rd /4th transplants

Clin Transplant. 2017 Sep 4. doi: 10.1111/ctr.13104. [Epub ahead of print]

The demand for kidney retransplantation following graft failure is rising. Repeat transplantation is often associated with poorer outcomes due to both immunological and surgical challenges. The aim of this study was to compare surgical and functional outcomes of kidney retransplantation in recipients that had previously had at least 2 kidney transplants with a focus on those with antibody incompatibility.

UHCW Research: Barnes, J. C. H., Lam, F. T., Kashi, S. H., Tan L. C., Higgins, R. amd Imray C. H. E.

Endovascular management of iliac artery dissection during renal transplantation

CIRSE 2017 - P-670

We present a renal failure patient who received a donor kidney complicated with flow-limiting external iliac dissection.We demonstrate through our case that this rare complication can be
successfully managed with endovascular techniques that salvage a failing donor kidney.

UHCW Research: M.J. Maddock and J. Harding

Commissioning policy: Reimbursement of expenses for living donors

This is an NHS England policy designed to inform healthcare professionals and commissioning authorities about the principles and processes that underpin financial reimbursement for living organ donors.

The UK National Registry of ABO and HLA Antibody Incompatible Renal Transplantation: Pretransplant Factors Associated With Outcome in 879 Transplants

Transplant Direct. 2017 Jun 26;3(7):e181. doi: 10.1097/TXD.0000000000000695. eCollection 2017 Jul.

ABO and HLA antibody incompatible (HLAi) renal transplants (AIT) now comprise around 10% of living donor kidney transplants. However, the relationship between pretransplant factors and medium-term outcomes are not fully understood, especially in relation to factors that may vary between centers.

Results of AIT were acceptable, certainly in the context of a choice between living donor AIT and an antibody compatible deceased donor transplant. Several factors were associated with increased chance of transplant loss, and these can lead to testable hypotheses for further improving therapy.

UHCW Research: Fuggle SV and Higgins RM

Presence of complement activating donor specific antibodies is associated with poor renal allograft survival: Two centre retrospective study

American Journal of Transplantation. Conference: 17thAmerican Transplant Congress, ATC2017. United States. 17 (pp 428-429), 2017. Date of Publication:April 2017.

Complement fixing donor specific antibodies (DSA) as detected by presence of C3d at the time of rejection is associated with poor graft outcome;no studies have explored the role pre-transplant; especially in Human leucocyte Antigen-Antibody incompatible transplants (HLA-AIT).
Analysed 117 patient samples either complement dependent cytotoxicity (CDC) or Flow Crossmatch(FC) positive at pre-conditioning who underwent direct transplantation after
desensitisation. C3d (Immucor) assay was performed and the results correlated with early antibody mediated rejection (EAMR) (within first 30 days) and death censored allograft survival (DCGF).

UHCW Research:  Babu, A., Krishnan N., Higgins R. and; Daga S.

Can pre-treatment cdc titres predict graft outcomes in HLA incompatible transplants?

American Journalof Transplantation. Conference: 17th American Transplant Congress, ATC2017. United States. 17 (pp 411), 2017. Date of Publication: April 2017.

Complement Dependent Cytotoxic (CDC) (non-augmented) cross matching and Flow cytometric (FC) cross matching are two commonly used techniques to identify anti-Human Leucocyte Antigen (HLA) antibodies. Preformed antibodies cause rejection by binding to HLA antigens expressed

on the endothelium of vessels in the transplanted kidney. It has been shown by Higgins etal that transplanting across HLA incompatibility has good outcomes if CDC crossmatch was negative. In that study, death censored graft survival in the CDC negative (but DSA positive) group was

88.6% compared to 54.2% in the CDC positive group. The aim of this study is to look at the predictive value of pre-treatment CDC titres in relation to graft survival.

UHCW Research: Prasad A., Yuvaraj A. and Krishnan N.

Patients with rare conditions to benefit from new treatments

NHS England hasconfirmed that three new specialised treatments will be made available for patients in England.

• Second allogeneic haematopoietic stem cell transplants – estimated to cover around 15 patients a year who suffer a relapse following a first transplant.
• Eculizumab for the treatment of the kidney condition C3 glomerulopathy – which includes C3 glomerulonephritis and dense deposit disease – estimated to benefit up to 5 patients a year who suffer a relapse following a kidney transplant.
• Riociguat for pulmonary arterial hypertension – estimated to benefit around 90-125 patients a year for whom other treatments have failed, subject to confirmation of a commercially in confidence discounted price offered by the manufacturer.

Post-transplant food safety is imperative

Journal of Kidney Care, 2.1 (January 2017): 4.

The British Dietetic Association's (2016) renal transplant guidelines were a welcome addition to clinical practice. They amalgamate up-to-date food safety evidence to guide dietitians in post-transplant nutritional advice. Informed by stem cell transplant research (due to the lack of evidence in renal), the recommendations addressed potential conflicting theoretical dietary advice reflected in differing historical dietetic practice throughout the UK. For example, at one time there was differing advice on the number of months recommended to avoid eating outside the home after a transplant. Now definitive best practice guidelines exist. References

UHCW Research: Andrew Morris

Decision tree and random forest models for outcome prediction in antibody incompatible kidney transplantation

Biomedical Signal Processing and Control Available online 9 February 2017

Clinical datasets are commonly limited in size, thus restraining applications of Machine Learning (ML) techniques for predictive modelling in clinical research and organ transplantation. We explored the potential of Decision Tree (DT) and Random Forest (RF) classification models, in the context of small dataset of 80 samples, for outcome prediction in high-risk kidney transplantation. The DT and RF models identified the key risk factors associated with acute rejection: the levels of the donor specific IgG antibodies, the levels of IgG4 subclass and the number of human leucocyte antigen mismatches between the donor and recipient. Furthermore, the DT model determined dangerous levels of donor-specific IgG subclass antibodies, thus demonstrating the potential of discovering new properties in the data when traditional statistical tools are unable to capture them. The DT and RF classifiers developed in this work predicted early transplant rejection with accuracy of 85%, thus offering an accurate decision support tool for doctors tasked with predicting outcomes of kidney transplantation in advance of the clinical intervention.

UHCW Research: Robert Higgins and Sunil Daga

A new data-driven model for post-transplant antibody dynamics in high risk kidney transplantation

Mathematical biosciences, 284 pp. 3-11. http://dx.doi.org/10.1016/j.mbs.2016.04.008

The dynamics of donor specific human leukocyte antigen antibodies during early stage after kidney transplantation are of great clinical interest as these antibodies are considered to be associated with short and long term clinical outcomes. The limited number of antibody time series and their diverse patterns have made the task of modelling difficult. Focusing on one typical post-transplant dynamic pattern with rapid falls and stable settling levels, a novel data-driven model has been developed for the first time. A variational Bayesian inference method has been applied to select the best model and learn its parameters for 39 time series from two groups of graft recipients, i.e. patients with and without acute antibody-mediated rejection (AMR) episodes. Linear and nonlinear dynamic models of different order were attempted to fit the time series, and the third order linear model provided the best description of the common features in both groups. Both deterministic and stochastic parameters are found to be significantly different in the AMR and no-AMR groups showing that the time series in the AMR group have significantly higher frequency of oscillations and faster dissipation rates. This research may potentially lead to better understanding of the immunological mechanisms involved in kidney transplantation.

UHCW Research: Krishnan, Nithya and Higgins, Robert